Risk of cardiovascular disease among cancer survivors: systematic review and meta-analysis

Abstract

Background: There have been conflicting studies on the associations between cancer and cardiovascular disease (CVD) risk. The hypothesis of this meta-analysis was to investigate whether cancer survivors had an increased risk of CVD compared to those without cancer based on population-based cohort studies.

Methods: We did a systematic review and meta-analysis of prospective and retrospective cohort studies. We searched PubMed, Embase, Web of Science, and Scopus published in any language from January 1, 1990 to February 24, 2025. We included cancer survivors and non-cancer controls. The primary outcome was the risk of CVD. The secondary outcomes included 17 CVD subtypes (e.g., ischemic heart, cerebrovascular, and peripheral vascular disease). Effect estimates (hazards ratios, HRs) with 95% CIs were pooled. Subgroup analyses, sensitivity analyses and meta-regression were performed to explore the stability of the results and the sources of heterogeneity. The protocol of this review was registered in PROSPERO: CRD42024559349.

Findings: A total of 160 population-based cohort studies involving 49,395,865 participants (9,092,869 cancer survivors vs. 40,302,996 non-cancer controls) were identified. Overall, the HR for CVD in cancer survivors was 1.47 [95% CI, 1.33-1.62] compared with that in non-cancer controls. Cancer increased the risk of all 17 CVD subtypes, with cancer having the greatest effect on venous embolism, thrombosis or thrombophlebitis (HR, 3.07 [2.03-4.65]) and the least on ischemic heart disease (HR, 1.13 [1.03-1.24]). The increased risk of CVD was consistently shown in cancer survivors of brain, hematological, respiratory, male genital, and breast cancers, whereas no significant higher CVD risk was observed for other cancer types. Elevated risk of CVD was consistently shown in subgroup analyses of study design, age at cancer diagnosis, sex, location, follow-up duration, control, disease diagnosis, and therapy. Male and younger cancer survivors had elevated risk of CVD than female and older cancer survivors.

Interpretation: This meta-analysis provides an up-to-date comprehensive global overview that cancer survivors had increased risk of CVD and 17 CVD subtypes than non-cancer controls. CVD risk evaluation and management need to be prioritized in cancer survivors, particularly among male, younger, and specific cancer survivors (brain, hematological, respiratory, male genital, and breast). This study provides supporting evidence that may inform future updates to guidelines for CVD prevention in cancer survivors, highlighting its public health relevance.

Funding: The National Key R&D Program of China, the National Natural Science Foundation of China and the Young Elite Scientists Sponsorship Program by CAST.

Keywords: Cancer; Cardiovascular disease; Cerebrovascular disease; Heart failure; Myocardial infarction.

Fig. 1

Flow diagram of this study. CVD: cardiovascular disease; RCT: randomized controlled trial.

Fig. 2

Datasets by year and population group. Size of circle is proportional to sample size.

Fig. 3

Forest plots for the associations of cancer with CVD. ∗Study used effect estimates other than HR. CVD: cardiovascular disease; HR: hazard ratio.

Fig. 4

Subgroup analyses on the associations of cancer with CVD. CVD: cardiovascular disease; HR: hazard ratio; ICD: International Classification of Disease.

Fig. 5

Associations of cancer with CVD by cancer type. CVD: cardiovascular disease; HR: hazard ratio.