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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Cardiovasc. Med.</journal-id><journal-title-group>
<journal-title>Frontiers in Cardiovascular Medicine</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Cardiovasc. Med.</abbrev-journal-title></journal-title-group>
<issn pub-type="epub">2297-055X</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fcvm.2026.1649064</article-id>
<article-version article-version-type="Version of Record" vocab="NISO-RP-8-2008"/>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Original Research</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Global, regional, and national burden and projections of severe heart failure attributable to hypertensive, ischemic, and rheumatic heart diseases: an analysis from the global burden of disease study 2021</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author"><name><surname>Xue</surname><given-names>Gang</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Data curation" vocab-term-identifier="https://credit.niso.org/contributor-roles/data-curation/">Data curation</role><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="conceptualization" vocab-term-identifier="https://credit.niso.org/contributor-roles/conceptualization/">Conceptualization</role><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="resources" vocab-term-identifier="https://credit.niso.org/contributor-roles/resources/">Resources</role><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="software" vocab-term-identifier="https://credit.niso.org/contributor-roles/software/">Software</role><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Writing &#x2013; review &#x0026; editing" vocab-term-identifier="https://credit.niso.org/contributor-roles/writing-review-editing/">Writing &#x2013; review &#x0026; editing</role></contrib>
<contrib contrib-type="author"><name><surname>Hou</surname><given-names>Yuyan</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Data curation" vocab-term-identifier="https://credit.niso.org/contributor-roles/data-curation/">Data curation</role><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="investigation" vocab-term-identifier="https://credit.niso.org/contributor-roles/investigation/">Investigation</role><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Project administration" vocab-term-identifier="https://credit.niso.org/contributor-roles/project-administration/">Project administration</role><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="validation" vocab-term-identifier="https://credit.niso.org/contributor-roles/validation/">Validation</role><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Writing &#x2013; original draft" vocab-term-identifier="https://credit.niso.org/contributor-roles/writing-original-draft/">Writing &#x2013; original draft</role></contrib>
<contrib contrib-type="author"><name><surname>Su</surname><given-names>Shuhong</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="validation" vocab-term-identifier="https://credit.niso.org/contributor-roles/validation/">Validation</role><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="conceptualization" vocab-term-identifier="https://credit.niso.org/contributor-roles/conceptualization/">Conceptualization</role><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Formal analysis" vocab-term-identifier="https://credit.niso.org/contributor-roles/formal-analysis/">Formal analysis</role><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="resources" vocab-term-identifier="https://credit.niso.org/contributor-roles/resources/">Resources</role><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="supervision" vocab-term-identifier="https://credit.niso.org/contributor-roles/supervision/">Supervision</role><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Writing &#x2013; original draft" vocab-term-identifier="https://credit.niso.org/contributor-roles/writing-original-draft/">Writing &#x2013; original draft</role></contrib>
<contrib contrib-type="author"><name><surname>Jin</surname><given-names>Weidong</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="conceptualization" vocab-term-identifier="https://credit.niso.org/contributor-roles/conceptualization/">Conceptualization</role><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Formal analysis" vocab-term-identifier="https://credit.niso.org/contributor-roles/formal-analysis/">Formal analysis</role><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="supervision" vocab-term-identifier="https://credit.niso.org/contributor-roles/supervision/">Supervision</role><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Writing &#x2013; original draft" vocab-term-identifier="https://credit.niso.org/contributor-roles/writing-original-draft/">Writing &#x2013; original draft</role></contrib>
<contrib contrib-type="author"><name><surname>Wu</surname><given-names>Xiao</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Formal analysis" vocab-term-identifier="https://credit.niso.org/contributor-roles/formal-analysis/">Formal analysis</role><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Writing &#x2013; original draft" vocab-term-identifier="https://credit.niso.org/contributor-roles/writing-original-draft/">Writing &#x2013; original draft</role><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="investigation" vocab-term-identifier="https://credit.niso.org/contributor-roles/investigation/">Investigation</role><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="methodology" vocab-term-identifier="https://credit.niso.org/contributor-roles/methodology/">Methodology</role><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="validation" vocab-term-identifier="https://credit.niso.org/contributor-roles/validation/">Validation</role></contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Gao</surname><given-names>Zhitao</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<xref ref-type="corresp" rid="cor1">&#x002A;</xref><uri xlink:href="https://loop.frontiersin.org/people/2966966/overview"/><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="methodology" vocab-term-identifier="https://credit.niso.org/contributor-roles/methodology/">Methodology</role><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Data curation" vocab-term-identifier="https://credit.niso.org/contributor-roles/data-curation/">Data curation</role><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Project administration" vocab-term-identifier="https://credit.niso.org/contributor-roles/project-administration/">Project administration</role><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Writing &#x2013; review &#x0026; editing" vocab-term-identifier="https://credit.niso.org/contributor-roles/writing-review-editing/">Writing &#x2013; review &#x0026; editing</role></contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Wang</surname><given-names>Zhifang</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="corresp" rid="cor1">&#x002A;</xref><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="investigation" vocab-term-identifier="https://credit.niso.org/contributor-roles/investigation/">Investigation</role><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="supervision" vocab-term-identifier="https://credit.niso.org/contributor-roles/supervision/">Supervision</role><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="visualization" vocab-term-identifier="https://credit.niso.org/contributor-roles/visualization/">Visualization</role><role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Writing &#x2013; review &#x0026; editing" vocab-term-identifier="https://credit.niso.org/contributor-roles/writing-review-editing/">Writing &#x2013; review &#x0026; editing</role></contrib>
</contrib-group>
<aff id="aff1"><label>1</label><institution>Xinxiang Central Hospital</institution>, <city>Xinxiang</city>, <state>Henan</state>, <country country="cn">China</country></aff>
<aff id="aff2"><label>2</label><institution>School of Medical Technology, Henan Medical University</institution>, <city>Xinxiang</city>, <state>Henan</state>, <country country="cn">China</country></aff>
<author-notes>
<corresp id="cor1"><label>&#x002A;</label><bold>Correspondence:</bold> Zhitao Gao <email xlink:href="mailto:gaozhitao@xxmu.edu.cn">gaozhitao@xxmu.edu.cn</email> Zhifang Wang <email xlink:href="mailto:wzf2146@163.com">wzf2146@163.com</email></corresp>
</author-notes>
<pub-date publication-format="electronic" date-type="pub" iso-8601-date="2026-03-09"><day>09</day><month>03</month><year>2026</year></pub-date>
<pub-date publication-format="electronic" date-type="collection"><year>2026</year></pub-date>
<volume>13</volume><elocation-id>1649064</elocation-id>
<history>
<date date-type="received"><day>18</day><month>06</month><year>2025</year></date>
<date date-type="rev-recd"><day>10</day><month>01</month><year>2026</year></date>
<date date-type="accepted"><day>20</day><month>02</month><year>2026</year></date>
</history>
<permissions>
<copyright-statement>&#x00A9; 2026 Xue, Hou, Su, Jin, Wu, Gao and Wang.</copyright-statement>
<copyright-year>2026</copyright-year><copyright-holder>Xue, Hou, Su, Jin, Wu, Gao and Wang</copyright-holder><license><ali:license_ref start_date="2026-03-09">https://creativecommons.org/licenses/by/4.0/</ali:license_ref><license-p>This is an open-access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License (CC BY)</ext-link>. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</license-p></license>
</permissions>
<abstract><sec><title>Background</title>
<p>Severe heart failure (SHF) caused by hypertensive heart disease (HHD), ischemic heart disease (IHD), and rheumatic heart disease (RHD) remains a significant global public health concern. Accurate assessments of the global and regional burdens, trends, and health inequalities related to these diseases are critical for formulating targeted health policies and interventions.</p>
</sec><sec><title>Methods</title>
<p>Data on the prevalence and years lived with disability (YLDs) due to severe heart failure resulting from HHD, IHD, and RHD from 1990 to 2021 were extracted from the Global Burden of Disease (GBD) Study 2021. Trends were analyzed according to age-standardized rates (ASRs) and sociodemographic index (SDI) stratifications. Predictions for 2022&#x2013;2040 were generated using Nordpred modeling and validated with the Bayesian Age-Period-Cohort (BAPC) model.</p>
</sec><sec><title>Results</title>
<p>In 2021, prevalent cases for severe heart failure attributable to HHD, IHD, and RHD reached 4.07 million, 6.24 million, and 0.74 million, respectively, with corresponding age-standardized prevalence rates (ASPR) of 48.3, 74.4, and 9.2 per 100,000. Compared with 1990, cases increased by 170.3&#x0025; for HHD, 140.7&#x0025; for IHD, and 39.0&#x0025; for RHD. YLDs rose to 700,272 (HHD), 1,075,512 (IHD), and 129,155 (RHD), respectively. The greatest burdens occurred in Eastern Sub-Saharan Africa for HHD (ASPR: 95.0), North Africa and the Middle East for IHD (ASPR: 103.1), and South Asia for RHD (ASPR: 21.0). Projections indicate continued increases in prevalent cases and YLDs for all conditions, with stable or slightly rising standardized rates, highlighting persistent regional and gender inequalities.</p>
</sec><sec><title>Conclusion</title>
<p>Severe heart failure burdens related to HHD, IHD, and RHD are increasing globally, influenced significantly by demographic shifts and socioeconomic disparities. Urgent implementation of context-specific preventive and healthcare strategies is essential to address health inequalities and reduce the future burden of severe heart failure worldwide.</p>
</sec>
</abstract>
<kwd-group>
<kwd>disease burden</kwd>
<kwd>global burden of disease (GBD)</kwd>
<kwd>health inequality</kwd>
<kwd>hypertensive heart disease</kwd>
<kwd>ischemic heart disease</kwd>
<kwd>rheumatic heart disease</kwd>
<kwd>severe heart failure</kwd>
</kwd-group><funding-group><funding-statement>The author(s) declared that financial support was not received for this work and/or its publication.</funding-statement></funding-group><counts>
<fig-count count="7"/>
<table-count count="6"/><equation-count count="2"/><ref-count count="41"/><page-count count="18"/><word-count count="0"/></counts><custom-meta-group><custom-meta><meta-name>section-at-acceptance</meta-name><meta-value>Cardiovascular Epidemiology and Prevention</meta-value></custom-meta></custom-meta-group>
</article-meta>
</front>
<body><sec id="s1" sec-type="intro"><title>Introduction</title>
<p>Cardiovascular diseases remain the foremost contributor to global mortality, with heart failure serving as a critical endpoint for diverse etiologies shaped by biological, environmental, and socioeconomic interplay (<xref ref-type="bibr" rid="B1">1</xref>). Hypertensive heart disease (HHD), ischemic heart disease (IHD), and rheumatic heart disease (RHD) collectively drive severe heart failure (SHF) worldwide, yet their epidemiological trajectories diverge markedly across developmental contexts. While IHD dominates in aging, high-income populations amid caloric excess and sedentary lifestyles, HHD thrives in regions with fragmented primary care, and RHD persists as a marker of neglected infectious disease control (<xref ref-type="bibr" rid="B2">2</xref>&#x2013;<xref ref-type="bibr" rid="B4">4</xref>). These disparities underscore a paradox of progress: socioeconomic advancement may alleviate historical burdens while incubating new risks, necessitating frameworks that capture nonlinear transitions.</p>
<p>Existing studies often isolate these etiologies or focus on short-term trends, neglecting the dynamic interaction between sociodemographic development and cardiovascular risk evolution. Conventional epidemiological transition models, which posit a linear shift from infectious to non-communicable diseases, fail to explain overlapping burdens in transitional economies where RHD legacies coexist with rising IHD rates (<xref ref-type="bibr" rid="B5">5</xref>, <xref ref-type="bibr" rid="B6">6</xref>). Similarly, gender and age-related disparities are frequently oversimplified as biological inevitabilities rather than outcomes of structural inequities in healthcare access and social determinants (<xref ref-type="bibr" rid="B7">7</xref>, <xref ref-type="bibr" rid="B8">8</xref>). This study addresses these gaps through a multidecadal, multilevel analysis of severe heart failure burdens, dissecting how uneven developmental trajectories, which marked by disparities in education, income, and healthcare, reshape risk portfolios.</p>
<p>The evolution of health inequities further reflects systemic biases in global health governance. Although targeted interventions have modestly reduced RHD disparities, widening gaps in HHD burden highlight the marginalization of chronic conditions in policy agendas. Conversely, the persistent prevalence of IHD in affluent societies illustrates how available preventive and therapeutic options often remain underutilized due to entrenched cultural norms and systemic barriers within health systems (<xref ref-type="bibr" rid="B9">9</xref>, <xref ref-type="bibr" rid="B10">10</xref>). These patterns demand interventions that transcend etiology-specific silos, addressing shared structural determinants such as antibiotic accessibility and salt reduction policies while adapting to regional transition phases.</p>
<p>Ultimately, this study seeks to redefine cardiovascular disease management paradigms by advocating integrated and equity-oriented strategies. By systematically documenting how severe heart failure burdens from HHD, IHD, and RHD align with socioeconomic and health system factors, it underscores the urgency for multidimensional interventions that address fundamental societal determinants. Only through comprehensive, context-specific, and integrated public health approaches can global stakeholders effectively mitigate the disproportionate and evolving burden of severe heart failure worldwide.</p>
</sec>
<sec id="s2" sec-type="methods"><title>Methods</title>
<sec id="s2a"><title>Study design and data sources</title>
<p>This investigation employed a retrospective analytical framework utilizing publicly accessible data from the Global Burden of Disease (GBD) Study 2021. We assessed the global, regional, and national burdens and temporal trends of severe heart failure (SHF) attributable to hypertensive heart disease (HHD), ischemic heart disease (IHD), and rheumatic heart disease (RHD) across 204 countries and territories from 1990 to 2021. Future burdens through 2040 were projected and validated using the Nordpred model and the Bayesian Age-Period-Cohort (BAPC) model with integrated nested Laplace approximations. The standardized methodology of GBD synthesizes diverse epidemiological data, ensuring comparability across regions and periods. Comprehensive descriptions of data collection, quality assurance, statistical modeling, and uncertainty estimation are detailed in prior GBD publications (<xref ref-type="bibr" rid="B11">11</xref>).</p>
</sec>
<sec id="s2b"><title>Key metrics and temporal trend analysis</title>
