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Observational Study
. 2025 Sep 1;32(9):1189-1202.
doi: 10.5551/jat.65520. Epub 2025 Mar 29.

Cholesterol Uptake Capacity as a Prognostic Marker of Cardiovascular Events for Patients with Coronary Artery Disease

Yusuke Yoshikawa  1 , Ryuji Toh  2 , Katsuhiro Murakami  3 , Amane Harada  3 , Jeeeun Kim  3 , Yuto Kobayash  3 , Keiko Miwa  3 , Manabu Nagao  2 , Tatsuro Ishida  4 , Ken-Ichi Hirata  5 , Misa Takegami  6   7 , Kunihiro Nishimura  1   7
Affiliations
Observational Study

Cholesterol Uptake Capacity as a Prognostic Marker of Cardiovascular Events for Patients with Coronary Artery Disease

Yusuke Yoshikawa et al. J Atheroscler Thromb. .

Abstract

Aim: Cholesterol uptake capacity (CUC) is a functional assessment of high-density lipoprotein (HDL) and has drawn attention for the risk stratification of atherosclerotic cardiovascular disease (ASCVD). This study evaluated the usefulness of HDL-CUC as a predictive marker for long-term ASCVD events in patients with coronary artery disease (CAD).

Methods: This retrospective observational study included 503 patients with CAD who underwent coronary revascularization. Blood was sampled from the participants within three months before or after index revascularization. The CUC was assayed using a previously reported automated system. The study population was divided into three groups according to the tertiles of CUC levels. The primary outcome was ASCVD events, which were defined as a composite of all-cause death, acute myocardial infarction, stroke, and peripheral artery disease.

Results: A total of 29 events were observed during the follow-up (median 2.8 years). The risk of the primary outcome in the low-CUC group was significantly higher than that in the high-CUC group (3-year incidence: low CUC 8.8% vs. high CUC 4.0%; log-rank p = 0.046). After adjusting for age and sex, the risk in the low-CUC group relative to that in the high-CUC group remained significantly high (hazard ratio 3.17, 95% confidence interval 1.05-9.54, p = 0.040).

Conclusion: Low CUC in patients with CAD were associated with a higher risk of ASCVD events after coronary revascularization than high CUC levels. The assessment of HDL functionality measured by CUC would be useful for the risk prediction of ASCVD after coronary revascularization.

Keywords: Cholesterol efflux capacity; Cholesterol uptake capacity; Coronary artery disease; Functionality of high-density lipoprotein; High-density lipoprotein; Secondary prevention.

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Conflict of interest statement

The authors declare the following financial interests/personal relationships that may be considered potential competing interests. Ryuji Toh, Manabu Nagao, and Ken-ichi Hirata belong to the Division of Evidence-based Laboratory Medicine, Kobe University Graduate School of Medicine, which developed the CUC measurement assay and was established by an endowment fund from the Sysmex Corporation. However, there is no declaration of a consultant or advisory role, stock ownership, honoraria, expert testimony, or patent. Katsuhiro Murakami, Amane Harada, Jeeeun Kim, Yuto Kobayashi, and Keiko Miwa are employees of Sysmex Corporation. The other authors have no known competing financial interests or personal relationships to declare.

Figures

Fig.1. Patient flowchart
Fig.1. Patient flowchart
NCVC, National Cerebral and Cardiovascular Center.
Supplementary Fig.1. Distribution of CUC levels
Supplementary Fig.1. Distribution of CUC levels
CUC, cholesterol uptake capacity.
Supplementary Fig.2.
Supplementary Fig.2.
Time-to-event analysis for the whole study population
Fig.2. The time-to-event analysis
Fig.2. The time-to-event analysis
Cumulative 3-year incidence of (A) primary and (B) secondary outcomes. The risks in patients with low and intermediate CUC were significantly higher than those in patients with high CUC. Restricted cubic spline analysis with CUC as a continuous variable for (C) the primary outcome and (D) the secondary outcome. The risk of primary atherosclerotic events relative to CUC 94.4 (A.U.), the second tertile point of CUC in the study population, decreased with increasing CUC until around the second tertile point and remained unchanged thereafter. CUC, cholesterol uptake capacity.
See this image and copyright information in PMC

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