Introduction

The metabolic syndrome (syndrome X, the insulin resistance syndrome) is diagnosed by the presence of 3 or more abnormal findings using the following 5 thresholds:

• Triglyceride level >/= 150 mg/dL (1.7 mmol/L)
• HDL cholesterol < 40 mg/dL (1.0 mmol/L) for men, >/= 50 mg/dL (1.29 mmol/L) for women
• Fasting glucose >/= 110 mg/dL (6.1 mmol/L)
• Systolic blood pressure >/= 130 mm Hg, or diastolic >/= 85 mm Hg, or on antihypertensive medication
• Waist size >/= 40 inches (102 cm) for men, >/= 35 inches (88 cm) for women.

An analysis of data from the large West of Scotland Coronary Prevention Study has now shown the predictive value of the metabolic syndrome for the occurrence of coronary heart disease events (as expected from the criteria), and also for type 2 diabetes. The authors used BMI instead of waist size; they took as the threshold level a BMI > 28.8 kg/m2. The results of the study, which was done in men to assess the efficacy of pravastatin, are published in Circulation.

Method

A collective of 6,595 moderately hypercholesterolemic men were randomly assigned to receive pravastatin or placebo, and followed for an average of 4.9 years. Men with frank diabetes or previous myocardial infarction were excluded. During the study, new-onset diabetes was defined by at least two glucose levels >/= 126 mg/dL (7.0 mmol/L) and at least one fasting glucose > 36 mg/dL (2.0 mmol/L) above the subject's baseline level.

After exclusions, there were 6,447 men available for the CHD analysis, and 5,974 men for evaluation of new-onset diabetes. There were 404 CHD events and 139 new cases of diabetes diagnosed during the study.

Results

Based on the modified criteria outlined above, 1,621 men (26%) had the metabolic syndrome. Age and LDL cholesterol levels were similar in those with and without the syndrome, whereas C-reactive protein (CRP) was significantly raised in those with the syndrome.

Having the metabolic syndrome increased the risk for a CHD event; the hazards ratio (HR) was 1.76 (95% CI, 1.44-2.15). Somewhat surprisingly, it also increased the risk for the onset of type 2 diabetes - HR 3.5 (95% CI, 2.51-4.9).

The level of increased risk for CHD with metabolic syndrome was roughly equivalent to that of a 10-year increase in age, or being a current smoker. The metabolic syndrome continued to predict CHD events after multivariate analyses adjusting for conventional risk factors - HR 1.3 (95% CI, 1.0-1.67).

When 4 or more criteria (of the 5) were used to select for an 'enhanced' metabolic syndrome (instead of 3), the HR for CHD events increased to 3.7 and for new-onset diabetes to 24.5. A raised CRP level (>3.0 mg/dL) was found to augment the risk level for CHD events and diabetes, independent of the presence of the metabolic syndrome.

Use of the statin drug, pravastatin, was found to reduce the level of risk for CHD events in men with the metabolic syndrome to that of men without the syndrome.

Comment

The criteria for diagnosing the metabolic syndrome point naturally towards an increased risk of cardiovascular events, as was found in this analysis. It was interesting to see that the risk was present despite LDL cholesterol concentrations similar to those without the syndrome - justifying the use of 'three of five criteria' in the diagnostic process.

More important, perhaps, was the finding that the metabolic syndrome carried a much higher risk for emergence of type 2 diabetes than for a CHD event. And elevated CRP levels predicted both CHD and diabetes, independent of the metabolic syndrome status.

The authors finish by observing that modifying the metabolic syndrome definition by adding a CRP threshold, or lowering the fasting glucose threshold, might improve the predictability for serious outcomes. The importance for medical practitioners of this analysis lies in the need to successfully manage the metabolic criteria in their patients - weight/waist, HDL and triglycerides, blood pressure, and blood sugar problems.