Background Impaired endothelial function is thought to contribute to the increased cardiovascular risk associated with above-normal blood pressure (BP). However, the association between endothelial function and BP classified by 2017 American College of Cardiology/American Heart Association guidelines is unknown. Our objective was to determine if endothelial function decreases in midlife/older adults across the 2017 American College of Cardiology/American Heart Association guidelines BP classifications and identify associated mechanisms of action. Methods and Results A retrospective analysis of endothelial function (brachial artery flow-mediated dilation) from 988 midlife/older adults (aged 50+ years) stratified by BP status (normal BP; elevated BP; stage 1 hypertension; stage 2 hypertension) was performed. Endothelium-independent dilation (sublingual nitroglycerin), reactive oxygen species-mediated suppression of endothelial function (∆brachial artery flow-mediated dilation with vitamin C infusion), and endothelial cell and plasma markers of oxidative stress and inflammation were assessed in subgroups. Compared with normal BP (n=411), brachial artery flow-mediated dilation was 12% (P=0.04), 15% (P<0.01) and 20% (P<0.01) lower with elevated BP (n=173), stage 1 hypertension (n=248) and stage 2 hypertension (n=156), respectively, whereas endothelium-independent dilation did not differ (P=0.14). Vitamin C infusion increased brachial artery flow-mediated dilation in those with above-normal BP (P≤0.02) but not normal BP (P=0.11). Endothelial cell p47phox (P<0.01), a marker of superoxide/reactive oxygen species-generating nicotinamide adenine dinucleotide phosphate oxidase, and circulating interleukin-6 concentrations (P=0.01) were higher in individuals with above-normal BP. Conclusions Vascular endothelial function is progressively impaired with increasing BP in otherwise healthy adults classified by 2017 American College of Cardiology/American Heart Association guidelines. Impaired endothelial function with above-normal BP is mediated by excessive reactive oxygen species signaling associated with increased endothelial expression of nicotinamide adenine dinucleotide phosphate oxidase and circulating interleukin-6.
Keywords: NADPH oxidase; hypertension; inflammation; oxidative stress.