Combined impact of depressive and anxiety symptoms and cardiovascular health metrics on major adverse cardiovascular events: A prospective cohort study

Background: The interplay between psychological health and traditional cardiovascular health (CVH) metrics, and their joint impact on the risk of major adverse cardiovascular events (MACE), remain unclear. Methods: This study investigated the prospective association of depressive and anxiety symptoms, assessed by Patient Health Questionnaire-4 (PHQ-4) scores, and traditional CVH, measured by Life's Essential 8 (LE8) scores, with MACE risk in the UK Biobank cohort. MACE was defined as a composite of nonfatal myocardial infarction, nonfatal stroke, and cardiovascular mortality. Cox proportional hazards models evaluated the association of LE8 and PHQ-4 with MACE risk. Results: Among 95,098 participants (mean +/- SD age, 55.58 +/- 7.75 years; 42,526 [44.72 %] male), 3001 (3.2 %) experienced MACE during a mean follow-up of 12.73 years. Participants with low PHQ-4 scores and ideal CVH had the lowest risk of MACE compared to those with high PHQ-4 scores and poor CVH (HR, 0.263 [95 % CI, 0.183-0.377]). Higher CVH scores were consistently associated with reduced MACE risk, regardless of depressive and anxiety symptoms. Each 10-point increase in LE8 scores was associated with a significantly lower MACE risk in both participants with PHQ-4 scores <6 (HR 0.784, 95 % CI [0.759-0.810]) and with PHQ-4 scores >= 6 (HR 0.782, 95 % CI [0.679-0.901]). These findings remained robust across sensitivity analyses and subgroups. Conclusions: Fewer symptoms of depression and anxiety, alongside optimal CVH, are independently and jointly associated with a lower risk of MACE. Integrating psychological health management with CVH optimization may enhance cardiovascular outcomes and reduce the burden of cardiovascular disease.