Differences in synthesis and absorption of cholesterol of two effective lipid-lowering therapies

Abstract

Effective statin therapy is associated with a marked reduction of cardiovascular events. However, the explanation for full benefits obtained for LDL cholesterol targets by combined lipid-lowering therapy is controversial. Our study compared the effects of two equally effective lipid-lowering strategies on markers of cholesterol synthesis and absorption. A prospective, open label, randomized, parallel design study, with blinded endpoints, included 116 subjects. We compared the effects of a 12-week treatment with 40 mg rosuvastatin or the combination of 40 mg simvastatin/10 mg ezetimibe on markers of cholesterol absorption (campesterol and β-sitosterol), synthesis (desmosterol), and their ratios to cholesterol. Both therapies similarly decreased total and LDL cholesterol, triglycerides and apolipoprotein B, and increased apolipoprotein A1 (P < 0.05 vs baseline for all). Simvastatin/ezetimibe increased plasma desmosterol (P = 0.012 vs baseline), and decreased campesterol and β-sitosterol (P < 0.0001 vs baseline for both), with higher desmosterol (P = 0.007) and lower campesterol and β-sitosterol compared to rosuvastatin, (P < 0.0001, for both). In addition, rosuvastatin increased the ratios of these markers to cholesterol (P < 0.002 vs baseline for all), whereas simvastatin/ezetimibe significantly decreased the campesterol/cholesterol ratio (P = 0.008 vs baseline) and tripled the desmosterol/cholesterol ratio (P < 0.0001 vs baseline). The campesterol/cholesterol and β-sitosterol/cholesterol ratios were lower, whereas the desmosterol/cholesterol ratio was higher in patients receiving simvastatin/ezetimibe (P < 0.0001 vs rosuvastatin, for all). Pronounced differences in markers of cholesterol absorption and synthesis were observed between two equally effective lipid-lowering strategies.

Nutraceutical approach for the management of cardiovascular risk – a combination containing the probiotic Bifidobacterium longum BB536 and red yeast rice extract: results from a randomized, double-blind, placebo-controlled study

“…The LDL-C goal recommended by the EAS guidelines (LDL-C < 115 mg/dL) [25] was reached by 4/16 subjects, whereas in 7/16 participants LDL-C was lower than 130 mg/dL, after nutraceutical treatment, although an expected variability due to individual responsiveness has been observed. The efficacy of this nutraceutical combination in terms of improvement of clinical lipid markers is comparable or even better than that of several other widely used nutraceuticals, evaluated by RCT studies [26–28].…”

“…We found no changes of campesterol:TC and sitosterol:TC upon active treatment. While this may be viewed as a negative finding, it should be noted that treatment with statins, including lovastatin, structurally identical to monacolin K, in addition to reduce liver cholesterol synthesis, with lathosterol:cholesterol reduction, tends to increase intestinal cholesterol absorption, shown by increased campesterol:cholesterol and beta-sitosterol:cholesterol ratios [26, 34].…”

Effects of ezetimibe on markers of synthesis and absorption of cholesterol in high-risk patients with elevated C-reactive protein

“…Therefore, the combined use of ezetimibe in subjects treated with atorvastatin appears to be a very interesting lipid-lowering approach. In fact, previous studies of our group have demonstrated that statins, especially those with short half-life, increase cholesterol absorption and do not reduce cholesterol synthesis effectively (Kasmas et al, 2012). ALT, alanine aminotransferase; AST, aspartate aminotransferase; Atorva, atorvastatin; CK, creatinekinase; Eze, ezetimibe; GGT, gamaglutamil transpeptidase; HbA1c, glycated hemoglobin; hs-CRP, high-sensitivity C-reactive protein; IQR, interquartile range; TSH, thyroid-stimulating hormone; SD, standard deviation.…”

Effects of simvastatin/ezetimibe on microparticles, endothelial progenitor cells and platelet aggregation in subjects with coronary heart disease under antiplatelet therapy

“…However, a decrease in the number of platelet and endothelial microparticles has been seen after therapy with simvastatin in diabetic and hypertensive subjects ( 15 ), while in vitro studies have revealed increased release of microparticles related to a simvastatin-mediated decrease of protein prenylation ( 16 ). In addition, because ezetimibe increases endogenous cholesterol synthesis ( 17 ), its combination with simvastatin may perturb the effects of the statin on microparticles when given alone.…”