Abstract

Background: In the FIELD trial, a 5-year randomized double-blind placebo-controlled trial of fenofibrate vs. placebo in 9,795 adults with type 2 diabetes (T2D), the only standard lipid parameter correlating with microvascular (renal) events was triglycerides. Given the high prevalence of stroke among diabetic patients, we explored associations between lipoprotein subfractions and risk for stroke in the FIELD trial. Methods: We performed ultracentrifugation using the vertical auto profile (VAP, Atherotech) on plasma (baseline and after 6 weeks of fenofibrate). Analyses were performed using Cox proportional hazards and logistic regression for new on-study events. Results were adjusted for gender and fenofibrate or placebo allocation. Results: HDL related analytes (HDL-C, HDL3-C, apo A1, apoA2) correlated with reduced risk for all stroke. LDL and its subfractions and Lp(a)-C did not. VLDL and its subfractions, non-HDL-C, triglycerides, apo B, apo En, various ratios incorporating apo C3, and the ratios of apoB/A1 and apoB/apoA2 all correlated with increased risk for stroke. Conclusions: VAP identifies multiple lipoprotein subclasses, apoproteins, and VAP subclass/apoprotein ratios associated with stroke. Many of these measures improved with fenofibrate therapy.

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