Eplerenone did not significantly change flow-mediated dilation compared to placebo (6.39% vs 6.23%; P=0.7), but individual improvements were associated with higher total and abdominal fat.
RCT (n=22)
Double-blind
Cross-over
Does eplerenone improve vascular endothelial function and oxidative stress in older adults without overt cardiovascular disease?
Mineralocorticoid receptor blockade with eplerenone does not improve vascular endothelial function overall in healthy older adults, but provides adiposity-dependent improvements in those with higher body fat.
Absolute Event Rate: 6.39% vs 6.23%
p-value: p=0.7
Obesity increases linearly with age and is associated with impaired vascular endothelial function and increased risk of cardiovascular disease. MRs (mineralocorticoid receptors) contribute to impaired vascular endothelial function in cardiovascular disease; however, their role in uncomplicated human obesity is unknown. Because plasma aldosterone levels are elevated in obesity and adipocytes may be a source of aldosterone, we hypothesized that MRs modulate vascular endothelial function in older adults in an adiposity-dependent manner. To test this hypothesis, we administered MR blockade (eplerenone; 100 mg/day) for 1 month in a balanced randomized double-blind placebo-controlled cross-over study to 22 older adults (ten men, 55-79 years) varying widely in adiposity BMI (body mass index): 20-45 kg/m², but who were free from overt cardiovascular disease. We evaluated vascular endothelial function brachial artery FMD (flow-mediated dilation) via ultrasonography) and oxidative stress (plasma F2-isoprostanes and vascular endothelial cell protein expression of nitrotyrosine and NADPH oxidase p47phox) during placebo and MR blockade. In the whole group, oxidative stress (P>0.05) and FMD did not change with MR blockade (6.39 ± 0.67 compared with 6.23 ± 0.73%; P=0.7). However, individual improvements in FMD in response to eplerenone were associated with higher total body fat (BMI: r=0.45, P=0.02; and dual-energy X-ray absorptiometry-derived percentage body fat: r=0.50, P=0.009) and abdominal fat (total: r=0.61, P=0.005; visceral: r=0.67, P=0.002; and subcutaneous: r=0.48, P=0.03). In addition, greater improvements in FMD with eplerenone were related to higher baseline fasting glucose (r=0.53, P=0.01). MRs influence vascular endothelial function in an adiposity-dependent manner in healthy older adults.
Hwang et al. (Fri,) conducted a rct in Obesity (n=22). Eplerenone vs. Placebo was evaluated on Vascular endothelial function (brachial artery flow-mediated dilation) (p=0.7). Eplerenone did not significantly change flow-mediated dilation compared to placebo (6.39% vs 6.23%; P=0.7), but individual improvements were associated with higher total and abdominal fat.