The ARIC study

INCREASED CARDIOVASCULAR MORBIDITY AND MORTALITY IN INDIVIDUALS WITH THE METABOLIC SYNDROME

McNeill AM, et al. The metabolic syndrome and 11-year risk of incident cardiovascular disease in the atherosclerosis risk in communities study. Diabetes Care 2005;28:385-90.

Several of the prospective studies reporting a twofold increase in cardiovascular disease (CVD) risk in people with the metabolic syndrome were conducted in Caucasians with a family history of type 2 diabetes. Other studies reported exclusively fatal CVD events. This prompted McNeill et al to assess the association between the metabolic syndrome and long-term CVD morbidity and mortality in the biracial population of the Atherosclerosis Risk in Communities (ARIC) study. The ARIC study was initiated between 1987 and 1989 in four US communities. The study cohort included 15 792 white and black men and women for whom anthropometrical data were collected and lipid profile and fasting blood glucose were determined. For the purpose of this analysis, subjects with overt diabetes, CHD, or a history of stroke were excluded. Mortality and morbidity data were examined after a mean follow-up of 11 years in the 12 089 participants (mean age: 53 years in black women, 54 years in all other groups) with complete data on metabolic syndrome components.

The influence of the metabolic syndrome on two categories of cardiovascular (CV) outcomes was assessed:

• Incident CHD events, including fatal or non-fatal hospitalised myocardial infarction (MI), fatal CHD, silent MI identified by electrocardiography, or coronary revascularisation.
• Incident ischaemic stroke events.

Relative risks of CV events were estimated using a Cox regression model. Approximately 24% of women and 23% of men had the metabolic syndrome as defined by NCEP ATP III criteria. Several race and sex differences were observed. Not surprisingly, 60% of black participants met the criteria for elevated blood pressure, compared with 23% of whites. Black men had a lower prevalence of metabolic syndrome than whites (18% vs 24%) and a lower prevalence of elevated triglycerides and low HDL-cholesterol components compared with other groups. Enlarged waist circumference was more prevalent in women than men (59% vs 31%). A total of 879 CHD and 216 ischaemic stroke events occurred during the 11-year follow-up. Incidence rates for both CHD and ischaemic stroke were significantly greater among individuals with the metabolic syndrome compared with those without (Figure). A significant (P<0.0006) difference between sexes was detected. Unadjusted hazard ratios (HRs) of CHD associated with the metabolic syndrome were 2.55 (95% CI 2.00-3.27) in women and 1.51 (1.27-1.79) in men. Race did not influence the results.

Figure. Relative risk of CHD and stroke events accociated with the metabolic syndrome in the ARIC study.

Individuals with the metabolic syndrome remained at significantly increased risk of CHD and stroke after adjustment for age, race/centre, LDLcholesterol, and smoking (Figure). However, the association between the metabolic syndrome and stroke was no longer significant in men, which the authors attribute to a lack of precision due to the small number of stroke events. Among the components of the metabolic syndrome, elevated blood pressure and low levels of HDL-cholesterol exhibited the strongest associations with CHD.

Additional analyses were made to take into account the lower threshold for impaired fasting glucose (100 mg/dl) recently recommended by the American Diabetes Association. This increased the overall prevalence of the syndrome to 32%, but yielded similar results with regard to the associations between the metabolic syndrome and incident CV events (adjusted HRs of CHD, 2.11 [95% CI 1.64-2.72] and 1.39 [1.18-1.63] in women and men, respectively; adjusted HRs of ischaemic stroke, 1.90 [1.25-2.89] and 1.52 [1.05-2.18], respectively). In this study, the risk of CHD associated with the metabolic syndrome was not in excess of the level explained by the presence of its individual components. This diverges from results of another analysis of data from the ARIC study: Golden et al reported that several combinations of metabolic syndrome components conferred excess additive risk of increased intima-media thickness beyond the level predicted by the individual components. Intima-media thickness is a measure of generalised atherosclerosis.¹

Inclusion of the metabolic syndrome did not add to CHD prediction models (comparison of receiver operating characteristic curves) that included the Framingham Risk Score (FRS). However, ARIC participants were categorised in this analysis as having <10% or ≥10% risk of CHD. The >20% risk category of the FRS algorithm was not used because the number of participants in this category was too low. The authors emphasise that patients falling in the category of <20% CHD risk who met the criteria for the metabolic syndrome had a higher absolute rate of CHD than those without the syndrome. This is consistent with data from large clinical trials indicating that individuals within the same FRS category who have the metabolic syndrome are at increased risk of CHD relative to subjects without the syndrome.

This prospective epidemiological study confirms the association between the metabolic syndrome and cardiovascular morbidity and mortality in both sexes and suggests that early interventions in subjects with the metabolic syndrome, but without overt diabetes or cardiovascular disease may contribute to the prevention of both coronary heart disease and ischaemic stroke.

REFERENCE

1. Golden SH, Folsom AR, Coresh J, et al. Risk factor groupings related to insulin resistance and their synergistic effects on subclinical atherosclerosis: the Atherosclerosis Risk in Communities study. Diabetes 2002;51:3069-76.