Characterization of lipidic plaque features in association with LDL-C<70 mg/dL and lipoprotein(a) <50 mg/dL

Daisuke Shishikura; Yu Kataoka; Stephen J Nicholls; Kausik K Ray; Rishi Puri; Hirofumi Kusumoto; Yohei Yamauchi; Kazushi Sakane; Tomohiro Fujisaka; Hideaki Morita; Kota Murai; Takamasa Iwai; Kenichiro Sawada; Hideo Matama; Satoshi Honda; Masashi Fujino; Shuichi Yoneda; Kensuke Takagi; Kazuhiro Nakao; Fumiyuki Otsuka; Kensaku Nishihira; Itaru Takamisawa; Yasuhide Asaumi; Teruo Noguchi; Mariko Harada-Shiba; Masaaki Hoshiga

doi:10.1016/j.jacl.2024.12.019

Characterization of lipidic plaque features in association with LDL-C<70 mg/dL and lipoprotein(a) <50 mg/dL

J Clin Lipidol. 2025 Jan 3:S1933-2874(24)00305-2. doi: 10.1016/j.jacl.2024.12.019. Online ahead of print.

Authors

Daisuke Shishikura¹, Yu Kataoka², Stephen J Nicholls³, Kausik K Ray⁴, Rishi Puri⁵, Hirofumi Kusumoto¹, Yohei Yamauchi¹, Kazushi Sakane¹, Tomohiro Fujisaka¹, Hideaki Morita¹, Kota Murai⁶, Takamasa Iwai⁶, Kenichiro Sawada⁶, Hideo Matama⁶, Satoshi Honda⁶, Masashi Fujino³, Shuichi Yoneda⁶, Kensuke Takagi⁶, Kazuhiro Nakao⁶, Fumiyuki Otsuka⁶, Kensaku Nishihira⁷, Itaru Takamisawa⁸, Yasuhide Asaumi⁶, Teruo Noguchi⁶, Mariko Harada-Shiba¹, Masaaki Hoshiga¹

Affiliations

¹ Osaka Medical and Pharmaceutical University, Department of Cardiology, Japan (Drs Shishikura, Kusumoto, Yamauchi, Sakane, Fujisaka, Morita, Harada-Shiba, and Hoshiga).
² Department of Cardiovascular Medicine, National Cerebral & Cardiovascular Center, Suita, Japan (Drs Kataoka, Murai, Iwai, Sawada, Matama, Honda, Yoneda, Takagi, Nakao, Otsuka, Asaumi, and Noguchi). Electronic address: yu.kataoka@ncvc.go.jp.
³ Victorian Heart Institute, Monash University, Melbourne, Australia (Drs Nicholls and Fujino).
⁴ Department of Primary Care and Public Health, School of Public Health, Imperial College London, London, United Kingdom (Dr Ray).
⁵ Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, USA (Dr Puri).
⁶ Department of Cardiovascular Medicine, National Cerebral & Cardiovascular Center, Suita, Japan (Drs Kataoka, Murai, Iwai, Sawada, Matama, Honda, Yoneda, Takagi, Nakao, Otsuka, Asaumi, and Noguchi).
⁷ Department of Cardiology, Miyazaki Medical Association Hospital, Miyazaki, Japan (Dr Nishihira).
⁸ Department of Cardiovascular Medicine, Sakakibara Heart Institute, Fuchu-shi, Tokyo, Japan (Dr Takamisawa).

PMID: 39955203
DOI: 10.1016/j.jacl.2024.12.019

Abstract

Background: The ongoing residual cardiovascular risks despite lowering low-density lipoprotein cholesterol (LDL-C) levels suggest the need to identify additional drivers associated with atherosclerosis. Circulating lipoprotein(a) [Lp(a)]promotes formation of foam cells via its proatherogenic properties. However, whether a lower Lp(a) level in combination with favorable LDL-C control could induce a more stable form of disease remains unknown. Near-infrared spectroscopy (NIRS) generates maximum lipid-core burden index in 4 mm (MaxLCBI_{4 mm}) which is a histologically validated measure of lipidic plaque material in vivo. Therefore, the current study employed NIRS imaging to characterize lipidic plaque in association with LDL-C < 70 mg/dL and Lp(a) <50 mg/dL.

Methods: We analyzed 439 patients with coronary artery disease (CAD) (554 de-novo target lesions receiving percutaneous coronary intervention) in the REASSURE-NIRS registry (NCT04864171). Clinical characteristics and NIRS-derived MaxLCBI₄_mm were compared among 4 groups according to LDL-C of 70 mg/dL and Lp(a) of 50 mg/dL.

Results: Almost one-third of study subjects (33.4%) exhibited both LDL-C < 70 mg/dL and Lp(a) <50 mg/dL. They were more likely male with a lower frequency of acute coronary syndrome and lipid lowering therapies were more frequently used in those with LDL-C < 70 mg/dL and Lp(a) <50 mg/dL. On NIRS imaging analysis, a smaller MaxLCBI₄_mm (P < .001) and a lower frequency of MaxLCBI₄_mm ≥400 (P = .001) were observed in those with both LDL-C < 70 mg/dL and Lp(a) <50 mg/dL. On multivariable logistic regression analysis, the coexistence of these 2 lipid controls showed an approximately 70% lower risk (adjusted odds ratio: 0.30; 95% confidence interval: 0.13-0.68) of MaxLCBI₄_mm ≥400 compared with the reference group (LDL-C ≥ 70 mg/dL and Lp(a) ≥50 mg/dL).

Conclusion: Our findings suggest circulating Lp(a) as a potential therapeutic target to stabilize coronary atherosclerosis in CAD patients who achieved LDL-C < 70 mg/dL.

Keywords: Coronary; LDL-C; Lipidic plaque; Lipoprotein(a); Near-infrared spectroscopy.