Abstract 12440: Depression and Anxiety Accelerate the Rate of Gain of Cardiovascular Risk Factors: Mechanism Leading to Increased Risk of Cardiac Events

Abstract

Introduction: Depression and anxiety are associated with a greater incidence of major adverse cardiovascular events (MACEs). Hypothesis: We hypothesized that: 1) depression and anxiety accelerate the development of cardiovascular risk factors (CVDRFs), which in turn significantly heightens MACE risk, and 2) a genetic marker of stress sensitivity (polygenic risk score for neuroticism; nPRS) also associates with accelerated gains of CVDRFs. Methods: Subjects enrolled in the Mass General Brigham Biobank were studied. Depression, anxiety, CVDRFs and MACE were defined using ICD codes. Subjects <18 years old, with previous MACE or who developed depression/anxiety after study start date were excluded. CVDRFs were defined as hypertension, hyperlipidemia, and diabetes mellitus. The time between study start date and development of first new CVDRF was measured over 10 years of follow-up. Additionally, nPRS was assessed for subjects who provided genetic data; age of first CVDRF diagnosis was ascertained in this subgroup. Results: Data were obtained for 71,262 subjects (age 49.0 ± 15.6 yrs, 44.7% male). 27,048 (38.0%) subjects gained a new CVDRF (mean time 4.8 ± 2.6 yrs). Depression (β=-0.591; p<0.001) and anxiety (β=-0.567; p<0.001) associated with earlier development of a new CVDRF after adjusting for age, sex, and preexisting CVDRFs ( Fig. 1A). Further, in adjusted analyses, depression and/or anxiety increased the risk of MACE (adjusted odds ratio: 1.353; p<0.001). Mediation analysis shows that 38.9% of the effect of depression and/or anxiety on MACE is explained by the accelerated gains in CVDRFs. Similarly, higher genetic sensitivity to stress (nPRS) associates with an earlier onset of first CVDRF (adjusted β=-0.317; p=0.005, Fig. 1B) . Conclusions: Depression and anxiety accelerate the acquisition of CVDRFs, which in turn significantly explains the heightened risk of MACE. Genetic risk associated with stress sensitivity also accelerates the development of CVDRFs.