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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 &lt;0.01) and 20% (P &lt;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 &lt;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.

journal of the american heart association. cardiovascular and cerebrovascular disease

Vascular Endothelial Function in Midlife/Older Adults Classified According to 2017 American College of Cardiology/American Heart Association Blood Pressure Guidelines