Junnichi Ishii1, Kosuke Kashiwabara2, Yukio Ozaki3, Hiroshi Takahashi4, Fumihiko Kitagawa5, Hideto Nishimura3, Hideki Ishii6, Satoshi Iimuro7, Hideki Kawai3, Takashi Muramatsu3, Hiroyuki Naruse8, Hiroshi Iwata9, Sadako Tanizawa-Motoyama3, Hiroyasu Ito5, Eiichi Watanabe3, Yutaka Matsuyama10, Yoshihiro Fukumoto11, Ichiro Sakuma12, Yoshihisa Nakagawa13, Kiyoshi Hibi14, Takafumi Hiro15, Seiji Hokimoto16, Katsumi Miyauchi9, Hiroshi Ohtsu17, Hideo Izawa3, Hisao Ogawa18, Hiroyuki Daida9, Hiroaki Shimokawa19, Yasushi Saito20, Takeshi Kimura21, Masunori Matsuzaki22, Ryozo Nagai23. 1. Department of Clinical Laboratory, Bantane Hospital, Fujita Health University School of Medicine. 2. Data Science Office, Clinical Research Promotion Center, The University of Tokyo Hospital. 3. Department of Cardiology, Fujita Health University School of Medicine. 4. Division of Statics, Fujita Health University School of Medicine. 5. Department of Joint Research Laboratory of Clinical Medicine, Fujita Health University School of Medicine. 6. Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine. 7. Innovation and Research Support Center, International University of Health and Welfare. 8. Faculty of Medical Technology, School of Health Sciences, Fujita Health University. 9. Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine. 10. Department of Biostatistics, School of Public Health, The University of Tokyo. 11. Division of Cardiovascular Medicine, Department of Internal Medicine, Kurume University School of Medicine. 12. Caress Sapporo Hokko Memorial Clinic. 13. Department of Cardiovascular Medicine, Shiga University of Medical Science. 14. Division of Cardiology, Yokohama City University Medical Center. 15. Division of Cardiology, Department of Medicine, Nihon University School of Medicine. 16. Kumamoto Municipal Ueki Hospital. 17. Clinical Pharmacology and Regulatory Science, Graduate School of Medicine, Juntendo University. 18. Kumamoto University. 19. Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan, and International University of Health and Welfare. 20. Chiba University. 21. Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine. 22. St. Hill Hospital. 23. Jichi Medical University.
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.
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.
Authors: Mie Balling; Børge G Nordestgaard; Anne Langsted; Anette Varbo; Pia R Kamstrup; Shoaib Afzal Journal: J Am Coll Cardiol Date: 2020-06-09 Impact factor: 24.094
Authors: Samia Mora; Nanette K Wenger; David A Demicco; Andrei Breazna; S Matthijs Boekholdt; Benoit J Arsenault; Prakash Deedwania; John J P Kastelein; David D Waters Journal: Circulation Date: 2012-03-29 Impact factor: 29.690
Authors: L Chancharme; P Thérond; F Nigon; S Lepage; M Couturier; M J Chapman Journal: Arterioscler Thromb Vasc Biol Date: 1999-03 Impact factor: 8.311
Authors: Nuntakorn Thongtang; Margaret R Diffenderfer; Esther M M Ooi; P Hugh R Barrett; Scott M Turner; Ngoc-Anh Le; W Virgil Brown; Ernst J Schaefer Journal: J Lipid Res Date: 2017-04-09 Impact factor: 5.922
Authors: John C LaRosa; Scott M Grundy; David D Waters; Charles Shear; Philip Barter; Jean-Charles Fruchart; Antonio M Gotto; Heiner Greten; John J P Kastelein; James Shepherd; Nanette K Wenger Journal: N Engl J Med Date: 2005-03-08 Impact factor: 91.245