Metabolic Syndrome Not Useful in Predicting Cardiovascular Risk

By Todd Neale
GLASGOW, Scotland, 24 may 2008-- A diagnosis of metabolic syndrome is strongly associated with a risk of developing diabetes, but not cardiovascular disease, researchers here concluded.
They reported the results of two prospective studies -- the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) and the British Regional Heart Study -- online this week in The Lancet.
In PROSPER, metabolic syndrome was not associated with increased risk of cardiovascular disease (HR 1.07, 95% CI 0.86 to 1.32) but was associated with a greater risk of diabetes (HR 4.41, 95% CI 3.33 to 5.84), Naveed Sattar, M.B.Ch.B., of the University of Glasgow, and colleagues found.
On the basis of initial findings in PROSPER, they conducted the British Regional Heart Study and found that metabolic syndrome was "modestly associated" with cardiovascular disease risk (HR 1.27, 95% CI 1.04 to 1.56) and strongly associated with risk of diabetes (HR 7.47, 95% CI 4.90 to 11.46).
"Our clear finding in both studies of substantial differing diabetes versus cardiovascular disease associations of metabolic syndrome and its components should aid better general understanding of differing risk patterns for these two diseases, which therefore should not be considered together," the researchers said.
The clinical usefulness of a diagnosis of metabolic syndrome in predicting risk of cardiovascular disease and diabetes is debated, according to the researchers.
To explore the issue, they first enrolled 4,812 men and women ages 70 to 82 in the PROSPER trial. To "corroborate and generalize" those findings, they enrolled 2,737 males ages 60 to 79 in the British Regional Heart Study. All participants were free from diabetes at baseline.
In PROSPER, after a mean follow-up of 3.2 years, there were 772 cases of incident cardiovascular disease and 287 cases of diabetes.
Overall, about 28% of participants met the criteria for metabolic syndrome.
Metabolic syndrome and each of its components were significantly associated with an increased risk of diabetes, with a fasting glucose of 6.1 mmol/L or higher most strongly predicting risk (HR 18.42, 95% CI 13.86 to 24.49).
Neither metabolic syndrome nor any of its components were significantly associated with risk of cardiovascular disease.
In the British Regional Heart Study, after a mean follow-up of seven years, there were 440 cases of cardiovascular disease and 105 cases of diabetes.
Overall, 27% of patients met the criteria for metabolic syndrome.
As in PROSPER, metabolic syndrome and each of its components were significantly associated with an increased risk of diabetes, with a fasting glucose of 6.1 mmol/L or higher representing the component that most strongly predicted risk (HR 5.97, 95% CI 4.07 to 8.76).
Metabolic syndrome (HR 1.27) and the components of low HDL cholesterol (HR 1.46, 95% CI 1.17 to 1.81) and high blood pressure (HR 1.68, 95% CI 1.26 to 2.24) were associated with risk of cardiovascular disease. The other three components of metabolic syndrome were not.
"These findings suggest that the pattern of risk factors for new-onset diabetes differs in many respects to that which predicts vascular events in elderly people," the researchers said.
"Our findings concur with data in middle-age populations for whom criteria for metabolic syndrome are inferior to, and do not enhance conventional methods for, risk prediction of coronary heart disease," they said.
In an accompanying comment, Richard Kahn, Ph.D., of the American Diabetes Association in Alexandria, Va., wrote that the findings of the study "put yet another nail in the coffin of the metabolic syndrome," noting that a simple, inexpensive test for fasting plasma glucose would be a better predictor of diabetes than the expensive procedure of diagnosing the syndrome.
"What seems to make the most sense is for clinicians to focus on global risk assessment that takes into account all the well-established cardiometabolic risk factors, and then to treat each abnormality appropriately," he said.
"Also," he said, "more research is needed to understand the cause of risk-factor clustering and the pathogenesis of insulin resistance. Both actions would better serve the health of those at risk of diabetes and cardiovascular disease than seeking a diagnosis of the metabolic syndrome."
The authors listed several limitations to the studies, including the lack of oral glucose tolerance tests, the use of BMI instead of waist circumference in PROSPER, and the potential weakening of associations by attrition bias.
The metabolic syndrome analysis for PROSPER was funded by a Diabetes U.K. project grant and the British Regional Heart Study is a British Heart Foundation Research Group. The study authors and Dr. Kahn declared no conflicts of interest.
Primary source: The LancetSource reference:Sattar N, et al "Can metabolic syndrome usefully predict cardiovascular disease and diabetes? Outcomes data from two prospective studies" Lancet 2008; DOI: 10.1016/S0140-6736(08)60602-9.