Response to Letters Regarding Article, “Evidence for Statin Pleiotropy in Humans: Differential Effects of Statins and Ezetimibe on Rho-Associated Coiled-Coil Containing Protein Kinase Activity, Endothelial Function, and Inflammation”

Abstract

We appreciate the comments by Settergren et al on differences in the patient population and response to lipid-lowering therapies between our 2 studies.1,2 We agree that our patient population had lower cardiovascular risks and higher on-treatment low-density lipoprotein cholesterol (LDL-C) levels. Thus, it is possible that LDL-C lowering alone may not be the overwhelming determinant of endothelial function as observed in our study. Furthermore, the lipid-lowering response to statin monotherapy and the combination of statin and ezetimibe may differ between white and Asian patients.3 Regardless of these ethnic and cardiovascular risk factor differences, the LDL reduction was similar between simvastatin 40 mg and simvastatin/ezetimibe 10 mg/10 mg in our study. However, endothelial function differed significantly between these 2 treatment groups (simvastatin 40 mg versus simvastatin/ezetimibe 10/10 mg: +32.1% versus −0.5%, P <0.01). Because of these contrasting results, we agree that there is a need for a larger-scale and perhaps multicenter study to further investigate whether changes in endothelial function with statin therapy are solely dependent on LDL-C lowering and, if so, whether they are affected by patient background and the degree of LDL-C lowering. From the results of the Pravastatin or Atorvastatin Evaluation and Infection Therapy/Thrombolysis in Myocardial Infarction 22 (PROVE-IT/TIMI 22) and the Treating to New Targets (TNT) trials, it is clear that a greater reduction in LDL-C with either a more potent statin, a higher dose of statin, or both leads to a greater reduction in cardiovascular events. …