Cardiovascular Disease Risk Among Childhood and Young Adult Cancer Survivors: A Systematic Review and Meta-Analysis.

IMPORTANCE: There is a growing population of childhood, adolescent, and young adult (CAYA) cancer survivors (younger than 40 years). Cardiovascular disease (CVD) becomes one of the primary sequelae during their survival, yet the relative risk and variations in each age group have not been comprehensively investigated. OBJECTIVE: To quantify the relative risk of CVD among CAYA cancer survivors compared with noncancer CAYA individuals, and to examine differences across various subgroups. DATA SOURCES: MEDLINE, Embase, and Cochrane Library databases were systematically searched from inception to November 5, 2025. STUDY SELECTION: Cohort studies reporting incident CVD after cancer diagnosis in CAYA populations with noncancer controls were eligible. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data and assessed study quality. Risk ratios (RRs) with 95% CIs were pooled using random-effects models. Meta-regression and subgroup analyses were conducted to evaluate sources of heterogeneity and the affect of study characteristics on relative risks. MAIN OUTCOMES AND MEASURES: Relative risk of incident CVD. RESULTS: Thirty-nine cohort studies, including 536 399 CAYA cancer survivors and 1 810 572 cancer-free peers, were analyzed. Overall, CAYA cancer survivors had a higher CVD risk compared with noncancer CAYA individuals (RR, 1.99; 95% CI, 1.66-2.40), corresponding to an excess of 90 CVD events per 1000 survivors. Childhood cancer survivors demonstrated a higher relative risk (RR, 2.48; 95% CI, 1.87-3.27) than young adult cancer survivors (RR, 1.61; 95% CI, 1.37-1.88). Meta-regression indicated that longer follow-up duration was associated with a smaller relative effect estimate (P = .02), but the increased CVD risk remained significant after 20 years of cancer diagnosis. Findings were consistent across subgroups stratified by follow-up time, CVD, and cancer subtypes, and remained robust in sensitivity analyses restricted to prospective, high-quality studies, population-based studies, studies including 5-year survivors, nonsibling control studies, and studies that adjusted for competing mortality risk. CONCLUSIONS AND RELEVANCE: In this study, CAYA cancer survivors experienced an increased risk of CVD, with the greatest vulnerability observed in those diagnosed during childhood. These results highlight the need for age-specific and time-sensitive CVD surveillance to improve well-being during the survival of this growing population.