Endothelial dysfunction is associated with reduced myocardial mechano-energetic efficiency in drug-naïve hypertensive individuals with a broad spectrum of glucose tolerance

AbstractBackground:Impaired myocardial mechano-energetics efficiency (MEEi) was shown to predict incident heart failure, but pathophysiological mechanisms linking impaired MEEi with heart failure have not been elucidated. Endothelial dysfunction is a plausible candidate because it has been associated with heart failure. This study aims to investigate the association between MEEi and endothelium‐dependent vasodilation, among drug-naïve hypertensive individuals with a broad spectrum of glucose tolerance.Methods:199 drug-naïve hypertensive individuals participating in the CATAnzaro MEtabolic RIsk factors (CATAMERI) study were included. All participants underwent to an oral glucose tolerance test and to an echocardiogram for myocardial MEEi measurement. Endothelial-dependent and endothelial-independent vasodilatation were measured by strain-gauge plethysmography during intra-arterial infusion of acetylcholine and sodium nitroprusside, respectively. A multivariate linear regression analysis was conducted to investigate the independent association between endothelial-dependent vasodilation and MEEi.Results:ACh-stimulated forearm blood flow (FBF) was associated to decreased myocardial MEEi at all the three doses tested: 7.5, 15, and 30 µg/mL-1 x min-1 (β =0.201, P=0.002; β =0.171, P=0.008; β =0.205, P=0.002 respectively) independently of well‐established cardiovascular risk factorsincluding age, sex, BMI, waist circumference, smoking status, total and HDL cholesterol, triglyceride, hsCRP, glucose tolerance status, and HOMA-IR index of insulin resistance. No association was observed between SNP-stimulated vasodilation and MEEi.Conclusions:We found that endothelium-mediated vasodilation contributed to reduced myocardial MEEi independently of several potential confounders. Because diminished myocardial MEE has been associated with incident heart failure, assessment of myocardial MEEi may improve the identification of individuals at risk of heart failure requiring a closer follow-up.