Serum Levels of Fibroblast Growth Factor 19 Are Inversely Associated with Coronary Artery Disease in Chinese Individuals

et al. (2013) Serum Levels of Fibroblast Growth Factor 19 Are Inversely Associated with Coronary Artery Disease in Chinese Individuals. PLoS ONE 8(8): e72345. doi:10.1371/journal.pone.0072345 Serum Levels of Fibroblast Growth Factor 19 Are Inversely Associated with Coronary Artery Disease in Chinese Individuals Yaping Hao Jian Zhou Mi Zhou Xiaojing Ma Zhigang Lu Meifang Gao Xiaoping Pan Junling Tang Yuqian Bao Weiping Jia Yan Gong, College of Pharmacy, University of Florida, United States of America Background: The fibroblast growth factor 19 (FGF19) has been implicated in recent studies as a potential regulator of glucose and lipid metabolism, which may lead to atherosclerosis. Here, we investigated the association of FGF19 with the presence and severity of coronary artery disease (CAD) in a Chinese population. Methods: A total of 315 patients with suspected or established CAD, including 205 males and 110 postmenopausal females, were enrolled and assessed by coronary angiography. CAD severity was determined by the Gensini score. Serum FGF19 was measured by quantitative sandwich ELISA. Results: FGF19 levels were not significantly different between male and female patients (median [interquartile range], 143.40 [87.96-250.80] vs. 141.60 [87.13-226.32] pg/mL, P = 0.773). CAD patients had lower levels of FGF19 than those without CAD (128.20 [80.62-226.58] vs. 188.00 [105.10-284.70] pg/mL, P = 0.007). FGF19 was negatively correlated with 2hPG (r = -0.150, P = 0.008), FINS (r = -0.169, P = 0.004), HOMA-IR (r = -0.171, P = 0.004), and the Gensini score (r = -0.141, P = 0.012), but positively correlated with HDL-c (r = 0.116, P = 0.041) and adiponectin (r = 0.128, P = 0.024). Moreover, FGF19 was found to be independently correlated with 2hPG (b = -0.146, P = 0.022) and adiponectin (b = 0.154, P = 0.016). After adjusting for other CAD risk factors, FGF19 was demonstrated to be an independent factor for Gensini score (b = -0.140, P = 0.019) and the presence of CAD (b = -1.248, P = 0.036). Conclusions: Serum FGF19 is associated with the presence and severity of CAD in a Chinese population. - Funding: This work was funded by 973 Program of China (2013CB530606), National Key Technology R&D Program of China (2012BAI02B03), Project of National Natural Science Foundation of China (81100590), Shanghai Municipal Hospitals Project of Appropriate Technology (SHDC12012201), and Key Discipline of Public Health of Shanghai (Epidemiology)(12GWZX0104). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. . These authors contributed equally to this work. Fibroblast growth factor 19 (FGF19) is mainly synthesized by the intestinal epithelium, and is believed to function predominantly as a regulator of human bile acid metabolism [1,2]. Recent studies, however, have uncovered a role of FGF19 in maintaining the balance of energy metabolism, presumably through its functions as an endocrine hormone [3,4]. Indeed, when FGF19 was overexpressed in a transgenic mouse model, the major phenotypic effects were lower levels of body weight and cholesterol than the wild-type mouse, and it was determined that FGF19 played a vital role in maintaining normal glucose tolerance and insulin sensitivity [5]. Similar results were obtained when high-fatfed mice were treated with recombinant FGF19 [6]. Despite these findings and the well-established link between metabolic disorders and cardiovascular disease, few clinical studies have reported on potential association of FGF19 with coronary artery disease (CAD). A decrease in FGF19 levels has been demonstrated in patients with metabolic syndrome (MS), obesity, and non-alcoholic fatty liver disease [79]. Each of these three particular diseases is theorized to be predisposing factor of CAD, and the relation with FGF19 may suggest its contribution to CAD. The current study was designed to investigate the relationship between FGF19 and CAD in human patients, using coronary angiographic findings (the gold standard of CAD diagnosis) and the Gensini score (to assess the severity of CAD [10]) to perform a correlation analysis of the factor-disease interrelation, including relations with various demographic and clinical factors. Ethics Statement The Ethics Committee of Shanghai Jiao Tong University Affiliated Sixth Peoples Hospital approved our study. All study participants provided written informed consent. Study participants Patients presenting at the Department of Cardiology of Shanghai Jiao Tong University Affiliated Sixth Peoples Hospital between July 2008 and Jan 2010 with suspected or established CAD were recruited for the study. Each study participant underwent coronary angiography and completed a standardized questionnaire about previous and present illness, medication history, and smoking status. Patients with the following characteristics were excluded from study enrollment: severe liver and kidney disease; biliary system disorders; recent myocardial infarction (,3 months prior); acute coronary syndrome; symptomatic heart failure; major trauma or surgery; or presence of tumor. A total of 315 patients, including 205 males and 110 postmenopausal females (mean age: 66.4610.1 years), were enrolled for analysis. Diagnostic criteria Coronary angiographic examinations were performed using the standard Judkins techniques [11], and angiograms were assessed by two experienced cardiologists who were blinded to the clinical traits of the patients. CAD diagnosis was made according to the presence of $50% stenosis in $1 main coronary artery. The Gensini score system was used to quantitatively assess the extent of each observed coronary lesion. Anthropometric evaluation Weight and height were recorded and used to calculate the body mass index (BMI; kg/m2). Waist circumference (W) was measured at the midpoint between the inferior border of the lowest rib and the upper margin of the iliac crest on the midaxillary line. Biochemical measurements Patients were instructed to fast overnight (10 h), and venous blood samples were collected and stored at 80uC until use. The Hitachi 7600-020 auto-analyzer (Tokyo, Japan) was used to measure fasting plasma glucose (FPG), 2 h postprandial glucose (2hPG) (both by the glucose oxidase method), and lipid profiles, including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) (by enzymatic methods). The Bio-Rad Variant II high-pressure liquid chromatogram (Hercules, CA, USA) was used to measure glycated hemoglobin A1c (HbA1c). Radioimmunoassay was used to measure serum fasting insulin (FINS) (Linco Research Inc., St Charles, MO, USA). The homeostasis model assessment index (HOMA-IR) was used to assay insulin resistance (IR) [12]. Quantitative sandwich enzymelinked immunosorbent assay (ELISA) kits (f (...truncated)