Clinical Institute of Medical and Chemical Laboratory Diagnostics, Division of Endocrinology and Nuclear Medicine, Medical University of Graz, Graz, Austria.
Circulation. 2010 Sep 7;122(10):967-75. doi: 10.1161/CIRCULATIONAHA.109.908988. Epub 2010 Aug 23.
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.
We assessed cardiovascular and all-cause mortality according to homoarginine levels in a cohort of 3,305 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 micromol/L. During a median follow-up of 7.7 years, 766 patients died. After adjustments for age and sex, patients in the lowest quartile (<1.85 micromol/L) had a >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 micromol/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 micromol/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 (<0.87 micromol/L) than in patients in the highest quartile (>1.4 micromol/L).
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.
精氨酸是一种氨基酸衍生物，可能会增加一氧化氮的供应并增强内皮功能。精氨酸水平对心血管结局和死亡率的影响尚不清楚。
我们根据冠状动脉造影患者队列中精氨酸的水平评估了心血管和全因死亡率，该队列来自 LUdwigshafen RIsk 和心血管健康研究（LURIC 研究）。在研究了精氨酸与肾功能和内皮功能障碍标志物的关系之后，我们在接受维持性血液透析的 1244 例 2 型糖尿病患者的第二个高危队列（4D 研究[德国糖尿病透析研究]）中探讨了其对不良结局的影响。在 LURIC 研究中，平均血清精氨酸水平为 2.6+/-1.1 微摩尔/升。在中位数为 7.7 年的随访期间，有 766 例患者死亡。在调整年龄和性别后，最低四分位数（<1.85 微摩尔/升）的患者死于心血管疾病的风险率高出 4 倍（危险比 4.1，95%置信区间 3.0 至 5.7）高于最高四分位数（>3.1 微摩尔/升）的患者。较低的精氨酸水平与估计肾小球滤过率降低和细胞间黏附分子-1 和血管细胞黏附分子-1 水平升高有关。血液透析患者的平均精氨酸水平较低，为 1.2+/-0.5 微摩尔/升，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）。精氨酸一致影响死亡率，4D 研究中最低四分位数（<0.87 微摩尔/升）的患者死亡率是最高四分位数（>1.4 微摩尔/升）患者的 2 倍。
精氨酸水平与接受冠状动脉造影和血液透析的患者的心血管和全因死亡率独立相关。需要进一步的研究来阐明潜在的发病机制。
