Anti-Inflammatory and Anticoagulant Effects of Pravastatin in Patients With Type 2 Diabetes

Abstract

OBJECTIVE -Type 2 diabetes is associated with increased plasma concentrations of coagulation and inflammation markers. Different studies have shown that treatment with hydroxymethylglutaryl-CoA reductase inhibitors (statins) is associated with antithrombotic and antiinflammatory effects in addition to a cholesterol-lowering effect. Our objective was to evaluate the effect of pravastatin (40 mg/day) on coagulation and inflammation markers in type 2 diabetic patients. RESEARCH DESIGN AND METHODS -This was an open, randomized, crossover study designed with an 8-week intervention period. The study group was comprised of 50 patients with type 2 diabetes (median HbA 1c 7.1%) and serum total cholesterol of 5-10 mmol/l. We evaluated plasma levels of fibrinogen, F1 ϩ 2, D-dimer, soluble tissue factor (sTF), von Willebrand Factor antigen (vWFag), and C-reactive protein (CRP) in blood samples drawn after fasting on day 1 and after 8 and 16 weeks.RESULTS -Significant reductions of total cholesterol (Ϫ22%; P Ͻ 0.001), LDL cholesterol (Ϫ32%; P Ͻ 0.001), and triglycerides (Ϫ10%; P Ͻ 0.05) were achieved after 8 weeks of treatment with pravastatin. In addition, significant reductions of plasma levels of F1 ϩ 2 (Ϫ4.4%; P Ͻ 0.05), vWFag (Ϫ5.3%; P Ͻ 0.05), and sTF (Ϫ3.4%; P Ͻ 0.05) were observed after treatment with pravastatin. Furthermore, plasma levels of CRP were also significantly reduced (Ϫ13%; P Ͻ 0.05). Levels of fibrinogen and D-dimer did not decrease after treatment with pravastatin.CONCLUSIONS -The results indicated that pravastatin reduces levels of coagulation and inflammation markers in type 2 diabetic patients. These antithrombotic and anti-inflammatory effects of treatment with statins could play a role in reducing cardiovascular complications in type 2 diabetic patients. Diabetes Care 27:468 -473, 2004T ype 2 diabetes is a leading cause of vascular morbidity and death. It is often complicated by other cardiovascular risk factors such as hypercholesterolemia, hypertension, obesity, and increased markers of coagulation (1) and inflammation (2). It has therefore been recommended that therapeutic prevention of cardiovascular disease in type 2 diabetes focus not only on optimal regulation of hyperglycemia but also on treatment of other cardiovascular risk factors (3,4).A subgroup analysis of several large randomized clinical trials (5,6) shows that the relative risk for cardiovascular complications in type 2 diabetic patients can be reduced by 25% using aggressive treatment of dyslipidemia with hydroxymethylglutaryl-CoA reductase inhibitors, also known as statins. Treatment with statins may be beneficial not only because of these agents' lipid-lowering action, but also because of their effect on inflammation, endothelial function, adhesion of leukocytes to endothelium, and thrombus formation (7). Although statins have proven to be effective in the prevention of cardiovascular disease in type 2 diabetes, little is known about these socalled pleiotropic effects in patients with type 2 diabetes.Our objective was to determi...

Effects of Atorvastatin on Inflammatory and Fibrinolytic Parameters in Patients with Chronic Kidney Disease

“…Statins diminish procoagulant activity, which is observed at various stages of the coagulation cascade (25). In some studies that were performed in patients who were on peritoneal dialysis, statins reduced fibrinogen levels and altered the levels and activities of t-PA and PAI-1 (26,27).…”

Effects of Pitavastatin on Serum Lipids and High Sensitivity C-Reactive Protein in Type 2 Diabetic Patients

“…In the present study we aimed to evaluate the effects of pitavastatin on serum lipids as well as on serum hsCRP levels in Japanese patients with type 2 diabetes mellitus accompanied by elevated serum LDL-C, which has not yet been proved. Our study patients showed much lower hsCRP levels than subjects in most studies conducted in western countries 27,29,30) .…”

“…Studies of the effects of statins on circulating hsCRP in type 2 diabetes have not shown consistent results [27][28][29][30] . BMI is known as a major independent determinant of hsCRP [11][12][13][14][15][16]32) and our study also showed that BMI was closely related to serum hsCRP levels in Japanese type 2 diabetic patients, although the mean BMI of our patients was 24.4 kg/m 2 , much lower than that in most studies conducted in western countries 27,29,30) .…”

“…In other studies, atorvastatin treatment resulted in a significant decrease in TG but failed to increase HDL-C levels in type 2 diabetes 27,28) . In a sub-analysis of the Heart Protection Study 6) , simvastatin produced a significant increase in HDL-C but failed to significantly reduce TG levels in diabetic patients, while pravastatin failed to increase HDL-C levels in patients with type 2 diabetes 29) . In a recent study of Japanese patients with type 2 diabetes mellitus, pitavastatin treatment resulted in a significant reduction in TG levels ( 10%) and an increase in HDL-C levels ( 3.1%) although the latter did not reach statistical significance (p 0.055) 36) .…”

“…Atorvastatin treatment (20 mg daily) for 3 months failed to lower hsCRP levels in type 2 diabetic patients 27) , but administration of 10 mg daily for 3 months, followed by 20 mg daily for 3 months, lowered hsCRP in type 2 diabetes patients after 6 months 28) . It has also been reported that pravastatin treatment for 8 weeks lowered hsCRP levels in patients with type 2 diabetes mellitus by 13% 29) . Treatment with simvastatin was found to reduce circulating hsCRP within 14 days but it had returned to baseline levels by day 28 30) .…”