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Anacetrapib reduces progression of atherosclerosis, mainly by reducing non-HDL-cholesterol, improves lesion stability and adds to the beneficial effects of atorvastatin.

Kühnast S, van der Tuin SJ, van der Hoorn JW, van Klinken JB, Simic B, Pieterman E, Havekes LM, Landmesser U, Lüscher TF, Willems van Dijk K, Rensen PC, Jukema JW, Princen HM - Eur. Heart J. (2014)

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.

View Article: PubMed Central - PubMed

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.

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Hypothetical scheme of factors contributing to the effect of anacetrapib on the atherosclerotic lesion area as suggested by statistical analyses. An analysis of covariance was performed to test for group differences in the lesion area with HDL-C and non-HDL-C exposure as covariates. HDL-C was not an independent predictor of the lesion area when non-HDL-C was included as covariate, suggesting that the effect of anacetrapib on atherosclerosis development was mainly mediated through the reduction of non-HDL-C. The higher dosages of anacetrapib (3 and 30 mg/kg/day) also revealed an effect on atherosclerosis that was independent of non-HDL-C, but this effect was not explained by the increase in HDL-C.
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EHU319F7: Hypothetical scheme of factors contributing to the effect of anacetrapib on the atherosclerotic lesion area as suggested by statistical analyses. An analysis of covariance was performed to test for group differences in the lesion area with HDL-C and non-HDL-C exposure as covariates. HDL-C was not an independent predictor of the lesion area when non-HDL-C was included as covariate, suggesting that the effect of anacetrapib on atherosclerosis development was mainly mediated through the reduction of non-HDL-C. The higher dosages of anacetrapib (3 and 30 mg/kg/day) also revealed an effect on atherosclerosis that was independent of non-HDL-C, but this effect was not explained by the increase in HDL-C.

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


Anacetrapib reduces progression of atherosclerosis, mainly by reducing non-HDL-cholesterol, improves lesion stability and adds to the beneficial effects of atorvastatin.

Kühnast S, van der Tuin SJ, van der Hoorn JW, van Klinken JB, Simic B, Pieterman E, Havekes LM, Landmesser U, Lüscher TF, Willems van Dijk K, Rensen PC, Jukema JW, Princen HM - Eur. Heart J. (2014)

Hypothetical scheme of factors contributing to the effect of anacetrapib on the atherosclerotic lesion area as suggested by statistical analyses. An analysis of covariance was performed to test for group differences in the lesion area with HDL-C and non-HDL-C exposure as covariates. HDL-C was not an independent predictor of the lesion area when non-HDL-C was included as covariate, suggesting that the effect of anacetrapib on atherosclerosis development was mainly mediated through the reduction of non-HDL-C. The higher dosages of anacetrapib (3 and 30 mg/kg/day) also revealed an effect on atherosclerosis that was independent of non-HDL-C, but this effect was not explained by the increase in HDL-C.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4286319&req=5

EHU319F7: Hypothetical scheme of factors contributing to the effect of anacetrapib on the atherosclerotic lesion area as suggested by statistical analyses. An analysis of covariance was performed to test for group differences in the lesion area with HDL-C and non-HDL-C exposure as covariates. HDL-C was not an independent predictor of the lesion area when non-HDL-C was included as covariate, suggesting that the effect of anacetrapib on atherosclerosis development was mainly mediated through the reduction of non-HDL-C. The higher dosages of anacetrapib (3 and 30 mg/kg/day) also revealed an effect on atherosclerosis that was independent of non-HDL-C, but this effect was not explained by the increase in HDL-C.
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

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.

View Article: PubMed Central - PubMed

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.

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Related in: MedlinePlus