Joint associations of cardiovascular polygenic risk and a health-related risk profile with incident cardiovascular disease among adults with depression: a UK Biobank study

Abstract

Adults with depression have higher cardiovascular disease (CVD) risk, but the joint associations of inherited CVD susceptibility and health-related risk profiles remain uncertain. We examined incident CVD according to CVD polygenic risk score (PRS) and a health-related risk profile among adults with depression. We identified 3,446 participants with depression. For participants with ICD-10 depression recorded before recruitment, the index was the recruitment assessment date. For those identified by a Patient Health Questionnaire-9 (PHQ-9) score ≥ 10, the index was the questionnaire assessment date. CVD PRS was standardized and categorized into low, intermediate, and high tertiles. A health-related risk profile was constructed from current smoking, frequent alcohol consumption, obesity, low physical-activity frequency, and insomnia; 0–1 factors defined a favorable profile, and at least two factors defined an adverse profile. Cox proportional-hazards models assessed incident CVD during years 0–5. Years 5–10 landmark analysis included 3,062 participants who were alive, CVD-free, uncensored, and under observation at 5 years. During years 0–5, 304 incident CVD events occurred. Compared with low PRS plus a favorable profile, high PRS plus a favorable profile was associated with higher CVD risk (adjusted hazard ratio [aHR], 2.00; 95% confidence interval [CI], 1.15–3.47). During years 5–10, 192 events occurred. Intermediate PRS plus an adverse profile (aHR, 2.02; 95% CI, 1.08–3.77) and high PRS plus an adverse profile (aHR, 1.89; 95% CI, 1.01–3.54) were associated with higher risk than low PRS plus a favorable profile. Inherited susceptibility was more evident in near-term CVD risk, whereas adverse health-related risk profiles were more evident in later risk among participants with intermediate or high PRS. These descriptive differences may provide complementary temporal risk information but do not establish that the relative importance of inherited and health-related factors changed over time.