<p>Primary outcome measures included annual prevalent cases, years lived with disability (YLDs), age-standardized prevalence rates (ASPR), and age-standardized YLD rates (ASYR) related to severe heart failure resulting from HHD, IHD, and RHD. Temporal trends were quantified using the estimated annual percentage change (EAPC), calculated through log-linear regression models applied to age-standardized rates (<xref ref-type="bibr" rid="B12">12</xref>):<disp-formula><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="UDM1"><mml:mrow><mml:mi mathvariant="normal">EAPC</mml:mi></mml:mrow><mml:mo>=</mml:mo><mml:mo stretchy="false">(</mml:mo><mml:msup><mml:mrow><mml:mi mathvariant="normal">e</mml:mi></mml:mrow><mml:mi>&#x03B2;</mml:mi></mml:msup><mml:mo>&#x2212;</mml:mo><mml:mn>1</mml:mn><mml:mo stretchy="false">)</mml:mo><mml:mo>&#x00D7;</mml:mo><mml:mn>100</mml:mn></mml:math></disp-formula>where <italic>&#x03B2;</italic> is the slope of the natural logarithm of the ASR over time, derived from the linear regression model:<disp-formula><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="UDM2"><mml:mrow><mml:mi mathvariant="normal">ln</mml:mi></mml:mrow><mml:mo stretchy="false">(</mml:mo><mml:mrow><mml:mrow><mml:mi mathvariant="normal">ASR</mml:mi></mml:mrow></mml:mrow><mml:mo stretchy="false">)</mml:mo><mml:mo>=</mml:mo><mml:mrow><mml:mi>&#x03B2;</mml:mi><mml:mo>&#x00D7;</mml:mo><mml:mi mathvariant="normal">Year</mml:mi></mml:mrow><mml:mo>+</mml:mo><mml:mi>&#x03B1;</mml:mi></mml:math></disp-formula>Here, <italic>&#x03B1;</italic> is the intercept. A positive EAPC indicates an increasing trend, while a negative EAPC suggests a decline. Statistical significance was defined as 95&#x0025; CIs not crossing zero.</p>
</sec>
<sec id="s2c"><title>Disease definition</title>
<p>In Global Burden Disease, HHD is classified as a distinct cause, defined as a group of conditions leading to mortality or disability. In GBD 2021, HHD was mapped to ICD-10 codes I11-I11.9 and ICD-9 codes 402-402.91.</p>
<p>IHD is heart damage caused by narrowed heart arteries. IHD includes acute myocardial infarction and chronic IHD. In GBD 2021, IHD was coded according to the International Classification of Diseases, 10th Revision (as ICD-10).</p>
<p>RHD is defined as valvular damage resulting from rheumatic fever. In GBD 2021, RHD was coded ICD-10 codes I01-I01.9, I02.0, and I05-109.9, and in ICD-9 codes 391-391.9, 392.0, and 393-398.99.</p>
</sec>
<sec id="s2d"><title>Socioeconomic and geographic stratification</title>
<p>Countries were stratified by the Sociodemographic Index (SDI)&#x2014;a composite measure integrating per capita income, educational attainment, and fertility rates&#x2014;to evaluate the relationship between socioeconomic development and severe heart failure burden from HHD, IHD, and RHD. Additionally, regional variations were analyzed according to 21 GBD-defined regions and five SDI quintiles (high, high-middle, middle, low-middle, low) to identify disparities in epidemiological trends and future burdens across developmental contexts (<xref ref-type="bibr" rid="B13">13</xref>).</p>
</sec>
<sec id="s2e"><title>Correlation between age-standardized rates and sociodemographic development</title>
<p>To further elucidate the relationship between sociodemographic development and severe heart failure burdens, Spearman&#x0027;s rank correlation analyses were performed between age-standardized rates (ASPR and ASYR) and SDI at the national level for HHD, IHD, and RHD. This analysis allowed for identification of non-linear or complex relationships between disease burdens and socioeconomic progress, highlighting epidemiological transition stages in different regions (<xref ref-type="bibr" rid="B14">14</xref>, <xref ref-type="bibr" rid="B15">15</xref>).</p>
</sec>
<sec id="s2f"><title>Cross-country and gender inequality analysis</title>
<p>Cross-country inequalities were quantified using the concentration index (CI), a measure commonly employed to assess the extent of socioeconomic inequalities in health outcomes. Countries were ranked by SDI, and CI values were calculated for ASPR and ASYR of severe heart failure from HHD, IHD, and RHD. A positive CI indicated a concentration of the disease burden among higher-SDI nations, whereas a negative CI reflected a higher burden in lower-SDI settings. Gender disparities were evaluated by comparing standardized prevalence and YLD rates between males and females globally and regionally, identifying significant differences indicative of underlying gender-specific health inequalities (<xref ref-type="bibr" rid="B16">16</xref>).</p>
</sec>
<sec id="s2g"><title>Projection analysis</title>
<p>Projections of severe heart failure burden from 2022 to 2040 were initially generated using the Nordpred modeling framework, accounting for age-period-cohort interactions. To enhance projection robustness and ensure accuracy, the Bayesian Age-Period-Cohort (BAPC) model with integrated nested Laplace approximations was utilized for validation. Consistency of results from both modeling approaches confirmed projection stability. Projected metrics included prevalent cases, YLDs, ASPR, and ASYR for each condition stratified by region and sex, thus providing a comprehensive view of future epidemiological trajectories (<xref ref-type="bibr" rid="B17">17</xref>).</p>
<p>All statistical analyses and geospatial visualizations were conducted using R statistical software (version 4.4.2).</p>
</sec>
</sec>
<sec id="s3" sec-type="results"><title>Results</title>
<sec id="s3a"><title>Global burden and trends of severe heart failure due to HHD, IHD, and RHD</title>
<sec id="s3a1"><title>Severe heart failure due to HHD</title>
<p>Globally, severe heart failure (SHF) due to HHD accounted for 4,073,302 prevalent cases in 2021 (ASPR: 48.312 per 100,000; EAPC&#x2009;&#x003D;&#x2009;0.56), an increase of 170.3&#x0025; from 1990. Females had a higher absolute burden (2,216,111 cases; ASPR: 47.767; EAPC&#x2009;&#x003D;&#x2009;0.68) than males (1,857,191 cases; ASPR: 48.487; EAPC&#x2009;&#x003D;&#x2009;0.38). SHF-related YLDs reached 700,272 globally (ASYR: 8.299; EAPC&#x2009;&#x003D;&#x2009;0.57), slightly higher among males (ASYR: 8.346; 320,450 YLDs; EAPC&#x2009;&#x003D;&#x2009;0.40) compared to females (ASYR: 8.190; 379,822 YLDs; EAPC&#x2009;&#x003D;&#x2009;0.69). Trends from 1990 to 2021 in ASRs were consistent across sexes (<xref ref-type="table" rid="T1">Tables&#x00A0;1</xref>, <xref ref-type="table" rid="T2">2</xref>, <xref ref-type="sec" rid="s13">Supplementary Tables S1, S2</xref> and <xref ref-type="fig" rid="F1">Figure&#x00A0;1</xref>).</p>
<table-wrap id="T1" position="float"><label>Table&#x00A0;1</label>
<caption><p>The prevalence of SHF due to HHD in 1990 and 2021.</p></caption>
<table>
<colgroup>
<col align="left"/>
<col align="left"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
</colgroup>
<thead>
<tr>
<th valign="top" align="left">Locations</th>
<th valign="top" align="left">Cause</th>
<th valign="top" align="center">Sex</th>
<th valign="top" align="center">1990 prevalence cases (95&#x0025; UI)</th>
<th valign="top" align="center">2021 prevalence cases (95&#x0025; UI)</th>
<th valign="top" align="center">1990 ASPR (95&#x0025; UI)</th>
<th valign="top" align="center">2021 ASPR (95&#x0025; UI)</th>
<th valign="top" align="center">1990&#x2013;2021 EAPC (95&#x0025;CI)</th>
<th valign="top" align="center">1990&#x2013;2021 prevalence cases changes (&#x0025;)</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Global</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="center">Both</td>
<td valign="top" align="center">1,506,979 (1,161,737&#x2013;1,933,553)</td>
<td valign="top" align="center">4,073,302 (3,078,489&#x2013;5,324,403)</td>
<td valign="top" align="center">40.859 (31.301&#x2013;52.529)</td>
<td valign="top" align="center">48.312 (36.774&#x2013;62.917)</td>
<td valign="top" align="center">0.56 (0.52&#x2013;0.59)</td>
<td valign="top" align="center">170.296</td>
</tr>
<tr>
<td valign="top" align="left">High SDI</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="center">Both</td>
<td valign="top" align="center">275,424 (208,999&#x2013;358,970)</td>
<td valign="top" align="center">793,747 (607,525&#x2013;1,034,136)</td>
<td valign="top" align="center">25.133 (19.43&#x2013;32.284)</td>
<td valign="top" align="center">36.93 (28.819&#x2013;47.203)</td>
<td valign="top" align="center">1.57 (1.46&#x2013;1.68)</td>
<td valign="top" align="center">188.191</td>
</tr>
<tr>
<td valign="top" align="left">High-middle SDI</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="center">Both</td>
<td valign="top" align="center">323,219 (240,938&#x2013;417,762)</td>
<td valign="top" align="center">892,801 (662,261&#x2013;1,174,875)</td>
<td valign="top" align="center">35.081 (26.276&#x2013;45.415)</td>
<td valign="top" align="center">45.554 (34.187&#x2013;59.712)</td>
<td valign="top" align="center">0.87 (0.83&#x2013;0.92)</td>
<td valign="top" align="center">176.222</td>
</tr>
<tr>
<td valign="top" align="left">Low SDI</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="center">Both</td>
<td valign="top" align="center">122,235 (92,366&#x2013;157,951)</td>
<td valign="top" align="center">298,258 (226,400&#x2013;382,208)</td>
<td valign="top" align="center">65.885 (49.281&#x2013;85.465)</td>
<td valign="top" align="center">67.884 (50.825&#x2013;89.191)</td>
<td valign="top" align="center">0.12 (0.09&#x2013;0.14)</td>
<td valign="top" align="center">144.004</td>
</tr>
<tr>
<td valign="top" align="left">Low-middle SDI</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="center">Both</td>
<td valign="top" align="center">241,675 (188,511&#x2013;305,778)</td>
<td valign="top" align="center">632,843 (479,532&#x2013;812,356)</td>
<td valign="top" align="center">47.399 (37.051&#x2013;60.286)</td>
<td valign="top" align="center">49.334 (37.576&#x2013;63.682)</td>
<td valign="top" align="center">0.08 (0.07&#x2013;0.1)</td>
<td valign="top" align="center">161.857</td>
</tr>
<tr>
<td valign="top" align="left">Middle SDI</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="center">Both</td>
<td valign="top" align="center">542,837 (424,289&#x2013;691,330)</td>
<td valign="top" align="center">1,451,596 (1,078,299&#x2013;1,912,457)</td>
<td valign="top" align="center">61.844 (47.752&#x2013;79.376)</td>
<td valign="top" align="center">57.998 (43.505&#x2013;76.028)</td>
<td valign="top" align="center">&#x2212;0.35 (&#x2212;0.47 to &#x2212;0.23)</td>
<td valign="top" align="center">167.409</td>
</tr>
<tr>
<td valign="top" align="left">Andean Latin America</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="center">Both</td>
<td valign="top" align="center">9,607 (7,521&#x2013;12,223)</td>
<td valign="top" align="center">27,997 (21,092&#x2013;36,725)</td>
<td valign="top" align="center">48.937 (37.783&#x2013;63.285)</td>
<td valign="top" align="center">48.335 (36.353&#x2013;63.816)</td>
<td valign="top" align="center">0.17 (0.07&#x2013;0.27)</td>
<td valign="top" align="center">191.423</td>
</tr>
<tr>
<td valign="top" align="left">Australasia</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="center">Both</td>
<td valign="top" align="center">2,374 (1,805&#x2013;3,068)</td>
<td valign="top" align="center">9,790 (7,649&#x2013;12,310)</td>
<td valign="top" align="center">10.221 (7.811&#x2013;13.143)</td>
<td valign="top" align="center">17.073 (13.402&#x2013;21.296)</td>
<td valign="top" align="center">1.95 (1.83&#x2013;2.06)</td>
<td valign="top" align="center">312.384</td>
</tr>
<tr>
<td valign="top" align="left">Caribbean</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="center">Both</td>
<td valign="top" align="center">11,731 (9,053&#x2013;15,284)</td>
<td valign="top" align="center">34,276 (26,011&#x2013;45,140)</td>
<td valign="top" align="center">46.089 (35.643&#x2013;60.327)</td>
<td valign="top" align="center">63.657 (48.306&#x2013;83.933)</td>
<td valign="top" align="center">1.24 (1.17&#x2013;1.3)</td>
<td valign="top" align="center">192.183</td>
</tr>
<tr>
<td valign="top" align="left">Central Asia</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="center">Both</td>
<td valign="top" align="center">11,437 (8,393&#x2013;15,531)</td>
<td valign="top" align="center">22,586 (15,244&#x2013;30,831)</td>
<td valign="top" align="center">26.089 (18.889&#x2013;35.855)</td>
<td valign="top" align="center">31.118 (20.735&#x2013;43.166)</td>
<td valign="top" align="center">0.95 (0.74&#x2013;1.16)</td>
<td valign="top" align="center">97.482</td>
</tr>
<tr>
<td valign="top" align="left">Central Europe</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="center">Both</td>
<td valign="top" align="center">46,482 (33,953&#x2013;62,654)</td>
<td valign="top" align="center">110,467 (79,889&#x2013;146,524)</td>
<td valign="top" align="center">32.659 (24.017&#x2013;43.471)</td>
<td valign="top" align="center">47.551 (35.01&#x2013;62.344)</td>
<td valign="top" align="center">1.7 (1.55&#x2013;1.84)</td>
<td valign="top" align="center">137.655</td>
</tr>
<tr>
<td valign="top" align="left">Central Latin America</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="center">Both</td>
<td valign="top" align="center">33,590 (25,977&#x2013;42,770)</td>
<td valign="top" align="center">92,673 (69,294&#x2013;121,504)</td>
<td valign="top" align="center">44.567 (34.24&#x2013;57.373)</td>
<td valign="top" align="center">38.754 (28.922&#x2013;51.164)</td>
<td valign="top" align="center">&#x2212;0.65 (&#x2212;0.72 to &#x2212;0.59)</td>
<td valign="top" align="center">175.895</td>
</tr>
<tr>
<td valign="top" align="left">Central Sub-Saharan Africa</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="center">Both</td>
<td valign="top" align="center">12,626 (8,966&#x2013;16,712)</td>
<td valign="top" align="center">34,634 (25,197&#x2013;46,102)</td>
<td valign="top" align="center">72.175 (50.752&#x2013;97.706)</td>
<td valign="top" align="center">77.883 (55.504&#x2013;105.375)</td>
<td valign="top" align="center">0.28 (0.22&#x2013;0.33)</td>
<td valign="top" align="center">174.307</td>
</tr>
<tr>
<td valign="top" align="left">East Asia</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="center">Both</td>
<td valign="top" align="center">504,991 (377,968&#x2013;654,323)</td>
<td valign="top" align="center">1,324,469 (959,524&#x2013;1,752,486)</td>
<td valign="top" align="center">70.579 (53.094&#x2013;90.49)</td>
<td valign="top" align="center">62.913 (46.746&#x2013;82.941)</td>
<td valign="top" align="center">&#x2212;0.63 (&#x2212;0.85 to &#x2212;0.4)</td>
<td valign="top" align="center">162.276</td>
</tr>
<tr>
<td valign="top" align="left">Eastern Europe</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="center">Both</td>
<td valign="top" align="center">25,346 (17,951&#x2013;34,740)</td>
<td valign="top" align="center">50,472 (34,371&#x2013;72,036)</td>
<td valign="top" align="center">9.338 (6.654&#x2013;12.677)</td>
<td valign="top" align="center">13.939 (9.575&#x2013;19.736)</td>
<td valign="top" align="center">1.73 (1.56&#x2013;1.91)</td>
<td valign="top" align="center">99.132</td>
</tr>
<tr>
<td valign="top" align="left">Eastern Sub-Saharan Africa</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="center">Both</td>
<td valign="top" align="center">57,014 (41,773&#x2013;74,691)</td>
<td valign="top" align="center">138,614 (103,620&#x2013;176,601)</td>
<td valign="top" align="center">91.912 (68.061&#x2013;121.952)</td>
<td valign="top" align="center">95.038 (70.589&#x2013;125.487)</td>
<td valign="top" align="center">0.08 (0.06&#x2013;0.1)</td>
<td valign="top" align="center">143.123</td>
</tr>
<tr>
<td valign="top" align="left">High-income Asia Pacific</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="center">Both</td>
<td valign="top" align="center">34,240 (24,997&#x2013;45,717)</td>
<td valign="top" align="center">96,838 (70,317&#x2013;129,926)</td>
<td valign="top" align="center">18.702 (13.496&#x2013;24.989)</td>
<td valign="top" align="center">18.753 (14.34&#x2013;24.422)</td>
<td valign="top" align="center">&#x2212;0.21 (&#x2212;0.4 to &#x2212;0.02)</td>
<td valign="top" align="center">182.821</td>
</tr>
<tr>
<td valign="top" align="left">High-income North America</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="center">Both</td>
<td valign="top" align="center">103,076 (77,776&#x2013;134,676)</td>
<td valign="top" align="center">309,288 (234,952&#x2013;391,869)</td>
<td valign="top" align="center">29.891 (22.761&#x2013;38.6)</td>
<td valign="top" align="center">49.089 (38.263&#x2013;61.358)</td>
<td valign="top" align="center">1.93 (1.79&#x2013;2.07)</td>
<td valign="top" align="center">200.058</td>
</tr>
<tr>
<td valign="top" align="left">North Africa and Middle East</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="center">Both</td>
<td valign="top" align="center">118,908 (94,277&#x2013;147,636)</td>
<td valign="top" align="center">334,721 (259,665&#x2013;422,722)</td>
<td valign="top" align="center">78.004 (60.621&#x2013;99.313)</td>
<td valign="top" align="center">79.243 (60.292&#x2013;101.327)</td>
<td valign="top" align="center">0.13 (0.08&#x2013;0.17)</td>
<td valign="top" align="center">181.496</td>
</tr>
<tr>
<td valign="top" align="left">Oceania</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="center">Both</td>
