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

Abstract

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 >or=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.

Figure 1

A: CVD event rates (percentage) in subjects receiving placebo who had diabetes (DM) alone or diabetes with any of one to four additional features of metabolic syndrome. B: CVD event rates (percentage) for subjects with hypertension, increased waist circumference, triglyceride levels (TG) >1.7 mmol/l, and low HDL cholesterol (HDLc) levels with or without metabolic syndrome (MS).

Figure 2

Forest plot of effects of fenofibrate on cardiovascular events adjusted for sex, prior CVD, age at visit 1, and baseline A1C (HR and 95% CI): ATP III waist circumference criteria (men >102 cm and women >88 cm), raised triglyceride levels (TG) (≥1.7 mmol/l or ≥2.3 mmol/l), reduced HDL cholesterol (HDLc) levels (men <1.03 mmol/l and women <1.29 mmol/l), and ATP III metabolic syndrome (MS) criteria (diabetes and two others).

Figure 3

Cox regression model for effect of metabolic syndrome features on total CVD events, adjusted for age, sex, prior CVD status, A1C, and LDL cholesterol levels at baseline. F, female; HDLc, HDL cholesterol; M, male.