Treatment

Metabolic syndrome is not defined by NCEP as a CAD risk equivalent. It is crucial that these patients undergo comprehensive evaluation of their global cardiovascular risk factor burden. Aggressive lifestyle modification with weight loss, increased exercise and physical activity, smoking cessation, and reductions in carbohydrate and saturated fat intake constitute front-line therapy for patients with the metabolic syndrome (Grundy et al., 2003b; Liu and Manson, 2001; Salmeron et al., 2002). Referral to a dietitian is frequently helpful. Weight loss and aerobic exercise are associated with improved insulin sensitivity and significant improvements in blood pressure and lipid levels (DeFronzo et al., 1987; Franssila-Kallunki et al., 1992). As shown in the Diabetes Prevention Project, aggressive lifestyle modification reduces risk for new-onset diabetes mellitus in obese middle-aged patients by 58% (Tuomilehto et al., 2001). In motivated patients unable to achieve adequate weight loss, pharma-cologic intervention is an option. Orlistat (Xenical) is a GI

lipase inhibitor that reduces the absorption of dietary fat from the gut. It facilitates weight reduction and should be taken with meals; its major side-effect is fatty, oily stools that can precipitate diarrhea. Bariatric surgery for morbidly obese patients has been shown to relieve insulin resistance, promote substantial weight loss, reduce BP, and improve dyslipidemia. The Mediterranean diet (increased consumption of fish, legumes, whole grains, olive oil) is associated with weight loss and improvements in lipid, insulin sensitivity, and inflammatory indices.

Serum LDL-C and non-HDL-C should be treated to NCEP-defined targets. Therapeutic effort should be expended to raise HDL-C. The choice of whether a statin or fibrate should be used as initial therapy should be dictated by the specific features of a patient's lipid profile. In post hoc analyses of the Helsinki Heart Study (Manninen et al., 1992), VA-HIT (Robins et al., 2002) and Bezafibrate Infarction Prevention trials (BIP Study Group, 2000), fibrate therapy significantly improved lipid profiles and reduced cardiovascular morbidity and mortality in patients with insulin resistance and the metabolic syndrome. Many of these patients will require combinations of antilipidemic medications to normalize their lipid profiles. Since patients with the metabolic syndrome have activation of the RAAS axis, many authorities on hypertension believe it is reasonable to treat the hypertension of these patients with ACEI and ARBs as first-line therapy (Grundy et al., 2004a, 2004b). However, no clinical trials help to establish whether this is the optimal approach compared to other available classes of anti-hypertensive medication. On the other hand, a number of studies, including the HOPE (Heart Outcomes Prevention Evaluation Study Investigators, 2000), VALUE (Julius et al., 2004), Captopril Prevention Project (Hansson et al., 1999) and LIFE (Dahlof et al., 2003) trials, among others, have shown that ACEI and ARBs can reduce the onset of diabetes mellitus by 20% to 34% compared to non-RAAS-affecting comparative antihypertensives. Aspirin prophylaxis should be considered in patients with a 10-year Framingham risk that exceeds 10%.

KEY TREATMENT

In metabolic syndrome, comprehensive risk factor evaluation should be undertaken in all patients at risk for diabetes and CVD (SOR: A). Lifestyle modification can reduce risk of developing diabetes mellitus by 58% (Diabetes Prevention Project) (SOR: A). Weight loss can be achieved through caloric restriction, exercise, and when indicated, pharmacologic intervention or bariatric surgery (SOR: A).

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