Impact of metabolic syndrome and its components on cardiovascular disease event rates in 4900 patients with type 2 diabetes assigned to placebo in the field randomised trial

Background: Patients with the metabolic syndrome are more likely to develop type 2 diabetes and may have an increased risk of cardiovascular disease (CVD) events. We aimed to establish whether CVD event rates were influenced by the metabolic syndrome as defined by the World Health Organisation (WHO), the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) and the International Diabetes Federation (IDF) and to determine which component(s) of the metabolic syndrome (MS) conferred the highest cardiovascular risk in in 4900 patients with type 2 diabetes allocated to placebo in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial. Research design and methods: We determined the influence of MS variables, as defined by NCEP ATPIII, IDF and WHO, on CVD risk over 5 years, after adjustment for CVD, sex, HbA(1c), creatinine, and age, and interactions between the MS variables in a Cox proportional-hazards model. Results: About 80% had hypertension, and about half had other features of the metabolic syndrome (IDF, ATPIII). There was no difference in the prevalence of metabolic syndrome variables between those with and without CVD at study entry. The WHO definition identified those at higher CVD risk across both sexes, all ages, and in those without prior CVD, while the ATPIII definition predicted risk only in those aged over 65 years and in men but not in women. Patients meeting the IDF definition did not have higher risk than those without IDF MS. CVD risk was strongly influenced by prior CVD, sex, age (particularly in women), baseline HbA1(c), renal dysfunction, hypertension, and dyslipidemia (low HDL-c, triglycerides > 1.7 mmol/L). The combination of low HDL-c and marked hypertriglyceridemia (> 2.3 mmol/L) increased CVD risk by 41%. Baseline systolic blood pressure increased risk by 16% per 10 mmHg in those with no prior CVD, but had no effect in those with CVD. In those without prior CVD, increasing numbers of metabolic syndrome variables (excluding waist) escalated risk. Conclusion: Absence of the metabolic syndrome (by the WHO definition) identifies diabetes patients without prior CVD, who have a lower risk of future CVD events. Hypertension and dyslipidemia increase risk.