Elevated Circulating Aldosterone and Platelet Activity in Overweight/Obese Young Adults: Roles in Vascular Remodeling and Cardiometabolic Health

摘要

Globally, cardiovascular disease (CVD) is the leading cause of morbidity and mortality. Overweight/obese individuals are at increased risk for CVD because the increased metabolic requirements and inflammation caused by excess weight drive adverse cardiovascular changes. Elevated circulating aldosterone and platelet activity are hypothesized to be important factors linking obesity to declining cardiometabolic health, but little longitudinal data is available in young adults with no clinically apparent obesity-related comorbidities. We sought to evaluate the roles of elevated serum aldosterone and plasma β-thromboglobulin, a marker of platelet activity, in vascular remodeling and cardiometabolic risk in overweight/obese young adults. These questions were investigated in a sample from the Slow Adverse Vascular Effects of excess weight trial, a randomized trial that evaluated the effects of a one year lifestyle intervention targeting weight loss, increased physical activity, and dietary sodium reduction on vascular health.ud We found that lower circulating platelet activity at the end of the two year study was associated with smaller common carotid artery IMT and greater weight loss during the study. In addition, non-Hispanic white individuals carrying the T allele of rs168753 in the gene encoding PAR-1, the main thrombin receptor, had greater carotid bulb IMT than non-carriers at baseline but not at the end of the study. In another analysis, higher arterial stiffness over the course the study was found to predict higher circulating platelet activity at the end of the study. However, this association was partly explained by the effect of obesity. Finally, in our study of serum aldosterone and obesity-related factors, we found that reductions in aldosterone were associated with reductions in insulin resistance, C-reactive protein, leptin, heart rate, tonic cardiac sympathovagal balance, and increases in adiponectin, independent of changes in dietary sodium and weight. In addition, weight loss and reduced intermuscular fat were associated with reduced aldosterone in individuals who had metabolic syndrome at baseline.ud The public health relevance of these findings is that elevated aldosterone and platelet activity are important modifiable cardiometabolic risk factors in overweight/obese otherwise healthy young adults. These factors may be useful targets for therapies to reduce the burden of CVD is this population.