Circulating MicroRNA-19 and cardiovascular risk reduction in response to weight-loss diets

Objective: MicroRNA-19 (miR-19) plays a critical role in cardiac development and cardiovascular disease (CVD). We examined whether change in circulating miR-19 was associated with change in CVD risk during weight loss. Methods: This study included 509 participants with overweight or obesity from the 24 -month weightloss diet intervention study (the POUNDS Lost trial) and with available data on circulating miR-19a-3p and miR-19b-3p at baseline and 6 months. The primary outcome for this analysis was the change in atherosclerotic CVD (ASCVD) risk at 6 and 24 months, which estimates the 10 -year probability of hard ASCVD events. Secondary outcomes were the changes in ASCVD risk score components. Results: Circulating miR-19a-3p and miR-19b-3p levels significantly decreased during the initial 6 -month dietary intervention period (P = 0.008, 0.0004, respectively). We found that a greater decrease in miR19a-3p or miR-19b-3p was related to a greater reduction in ASCVD risk (b[SE] = 0.33 [0.13], P = 0.01 for miR-19a-3p; b[SE] = 0.3 [0.12], P = 0.017 for miR-19b-3p) over 6 months, independent of concurrent weight loss. Moreover, we found significant interactions between change in miR-19 and sleep disturbance on change in ASCVD risk over 24 months of intervention (P interaction = 0.01 and 0.008 for miR19a-3p and miR-19b-3p, respectively). Participants with a greater decrease in miR-19 without sleep disturbance had a greater reduction of ASCVD risk than those with slight/moderate/great amounts of sleep disturbance. In addition, change in physical activity significantly modified the associations between change in miR-19 and change in ASCVD risk over 24 months (P interaction = 0.006 and 0.004 for miR19a-3p and miR-19b-3p, respectively). A greater decrease in miR-19 was significantly associated with a greater reduction in ASCVD risk among participants with an increase in physical activity, while nonsignificant inverse associations were observed among those without an increase in physical activity. Conclusions: In conclusion, decreased circulating miR-19 levels during dietary weight -loss interventions were related to a significant reduction in ASCVD risk, and these associations were more evident in people with no sleep disturbance or increase in physical activity. Trial registration: ClinicalTrials.gov NCT00072995. (c) 2024 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).