Lipoprotein Subfractions Are Associated With Diabetic Cardiovascular Disease And Death Among 9,795 Patients In The Field Trial

Background: The FIELD study, a 5-year randomized double-blind placebo-controlled trial of fenofibrate vs. placebo in 9,795 adults with type 2 diabetes (T2D), was designed to evaluate effects on coronary and cardiovascular (CV) events. In this analysis we explored associations between lipoprotein subfractions and on-study CV events and death. Methods: We performed ultracentrifugation using the vertical auto profile (VAP, Atherotech) on plasma at baseline and after 6 weeks of fenofibrate (active run-in) exposure. Analyses were performed using Cox proportional hazards and logistic regression analysis. Results were adjusted for gender, with log transformation as necessary. Results: Total CVD and CV death correlated negatively with HDL-C and its subfractions, as well as apoA1 and apoA2. In addition to LDL-C, small, dense LDL (LDL4-C), non-HDL-C, apo B, triglycerides, and apoC3 increased risk for total CVD. For CVD death, HDL-C and its subfractions were protective, while apo B, triglycerides, apo C3, and various VLDL-C species were associated with increased risk. Conclusions: Detailed lipoprotein analysis identifies multiple lipoprotein subclasses and apolipoproteins and their ratios associated with acute cardiovascular events and death. Serum levels of a number of these lipoprotein and apoprotein species were improved by fenofibrate therapy. Disclosure S.R. Jones: None. A.J. Jenkins: Advisory Panel; Self; Abbott, Australian Diabetes Society, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Mylan. Speaker’s Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc. A.S. Januszewski: None. R.L. OConnell: None. L. Li: None. D. Sullivan: None. M. Taskinen: Advisory Panel; Self; Novo Nordisk A/S. Consultant; Self; Akcea Therapeutics, Chiesi USA, Inc. Research Support; Self; Amgen Inc., Novo Nordisk A/S. Speaker’s Bureau; Self; Amgen Inc. R. Scott: None. G.F. Watts: None. P.J. Barter: Advisory Panel; Self; Merck & Co., Inc., Pfizer Inc. R. Simes: None. P.P. Toth: Consultant; Self; Amarin Corporation, Amgen Inc., AstraZeneca, Kowa Pharmaceutical Europe Co. Ltd., Novo Nordisk Inc. Speaker’s Bureau; Self; Amarin Corporation, Amgen Inc., Merck & Co., Inc., Novo Nordisk Inc., Regeneron Pharmaceuticals, Sanofi US. A.C. Keech: None.