Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria.
Medical Clinic V, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Int J Cardiol. 2014 Jun 1;174(1):96-105. doi: 10.1016/j.ijcard.2014.03.168. Epub 2014 Apr 3.
The phagocytic enzyme myeloperoxidase (MPO) acts as a front-line defender against microorganisms. However, increased MPO levels have been found to be associated with complex and calcified atherosclerotic lesions and incident cardiovascular disease. Therefore, this study aimed to investigate a predictive role of MPO, a biomarker of inflammation and oxidative stress, for total and cardiovascular mortality in patients referred to coronary angiography.
MPO plasma concentrations along with eight MPO polymorphisms were determined in 3036 participants of the Ludwigshafen Risk and Cardiovascular Health study (median follow-up 7.75 years). MPO concentrations were positively associated with age, diabetes, smoking, markers of systemic inflammation (interleukin-6, fibrinogen, C-reactive protein, serum amyloid A) and vascular damage (vascular cellular adhesion molecule-1 and intercellular adhesion molecule-1) but negatively associated with HDL-cholesterol and apolipoprotein A-I. After adjustment for cardiovascular risk factors MPO concentrations in the highest versus the lowest quartile were associated with a 1.34-fold risk (95% CI: 1.09-1.67) for total mortality. In the adjusted model the hazard ratio for cardiovascular mortality in the highest MPO quartile was 1.42 (95% CI: 1.07-1.88). Five MPO polymorphisms were positively associated with MPO concentrations but not with mortality. Using Mendelian randomization, we did not obtain evidence for a causal association of MPO with either total or cardiovascular mortality.
MPO concentrations but not genetic variants at the MPO locus are independently associated with risk for total and cardiovascular mortality in coronary artery disease patients.
吞噬酶髓过氧化物酶 (MPO) 作为对抗微生物的第一道防线。然而,已发现高水平的 MPO 与复杂和钙化的动脉粥样硬化病变以及心血管疾病事件相关。因此,本研究旨在探讨 MPO(炎症和氧化应激的生物标志物)对接受冠状动脉造影检查的患者的全因和心血管死亡率的预测作用。
在路德维希港风险和心血管健康研究(中位随访 7.75 年)的 3036 名参与者中,测定了 MPO 血浆浓度以及 8 种 MPO 多态性。MPO 浓度与年龄、糖尿病、吸烟、全身炎症标志物(白细胞介素-6、纤维蛋白原、C 反应蛋白、血清淀粉样蛋白 A)和血管损伤(血管细胞黏附分子-1 和细胞间黏附分子-1)呈正相关,但与高密度脂蛋白胆固醇和载脂蛋白 A-I 呈负相关。在校正心血管危险因素后,最高与最低四分位的 MPO 浓度与全因死亡率的 1.34 倍风险(95%CI:1.09-1.67)相关。在调整后的模型中,最高 MPO 四分位的心血管死亡率的危险比为 1.42(95%CI:1.07-1.88)。五种 MPO 多态性与 MPO 浓度呈正相关,但与死亡率无关。使用孟德尔随机化,我们没有获得 MPO 与全因或心血管死亡率之间存在因果关系的证据。
MPO 浓度而非 MPO 基因座的遗传变异与冠心病患者的全因和心血管死亡率的风险独立相关。