Despite the debate about the utility of this diagnosis, its hazards are clear. Patients should start on a treatment regimen sooner rather than later.
Metabolic syndrome is classified as the simultaneous presence of metabolic factors known to increase risk for developing type 2 diabetes and cardiovascular disease (CVD). These factors are abdominal obesity, hyperglycemia, dyslipidemia, and hypertension. This condition has also been called “syndrome X,” “insulin resistance syndrome,” “the deadly quartet,” or “obesity dyslipidemia syndrome.” Whatever the name and irrespective of the questions associated with it, metabolic syndrome should serve as a call for primary-care clinicians and patients to begin aggressive treatment regimens that include lifestyle modifications to lower the risks for associated comorbidities.
Over the past decade, metabolic syndrome has been defined by three different organizations. The 1998 World Health Organization definition was refined by the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel [ATP] III) in 2001. The most recent definition was released by the International Diabetes Federation (IDF) in 2004. A summary of these criteria is presented in Table 1.
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The role of inflammation
The definition of metabolic syndrome remains unsettled because other potential contributing factors may play a role. These include pro-inflammatory markers, measures of a prothrombotic state, elevated C-reactive protein, elevated interleukin (IL)-6, and elevated plasminogen activator. Elevated levels of high sensitivity C reactive protein (hs-CRP) have been associated with an increased risk for CVD and diabetes mellitus. Patients with hs-CRP levels ≥3 mg/dL and metabolic syndrome as defined by NCEP had increased risk of CAD events and new-onset diabetes. There is some evidence that elevated hs-CRP levels can predict the development of metabolic syndrome in women.1
Epidemiology
Disagreements about prevalence stem from the differences in definitions. Estimates derived from the National Health and Nutrition Examination Survey (1999-2002) indicate that 34.5% of the adult population can be classified as having metabolic syndrome when the NCEP definition is used. When the IDF definition is used, 39% of the National Health and Nutrition Examination Survey sample can be classified as having metabolic syndrome.2 Given the evolving definition, it will be difficult to produce definitive prevalence estimates for some time.
Metabolic syndrome is a growing concern in pediatric and adolescent populations. The Third National Health and Nutrition Survey, 1988-1994, showed that 31.2% of overweight/obese adolescents have the syndrome. It is also a concern for racial/ethnic minority populations. Mexican Americans, followed by non-Hispanic whites, have a greater prevalence of metabolic syndrome compared with non-Hispanic blacks (12.9%, 10.9%, and 2.5% respectively).3
Metabolic syndrome has been associated with drug therapy. Such drugs as corticosteroids, antidepressants, antipsychotics, and antihistamines can produce weight gain that can lead to the syndrome. Moreover, metabolic syndrome has been linked to protease inhibitors used in HIV treatment.4 These findings suggest that metabolic syndrome can be a side effect of other conditions and the drug(s) used to treat them.
Clinical implications
Using the NCEP definition, the risk among metabolic syndrome patients of developing type 2 diabetes ranges from 30%-52%.5 This may actually understate the risk. A study investigating a cohort of 3,323 middle-aged adults found that 62% of men and 47% of women with metabolic syndrome developed type 2 diabetes.6Metabolic syndrome has been shown to increase coronary heart disease threefold and CV mortality 1.8-fold.7 For example, a recent study showed that its presence in middle-aged men increased the risk of stroke in the absence of previous stroke, diabetes, or CVD at baseline. Using the NCEP definition, middle-aged men with metabolic syndrome had a 2.78 risk of ischemic stroke.8 Using the WHO definition, the risk for ischemic stroke was 2.47.
Young adults with metabolic syndrome have been found to have increased rates of subclinical atherosclerosis, thereby increasing their CV risk.9 Metabolic syndrome has also been associated with increased risk of fatty liver disease, chronic kidney disease, polycystic ovary disease, sleep-disordered breathing, and cognitive decline and dementia.
Management
Lifestyle modifications that address such underlying risk factors as obesity, physical inactivity, and atherogenic diet comprise first-line therapy. Weight loss and healthy weight maintenance should be encouraged to prevent or reduce obesity, especially abdominal obesity. Overweight and obese patients should be advised to lose 7%-10% of their body weight over 6-12 months through a reduction in caloric consumption and changes in dietary composition.
