Department of Veterans Affairs New Jersey Health Care System, Medical Service, Lyons, NJ 07939, USA.
Metabolism. 2011 Feb;60(2):284-91. doi: 10.1016/j.metabol.2010.02.003. Epub 2010 Mar 6.
Basic fibroblast growth factor (bFGF) is a potent endothelial and smooth muscle cell mitogen that does not normally circulate. Plasma bFGF-like bioactivity was increased in association with persistent microalbuminuria (a risk marker for cardiovascular disease) in adult type 2 diabetes mellitus. In the present study, we tested whether baseline plasma bFGF immunoreactivity (IR) predicts the occurrence of a subset of cardiovascular disease outcomes in adults with advanced type 2 diabetes mellitus from the Veterans Affairs Diabetes Trial (mean: age, 59 years; diabetes duration, 11 years; baseline hemoglobin A(1c), 9.5%). Plasma bFGF-IR was determined with a sensitive and specific 2-site enzyme-linked immunoassay in 399 patients at the baseline visit. These results were then evaluated as possible predictors of the occurrence of prespecified cardiovascular or coronary heart disease end points. There was a borderline-significant association (P = .07) between plasma bFGF-IR and the main study cardiovascular disease outcome (myocardial infarction, congestive heart failure, cerebrovascular accident, amputation, cardiovascular death, coronary, cerebrovascular or peripheral revascularization, and inoperable coronary artery disease). Plasma bFGF-IR was significantly associated with the occurrence of coronary heart disease (P = .01). After adjusting for clinical risk factors, bFGF (hazard ratio [HR], 1.013; 95% confidence interval [CI], 1.007-1.019; P < .0001), prior macrovascular event (HR, 3.55; 95% CI, 2.154-5.839; P < .0001), and duration of diabetes (HR, 1.041; 95% CI, 1.012-1.071; P = .0055) were all significantly associated with time to first postrandomization coronary heart disease occurrence. These results suggest that increased plasma bFGF-IR may be a novel risk marker for coronary heart disease occurrence in adult men with advanced type 2 diabetes mellitus.
碱性成纤维细胞生长因子 (bFGF) 是一种有效的内皮和平滑肌细胞有丝分裂原,通常不会在循环中出现。在成年 2 型糖尿病患者中,与持续性微量白蛋白尿(心血管疾病的风险标志物)相关的血浆 bFGF 样生物活性增加。在本研究中,我们测试了基线血浆 bFGF 免疫反应性(IR)是否可以预测退伍军人事务糖尿病试验(平均年龄:59 岁;糖尿病病程:11 年;基线血红蛋白 A1c:9.5%)中患有晚期 2 型糖尿病的成年人发生心血管疾病结局的一部分。在基线就诊时,使用敏感和特异性的 2 位点酶联免疫吸附试验测定 399 例患者的血浆 bFGF-IR。然后将这些结果评估为预测预先指定的心血管或冠心病终点发生的可能性。血浆 bFGF-IR 与主要研究心血管疾病结局(心肌梗死、充血性心力衰竭、脑血管意外、截肢、心血管死亡、冠状动脉、脑血管或外周血运重建以及无法手术的冠状动脉疾病)之间存在边缘显著相关性(P=0.07)。血浆 bFGF-IR 与冠心病的发生明显相关(P=0.01)。在校正临床危险因素后,bFGF(危险比[HR],1.013;95%置信区间[CI],1.007-1.019;P<.0001)、先前的大血管事件(HR,3.55;95%CI,2.154-5.839;P<.0001)和糖尿病病程(HR,1.041;95%CI,1.012-1.071;P=0.0055)均与首次随机后冠心病发生时间显著相关。这些结果表明,血浆 bFGF-IR 增加可能是成年 2 型糖尿病男性冠心病发生的新的风险标志物。