Hypertension and depression represent two critical global health concerns. Hypertension is a major modifiable risk factor for cardiovascular disease, the leading cause of death worldwide. Its prevalence and clinical management in older adult populations are particularly challenging due to physiological vulnerability, multimorbidity, and polypharmacy (1). Depression affects over 300 million individuals worldwide, substantially reducing quality of life and aggravating chronic illnesses, particularly in older adult. Increasing evidence suggests a bidirectional and complex interplay between hypertension and depression, highlighting the importance of considering their joint impact on patient outcomes (2, 3). For instance, depressive symptoms can contribute to the development and poor management of hypertension, and in turn, hypertension can exacerbate depressive states (1, 3). Specifically, studies such as the Hypertension in the Very Older adult Trial (HYVET) have shown that older adult individuals with hypertension and depressive symptoms have higher risks of cardiovascular morbidity and mortality, as well as cognitive decline (1).

Recent epidemiological studies have provided additional support for this association. Almeida et al. demonstrated that depression significantly elevates the risk of cardiovascular events and mortality in older men (2). Furthermore, the SPRINT trial indicated that depressive symptoms in hypertensive patients are strongly correlated with adverse clinical outcomes, including all-cause mortality (4). Other cohort studies have found consistent results among diverse populations, highlighting mood disorders as important determinants of cardiometabolic health trajectories and life expectancy in older adult populations (3, 5, 6). Given these findings, it is evident that the interaction between depression and hypertension profoundly influences health outcomes in older adult.

Although several prior meta-analyses have investigated the association between depression and mortality among hypertensive patients, important gaps remain. Many previous studies have limitations such as short follow-up durations, inconsistent adjustment for confounding factors, and a lack of comprehensive subgroup analyses (e.g., by gender or follow-up period). Additionally, few studies have focused specifically on older adult populations, who may have unique clinical characteristics and higher vulnerability. Therefore, our review aims to address these gaps by synthesizing the most recent evidence, incorporating detailed subgroup and sensitivity analyses, and providing updated insights into the impact of depression on mortality in older adult hypertensive patients.

Despite accumulating evidence, the relationship between depression and hypertension in older adult populations remains inadequately understood, particularly concerning long-term prognosis and underlying mechanisms. Older adult frequently experience multimorbidity and require complex medication regimens, conditions that may influence both cardiovascular outcomes and overall quality of life (3, 5). Thus, elucidating how depression exacerbates hypertension-related complications through physiological, psychological, and behavioral pathways is critically important. Comprehensive management strategies addressing depression could significantly impact cardiovascular health, potentially reducing the risk of mortality and morbidity in this high-risk population.

This study aims to systematically evaluate the impact of depression on the long-term prognosis of older adult patients with hypertension, specifically focusing on all-cause mortality and cardiovascular risks. The primary objectives of this study are as follows:

This study was designed and reported following the PRISMA guidelines. By synthesizing existing research data, this review aims to offer a new perspective on how mental health status influences the health outcomes of older adult hypertensive patients.

The protocol for this study was prospectively registered in PROSPERO (CRD420251019904), an international database of prospectively registered systematic reviews.

To clarify the scope and eligibility of this systematic review, we formulated the review question using the PECOS framework: Population (P):** Older adult patients (aged ≥60 years) with hypertension; Exposure (E): Depression or depressive symptoms, as assessed by clinical diagnosis or validated scales; Comparator (C): Older adult hypertensive patients without depression; Outcomes (O): All-cause mortality, cardiovascular mortality, and major adverse cardiovascular events; Study Design (S): Cohort studies (prospective or retrospective), randomized controlled trials, and longitudinal studies.

To comprehensively collect studies evaluating the impact of depression and hypertension on cardiovascular health in older adult populations, we systematically searched the following databases: PubMed, Embase, Cochrane Library, and Web of Science. The search period was restricted to 2010 to 2024 in order to capture the most up-to-date treatment strategies, diagnostic criteria, and research methodologies related to hypertension and depression. This timeframe also aligns with the publication of the majority of large-scale cohort studies and registry data in this field.