The DASH (Dietary Approaches to Stop Hypertension) eating plan decreases metabolic syndrome risk factors. Specifically, the DASH diet reduces LDL, triglycerides, systolic BP, diastolic BP, fasting blood sugar, and weight while increasing HDL. The Mediterranean-style diet, which emphasizes whole grains and vegetables over meat, has been associated with a decrease in the prevalence of metabolic syndrome and associated CV risk.10
Increased physical activity can aid with weight loss as well as positively affect other components associated with metabolic syndrome. Patients should engage in moderately intense exercise for at least 30 minutes a day. One study found that greater cardiorespiratory fitness is a form of primary prevention of metabolic syndrome.11
Treatment must also include CV risk reduction. To assess the patient’s risk for CVD, the Framingham risk equations can be used. Lipid lowering can be accomplished through lifestyle modifications in addition to drug therapy. The NCEP ATP III guidelines for lipid lowering should be followed. If the patient with metabolic syndrome has diabetes, devise a treatment plan designed to keep serum LDL levels <100.
According to the current guidelines, antihypertensive therapy should be initiated at a BP ≥140/%ge;90. To date, no particular agent has been found effective for treating hypertensive patients with metabolic syndrome. There is some thought that ACE inhibitors and angiotensin II receptor blockers (ARBs) may help reduce insulin resistance. All patients with metabolic syndrome should be advised to discontinue smoking and take an aspirin every day for cardioprotection.
Complementary therapies have shown mixed results. Omega-3 fatty acids have had a favorable effect on triglycerides but no impact on total cholesterol, HDL, LDL, fasting blood sugar, plasma insulin, or insulin resistance.12 A systematic review of 70 studies suggests that yoga may improve lipid profiles and insulin resistance while lowering weight and BP, but more rigorous randomized control trials are needed to establish yoga as a definitive treatment for metabolic syndrome.
Dr. Zoorob is professor and chair in the Department of Family and Community Medicine, Meharry Medical College and Vanderbilt University, both in Nashville. Dr. Smith is assistant professor and associate residency director at the Department of Family and Community Medicine at Meharry Medical College.
References
1. Haffner SM. The metabolic syndrome: inflammation, diabetes mellitus, and cardiovascular disease. Am J Cardiol. 2006;97(2A):3A-11A.
2. Ford ES. Prevalence of the metabolic syndrome defined by the International Diabetes Federation among adults in the U.S. Diabetes Care. 2005;28:2745-2749.
3. de Ferranti SD, Gauvreau K, Ludwig DS, et al. Prevalence of the metabolic syndrome in American adolescents: findings from The Third National Health and Nutrition Examination Survey. Circulation. 2004;110:2494-2497.
4. Grundy SM, Hansen B, Smith SC Jr, et al. Clinical management of metabolic syndrome: report of the American Heart Association/National Heart, Lung, and Blood Institute/American Diabetes Association Conference on scientific issues related to management. Circulation. 2004;109:551-556.
5. Ford ES. Risks for all-cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome: a summary of the evidence.Diabetes Care. 2005;28:1769-1778.
6. Wilson PW, D’Agostino RB, Parise H, et al. Metabolic syndrome as precursor of cardiovascular disease and type 2 diabetes mellitus. Circulation. 2005;112:3066-3072.
7. Isomaa B, Almgren P, Tuomi T, et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care. 2001;24:683-689.
8. Kurl S, Laukkanen JA, Niskanen L, et al. Metabolic syndrome and the risk of stroke in middle-aged men. Stroke. 2006;37:806-811.
9. Tzou WS, Douglas PS, Srinavasan SR, et al. Increased subclinical atherosclerosis in young adults with metabolic syndrome: the Bogalusa Heart Study. J Am Coll Cardiol. 2005;46:457-463.
10. Esposito K, Marfella R, Ciotola M, et al. Effect of a Mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome. JAMA. 2004;292:1440-1446.
11. LaMonte MJ, Barlow CE, Jurca R, et al. Cardiorespiratory fitness is inversely associated with the incidence of metabolic syndrome: a prospective study of men and women. Circulation. 2005;112:505-512.
12. Agency for Healthcare Research and Quality. Effects of omega-3 fatty acids on lipids and glycemic control in type II diabetes and the metabolic syndrome and on inflammatory bowel disease, rheumatoid arthritis, renal disease, systemic lupus erythematosus, and osteoporosis. Rockville, Md.: Agency for Healthcare Research and Quality, U.S. Dept. of Health and Human Services; 2004. AHRQ publication 04-E012-2.
