Background-Biological mechanisms underlying statin and angiotensin II type 1 receptor blocker therapies differ.Therefore, we compared vascular and metabolic responses to these therapies either alone or in combination in hypercholesterolemic, hypertensive patients. Methods and Results-This was a randomized, double-blind, placebo-controlled crossover trial with 3 treatment arms (each 2 months) and 2 washout periods (each 2 months). Forty-seven hypertensive, hypercholesterolemic patients were given simvastatin 20 mg and placebo, simvastatin 20 mg and losartan 100 mg, or losartan 100 mg and placebo daily during each 2-month treatment period. Losartan alone or combined therapy significantly reduced blood pressure compared with simvastatin alone. Compared with losartan alone, simvastatin alone or combined therapy significantly changed lipoproteins. All 3 treatment arms significantly improved flow-mediated dilator response to hyperemia and decreased plasma malondialdehyde and monocyte chemoattractant protein-1 levels relative to baseline measurements. However, these parameters were changed to a greater extent with combined therapy compared with simvastatin or losartan alone (both PϽ0.001 and Pϭ0.030 for monocyte chemoattractant protein-1 by ANOVA). Combined therapy or losartan alone significantly increased plasma adiponectin levels and insulin sensitivity (determined by QUICKI) relative to baseline measurements. These changes were significantly greater than in the group treated with simvastatin alone (PϽ0.001 for adiponectin, Pϭ0.029 for QUICKI by ANOVA). Conclusions-Simvastatin combined with losartan improves endothelial function and reduces inflammatory markers to a greater extent than monotherapy with either drug in hypercholesterolemic, hypertensive patients.

These findings suggest that UGT1A1*6 and UGT1A9*22 genotypes may be important for SN-38 glucuronidation and associate with irinotecan-related severe toxicity. Specifically, UGT1A1*6 might be useful for predicting tumor response and survival outcome of Korean patients with NSCLC treated with irinotecan-based chemotherapy.

Objectives We investigated whether atorvastatin might decrease insulin sensitivity and increase ambient glycemia in hypercholesterolemic patients. Background Clinical trials suggest that some statin treatments might increase the incidence of diabetes despite reductions in low-density lipoprotein (LDL) cholesterol and improvement in endothelial dysfunction. Methods A randomized, single-blind, placebo-controlled parallel study was conducted in 44 patients taking placebo and in 42, 44, 43, and 40 patients given daily atorvastatin 10, 20, 40, and 80 mg, respectively, during a 2-month treatment period. Results Atorvastatin 10, 20, 40, and 80 mg significantly reduced LDL cholesterol (39%, 47%, 52%, and 56%, respectively) and apolipoprotein B levels (33%, 37%, 42%, and 46%, respectively) after 2 months of therapy when compared with either baseline (all p < 0.001 by paired t test) or placebo (p < 0.001 by analysis of variance [ANOVA]). Atorvastatin 10, 20, 40, and 80 mg significantly increased fasting plasma insulin (mean changes: 25%, 42%, 31%, and 45%, respectively) and glycated hemoglobin levels (2%, 5%, 5%, and 5%, respectively) when compared with either baseline (all p < 0.05 by paired t test) or placebo (p = 0.009 for insulin and p = 0.008 for glycated hemoglobin by ANOVA). Atorvastatin 10, 20, 40, and 80 mg decreased insulin sensitivity (1%, 3%, 3%, and 4%, respectively) when compared with either baseline (p = 0.312, p = 0.008, p < 0.001, and p = 0.008, respectively, by paired t test) or placebo (p = 0.033 by ANOVA). Conclusions Despite beneficial reductions in LDL cholesterol and apolipoprotein B, atorvastatin treatment resulted in significant increases in fasting insulin and glycated hemoglobin levels consistent with insulin resistance and increased ambient glycemia in hypercholesterolemic patients. (Effects of Atorvastatin on Adiponectin Levels and Insulin Sensitivity In Hypercholesterolemic Patients; NCT00745836)