This approach aimed to enhance the clinical relevance and consistency of the included studies. Only English-language studies were included due to their typically rigorous peer-review standards and broader international recognition. Although these restrictions might introduce potential language and time-related biases, we believe this approach ensures higher consistency, relevance, and methodological quality of the studies included. The search terms included: (“Hypertension” or “High blood pressure” or “Essential hypertension”) and (“Depression” or “Depressive Disorder” or “Depressive symptoms” or “Major depression” or “Mental health”) and (“Prognosis” or “Mortality” or “Survival Analysis” or “Cardiovascular Events” or “Long-term outcome” or “All-cause mortality” or “Major Adverse Cardiovascular Events” or “MACE”) and (“Cohort Studies” or “Longitudinal Studies” or “Follow-Up Studies” or “Prospective Studies” or “Retrospective Studies” or “Randomized Controlled Trial” or “RCT”) and (“Aged” or “Aged, 80 and over” or “Older adult” or “Older adult” or “Geriatric” or “Aging population” or “≥60 years”).

Five reviewers independently screened titles and abstracts, retrieved full texts, and selected eligible studies according to the predefined PECOS framework. The inclusion criteria were as follows:

Exclusion criteria: Studies were excluded if they focused on non-older adult populations, did not assess depression in hypertensive patients, examined only short-term blood pressure fluctuations, or were case reports, conference abstracts, review articles, commentaries, or had incomplete data or insufficient information to calculate effect estimates.

To ensure data accuracy and study objectivity, four reviewers independently performed data extraction and quality assessment, with all procedures supervised by the first author. Any disagreements were resolved through team discussions to reach a consensus. The following data were extracted from eligible studies: first author, year of publication, study region, study design type, follow-up duration, sample size, mean age of participants, gender distribution, depression assessment tools, primary study outcomes, hazard ratio (HR) with 95% confidence interval (CI) and p-value, as well as covariates considered for adjustment.

We used the Cochrane Risk of Bias Tool to assess the quality of randomized controlled trials (RCTs), categorizing studies into low risk of bias, some concerns, and high risk of bias. For cohort studies, we adopted the Quality in Prognosis Studies (QUIPS) tool, which evaluates six domains: study participation, study attrition, prognostic factor measurement, outcome measurement, study confounding, and statistical analysis and reporting. Each domain was judged as having a low, moderate, or high risk of bias. A traffic light plot was generated to visualize the risk-of-bias judgments across all included studies (Figure 1).

All statistical analyses were performed using Stata 18.0 software.

First, study results were pooled to assess the association between depression and mortality in older adult hypertensive patients. To evaluate heterogeneity across studies, Cochran’s Q test and I² statistics were applied. Given the significant clinical heterogeneity of depression, all analyses were conducted using a random-effects model.

Second, to explore potential sources of heterogeneity, subgroup analyses were performed based on patient gender, sample size, follow-up duration, and depression assessment tools. Sensitivity analysis was conducted by sequentially excluding each study to evaluate the robustness of the overall risk estimate. Additionally, potential publication bias was assessed using funnel plots, Begg’s rank correlation test, and Egger’s regression test. The symmetry of the funnel plot was examined visually, while Begg’s and Egger’s statistical tests were used to quantify the potential impact of small-study effects. A statistical significance level of p < 0.05 was set for all tests.

Finally, the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach was employed to comprehensively assess the quality of evidence, ensuring the credibility and applicability of the study findings.

A total of 443 potentially relevant studies were identified through the initial database search. After removing duplicates and screening titles and abstracts, 78 studies were selected for full-text review. Following a detailed evaluation, 65 studies were excluded based on the predefined exclusion criteria. Finally, 2 randomized controlled trials and 11 cohort studies (1–13) were included in the final meta-analysis. The study selection process is detailed in Figure 2.

