Small Dense Low-Density Lipoprotein Cholesterol and Cardiovascular Risk in Statin-Treated Patients with Coronary Artery Disease

• Published in: Journal of Atherosclerosis and Thrombosis Vol. 29; no. 10; pp. 1458 - 1474
• Main Authors: Ishii, Junnichi, Kashiwabara, Kosuke, Ozaki, Yukio, Takahashi, Hiroshi, Kitagawa, Fumihiko, Nishimura, Hideto, Ishii, Hideki, Iimuro, Satoshi, Kawai, Hideki, Muramatsu, Takashi, Naruse, Hiroyuki, Iwata, Hiroshi, Tanizawa-Motoyama, Sadako, Ito, Hiroyasu, Watanabe, Eiichi, Matsuyama, Yutaka, Fukumoto, Yoshihiro, Sakuma, Ichiro, Nakagawa, Yoshihisa, Hibi, Kiyoshi, Hiro, Takafumi, Hokimoto, Seiji, Miyauchi, Katsumi, Ohtsu, Hiroshi, Izawa, Hideo, Ogawa, Hisao, Daida, Hiroyuki, Shimokawa, Hiroaki, Saito, Yasushi, Kimura, Takeshi, Matsuzaki, Masunori, Nagai, Ryozo
• Format: Journal Article
• Language: English
• Published: Japan Atherosclerosis Society 01-10-2022
• Subjects: Coronary artery disease; Original; Secondary prevention; Small dense LDL cholesterol; Statin therapy
• ISSN: 1340-3478; 1880-3873
• DOI: 10.5551/jat.63229

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.