<td valign="top" align="center">901 (696&#x2013;1,154)</td>
<td valign="top" align="center">2,194 (1,698&#x2013;2,797)</td>
<td valign="top" align="center">37.694 (28.605&#x2013;49.137)</td>
<td valign="top" align="center">34.815 (26.246&#x2013;44.726)</td>
<td valign="top" align="center">&#x2212;0.36 (&#x2212;0.42 to &#x2212;0.31)</td>
<td valign="top" align="center">143.507</td>
</tr>
<tr>
<td valign="top" align="left">South Asia</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="center">Both</td>
<td valign="top" align="center">153,342 (118,770&#x2013;192,645)</td>
<td valign="top" align="center">466,689 (346,487&#x2013;613,529)</td>
<td valign="top" align="center">33.92 (26.111&#x2013;43.46)</td>
<td valign="top" align="center">36.202 (26.884&#x2013;47.618)</td>
<td valign="top" align="center">0.19 (0.17&#x2013;0.21)</td>
<td valign="top" align="center">204.345</td>
</tr>
<tr>
<td valign="top" align="left">Southeast Asia</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="center">Both</td>
<td valign="top" align="center">120,672 (95,719&#x2013;152,755)</td>
<td valign="top" align="center">312,751 (242,388&#x2013;396,699)</td>
<td valign="top" align="center">54.752 (43.048&#x2013;69.89)</td>
<td valign="top" align="center">53.198 (41.106&#x2013;68.691)</td>
<td valign="top" align="center">&#x2212;0.19 (&#x2212;0.23 to &#x2212;0.14)</td>
<td valign="top" align="center">159.174</td>
</tr>
<tr>
<td valign="top" align="left">Southern Latin America</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="center">Both</td>
<td valign="top" align="center">12,711 (9,344&#x2013;17,112)</td>
<td valign="top" align="center">32,189 (22,432&#x2013;43,374)</td>
<td valign="top" align="center">28.695 (21.155&#x2013;38.29)</td>
<td valign="top" align="center">35.865 (25.334&#x2013;47.929)</td>
<td valign="top" align="center">0.98 (0.92&#x2013;1.03)</td>
<td valign="top" align="center">153.237</td>
</tr>
<tr>
<td valign="top" align="left">Southern Sub-Saharan Africa</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="center">Both</td>
<td valign="top" align="center">15,635 (11,316&#x2013;20,350)</td>
<td valign="top" align="center">35,176 (26,033&#x2013;45,785)</td>
<td valign="top" align="center">64.103 (47.337&#x2013;85.173)</td>
<td valign="top" align="center">68.6 (51.068&#x2013;90.444)</td>
<td valign="top" align="center">0.24 (0.19&#x2013;0.3)</td>
<td valign="top" align="center">124.982</td>
</tr>
<tr>
<td valign="top" align="left">Tropical Latin America</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="center">Both</td>
<td valign="top" align="center">39,985 (31,018&#x2013;50,768)</td>
<td valign="top" align="center">133,972 (100,547&#x2013;177,427)</td>
<td valign="top" align="center">48.838 (37.747&#x2013;62.345)</td>
<td valign="top" align="center">54.078 (40.721&#x2013;71.847)</td>
<td valign="top" align="center">0.32 (0.29&#x2013;0.36)</td>
<td valign="top" align="center">235.056</td>
</tr>
<tr>
<td valign="top" align="left">Western Europe</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="center">Both</td>
<td valign="top" align="center">128,443 (94,797&#x2013;172,695)</td>
<td valign="top" align="center">356,698 (264,801&#x2013;471,838)</td>
<td valign="top" align="center">21.431 (15.921&#x2013;28.33)</td>
<td valign="top" align="center">32.851 (24.752&#x2013;42.65)</td>
<td valign="top" align="center">2.02 (1.71&#x2013;2.33)</td>
<td valign="top" align="center">177.709</td>
</tr>
<tr>
<td valign="top" align="left">Western Sub-Saharan Africa</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="center">Both</td>
<td valign="top" align="center">63,866 (48,160&#x2013;82,425)</td>
<td valign="top" align="center">146,806 (112,460&#x2013;187,911)</td>
<td valign="top" align="center">83.844 (64.012&#x2013;107.663)</td>
<td valign="top" align="center">86.717 (65.99&#x2013;112.424)</td>
<td valign="top" align="center">0.14 (0.1&#x2013;0.19)</td>
<td valign="top" align="center">129.866</td>
</tr>
</tbody>
</table>
</table-wrap>
<table-wrap id="T2" position="float"><label>Table&#x00A0;2</label>
<caption><p>The YLDs of SHF due to HHD in 1990 and 2021.</p></caption>
<table>
<colgroup>
<col align="left"/>
<col align="left"/>
<col align="left"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
</colgroup>
<thead>
<tr>
<th valign="top" align="left">Locations</th>
<th valign="top" align="left">Cause</th>
<th valign="top" align="left">Sex</th>
<th valign="top" align="center">1990 YLDs cases(95&#x0025; UI)</th>
<th valign="top" align="center">2021 YLDs cases(95&#x0025; UI)</th>
<th valign="top" align="center">1990 ASYR(95&#x0025; UI)</th>
<th valign="top" align="center">2021 ASYR(95&#x0025; UI)</th>
<th valign="top" align="center">1990&#x2212;2021 EAPC (95&#x0025;CI)</th>
<th valign="top" align="center">1990&#x2013;2021 YLDs cases changes</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Global</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">259,063 (164,169&#x2013;376,322)</td>
<td valign="top" align="center">700,272 (440,202&#x2013;1,028,642)</td>
<td valign="top" align="center">6.998 (4.42&#x2013;10.171)</td>
<td valign="top" align="center">8.299 (5.205&#x2013;12.121)</td>
<td valign="top" align="center">0.57 (0.53&#x2013;0.61)</td>
<td valign="top" align="center">170.31</td>
</tr>
<tr>
<td valign="top" align="left">High SDI</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">47,887 (29,448&#x2013;70,046)</td>
<td valign="top" align="center">137,579 (84,087&#x2013;203,139)</td>
<td valign="top" align="center">4.37 (2.706&#x2013;6.367)</td>
<td valign="top" align="center">6.425 (4.014&#x2013;9.342)</td>
<td valign="top" align="center">1.57 (1.46&#x2013;1.68)</td>
<td valign="top" align="center">187.299</td>
</tr>
<tr>
<td valign="top" align="left">High-middle SDI</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">55,736 (33,935&#x2013;82,708)</td>
<td valign="top" align="center">153,745 (94,369&#x2013;226,853)</td>
<td valign="top" align="center">6.031 (3.706&#x2013;8.872)</td>
<td valign="top" align="center">7.843 (4.818&#x2013;11.524)</td>
<td valign="top" align="center">0.88 (0.84&#x2013;0.92)</td>
<td valign="top" align="center">175.845</td>
</tr>
<tr>
<td valign="top" align="left">Low SDI</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">20,861 (13,261&#x2013;30,428)</td>
<td valign="top" align="center">51,110 (33,181&#x2013;74,639)</td>
<td valign="top" align="center">11.121 (7.089&#x2013;16.207)</td>
<td valign="top" align="center">11.524 (7.409&#x2013;16.914)</td>
<td valign="top" align="center">0.13 (0.11&#x2013;0.16)</td>
<td valign="top" align="center">145.003</td>
</tr>
<tr>
<td valign="top" align="left">Low-middle SDI</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">41,104 (26,229&#x2013;60,167)</td>
<td valign="top" align="center">108,037 (68,843&#x2013;158,662)</td>
<td valign="top" align="center">7.984 (5.107&#x2013;11.492)</td>
<td valign="top" align="center">8.371 (5.277&#x2013;12.184)</td>
<td valign="top" align="center">0.11 (0.09&#x2013;0.12)</td>
<td valign="top" align="center">162.838</td>
</tr>
<tr>
<td valign="top" align="left">Middle SDI</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">93,199 (58,090&#x2013;136,290)</td>
<td valign="top" align="center">249,101 (155,822&#x2013;368,407)</td>
<td valign="top" align="center">10.543 (6.577&#x2013;15.364)</td>
<td valign="top" align="center">9.925 (6.197&#x2013;14.562)</td>
<td valign="top" align="center">&#x2212;0.34 (&#x2212;0.46 to &#x2212;0.22)</td>
<td valign="top" align="center">167.279</td>
</tr>
<tr>
<td valign="top" align="left">Andean Latin America</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">1,658 (1,058&#x2013;2,407)</td>
<td valign="top" align="center">4,838 (2,989&#x2013;7,258)</td>
<td valign="top" align="center">8.405 (5.296&#x2013;12.416)</td>
<td valign="top" align="center">8.341 (5.09&#x2013;12.535)</td>
<td valign="top" align="center">0.19 (0.09&#x2013;0.29)</td>
<td valign="top" align="center">191.797</td>
</tr>
<tr>
<td valign="top" align="left">Australasia</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">413 (247&#x2013;602)</td>
<td valign="top" align="center">1,695 (1,032&#x2013;2,462)</td>
<td valign="top" align="center">1.775 (1.084&#x2013;2.573)</td>
<td valign="top" align="center">2.965 (1.803&#x2013;4.342)</td>
<td valign="top" align="center">1.93 (1.82&#x2013;2.05)</td>
<td valign="top" align="center">310.412</td>
</tr>
<tr>
<td valign="top" align="left">Caribbean</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">2,028 (1,291&#x2013;3,005)</td>
<td valign="top" align="center">5,914 (3,681&#x2013;8,915)</td>
<td valign="top" align="center">7.942 (5.045&#x2013;11.703)</td>
<td valign="top" align="center">10.99 (6.843&#x2013;16.563)</td>
<td valign="top" align="center">1.24 (1.18&#x2013;1.3)</td>
<td valign="top" align="center">191.617</td>
</tr>
<tr>
<td valign="top" align="left">Central Asia</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">1,971 (1,189&#x2013;2,966)</td>
<td valign="top" align="center">3,905 (2,294&#x2013;5,981)</td>
<td valign="top" align="center">4.482 (2.66&#x2013;6.786)</td>
<td valign="top" align="center">5.36 (3.055&#x2013;8.227)</td>
<td valign="top" align="center">0.95 (0.74&#x2013;1.16)</td>
<td valign="top" align="center">98.123</td>
</tr>
<tr>
<td valign="top" align="left">Central Europe</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">8,053 (4,706&#x2013;12,061)</td>
<td valign="top" align="center">19,103 (11,181&#x2013;28,383)</td>
<td valign="top" align="center">5.649 (3.351&#x2013;8.33)</td>
<td valign="top" align="center">8.235 (4.878&#x2013;12.124)</td>
<td valign="top" align="center">1.7 (1.55&#x2013;1.85)</td>
<td valign="top" align="center">137.216</td>
</tr>
<tr>
<td valign="top" align="left">Central Latin America</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">5,790 (3,654&#x2013;8,412)</td>
<td valign="top" align="center">15,946 (9,911&#x2013;23,588)</td>
<td valign="top" align="center">7.637 (4.732&#x2013;11.073)</td>
<td valign="top" align="center">6.66 (4.123&#x2013;9.95)</td>
<td valign="top" align="center">&#x2212;0.65 (&#x2212;0.71 to &#x2212;0.58)</td>
<td valign="top" align="center">175.406</td>
</tr>
<tr>
<td valign="top" align="left">Central Sub-Saharan Africa</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">2,177 (1,297&#x2013;3,310)</td>
<td valign="top" align="center">5,991 (3,721&#x2013;9,195)</td>
<td valign="top" align="center">12.316 (7.334&#x2013;18.55)</td>
<td valign="top" align="center">13.349 (8.242&#x2013;20.478)</td>
<td valign="top" align="center">0.29 (0.23&#x2013;0.35)</td>
<td valign="top" align="center">175.195</td>
</tr>
<tr>
<td valign="top" align="left">East Asia</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">86,852 (52,382&#x2013;128,067)</td>
<td valign="top" align="center">227,600 (141,048&#x2013;343,854)</td>
<td valign="top" align="center">12.057 (7.307&#x2013;17.669)</td>
<td valign="top" align="center">10.792 (6.678&#x2013;16.119)</td>
<td valign="top" align="center">&#x2212;0.61 (&#x2212;0.83 to &#x2212;0.39)</td>
<td valign="top" align="center">162.055</td>
</tr>
<tr>
<td valign="top" align="left">Eastern Europe</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">4,377 (2,605&#x2013;6,741)</td>
<td valign="top" align="center">8,694 (4,914&#x2013;14,059)</td>
<td valign="top" align="center">1.611 (0.967&#x2013;2.44)</td>
<td valign="top" align="center">2.402 (1.369&#x2013;3.87)</td>
<td valign="top" align="center">1.72 (1.54&#x2013;1.9)</td>
<td valign="top" align="center">98.629</td>
</tr>
<tr>
<td valign="top" align="left">Eastern Sub-Saharan Africa</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">9,756 (6,124&#x2013;14,472)</td>
<td valign="top" align="center">23,808 (15,363&#x2013;34,959)</td>
<td valign="top" align="center">15.563 (9.777&#x2013;22.697)</td>
<td valign="top" align="center">16.174 (10.426&#x2013;23.744)</td>
<td valign="top" align="center">0.09 (0.07&#x2013;0.11)</td>
<td valign="top" align="center">144.034</td>
</tr>
<tr>
<td valign="top" align="left">High-income Asia Pacific</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">5,971 (3,584&#x2013;8,915)</td>
<td valign="top" align="center">16,711 (10,070&#x2013;25,305)</td>
<td valign="top" align="center">3.251 (1.982&#x2013;4.889)</td>
<td valign="top" align="center">3.262 (1.983&#x2013;4.796)</td>
<td valign="top" align="center">&#x2212;0.21 (&#x2212;0.4 to &#x2212;0.02)</td>
<td valign="top" align="center">179.869</td>
</tr>
<tr>
<td valign="top" align="left">High-income North America</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">17,981 (10,690&#x2013;26,473)</td>
<td valign="top" align="center">53,804 (32,784&#x2013;78,613)</td>
<td valign="top" align="center">5.22 (3.168&#x2013;7.637)</td>
<td valign="top" align="center">8.563 (5.262&#x2013;12.383)</td>
<td valign="top" align="center">1.92 (1.78&#x2013;2.06)</td>
<td valign="top" align="center">199.227</td>
</tr>
<tr>
<td valign="top" align="left">North Africa and Middle East</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">20,467 (13,163&#x2013;29,767)</td>
<td valign="top" align="center">57,870 (37,031&#x2013;84,216)</td>
<td valign="top" align="center">13.308 (8.501&#x2013;19.389)</td>
<td valign="top" align="center">13.619 (8.557&#x2013;19.832)</td>
<td valign="top" align="center">0.15 (0.11&#x2013;0.2)</td>
<td valign="top" align="center">182.748</td>
</tr>
<tr>
<td valign="top" align="left">Oceania</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">155 (98&#x2013;231)</td>
<td valign="top" align="center">380 (231&#x2013;565)</td>
<td valign="top" align="center">6.419 (4.052&#x2013;9.555)</td>
<td valign="top" align="center">5.969 (3.558&#x2013;9.179)</td>
<td valign="top" align="center">&#x2212;0.35 (&#x2212;0.41 to &#x2212;0.29)</td>
<td valign="top" align="center">145.161</td>
</tr>
<tr>
<td valign="top" align="left">South Asia</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">25,772 (16,260&#x2013;37,626)</td>
<td valign="top" align="center">78,804 (48,891&#x2013;117,445)</td>
<td valign="top" align="center">5.63 (3.541&#x2013;8.185)</td>
<td valign="top" align="center">6.07 (3.786&#x2013;8.964)</td>
<td valign="top" align="center">0.22 (0.2&#x2013;0.24)</td>
<td valign="top" align="center">205.774</td>
</tr>
<tr>
<td valign="top" align="left">Southeast Asia</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">20,658 (13,388&#x2013;30,232)</td>
<td valign="top" align="center">53,686 (34,131&#x2013;77,637)</td>
<td valign="top" align="center">9.303 (5.94&#x2013;13.481)</td>
<td valign="top" align="center">9.088 (5.764&#x2013;13.096)</td>
<td valign="top" align="center">&#x2212;0.17 (&#x2212;0.21 to &#x2212;0.12)</td>
<td valign="top" align="center">159.88</td>
</tr>
<tr>
<td valign="top" align="left">Southern Latin America</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">2,216 (1,328&#x2013;3,376)</td>
<td valign="top" align="center">5,578 (3,220&#x2013;8,388)</td>
<td valign="top" align="center">4.988 (3.009&#x2013;7.597)</td>
<td valign="top" align="center">6.221 (3.618&#x2013;9.353)</td>
<td valign="top" align="center">0.98 (0.92&#x2013;1.04)</td>
<td valign="top" align="center">151.715</td>
</tr>
<tr>
<td valign="top" align="left">Southern Sub-Saharan Africa</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">2,690 (1,691&#x2013;4,020)</td>
<td valign="top" align="center">6,076 (3,785&#x2013;9,075)</td>
<td valign="top" align="center">10.98 (6.806&#x2013;16.376)</td>
<td valign="top" align="center">11.794 (7.3&#x2013;17.603)</td>
<td valign="top" align="center">0.25 (0.2&#x2013;0.31)</td>
<td valign="top" align="center">125.874</td>
</tr>
<tr>
<td valign="top" align="left">Tropical Latin America</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">6,872 (4,354&#x2013;9,947)</td>
<td valign="top" align="center">22,973 (13,977&#x2013;34,164)</td>
<td valign="top" align="center">8.335 (5.199&#x2013;12.052)</td>
<td valign="top" align="center">9.263 (5.614&#x2013;13.719)</td>
<td valign="top" align="center">0.32 (0.29&#x2013;0.36)</td>
<td valign="top" align="center">234.299</td>
</tr>
<tr>
<td valign="top" align="left">Western Europe</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">22,279 (13,196&#x2013;33,322)</td>
<td valign="top" align="center">61,628 (36,880&#x2013;90,733)</td>
<td valign="top" align="center">3.717 (2.239&#x2013;5.53)</td>
<td valign="top" align="center">5.701 (3.413&#x2013;8.3)</td>
<td valign="top" align="center">2.02 (1.71&#x2013;2.33)</td>
<td valign="top" align="center">176.619</td>
</tr>
<tr>
<td valign="top" align="left">Western Sub-Saharan Africa</td>
<td valign="top" align="left">Hypertensive heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">10,925 (6,898&#x2013;15,826)</td>
<td valign="top" align="center">25,271 (16,349&#x2013;37,005)</td>
<td valign="top" align="center">14.231 (9.219&#x2013;20.502)</td>
<td valign="top" align="center">14.807 (9.579&#x2013;21.567)</td>
<td valign="top" align="center">0.16 (0.12&#x2013;0.2)</td>
<td valign="top" align="center">131.314</td>
</tr>
</tbody>
</table>
</table-wrap>
<fig id="F1" position="float"><label>Figure&#x00A0;1</label>
