A plasma long-chain acylcarnitine predicts cardiovascular mortality in incident dialysis patients.
A plasma long-chain acylcarnitine predicts cardiovascular mortality in incident dialysis patients.
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DOI：
10.1161/jaha.113.000542
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发表时间：
2013-12-05
影响因子：
5.4
通讯作者：
Rhee EP
中科院分区：
文献类型：
--
作者：
Kalim S;Clish CB;Wenger J;Elmariah S;Yeh RW;Deferio JJ;Pierce K;Deik A;Gerszten RE;Thadhani R;Rhee EP
尿毒症导致的心血管死亡率的显著增加仍然知之甚少。在2项独立的巢式病例对照研究中，我们对从一个大型血液透析患者队列的参与者中获得的血浆进行了基于液相色谱-质谱的代谢物分析。首先，随机选择100名在开始血液透析1年内死于心血管原因的患者（病例）沿着100名存活至少1年的患者（对照组），年龄、性别和种族匹配。四种高度相关的长链酰基肉毒碱达到了多重检验调整的显著性阈值（P<0.0003）。油酰肉毒碱是在未校正分析中与心血管死亡率相关性最强的长链酰基肉毒碱，在多变量校正后仍与1年心血管死亡相关（根据SD的比值比为2.3 [95%置信区间，1.4至3.8]; P=0.001）。然后在独立样本中重复油酰肉碱与1年心血管死亡之间的相关性（n=300，每SD的比值比为1.4 [95%置信区间，1.1至1.9]; P=0.008）。在临床变量中加入油酰卡尼汀改善了使用净重新分类的心血管风险预测（NRI，0.38 [95%置信区间，0.20至0.56]; P<0.0001）。在生理分析研究中，我们证明了从主动脉到肾静脉以及从血液透析前到血液透析后样本的血浆酰基肉毒碱水平的倍数变化排除了长链酰基肉毒碱的肾脏或透析清除率作为我们分析中的混杂因素。我们的数据突出了透析开始时酰基卡尼汀稳态的临床意义的改变，这可能代表尿毒症心血管风险的早期标志物、效应物或两者兼而有之。
The marked excess in cardiovascular mortality that results from uremia remains poorly understood. In 2 independent, nested case‐control studies, we applied liquid chromatography‐mass spectrometry‐based metabolite profiling to plasma obtained from participants of a large cohort of incident hemodialysis patients. First, 100 individuals who died of a cardiovascular cause within 1 year of initiating hemodialysis (cases) were randomly selected along with 100 individuals who survived for at least 1 year (controls), matched for age, sex, and race. Four highly intercorrelated long‐chain acylcarnitines achieved the significance threshold adjusted for multiple testing (P<0.0003). Oleoylcarnitine, the long‐chain acylcarnitine with the strongest association with cardiovascular mortality in unadjusted analysis, remained associated with 1‐year cardiovascular death after multivariable adjustment (odds ratio per SD 2.3 [95% confidence interval, 1.4 to 3.8]; P=0.001). The association between oleoylcarnitine and 1‐year cardiovascular death was then replicated in an independent sample (n=300, odds ratio per SD 1.4 [95% confidence interval, 1.1 to 1.9]; P=0.008). Addition of oleoylcarnitine to clinical variables improved cardiovascular risk prediction using net reclassification (NRI, 0.38 [95% confidence interval, 0.20 to 0.56]; P<0.0001). In physiologic profiling studies, we demonstrate that the fold change in plasma acylcarnitine levels from the aorta to renal vein and from pre‐ to post hemodialysis samples exclude renal or dialytic clearance of long‐chain acylcarnitines as confounders in our analysis. Our data highlight clinically meaningful alterations in acylcarnitine homeostasis at the time of dialysis initiation, which may represent an early marker, effector, or both of uremic cardiovascular risk.