Metabolic Syndrome Helps Predict Cardiovascular Disease and Diabetes Risk News Author: Laurie Barclay, MD CME Author: Charles Vega, MD, FAAFP Disclosures Release Date: January 4, 2007; Valid for credit through January 4, 2008 Credits Available Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)™ for physicians; Family Physicians - up to 0.25 AAFP Prescribed credit(s) for physicians January 4, 2007 — Metabolic syndrome, as defined by 3 different groups, helps predict cardiovascular disease and diabetes risk, according to the results of a study reported in the January issue of Diabetes Care. "The clinical value of metabolic syndrome is uncertain," write Carlos Lorenzo, MD, of the University of Texas Heath Science Center at San Antonio, and colleagues. "Thus, we examined cardiovascular disease (CVD) and diabetes risk prediction by the National Cholesterol Education Program (NCEP)–Adult Treatment Panel III (ATPIII), International Diabetes Federation, and World Health Organization definitions of the metabolic syndrome." Using data from the San Antonio Heart Study (n = 2559), the investigators analyzed the risks associated with the metabolic syndrome, the NCEP multiple risk-factor categories, and 2-hour glucose values. Age range was 25 to 64 years, and mean duration of follow-up was 7.4 years. Both ATPIII-defined metabolic syndrome plus age of at least 45 years and multiple (≥ 2) risk factors plus a 10-year coronary heart disease risk of 10% to 20% were associated with similar cardiovascular disease risk in men without coronary heart disease, as well as those with coronary heart disease risk equivalents. For ATPIII-defined metabolic syndrome plus age of 45 years or older, the odds ratio (OR) was 9.25 (95% confidence interval [CI], 4.85 - 17.7). For multiple risk factors plus a 10-year coronary heart disease risk of 10% to 20%, OR was 11.9 (95% CI, 6.00 - 23.6). In women, multiple risk factors plus a 10-year coronary heart disease risk of 10% to 20% was infrequent, occurring in only 10 of 1254 women. However, predictors of cardiovascular disease in women were either a 10-year coronary heart disease risk of 5% to 20% (OR, 7.72; 95% CI, 3.42 - 17.4) or ATPIII-defined metabolic syndrome plus age 55 years or older (OR, 4.98; 95% CI, 2.08 - 12.0). In a model containing age, sex, ethnic origin, family history of diabetes, and 2-hour and fasting glucose values, ATPIII-defined metabolic syndrome increased the area under the receiver operating characteristic curve (0.857 vs 0.842; P = .013). All 3 metabolic syndrome definitions were associated with similar risks for CVD and diabetes. "Metabolic syndrome is associated with a significant CVD risk, particularly in men aged ≥ 45 years and women aged ≥ 55 years," the authors write. "The metabolic syndrome predicts diabetes beyond glucose intolerance alone." Study limitations include wide CIs for some of the results, particularly in the assessment of cardiovascular disease risk among women, and data on cardiovascular-disease outcomes derived from questionnaires and death certificates, leading to the possible underestimation of the risk for cardiovascular disease. "ATPIII, IDF [International Diabetes Federation], and WHO [World Health Organization] definitions of the metabolic syndrome have a similar ability to predict incident CVD and diabetes, even though they have different sensitivity and FPR [false-positive rate]," the authors conclude. "The metabolic syndrome is a simple method that can be used to identify individuals who are free of coronary heart disease and/or coronary heart disease risk equivalents but who are at increased risk for future CVD risk. This might be a step forward over routine Framingham risk scoring in some subjects." The National Heart, Lung, and Blood Institute supported this work. Diabetes Care. 2007;30:8-13. Clinical Context Although the metabolic syndrome has been proven to predict incident type 2 diabetes, it has come under some criticism recently because of a possible lack of overall clinical utility. First, different definitions of the metabolic syndrome can confuse clinicians and patients. Second, the value of the metabolic syndrome in predicting incident cardiovascular events is not clear, especially compared with established risk factors. Clinicians' confusion over the role of the metabolic syndrome might lead to the mismanagement of patients with moderate cardiovascular risk. The current study uses an established cohort of patients to determine the relative utility of the metabolic syndrome in predicting incident diabetes and cardiovascular disease. Study Highlights The patient cohort was drawn from the San Antonio Heart Study, a prospective evaluation of Mexican American and non-Hispanic white individuals between the ages of 25 and 64 years. Participants underwent a baseline assessment of cardiovascular risk factors, including measurement of fasting serum glucose and serum glucose following a carbohydrate load. Participants were followed up for incident cardiovascular disease during a median period of 7.4 years. Cardiovascular disease was defined by self-reports of heart attack, stroke, and coronary heart revascularization procedures, or by any mention of cardiovascular death on the death certificate. The authors compared the metabolic syndrome, as defined by NCEP-ATPIII, the International Diabetes Federation, and the World Health Organization, with stratification of cardiovascular risk based on the Framingham data system. 2559 subjects were followed up for incident cardiovascular disease, which occurred at rates of 8.5% and 4.3% among men and women, respectively. The mean age of participants at baseline was 43 years, and 65.5% of subjects were women. All definitions of the metabolic syndrome were significant in predicting a higher risk for cardiovascular disease above and beyond the risk associated with single traditional cardiovascular risk factors. The International Diabetes Federation definition of the metabolic syndrome had the highest sensitivity in predicting cardiovascular disease, but it was also associated with the highest false-positive rate. The metabolic syndrome was most effective in predicting cardiovascular disease among men older than 45 years and women older than 55 years. Among men, the predictive value of ATPIII-defined metabolic syndrome plus age of at least 45 years was similar to a Framingham 10-year coronary heart disease risk between 10% to 20% plus at least 2 known cardiovascular risk factors (ORs, 9.25 and 11.9, respectively). Among women, a Framingham 10-year coronary heart disease risk of 5% to 20% produced an OR of cardiovascular disease of 7.72, which was similar to the OR of 4.98 associated with ATPIII-defined metabolic syndrome plus age older than 55 years. The metabolic syndrome was not useful in predicting cardiovascular events in patients with a history of coronary heart disease or coronary heart disease equivalents. The predictive value of the metabolic syndrome for diabetes was similar to that of the 2-hour post-glucose test. Again, the International Diabetes Federation definition of the metabolic syndrome was the most sensitive in predicting diabetes, but also carried the highest false-positive rates. When glucose intolerance was discounted as part of the metabolic syndrome, the metabolic syndrome remained a significant risk factor for diabetes. The presence of impaired fasting glucose with the metabolic syndrome raised the risk for diabetes significantly over either risk factor alone.