Heart Failure, Left Ventricular Remodeling, and Circulating Nitric Oxide Metabolites.
Heart Failure, Left Ventricular Remodeling, and Circulating Nitric Oxide Metabolites.
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DOI：
10.1161/jaha.116.004133
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发表时间：
2016-10-14
影响因子：
5.4
通讯作者：
Zamani P
中科院分区：
文献类型：
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作者：
Chirinos JA;Akers SR;Trieu L;Ischiropoulos H;Doulias PT;Tariq A;Vasim I;Koppula MR;Syed AA;Soto-Calderon H;Townsend RR;Cappola TP;Margulies KB;Zamani P
稳定的血浆一氧化氮代谢产物（NOM）主要由硝酸盐和亚硝酸盐组成，是一氧化氮生物利用度的重要生物标志物。NOM水平综合了NO -合成酶衍生的NO生成/代谢、膳食中无机硝酸盐/亚硝酸盐的摄入以及NOM清除的影响。此外，最丰富的硝酸盐和亚硝酸盐可以通过硝酸盐-亚硝酸盐- NO途径被还原为NO。我们比较了无心力衰竭（n=126）、心力衰竭和保留射血分数（HFpEF, n=43）和心力衰竭和射血分数降低（HFrEF, n=32）受试者的血清NOM。用心脏MRI测量左室质量和细胞外体积分数。通过钒(III)/盐酸反应还原为NO后，测定血浆NOM水平。HFpEF组的未调整NOM水平（8.0 μmol/L, 95% CI 6.2 ~ 10.4 μmol/L，方差分析P=0.013）明显低于非HF组（12.0 μmol/L, 95% CI 10.4 ~ 13.9 μmol/L）或HFrEF组（13.5 μmol/L, 95% CI 9.7 ~ 18.9 μmol/L）。HFrEF组与非HF组的NOM无显著差异。在一个校正了年龄、性别、种族、糖尿病、体重指数、当前吸烟、收缩压和肾小球滤过率的多变量模型中，HFpEF仍然是较低NOM的预测因子（β= - 0.43； P=0.013）。NOM与左室肿块或左室弥漫性纤维化无关。HFpEF与血浆NOM降低相关，但与HFrEF无关，提示内皮功能障碍加重、清除增强或饮食摄入无机硝酸盐不足。我们的发现可能是最近在HFpEF临床试验中证明的无机硝酸盐补充剂有益作用的基础。
Stable plasma nitric oxide (NO) metabolites (NOM), composed predominantly of nitrate and nitrite, are attractive biomarkers of NO bioavailability. NOM levels integrate the influence of NO‐synthase‐derived NO production/metabolism, dietary intake of inorganic nitrate/nitrite, and clearance of NOM. Furthermore, nitrate and nitrite, the most abundant NOM, can be reduced to NO via the nitrate‐nitrite‐NO pathway. We compared serum NOM among subjects without heart failure (n=126), subjects with heart failure and preserved ejection fraction (HFpEF; n=43), and subjects with heart failure and reduced ejection fraction (HFrEF; n=32). LV mass and extracellular volume fraction were measured with cardiac MRI. Plasma NOM levels were measured after reduction to NO via reaction with vanadium (III)/hydrochloric acid. Subjects with HFpEF demonstrated significantly lower unadjusted levels of NOM (8.0 μmol/L; 95% CI 6.2–10.4 μmol/L; ANOVA P=0.013) than subjects without HF (12.0 μmol/L; 95% CI 10.4–13.9 μmol/L) or those with HFrEF (13.5 μmol/L; 95% CI 9.7–18.9 μmol/L). There were no significant differences in NOM between subjects with HFrEF and subjects without HF. In a multivariable model that adjusted for age, sex, race, diabetes mellitus, body mass index, current smoking, systolic blood pressure, and glomerular filtration rate, HFpEF remained a predictor of lower NOM (β=−0.43; P=0.013). NOM did not correlate with LV mass, or LV diffuse fibrosis. HFpEF, but not HFrEF, is associated with reduced plasma NOM, suggesting greater endothelial dysfunction, enhanced clearance, or deficient dietary ingestion of inorganic nitrate. Our findings may underlie the salutary effects of inorganic nitrate supplementation demonstrated in recent clinical trials in HFpEF.