Abstract
BackgroundAbove‐normal levels of casual blood pressure (BP) increase the risk of cardiovascular disease, kidney disease, cognitive impairment, and other chronic disorders. The mechanisms linking higher BP to these conditions are incompletely understood but are thought to include vascular endothelial dysfunction based on previous BP guidelines. Changes to these guidelines by the American College of Cardiology/American Heart Association (ACC/AHA) in 2017 lowered the absolute levels classifying above‐normal BP. However, whether adults with above‐normal BP stratified according to 2017 ACC/AHA classifications exhibit vascular endothelial dysfunction remains unknown.PurposeTo determine whether otherwise healthy adults with varying BP in above‐normal (i.e., elevated, stage 1 hypertension, or stage 2 hypertension) ranges exhibit endothelial dysfunction relative to adults with normal BP, and to determine if BP‐associated endothelial dysfunction is oxidative stress‐mediated.MethodsA retrospective analysis was performed on 1151 adults (18–79 years) who underwent testing for casual BP and vascular endothelial function at the Integrative Physiology of Aging Laboratory at the University of Colorado Boulder. Brachial artery BP was measured in triplicate after ≥5 minutes of quiet rest. Endothelial function was measured with brachial artery flow‐mediated dilation (FMDBA). Endothelium‐independent dilation (sublingual nitroglycerin), oxidative stress‐mediated suppression of endothelial function (vitamin C infusion), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression in biopsied endothelial cells (protein marker of oxidative stress) were measured in subsets of subjects. Subjects were separated into 4 groups: normal BP (<120/80 mmHg; n=556), elevated BP (systolic 120–129 and diastolic <80 mmHg; n=196), stage 1 hypertension (systolic 130–139 or diastolic 80–89 mmHg; n=244), and stage 2 hypertension (systolic ≥140 or diastolic ≥90 mmHg; n=155) according to 2017 ACC/AHA guidelines.ResultsThose with normal BP (53 ± 1 years) were younger than subjects in the elevated (60 ± 1 years), stage 1 hypertension (61 ± 1 years), and stage 2 hypertension (63 ± 1 years; all p<0.05) ranges. Compared to those with normal BP (FMDBA: 6.20 ± 0.13 %Δ), FMDBA was lower in those with elevated BP (5.41 ± 0.19 %Δ; p=0.004), stage 1 hypertension (5.15 ± 0.17 %Δ; p<0.001), and stage 2 hypertension (4.96 ± 0.18 %Δ; p<0.001). After correcting for age, FMDBA remained lower in the stage 1 (p=0.04) and stage 2 hypertension (p=0.03) groups relative to normal BP. Endothelium‐independent dilation was not different between groups (p>0.05). Vitamin C infusion increased FMDBA significantly in the elevated (1.12 ± 0.35 %Δ, p=0.01), stage 1 (0.65 ± 0.23 %Δ, p=0.02), and stage 2 (0.93 ± 0.28 %Δ, p=0.01) groups, but not in the normal BP group (0.50 ± 0.17 %Δ, p=0.07). NADPH oxidase expression was 22% higher in those with above‐normal BP (p=0.01).ConclusionThese data suggest endothelial function is impaired in otherwise healthy adults with above‐normal BP according to 2017 ACC/AHA guidelines. This dysfunction is likely mediated, in part, by increased oxidative stress in those with above‐normal BP.Support or Funding Information18POST33990034 (DHC)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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