<caption><p>EAPC in ASPR and ASYR by global, SDI, and GBD regions from 1990 to 2021 and age-specific ASPR, ASYR, and number in 2021 for HHD, IHD, and RHD. ASPR, age-standardized prevalence rate; ASYR, age-standardized YLD rate; EAPC, estimated annual percentage change; IHD, ischemic heart disease; HHD, hypertensive heart disease; RHD, rheumatic heart disease; SDI, sociodemographic index; GBD, Global Burden of Disease.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="fcvm-13-1649064-g001.tif"><alt-text content-type="machine-generated">Composite figure with multiple bar charts and horizontal bar graphs displaying data by sex and region on Years Lived with Disability (YLDs) from hypertensive heart disease, ischemic heart disease, and rheumatic heart disease. Graphs are grouped by disease, sex (both, female, male), and region or age. Color codes indicate sex.</alt-text>
</graphic>
</fig>
<p>SHF burden due to HHD peaked in the 70&#x2013;74 age group. ASRs increased progressively with age, reaching maximum levels in individuals aged &#x2265;90 years, especially among females. Low SDI regions had the highest standardized SHF burden (ASPR: 67.884; EAPC&#x2009;&#x003D;&#x2009;0.12; ASYR: 11.524; EAPC&#x2009;&#x003D;&#x2009;0.13), while Middle SDI regions had the highest absolute burden (1,451,596 cases; 249,101 YLDs). Notably, ASPR and ASYR showed rising trends predominantly in High and High-middle SDI regions, with declines only observed in Middle SDI regions (<xref ref-type="table" rid="T1">Tables&#x00A0;1</xref>, <xref ref-type="table" rid="T2">2</xref>, <xref ref-type="fig" rid="F1">Figure&#x00A0;1</xref> and <xref ref-type="fig" rid="F2">Figure&#x00A0;2</xref>).</p>
<fig id="F2" position="float"><label>Figure&#x00A0;2</label>
<caption><p>Trends in ASPR and ASYR of HHD, IHD, and RHD by global, sex, and SDI regions, 1990&#x2013;2021. ASPR, age-standardized prevalence rate; ASYR, age-standardized YLD rate; SDI, sociodemographic index.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="fcvm-13-1649064-g002.tif"><alt-text content-type="machine-generated">Grouped line graphs show age-standardized rates of hypertensive, ischemic, and rheumatic heart disease YLDs and prevalence from 1990 to 2020 by SDI (left, five locations) and by sex (right, both, female, male). Each panel&#x2019;s shaded regions represent uncertainty intervals, and trends vary by heart disease type and demographic breakdown.</alt-text>
</graphic>
</fig>
<p>Eastern Sub-Saharan Africa had the highest standardized SHF burden due to HHD (ASPR: 95.038; ASYR: 16.174), whereas East Asia had the largest absolute burden (1,324,469 cases; 227,600 YLDs), despite lower standardized rates (ASPR: 44.308; EAPC&#x2009;&#x003D;&#x2009;&#x2212;0.63; ASYR: 7.573; EAPC&#x2009;&#x003D;&#x2009;&#x2212;0.61). At the national level, China reported the greatest absolute SHF burden (1,274,212 cases; 218,890 YLDs), followed by India and the United States of America. Jordan had the highest national ASPR (111.388) and ASYR (19.201). Latvia showed the steepest rise (ASPR EAPC&#x2009;&#x003D;&#x2009;6.76; ASYR EAPC&#x2009;&#x003D;&#x2009;6.74), while Belarus experienced the sharpest decline (ASPR EAPC&#x2009;&#x003D;&#x2009;&#x2212;3.77; ASYR EAPC&#x2009;&#x003D;&#x2009;&#x2212;3.74) (<xref ref-type="table" rid="T1">Tables&#x00A0;1</xref>, <xref ref-type="table" rid="T2">2</xref>, <xref ref-type="sec" rid="s13">Supplementary Tables S3, S4</xref>, <xref ref-type="fig" rid="F1">Figures&#x00A0;1</xref>, <xref ref-type="fig" rid="F2">2</xref> and <xref ref-type="fig" rid="F3">Figure&#x00A0;3</xref>).</p>
<fig id="F3" position="float"><label>Figure&#x00A0;3</label>
<caption><p>Global distribution of ASPR, ASYR, and EAPC for HHD, IHD, and RHD in 204 countries and territories, 1990&#x2013;2021. ASPR, age-standardized prevalence rate; ASYR, age-standardized YLD rate; EAPC, estimated annual percentage change.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="fcvm-13-1649064-g003.tif"><alt-text content-type="machine-generated">Grid of twelve world maps with inset regional maps, each using color gradients to display various data measures related to GDP per capita growth rates by country and region from 2010 to 2029, with legends indicating specific numeric ranges.</alt-text>
</graphic>
</fig>
</sec>
<sec id="s3a2"><title>Severe heart failure due to IHD</title>
<p>In 2021, SHF resulting from IHD caused 6,242,655 prevalent cases worldwide (ASPR: 74.384 per 100,000; EAPC&#x2009;&#x003D;&#x2009;0.10), increasing by 140.7&#x0025; since 1990. The burden was greater in males (3,351,396 cases; ASPR: 88.469; EAPC&#x2009;&#x003D;&#x2009;0.22) than females (2,891,259 cases; ASPR: 62.290; EAPC&#x2009;&#x003D;&#x2009;&#x2212;0.04). Global SHF-related YLDs due to IHD were 1,075,512 (ASYR: 12.803; EAPC&#x2009;&#x003D;&#x2009;0.10), higher among males (ASYR: 15.246; 579,142 YLDs; EAPC&#x2009;&#x003D;&#x2009;0.22) compared to females (ASYR: 10.699; 496,370 YLDs; EAPC&#x2009;&#x003D;&#x2009;&#x2212;0.05), with consistent ASR trends across sexes over the study period (<xref ref-type="table" rid="T3">Tables&#x00A0;3</xref>, <xref ref-type="table" rid="T4">4</xref>, <xref ref-type="sec" rid="s13">Supplementary Tables S1, S2</xref> and <xref ref-type="fig" rid="F1">Figure&#x00A0;1</xref>).</p>
<table-wrap id="T3" position="float"><label>Table&#x00A0;3</label>
<caption><p>The prevalence of SHF due&#x2013;IHD in 1990 and 2021.</p></caption>
<table>
<colgroup>
<col align="left"/>
<col align="left"/>
<col align="left"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
</colgroup>
<thead>
<tr>
<th valign="top" align="left">Locations</th>
<th valign="top" align="left">Cause</th>
<th valign="top" align="left">Sex</th>
<th valign="top" align="center">1990 prevalence cases(95&#x0025; UI)</th>
<th valign="top" align="center">2021 prevalence cases(95&#x0025; UI)</th>
<th valign="top" align="center">1990 ASPR(95&#x0025; UI)</th>
<th valign="top" align="center">2021 ASPR(95&#x0025; UI)</th>
<th valign="top" align="center">1990&#x2013;2021 EAPC (95&#x0025;CI)</th>
<th valign="top" align="center">1990&#x2013;2021 prevalence cases changes(&#x0025;)</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Global</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">2,593,437 (2,014,066&#x2013;3,290,834)</td>
<td valign="top" align="center">6,242,655 (4,915,567&#x2013;7,878,649)</td>
<td valign="top" align="center">72.303 (56.299&#x2013;92.296)</td>
<td valign="top" align="center">74.384 (58.582&#x2013;93.602)</td>
<td valign="top" align="center">0.1 (0.07&#x2013;0.14)</td>
<td valign="top" align="center">140.71</td>
</tr>
<tr>
<td valign="top" align="left">High SDI</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">995,638 (746,571&#x2013;1,288,470)</td>
<td valign="top" align="center">1,758,646 (1,375,180&#x2013;2,215,851)</td>
<td valign="top" align="center">89.604 (67.644&#x2013;115.61)</td>
<td valign="top" align="center">78.99 (62.727&#x2013;98.248)</td>
<td valign="top" align="center">&#x2212;0.62 (&#x2212;0.7 to &#x2212;0.53)</td>
<td valign="top" align="center">76.635</td>
</tr>
<tr>
<td valign="top" align="left">High-middle SDI</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">690,009 (532,479&#x2013;878,149)</td>
<td valign="top" align="center">1,594,270 (1,254,418&#x2013;2,010,107)</td>
<td valign="top" align="center">76.767 (59.742&#x2013;97.816)</td>
<td valign="top" align="center">81.651 (64.212&#x2013;102.377)</td>
<td valign="top" align="center">0.31 (0.26&#x2013;0.37)</td>
<td valign="top" align="center">131.051</td>
</tr>
<tr>
<td valign="top" align="left">Low SDI</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">83,741 (65,317&#x2013;106,164)</td>
<td valign="top" align="center">226,042 (177,077&#x2013;285,212)</td>
<td valign="top" align="center">44.228 (33.561&#x2013;57.049)</td>
<td valign="top" align="center">50.7 (38.537&#x2013;65.656)</td>
<td valign="top" align="center">0.5 (0.48&#x2013;0.53)</td>
<td valign="top" align="center">169.93</td>
</tr>
<tr>
<td valign="top" align="left">Low-middle SDI</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">299,874 (244,407&#x2013;366,079)</td>
<td valign="top" align="center">845,700 (669,223&#x2013;1,054,400)</td>
<td valign="top" align="center">55.213 (43.888&#x2013;69.18)</td>
<td valign="top" align="center">63.875 (50.267&#x2013;80.518)</td>
<td valign="top" align="center">0.57 (0.54&#x2013;0.61)</td>
<td valign="top" align="center">182.018</td>
</tr>
<tr>
<td valign="top" align="left">Middle SDI</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">520,363 (417,646&#x2013;642,850)</td>
<td valign="top" align="center">1,811,640 (1,414,550&#x2013;2,270,582)</td>
<td valign="top" align="center">58.809 (46.768&#x2013;73.574)</td>
<td valign="top" align="center">72.816 (56.589&#x2013;91.51)</td>
<td valign="top" align="center">0.9 (0.83&#x2013;0.97)</td>
<td valign="top" align="center">248.149</td>
</tr>
<tr>
<td valign="top" align="left">Andean Latin America</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">14,563 (11,517&#x2013;18,390)</td>
<td valign="top" align="center">45,796 (35,593&#x2013;58,975)</td>
<td valign="top" align="center">74.263 (57.814&#x2013;96.136)</td>
<td valign="top" align="center">79.003 (60.568&#x2013;102.692)</td>
<td valign="top" align="center">&#x2212;0.01 (&#x2212;0.14&#x2013;0.13)</td>
<td valign="top" align="center">214.468</td>
</tr>
<tr>
<td valign="top" align="left">Australasia</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">29,586 (22,588&#x2013;38,530)</td>
<td valign="top" align="center">57,763 (45,201&#x2013;73,066)</td>
<td valign="top" align="center">125.113 (95.911&#x2013;163.056)</td>
<td valign="top" align="center">100.069 (79.246&#x2013;125.703)</td>
<td valign="top" align="center">&#x2212;1.36 (&#x2212;1.58 to &#x2212;1.14)</td>
<td valign="top" align="center">95.238</td>
</tr>
<tr>
<td valign="top" align="left">Caribbean</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">26,360 (20,329&#x2013;34,589)</td>
<td valign="top" align="center">45,117 (34,582&#x2013;59,742)</td>
<td valign="top" align="center">106.075 (81.185&#x2013;139.721)</td>
<td valign="top" align="center">83.37 (63.898&#x2013;109.781)</td>
<td valign="top" align="center">&#x2212;0.91 (&#x2212;0.97 to &#x2212;0.86)</td>
<td valign="top" align="center">71.157</td>
</tr>
<tr>
<td valign="top" align="left">Central Asia</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">45,609 (33,065&#x2013;61,458)</td>
<td valign="top" align="center">64,662 (46,539&#x2013;86,450)</td>
<td valign="top" align="center">107.439 (76.449&#x2013;146.041)</td>
<td valign="top" align="center">93.277 (65.834&#x2013;127.075)</td>
<td valign="top" align="center">&#x2212;0.65 (&#x2212;0.75 to &#x2212;0.55)</td>
<td valign="top" align="center">41.775</td>
</tr>
<tr>
<td valign="top" align="left">Central Europe</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">134,701 (101,530&#x2013;175,089)</td>
<td valign="top" align="center">205,971 (160,176&#x2013;260,835)</td>
<td valign="top" align="center">97.442 (74.555&#x2013;126.954)</td>
<td valign="top" align="center">87.903 (69.141&#x2013;110.901)</td>
<td valign="top" align="center">&#x2212;0.4 (&#x2212;0.47 to &#x2212;0.33)</td>
<td valign="top" align="center">52.91</td>
</tr>
<tr>
<td valign="top" align="left">Central Latin America</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">62,986 (50,962&#x2013;77,582)</td>
<td valign="top" align="center">212,632 (167,079&#x2013;265,563)</td>
<td valign="top" align="center">81.046 (64.29&#x2013;101.615)</td>
<td valign="top" align="center">88.053 (69.027&#x2013;110.686)</td>
<td valign="top" align="center">0.31 (0.28&#x2013;0.35)</td>
<td valign="top" align="center">237.586</td>
</tr>
<tr>
<td valign="top" align="left">Central Sub-Saharan Africa</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">7,359 (5,248&#x2013;10,003)</td>
<td valign="top" align="center">19,852 (14,516&#x2013;26,285)</td>
<td valign="top" align="center">44.638 (31.175&#x2013;61.938)</td>
<td valign="top" align="center">46.618 (33.785&#x2013;63.698)</td>
<td valign="top" align="center">0.07 (0.05&#x2013;0.09)</td>
<td valign="top" align="center">169.765</td>
</tr>
<tr>
<td valign="top" align="left">East Asia</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">344,281 (265,344&#x2013;441,136)</td>
<td valign="top" align="center">1,538,293 (1,171,146&#x2013;1,973,700)</td>
<td valign="top" align="center">47.903 (37.166&#x2013;61.622)</td>
<td valign="top" align="center">74.422 (56.939&#x2013;94.8)</td>
<td valign="top" align="center">1.87 (1.68&#x2013;2.06)</td>
<td valign="top" align="center">346.813</td>
</tr>
<tr>
<td valign="top" align="left">Eastern Europe</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">284,752 (220,716&#x2013;361,262)</td>
<td valign="top" align="center">373,085 (289,689&#x2013;478,798)</td>
<td valign="top" align="center">110.438 (85.632&#x2013;140.409)</td>
<td valign="top" align="center">102.904 (80.061&#x2013;131.81)</td>
<td valign="top" align="center">&#x2212;0.21 (&#x2212;0.28 to &#x2212;0.14)</td>
<td valign="top" align="center">31.021</td>
</tr>
<tr>
<td valign="top" align="left">Eastern Sub-Saharan Africa</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">23,974 (17,615&#x2013;32,275)</td>
<td valign="top" align="center">63,142 (46,771&#x2013;84,137)</td>
<td valign="top" align="center">40.709 (29.269&#x2013;56.547)</td>
<td valign="top" align="center">45.016 (32.745&#x2013;61.157)</td>
<td valign="top" align="center">0.3 (0.26&#x2013;0.34)</td>
<td valign="top" align="center">163.377</td>
</tr>
<tr>
<td valign="top" align="left">High-income Asia Pacific</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">73,129 (52,323&#x2013;95,730)</td>
<td valign="top" align="center">202,625 (152,245&#x2013;258,790)</td>
<td valign="top" align="center">39.084 (27.955&#x2013;51.517)</td>
<td valign="top" align="center">42.722 (33.72&#x2013;53.524)</td>
<td valign="top" align="center">0.23 (0.11&#x2013;0.35)</td>
<td valign="top" align="center">177.079</td>
</tr>
<tr>
<td valign="top" align="left">High-income North America</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">388,394 (292,040&#x2013;497,290)</td>
<td valign="top" align="center">630,057 (488,452&#x2013;789,134)</td>
<td valign="top" align="center">107.601 (81.923&#x2013;136.078)</td>
<td valign="top" align="center">91.942 (72.052&#x2013;114.772)</td>
<td valign="top" align="center">&#x2212;0.87 (&#x2212;0.97 to &#x2212;0.76)</td>
<td valign="top" align="center">62.221</td>
</tr>
<tr>
<td valign="top" align="left">North Africa and Middle East</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">157,852 (127,782&#x2013;194,866)</td>
<td valign="top" align="center">450,387 (361,175&#x2013;561,053)</td>
<td valign="top" align="center">97.209 (77.061&#x2013;122.203)</td>
<td valign="top" align="center">103.137 (81.493&#x2013;129.339)</td>
<td valign="top" align="center">0.15 (0.1&#x2013;0.2)</td>
<td valign="top" align="center">185.322</td>
</tr>
<tr>
<td valign="top" align="left">Oceania</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">1,335 (1,045&#x2013;1,697)</td>
<td valign="top" align="center">4,045 (3,208&#x2013;5,156)</td>
<td valign="top" align="center">59.284 (45.873&#x2013;76.694)</td>
<td valign="top" align="center">69.215 (53.704&#x2013;90.454)</td>
<td valign="top" align="center">0.54 (0.5&#x2013;0.57)</td>
<td valign="top" align="center">202.996</td>
</tr>
<tr>
<td valign="top" align="left">South Asia</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">291,010 (236,771&#x2013;351,108)</td>
<td valign="top" align="center">945,521 (749,832&#x2013;1,165,943)</td>
<td valign="top" align="center">56.69 (45.878&#x2013;69.885)</td>
<td valign="top" align="center">69.179 (54.752&#x2013;85.642)</td>
<td valign="top" align="center">0.8 (0.75&#x2013;0.85)</td>
<td valign="top" align="center">224.91</td>
</tr>
<tr>
<td valign="top" align="left">Southeast Asia</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">116,413 (93,623&#x2013;146,374)</td>
<td valign="top" align="center">355,497 (280,008&#x2013;449,660)</td>
<td valign="top" align="center">52.682 (41.366&#x2013;67.07)</td>
<td valign="top" align="center">62.234 (48.921&#x2013;78.939)</td>
<td valign="top" align="center">0.66 (0.62&#x2013;0.69)</td>
<td valign="top" align="center">205.376</td>
</tr>
<tr>
<td valign="top" align="left">Southern Latin America</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">21,496 (15,875&#x2013;28,290)</td>
<td valign="top" align="center">35,284 (25,050&#x2013;47,276)</td>
<td valign="top" align="center">49.436 (36.442&#x2013;65.942)</td>
<td valign="top" align="center">39.946 (28.604&#x2013;53.039)</td>
<td valign="top" align="center">&#x2212;0.88 (&#x2212;0.97 to &#x2212;0.79)</td>
<td valign="top" align="center">64.142</td>
</tr>
<tr>
<td valign="top" align="left">Southern Sub-Saharan Africa</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">13,896 (10,481&#x2013;17,956)</td>
<td valign="top" align="center">29,504 (22,541&#x2013;38,353)</td>
<td valign="top" align="center">58.337 (43.707&#x2013;76.016)</td>
<td valign="top" align="center">59.035 (44.535&#x2013;77.846)</td>
<td valign="top" align="center">0.06 (&#x2212;0.02&#x2013;0.14)</td>
