Lee Chi Ho, Woo Yu Cho, Chow Wing Sun, Cheung Chloe Yu Yan, Fong Carol Ho Yi, Yuen Michele Mae Ann, Xu Aimin, Tse Hung Fat, Lam Karen Siu Ling
Department of Medicine, The University of Hong Kong, China.
Research Centre of Heart, Brain, Hormone and Aging, The University of Hong Kong, China.
J Am Heart Assoc. 2017 Jun 6;6(6):e005344. doi: 10.1161/JAHA.116.005344.
Fibroblast growth factor 21 (FGF21) has demonstrated beneficial effects on lipid and carbohydrate metabolism. In cross-sectional studies, an association of raised circulating FGF21 levels with coronary heart disease (CHD) was found in some but not all studies. Here we investigated prospectively whether baseline serum FGF21 levels could predict incident CHD in subjects with type 2 diabetes mellitus and no known cardiovascular diseases.
Baseline serum FGF21 levels were measured in 3528 Chinese subjects with type 2 diabetes mellitus recruited from the Hong Kong West Diabetes Registry. The role of baseline serum FGF21 levels in predicting incident CHD over a median follow-up of 3.8 years was analyzed using Cox regression analysis. Among 3528 recruited subjects without known cardiovascular diseases, 147 (4.2%) developed CHD over a mean follow-up of 4 years. Baseline serum log-transformed FGF21 levels were significantly higher in those who had incident CHD than those who did not (222.7 pg/mL [92.8-438.4] versus 151.1 pg/mL [75.6-274.6]; <0.001). On multivariable Cox regression analysis, baseline serum FGF21 levels, using an optimal cutoff of 206.22 pg/mL derived from our study, independently predicted incident CHD (hazard ratio, 1.55; 95% CI, 1.10-2.19; =0.013) and significantly improved net reclassification index and integrated discrimination improvement after adjustment for conventional cardiovascular risk factors.
We have demonstrated, for the first time, that serum FGF21 level is an independent predictor of incident CHD and might be usefully utilized as a biomarker for identifying type 2 diabetes mellitus subjects with raised CHD risk, for primary prevention.
成纤维细胞生长因子21(FGF21)已被证明对脂质和碳水化合物代谢具有有益作用。在横断面研究中,一些但并非所有研究都发现循环FGF21水平升高与冠心病(CHD)有关。在此,我们前瞻性地研究了基线血清FGF21水平是否能够预测2型糖尿病且无已知心血管疾病的受试者发生冠心病的情况。
对从香港西区糖尿病登记处招募的3528名2型糖尿病中国受试者进行了基线血清FGF21水平检测。使用Cox回归分析,分析了基线血清FGF21水平在中位随访3.8年期间预测冠心病发病的作用。在3528名招募的无已知心血管疾病的受试者中,147名(4.2%)在平均4年的随访中发生了冠心病。发生冠心病的受试者基线血清经对数转换的FGF21水平显著高于未发生冠心病的受试者(222.7 pg/mL [92.8 - 438.4] 对比151.1 pg/mL [75.6 - 274.6];P<0.001)。在多变量Cox回归分析中,根据我们研究得出的最佳临界值206.22 pg/mL,基线血清FGF21水平可独立预测冠心病发病(风险比,1.55;95%置信区间,1.10 - 2.19;P = 0.013),并且在调整传统心血管危险因素后,显著改善了净重新分类指数和综合判别改善情况。
我们首次证明,血清FGF21水平是冠心病发病的独立预测因子,可能作为一种生物标志物,用于识别具有较高冠心病风险的2型糖尿病受试者,以进行一级预防。