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Observational Study
. 2025 May-Jun;19(3):509-520.
doi: 10.1016/j.jacl.2024.12.019. Epub 2025 Jan 3.

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

Daisuke Shishikura  1 , Yu Kataoka  2 , Stephen J Nicholls  3 , Kausik K Ray  4 , Rishi Puri  5 , Hirofumi Kusumoto  1 , Yohei Yamauchi  1 , Kazushi Sakane  1 , Tomohiro Fujisaka  1 , Hideaki Morita  1 , Kota Murai  6 , Takamasa Iwai  6 , Kenichiro Sawada  6 , Hideo Matama  6 , Satoshi Honda  6 , Masashi Fujino  3 , Shuichi Yoneda  6 , Kensuke Takagi  6 , Kazuhiro Nakao  6 , Fumiyuki Otsuka  6 , Kensaku Nishihira  7 , Itaru Takamisawa  8 , Yasuhide Asaumi  6 , Teruo Noguchi  6 , Mariko Harada-Shiba  1 , Masaaki Hoshiga  1
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Free article
Observational Study

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

Daisuke Shishikura et al. J Clin Lipidol. 2025 May-Jun.
Free article

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 (MaxLCBI4 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 MaxLCBI4mm 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 MaxLCBI4mm (P < .001) and a lower frequency of MaxLCBI4mm ≥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% CI: 0.13-0.68) of MaxLCBI4mm ≥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.

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