Abstract
BACKGROUND: Frailty and depression frequently co-occur in older patients with coronary heart disease (CHD) and are each associated with adverse outcomes. However, the strength and nature of their association in this population have not been systematically quantified. METHODS: We systematically searched PubMed, Embase, and Web of Science and other major databases from inception to April 2025 for observational studies examining the association between frailty and depression in adults with CHD. Two reviewers independently screened studies, extracted data, and assessed quality using the Newcastle-Ottawa Scale for cohort studies and the AHRQ checklist for cross-sectional studies. Both cross-sectional and cohort studies were eligible. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model, prioritizing adjusted estimates where available. Heterogeneity was quantified using the I(2) statistic. Subgroup analyses were planned by region, study design and assessment tool. RESULTS: Of 2,160 records screened, 6 studies met the inclusion criteria, comprising 2,628 patients with CHD. All included studies focused on older adults (mean/median age ≥60 years), reflecting the current evidence base in this population. Meta-analysis showed a significant positive association between frailty and depression (pooled OR = 2.45; 95% CI: 1.22-4.92), with substantial heterogeneity (I(2) = 90%). When analyzed by study design, the association appeared more pronounced in cohort studies (OR = 3.92; 95% CI: 1.66-9.27; I(2) = 71%) than in cross-sectional studies (OR = 1.91; 95% CI: 1.02-3.58; I(2) = 74%). CONCLUSION: Frailty and depression are significantly associated in older adults with CHD, supporting integrated screening approaches. However, given the predominance of cross-sectional data, high heterogeneity, and limited cohort evidence, prospective studies are needed to establish temporality and better inform causal inference. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251036929, PROSPERO (CRD420Ò51036929).