PDF(Pubmed)
Abstract：
Heart failure with preserved ejection fraction (HFpEF) is characterized by impaired vascular endothelial function that may be improved by hydroxy-methylglutaryl-CoA (HMG-CoA) reductase enzyme inhibition. Thus, using a parallel, double-blind, placebo-controlled design, this study evaluated the efficacy of 30-day atorvastatin administration (10 mg daily) on peripheral vascular function and biomarkers of inflammation and oxidative stress in 16 patients with HFpEF [Statin: n = 8, 74 ± 6 yr, ejection fraction (EF) 52-73%; Placebo: n = 8, 67 ± 9 yr, EF 56-72%]. Flow-mediated dilation (FMD) and sustained-stimulus FMD (SS-FMD) during handgrip (HG) exercise, reactive hyperemia (RH), and blood flow during HG exercise were evaluated to assess conduit vessel function, microvascular function, and exercising muscle blood flow, respectively. FMD improved following statin administration (pre, 3.33 ± 2.13%; post, 5.23 ± 1.35%; P < 0.01), but was unchanged in the placebo group. Likewise, SS-FMD, quantified using the slope of changes in brachial artery diameter in response to increases in shear rate, improved following statin administration (pre: 5.31e-5 ± 3.85e-5 mm/s-1; post: 8.54e-5 ± 4.98e-5 mm/s-1; P = 0.03), with no change in the placebo group. Reactive hyperemia and exercise hyperemia responses were unchanged in both statin and placebo groups. Statin administration decreased markers of lipid peroxidation (malondialdehyde, MDA) (pre, 0.652 ± 0.095; post, 0.501 ± 0.094; P = 0.04), whereas other inflammatory and oxidative stress biomarkers were unchanged. Together, these data provide new evidence for the efficacy of low-dose statin administration to improve brachial artery endothelium-dependent vasodilation, but not microvascular function or exercising limb blood flow, in patients with HFpEF, which may be due in part to reductions in oxidative stress.NEW & NOTEWORTHY This is the first study to investigate the impact of statin administration on vascular function and exercise hyperemia in patients with heart failure with preserved ejection fraction (HFpEF). In support of our hypothesis, both conventional flow-mediated dilation (FMD) testing and brachial artery vasodilation in response to sustained elevations in shear rate during handgrip exercise increased significantly in patients with HFpEF following statin administration, beneficial effects that were accompanied by a decrease in biomarkers of oxidative damage. However, contrary to our hypothesis, reactive hyperemia and exercise hyperemia were unchanged in patients with HFpEF following statin therapy. These data provide new evidence for the efficacy of low-dose statin administration to improve brachial artery endothelium-dependent vasodilation, but not microvascular reactivity or exercising muscle blood flow in patients with HFpEF, which may be due in part to reductions in oxidative stress.
摘要：
射血分数保留的心力衰竭（HFpEF）的特征是血管内皮功能受损，可以通过抑制羟甲基戊二酰辅酶A（HMG-CoA）还原酶来改善。因此，使用并行，双盲,安慰剂对照设计，这项研究评估了16例HFpEF患者的30天阿托伐他汀给药（10mgQD）对外周血管功能以及炎症和氧化应激生物标志物的疗效（他汀类药物：n=8，74±6年，EF52-73%；安慰剂：n=8，67±9年，EF56-72%）。手握（HG）运动期间的流量介导扩张（FMD）和持续刺激FMD（SS-FMD），反应性充血（RH），并对HG运动期间的血流进行评估，以评估导管血管功能，微血管功能,锻炼肌肉血流，分别。他汀类药物给药后口蹄疫改善(前，3.33±2.13%；员额，5.23±1.35%；P<0.01），但安慰剂组没有变化。同样，SS-FMD,使用响应于剪切速率增加的肱动脉直径变化的斜率进行量化，他汀类药物给药后改善（前：5.31e-5±3.85e-5mm/sec-1；后：8.54e-5±4.98e-5mm/sec-1；P=0.03），安慰剂组没有变化。两组反应性充血和运动充血反应均未改变。他汀类药物的施用降低了脂质过氧化的标志物（丙二醛，MDA)(预,0.652±0.095;岗位,0.501±0.094;P=0.04),而其他生物标志物没有变化。一起,这些数据为低剂量他汀类药物改善肱动脉内皮依赖性血管舒张的疗效提供了新的证据,但不是微血管功能或锻炼肢体血流，在HFpEF患者中，这可能部分是由于氧化应激的减少。
