Abstract P338: Circulating microRNA-19 and Cardiovascular Risk Reduction in Response to Weight-Loss Diets: The Preventing Overweight Using Novel Dietary Strategies (Pounds Lost) Trial

Abstract

Introduction: MicroRNA-19 (MiR-19) plays a critical role in cardiac development and cardiovascular disease (CVD). Hypothesis: We assessed the hypothesis that change in circulating miR-19 would be associated with changes in 10-year atherosclerotic CVD (ASCVD) risk and individual cardiovascular risk factors in a dietary weight-loss intervention. Methods: This study included 509 participants with overweight or obesity from the 2-year weight-loss diet intervention study (the POUNDS LOST trial) and with available data on circulating miR-19a/b-3p at baseline and 6 months. The primary outcome was the 6-month change in the ASCVD risk score, which estimates the 10-year probability of hard ASCVD events. Secondary outcomes were the change in each ASCVD component including blood pressure, lipid profiles, insulin resistance, glucose metabolism, and adiposity measures. Change in habitual physical activity and sleep disturbance were assessed from baseline to 6 months. Results: Circulating miR-19a/b-3p levels significantly decreased during the initial 6-month dietary intervention period (P=0.008, 0.0004, respectively). We found that greater decreases in log-transformed miR-19a/b-3p were related to a greater reduction in ASCVD risk (β[SE]=0.35 [0.13], P=0.01 for miR-19a-3p; β[SE]=0.33 [0.13], P=0.01 for miR-19b-3p) over 6 months. Similar positive associations were observed for changes in diastolic blood pressure with miR-19a/b-3p. Moreover, we found that sleep disturbance was significantly associated with reductions in miR-19a/b-3p from baseline to 6 months (P trend <0.05). There were significant interactions between changes in miR-19a/b-3p and sleep disturbance for changes in ASCVD risk (P interaction<0.005). Participants with greater decreases in miR-19a/b-3p with no/slight amount of sleep disturbance had a greater reduction of ASCVD risk from baseline to 6 months than those with moderate/great amount of sleep disturbance. In addition, changes in physical activity modified the associations between changes in miR-19a-3p and ASCVD risk. A greater decrease in miR-19a-3p was significantly associated with a greater reduction in ASCVD among participants with an increase in physical activity from baseline to 6 months. These positive associations were reversed and not significant among participants with no change/decrease in physical activity and moderate/great amount of sleep disturbance. Conclusions: In conclusion, decreased circulating miR-19 levels induced by dietary weight-loss interventions were related to a significant reduction in ASCVD risk, and such associations were more evident in people with no/slight amount of sleep disturbance and an increase in physical activity.