Does valsartan improve vascular function and insulin sensitivity in healthy overweight adults without cardiovascular risk factors?
In healthy overweight adults, valsartan improves insulin sensitivity but does not alter vascular function, suggesting a potential role in diabetes prevention but not supporting RAS-hyperactivity as the primary cause of obesity-related vascular dysfunction.
Background. We investigated hyperactivity of the renin-angiotensin system (RAS) as a cause of endothelial dysfunction in obese humans. Methods. Thirty five healthy overweight (BMI = 33.6 +/- 6.6 kg m (2)) adults (33 +/- 10 years old) without cardiovascular risk factors received valsartan (160 mg) orally daily or a matching placebo for 6 weeks each. Results. Baseline flow-mediated dilatation (FMD) and nitroglycerin-mediated dilatation (NMD) were not altered by placebo or valsartan. However, fasting plasma insulin was significantly decreased by valsartan compared to placebo (-4.6 +/- 16.0 muUmL(1) versus -0.4 +/- 11.6 muUmL(1), P = 0.032) with no changes in glucose. A secondary analysis in patients with elevated waist to hip ratios (ÿ0.85, n = 18) showed an increase in FMD with valsartan. Conclusions. Our findings suggest that angiotensin 2 receptor blockade may aid in the prevention of diabetes even at the earliest stages of risk due solely to uncomplicated obesity. The lack of an improvement in FMD does not support a central role of RAS-hyperactivity in the etiology of the vascular dysfunction due solely to obesity. However, it is possible that obese patients with central adiposity may improve FMD with RAS blockade, and future investigation is warranted in this subgroup.
Brook et al. (2007) studied this question.
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