Department of Endocrinology and Metabolism Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai China.
Shanghai Key Laboratory of Diabetes Mellitus Shanghai Clinical Center of Diabetes Shanghai China.
J Am Heart Assoc. 2020 Jun 2;9(11):e015226. doi: 10.1161/JAHA.119.015226. Epub 2020 May 20.
Background FGF21 (fibroblast growth factor 21), a novel hepatokine regulating lipid metabolism, has been linked to atherosclerotic disease. However, whether this relationship exists in patients without nonalcoholic fatty liver disease is unclear. We assessed the association between serum FGF21 levels and atherosclerosis in patients without nonalcoholic fatty liver disease, and investigated whether baseline FGF21 could predict incident atherosclerotic cardiovascular disease in a 7-year prospective cohort. Methods and Results Baseline serum FGF21 was measured in a cross-sectional cohort of 371 patients with type 2 diabetes mellitus without nonalcoholic fatty liver disease (determined by hepatic magnetic resonance spectroscopy), and in a population-based prospective cohort of 705 patients from the Shanghai Diabetes Study. In the cross-sectional study, FGF21 was significantly higher in patients with than in those without subclinical carotid atherosclerosis (<0.01). The association remained significant after adjusting for demographic and traditional cardiovascular risk factors. In the prospective cohort, 80 patients developed atherosclerotic cardiovascular disease during follow-up. Baseline FGF21 was significantly higher in those who developed ischemic heart disease or cerebral infarction than in those who did not. Using a cutoff serum concentration of 232.0 pg/mL, elevated baseline FGF21 independently predicted incident total atherosclerotic cardiovascular disease events, ischemic heart disease, and cerebral infarction in a nondiabetic population (all <0.05), and significantly improved the discriminatory and reclassifying abilities of our prediction model after adjustment for established cardiovascular risk factors. Conclusions This study provides the first evidence that FGF21 levels are elevated in patients without nonalcoholic fatty liver disease with subclinical atherosclerosis. Baseline FGF21 is an independent predictor of atherosclerotic cardiovascular disease and represents a novel biomarker for primary prevention in the general population.
成纤维细胞生长因子 21（fibroblast growth factor 21，FGF21）是一种新型的肝源细胞因子，可调节脂代谢，与动脉粥样硬化疾病有关。然而，在没有非酒精性脂肪肝疾病的患者中，这种关系是否存在尚不清楚。我们评估了血清 FGF21 水平与无非酒精性脂肪肝患者动脉粥样硬化之间的关系，并研究了基线 FGF21 是否可以预测 7 年前瞻性队列中的动脉粥样硬化性心血管疾病事件。
在无非酒精性脂肪肝（通过肝脏磁共振波谱测定）的 2 型糖尿病患者的横断面队列（n=371）和来自上海糖尿病研究的基于人群的前瞻性队列（n=705）中测量了基线血清 FGF21。在横断面研究中，患有亚临床颈动脉粥样硬化的患者血清 FGF21 明显高于无亚临床颈动脉粥样硬化的患者（<0.01）。在调整了人口统计学和传统心血管危险因素后，这种关联仍然具有统计学意义。在前瞻性队列中，80 例患者在随访期间发生了动脉粥样硬化性心血管疾病。与未发生缺血性心脏病或脑梗死的患者相比，发生缺血性心脏病或脑梗死的患者基线 FGF21 明显更高。使用 232.0 pg/mL 的截断血清浓度，基线 FGF21 可独立预测非糖尿病人群中总动脉粥样硬化性心血管疾病事件、缺血性心脏病和脑梗死的发生（均<0.05），并且在调整了已建立的心血管危险因素后，显著改善了我们的预测模型的区分能力和再分类能力。
本研究首次提供了证据，表明亚临床动脉粥样硬化患者无非酒精性脂肪肝疾病的 FGF21 水平升高。基线 FGF21 是动脉粥样硬化性心血管疾病的独立预测因子，是普通人群一级预防的新的生物标志物。
