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Atorvastatin May Improve Endothelial Function In Patients with Diabetes and in Healthy Persons At Risk for Type 2 Diabetes

Atorvastatin therapy may improve endothelial function in patients with diabetes and in healthy individuals at risk for type 2 diabetes, according to a new American study.

Statins have been shown to lower serum cholesterol levels, leading to a reduction in cardiovascular morbidity and mortality. New studies have suggested that additional mechanisms independent of the lipid-lowering activity, such as direct action on the endothelial cell, may also contribute to the beneficial effect of statin therapy.

Panayiotis A. Economides, of Joslin Diabetes Center, Boston, Massachusetts, and colleagues, performed a study to examine the effect of atorvastatin treatment on endothelial function in 40 patients with diabetes (mean age, 53; 23 males; type 1 diabetes, 20) and in 37 healthy individuals at risk for developing diabetes (mean age, 49; 20 males). Both of these groups are known to have impaired endothelial function.

Individuals were considered at risk for developing diabetes by having a first-degree relative with the disease. Participants in both the diabetic group and the at-risk group were randomised to receive either 20 mg atorvastatin or placebo for a period of 12 weeks. Endothelial-dependent and -independent functions were assessed in the microcirculation by measuring vascular reactivity of the forearm and in the macrocirculation by measuring flow-mediated dilation of the brachial artery.

At-risk participants receiving atorvastatin experienced a significant improvement in flow-mediated dilation of the brachial artery compared with baseline (5.6% vs. 4.2%, P = .07). Atorvastatin-treated diabetic subjects also showed a trend toward improved endothelial function in the macrocirculation, although the change did not reach statistical significance (7.2% vs. 6.6%, P < .05). Neither group experienced changes in endothelium-dependent responses of the microcirculation, and no changes were detected for any endothelial function assessed in the placebo-treated groups.

The researchers also measured several inflammatory cytokines and biochemical markers of endothelial function. Atorvastatin-treated individuals at risk for diabetes showed a reduction in C-reactive protein (baseline, 0.24 mg/mL; exit, 0.12 mg/mL; P<0.05) and TNF-alpha (2.6 vs. 4.4 pg/mL, P < .05), whereas diabetic patients receiving the treatment showed a reduction in levels of endothelin-1 (0.97 vs. 1.19 pg/mL, P < .05) and plasminogen activator inhibitor-1 levels (18 vs. 27 ng/mL, P < .05).

"Atorvastatin improves the endothelial function of the macrocirculation and decreases levels of markers of endothelial activation in diabetic patients and in subjects at risk of developing type 2 diabetes," the researchers conclude.

Furthermore, they note that dyslipidaemia was not an inclusion criteria for the study and baseline mean cholesterol levels were close to the recommended therapeutic targets in the participant groups. Based on this observation, they suggest that, "statins can be beneficial even in the presence of normal plasma total and LDL cholesterol concentrations."

J Clin Endocrinol Metab 2004 Feb;89:2:740-7. "The Effects of Atorvastatin on Endothelial Function in Diabetic Patients and Subjects at Risk for Type 2 Diabetes"

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