Two Heart Groups Defend Metabolic Syndrome Validity

Elsevier Global Medical News

Less than a month after two major diabetes organizations called metabolic syndrome a poorly defined and misleading diagnosis, the American Heart Association and the National Heart, Lung, and Blood Institute issued a joint statement reaffirming that the syndrome is valid and clinically useful.

The new AHA/NHLBI scientific statement basically confirms the recommendations on diagnosis and management of metabolic syndrome that were issued in 2001 as part of the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) report.

The statement also clarifies some issues, however, and provides some minor modifications to the ATP III definition of the metabolic syndrome--a term that denotes the clustering of interrelated metabolic risk factors for atherosclerotic cardiovascular disease.

Compared with the joint statement published last month by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD), the AHA/NHLBI statement offers a clearly different perspective on the meaning and value of a term that's now commonplace in the medical literature.

ADA and EASD Recommendations

Providers should avoid labeling patients with the term metabolic syndrome, as this might create the impression that the syndrome denotes greater risk than its components or is more serious than other CVD risk factors. Adults with any major CVD risk factor should be evaluated for the presence of other CVD risk factors. All CVD risk factors should be individually and aggressively treated. Patients with CVD risk variables above normal levels should receive counseling for lifestyle modification. At levels indicative of frank disease--such as blood pressure above 140/90 mm Hg or fasting plasma glucose of at least 126 mg/dL--treatment should correspond to established guidelines issued by the NHLBI and the ADA or other bodies. Until randomized controlled trials have been completed, there is no appropriate pharmacologic treatment for the metabolic syndrome, nor should it be assumed that pharmacologic therapy to reduce insulin resistance will be beneficial to patients with the metabolic syndrome. In population studies, the prevalence of metabolic syndrome differs by up to 24% between the ATP III and WHO definitions, depending on gender and ethnicity.

"Metabolic syndrome is a valuable clinical tool. Physicians must pay attention to it, and they must give enough attention to lifestyle (intervention)," said Scott M. Grundy, M.D., director of the Center for Human Nutrition at the University of Texas Southwestern Medical Center in Dallas. Dr. Grundy chaired the panel that wrote the joint statement.

While the diabetes organizations questioned the value of the syndrome as a predictor of cardiovascular disease--they said, for instance, that it's "uncertain" whether it's a useful marker of cardiovascular disease risk "above and beyond the risks associated with its individual components"--the AHA/NHLBI panel maintained that it's an important and useful predictor.

The absolute short-term (10-year) risk for major coronary heart disease events is not necessarily high--and may be best assessed by Framingham risk scoring--but the longer-term risk associated with the metabolic syndrome is "undoubtedly" elevated, regardless of the Framingham score, the panel said (Circulation 2005;DOI:10.1161/circulationaha.105.169404).

"The long-term risk is more than the sum of the parts--the risk multiplies," said Dr. Grundy.

"Nobody is asserting that metabolic syndrome is a disease. No one is saying it's a unified entity. It's a group of factors that tend to cluster together, and the diagnosis gives physicians an opportunity to identify people at long-term risk," said James I. Cleeman, M.D., cochair of the panel and coordinator of the NHLBI's National Cholesterol Education Program. "There's no question that risk increases when these risk factors (cluster)," he said in an interview.

Overall, the syndrome increases the risk for atherosclerotic cardiovascular disease 1.5-3 times and raises the risk for type 2 diabetes 3-5 times, he and Dr. Grundy said in an interview. The new statement essentially "ties up loose ends" and synthesizes information presented at NIH-sponsored conferences held after the ATP III report was released, Dr. Grundy said.

The statement maintains the same diagnostic criteria for metabolic syndrome--elevated waist circumference, elevated triglycerides, reduced HDL-C, elevated blood pressure, and elevated fasting glucose--and the requirement that three of the five criteria be present for a diagnosis.

Definitions of the Metabolic Syndrome

National Cholesterol Education Program/Adult Treatment Panel III Any three or more of the following criteria: Waist circumference greater than 102 cm in men and greater than 88 cm in women. Serum triglycerides greater than or equal to 150 mg/dL. Blood pressure greater than or equal to 130/85 mm Hg. HDL cholesterol less than 40 mg/dL in men and less than 50 mg/dL in women. Serum glucose greater than or equal to 110 mg/dL. (Greater than or equal to 100 mg/dL may be applicable.) World Health Organization Diabetes, impaired fasting glucose, impaired glucose tolerance, or insulin resistance (assessed by clamp studies) and at least two of the following criteria: Waist-to-hip ratio greater than 0.90 in men or greater than 0.85 in women. Serum triglycerides greater than or equal to 150 mg/dL or HDL cholesterol less than 35 mg/dL in men and less than 39 mg/dL in women. Blood pressure greater than or equal to 140/90 mm Hg. Urinary albumin excretion rate greater than 20 mg/min or albumin:creatinine ratio greater than or equal to 30 mg/g. Sources: American Diabetes Association and European Association for the Study of Diabetes

It also offers the following modifications and clarifications:

PIThe threshold for elevated fasting glucose is reduced from 110 to 100 mg/dL, in accordance with the revised ADA definition.

PITriglycerides, HDL-C levels, and blood pressure may be counted as abnormal when a patient is taking drug treatment for these factors.

PIThe threshold for waist circumference (102 cm in men and 88 cm in women) may be lowered in individuals or ethnic groups, particularly Asian Americans, who are prone to insulin resistance.

The panel stated that individuals who have established atherosclerotic cardiovascular disease or type 2 diabetes can still have the metabolic syndrome--a position that is at odds with the ADA-EASD statement.

The modified ATP III definition is almost identical to the definition released--also last month--by the International Diabetes Federation, Dr. Cleeman said. One difference is that the IDF requires the presence of abdominal obesity for diagnosis.

More research is needed on the most appropriate therapies for patients with the metabolic syndrome, but for now the "prime emphasis" should continue to focus on lifestyle interventions, the joint statement said.

Drug therapies for specific risk factors "may be indicated" when lifestyle changes are not sufficient.