Effects of fenofibrate treatment on cardiovascular disease risk in 9,795 individuals with type 2 diabetes and various components of the metabolic syndrome: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study

OBJECTIVE—We explored whether cardiovascular disease (CVD) risk and the effects of fenofibrate differed in subjects with and without metabolic syndrome and according to various features of metabolic syndrome defined by the Adult Treatment Panel III (ATP III) in subjects with type 2 diabetes in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study.RESEARCH DESIGN AND METHODS—The prevalence of metabolic syndrome and its features was calculated. Cox proportional models adjusted for age, sex, CVD status, and baseline A1C levels were used to determine the independent contributions of metabolic syndrome features to total CVD event rates and the effects of fenofibrate.RESULTS—More than 80% of FIELD participants met the ATP III criteria for metabolic syndrome. Each ATP III feature of metabolic syndrome, apart from increased waist circumference, increased the absolute risk of CVD events over 5 years by at least 3%. Those with marked dyslipidemia (elevated triglycerides ≥2.3 mmol/l and low HDL cholesterol) were at the highest risk of CVD (17.8% over 5 years). Fenofibrate significantly reduced CVD events in those with low HDL cholesterol or hypertension. The largest effect of fenofibrate to reduce CVD risk was observed in subjects with marked dyslipidemia in whom a 27% relative risk reduction (95% CI 9–42, P = 0.005; number needed to treat = 23) was observed. Subjects with no prior CVD had greater risk reductions than the entire group.CONCLUSIONS—Metabolic syndrome components identify higher CVD risk in individuals with type 2 diabetes, so the absolute benefits of fenofibrate are likely to be greater when metabolic syndrome features are present. The highest risk and greatest benefits of fenofibrate are seen among those with marked hypertriglyceridemia.Subjects with metabolic syndrome have a higher risk for future cardiovascular disease (CVD) events and are more likely to develop diabetes (1). The various components of metabolic syndrome (abdominal obesity, dyslipidemia, hypertension, and glucose deregulation) confer differential risk for CVD based on the extent to which they deviate from healthy normality. The guidelines most commonly used clinically to define metabolic syndrome are the National Cholesterol Education Program Adult Treatment Panel III (ATP III) guidelines (2). The exact role of each individual metabolic syndrome component in modifying risk once diabetes is present has varied in previous studies (3,4).The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study was designed to assess the long-term effect of fenofibrate on CVD events in subjects with type 2 diabetes (5–7). The cohort of 9,795 subjects followed for an average of 5 years was sufficient to explore whether CVD event rates were increased in subjects with or without various metabolic syndrome features. Because fenofibrate modifies lipid parameters by changing LDL particle morphology, increasing HDL cholesterol, and reducing triglycerides, CVD event rates may be reduced to a larger degree in those with metabolic syndrome features reflecting a more atherogenic lipid profile at baseline.In this article, we explored the clinical relevance of metabolic syndrome and its features when type 2 diabetes is established and whether reductions in CVD event rates with fenofibrate differ according to the presence of metabolic syndrome or its particular features. We also explored the value of a higher cut point for marked dyslipidemia, using an elevated triglyceride level (≥2.3 mmol/l) either alone or in combination with a low plasma HDL cholesterol level as defined in the Helsinki Heart Study (HHS) (8).