Cardiovascular disease (CVD) constitutes the primary cause of death worldwide. Its high incidence, mortality, and complex pathological subtypes, impose a significant burden on healthcare services and on society (1, 2). Global Burden of Disease 2022 assessment reveals notable regional variation in age-standardized CVD mortality (73.6 per 100,000 in high-income Asia Pacific to 432.3 per 100,000 in Eastern Europe). Despite a 34.9% global decline in age-standardized CVD mortality over the past three decades due to therapeutic advances (3), the absolute number of CVD deaths has risen substantially due to population growth, placing immense pressure on healthcare systems (4). Preventing CVD is therefore critically important for global public health.

Cancer is the second major cause of death in the world, imposing a substantial and expanding global burden. In 2022, about 20,000,000 new cancer cases and 9,700,000 cancer deaths worldwide (5). Advances in screening methods and treatment technologies have reduced mortality, extended survival, and contributed to the continued increase in the number of cancer survivors worldwide (6, 7). This extended survival has shifted focus to managing non-cancer-related comorbidities, particularly given the high risk of CVD mortality in cancer patients (8). Cancer and CVD, two major causes of death, have long been primary focal points of health research, with previous studies reporting shared pathophysiological mechanisms (9, 10). However, cancer remains a subject of debate regarding its association with an increased risk of CVD (11).

It is plausible that cancer survivors experience an elevated risk of CVD owing to shared risk factors, including advanced age, hyperglycemia, hypertension, dyslipidemia, and obesity (12). Furthermore, cancer therapies, including radiotherapy, anthracycline chemotherapy, immunotherapy, can induce cardiotoxicity by directly damaging vascular endothelium or cardiomyocytes, exacerbating cardiovascular injury (13). Nevertheless, other studies have found lower CVD risk in specific cancer survivor groups, such as gastric cancer survivors or those with localized prostate cancer (14, 15). These conflicting findings challenge the consistency of the cancer-survivorship–CVD risk association. It is necessary to conduct a thorough, systematic study to ascertain whether cancer survivors indeed face a higher CVD risk.

Given the complex and debated interplay between cancer and CVD, this study utilized datasets of the US Behavioral Risk Factor Surveillance System (BRFSS). Propensity score matching (PSM) was applied to address potential confounding factors. This study addresses three research questions: (1) Is a history of cancer independently associated with CVD risk? (2) Does this association exhibit heterogeneity across different demographic and clinical subgroups? (3) Which groups of cancer survivors face a high risk of CVD? and which modifiable factors might prevent it? The findings provide crucial evidence for cardiovascular risk stratification and targeted prevention in cancer survivors.

Cancer and CVD are the major causes of death globally (18, 19). In recent years, improvements in diagnostic and therapeutic technologies have markedly extended survival, yielding a growing cohort of cancer survivors (20). Substantial epidemiological evidence indicates that CVD is the leading cause of death among cancer survivors, excluding cancer as a cause of death (21), international cardiology and oncology societies increasingly recognize the clinical significance of CVD in cancer survivors (22). However, the relationship between malignant tumors and the risk of CVD remains debated (11).

This study, based on the U.S. BRFSS database, employed PSM to assess whether cancer survivors face a high risk of CVD. Additionally, we analyzed risk factors for CVD development in cancer survivors. After rigorous adjustment for confounders and PSM, our study found that cancer survivors face a 10% to 18% increased risk of developing CVD, consistent with most prior studies reporting elevated CVD risk in this population, particularly among those treated with chemotherapy or radiotherapy (23, 24). In contrast, studies reporting an inverse association between cancer and CVD primarily involved specific cancer types or unique subpopulations (25, 26). Although we did not analyze CVD risk in survivors of specific cancer types—a limitation that future research should address—we examined CVD risk in cancer survivors across different demographic subgroups.

Subgroup analyses further validated the consistency of findings across different populations. Among 22 subgroups, 20 demonstrated a positive association between cancer status and CVD risk, reinforcing the robustness of this association. Notably, no significant association was found in diabetes and CKD subgroups, where the extremely high baseline CVD risk may overshadow any additional impact from cancer (27, 28). Critically, no subgroups showed an inverse association between cancer and CVD risk, a finding corroborated by recent research (29).

