Abstract 15450: Plasma Levels of Fatty Acid-binding Protein 4 and Cardiovascular Mortality Among Diabetes Patients: a Prospective Investigation in the Health Professionals Follow-up Study
Background: Fatty acid-binding protein 4 (FABP4) is highly expressed in adipocytes and macrophages. Animal studies and limited human evidence from general populations have suggested a positive association between circulating FABP4 levels and an array of cardiovascular disease (CVD) outcomes, though little prospective evidence exists regarding FABP4 levels in relation to CVD mortality among patients with diabetes. FABP4 expression is regulated by free fatty acids and insulin, both of which are elevated in patients with diabetes or insulin resistance. Therefore, we want to examine whether FABP4 may explain the particularly high CVD mortality observed among diabetics.
Methods: We measured plasma FABP4 levels among 950 men who participated in the Health Professionals Follow-up Study and reported having diabetes through 2004. Linear regression models were applied to evaluate the association between FABP4 levels and CVD risk factors. Hazard ratios (HRs) of CVD mortality were computed using Cox proportional hazard regression.
Results: Higher levels of FABP4 were significantly associated with an adverse profile of CVD risk biomarkers, including elevated levels of triglycerides and inflammatory markers, and lower levels of high-density lipoprotein cholesterol, and adiponectin (all P<0.003). Between baseline blood draw (1993-1995) and 2010, we documented 201 CVD deaths during a total of 12787.5 person-years of follow-up. After multivariate adjustment for potential confounders, including age at blood collection, smoking, BMI, physical activity, and diet quality, higher FABP4 levels were associated with an increased CVD mortality: the HRs (95% CIs) across tertiles of FABP4 levels were 1.0, 1.09 (0.74, 1.61) and 1.79 (1.24, 2.59) for CVD mortality (Ptrend<0.001). The associations for CVD mortality were attenuated but remained significant after adjustment for triglycerides, hsCRP, TNF-r2, and adiponectin, with HRs (95%CIs) across tertiles of FABP4 levels of 1.0, 1.12 (0.74, 1.67), and 1.56 (1.04, 2.33) (Ptrend=0.02).
Conclusions: These data indicate that elevated circulating FABP4 levels are independently associated with an elevated CVD mortality in U.S. men with diabetes.
Author Disclosures: H. Wu: None. J. Huang: None. S.E. Chiuve: None. E.B. Rimm: None. P. Selberg-Franks: None. J.B. Meigs: None. F.B. Hu: None. Q. Sun: None.
- © 2014 by American Heart Association, Inc.