Metabolic Syndrome: A Warning of Cardiovascular Disease and Type 2 Diabetes Mellitus?
Abstract & Commentary
By Jonathan Abrams, MD, Professor of Medicine, Division of Cardiology, University of New Mexico, Albuquerque. Dr. Abrams serves on the speaker's bureau for Merck, Pfizer, and Parke-Davis.
Synopsis: Metabolic syndrome is common and is associated with an increased risk for CVD and T2DM in both sexes.
Sources: Wilson PW, et al. Metabolic Syndrome As a Precursor of Cardiovascular Disease and Type 2 Diabetes Mellitus. Circulation. 2005;112:3066-3072; Reaven G. Insulin Resistance, Type 2 Diabetes Mellitus, and Cardiovascular Disease: The End of the Beginning. Circulation. 2005;112:3030-3032.
The metabolic syndrome (MS) has become a household phrase, and a subject of enormous interest. In simple terms, MS represents a cluster or grouping of specific clinical abnormalities that appear to be linked together. Most of these features have a common denominator of insulin resistance, which appears to be a causal factor for the varied clinical manifestations. Wilson and colleagues analyzed the Framingham Heart Study Offspring Study over a period of 8 years to assess the hazard of MS and its individual components for the subsequent development of cardiovascular disease (CVD) and type 2 diabetes mellitus (DM).
In this analysis, approximately 3300 non-diabetic individuals, free from clinical heart disease, but with MS (defined by 3 or more criteria, including fasting plasma glucose of 100-125mg/dL; blood pressure >130/85; low HDL cholesterol; high triglycerides; and an increased waist circumference per the NCEP/ATP III definition of MS) were followed from 1989 to 1993; at the time of the fourth examination of Framingham Offspring Study. Interim follow-up examinations took place at 4 and 8 years. Mean baseline age for men and women was 50 years. The baseline prevalence of MS was 21% in men and 12.5% in women. By 8 years, the proportion of men with MS rose to 39%, and in women, from 12.5% to 30.6% (an increase of 47%). The relative risk of new CVD in males was 2.9, and for all coronary heart disease (CHD) was 2.5. The population attributable risk (PAR) was 30% for both CHD and CVD, indicating the fraction of vascular events that could be attributed to MS at baseline. An analysis of the specific number of MS traits per person demonstrated an additive effect for CVD and DM, although with a much steeper gradient for the development of DM. The most powerful metabolic syndrome traits related to CVD outcomes were blood pressure and HDL cholesterol; hypertension was present in half of all participants at baseline and imparted a risk of 49% for CVD. Furthermore, impaired fasting glucose (IFG) predicted a 12 fold increase in the risk for DM. Wilson et al point out a 50% increase in the prevalence in MS over an 8-year period.
Overall, CHD and CVD risk for MS doubled in men, less so for women. More MS traits increased the rate of CVD events, although 2 vs 3 risk factors for MS did not increase CVD risk substantially. Traditional CVD risk factors do increase the risk of developing CVD in MS subjects.
These data are "concordant with the NHANES 1988-1994 survey results that reported that approximately 23% of United States adults had the metabolic syndrome." Other data in the literature are supportive of these finding; baseline MS imparts much greater risk for the development of DM than CVD, approximately 4-fold. MS traits, other than a high IFG, were related to new DM, consistent with the importance of insulin resistance. Wilson et al noted "a large fraction of persons who developed diabetes had MS during the observation period, with a significantly greater relative risk for the development of diabetes than overt CVD." Wilson et al conclude, "Amelioration of MS traits through lifestyle interventions or medications in patients with impaired glucose tolerance "may retard or prevent new DM." These findings have important implications for prevention. There may be value in diagnosing MS to identify "an extremely adverse metabolic state that warrants aggressive interventions for specific traits." In a companion editorial, Gerald Reaven reviews the data supporting insulin resistance and/or compensatory hyperinsulinemia as a predictor of DM and CVD. He downplays the usefulness of counting risk factors, noting that 2 traits seemed as predictive as 3 for the development of CVD or DM in the Framingham cohort. He calls for vigorous treatment of each risk factor individually, and emphasizes the role of insulin resistance and the need to treat all of its manifestations. He downgrades the importance of abdominal girth, stating that obesity is more a result of metabolic risk factors, rather than being causal.
Commentary
This article from the Framingham Offspring Study clearly demonstrates that MS is highly predictive for the development of subsequent DM type 2, more so than for clinical CVD events. The data support treatment of each individual MS trait, including vigorous use of lifestyle behavior (diet, physical activity, etc). While the Framingham cohort reflect an all white, middle class population, it is likely that other ethnic groups will be similar in demonstrating increased risk of DM and CVD associated with IFG, low HDL, high triglycerides, and hypertension. The role of adiposity as a player or camp follower remains unclear. Other data sets are comparable, to this report, supporting a greater risk for DM than clinical cardiovascular events in subjects with MS. While not studied here, the combination of DM and MS is particularly lethal.
There are a number of active controversies regarding MS, including a precise definition, the need (or not) for assessing insulin sensitivity, and the optimal treatment (eg, insulin sensitizers, inclusion of MS as a high risk factor for aggressive LDL lowering).
It behooves us all to acknowledge that both MS and DM are on the rise, and these conditions predict an increasing burden of CVD. It would seem that an army of preventionists will need to be rapidly trained and deployed for much important work.
Other Recent Readings
• Grundy S, et al. Diagnosis and Management of the Metabolic Syndrome: An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005;112:2735-2752.
• Davidson MH. Management of Dyslipidemia in Patients with Complicated Metabolic Syndrome. Am J Cardiol. 2005;96:22E-25E.
Metabolic syndrome is common and is associated with an increased risk for CVD and T2DM in both sexes.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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