Sleep Variability, Depressive Symptoms, and Risk of Cardiovascular Events: The Multi-Ethnic Study of Atherosclerosis

• We found no significant interaction effects between sleep duration and onset variability with depressive symptoms on cardiovascular disease (CVD) risk. • More regular sleep onset timing, however, significantly reduced CVD risk, independent of depressive symptoms, traditional CVD, and sleep-related risk factors. • Future studies should evaluate complications of chronic sleep variability over several weeks to months and clarify the causal pathways through which sleep variability contributes to cardiovascular disease. Sleep variability and depressive symptoms have been linked to several cardiometabolic risk factors and disease, warranting further exploration of the pathways through which these variables contribute to the pathophysiology of cardiovascular disease (CVD). While the independent associations of variability in sleep duration and onset timing and depressive symptoms on CVD have been studied, the interaction effects of sleep variability and depression have not been explored. We examined self-reported depressive symptoms and two measures of sleep irregularity-within subject standard deviation (SD) of daily variation of actigraphy-measured sleep duration and onset timing in the Multi-Ethnic Study of Atherosclerosis. Cox proportional hazards models were used to estimate hazard ratios for incident CVD events, adjusting for traditional CVD and sleep-related risk factors. Among 1994 participants, 191 incident CVD events occurred over a median follow-up of 8.77 years. Each 1-hour increase in sleep onset timing SD was associated with a 12% higher risk of CVD (adjusted 95% CI, 1.04-1.20, p=0.003). While sleep duration SD was significantly associated with a 27% higher risk of CVD in the unadjusted model (95% CI, 1.03-1.58, p=0.03), it was no longer significant after adjusting for demographics and risk factors. Severe depressive symptoms were not associated with CVD risk. When depressive symptoms and sleep variability measures were simultaneously included in the models, no significant interactions were found in predicting CVD risk. Our findings support the role of sleep variability as a modifiable risk factor for CVD, independent of depressive symptoms.