Higher CETP mass independently predicts a lower leukocyte count, and switching atorvastatin to pitavastatin raises CETP mass by 8.8 percent (Am J Cardiovasc Drugs 2012)

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 (10 mg/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/μL. On atorvastatin therapy, the CETP mass correlated negatively with the peripheral leukocyte count (r = -0.418, p = 0.02). In univariate regression analysis, on-atorvastatin 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 μg/mL (8.8%, p = 0.007), and the peripheral leukocyte count was significantly decreased from 6209 to 5778 cells/μL (-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.