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Am Fam Physician. 2003;68(7):1407

The cardiovascular metabolic syndrome is a combination of risk factors that greatly increases the likelihood of diabetes. Diabetes is a strong risk factor for cardiovascular disease and end-stage renal disease, with cardiovascular disease being the most common cause of death in persons with diabetes. This risk for cardiovascular disease begins before diabetes is diagnosed, during a preceding period of increased insulin resistance and impaired glucose tolerance. Sowers reviews the usefulness of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) in patients with metabolic syndrome.

The Health Protection Study looked at the effect of lowering lipids in a large cohort of persons with type 1 and type 2 diabetes. After five years of treatment with simvastatin in a dosage of 40 mg, there was a significant decrease in first major coronary vascular events in persons with no history of coronary disease and persons with prior coronary disease. These results have since been confirmed with pravastatin in a dosage of 40 mg and gemfibrozil in a dosage of 1,200 mg per day.

The dyslipidemia of persons with metabolic syndrome or diabetes characteristically demonstrates small low-density lipoprotein (LDL) particles, high triglyceride levels, and low high-density lipoprotein (HDL) cholesterol levels. Statin therapy reduces LDL cholesterol and triglyceride levels and may increase HDL cholesterol levels slightly, but the benefits of statins seem to be independent of the change in lipid components, because improved outcomes with statin therapy may be noted as soon as four months after initiation of therapy.

Statins may have a direct positive effect on vascular walls through an improvement of endothelial function, anti-inflammatory and antithrombotic actions, and attenuation of atherogenesis. Simvastatin increases endothelial nitric oxide production and improves nitric oxide–dependent vasorelaxation. Statins also reduce plasma levels of C-reactive protein and cytokines independently of reduction in LDL cholesterol levels and increase levels of natural antioxidants. Statins decrease fibrinogen levels, decrease blood viscosity, and reduce platelet aggregation and adhesion.

The author concludes that statins have direct beneficial effects on vasculature independent of LDL cholesterol lowering. These effects likely contribute to the decrease in cardiovascular disease and strokes in persons with diabetes who are treated with statins.

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