September/October 2003

Lipid Education Service
Newsbrief
J. David Schnatz, M.D.

The metabolic syndrome (MS) has been defined by the National Cholesterol Education Program, Adult Treatment Panel III (JAMA 285:2486, 2001), in the following way:

A category of risk containing 3 or more of the following:

• Abdominal obesity: Male waist >40 inches, Female waist >35 inches
• Elevated triglyceride: 150 mg/dl
• Low HDL: Male <40 mg/dl, Female <50 mg/dl
• Hypertension: 130/85 mm Hg.
• Elevated glucose: 110 mg/dl

At the 52nd Annual Meeting of the American College of Cardiology, a number of presentations dealt with the metabolic syndrome, and some of these are recorded here.

Abstract 845-1 The Influence of the Metabolic Syndrome on 24-year Mortality Among Middle-Aged Men in the Multiple Risk Factor Intervention Trial (MRFIT).� The authors classified 12,617 men in MRFIT as to baseline MS or diabetes mellitus (DM), using a BMI of 30+ rather than waist measurement and a glucose of >126 to define DM. Four thousand seven hundred thirty five had MS only, 57 DM only, and 355 had both. In a 24 year follow-up, the hazard ratios for cardiovascular mortality compared to those with neither MS or DM were 1.27 with MS (p<0.0001), 1.37 with DM (p=0.28) and 1.99 with MS and DM (p<0.0001). Thus, the presence of MS increased the risk of death. Treatment of MS is an important strategy in preventing cardiovascular death.

Abstract 845-2 Niacin Decreases Myocardial Infarction and Total Mortality in Patients with Metabolic Syndrome: Results From the Coronary Drug Project� The results of the Coronary Drug Project (CDP), a study carried out in the 1960s and 1970s, were reanalyzed in terms of the MS, using a BMI of 28 as a substitute for waist measurement. Previously, niacin had been shown to decrease non-fatal myocardial infarction by 28% at 6 years and total mortality by 11% at 15 years. In this analysis, those reductions occurred both in patients with and without MS.

Abstract 845-3 The Metabolic Syndrome is an Independent Predictor of Cardiac Events in WOSCOPS Males� Data from the WOSCOPS Trial were analyzed in 6,447 males (ages 45-64 years, LDL 156-255 mg/dl). Diabetics and patients with fasting glucose 126 mg/dl were excluded. They defined excessive abdominal girth as a BMI >30 as a substitute for waist circumference. MS was present in 23.8% of the patients. Cardiac events occurred in 12.6% of those with MS compared with 7.3% of those without (p<0.0001). The hazard ratio associating cardiac events with MS was 1.8 (p<0.001), comparable to an increment of 10 years of age (1.8, p<0.001), and greater than smoking (1.5) and LDL (1.4, p<0.001).

Abstract 845-4 Differential Effects of Statins on Hypercholesterolemic Patients With Metabolic Syndrome� Post-hoc analysis was carried out on a 36 week, double blind, dose titration to assess the effects of Simvastatin, 40-80mg (S) and Atorvastatin, 20-80mg (A), on HDL in hypercholesterolemic patients (LDL160 mg/dl). Patients were classified as having MS or not having MS using a BMI of 30 as a surrogate for waist circumference. Twenty-six percent of 808 patients had MS. At comparable LDL or non HDL lowering doses, both drugs produced significant triglyceride reductions with A having the edge over S. However, S produced HDL increases that were 1.5-3 fold greater than those observed with A. Approximately one half of the patients converted to non-MS status in the 36 week treatment period.

Abstract 845-5 Elevated C-Reactive Protein in High-Risk Asymptomatic Individuals is Strongly Associated with the Metabolic Syndrome� The investigators explored whether highly sensitive CRP (HS CRP) was associated with MS in 388 healthy siblings of patients with coronary artery disease (CAD). They found a significant difference in HS CRP in those with MS (5.7) vs those without (4.0) (p<0.0001). With an increasing number of MS components, there was an increase in HS CRP (0 components = CRP of 2.2 to 5 components =CRP of 6.1, p<0.0001).

Abstract 845-6 The Association of the Metabolic Syndrome with Myocardial Infarction and Stroke in the National Health and Nutrition Examination Survey III� The investigators evaluated data on 10,357 subjects collected from 1988 to 1994. The results indicate a strong, consistent relationship of the Metabolic Syndrome, as defined in NCEP-ATP III, with history of MI and stroke.� These results emphasize the importance of the Metabolic Syndrome in the progression of atherosclerotic disease.�

Abstract 1050-104 Which Features of the Metabolic Syndrome Predict the Presence of Angiographic Coronary Artery Disease?� In 3,528 subjects, 67% male, 63 �12 years, undergoing coronary angiography, MS was analyzed for predictive value, using a BMI>27 as a surrogate for waist circumference. MS was present in 48% and predicted increased risk of significant CAD (odds ratio, OR, =1.4, p<0.001). High fasting glucose (FG) (OR=1.91, p<0.001) and low HDL (OR=1.38, p<0.001), but not triglyceride, BP or BMI, were predictive of CAD. FG and HDL deserve particular attention in risk factor assessment.�

Abstract 822-4 Which Features of the Metabolic Syndrome Predict Clinical Outcomes (Death/Myocardial Infarction) in Patients with Angiographic Coronary Artery Disease� The same group of investigators as that presenting the preceding abstract, explored the predictive value of MS for death (D) or myocardial infarction (MI) in patients with advanced CAD (70% stenosis), using BMI27 as a surrogate for waist circumference. MS was present in 51%, but in contrast to our prior finding that MS predicts CAD diagnosis, MS failed to predict D/MI in patients with existing CAD (p=0.81). Only high FG, a MS component, predicted D/MI.�

In a recent article:

Preventing Coronary Events by Optimal Control of Blood Pressure and Lipids in Patients with the Metabolic Syndrome (Am J. Cardiol 91:1421, 2003) Using data from the Third National Health and Nutrition Examination Survey and Framingham algorithms that included B.P., HDL and LDL, but not obesity, triglyceride or glucose, the authors calculated significant reduction of CAD events for control of each risk factor. When B.P., HDL and LDL were considered together, control (BP 120-129/80-84, HDL45, LDL 100-129), was estimated to prevent 51.3% events in men and 42.6% in women. Optimal levels (BP <120/<80, HDL60 and LDL<100) was estimated to prevent 80.5% events in men and 82.1% in women. The authors say, Clinical endpoint trial data are needed to confirm this.