TY - JOUR
T1 - Small Dense Low-Density Lipoprotein Cholesterol and Cardiovascular Risk in Statin-Treated Patients with Coronary Artery Disease
AU - Ishii, Junnichi
AU - Kashiwabara, Kosuke
AU - Ozaki, Yukio
AU - Takahashi, Hiroshi
AU - Kitagawa, Fumihiko
AU - Nishimura, Hideto
AU - Ishii, Hideki
AU - Iimuro, Satoshi
AU - Kawai, Hideki
AU - Muramatsu, Takashi
AU - Naruse, Hiroyuki
AU - Iwata, Hiroshi
AU - Tanizawa-Motoyama, Sadako
AU - Ito, Hiroyasu
AU - Watanabe, Eiichi
AU - Matsuyama, Yutaka
AU - Fukumoto, Yoshihiro
AU - Sakuma, Ichiro
AU - Nakagawa, Yoshihisa
AU - Hibi, Kiyoshi
AU - Hiro, Takafumi
AU - Hokimoto, Seiji
AU - Miyauchi, Katsumi
AU - Ohtsu, Hiroshi
AU - Izawa, Hideo
AU - Ogawa, Hisao
AU - Daida, Hiroyuki
AU - Shimokawa, Hiroaki
AU - Saito, Yasushi
AU - Kimura, Takeshi
AU - Matsuzaki, Masunori
AU - Nagai, Ryozo
N1 - Publisher Copyright:
© 2022 Japan Atherosclerosis Society.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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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U2 - 10.5551/jat.63229
DO - 10.5551/jat.63229
M3 - Article
C2 - 34880156
AN - SCOPUS:85139508012
SN - 1340-3478
VL - 29
SP - 1458
EP - 1474
JO - Journal of atherosclerosis and thrombosis
JF - Journal of atherosclerosis and thrombosis
IS - 10
ER -