<td valign="top" align="center">112.32</td>
</tr>
<tr>
<td valign="top" align="left">Tropical Latin America</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">47,598 (38,029&#x2013;58,695)</td>
<td valign="top" align="center">140,828 (109,235&#x2013;178,857)</td>
<td valign="top" align="center">58.507 (45.836&#x2013;73.262)</td>
<td valign="top" align="center">56.305 (43.761&#x2013;71.734)</td>
<td valign="top" align="center">&#x2212;0.02 (&#x2212;0.07&#x2013;0.04)</td>
<td valign="top" align="center">195.87</td>
</tr>
<tr>
<td valign="top" align="left">Western Europe</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">484,688 (358,116&#x2013;635,335)</td>
<td valign="top" align="center">758,308 (578,046&#x2013;979,903)</td>
<td valign="top" align="center">82.257 (62.035&#x2013;107.713)</td>
<td valign="top" align="center">73.69 (57.546&#x2013;95.007)</td>
<td valign="top" align="center">&#x2212;0.53 (&#x2212;0.7 to &#x2212;0.37)</td>
<td valign="top" align="center">56.453</td>
</tr>
<tr>
<td valign="top" align="left">Western Sub-Saharan Africa</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">23,455 (17,163&#x2013;31,141)</td>
<td valign="top" align="center">64,287 (47,650&#x2013;84,397)</td>
<td valign="top" align="center">31.459 (22.601&#x2013;42.764)</td>
<td valign="top" align="center">38.876 (28.22&#x2013;52.462)</td>
<td valign="top" align="center">0.74 (0.71&#x2013;0.76)</td>
<td valign="top" align="center">174.087</td>
</tr>
</tbody>
</table>
</table-wrap>
<table-wrap id="T4" position="float"><label>Table&#x00A0;4</label>
<caption><p>The YLDs of SHF due&#x2013;IHD in 1990 and 2021.</p></caption>
<table>
<colgroup>
<col align="left"/>
<col align="left"/>
<col align="left"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
</colgroup>
<thead>
<tr>
<th valign="top" align="left">Locations</th>
<th valign="top" align="left">cause</th>
<th valign="top" align="left">sex</th>
<th valign="top" align="center">1990 YLDs cases(95&#x0025; UI)</th>
<th valign="top" align="center">2021 YLDs cases(95&#x0025; UI)</th>
<th valign="top" align="center">1990 ASYR(95&#x0025; UI)</th>
<th valign="top" align="center">2021 ASYR(95&#x0025; UI)</th>
<th valign="top" align="center">1990&#x2013;2021 EAPC (95&#x0025;CI)</th>
<th valign="top" align="center">1990&#x2013;2021 YLDs cases changes</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Global</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">448,419 (283,192&#x2013;662,990)</td>
<td valign="top" align="center">1,075,512 (683,301&#x2013;1,576,580)</td>
<td valign="top" align="center">12.449 (7.865&#x2013;18.59)</td>
<td valign="top" align="center">12.803 (8.179&#x2013;18.638)</td>
<td valign="top" align="center">0.1 (0.07&#x2013;0.14)</td>
<td valign="top" align="center">139.845</td>
</tr>
<tr>
<td valign="top" align="left">High SDI</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">173,387 (109,050&#x2013;261,732)</td>
<td valign="top" align="center">304,914 (195,771&#x2013;442,525)</td>
<td valign="top" align="center">15.602 (9.872&#x2013;23.391)</td>
<td valign="top" align="center">13.739 (8.864&#x2013;19.843)</td>
<td valign="top" align="center">&#x2212;0.62 (&#x2212;0.7 to &#x2212;0.53)</td>
<td valign="top" align="center">75.857</td>
</tr>
<tr>
<td valign="top" align="left">High-middle SDI</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">119,283 (74,658&#x2013;176,817)</td>
<td valign="top" align="center">274,875 (174,175&#x2013;406,314)</td>
<td valign="top" align="center">13.216 (8.362&#x2013;19.722)</td>
<td valign="top" align="center">14.077 (8.964&#x2013;20.7)</td>
<td valign="top" align="center">0.32 (0.26&#x2013;0.37)</td>
<td valign="top" align="center">130.439</td>
</tr>
<tr>
<td valign="top" align="left">Low SDI</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">14,294 (9,128&#x2013;21,077)</td>
<td valign="top" align="center">38,643 (25,560&#x2013;57,384)</td>
<td valign="top" align="center">7.449 (4.756&#x2013;11.076)</td>
<td valign="top" align="center">8.575 (5.573&#x2013;12.608)</td>
<td valign="top" align="center">0.52 (0.49&#x2013;0.54)</td>
<td valign="top" align="center">170.344</td>
</tr>
<tr>
<td valign="top" align="left">Low-middle SDI</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">51,215 (33,613&#x2013;74,529)</td>
<td valign="top" align="center">144,714 (93,296&#x2013;213,336)</td>
<td valign="top" align="center">9.324 (6.058&#x2013;13.599)</td>
<td valign="top" align="center">10.857 (7.054&#x2013;15.879)</td>
<td valign="top" align="center">0.59 (0.56&#x2013;0.63)</td>
<td valign="top" align="center">182.562</td>
</tr>
<tr>
<td valign="top" align="left">Middle SDI</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">89,579 (58,533&#x2013;130,763)</td>
<td valign="top" align="center">311,268 (198,445&#x2013;460,743)</td>
<td valign="top" align="center">10.021 (6.521&#x2013;14.617)</td>
<td valign="top" align="center">12.468 (7.959&#x2013;18.239)</td>
<td valign="top" align="center">0.92 (0.85&#x2013;0.99)</td>
<td valign="top" align="center">247.479</td>
</tr>
<tr>
<td valign="top" align="left">Andean Latin America</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">2,511 (1,570&#x2013;3,708)</td>
<td valign="top" align="center">7,913 (4,992&#x2013;11,937)</td>
<td valign="top" align="center">12.737 (7.907&#x2013;18.739)</td>
<td valign="top" align="center">13.63 (8.614&#x2013;20.61)</td>
<td valign="top" align="center">0.02 (&#x2212;0.12&#x2013;0.16)</td>
<td valign="top" align="center">215.133</td>
</tr>
<tr>
<td valign="top" align="left">Australasia</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">5,142 (3,148&#x2013;7,703)</td>
<td valign="top" align="center">10,017 (6,359&#x2013;14,879)</td>
<td valign="top" align="center">21.721 (13.518&#x2013;32.219)</td>
<td valign="top" align="center">17.39 (11.131&#x2013;25.73)</td>
<td valign="top" align="center">&#x2212;1.36 (&#x2212;1.59 to &#x2212;1.14)</td>
<td valign="top" align="center">94.807</td>
</tr>
<tr>
<td valign="top" align="left">Caribbean</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">4,549 (2,797&#x2013;6,862)</td>
<td valign="top" align="center">7,774 (4,898&#x2013;11,588)</td>
<td valign="top" align="center">18.251 (11.18&#x2013;27.636)</td>
<td valign="top" align="center">14.376 (9.018&#x2013;21.455)</td>
<td valign="top" align="center">&#x2212;0.91 (&#x2212;0.96 to &#x2212;0.86)</td>
<td valign="top" align="center">70.895</td>
</tr>
<tr>
<td valign="top" align="left">Central Asia</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">7,864 (4,770&#x2013;12,086)</td>
<td valign="top" align="center">11,179 (6,551&#x2013;17,554)</td>
<td valign="top" align="center">18.463 (11.104&#x2013;28.365)</td>
<td valign="top" align="center">16.058 (9.14&#x2013;24.99)</td>
<td valign="top" align="center">&#x2212;0.64 (&#x2212;0.74 to &#x2212;0.54)</td>
<td valign="top" align="center">42.154</td>
</tr>
<tr>
<td valign="top" align="left">Central Europe</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">23,369 (14,334&#x2013;35,047)</td>
<td valign="top" align="center">35,634 (22,390&#x2013;52,961)</td>
<td valign="top" align="center">16.863 (10.468&#x2013;25.258)</td>
<td valign="top" align="center">15.228 (9.645&#x2013;22.569)</td>
<td valign="top" align="center">&#x2212;0.4 (&#x2212;0.47 to &#x2212;0.32)</td>
<td valign="top" align="center">52.484</td>
</tr>
<tr>
<td valign="top" align="left">Central Latin America</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">10,886 (7,206&#x2013;15,703)</td>
<td valign="top" align="center">36,667 (23,682&#x2013;54,176)</td>
<td valign="top" align="center">13.911 (8.831&#x2013;20.557)</td>
<td valign="top" align="center">15.162 (9.712&#x2013;22.361)</td>
<td valign="top" align="center">0.32 (0.29&#x2013;0.36)</td>
<td valign="top" align="center">236.827</td>
</tr>
<tr>
<td valign="top" align="left">Central Sub-Saharan Africa</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">1,268 (762&#x2013;1,996)</td>
<td valign="top" align="center">3,424 (2,100&#x2013;5,342)</td>
<td valign="top" align="center">7.593 (4.657&#x2013;11.872)</td>
<td valign="top" align="center">7.964 (4.898&#x2013;12.304)</td>
<td valign="top" align="center">0.08 (0.06&#x2013;0.11)</td>
<td valign="top" align="center">170.032</td>
</tr>
<tr>
<td valign="top" align="left">East Asia</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">59,410 (37,771&#x2013;87,850)</td>
<td valign="top" align="center">264,495 (167,320&#x2013;394,035)</td>
<td valign="top" align="center">8.192 (5.268&#x2013;12.3)</td>
<td valign="top" align="center">12.773 (8.163&#x2013;18.931)</td>
<td valign="top" align="center">1.89 (1.7&#x2013;2.08)</td>
<td valign="top" align="center">345.203</td>
</tr>
<tr>
<td valign="top" align="left">Eastern Europe</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">49,086 (30,884&#x2013;72,305)</td>
<td valign="top" align="center">64,250 (40,523&#x2013;95,967)</td>
<td valign="top" align="center">18.988 (12.186&#x2013;28.054)</td>
<td valign="top" align="center">17.723 (11.229&#x2013;26.466)</td>
<td valign="top" align="center">&#x2212;0.21 (&#x2212;0.28 to &#x2212;0.14)</td>
<td valign="top" align="center">30.893</td>
</tr>
<tr>
<td valign="top" align="left">Eastern Sub-Saharan Africa</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">4,103 (2,517&#x2013;6,423)</td>
<td valign="top" align="center">10,840 (6,823&#x2013;16,397)</td>
<td valign="top" align="center">6.88 (4.388&#x2013;10.591)</td>
<td valign="top" align="center">7.645 (4.85&#x2013;11.928)</td>
<td valign="top" align="center">0.32 (0.28&#x2013;0.36)</td>
<td valign="top" align="center">164.197</td>
</tr>
<tr>
<td valign="top" align="left">High-income Asia Pacific</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">12,785 (7,963&#x2013;19,820)</td>
<td valign="top" align="center">35,120 (22,805&#x2013;51,064)</td>
<td valign="top" align="center">6.81 (4.26&#x2013;10.422)</td>
<td valign="top" align="center">7.461 (4.925&#x2013;11.049)</td>
<td valign="top" align="center">0.24 (0.12&#x2013;0.37)</td>
<td valign="top" align="center">174.697</td>
</tr>
<tr>
<td valign="top" align="left">High-income North America</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">67,625 (42,025&#x2013;101,632)</td>
<td valign="top" align="center">109,239 (69,989&#x2013;156,574)</td>
<td valign="top" align="center">18.749 (11.801&#x2013;28.047)</td>
<td valign="top" align="center">15.969 (10.27&#x2013;23.035)</td>
<td valign="top" align="center">&#x2212;0.88 (&#x2212;0.98 to &#x2212;0.78)</td>
<td valign="top" align="center">61.536</td>
</tr>
<tr>
<td valign="top" align="left">North Africa and Middle East</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">27,307 (17,919&#x2013;39,850)</td>
<td valign="top" align="center">78,167 (50,327&#x2013;114,200)</td>
<td valign="top" align="center">16.66 (10.708&#x2013;24.375)</td>
<td valign="top" align="center">17.776 (11.652&#x2013;25.987)</td>
<td valign="top" align="center">0.17 (0.12&#x2013;0.21)</td>
<td valign="top" align="center">186.253</td>
</tr>
<tr>
<td valign="top" align="left">Oceania</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">231 (146&#x2013;343)</td>
<td valign="top" align="center">697 (444&#x2013;1,031)</td>
<td valign="top" align="center">10.108 (6.363&#x2013;15.042)</td>
<td valign="top" align="center">11.809 (7.63&#x2013;17.621)</td>
<td valign="top" align="center">0.54 (0.51&#x2013;0.58)</td>
<td valign="top" align="center">201.732</td>
</tr>
<tr>
<td valign="top" align="left">South Asia</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">49,437 (32,606&#x2013;71,498)</td>
<td valign="top" align="center">160,878 (106,309&#x2013;236,348)</td>
<td valign="top" align="center">9.495 (6.253&#x2013;13.744)</td>
<td valign="top" align="center">11.683 (7.598&#x2013;16.981)</td>
<td valign="top" align="center">0.83 (0.78&#x2013;0.88)</td>
<td valign="top" align="center">225.42</td>
</tr>
<tr>
<td valign="top" align="left">Southeast Asia</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">20,002 (12,973&#x2013;29,336)</td>
<td valign="top" align="center">61,101 (39,866&#x2013;90,537)</td>
<td valign="top" align="center">8.956 (5.632&#x2013;13.344)</td>
<td valign="top" align="center">10.633 (6.843&#x2013;15.802)</td>
<td valign="top" align="center">0.68 (0.64&#x2013;0.71)</td>
<td valign="top" align="center">205.474</td>
</tr>
<tr>
<td valign="top" align="left">Southern Latin America</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">3,734 (2,252&#x2013;5,629)</td>
<td valign="top" align="center">6,132 (3,654&#x2013;9,398)</td>
<td valign="top" align="center">8.563 (5.225&#x2013;12.853)</td>
<td valign="top" align="center">6.95 (4.181&#x2013;10.622)</td>
<td valign="top" align="center">&#x2212;0.87 (&#x2212;0.97 to &#x2212;0.78)</td>
<td valign="top" align="center">64.221</td>
</tr>
<tr>
<td valign="top" align="left">Southern Sub-Saharan Africa</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">2,388 (1,534&#x2013;3,568)</td>
<td valign="top" align="center">5,090 (3,289&#x2013;7,657)</td>
<td valign="top" align="center">9.974 (6.415&#x2013;15.056)</td>
<td valign="top" align="center">10.128 (6.54&#x2013;15.245)</td>
<td valign="top" align="center">0.07 (&#x2212;0.01&#x2013;0.15)</td>
<td valign="top" align="center">113.149</td>
</tr>
<tr>
<td valign="top" align="left">Tropical Latin America</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">8,188 (5,215&#x2013;11,889)</td>
<td valign="top" align="center">24,201 (15,517&#x2013;35,996)</td>
<td valign="top" align="center">9.99 (6.34&#x2013;14.568)</td>
<td valign="top" align="center">9.666 (6.213&#x2013;14.378)</td>
<td valign="top" align="center">0 (&#x2212;0.06&#x2013;0.05)</td>
<td valign="top" align="center">195.567</td>
</tr>
<tr>
<td valign="top" align="left">Western Europe</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">84,516 (51,411&#x2013;127,191)</td>
<td valign="top" align="center">131,627 (83,041&#x2013;193,398)</td>
<td valign="top" align="center">14.348 (8.936&#x2013;21.513)</td>
<td valign="top" align="center">12.846 (8.215&#x2013;18.875)</td>
<td valign="top" align="center">&#x2212;0.53 (&#x2212;0.69 to &#x2212;0.37)</td>
<td valign="top" align="center">55.742</td>
</tr>
<tr>
<td valign="top" align="left">Western Sub-Saharan Africa</td>
<td valign="top" align="left">Ischemic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">4,016 (2,524&#x2013;6,195)</td>
<td valign="top" align="center">11,069 (7,009&#x2013;16,795)</td>
<td valign="top" align="center">5.337 (3.421&#x2013;8.166)</td>
<td valign="top" align="center">6.629 (4.219&#x2013;10.218)</td>
<td valign="top" align="center">0.75 (0.73&#x2013;0.78)</td>
<td valign="top" align="center">175.623</td>
</tr>
</tbody>
</table>
</table-wrap>
<p>SHF due to IHD peaked in individuals aged 70&#x2013;74 years, with ASRs rising progressively with advancing age, reaching highest levels among those aged &#x2265;95 years. Females consistently exhibited lower burden than males across most age groups. High-middle SDI regions had the highest standardized burden (ASPR: 81.651; EAPC&#x2009;&#x003D;&#x2009;0.31), while Middle SDI regions carried the greatest absolute burden (1,811,640 cases; 311,268 YLDs) and largest increases in ASPR and ASYR. High SDI regions uniquely showed declining trends (ASPR EAPC&#x2009;&#x003D;&#x2009;&#x2212;0.17; ASYR EAPC&#x2009;&#x003D;&#x2009;&#x2212;0.16) (<xref ref-type="table" rid="T3">Tables&#x00A0;3</xref>, <xref ref-type="table" rid="T4">4</xref>, <xref ref-type="fig" rid="F1">Figures&#x00A0;1</xref>, <xref ref-type="fig" rid="F2">2</xref>).</p>
<p>At the super-region level, North Africa and the Middle East had the highest standardized SHF burden due to IHD (ASPR: 103.137; ASYR: 17.776). China had the largest national absolute burden (1,494,576 cases; 256,916 YLDs), followed by India and the United States of America. Sweden recorded the highest national ASPR (147.253) and ASYR (25.803). Between 1990 and 2021, China had the steepest increases in both ASPR (EAPC&#x2009;&#x003D;&#x2009;1.92) and ASYR (EAPC&#x2009;&#x003D;&#x2009;1.94), while Georgia showed the largest declines (ASPR EAPC&#x2009;&#x003D;&#x2009;&#x2212;3.77; ASYR EAPC&#x2009;&#x003D;&#x2009;&#x2212;3.76) (<xref ref-type="table" rid="T3">Tables&#x00A0;3</xref>, <xref ref-type="table" rid="T4">4</xref>, <xref ref-type="sec" rid="s13">Supplementary Tables S5, S6</xref>, <xref ref-type="fig" rid="F1">Figures&#x00A0;1</xref>&#x2013;<xref ref-type="fig" rid="F3">3</xref>).</p>
</sec>
<sec id="s3a3"><title>Severe heart failure due to RHD</title>
<p>Globally, SHF due to RHD caused 740,018 prevalent cases in 2021 (ASPR: 9.237 per 100,000; EAPC&#x2009;&#x003D;&#x2009;&#x2212;0.53), increasing by 38.95&#x0025; since 1990. Females had higher absolute burden (412,024 cases; ASPR: 9.971; EAPC&#x2009;&#x003D;&#x2009;&#x2212;0.51) compared to males (327,994 cases; ASPR: 8.412; EAPC&#x2009;&#x003D;&#x2009;&#x2212;0.56). SHF-related YLDs reached 129,155 (ASYR: 1.613; EAPC&#x2009;&#x003D;&#x2009;&#x2212;0.53), higher among females (ASYR: 1.737; 71,664 YLDs; EAPC&#x2009;&#x003D;&#x2009;&#x2212;0.52) than males (ASYR: 1.474; 57,491 YLDs; EAPC&#x2009;&#x003D;&#x2009;&#x2212;0.55). Trends in ASRs between sexes were similar over the study period (<xref ref-type="table" rid="T5">Tables&#x00A0;5</xref>, <xref ref-type="table" rid="T6">6</xref>, <xref ref-type="sec" rid="s13">Supplementary Tables S1, S2</xref> and <xref ref-type="fig" rid="F1">Figure&#x00A0;1</xref>).</p>
