Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan
J Am Heart Assoc. 2017 Oct 3;6(10):e006885. doi: 10.1161/JAHA.117.006885.
Cardiovascular disease is the leading cause of morbidity and mortality in patients receiving hemodialysis. Systemic metabolic perturbation is one of the hallmark abnormalities in patients at high cardiovascular risk. We sought to determine the relationship between circulating ketone body and clinical outcomes in patients with prevalent hemodialysis.
We retrospectively assessed the relationship between serum β-hydroxybutyrate (βOHB), the most abundant ketone body in the circulation, and prognosis in 405 stable hemodialysis patients. During a mean follow-up of 3.2±0.9 years, there were 54 major adverse cardiovascular events (defined as cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization attributed to heart failure) and 67 all-cause deaths. Major adverse cardiovascular events rates increased from 11.1 per 1000 person-years in the lowest βOHB quintile (<89 μmol/L) to 80.1 per 1000 person-years in the highest quintile (>409 μmol/L). After adjusting for demographic characteristics, coronary artery disease, and atrial fibrillation, the highest βOHB quintile was associated with increased risk of major adverse cardiovascular events compared with the lowest quintile (hazard ratio, 10.2; 95% confidence interval [3.35-44.0]; <0.001). Increased quintiles of βOHB were independently and incrementally associated with major adverse cardiovascular events over the model based on an established risk score (the second Analyzing Data, Recognizing Excellence and Optimizing Outcomes cohort score) and N-terminal pro-B-type natriuretic peptide (chi square 39.9 versus 21.7; <0.001; c-statistics, 0.713). Sensitivity analyses also confirmed the robustness of association between βOHB and all-cause death.
Increased serum βOHB levels were independently associated with cardiovascular events and all-cause death in patients receiving hemodialysis. These results highlight the need for future studies to understand the mechanisms underlying these observations.
心血管疾病是接受血液透析患者发病率和死亡率的主要原因。系统性代谢紊乱是心血管高危患者的标志异常之一。我们试图确定循环酮体与现患血液透析患者临床结局之间的关系。
我们回顾性评估了 405 例稳定血液透析患者血清β-羟丁酸（βOHB）与预后之间的关系，βOHB 是循环中最丰富的酮体。在平均 3.2±0.9 年的随访期间，有 54 例主要不良心血管事件（定义为心血管死亡、非致死性心肌梗死、非致死性卒中和心力衰竭归因的住院治疗）和 67 例全因死亡。主要不良心血管事件发生率从最低βOHB 五分位组（<89μmol/L）的 11.1/1000 人年增加到最高五分位组（>409μmol/L）的 80.1/1000 人年。在校正人口统计学特征、冠状动脉疾病和心房颤动后，与最低五分位组相比，最高βOHB 五分位组发生主要不良心血管事件的风险增加（风险比，10.2；95%置信区间 [3.35-44.0]；<0.001）。随着基于既定风险评分（第二个分析数据、识别卓越和优化结果队列评分）和 N 端脑钠肽前体（NT-proBNP）的模型中βOHB 五分位的增加，独立且递增地与主要不良心血管事件相关（卡方值 39.9 与 21.7；<0.001；c 统计量，0.713）。敏感性分析也证实了βOHB 与全因死亡之间关联的稳健性。
血清βOHB 水平升高与接受血液透析的患者心血管事件和全因死亡独立相关。这些结果强调了未来研究理解这些观察结果背后机制的必要性。
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