Am J Cardiovasc Dis 2013;3(4):255-263

Original Article
A predictor of atheroma progression in patients achieving very low levels of
low-density lipoprotein cholesterol

Tsuyoshi Nozue, Shingo Yamamoto, Shinichi Tohyama, Kazuki Fukui, Shigeo Umezawa, Yuko Onishi, Tomoyuki
Kunishima, Kiyoshi Hibi, Mitsuyasu Terashima, Ichiro Michishita

Division of Cardiology, Department of Internal Medicine, Yokohama Sakae Kyosai Hospital, Yokohama, Japan; Department
of Cardiology, Tsurumi Nishiguchi Hospital, Yokohama, Japan; Department of Cardiology, Yokohama Seamen’s Insurance
Hospital, Yokohama, Japan; Department of Cardiology, Kanagawa Cardiovascular and Respiratory Center, Yokohama,
Japan; Department of Cardiology, Hiratsuka Kyosai Hospital, Hiratsuka, Japan; Fourth Department of Internal Medicine,
Mizonokuchi Hospital, Teikyo University School of Medicine, Kawasaki, Japan; 7Division of Cardiology, Yokohama City
University Medical Center, Yokohama, Japan; Cardiovascular Imaging Center, Toyohashi, Japan

Received October 10, 2013; Accepted October 20, 2013; Epub November 1, 2013; Published November 15, 2013

Abstract: An aggressive reduction in low-density lipoprotein cholesterol (LDL-C) with statins produces regression or
stabilization of coronary artery plaques. However, after achieving very low levels of LDL-C, atheroma regression is not
observed in all patients. The purpose of the present study was to evaluate the determinants of atheroma progression
despite achieving very low levels of LDL-C. The effects of 8-month statin therapy on coronary atherosclerosis were
evaluated using virtual histology intravascular ultrasound in the TRUTH study. Of these, 33 patients who achieved an on-
treatment LDL-C level of <70 mg/dl were divided into 2 groups according to increase in plaque volume (progressors, n=
16) or decrease in plaque volume (regressors, n= 17) during an 8-month follow-up period. At the 8-month follow-up, serum
LDL-C and apolipoprotein B levels were significantly lower in progressors than in regressors; however, significant
increases in high-density lipoprotein cholesterol and apolipoprotein AI and decreases in high-sensitivity C-reactive protein
and oxidized LDL were observed only in regressors. The changes in the n-3 to n-6 polyunsaturated fatty acid ratios
significantly differed between the 2 groups. Multivariate regression analysis showed that a decrease in the
eicosapentaenoic acid + docosahexaenoic acid/arachidonic acid ratio was a significant predictor associated with
atheroma progression (β= -0.512, p= 0.004). In conclusions, n-3 to n-6 polyunsaturated fatty acid ratios affected coronary
artery plaque progression and regression in patients who achieved very low levels of LDL-C during statin therapy.
(AJCD1310003).

Keywords: Atheroma, low-density lipoprotein cholesterol, polyunsaturated fatty acid, statin, virtual histology intravascular
ultrasound

Address correspondence to: Dr. Tsuyoshi Nozue, Division of Cardiology, Department of Internal Medicine, Yokohama
Sakae Kyosai Hospital, Federation of National Public Service Personnel Mutual Asso-ciations, 132 Katsura-cho, Sakae-ku,
Yokohama 247-8581, Japan. Tel: +81-45-891-2171; Fax: +81-45-895-8352; E-mail: nozue2493@yahoo.co.jp
AJCD Copyright © 2011-present, All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711, USA