<table-wrap id="T5" position="float"><label>Table&#x00A0;5</label>
<caption><p>The prevalence of SHF due&#x2013;RHD in 1990 and 2021.</p></caption>
<table>
<colgroup>
<col align="left"/>
<col align="left"/>
<col align="left"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
</colgroup>
<thead>
<tr>
<th valign="top" align="left">Locations</th>
<th valign="top" align="left">Cause</th>
<th valign="top" align="left">Sex</th>
<th valign="top" align="center">1990 prevalence cases(95&#x0025; UI)</th>
<th valign="top" align="center">2021 prevalence cases(95&#x0025; UI)</th>
<th valign="top" align="center">1990 ASPR(95&#x0025; UI)</th>
<th valign="top" align="center">2021 ASPR(95&#x0025; UI)</th>
<th valign="top" align="center">1990&#x2013;2021 EAPC (95&#x0025;CI)</th>
<th valign="top" align="center">1990&#x2013;2021 prevalence cases changes(&#x0025;)</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Global</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">532,566 (441,502&#x2013;641,872)</td>
<td valign="top" align="center">740,018 (605,227&#x2013;906,872)</td>
<td valign="top" align="center">10.603 (8.84&#x2013;12.778)</td>
<td valign="top" align="center">9.237 (7.527&#x2013;11.336)</td>
<td valign="top" align="center">&#x2212;0.53 (&#x2212;0.56 to &#x2212;0.5)</td>
<td valign="top" align="center">38.953</td>
</tr>
<tr>
<td valign="top" align="left">High SDI</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">46,739 (36,788&#x2013;58,468)</td>
<td valign="top" align="center">64,824 (50,144&#x2013;81,826)</td>
<td valign="top" align="center">4.493 (3.592&#x2013;5.531)</td>
<td valign="top" align="center">3.48 (2.826&#x2013;4.25)</td>
<td valign="top" align="center">&#x2212;0.85 (&#x2212;0.96 to &#x2212;0.75)</td>
<td valign="top" align="center">38.694</td>
</tr>
<tr>
<td valign="top" align="left">High-middle SDI</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">70,650 (57,105&#x2013;86,672)</td>
<td valign="top" align="center">91,781 (69,030&#x2013;120,083)</td>
<td valign="top" align="center">6.954 (5.648&#x2013;8.535)</td>
<td valign="top" align="center">5.262 (4.142&#x2013;6.747)</td>
<td valign="top" align="center">&#x2212;1.19 (&#x2212;1.28 to &#x2212;1.1)</td>
<td valign="top" align="center">29.909</td>
</tr>
<tr>
<td valign="top" align="left">Low SDI</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">59,952 (48,910&#x2013;74,989)</td>
<td valign="top" align="center">104,948 (84,367&#x2013;131,020)</td>
<td valign="top" align="center">12.478 (10.278&#x2013;15.256)</td>
<td valign="top" align="center">10.259 (8.36&#x2013;12.631)</td>
<td valign="top" align="center">&#x2212;0.63 (&#x2212;0.65 to &#x2212;0.6)</td>
<td valign="top" align="center">75.053</td>
</tr>
<tr>
<td valign="top" align="left">Low-middle SDI</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">192,636 (157,898&#x2013;234,773)</td>
<td valign="top" align="center">268,803 (222,023&#x2013;330,835)</td>
<td valign="top" align="center">17.559 (14.69&#x2013;21.066)</td>
<td valign="top" align="center">14.581 (12.017&#x2013;17.912)</td>
<td valign="top" align="center">&#x2212;0.68 (&#x2212;0.71 to &#x2212;0.64)</td>
<td valign="top" align="center">39.539</td>
</tr>
<tr>
<td valign="top" align="left">Middle SDI</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">162,209 (134,497&#x2013;195,540)</td>
<td valign="top" align="center">209,309 (166,018&#x2013;257,403)</td>
<td valign="top" align="center">10.729 (8.923&#x2013;12.893)</td>
<td valign="top" align="center">8.49 (6.836&#x2013;10.442)</td>
<td valign="top" align="center">&#x2212;0.87 (&#x2212;0.91 to &#x2212;0.84)</td>
<td valign="top" align="center">29.037</td>
</tr>
<tr>
<td valign="top" align="left">Andean Latin America</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">1,655 (1,329&#x2013;2,048)</td>
<td valign="top" align="center">1,818 (1,477&#x2013;2,237)</td>
<td valign="top" align="center">5.064 (4.12&#x2013;6.177)</td>
<td valign="top" align="center">2.868 (2.328&#x2013;3.518)</td>
<td valign="top" align="center">&#x2212;1.93 (&#x2212;2.01 to &#x2212;1.86)</td>
<td valign="top" align="center">9.849</td>
</tr>
<tr>
<td valign="top" align="left">Australasia</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">1,211 (979&#x2013;1,462)</td>
<td valign="top" align="center">2,469 (2,002&#x2013;2,996)</td>
<td valign="top" align="center">5.519 (4.474&#x2013;6.561)</td>
<td valign="top" align="center">5.633 (4.619&#x2013;6.683)</td>
<td valign="top" align="center">0.19 (0.04&#x2013;0.35)</td>
<td valign="top" align="center">103.881</td>
</tr>
<tr>
<td valign="top" align="left">Caribbean</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">3,089 (2,404&#x2013;3,987)</td>
<td valign="top" align="center">2,562 (2,011&#x2013;3,213)</td>
<td valign="top" align="center">8.213 (6.449&#x2013;10.498)</td>
<td valign="top" align="center">5.633 (4.389&#x2013;7.099)</td>
<td valign="top" align="center">&#x2212;1.45 (&#x2212;1.53 to &#x2212;1.36)</td>
<td valign="top" align="center">&#x2212;17.061</td>
</tr>
<tr>
<td valign="top" align="left">Central Asia</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">6,655 (5,290&#x2013;8,379)</td>
<td valign="top" align="center">4,863 (3,833&#x2013;5,988)</td>
<td valign="top" align="center">9.114 (7.272&#x2013;11.203)</td>
<td valign="top" align="center">5.363 (4.225&#x2013;6.652)</td>
<td valign="top" align="center">&#x2212;1.82 (&#x2212;1.95 to &#x2212;1.68)</td>
<td valign="top" align="center">&#x2212;26.927</td>
</tr>
<tr>
<td valign="top" align="left">Central Europe</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">8,217 (6,543&#x2013;10,246)</td>
<td valign="top" align="center">4,902 (3,762&#x2013;6,375)</td>
<td valign="top" align="center">5.916 (4.783&#x2013;7.31)</td>
<td valign="top" align="center">2.77 (2.258&#x2013;3.425)</td>
<td valign="top" align="center">&#x2212;2.65 (&#x2212;2.89 to &#x2212;2.4)</td>
<td valign="top" align="center">&#x2212;40.343</td>
</tr>
<tr>
<td valign="top" align="left">Central Latin America</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">8,619 (7,193&#x2013;10,493)</td>
<td valign="top" align="center">3,831 (3,035&#x2013;4,805)</td>
<td valign="top" align="center">5.879 (4.918&#x2013;7.054)</td>
<td valign="top" align="center">1.519 (1.202&#x2013;1.907)</td>
<td valign="top" align="center">&#x2212;4.94 (&#x2212;5.12 to &#x2212;4.75)</td>
<td valign="top" align="center">&#x2212;55.552</td>
</tr>
<tr>
<td valign="top" align="left">Central Sub-Saharan Africa</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">4,051 (2,767&#x2013;5,793)</td>
<td valign="top" align="center">6,873 (4,575&#x2013;9,946)</td>
<td valign="top" align="center">6.181 (4.359&#x2013;8.643)</td>
<td valign="top" align="center">4.537 (3.105&#x2013;6.318)</td>
<td valign="top" align="center">&#x2212;1.14 (&#x2212;1.21 to &#x2212;1.07)</td>
<td valign="top" align="center">69.662</td>
</tr>
<tr>
<td valign="top" align="left">East Asia</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">104,756 (84,302&#x2013;128,381)</td>
<td valign="top" align="center">154,517 (112,249&#x2013;205,189)</td>
<td valign="top" align="center">11.092 (8.855&#x2013;13.439)</td>
<td valign="top" align="center">7.52 (5.717&#x2013;9.77)</td>
<td valign="top" align="center">&#x2212;1.57 (&#x2212;1.68 to &#x2212;1.46)</td>
<td valign="top" align="center">47.502</td>
</tr>
<tr>
<td valign="top" align="left">Eastern Europe</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">10,186 (7,899&#x2013;13,053)</td>
<td valign="top" align="center">4,395 (3,035&#x2013;6,200)</td>
<td valign="top" align="center">4.128 (3.285&#x2013;5.233)</td>
<td valign="top" align="center">1.476 (1.088&#x2013;1.954)</td>
<td valign="top" align="center">&#x2212;3.82 (&#x2212;4.1 to &#x2212;3.53)</td>
<td valign="top" align="center">&#x2212;56.853</td>
</tr>
<tr>
<td valign="top" align="left">Eastern Sub-Saharan Africa</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">9,455 (6,618&#x2013;13,139)</td>
<td valign="top" align="center">14,736 (10,159&#x2013;20,296)</td>
<td valign="top" align="center">4.369 (3.178&#x2013;5.83)</td>
<td valign="top" align="center">3.342 (2.427&#x2013;4.507)</td>
<td valign="top" align="center">&#x2212;0.93 (&#x2212;0.97 to &#x2212;0.89)</td>
<td valign="top" align="center">55.854</td>
</tr>
<tr>
<td valign="top" align="left">High-income Asia Pacific</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">5,544 (4,030&#x2013;7,268)</td>
<td valign="top" align="center">8,887 (6,456&#x2013;11,498)</td>
<td valign="top" align="center">2.974 (2.205&#x2013;3.86)</td>
<td valign="top" align="center">2.171 (1.713&#x2013;2.693)</td>
<td valign="top" align="center">&#x2212;1.17 (&#x2212;1.26 to &#x2212;1.08)</td>
<td valign="top" align="center">60.299</td>
</tr>
<tr>
<td valign="top" align="left">High-income North America</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">13,513 (10,357&#x2013;17,415)</td>
<td valign="top" align="center">15,341 (11,542&#x2013;19,703)</td>
<td valign="top" align="center">4.112 (3.218&#x2013;5.206)</td>
<td valign="top" align="center">2.767 (2.151&#x2013;3.451)</td>
<td valign="top" align="center">&#x2212;1.37 (&#x2212;1.76 to &#x2212;0.97)</td>
<td valign="top" align="center">13.528</td>
</tr>
<tr>
<td valign="top" align="left">North Africa and Middle East</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">29,315 (23,249&#x2013;37,317)</td>
<td valign="top" align="center">31,946 (25,675&#x2013;39,845)</td>
<td valign="top" align="center">7.735 (6.279&#x2013;9.628)</td>
<td valign="top" align="center">5.281 (4.26&#x2013;6.517)</td>
<td valign="top" align="center">&#x2212;1.43 (&#x2212;1.5 to &#x2212;1.36)</td>
<td valign="top" align="center">8.975</td>
</tr>
<tr>
<td valign="top" align="left">Oceania</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">951 (738&#x2013;1,228)</td>
<td valign="top" align="center">1,778 (1,382&#x2013;2,265)</td>
<td valign="top" align="center">15.192 (12.257&#x2013;18.658)</td>
<td valign="top" align="center">13.281 (10.746&#x2013;16.424)</td>
<td valign="top" align="center">&#x2212;0.52 (&#x2212;0.55 to &#x2212;0.49)</td>
<td valign="top" align="center">86.961</td>
</tr>
<tr>
<td valign="top" align="left">South Asia</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">240,080 (196,850&#x2013;292,317)</td>
<td valign="top" align="center">376,330 (310,054&#x2013;462,471)</td>
<td valign="top" align="center">23.73 (19.848&#x2013;28.641)</td>
<td valign="top" align="center">21.01 (17.409&#x2013;25.693)</td>
<td valign="top" align="center">&#x2212;0.45 (&#x2212;0.47 to &#x2212;0.42)</td>
<td valign="top" align="center">56.752</td>
</tr>
<tr>
<td valign="top" align="left">Southeast Asia</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">27,912 (22,869&#x2013;34,330)</td>
<td valign="top" align="center">25,772 (21,274&#x2013;31,563)</td>
<td valign="top" align="center">5.5 (4.57&#x2013;6.581)</td>
<td valign="top" align="center">3.883 (3.199&#x2013;4.746)</td>
<td valign="top" align="center">&#x2212;1.35 (&#x2212;1.42 to &#x2212;1.28)</td>
<td valign="top" align="center">&#x2212;7.667</td>
</tr>
<tr>
<td valign="top" align="left">Southern Latin America</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">2,412 (1,942&#x2013;3,000)</td>
<td valign="top" align="center">1,480 (1,141&#x2013;1,871)</td>
<td valign="top" align="center">5.06 (4.059&#x2013;6.276)</td>
<td valign="top" align="center">1.87 (1.466&#x2013;2.32)</td>
<td valign="top" align="center">&#x2212;3.77 (&#x2212;4.1 to &#x2212;3.44)</td>
<td valign="top" align="center">&#x2212;38.64</td>
</tr>
<tr>
<td valign="top" align="left">Southern Sub-Saharan Africa</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">5,974 (4,389&#x2013;7,918)</td>
<td valign="top" align="center">6,333 (4,505&#x2013;8,548)</td>
<td valign="top" align="center">9.422 (7.092&#x2013;12.326)</td>
<td valign="top" align="center">7.668 (5.581&#x2013;10.302)</td>
<td valign="top" align="center">&#x2212;0.69 (&#x2212;0.74 to &#x2212;0.65)</td>
<td valign="top" align="center">6.009</td>
</tr>
<tr>
<td valign="top" align="left">Tropical Latin America</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">10,620 (8,227&#x2013;13,696)</td>
<td valign="top" align="center">8,267 (6,408&#x2013;10,436)</td>
<td valign="top" align="center">6.461 (5.138&#x2013;8.121)</td>
<td valign="top" align="center">3.704 (2.866&#x2013;4.664)</td>
<td valign="top" align="center">&#x2212;2.05 (&#x2212;2.12 to &#x2212;1.98)</td>
<td valign="top" align="center">&#x2212;22.156</td>
</tr>
<tr>
<td valign="top" align="left">Western Europe</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">24,518 (19,222&#x2013;31,117)</td>
<td valign="top" align="center">40,030 (31,380&#x2013;49,575)</td>
<td valign="top" align="center">4.566 (3.661&#x2013;5.68)</td>
<td valign="top" align="center">4.549 (3.674&#x2013;5.561)</td>
<td valign="top" align="center">0.13 (0.05&#x2013;0.2)</td>
<td valign="top" align="center">63.268</td>
</tr>
<tr>
<td valign="top" align="left">Western Sub-Saharan Africa</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">13,832 (9,907&#x2013;18,800)</td>
<td valign="top" align="center">22,889 (15,911&#x2013;31,751)</td>
<td valign="top" align="center">6.275 (4.63&#x2013;8.405)</td>
<td valign="top" align="center">4.304 (3.11&#x2013;5.742)</td>
<td valign="top" align="center">&#x2212;1.4 (&#x2212;1.48 to &#x2212;1.33)</td>
<td valign="top" align="center">65.479</td>
</tr>
</tbody>
</table>
</table-wrap>
<table-wrap id="T6" position="float"><label>Table&#x00A0;6</label>
<caption><p>The YLDs of SHF due&#x2013;RHD in 1990 and 2021.</p></caption>
<table>
<colgroup>
<col align="left"/>
<col align="left"/>
<col align="left"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
</colgroup>
<thead>
<tr>
<th valign="top" align="left">Locations</th>
<th valign="top" align="left">Cause</th>
<th valign="top" align="left">Sex</th>
<th valign="top" align="center">1990 YLDs cases(95&#x0025; UI)</th>
<th valign="top" align="center">2021 YLDs cases(95&#x0025; UI)</th>
<th valign="top" align="center">1990 ASYR(95&#x0025; UI)</th>
<th valign="top" align="center">2021 ASYR(95&#x0025; UI)</th>
<th valign="top" align="center">1990&#x2013;2021 EAPC (95&#x0025;CI)</th>
<th valign="top" align="center">1990&#x2013;2021 YLDs cases changes</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Global</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">93,234 (60,128&#x2013;135,172)</td>
<td valign="top" align="center">129,155 (82,012&#x2013;188,537)</td>
<td valign="top" align="center">1.851 (1.21&#x2013;2.664)</td>
<td valign="top" align="center">1.613 (1.026&#x2013;2.357)</td>
<td valign="top" align="center">&#x2212;0.53 (&#x2212;0.56 to &#x2212;0.5)</td>
<td valign="top" align="center">38.528</td>
</tr>
<tr>
<td valign="top" align="left">High SDI</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">8,200 (5,150&#x2013;12,419)</td>
<td valign="top" align="center">11,300 (7,144&#x2013;16,902)</td>
<td valign="top" align="center">0.79 (0.501&#x2013;1.163)</td>
<td valign="top" align="center">0.611 (0.389&#x2013;0.891)</td>
<td valign="top" align="center">&#x2212;0.86 (&#x2212;0.97 to &#x2212;0.76)</td>
<td valign="top" align="center">37.805</td>
</tr>
<tr>
<td valign="top" align="left">High-middle SDI</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">12,401 (7,993&#x2013;17,825)</td>
<td valign="top" align="center">15,978 (9,648&#x2013;24,251)</td>
<td valign="top" align="center">1.218 (0.789&#x2013;1.749)</td>
<td valign="top" align="center">0.919 (0.57&#x2013;1.377)</td>
<td valign="top" align="center">&#x2212;1.2 (&#x2212;1.29 to &#x2212;1.11)</td>
<td valign="top" align="center">28.844</td>
</tr>
<tr>
<td valign="top" align="left">Low SDI</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">10,477 (6,672&#x2013;15,321)</td>
<td valign="top" align="center">18,396 (11,667&#x2013;27,671)</td>
<td valign="top" align="center">2.167 (1.377&#x2013;3.182)</td>
<td valign="top" align="center">1.784 (1.127&#x2013;2.596)</td>
<td valign="top" align="center">&#x2212;0.62 (&#x2212;0.64 to &#x2212;0.59)</td>
<td valign="top" align="center">75.585</td>
</tr>
<tr>
<td valign="top" align="left">Low-middle SDI</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">33,589 (21,784&#x2013;48,698)</td>
<td valign="top" align="center">46,913 (29,707&#x2013;68,432)</td>
<td valign="top" align="center">3.042 (1.968&#x2013;4.393)</td>
<td valign="top" align="center">2.535 (1.609&#x2013;3.694)</td>
<td valign="top" align="center">&#x2212;0.67 (&#x2212;0.7 to &#x2212;0.63)</td>
<td valign="top" align="center">39.668</td>
</tr>
<tr>
<td valign="top" align="left">Middle SDI</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">28,501 (18,337&#x2013;41,156)</td>
<td valign="top" align="center">36,506 (22,975&#x2013;53,040)</td>
<td valign="top" align="center">1.874 (1.211&#x2013;2.713)</td>
<td valign="top" align="center">1.481 (0.938&#x2013;2.136)</td>
