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Abstract：
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.
摘要：
背景技术内皮功能受损被认为是与高于正常血压(BP)相关的心血管风险增加的原因。然而,根据2017年美国心脏病学会/美国心脏协会指南分类的内皮功能与BP之间的关联未知.我们的目标是确定2017年美国心脏病学会/美国心脏协会指南BP分类中中年/老年人的内皮功能是否下降，并确定相关的作用机制。方法和结果对988例中老年人（年龄50岁以上）的内皮功能（肱动脉血流介导的扩张）进行了回顾性分析，并根据BP状态（正常BP；BP升高；1期高血压；2期高血压）进行了分层。内皮非依赖性扩张（舌下硝酸甘油），活性氧-介导的内皮功能抑制（Δ肱动脉血流介导的扩张与维生素C输注），在亚组中评估了氧化应激和炎症的内皮细胞和血浆标志物。与正常血压(n=411)相比，肱动脉血流介导的扩张为12％（P=0.04），血压升高降低15%(P<0.01)和20%(P<0.01)(n=173)，1期高血压（n=248）和2期高血压（n=156），分别,而非内皮依赖性扩张没有差异（P=0.14）。维生素C输注增加了血压高于正常（P≤0.02）但血压正常（P=0.11）的肱动脉血流介导的扩张。内皮细胞p47phox(P<0.01),产生超氧化物/活性氧的烟酰胺腺嘌呤二核苷酸磷酸氧化酶的标记，在血压高于正常的个体中，循环白细胞介素6浓度较高（P=0.01）。结论在2017年美国心脏病学会/美国心脏协会指南分类的健康成人中，随着血压的增加，血管内皮功能逐渐受损。高于正常BP的内皮功能受损是由与烟酰胺腺嘌呤二核苷酸磷酸氧化酶和循环白细胞介素-6的内皮表达增加相关的过度活性氧信号介导的。