The characteristics of the included studies are summarized in Table 1. These studies were published between 2010 and 2024 and were conducted across multiple countries and regions. The total number of participants covered in the included studies was 483,560, with individual study sample sizes ranging from 555 to 261,297. The follow-up period varied between 2.1 years and 13.3 years. The included studies reported outcomes such as all-cause mortality, cardiovascular mortality and fatal stroke.

The tools used to assess depression included the 15-item Geriatric Depression Scale (GDS-15), the Center for Epidemiologic Studies Depression Scale (CES-D), the Patient Health Questionnaire-9 (PHQ-9), the Geriatric Mental State Examination (GMS), and the International Classification of Diseases, 10th Revision (ICD-10) diagnosis.

Risk of bias assessments were performed for all included studies. The two randomized controlled trials were evaluated using the Cochrane Risk of Bias Tool and were classified as having some concerns. For the 13 included cohort studies, the Quality in Prognosis Studies (QUIPS) tool was used to assess domain-specific risks of bias. While most studies were rated as low risk in prognostic factor and outcome measurements, moderate risk was frequently identified in confounding and participation domains. Details are provided in Supplementary Text 1 and Figure 1.

A random-effects model was used for meta-analysis, and the results are presented in Figure 3. The analysis showed that depression was significantly associated with an increased the risk of mortality in older adult hypertensive patients, with a pooled hazard ratio (HR) of 1.32 (95% confidence interval: 1.23–1.41). As illustrated in the figure, 11 out of the 13 included studies reported an HR greater than 1, indicating an increased mortality risk associated with depression. Among these, four studies had 95% confidence intervals that did not include 1, suggesting statistically significant effects of depression on mortality. The heterogeneity among studies was moderate (I² = 38.2%, p = 0.079), indicating some degree of variability between studies while maintaining an overall consistent trend. The sample sizes across studies ranged from 555 to 261,297, ensuring the representativeness of this meta-analysis. These findings suggest that depression is associated with an increased mortality risk among older adult hypertensive patients. Therefore, depression screening and psychological interventions should be incorporated into hypertension management strategies to mitigate adverse prognostic outcomes.

To assess potential publication bias, a funnel plot was generated (Figure 4). The funnel plot exhibited slight asymmetry, particularly with fewer studies observed in the lower left region, which may indicate the presence of potential publication bias. However, statistical tests for publication bias, including Begg’s test (p = 0.428) and Egger’s test (p = 0.985), did not reveal statistically significant bias. This suggests that, despite some asymmetry in the funnel plot, publication bias is unlikely to have a substantial impact on the overall findings of this study.

To explore the sources of heterogeneity, subgroup analyses were conducted based on gender, sample size, follow-up duration, and depression assessment methods (Table 2).

The overall GRADE assessment indicated that the quality of evidence was moderate (detailed information available in Supplementary Text 2).

Depression is associated with increased all-cause mortality in older adult hypertensive patients. This association is likely driven by physiological and behavioral mechanisms, such as autonomic dysfunction, chronic inflammation, and poor adherence to treatment.

In summary, depression exacerbates the long-term prognosis of hypertensive patients through multiple mechanisms, including sympathetic nervous system activation, HPA axis dysregulation, chronic inflammatory states, and unhealthy lifestyle behaviors.

In addition to increased all-cause mortality, several studies also reported a higher risk of fatal stroke in depressed older adult hypertensive patients. This elevated risk may be explained by similar pathophysiological pathways, including systemic inflammation, vascular endothelial dysfunction, and platelet hyperreactivity. These processes can predispose individuals to acute cerebrovascular events, further underscoring the importance of mental health management in this population.

This finding is consistent with a recent meta-analysis by Ashraf et al. (14), which demonstrated that depression significantly increases the risk of stroke, including ischemic, hemorrhagic, and fatal subtypes (HR = 1.41, 95% CI: 1.32–1.50), with variations by follow-up duration. Their findings underscore the broader vascular impact of depression and reinforce the importance of integrated mental health strategies in cardiovascular disease prevention. Our study extends this perspective by focusing specifically on all-cause mortality in older adult hypertensive patients, further highlighting the multifactorial burden of depression in this high-risk population.