<td valign="top" align="center">&#x2212;0.88 (&#x2212;0.91 to &#x2212;0.84)</td>
<td valign="top" align="center">28.087</td>
</tr>
<tr>
<td valign="top" align="left">Andean Latin America</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">294 (189&#x2013;432)</td>
<td valign="top" align="center">323 (205&#x2013;473)</td>
<td valign="top" align="center">0.893 (0.581&#x2013;1.288)</td>
<td valign="top" align="center">0.508 (0.323&#x2013;0.746)</td>
<td valign="top" align="center">&#x2212;1.93 (&#x2212;2 to &#x2212;1.85)</td>
<td valign="top" align="center">9.864</td>
</tr>
<tr>
<td valign="top" align="left">Australasia</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">213 (136&#x2013;311)</td>
<td valign="top" align="center">432 (268&#x2013;656)</td>
<td valign="top" align="center">0.973 (0.622&#x2013;1.404)</td>
<td valign="top" align="center">0.992 (0.63&#x2013;1.458)</td>
<td valign="top" align="center">0.17 (0.02&#x2013;0.33)</td>
<td valign="top" align="center">102.817</td>
</tr>
<tr>
<td valign="top" align="left">Caribbean</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">545 (340&#x2013;823)</td>
<td valign="top" align="center">456 (290&#x2013;695)</td>
<td valign="top" align="center">1.45 (0.912&#x2013;2.194)</td>
<td valign="top" align="center">1.001 (0.631&#x2013;1.548)</td>
<td valign="top" align="center">&#x2212;1.43 (&#x2212;1.52 to &#x2212;1.35)</td>
<td valign="top" align="center">&#x2212;16.33</td>
</tr>
<tr>
<td valign="top" align="left">Central Asia</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">1,174 (731&#x2013;1,761)</td>
<td valign="top" align="center">868 (528&#x2013;1,282)</td>
<td valign="top" align="center">1.607 (1.022&#x2013;2.375)</td>
<td valign="top" align="center">0.955 (0.576&#x2013;1.415)</td>
<td valign="top" align="center">&#x2212;1.79 (&#x2212;1.92 to &#x2212;1.66)</td>
<td valign="top" align="center">&#x2212;26.065</td>
</tr>
<tr>
<td valign="top" align="left">Central Europe</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">1,446 (920&#x2013;2,146)</td>
<td valign="top" align="center">858 (533&#x2013;1,297)</td>
<td valign="top" align="center">1.042 (0.665&#x2013;1.537)</td>
<td valign="top" align="center">0.488 (0.308&#x2013;0.718)</td>
<td valign="top" align="center">&#x2212;2.65 (&#x2212;2.9 to &#x2212;2.4)</td>
<td valign="top" align="center">&#x2212;40.664</td>
</tr>
<tr>
<td valign="top" align="left">Central Latin America</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">1,531 (985&#x2013;2,193)</td>
<td valign="top" align="center">681 (431&#x2013;1,005)</td>
<td valign="top" align="center">1.04 (0.661&#x2013;1.473)</td>
<td valign="top" align="center">0.27 (0.17&#x2013;0.4)</td>
<td valign="top" align="center">&#x2212;4.92 (&#x2212;5.1 to &#x2212;4.73)</td>
<td valign="top" align="center">&#x2212;55.519</td>
</tr>
<tr>
<td valign="top" align="left">Central Sub-Saharan Africa</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">712 (409&#x2013;1,137)</td>
<td valign="top" align="center">1,226 (706&#x2013;1,940)</td>
<td valign="top" align="center">1.089 (0.624&#x2013;1.715)</td>
<td valign="top" align="center">0.809 (0.48&#x2013;1.271)</td>
<td valign="top" align="center">&#x2212;1.11 (&#x2212;1.19 to &#x2212;1.04)</td>
<td valign="top" align="center">72.191</td>
</tr>
<tr>
<td valign="top" align="left">East Asia</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">18,314 (11,782&#x2013;26,799)</td>
<td valign="top" align="center">26,732 (15,864&#x2013;40,910)</td>
<td valign="top" align="center">1.926 (1.265&#x2013;2.837)</td>
<td valign="top" align="center">1.304 (0.787&#x2013;1.96)</td>
<td valign="top" align="center">&#x2212;1.57 (&#x2212;1.68 to &#x2212;1.46)</td>
<td valign="top" align="center">45.965</td>
</tr>
<tr>
<td valign="top" align="left">Eastern Europe</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">1,802 (1,132&#x2013;2,652)</td>
<td valign="top" align="center">774 (437&#x2013;1,241)</td>
<td valign="top" align="center">0.732 (0.47&#x2013;1.076)</td>
<td valign="top" align="center">0.261 (0.154&#x2013;0.405)</td>
<td valign="top" align="center">&#x2212;3.82 (&#x2212;4.1 to &#x2212;3.55)</td>
<td valign="top" align="center">&#x2212;57.048</td>
</tr>
<tr>
<td valign="top" align="left">Eastern Sub-Saharan Africa</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">1,676 (979&#x2013;2,565)</td>
<td valign="top" align="center">2,629 (1,537&#x2013;4,073)</td>
<td valign="top" align="center">0.774 (0.47&#x2013;1.184)</td>
<td valign="top" align="center">0.595 (0.36&#x2013;0.92)</td>
<td valign="top" align="center">&#x2212;0.91 (&#x2212;0.95 to &#x2212;0.88)</td>
<td valign="top" align="center">56.862</td>
</tr>
<tr>
<td valign="top" align="left">High-income Asia Pacific</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">979 (613&#x2013;1,505)</td>
<td valign="top" align="center">1,547 (951&#x2013;2,357)</td>
<td valign="top" align="center">0.524 (0.326&#x2013;0.799)</td>
<td valign="top" align="center">0.382 (0.238&#x2013;0.566)</td>
<td valign="top" align="center">&#x2212;1.17 (&#x2212;1.26 to &#x2212;1.08)</td>
<td valign="top" align="center">58.018</td>
</tr>
<tr>
<td valign="top" align="left">High-income North America</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">2,378 (1,445&#x2013;3,601)</td>
<td valign="top" align="center">2,682 (1,657&#x2013;4,092)</td>
<td valign="top" align="center">0.725 (0.452&#x2013;1.067)</td>
<td valign="top" align="center">0.486 (0.301&#x2013;0.726)</td>
<td valign="top" align="center">&#x2212;1.38 (&#x2212;1.78 to &#x2212;0.98)</td>
<td valign="top" align="center">12.784</td>
</tr>
<tr>
<td valign="top" align="left">North Africa and Middle East</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">5,196 (3,236&#x2013;7,687)</td>
<td valign="top" align="center">5,688 (3,628&#x2013;8,451)</td>
<td valign="top" align="center">1.368 (0.874&#x2013;2.013)</td>
<td valign="top" align="center">0.939 (0.594&#x2013;1.401)</td>
<td valign="top" align="center">&#x2212;1.41 (&#x2212;1.48 to &#x2212;1.35)</td>
<td valign="top" align="center">9.469</td>
</tr>
<tr>
<td valign="top" align="left">Oceania</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">167 (105&#x2013;252)</td>
<td valign="top" align="center">313 (184&#x2013;485)</td>
<td valign="top" align="center">2.656 (1.711&#x2013;3.869)</td>
<td valign="top" align="center">2.329 (1.431&#x2013;3.538)</td>
<td valign="top" align="center">&#x2212;0.51 (&#x2212;0.54 to &#x2212;0.49)</td>
<td valign="top" align="center">87.425</td>
</tr>
<tr>
<td valign="top" align="left">South Asia</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">41,754 (26,831&#x2013;60,776)</td>
<td valign="top" align="center">65,471 (41,803&#x2013;95,491)</td>
<td valign="top" align="center">4.097 (2.652&#x2013;5.918)</td>
<td valign="top" align="center">3.643 (2.331&#x2013;5.278)</td>
<td valign="top" align="center">&#x2212;0.43 (&#x2212;0.45 to &#x2212;0.41)</td>
<td valign="top" align="center">56.802</td>
</tr>
<tr>
<td valign="top" align="left">Southeast Asia</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">4,955 (3,221&#x2013;7,311)</td>
<td valign="top" align="center">4,595 (2,922&#x2013;6,681)</td>
<td valign="top" align="center">0.976 (0.634&#x2013;1.409)</td>
<td valign="top" align="center">0.692 (0.439&#x2013;1.01)</td>
<td valign="top" align="center">&#x2212;1.34 (&#x2212;1.41 to &#x2212;1.27)</td>
<td valign="top" align="center">&#x2212;7.265</td>
</tr>
<tr>
<td valign="top" align="left">Southern Latin America</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">426 (270&#x2013;637)</td>
<td valign="top" align="center">261 (159&#x2013;395)</td>
<td valign="top" align="center">0.892 (0.56&#x2013;1.331)</td>
<td valign="top" align="center">0.331 (0.201&#x2013;0.495)</td>
<td valign="top" align="center">&#x2212;3.76 (&#x2212;4.09 to &#x2212;3.43)</td>
<td valign="top" align="center">&#x2212;38.732</td>
</tr>
<tr>
<td valign="top" align="left">Southern Sub-Saharan Africa</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">1,054 (628&#x2013;1,646)</td>
<td valign="top" align="center">1,114 (646&#x2013;1,749)</td>
<td valign="top" align="center">1.664 (1.008&#x2013;2.576)</td>
<td valign="top" align="center">1.349 (0.787&#x2013;2.108)</td>
<td valign="top" align="center">&#x2212;0.68 (&#x2212;0.73 to &#x2212;0.64)</td>
<td valign="top" align="center">5.693</td>
</tr>
<tr>
<td valign="top" align="left">Tropical Latin America</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">1,883 (1,153&#x2013;2,812)</td>
<td valign="top" align="center">1,464 (907&#x2013;2,163)</td>
<td valign="top" align="center">1.144 (0.718&#x2013;1.708)</td>
<td valign="top" align="center">0.656 (0.403&#x2013;0.968)</td>
<td valign="top" align="center">&#x2212;2.04 (&#x2212;2.11 to &#x2212;1.97)</td>
<td valign="top" align="center">&#x2212;22.252</td>
</tr>
<tr>
<td valign="top" align="left">Western Europe</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">4,294 (2,609&#x2013;6,493)</td>
<td valign="top" align="center">6,974 (4,360&#x2013;10,300)</td>
<td valign="top" align="center">0.802 (0.498&#x2013;1.183)</td>
<td valign="top" align="center">0.797 (0.511&#x2013;1.155)</td>
<td valign="top" align="center">0.11 (0.04&#x2013;0.19)</td>
<td valign="top" align="center">62.413</td>
</tr>
<tr>
<td valign="top" align="left">Western Sub-Saharan Africa</td>
<td valign="top" align="left">Rheumatic heart disease</td>
<td valign="top" align="left">Both</td>
<td valign="top" align="center">2,441 (1,485&#x2013;3,691)</td>
<td valign="top" align="center">4,069 (2,407&#x2013;6,277)</td>
<td valign="top" align="center">1.108 (0.687&#x2013;1.685)</td>
<td valign="top" align="center">0.765 (0.459&#x2013;1.18)</td>
<td valign="top" align="center">&#x2212;1.38 (&#x2212;1.46 to &#x2212;1.31)</td>
<td valign="top" align="center">66.694</td>
</tr>
</tbody>
</table>
</table-wrap>
<p>SHF burden due to RHD displayed a bimodal age distribution, peaking among individuals aged 5&#x2013;29 and 60&#x2013;84 years, whereas ASRs were predominantly concentrated among individuals aged &#x2265;65 years, with relatively even distribution in elderly groups. Low-middle SDI regions had the highest standardized burden (ASPR: 14.581; EAPC&#x2009;&#x003D;&#x2009;&#x2212;0.68; ASYR: 2.535; EAPC&#x2009;&#x003D;&#x2009;&#x2212;0.67), followed by Low and Middle SDI regions. The largest absolute burden was also observed in Low-middle SDI regions (268,803 cases; 46,913 YLDs). ASPR and ASYR declined across all SDI levels, with the slowest decline in Low SDI and the most pronounced decline in High-middle SDI regions (<xref ref-type="table" rid="T5">Tables&#x00A0;5</xref>, <xref ref-type="table" rid="T6">6</xref>, <xref ref-type="fig" rid="F1">Figures&#x00A0;1</xref>, <xref ref-type="fig" rid="F2">2</xref>).</p>
<p>At the super-region level, South Asia reported the highest standardized SHF burden due to RHD (ASPR: 21.010; EAPC&#x2009;&#x003D;&#x2009;&#x2212;0.45; ASYR: 3.643; EAPC&#x2009;&#x003D;&#x2009;&#x2212;0.43) and the largest absolute burden (376,330 cases; 65,471 YLDs). At the national level, India had the highest absolute burden (290,436 cases; 50,498 YLDs), followed by China and Pakistan. Pakistan showed the highest national ASPR (21.855) and ASYR (3.792). Between 1990 and 2021, the Netherlands experienced the greatest increases in ASPR (EAPC&#x2009;&#x003D;&#x2009;2.27) and ASYR (EAPC&#x2009;&#x003D;&#x2009;2.22), while Guatemala exhibited the sharpest declines (ASPR EAPC&#x2009;&#x003D;&#x2009;&#x2212;5.81; ASYR EAPC&#x2009;&#x003D;&#x2009;&#x2212;5.82) (<xref ref-type="table" rid="T5">Tables&#x00A0;5</xref>, <xref ref-type="table" rid="T6">6</xref>, <xref ref-type="sec" rid="s13">Supplementary Tables S7, S8</xref>, <xref ref-type="fig" rid="F1">Figures&#x00A0;1</xref>&#x2013;<xref ref-type="fig" rid="F3">3</xref>).</p>
</sec>
<sec id="s3a4"><title>Correlation between SHF-related ASRs and sociodemographic development</title>
<p>From 1990 to 2021, ASPR and ASYR of SHF due to HHD, IHD, and RHD demonstrated distinct, non-linear relationships with SDI across the 21 GBD regions. For HHD, both ASPR and ASYR generally declined as SDI increased (ASPR: <italic>&#x03C1;</italic>&#x2009;&#x003D;&#x2009;&#x2013;0.22; ASYR: <italic>&#x03C1;</italic>&#x2009;&#x003D;&#x2009;&#x2013;0.19; <italic>P</italic>&#x2009;&#x003C;&#x2009;0.001), with moderate increases at SDI levels between 0.4 and 0.6, and again slightly above 0.8, indicating a bimodal distribution. In contrast, IHD-related ASPR and ASYR positively correlated with rising SDI, peaking at approximately SDI 0.75 (ASPR: <italic>&#x03C1;</italic>&#x2009;&#x003D;&#x2009;0.45; ASYR: <italic>&#x03C1;</italic>&#x2009;&#x003D;&#x2009;0.47; <italic>P</italic>&#x2009;&#x003C;&#x2009;0.001) and subsequently declining slightly. For RHD, ASPR and ASYR increased rapidly at lower SDI levels, peaked at around SDI&#x223C;0.4, and then decreased markedly, with the decline slowing at higher SDI levels (<italic>&#x03C1;</italic>&#x2009;&#x003D;&#x2009;&#x2013;0.63; <italic>P</italic>&#x2009;&#x003C;&#x2009;0.001) (<xref ref-type="fig" rid="F4">Figure&#x00A0;4</xref>).</p>
<fig id="F4" position="float"><label>Figure&#x00A0;4</label>
<caption><p>Trends in ASPR and ASYR of IHD, HHD, and RHD in 21 GBD regions by SDI from 1990 to 2021 and across countries and territories in 2021. ASPR, age-standardized prevalence rate; ASYR, age-standardized YLD rate; SDI, sociodemographic index; GBD, Global Burden of Disease.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="fcvm-13-1649064-g004.tif"><alt-text content-type="machine-generated">Side-by-side collection of scatterplots and line graphs show relationships between age-standardized rates for rheumatic, ischemic, and hypertensive heart diseases and years lived with disability, with data points color-coded and shaped by world region; all plots are charted against Socio-demographic Index (SDI), and black lines indicate trend curves, with detailed legend at center.</alt-text>
</graphic>
</fig>
<p>In 2021, similar patterns were observed across 204 countries and territories. SHF due to HHD displayed weak negative correlations with national SDI (ASPR: <italic>&#x03C1;</italic>&#x2009;&#x003D;&#x2009;&#x2013;0.45; ASYR: <italic>&#x03C1;</italic>&#x2009;&#x003D;&#x2009;&#x2013;0.45; <italic>P</italic>&#x2009;&#x003C;&#x2009;0.001), predominantly affecting low-SDI countries, although some high-SDI countries also exhibited high rates. SHF due to IHD positively correlated with SDI (ASPR: <italic>&#x03C1;</italic>&#x2009;&#x003D;&#x2009;0.37; ASYR: <italic>&#x03C1;</italic>&#x2009;&#x003D;&#x2009;0.39; <italic>P</italic>&#x2009;&#x003C;&#x2009;0.001), increasing steadily until SDI exceeded &#x223C;0.8, followed by slight declines. SHF from RHD negatively correlated with SDI (ASPR: <italic>&#x03C1;</italic>&#x2009;&#x003D;&#x2009;&#x2013;0.54; ASYR: <italic>&#x03C1;</italic>&#x2009;&#x003D;&#x2009;&#x2013;0.53; <italic>P</italic>&#x2009;&#x003C;&#x2009;0.001), reaching the highest levels around SDI &#x223C;0.5, thereafter declining with rising SDI (<xref ref-type="fig" rid="F4">Figure&#x00A0;4</xref>).</p>
</sec>
<sec id="s3a5"><title>Cross-country and gender inequality in SHF burden</title>
<p>Health inequalities in SHF due to HHD, IHD, and RHD were assessed using regression and concentration curve analyses from 1990 to 2021. For SHF due to HHD, prevalence and YLD rates increasingly concentrated in higher-SDI countries, as shown by regression trends (prevalence fitted values: &#x2212;4&#x2013;35; YLDs: &#x2212;1&#x2013;6). The CI increased notably (prevalence: 0.05&#x2013;0.21; YLDs: 0.06&#x2013;0.22), indicating rising inequality. India and China substantially influenced this burden. For SHF from IHD, burdens remained concentrated in high-SDI countries, with stable regression patterns (prevalence: 74&#x2013;118; YLDs: 13&#x2013;21). The CI slightly decreased from 0.36 to 0.32 for both indicators, reflecting minimal changes in inequality. India and China remained major contributors. In contrast, SHF due to RHD burden concentrated in lower-SDI countries, reflected by negative regression slopes (prevalence: &#x2212;4 to &#x2212;2; YLDs: &#x2212;1&#x2013;0). The CI moderately increased (prevalence: &#x2212;0.22 to &#x2212;0.11; YLDs: &#x2212;0.22 to &#x2212;0.12), suggesting reduced inequality over time. India and China maintained substantial but less disproportionate burdens than in 1990 (<xref ref-type="fig" rid="F5">Figure&#x00A0;5</xref>).</p>
<fig id="F5" position="float"><label>Figure&#x00A0;5</label>
<caption><p>Health inequality regression and concentration curves of ASPR and ASYR for HHD, IHD, and RHD by SDI, 2021. ASPR, age-standardized prevalence rate; ASYR, age-standardized YLD rate; SDI, sociodemographic index; YLD: Years Lived with Disability.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="fcvm-13-1649064-g005.tif"><alt-text content-type="machine-generated">Grid of ten scatter plots and Lorenz curves compare crude prevalence rates and years lived with disability (YLD) rates for disease burden by socioeconomic development index (SDI) across countries, contrasting data from 1990 and 2021. Circle sizes represent population, while blue and orange indicate the respective years. Lorenz curves on the right of each pair show concentration indices, illustrating inequality in disease burden distribution.</alt-text>
