Inverse association between remnant cholesterol and MACCE in Japanese patients with CCS: insights from the clinical deep data accumulation system (CLIDAS)

Abstract Background Remnant cholesterol (RC) has been identified as a key lipid parameter associated with the incidence of coronary heart disease; however, its prognostic value in CCS patients following PCI remains unclear. Purpose This study aimed to investigate the relationship between RC levels and the risk of major adverse cardiac and cerebrovascular events (MACCE) and to assess the potential of RC as a risk stratification factor using the Clinical Deep Data Accumulation System (CLIDAS) database. Methods CLIDAS is a database that compiles electronic medical records from seven tertiary hospitals in Japan, encompassing patient demographics, medications, laboratory results, physiological tests, cardiac catheterisation, and PCI treatment details. We analysed 5,015 CCS patients who underwent PCI between April 2014 and March 2019. These patients were categorised into four groups based on remnant cholesterol levels: low (19 mg/dL, N=1,492), moderate (19–39 mg/dL, N=2,673), high (39–60 mg/dL, N=648), and very high (60 mg/dL, N=202). The primary endpoint was a composite of MACCE, including cardiovascular death, non-fatal myocardial infarction, stroke, and hospitalisation for heart failure. Results The median RC level in the overall cohort was 24 mg/dL. Patients in the low RC group exhibited a higher prevalence of baseline cardiovascular risk factors including older age, lower BMI, a higher prevalence of prior heart failure hospitalisations, higher BNP levels, and lower ejection fraction compared with the other groups. Kaplan-Meier analysis revealed that the very high RC group and the low RC group had higher event rates of MACCE than the other groups (log-rank p = 0.0001). Further analysis of the MACCE components showed that the very high RC group had a higher incidence of MI, whereas the low RC group exhibited higher rates of cardiovascular death and hospitalisation for heart failure. Importantly, after adjusting for age, sex, BMI, eGFR, history of heart failure hospitalisation, and statin use, the association between RC levels and MACCE followed a U-shaped pattern, indicating that both low and very high RC levels were associated with an increased risk. In this analysis, HR was set to 1 at an RC level of 19 mg/dL (Figure 1). Conclusion In CCS patients, very high RC levels were associated with a higher risk of MACCE, while low RC levels were linked to worse outcomes, likely due to underlying patient characteristics rather than RC levels themselves. The U-shaped association suggests that RC may serve as a potential marker for risk stratification, highlighting the need for comprehensive cardiovascular risk assessment and close monitoring in this population.Figure 1