The association between depression and mortality appeared stronger in women than in men, which aligns with findings from previous studies. This may be due to hormonal changes post-menopause, which influence cardiovascular regulation, and increased psychosocial stress from loneliness and caregiving responsibilities (3, 4). These findings highlight the need for gender-specific interventions in hypertension and mental health care. This stronger association may also reflect cumulative effects of inflammation, autonomic dysregulation, and mood instability, which disproportionately affect older women.

The association between depression and mortality risk persisted across both short-term and long-term follow-up periods. In our study, short follow-up (<10 years) showed a higher risk (HR = 1.40, 95% CI: 1.25–1.56), likely due to acute cardiovascular events and comorbidities, while long-term follow-up (≥10 years) confirmed a persistent, though slightly attenuated, effect (HR = 1.27, 95% CI: 1.17–1.37). These findings underscore the necessity of sustained psychological health management for hypertensive patients.

Despite variations in depression assessment tools (GDS-15, CES-D, ICD-10, PHQ-9), the overall trend remained consistent, confirming the robustness of findings. However, studies using ICD-10 showed the highest heterogeneity (I² = 79.8%), highlighting the need for standardized diagnostic criteria in future research.

The observed heterogeneity across studies may, in part, be attributed to differences in depression assessment tools. Instruments such as PHQ-9 and CES-D are self-reported symptom scales with lower diagnostic thresholds and high sensitivity, which may identify milder or subclinical cases. In contrast, ICD-10 relies on structured clinical diagnosis and may capture more severe depression. These differences in diagnostic rigor and symptom threshold likely affect which participants are classified as depressed, thus contributing to variability in effect estimates. The high heterogeneity observed in the ICD-10 subgroup may also reflect inconsistencies in the application of diagnostic criteria across different healthcare settings.

The findings of this study have significant clinical implications for hypertension management and cardiovascular disease prevention. While hypertension management traditionally focuses on blood pressure control, our results emphasize the need to integrate mental health assessment. Based on these findings, three key strategies warrant further attention:

Our findings suggest that integrating depression screening and treatment into hypertension management for older adult patients could help reduce both mortality and healthcare costs. Depression in this population increases healthcare utilization and resource burden. Early intervention may improve patient outcomes and lessen the financial strain on health systems. These results support multidisciplinary care models addressing both physical and mental health in older adult with hypertension.

While this meta-analysis confirmed a significant association between depression and increased mortality risk in older adult hypertensive patients, several limitations should be considered when interpreting these findings.

First, the included studies varied in study design, geographic regions, sample characteristics, and adjustment variables, contributing to heterogeneity despite the use of a random-effects model. Residual confounding cannot be ruled out, as unmeasured or inadequately adjusted variables—such as differences in depression diagnostic criteria, socioeconomic status, comorbidities, and antidepressant use—may have influenced the results. As the included studies are observational in nature, causality cannot be inferred from the reported associations. Future research should refine patient stratification and focus on more homogeneous populations to improve generalizability.

Second, differences in depression assessment tools may have introduced bias. While ICD-10 likely identifies more severe cases, CES-D and PHQ-9 capture a broader spectrum of depressive symptoms, leading to variability in effect estimates. The highest heterogeneity was observed in ICD-10 studies (I² = 79.8%), highlighting the need for standardized diagnostic tools in future research.

Third, follow-up durations ranged from 2.1 to 13.3 years, with some studies having shorter observation periods, potentially limiting the ability to assess long-term effects. Future studies should prioritize long-term prospective cohorts to clarify depression’s sustained impact on hypertensive patients and mitigate potential biases from short-term stress responses.

Finally, while Begg’s (p = 0.428) and Egger’s (p = 0.985) tests did not indicate significant publication bias, the potential for selective reporting and underrepresentation of null results remains, as suggested by the slight funnel plot asymmetry. Studies with statistically significant findings may have been more likely to be published, while non-significant results could remain unpublished, warranting cautious interpretation of the findings. For further supporting literature, methodological details, and related evidence, see also references (15–40).