Prevention of Cardiovascular Complications of the Metabolic Syndrome: Focus on Pharmacotherapy

Abstract

The metabolic syndrome increases the risk of atherothrombotic cardiovascular disease (CVD) and diabetes. In turn, diabetes promotes the development of atheroma and is regarded as a coronary heart disease risk equivalent. A multifactorial therapeutic strategy is advocated for patients with the metabolic syndrome to improve cardiovascular risk factor profiles and to reduce the chances of developing type 2 diabetes. Individual components of the syndrome must be addressed using safe, efficacious, and cost-effective measures. There is general agreement that lifestyle modifications, including control of body weight, avoidance of central adiposity, adoption of an antiatherogenic diet, and regular physical activity, are crucial. However, as the magnitude of the individual components of the metabolic syndrome increases with time, lifestyle measures are often insufficient. An individual with metabolic syndrome will often require drug treatment for hyperglycemia, atherogenic dyslipidemia, and high blood pressure, together with antiplatelet therapy. Reducing the need for polypharmacy is an increasingly important consideration for clinicians and the pharmaceutical industry; to date, no single therapy has emerged that targets the root cause(s) of the syndrome. HMG-CoA reductase inhibitors are important agents that reduce CVD morbidity and mortality, in people with impaired fasting glucose or metabolic syndrome. Selective cannabinoid receptor antagonists appear promising because they improve or attenuate several key defects of the syndrome. Thiazolidinediones and metformin are presently licensed for treatment of type 2 diabetes but may prove to have a broader role in future. Novel insulin-sensitizing drugs are under investigation. Drugs that act to prevent or reverse endothelial dysfunction may be of particular utility in preventing cardiovascular disease, especially if initiated before tissue damage has become irreversible. Insulin therapy, which has antiinflammatory and endothelial protective properties, has been shown to reduce morbidity and mortality in high-risk nondiabetic patients during critical illness. Potential synergy between different classes of drugs with metabolic and/or cardiovascular protective properties merits further investigation.