Abstract P2121: Associations of Physical Activity and Sedentary Behavior with CVD Risk: Mediation by Cardiac Autonomic Function (Pooled Analysis of Six NHLBI Cohorts)

Abstract

Objective: High sedentary behavior (SB) and low physical activity (PA) can worsen glycemic control, impairing cardiac autonomic function (CAF) and increasing cardiovascular disease (CVD) risk. We examined 1) associations of PA and SB with CVD risk and 2) whether CAF, assessed by heart rate variability (HRV), mediated these associations overall and in those with and without type 2 diabetes (T2D). Methods: We analyzed data from 28,897 participants from six NHLBI cohorts: Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Cardiovascular Health Study, Framingham Heart Study, Jackson Heart Study, and the Multi-Ethnic Study of Atherosclerosis. We harmonized self-reported PA and SB data as the cumulative average of PA and SB percentiles over all timepoints prior to a fatal/non-fatal CVD event or end of follow-up. HRV was expressed as the SD of normal-to-normal RR intervals (SDNN)—a time-domain measure of HRV and our proxy for CAF. Covariates included harmonized data on age, race/ethnicity, sex, study center, education, smoking, alcohol, diet, and lipid, blood pressure, and T2D medications. We used Cox regression to examine associations of PA and SB with CVD risk, reporting standardized betas for PA and SB. Estimate pooling was performed with a random effects model. HRV mediation was the % difference in pooled PA and SB betas when HRV was in vs. out of the model, with ≥10% beta attenuation defined as mediation. Results: Across cohorts, mean age was 30-71 years, with 8,780 CVD events observed and a mean follow-up of 7,090 days until a CVD event. PA was strongly inversely associated with CVD risk, while SB had a marginal positive association with CVD risk. There was no evidence of CAF mediation for PA. For SB, we observed no evidence of CAF mediation overall but, for those with and without T2D, we observed 16.1% and 7.7% mediation, respectively (Table). Conclusion: Additional research is needed with more robust HRV and SB measures to discern whether the relationship between SB and CVD risk is truly mediated by CAF and whether this mediation varies by T2D status.