</graphic>
</fig>
<p>Gender inequalities were minimal for SHF from HHD. For SHF due to IHD, females showed slightly greater inequalities (CI: 0.35 females vs. 0.30 males). Conversely, males experienced higher inequalities for SHF related to RHD in low-SDI settings (CI: &#x2212;0.18 males vs. &#x2212;0.06 females). Overall, gender disparities were modest compared with cross-country inequalities (<xref ref-type="fig" rid="F6">Figure&#x00A0;6</xref>).</p>
<fig id="F6" position="float"><label>Figure&#x00A0;6</label>
<caption><p>Sex-specific inequality regression and concentration curves of ASPR and ASYR for HHD, IHD, and RHD, 2021. ASPR, age-standardized prevalence rate; ASYR, age-standardized YLD rate; SDI, sociodemographic index; YLD: Years Lived with Disability.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="fcvm-13-1649064-g006.tif"><alt-text content-type="machine-generated">Collection of ten side-by-side scatterplots and line graphs compares crude prevalence rates and years lived with disability (YLD) rates by sex (male in blue, female in orange) across various populations. Population size is indicated by circle size, and graphs are labeled with concentration indices and confidence intervals. Both crude rates and cumulative fractions are shown relative to sociodemographic rank and population.</alt-text>
</graphic>
</fig>
</sec>
<sec id="s3a6"><title>Projected global SHF burden due to HHD, IHD, and RHD</title>
<p>Global SHF burdens from HHD, IHD, and RHD (2022&#x2013;2040) were projected using Nordpred and validated by BAPC. For SHF due to HHD, prevalent cases and YLDs are expected to steadily rise, with stable to slightly increasing ASPR and ASYR. SHF burden from IHD is projected to continuously increase in absolute numbers, while ASPR and ASYR remain relatively stable. SHF from RHD is projected to remain stable or slightly increase in absolute terms, with steady ASPR and ASYR. BAPC models confirmed Nordpred&#x0027;s overall forecasts. Specifically, for SHF from HHD, BAPC indicated slight ASPR and ASYR increases among males but modest declines among females. For SHF from IHD, BAPC projected mild declines in ASPR and ASYR across both sexes. SHF from RHD remained stable, consistent with Nordpred projections (<xref ref-type="fig" rid="F7">Figure&#x00A0;7</xref>).</p>
<fig id="F7" position="float"><label>Figure&#x00A0;7</label>
<caption><p>BAPC(left column) and nordpred(right column) projections of ASPR, ASYR, and number of HHD, IHD, and RHD cases from 2022 to 2040 with prevalence on the first row and YLDs on the second row. ASPR, age-standardized prevalence rate; ASYR, age-standardized YLD rate; BAPC, Bayesian age-period-cohort model; ASR, Age-Standardized Rate.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="fcvm-13-1649064-g007.tif"><alt-text content-type="machine-generated">Four panels of grouped bar charts and line graphs show observed and predicted cases of hypertensive, ischemic, and rheumatic heart disease from 1990 to 2040, segmented by gender. Panels differ by y-axis scale and normalization.</alt-text>
</graphic>
</fig>
</sec>
</sec>
</sec>
<sec id="s4" sec-type="discussion"><title>Discussion</title>
<p>The present study provides a comprehensive overview of the global burden and evolving trends of severe heart failure resulting from HHD, IHD, and RHD from 1990 to 2021, highlighting significant shifts in prevalence, disability burden, and distinct epidemiological patterns. Notably, severe heart failure related to HHD and IHD exhibited marked increases in global prevalence, while severe heart failure resulting from RHD showed relatively modest changes, indicating varied epidemiological transitions and differing public health responses internationally.</p>
<p>Our findings emphasize a substantial rise in severe heart failure prevalence and associated disability burden due to HHD, particularly pronounced in regions with lower SDI, such as Eastern Sub-Saharan Africa. This increase likely stems from demographic changes, notably aging populations, alongside escalating hypertension prevalence driven by rapid urbanization, shifts towards energy-dense diets high in saturated fats, sugars, and sodium, increased sedentary behavior, and inadequate preventive healthcare services, particularly in resource-poor settings (<xref ref-type="bibr" rid="B18">18</xref>, <xref ref-type="bibr" rid="B19">19</xref>). Additionally, limited awareness and poor adherence to antihypertensive treatments may exacerbate progression from hypertension to severe heart failure, highlighting critical gaps in public health education and healthcare accessibility (<xref ref-type="bibr" rid="B20">20</xref>, <xref ref-type="bibr" rid="B21">21</xref>). The disparity between low and high SDI regions underscores a dual epidemiological challenge, with resource-limited areas struggling with persistent high-baseline burdens due to inadequate infrastructure, whereas affluent regions face growing severe heart failure incidence associated with aging populations and lifestyle factors, necessitating tailored intervention programs (<xref ref-type="bibr" rid="B22">22</xref>).</p>
<p>In contrast, severe heart failure resulting from IHD demonstrated significant absolute growth but relatively stable standardized rates, reflecting differing population dynamics and healthcare contexts. Higher-SDI regions exhibited consistently elevated prevalence, likely related to increased life expectancy, improved acute cardiac care prolonging survival, and chronic exposure to cardiovascular risk factors such as diabetes, obesity, smoking, and dyslipidemia, cumulatively leading to advanced disease states including severe heart failure (<xref ref-type="bibr" rid="B23">23</xref>). Rapidly developing regions, particularly East Asia, have faced pronounced increases in severe heart failure due to dietary shifts, and environmental risk factors like air pollution, exacerbating cardiovascular risk profiles despite economic improvements (<xref ref-type="bibr" rid="B24">24</xref>, <xref ref-type="bibr" rid="B25">25</xref>). These trends underscore persistent challenges and suggest economic development alone may be insufficient without parallel advancements in public health infrastructure and preventive interventions (<xref ref-type="bibr" rid="B26">26</xref>, <xref ref-type="bibr" rid="B27">27</xref>).</p>
<p>Severe heart failure due to RHD showed distinct epidemiological characteristics, with a slower global increase and declining trends in standardized prevalence, particularly in high and high-middle SDI regions. The observed bimodal age distribution is consistent with RHD&#x0027;s pathophysiology, linking early-life streptococcal exposure in lower-resource settings to chronic disease progression and eventual heart failure in older populations previously exposed decades earlier (<xref ref-type="bibr" rid="B28">28</xref>, <xref ref-type="bibr" rid="B29">29</xref>). Declines in high-resource settings reflect successful implementation of primary prevention measures such as improved hygiene, widespread antibiotic use, and early medical interventions, significantly reducing progression to severe heart failure (<xref ref-type="bibr" rid="B30">30</xref>). Persistent high burdens in low-resource regions indicate unmet needs in primary and secondary prevention, reflecting broader socioeconomic inequities, insufficient healthcare access, and inadequate sanitation, demanding sustained international efforts and resource allocation (<xref ref-type="bibr" rid="B31">31</xref>).</p>
<p>Gender disparities observed across these cardiovascular conditions further highlight critical public health considerations. Males exhibited higher disability burdens associated with severe heart failure due to HHD and IHD, whereas females disproportionately experienced severe heart failure resulting from RHD. Complex interactions among biological factors, hormonal differences, differential risk factor exposure, health-seeking behaviors, and potential biases in healthcare delivery may drive these disparities, warranting targeted research and interventions to mitigate gender-based inequalities (<xref ref-type="bibr" rid="B32">32</xref>, <xref ref-type="bibr" rid="B33">33</xref>).</p>
<p>Correlation analyses between SDI and severe heart failure burdens due to cardiovascular diseases reveal distinct epidemiological patterns. HHD-related severe heart failure generally declined with higher SDI, yet demonstrated a bimodal distribution indicative of transitional epidemiological dynamics in intermediate SDI regions. These patterns likely result from transitional healthcare infrastructures, partial implementation of effective preventive strategies, and concurrent increases in lifestyle-related risk factors (<xref ref-type="bibr" rid="B34">34</xref>). Conversely, IHD-related severe heart failure prevalence positively correlated with SDI, peaking at intermediate-high SDI levels, possibly due to increased cardiovascular risk factors during economic transitions and varying effectiveness of healthcare interventions across different development stages (<xref ref-type="bibr" rid="B35">35</xref>). Severe heart failure from RHD followed an inverted U-shaped pattern with highest prevalence in transitioning regions, reflecting disparities in healthcare accessibility, sanitation, and prevention strategies (<xref ref-type="bibr" rid="B36">36</xref>, <xref ref-type="bibr" rid="B37">37</xref>).</p>
<p>Significant cross-country inequalities and gender-specific differences in severe heart failure burdens underscore broader systemic health inequities. Increased concentration of HHD-related severe heart failure in higher SDI countries highlights persistent lifestyle risk factors despite advanced healthcare, emphasizing preventive strategies alongside economic growth (<xref ref-type="bibr" rid="B38">38</xref>, <xref ref-type="bibr" rid="B39">39</xref>). Persistent high burdens of severe heart failure from IHD in affluent nations illustrate ongoing challenges posed by traditional cardiovascular risks, requiring intensified public health measures (<xref ref-type="bibr" rid="B18">18</xref>, <xref ref-type="bibr" rid="B23">23</xref>). The dominance of RHD-related severe heart failure in lower-SDI settings highlights fundamental socioeconomic disparities, underscoring the need for targeted interventions addressing social determinants of health (<xref ref-type="bibr" rid="B28">28</xref>, <xref ref-type="bibr" rid="B39">39</xref>).</p>
<p>Future projections indicate divergent ways in severe heart failure burdens from these diseases, necessitating continuous monitoring and adaptive strategies. Stable or increasing HHD-related severe heart failure emphasizes enhanced hypertension management in resource-limited settings. Anticipated declines in IHD-related severe heart failure suggest advancements in preventive medicine; however, demographic aging may sustain overall burdens, emphasizing holistic risk management policies (<xref ref-type="bibr" rid="B40">40</xref>, <xref ref-type="bibr" rid="B41">41</xref>). Stable burdens projected for RHD-related severe heart failure highlight significant public health challenges, particularly where prevention remains inadequate, necessitating sustained international cooperation and healthcare infrastructure investments (<xref ref-type="bibr" rid="B31">31</xref>).</p>
</sec>
<sec id="s5"><title>Limitations</title>
<p>This study&#x0027;s strengths include extensive global coverage, longitudinal analysis, and incorporation of socioeconomic determinants, enhancing understanding of severe heart failure epidemiology. Several limitations should be acknowledged in the interpretation of this study. Although the GBD study provides extensive global coverage with standardized methods, inherent variations in the quality, completeness, and reporting practices of data across different countries and regions may introduce bias. Our projections were conducted using Nordpred and validated by the Bayesian Age-Period-Cohort (BAPC) model, but these predictions depend on assumptions regarding current epidemiological, demographic, and healthcare trends continuing unchanged into the future. Sudden changes in risk factors, healthcare policy, or global health events may significantly alter actual future burdens. While we explored correlations between severe heart failure burdens and the SDI, other potentially relevant socioeconomic, behavioral, and environmental factors were not explicitly assessed, and their contributions to the disease burden may thus have been overlooked.</p>
</sec>
<sec id="s6" sec-type="conclusions"><title>Conclusion</title>
<p>The global and regional burdens of severe heart failure attributable to HHD, IHD, and RHD exhibited distinct epidemiological patterns from 1990 to 2021, underscoring significant health inequities across different SDI settings and between genders. While HHD and IHD related severe heart failure burdens continue to rise substantially, particularly driven by demographic aging and lifestyle factors, RHD related severe heart failure burdens remained relatively stable, reflecting uneven implementation of preventive measures globally. Projections to 2040 highlight ongoing challenges, with increasing prevalent cases and disability burdens, particularly for HHD and IHD, emphasizing the critical need for enhanced prevention, targeted public health interventions, and equitable healthcare resource allocation. Future public health strategies should prioritize addressing socioeconomic disparities, reinforcing primary and secondary prevention measures, and strengthening global cooperation to effectively mitigate the severe heart failure burden.</p>
</sec>
</body>
<back>
<sec id="s7" sec-type="data-availability"><title>Data availability statement</title>
<p>The original contributions presented in the study are included in the article/<xref ref-type="sec" rid="s13">Supplementary Material</xref>, further inquiries can be directed to the corresponding authors.</p>
</sec>
<sec id="s8" sec-type="ethics-statement"><title>Ethics statement</title>
<p>Ethical approval was not required for the study involving humans in accordance with the local legislation and institutional requirements. Written informed consent to participate in this study was not required from the participants or the participants&#x2019; legal guardians/next of kin in accordance with the national legislation and the institutional requirements.</p>
</sec>
<sec id="s9" sec-type="author-contributions"><title>Author contributions</title>
<p>GX: Data curation, Conceptualization, Resources, Software, Writing &#x2013; review &#x0026; editing. YH: Data curation, Investigation, Project administration, Validation, Writing &#x2013; original draft. SS: Validation, Conceptualization, Formal analysis, Resources, Supervision, Writing &#x2013; original draft. WJ: Conceptualization, Formal analysis, Supervision, Writing &#x2013; original draft. XW: Formal analysis, Writing &#x2013; original draft, Investigation, Methodology, Validation. ZG: Methodology, Data curation, Project administration, Writing &#x2013; review &#x0026; editing. ZW: Investigation, Supervision, Visualization, Writing &#x2013; review &#x0026; editing.</p>
</sec>
<sec id="s11" sec-type="COI-statement"><title>Conflict of interest</title>
<p>The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec id="s12" sec-type="ai-statement"><title>Generative AI statement</title>
<p>The author(s) declared that generative AI was not used in the creation of this manuscript.</p>
<p>Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.</p>
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<sec id="s13" sec-type="supplementary-material"><title>Supplementary material</title>
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<supplementary-material xlink:href="Table1.docx" id="SM1" mimetype="application/vnd.openxmlformats-officedocument.wordprocessingml.document"/>
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<fn-group>
<fn id="n1" fn-type="custom" custom-type="edited-by"><p>Edited by: <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/1440639/overview">Alicia Del Saz Lara</ext-link>, University of Castilla-La Mancha, Spain</p></fn>
<fn id="n2" fn-type="custom" custom-type="reviewed-by"><p>Reviewed by: <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/1313697/overview">Yuling Yu</ext-link>, Guangdong Academy of Medical Sciences, China</p>
<p><ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/3028128/overview">Taner Ulus</ext-link>, Eski&#x015F;ehir Osmangazi University, T&#x00FC;rkiye</p></fn>
<fn fn-type="abbr" id="abbrev1"><p>Abbreviations ASPR, age-standardized prevalence rate; ASYR, age-standardized YLD rate; ASR, Age-standardized rate; BAPC, Bayesian age-period-cohort; CI, concentration index; EAPC, estimated annual percentage change; GBD, Global burden of disease; HHD, hypertensive heart disease; IHD, ischemic heart disease; RHD, rheumatic heart disease; SDI, sociodemographic index; SHF, severe heart failure; YLD, years lived with disability.</p></fn>
</fn-group>
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</article>