The metabolic syndrome, a clustering of metabolic risk factors, has been reported to be associated with the risk of cardiovascular disease (CVD) (1). Questions have been raised about which components of the metabolic syndrome are more strongly associated with CVD (2), whether other combinations of the components have stronger associations (3), and the role of waist circumference in the definition of metabolic syndrome in Asian populations (4), where obesity is typically less common than in the West. We address these questions using data from the Electricity Generating Authority of Thailand (EGAT) Study.

Details of the EGAT study have been reported elsewhere (5,6). Briefly, a total of 3,499 employees (2,702 men) aged 35–54 years were surveyed in 1985; blood samples were obtained after a 12-h overnight fast. The current analysis is limited to 2,545 men and 671 women with complete baseline data on metabolic and anthropometric measurements and for whom outcomes were available. No subjects had a history of myocardial infarction (MI) or stroke at entry.

According to the Adult Treatment Panel (ATP) III (7), the metabolic syndrome is present if an individual has three or more of the following: high triglycerides, low HDL cholesterol, high blood pressure, high fasting plasma glucose (FPG) or previously diagnosed type 2 diabetes (high FPG), and central obesity. The International Diabetes Federation (IDF) uses the same criteria as ATP III, except with the addition of central obesity as a requirement. To qualify as having the metabolic syndrome, an individual must have central obesity plus any two of the following: high triglycerides, low HDL cholesterol, hypertension, and diabetes (8). Outcomes analyzed were all-cause mortality and CVD (fatal or nonfatal MI or stroke) during a 17-year period (1985–2002). CVD was adjudicated by a committee, using standard criteria for confirmation (9,10).

McNemar's test was used to compare prevalence of the metabolic syndrome by ATP II and IDF definitions. Cox regression models were used to estimate associations with mortality and CVD. All models were adjusted for age, sex, current smoking status (yes/no), current alcohol consumption (yes/no), physical activity (<3 times per week or ≥3 times per week), and income (<5,000, 5,001–10,000, or ≥10,000 baht per month). Areas under receiver-operating characteristics curves (AUCs) were used to compare the predictive performance of models.

The prevalence of metabolic syndrome in 1985, according to ATP III and IDF, was 19.3 and 11.7% (P < 0.001) in men and 11.8 and 10.3% (P = 0.03) in women, respectively. Over 17 years, there were 135 (120 male and 15 female) CVD events (3.0 and 1.4 per 1,000 person-years in men and women, respectively) and 309 (276 male and 33 female) deaths (6.8 and 3.0 per 1,000 person-years in men and women). Subsequent analyses were limited to men because there were too few CVD events in women for reliable analyses.

Both metabolic syndrome definitions were more strongly associated with CVD than with all-cause mortality (Table 1). Compared with IDF, the ATP III criteria showed stronger, but not significantly different (P ≥ 0.14), associations. Among all possible sets of qualifying criteria, the combination of central obesity, high blood pressure, high FPG, and low HDL cholesterol yielded the greatest hazards ratio (HR) for CVD, followed by all five and then by low HDL cholesterol, high blood pressure, and high FPG. When all individual components were cross-adjusted for each other in the same model, only high blood pressure and high FPG were independently associated with CVD and mortality. An additional analysis, excluding those with diabetes at baseline, found that only high blood pressure was independently associated with each outcome.

Regardless of whether participants had central obesity, HRs comparing those with qualifying sets of metabolic syndrome components to those without were between 1.59 and 5.49. Only for the comparison of those with high triglyceride, high blood pressure, and high FPG versus those without were the HRs all significantly different from unity for both outcomes, with and without central obesity. The HRs and AUCs were higher for those with central obesity than for those without central obesity except for the comparison of high triglycerides, low HDL cholesterol, and high blood pressure but not for mortality.

In this study, the ATP III definition, using the Asian cutoff for waist circumference, produced a higher prevalence of metabolic syndrome and a stronger association with both CVD and all-cause mortality compared with the IDF definition. High blood pressure and high FPG were shown to be the most crucial components of the metabolic syndrome because only these components had independent effects, whereas with the three strongest associations with CVD, all included these two components; adding other components sometimes weakened the effect. It is likely that the effect of high FPG is due to diabetes at baseline or incidence of diabetes afterward. Whereas our findings support the theory that obesity increases the risk of CVD (4), they do not suggest that central obesity is a necessary component of metabolic syndrome because individuals without central obesity also have excess risk factors for CVD and death in this Asian population. This study found that the metabolic syndrome, as defined by either definition, performed no better than many of the models made up of constituent risk factors in predicting or discriminating CVD or all-cause mortality.

The authors thank the Faculty of Medicine, Ramathibodi Hospital, Mahidol University; the EGAT Study; and the Thai Health Promotion Foundation for their support.

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Published ahead of print at on 27 April 2007. DOI: 10.2337/dc07-0388.

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