The relationship of fibroblast growth factor 21 with cardiovascular outcome events in the Fenofibrate Intervention and Event Lowering in Diabetes study

Abstract

Aims/hypothesis Circulating fibroblast growth factor 21 (FGF21) levels are often elevated in obesity, dyslipidaemia, insulin resistance and type 2 diabetes. This study investigated the relationship of plasma FGF21 levels with cardiovascular events in patients with type 2 diabetes. Methods Plasma FGF21 levels were measured by ELISA at baseline in 9,697 individuals with type 2 diabetes participating in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. We assessed the association of FGF21 levels with the incidence of different cardiovascular outcomes over 5 years. The primary outcome was total cardiovascular disease (CVD) events and the secondary outcomes were the four individual components: coronary heart disease events, total stroke, CVD mortality and coronary and carotid revascularisation. The tertiary outcome was hospitalisation for angina pectoris. Results Higher baseline FGF21 levels were associated with higher risks of all cardiovascular outcome events after adjusting for the study treatment allocation (all p<0.01). The Anthony C. Keech and Kerry-Anne Rye are joint senior authors.Electronic supplementary material The online version of this article (doi:10.1007/s00125-014-3458-7) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Role of Circulating Fibroblast Growth Factor 21 Measurement in Primary Prevention of Coronary Heart Disease Among Chinese Patients With Type 2 Diabetes Mellitus

“…Circulating FGF21 levels were found to be predictive of the primary outcome of total CVD over a median follow‐up of 5 years. However, analyses of secondary outcomes showed that the associations were positive for stroke, coronary, and carotid revascularization, but not CHD events, after adjusting for established CVD risk factors 20. A small study on 87 T2DM subjects from Poland also reported a predictive role of serum FGF21 levels with incident cardiovascular morbidity and mortality over 2 years,24 but no information on the prediction of incident CHD was provided.…”

“…Serum creatinine was measured and the eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation as described previously 18. Serum high‐sensitivity C‐reactive protein was measured with a high‐sensitivity, particle‐enhanced immunoturbidimetric assay (Roche Diagnostics, GmbH, Mannheim, Germany) and serum FGF21 was measured with ELISA kits (Antibody and Immunoassay Services, University of Hong Kong, Hong Kong, China) 19, 20…”

Relationship of fibroblast growth factor 21 with baseline and new on-study microvascular disease in the Fenofibrate Intervention and Event Lowering in Diabetes study

“…In the present study, baseline plasma samples were available for FGF21 measurement from 9697 (99.0%) out of 9795 patients from the FIELD study. FGF21 levels were measured using enzyme-linked immunosorbent assay kits (Antibody and Immunoassay Services, University of Hong Kong, Hong Kong) as described previously [7,12,17]. Briefly, a 60 μl plasma sample was diluted 1:1 (vol.:vol.)…”

“…Other variables of interest The measurement of clinical characteristics and details of the primary endpoint and other outcomes of the FIELD trial have been described previously [9][10][11][12][15][16][17]. Previous CVD comprised angina, myocardial infarction, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, stroke, peripheral vascular disease and revascularisation.…”

“…In the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, fenofibrate treatment has been demonstrated to reduce the risk of total cardiovascular disease (CVD) events as well as the risks of albuminuria, laser treatment for diabetic retinopathy and amputation in patients with type 2 diabetes over a follow-up period of 5 years [9][10][11]. Recently, we have reported that higher FGF21 levels at baseline predict a higher risk of total cardiovascular disease (CVD) events in patients with type 2 diabetes taking part in the FIELD study [12]. Previous studies have demonstrated an association between higher circulating FGF21 levels and diabetic nephropathy and retinopathy [13,14].…”