Association of Cholesteryl Ester Transfer Protein Mass with Peripheral Leukocyte Count Following Statin Therapy
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Background: HMG-CoA reductase inhibitors (statins) can effectively reduce serum low-density lipoprotein cholesterol (LDL-C) levels in the majority of patients at increased cardiovascular risk. However, some patients at increased cardiovascular risk have a high peripheral leukocyte count and this inflammatory marker has correlated with an increased incidence of coronary events. Recently, in a large clinical trial-based cohort, an increasing on-statin cholesteryl ester transfer protein (CETP) mass was inversely related to coronary events, particularly among those with a low serum LDL-C level. However, the role of the CETP mass in the development of atherosclerosis is still unclear.
Objective: We investigated the possibility of whether the CETP mass was associated with the peripheral leukocyte count after intensive statin therapy, and whether the CETP mass was changed by switching statins.
Methods: This study was an open-label lipid interventional study switching from atorvastatin to pitavastatin without a washout period. Between 1 April 2010 and 31 March 2011, 32 patients (mean age 64.0 ± 9.0 years, 63% male) with hypercholesterolemia receiving atorvastatin (10mg/day) were enrolled. Next, they were switched to pitavastatin (2 mg/day) for 6 months. The peripheral leukocyte count, the CETP mass measured by enzyme-linked immunosorbent assay, and lipid parameters were measured at baseline and at follow-up. The type and dosage of concomitant drugs were not changed during the study periods.
Results: The on-atorvastatin LDL-C level was well controlled with 94.4 ± 23.1 mg/dL, and peripheral leukocyte count was 6209 ± 1142 cells/mL. On atorvastatin therapy, the CETP mass correlated negatively with the peripheral leukocyte count (r = −0.418, p = 0.02). In univariate regression analysis, onatorvastatin peripheral leukocyte count was significantly correlated with high-density lipoprotein cholesterol (β = −42.1, p = 0.008), triglycerides (β = 8.2, p = 0.005), and the CETP mass (β = −1296.3, p = 0.02). In a multivariate analysis after adjusting for traditional risk factors, the CETP mass remained an independent negative determinant of the peripheral leukocyte count (β = −1162, p = 0.02). By switching atorvastatin to pitavastatin, the CETP mass was significantly increased from 1.9 to 2.1 mg/mL (8.8%, p = 0.007), and the peripheral leukocyte count was significantly decreased from 6209 to 5778 cells/mL (-5.9%, p = 0.005). As a result, the relationship between CETP mass and peripheral leukocyte count after pitavastatin treatment was diminished (r=−0.276, p = 0.13). Moreover, the change in peripheral leukocyte count was negatively correlated with the change in the CETP mass (r = −0.39, p = 0.03), suggesting that a decreased CETP mass may be closely associated with an elevated peripheral leukocyte count in atorvastatin-treated patients.
Conclusion: The results suggest that residual cardiovascular risk after atorvastatin treatment may be associated with the CETP mass, which may be increased by switching to pitavastatin. Furthermore, a CETP mass-activating strategy may assist the therapeutic efficacy of statins.
KeywordsAtorvastatin Cholesteryl Ester Transfer Protein Pitavastatin Torcetrapib Intensive Statin Therapy
No funding was received for this study. None of the authors have any conflicts of interest that are directly related to this study. We thank Mr Kenji Kawamata for helpful discussions and statistical analysis.
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