Journal of Atherosclerosis and Thrombosis
Online ISSN : 1880-3873
Print ISSN : 1340-3478
ISSN-L : 1340-3478
Original Article
Small Dense Low-Density Lipoprotein Cholesterol and Cardiovascular Risk in Statin-Treated Patients with Coronary Artery Disease
Junnichi Ishii, Kosuke Kashiwabara, Yukio Ozaki, Hiroshi Takahashi, Fumihiko Kitagawa, Hideto Nishimura, Hideki Ishii, Satoshi Iimuro, Hideki Kawai, Takashi Muramatsu, Hiroyuki Naruse, Hiroshi Iwata, Sadako Tanizawa-Motoyama, Hiroyasu Ito, Eiichi Watanabe, Yutaka Matsuyama, Yoshihiro Fukumoto, Ichiro Sakuma, Yoshihisa Nakagawa, Kiyoshi Hibi, Takafumi Hiro, Seiji Hokimoto, Katsumi Miyauchi, Hiroshi Ohtsu, Hideo Izawa, Hisao Ogawa, Hiroyuki Daida, Hiroaki Shimokawa, Yasushi Saito, Takeshi Kimura, Masunori Matsuzaki, Ryozo Nagai
Author information
Keywords: Small dense LDL cholesterol, Coronary artery disease, Statin therapy, Secondary prevention
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2022 Volume 29 Issue 10 Pages 1458-1474

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Abstract

Aim: We investigated the relationship between small dense low-density cholesterol (sdLDL-C) and risk of major adverse cardiovascular events (MACE) in patients treated with high- or low-dose statin therapy.

Methods: This was a prospective case-cohort study within the Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) study, a randomized trial of high- or low-dose (4 or 1 mg/d pitavastatin, respectively) statin therapy, in patients with stable coronary artery disease (CAD). Serum sdLDL-C was determined using an automated homogenous assay at baseline (randomization after a rule-in period, ＞1 month with 1 mg/d pitavastatin) and 6 months after randomization, in 497 MACE cases, and 1543 participants randomly selected from the REAL-CAD study population.

Results: High-dose pitavastatin reduced sdLDL-C by 20% than low-dose pitavastatin (p for interaction ＜0.001). Among patients receiving low-dose pitavastatin, baseline sdLDL-C demonstrated higher MACE risk independent of LDL-C (hazard ratio [95% confidence interval], 4th versus 1st quartile, 1.67 [1.04–2.68]; p for trend=0.034). High-dose (versus low-dose) pitavastatin reduced MACE risk by 46% in patients in the highest baseline sdLDL-C quartile (＞34.3 mg/dL; 0.54 [0.36–0.81]; p=0.003), but increased relative risk by 40% in patients with 1st quartile (≤ 19.5 mg/dL; 1.40 [0.94–2.09]; p=0.099) and did not alter risk in those in 2nd and 3rd quartiles (p for interaction=0.002).

Conclusions: These findings associate sdLDL-C and cardiovascular risk, independent of LDL-C, in statin-treated CAD patients. Notably, high-dose statin therapy reduces this risk in those with the highest baseline sdLDL-C.

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