BackgroundDepression is a global health issue, associated with increased risk of cardiovascular disease (CVD) and premature death, but whether the association varied across different socioeconomic status (SES), and mechanisms responsible for this association is unclear. We aimed to evaluate the association of depressive symptoms with the risk of incident CVD and mortality in people of low, medium, and high SES, and determine the extent to which lifestyle behaviors could explain the association. MethodsThis study included 314,800 participants from the UK Biobank. Depressive symptoms were assessed using the Patient Health Questionnaire-2 (PHQ-2). Information on socioeconomic status and lifestyle was obtained from baseline assessment. ResultsDuring 12 years of follow-up, 29,074 incident CVD cases and 16,673 deaths were documented. The increased CVD risk in participants with depressive symptoms (versus without) was more pronounced as SES decreased, with hazard ratios (HRs) and 95% confidence intervals (CIs) of 1.30 (1.22, 1.39), 1.27 (1.17, 1.37), and 1.17 (0.97, 1.41) in participants of low, medium, and high SES, respectively. The corresponding HRs (95% CIs) for all-cause mortality were 1.16 (1.07, 1.26), 1.21 (1.08, 1.36), and 1.24 (0.95, 1.61). In addition, multiple lifestyle factors together explained 14.4% to 32.8% of the elevated CVD and mortality risk due to depressive symptoms. LimitationsModerate sensitivity of PHQ-2, lacked information on the severity of depression, baseline measurement of lifestyle. ConclusionsDepressive symptoms were associated with higher risks of incident CVD and mortality, especially in low SES groups, and lifestyle behaviors only explained a moderate proportion of the association. These findings indicated that health policies targeting healthy lifestyle promotion alone might not be sufficient, and other measures tackling social inequity are warranted to attenuate the elevated health risk due to depression.