"In women suspected of having an insufficient supply of blood to the heart, called myocardial ischemia, the presence of the metabolic syndrome is highly prognostic of future cardiovascular risk, whereas measurement of BMI alone appears to confer little independent value in determining cardiovascular risk," said Steven Reis, M.D., associate professor of medicine at the University of Pittsburgh School of Medicine and senior author of the study. "Abnormal metabolism was independently associated with a significantly increased risk of death or a major adverse cardiovascular event."
People with three or more of the following criteria are classified as having metabolic syndrome: waist circumference greater than 35 inches, fasting triglycerides greater than 150mg/dl, HDL cholesterol less than 50mg/dl, hypertension or the use of anti-hypertensive drug therapy, and fasting glucose greater than 110mg/dl.
The study included 780 women enrolled in the WISE study, ages 21 to 86 years, in whom the presence or absence of metabolic syndrome could be determined. All women were clinically referred for coronary angiography to evaluate suspected myocardial ischemia at one of four study sites. Each woman had a baseline evaluation that included collection of demographic information, risk factors for coronary artery disease, medication use, medical and reproductive history, symptom and psychosocial evaluation, a physical examination with blood pressure and physical measurements, and sampling of blood in the fasting state for lipid, glucose, insulin, reproductive hormone, and inflammatory marker core lab evaluations.
Follow-up for the occurrence of untoward cardiovascular events was obtained by annual telephone and/or mail contact. The primary clinical outcomes of interest were death or a major adverse cardiovascular event (nonfatal myocardial infarction, stroke, congestive heart failure). The median length of follow-up was 3.5 years among the 739 surviving women and 1.3 years for the 41 non-surviving women.
The study found that compared with normal-weight women with normal metabolic status, dysmetabolic women (with diabetes and metabolic syndrome) who were normal weight, overweight or obese had approximately 3.1, 2.6 and 1.9 times higher adjusted odds of having significant coronary artery disease. The three-year survival rate was significantly higher in women with normal metabolic status than in those who were dysmetabolic (97.2% vs. 91.5%), with consistently higher survival observed at all levels of BMI. Within levels of metabolic status, obese and overweight individuals appeared to have nominally better three-year event-free survival than those with normal BMI.
Study findings also indicate that normal-weight women with metabolic syndrome had a significantly increased cardiovascular risk. Similarly, overweight and obese women with normal metabolism have a relatively low cardiovascular risk.
"These results suggest that the clinical evaluation of abnormal metabolism (metabolic syndrome and diabetes) should play a more important role than determination of obesity alone in cardiovascular risk stratification in women," said Kevin Kip, Ph.D., study author and assistant professor of epidemiology at the University of Pittsburgh Graduate School of Public Health. "One possible explanation for this finding is that measurement of BMI to define overweight and obesity does not quantify the magnitude or ratio of subcutaneous-to-visceral fat in a given individual. The visceral fat area, which is associated with insulin resistance, appears to be an important link among many components of the metabolic syndrome, such as dyslipidemia and hypertension."
According to study researchers, the evaluation of metabolic status should be considered in all women regardless of weight status.
"While recommending weight loss in overweight and obese women remains prudent, control of all modifiable risk factors in both normal and overweight persons to prevent the transition to, or reduce the manifestations of, the metabolic syndrome should be considered the ultimate goal," Dr. Reis stated.
Future studies of cardiovascular risk should not only incorporate the classification of metabolic status, but should also evaluate the role of inflammatory activity as a potential mediator of the epidemiologic association among obesity, metabolic status and cardiovascular risk, the study concluded.
In addition to the University of Pittsburgh, other WISE study centers include the University of Alabama at Birmingham; University of Florida, Gainesville; and Allegheny General Hospital in Pittsburgh.