Work

Remnant cholesterol, C-reactive protein, cholesterol-lowering medication, and cardiovascular outcome: novel findings from UK Biobank

Year: 2026

Type: article

Abstract: Background: Despite substantial reductions in cardiovascular events with intensive LDL-C lowering, significant residual risk persists. Remnant cholesterol (RC) and C-reactive protein (CRP) reflect lipid dysregulation and inflammation, respectively, and may synergistically promote atherosclerosis. However, large-scale cohort evidence on their combined impact, particularly the quantitative interaction between the two and the modifying role of cholesterol-lowering therapy, remains limited. Methods: This study included 376,817 participants with a median follow-up of 13.4 years. Cox proportional hazards regression models were used to evaluate the individual and joint associations of RC and CRP with major adverse cardiovascular events (MACE) risk. Stratified analyses by cholesterol-lowering therapy were further conducted to explore its modifying effect on the combined risk. Results: Both RC (≥0.8 mmol/L) and CRP (≥2 mg/L) were independently associated with MACE risk, with adjusted hazard ratios (HR) of 1.074 [95% confidence interval (CI): 1.024-1.126] and 1.168 (95% CI: 1.129-1.207), respectively. Concurrent elevation of both biomarkers conferred the highest risk (HR = 1.239, 95% CI: 1.167-1.316), and a significant positive multiplicative interaction was observed between RC and CRP. Stratified analyses suggested effect modification by cholesterol-lowering medication: the association between isolated RC elevation and MACE was attenuated in medication users, whereas risks remained significant for isolated CRP elevation and combined elevation of both markers. Conclusion: Concurrent elevation of RC and CRP yields the highest MACE risk with a positive additive interaction. Cholesterol-lowering therapy reduces RC-related risk but not inflammation-driven risk in isolated CRP elevation. These findings support combined assessment of both biomarkers for personalized cardiovascular risk stratification.

Source: Frontiers in Nutrition

DOI: 10.3389/fnut.2026.1920077

Authors: Jing Chen, Xuan Song, Jian-Jun Li, Li-Chan Tao

Institutions: Soochow University, Chinese Academy of Medical Sciences & Peking Union Medical College, Fu Wai Hospital, State Key Laboratory of Cardiovascular Disease

Language: English

Topic: Lipoproteins and Cardiovascular Health

Subfield: Cardiology and Cardiovascular Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801