Colestimide co-administered with atorvastatin attenuates the progression of vascular calcification in haemodialysis patients.

Abstract

Vascular calcification is believed to have a crucial role in the excess cardiovascular mortality and morbidity in patients with end-stage renal disease (ESRD). Recent evidence suggests that uraemic vascular calcification is an active cellmediated process [1]. An epidemiological study observed an association between lipid-lowering therapy and vascular calcification [2]. However, no prospective investigation has been published to prove an effect of lipid-lowering therapy on the progression of vascular calcification in patients with ESRD. We therefore conducted the present study that prospectively compared the rate of change in the amount of vascular calcification before and during lipid-lowering therapy in haemodialysis patients. The aortic calcification index (ACI) was estimated by computed tomography (CT) as described previously [3]. At the time of the first CT, fasting lipid levels as well as serum levels of calcium (Ca) and phosphorus levels were measured and lipid-lowering therapy with colestimide (1.5 g/day) and atorvastatin (10mg/day) was initiated. Patients were instructed to keep any other medical therapy unchanged. A total of 29 patients completed the protocol and could be evaluated. Progression of aortic calcification was significantly less pronounced during treatment with colestimide and atorvastatin compared with the period before treatment was initiated. The mean ACI in the first CT was 35.6±20.2%. The median ACI in the second CT, after an average interval of 22.9±3.2 months on treatment, was 29.0±16.2% (P<0.05). Average total cholesterol and LDL cholesterol levels in the untreated period were 246±38 and 156±41mg/dl, respectively. A mean reduction of 21 (total cholesterol) and 44% (LDL cholesterol) was achieved. Triglyceride levels fell by 25%. Serum phosphorus levels decreased significantly with the treatment from 6.8±1.4 to 5.4±1.2mg/dl, whereas serum Ca levels showed no significant difference (9.8±0.6 vs 9.6±0.8mg/dl). Our preliminary, uncontrolled investigation is the first report that prospectively examines the influence of both colestimide and atorvastatin on the progression of vascular calcification in haemodialysis patients. It is unclear how changes in aortic calcification were achieved by lipid-lowering therapy. One possible explanation is that colestimide acts as a bile acid sequestrant and is therefore capable of reducing serum phosphorus levels as described previously [4], and that atorvastatin and colestimide significantly reduced LDL cholesterol levels. A randomized, placebo-controlled study is required to determine whether colestimide and atorvastatin inhibit vascular calcification in patients with ESRD.