Anacetrapib reduces progression of atherosclerosis, mainly by reducing non-HDL-cholesterol, improves lesion stability and adds to the beneficial effects of atorvastatin.
Bottom Line: Anacetrapib dose-dependently reduced the atherosclerotic lesion area (-41 to -92%, P < 0.01) and severity, increased plaque stability index and added to the effects of atorvastatin by further decreasing lesion size (-95%, P < 0.001) and severity.Anacetrapib dose-dependently reduces atherosclerosis, and adds to the anti-atherogenic effects of atorvastatin, which is mainly ascribed to a reduction in non-HDL-C.In addition, anacetrapib improves lesion stability.
Affiliation: Gaubius Laboratory, TNO, Metabolic Health Research, Zernikedreef 9, 2333 CK, PO Box 2215, 2301 CE, Leiden, The Netherlands Department of Cardiology, LUMC, Leiden, The Netherlands Einthoven Laboratory for Experimental Vascular Medicine, LUMC, Leiden, The Netherlands.Show MeSH
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Mentions: We evaluated whether the effects of anacetrapib and atorvastatin on atherosclerosis development could be explained by either an increase in HDL-C or a decrease in non-HDL-C or both. The lesion area was normalized by cubic root transformation (lesion area(1/3)). Univariate regression analysis showed that the lesion area was predicted by TC (Figure 6A), mainly non-HDL-C (Figure 6B) and to a lesser extent by HDL-C (Figure 6C). Analysis of covariance showed that both anacetrapib treatment, at the dosages of 3 and 30 mg/kg/day (P < 0.05) and non-HDL-C (P < 0.001), but not HDL-C (P = 0.76), independently determined lesion size. Importantly, the variance inflation factors of HDL-C and non-HDL-C (VIF = 4.42 and 3.18, respectively) and the condition index (CI = 4.43) did not exceed the threshold for collinearity between the explanatory variables. Collectively, these data are compatible with a mechanism that anacetrapib mainly decreases atherosclerotic lesion development via a reduction of non-HDL-C with an additional effect by the compound itself at the higher doses (Figure 7).Figure 6
Affiliation: Gaubius Laboratory, TNO, Metabolic Health Research, Zernikedreef 9, 2333 CK, PO Box 2215, 2301 CE, Leiden, The Netherlands Department of Cardiology, LUMC, Leiden, The Netherlands Einthoven Laboratory for Experimental Vascular Medicine, LUMC, Leiden, The Netherlands.