Urinary 8-iso-prostaglandin F2α as a risk marker in patients with coronary heart disease -: A matched case-control study
Urinary 8-iso-prostaglandin F2α as a risk marker in patients with coronary heart disease -: A matched case-control study
复制标题
DOI：
10.1161/01.cir.0000116761.93647.30
复制
发表时间：
2004-02-24
期刊：
影响因子：
37.8
通讯作者：
Böger, RH
中科院分区：
文献类型：
--
作者：
Schwedhelm, E;Bartling, A;Böger, RH
背景 - 氧化应激参与动脉粥样硬化、糖尿病、高血压、肥胖和吸烟的病理生理学过程，所有这些都是冠心病（CHD）的危险因素。我们检验了冠心病危险因素与大量全身性氧化应激相关的假设。
方法与结果 - 我们进行了一项病例对照研究，纳入93例冠心病患者和93例按年龄和性别进行频数匹配的对照受试者。通过气相色谱 - 串联质谱法测定尿中F - 2 - 异前列腺素8 - 异 - 前列腺素（PG）F - 2α及其主要尿代谢产物2,3 - 二去甲 - 5,6 - 二氢 - 8 - 异 - PGF(2α)的排泄量。冠心病患者的体重指数、收缩压和C - 反应蛋白升高（P < 0.01）。尿中8 - 异 - PGF(2α)和2,3 - 二去甲 - 5,6 - 二氢 - 8 - 异 - PGF(2α)也存在差异，对照受试者分别为77（四分位间距，61 - 101）和120（91 - 151）pmol/mmol肌酐，病例受试者分别为139（93 - 231）和193（140 - 275）pmol/mmol肌酐（P < 0.001）。8 - 异 - PGF(2α)及其代谢产物高度相关（斯皮尔曼相关系数ρ = 0.664，P < 0.001）。冠心病患者的高密度脂蛋白胆固醇降低（P < 0.001）。所有这些特征在单变量分析中都可预测冠心病。在多变量模型中，仅8 - 异 - PGF(2α)（≥131 pmol/mmol，P < 0.001）和C - 反应蛋白（>3 mg/L，P < 0.01）的优势比增加，分别为30.8（95%置信区间，7.7 - 124）和7.2（1.9 - 27.6）。8 - 异 - PGF(2α)被发现是除已知冠心病危险因素（即糖尿病、高胆固醇血症、高血压和吸烟）之外的一种新标志物。所有受试者尿中8 - 异 - PGF(2α)的排泄量与危险因素数量相关（趋势P < 0.001）。
结论 - 8 - 异 - PGF(2α)是冠心病的一种敏感且独立的危险标志物。
Background - Oxidative stress is involved in the pathophysiology of atherosclerosis, diabetes mellitus, hypertension, obesity, and cigarette smoking, all of these being risk factors for coronary heart disease (CHD). We tested the hypothesis that risk factors of CHD are associated with abundant systemic oxidative stress.Methods and Results - We conducted a case-control study with 93 CHD patients and 93 control subjects frequency-matched by age and sex. Urinary excretion of the F-2-isoprostane 8-iso-prostaglandin (PG) F-2alpha and its major urinary metabolite, 2,3-dinor-5,6-dihydro-8-iso-PGF(2alpha), were measured by gas chromatography - tandem mass spectrometry. Body mass index, systolic blood pressure, and C-reactive protein were elevated in CHD patients ( P < 0.01). Urinary 8-iso-PGF(2α) and 2,3-dinor-5,6-dihydro-8-iso-PGF(2α) also differed, from 77 (interquartile range, 61 - 101) to 139 ( 93 - 231) pmol/mmol creatinine and from 120 (91 - 151) to 193 (140 - 275) pmol/mmol in control subjects and case subjects, respectively (P < 0.001). 8-iso-PGF(2alpha) and its metabolite were highly correlated (Spearman's rho = 0.664, P < 0.001). HDL cholesterol was diminished in CHD patients ( P < 0.001). All of these characteristics predicted CHD in univariate analysis. In a multivariate model, the odds ratios were increased only for 8-iso-PGF(2alpha) (greater than or equal to131 pmol/mmol, P < 0.001) and C-reactive protein (>3 mg/ L, P < 0.01), ie, by 30.8 (95% CI, 7.7 - 124) and 7.2 (1.9 - 27.6), respectively. 8-iso-PGF(2α) was found to be a novel marker in addition to known risk factors of CHD, ie, diabetes mellitus, hypercholesterolemia, hypertension, and smoking. Urinary excretion of 8-iso-PGF(2α) correlated with the number of risk factors for all subjects ( P < 0.001 for trend).Conclusions - 8-iso-PGF(2alpha) is a sensitive and independent risk marker of CHD.