Homoarginine, Cardiovascular Risk, and Mortality
Homoarginine, Cardiovascular Risk, and Mortality
复制标题
DOI：
10.1161/circulationaha.109.908988
复制
发表时间：
2010-09-07
期刊：
影响因子：
37.8
通讯作者：
Wanner, Christoph
中科院分区：
文献类型：
--
作者：
Maerz, Winfried;Meinitzer, Andreas;Wanner, Christoph
背景-高精氨酸是一种氨基酸衍生物，可以增加一氧化氮的利用率并增强内皮功能。高精氨酸水平对心血管结局和死亡率的影响尚不清楚。 方法和结果 - 我们根据路德维希港 RIsk 和心血管健康 (LURIC) 研究转诊进行冠状动脉造影的 3305 名受试者队列中的高精氨酸水平评估心血管和全因死亡率。在研究了高精氨酸与肾功能和内皮功能障碍标志物的关系后，我们在第二个由 1244 名接受维持性血液透析的 2 型糖尿病患者组成的高危队列中探讨了其对不良结果的影响（4D 研究 [Die Deutsche Diabetes Dialyse Study]）。在 LURIC 研究中，平均血清高精氨酸水平为 2.6 +/- 1.1 mumol/L。在中位随访 7.7 年期间，766 名患者死亡。调整年龄和性别后，最低四分位数的患者（心血管疾病死亡率（风险比 4.1，95% 置信区间 3.0 至 5.7）比最高四分位数的患者 (>3.1 μmol/L) 高 4 倍。较低的高精氨酸水平与较低的估计肾小球滤过率和较高的细胞间粘附分子-1 和血管细胞粘附分子-1 水平相关。血液透析患者的平均死亡率较低高精氨酸水平为 1.2 +/- 0.5 μmol/L，与 LURIC 患者相比，死亡率增加了 5 倍（中位随访 4 年期间有 608 例死亡），高精氨酸持续影响死亡率，最低四分位数的 4D 研究患者的死亡率高出 2 倍（1.4 μmol/L）。结论 - 高精氨酸水平与转诊患者的心血管死亡率和全因死亡率独立相关。需要进一步的研究来阐明其潜在的病理机制（Circulation. 2010;122:967-975）。
Background-Homoarginine is an amino acid derivative that may increase nitric oxide availability and enhance endothelial function. The effect of the level of homoarginine on cardiovascular outcome and mortality is unknown.Methods and Results-We assessed cardiovascular and all-cause mortality according to homoarginine levels in a cohort of 3305 subjects referred for coronary angiography from the LUdwigshafen RIsk and Cardiovascular Health (LURIC) Study. After investigating the relation of homoarginine with kidney function and markers of endothelial dysfunction, we explored its effects on adverse outcomes in a second high-risk cohort of 1244 patients with type 2 diabetes mellitus receiving maintenance hemodialysis (4D study [Die Deutsche Diabetes Dialyse Studie]). In the LURIC study, mean serum homoarginine levels were 2.6 +/- 1.1 mu mol/L. During a median follow-up of 7.7 years, 766 patients died. After adjustments for age and sex, patients in the lowest quartile (4-fold higher rate of dying of cardiovascular disease (hazard ratio 4.1, 95% confidence interval 3.0 to 5.7) than patients in the highest quartile (>3.1 mu mol/L). Lower homoarginine levels were associated with lower estimated glomerular filtration rate and higher levels of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. Hemodialysed patients had lower mean homoarginine levels of 1.2 +/- 0.5 mu mol/L and experienced a 5-fold increased mortality rate compared with LURIC patients (608 deaths during a median follow-up of 4 years). Homoarginine consistently affected mortality, which was 2-fold higher in 4D study patients in the lowest quartile (1.4 mu mol/L).Conclusions-Homoarginine levels are independently associated with cardiovascular and all-cause mortality in patients referred for coronary angiography and in patients undergoing hemodialysis. Future studies are needed to elucidate the underlying pathomechanisms. (Circulation. 2010;122:967-975.)