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Pravastatin Therapy May Produce Anti-Inflammatory and Anticoagulant Effects in Patients with Type 2 Diabetes

Statin therapy is associated with a reduction of coagulation and inflammation marker levels in patients with type 2 diabetes, potentially contributing to a beneficial effect on cardiovascular risk.

Previous studies have shown that aggressive treatment of dyslipidaemia with statins can significantly reduce the risk of cardiovascular complications in patients with type 2 diabetes. In addition to the known cholesterol-lowering effect of statins, some evidence has suggested that antithrombotic and anti-inflammatory activities may also contribute to this risk reduction.

Dirkje W. Sommeijer, MD, from the University of Amsterdam, the Netherlands, and colleagues performed an open, randomised crossover trial to specifically determine the effects of pravastatin on inflammation, coagulation, and endothelial activation markers in type 2 diabetic patients.

Fifty patients with well-controlled type 2 diabetes (median age=59; 25 males; median HbA1c=6.9%) and serum total cholesterol of 5 to 10 mmol/L completed the 16-week study. Patients were randomised to receive either pravastatin 40 mg/day or no treatment for a period of 8 weeks and then switched to the opposite treatment for the following 8 weeks. Blood samples were taken for analysis at days 1, 8 and 16.

As expected, treatment with pravastatin for 8 weeks led to a significant reduction in serum lipids, including total cholesterol (-1.4mmol/L, P < .001), LDL cholesterol (-1.3 mmol/L, P < .001), and triglycerides (-0.19 mmol/L, P < .05). Pravastatin also produced a decrease in several coagulation and inflammation markers; significant changes were detected for plasma levels of the prothrombin activation marker F1 + 2 (-0.04 nmol/l, P = .007), von Willebrand Factor antigen (-7%, P = .027), soluble tissue factor (-4 pg/mL, P = .044), and C-reactive protein (-0.52 mg/dl, P = .019). No significant reductions were observed for fibrinogen or D-dimer.

Furthermore, the researchers found a statistically significant correlation between the change in F1 + 2 and the degree of change of D-dimer (r=0.534; P < .0001), a finding that "fits the notion that thrombin generation (F1 + 2) is associated with fibrin formation and proteolytic cleavage (D-dimer)."

"Our data demonstrate that treatment with pravastatin for 2 months induces anti-inflammatory, antithrombotic, and endothelial-improving actions in patients with type 2 diabetes and mild hypercholesterolemia," concludes Dr. Sommeijer. The researchers suggest that these alterations may have clinical significance because type 2 diabetes is associated with increased inflammation and coagulation activity and impaired endothelial function.

Diabetes Care 2004 Feb;27:2:468-473. "Anti-Inflammatory and Anticoagulant Effects of Pravastatin in Patients With Type 2 Diabetes"

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