Abstract
Metabolic syndrome (MS) is characterized by an increased risk of incident diabetes and cardiovascular (CV) events, identifying insulin resistance (IR) and endothelial dysfunction as key elements. Moreover, non-alcoholic fatty liver disease (NAFLD) is bidirectionally linked with MS as a consequence of metabolic and inflammatory abnormalities. We addressed the question if the evolution in NAFLD might worsen endothelium-dependent vasodilating response in MS hypertensives. We recruited 272 Caucasian newly-diagnosed never-treated hypertensive outpatients divided into three groups according to the presence/absence of MS alone or in combination with NAFLD. MS and NAFLD were defined according to the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) and non-invasive fatty liver index, respectively. We determined IR by using the homeostasis model assessment (HOMA) index. Vascular function, as forearm blood flow (FBF), was determined through strain-gauge plethysmography after intra-arterial infusion of acetylcholine (ACh) and sodium nitroprusside. MS+NAFLD+ group showed worse metabolic, inflammatory and vascular profiles compared with MS−NAFLD− and MS+NAFLD−. HOMA resulted in being the strongest predictor of FBF both in the MS+NAFLD− and in the MS+NAFLD+ groups, accounting for 20.5% and 33.2% of its variation, respectively. In conclusion, we demonstrated that MS+NAFLD+ hypertensives show a worse endothelium-dependent vasodilation compared with MS+NAFLD−, allowing for consideration of NAFLD as an early marker of endothelial dysfunction in hypertensives.
Highlights
Metabolic syndrome (MS) is a clinical condition characterized by a clustering of hemodynamic and metabolic risk factors including raised blood pressure (BP), atherogenic dyslipidemia, raised fasting glucose and central obesity [1]
The excessive intrahepatic triglyceride content further impairs insulin sensitivity of these subjects, creating a vicious circle explaining the observed metabolic and hemodynamic alterations. This is supported by the finding that, in the linear regression analysis, the main covariate related to forearm blood flow (FBF) was pulse pressure (PP) in MSNAFLDgroup, while, in the other groups, FBF resulted primarily related to homeostasis model assessment (HOMA), regardless of the highest BP values
insulin resistance (IR) is strongly associated with non-alcoholic fatty liver disease (NAFLD), a condition that can be considered as an epiphenomenon of the interaction between the inflammatory and metabolic factors featuring the MS
Summary
Metabolic syndrome (MS) is a clinical condition characterized by a clustering of hemodynamic and metabolic risk factors including raised blood pressure (BP), atherogenic dyslipidemia, raised fasting glucose and central obesity [1]. All of these factors are interrelated and associated with an increased risk for incident diabetes and cardiovascular (CV) diseases [2,3]. Some experimental and clinical data have demonstrated that NO-mediated vasodilation is impaired in patients with IR [10,11,12], representing a possible pathogenetic mechanism linking MS to increased CV risk
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