Are Patients with Low Non-HDL Cholesterol “Non-responders” to Statin Therapy on Coronary Plaque Regression?

Relationship between coronary plaque progression , as determined by intravascular ultrasound (IVUS), and prospective risk for cardiovascular events has been proven by the analysis of six clinical trials 1). IVUS studies showed only a minimal improvement of atheroma volume with statin therapy 2). A meta-analysis of nine studies using virtual histology IVUS (VH-IVUS) imaging with 16 treatment arms and 830 participants (737 in statin and 93 in placebo) showed that statin therapy reduced plaque volume, external elastic membrane volume, and fibrous plaque volume; however, that did not affect lumen volume, fibro-fatty, and necrotic core 3). The changes in plaque volume induced by statins were not associated with baseline levels of LDL cholesterol (LDL-C) 3). Wakabayashi et al. 4) reported a subanalysis of the TRUTH study, a prospective, open-labeled, randomized, multicenter trial of VH-IVUS study that compared the effects of intensive lipid-lowering therapy with 4 mg/day of pitavastatin versus moderate lipid-lowering therapy with 20 mg/day of pravastatin for 8 months on coronary artery plaque composition in statin-naïve patients with stable or unstable angina pectoris. They investigated how baseline non-high-density lipoprotein cholesterol (non-HDL-C) levels affect the efficacy of statin therapy on plaque regression. Non-HDL-C reflects cholesterol contents of both LDL and other atherogenic lipoproteins such as very low density lipo-protein and remnant lipoproteins. The latter lipopro-tein cholesterol is positively associated with triglycer-ides. The patients were divided into the following three groups based on non-HDL-C levels at baseline: low, ≤ 140 mg/dl, n 38; moderate, 141 – 169 mg/dl, n 42; and high, ≥ 170 mg/dl, n 39. The patients in the low non-HDL-C group were significantly older and had a significantly lower body mass index as compared to those in the higher non-HDL-C groups. Furthermore , slightly more patients treated with pitavas-tatin and slightly more patients with stable CAD were seen in the low non-HDL-C group. Although non-HDL-C and LDL-C at 8-month follow-up decreased to 8719 and 6718 mg/dl, respectively, in the low non-HDL-C group, percent atheroma volume and fibrous tissue significantly increased, whereas plaque regression was noted in the moderate and high cholesterol groups. After adjusting for all variables, a low non-HDL-C level at baseline (≤ 140 mg/dl) was an independent predictor of coronary plaque progression under statin therapy. Other substudies from the TRUTH study investigated several factors that affect plaque progression under statin treatment 5-7). The study of 101 patients whose serum levels of eicosapen-taenoic acid (EPA), docosahexaenoic acid (DHA), …