The mechanisms linking cancer to elevated CVD risk are multifaceted. Based on our results and prior studies, we propose several explanations. Shared risk factors and pathogenic pathways, such as aging, hyperglycemia, alcohol use, smoking, and physical inactivity, may contribute to the increased risk (30). Additionally, cardiac toxicity directly induced by cancer treatments may also play a role, such as those associated with chemotherapy, radiotherapy, and immunotherapy (31). Cancer-associated hypercoagulability, increasing the risk of arterial and venous thrombosis (32), and psychological sequelae like stress, depression, and anxiety post-cancer diagnosis and treatment may also independently elevate CVD risk (33, 34). Of course, as this study is cross-sectional, the association between cancer history and CVD risk may reflect residual confounding, mediation by unmeasured treatment-related factors, or survival bias. The observed higher CVD prevalence among cancer patients may be attributable to age and traditional risk factors; cancer history largely signifies accumulated cardiovascular risk. Therefore, future longitudinal studies are needed to assess temporality and causality.

To identify high-risk subgroups and inform CVD prevention strategies, we analyzed risk factors among cancer survivors. Older age and male sex were related to an elevated risk of CVD, aligning with classical CVD epidemiology (35). Higher income correlated with lower CVD risk, likely due to better access to cancer treatment, CVD screening, and therapies (36, 37). Conversely, low income exacerbates financial toxicity, especially in rural areas where access to healthcare is limited (38). Cardiometabolic comorbidities (including hypertension, dyslipidemia, diabetes, and chronic kidney disease) represent shared risk factors between cancer and CVD. For instance, hypertension induces oxidative stress on arterial walls, a primary mechanism influencing atherosclerosis development (39), while also exhibiting a particularly strong association with renal cell carcinoma (40). Atherosclerosis originates from excessive accumulation of low-density lipoprotein beneath the endothelium (41), while high-fat intake may promote bile acid-mediated carcinogenesis and increase colorectal cancer risk (42). Among cancer survivors, these comorbidities further elevate the risk of cardiovascular disease (43, 44). Depression and other mental health factors are also associated with a higher incidence of CVD (45). Lifestyle factors played a significant role in CVD risk among cancer survivors. Current and former smokers faced elevated CVD risk, as smoking is a shared etiology for cancer and CVD (46). Adequate aerobic exercise reduced CVD risk by 22%, potentially mitigating chemotherapy-induced cardiotoxicity and coronary artery disease. Surprisingly, overweight/obese cancer survivors show an inverse relationship with CVD risk—a finding inconsistent with conventional views that warrants further investigation in prospective studies (47, 48).

The significantly elevated CVD risk among cancer survivors carries important clinical implications. Multidisciplinary collaboration between oncologists and cardiologists is essential for systematic risk management. Regular CVD risk stratification and monitoring can help identify high-risk individuals for early intervention. Lifestyle modifications, such as smoking cessation and structured aerobic exercise, may reduce CVD incidence and improve long-term quality of life.

This study benefits from several key strengths: 1) A large sample size, enhancing result accuracy; 2) Utilization of multiple analytical approaches (multivariable adjustment, PSM) to robustly demonstrate higher CVD risk among cancer survivors compared with non-cancer controls; 3) Identification of specific CVD risk and protective factors within the cancer survivor population, informing targeted prevention and management. Limitations include: 1) Based on telephone survey data, this retrospective cross-sectional study lacks temporal sequencing, making it difficult to establish causality, and may rely on participants’ recall and be subject to participant bias; 2) Absence of detailed information on cancer stage, type, and specific treatment regimens limits the ability to assess how these factors influence long-term cardiovascular outcomes. 3) Lack of longitudinal follow-up data within BRFSS prevents assessment of incident CVD risk over time; 4) The predominantly US-based population may limit applicability to other countries and ethnicities. Collectively, these limitations restrict the clinical applicability of the findings in modern cardio-oncology practice. Future prospective studies should include more detailed risk variables and incident CVD events during follow-up period to corroborate the robustness of our results.

There is a significant positive correlation between cancer and CVD risk, and this finding is confirmed across the majority of clinical subgroups. In cancer survivors, the main positive associations with CVD risk are age, hypertension, diabetes, dyslipidemia, CKD, and smoking. This study provides evidence for strengthening CVD risk assessment and prevention efforts among cancer survivors. Due to the study’s limitations, large prospective studies are warranted for further validation.