Association of plasma ceramides with short-term and lifetime risk of MACE in coronary atherosclerotic heart disease patients: a prospective cohort study

  • BMJ Open. 2025 Oct 21;15(10):e094100. doi: 10.1136/bmjopen-2024-094100.
Xiaolu Li  #  1 Rui Zhang  #  2 Xu Chen  #  1 Suya Bao  1 Hongfeng Jiang  3
Affiliations
  • 1. Experimental Research Center, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing, China.
  • 2. The Science and Technology Service Office, Jinan Vocational College, Jinan, Shandong, China.
  • 3. Experimental Research Center, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing, China [email protected].
  • # Contributed equally.
Abstract

Objectives: To develop a CERT SCORE utilising both odd-chain and even-chain ceramide species, and to evaluate its association with short-term and lifetime cardiovascular risk in patients with coronary atherosclerotic heart disease (CAD).

Design: Prospective cohort study.

Setting: A patients-based cohort in the Beijing Anzhen Hospital, Capital Medical University.

Participants: CAD patients were defined as having at least one coronary artery stenosis of ≥50% as assessed by coronary angiography or CT angiography.

Main outcomes and measures: Major adverse cardiac events (MACE) including all-cause death, myocardial infarction, heart failure, cerebral infarction and readmission.

Results: We quantified 13 ceramide species and calculated the ratios of Cer(d18:1/14:0) and Cer(d18:1/24:0). Based on these measurements, Cer(d18:1/19:0), Cer(d18:1/19:0)/Cer(d18:1/14:0), Cer(d18:1/19:0)/Cer(d18:1/24:0) and Cer(d18:1/21:0)/Cer(d18:1/24:0) were selected to construct the CERT SCORE. Using this score, patients were classified into two distinct risk categories for MACE: low-risk (score 0-6) and high-risk (score 7-12). The high-risk group exhibited a significantly higher short-term risk of MACE (HR 2.10; 95% CI 1.50 to 2.94) compared with the low-risk group. The cumulative MACE risk in the low- and high-risk groups during the 1000-day follow-up was 25.45% and 44%, respectively. Subgroup analyses revealed that the presence of multivessel coronary artery lesions did not significantly modify the association between the CERT SCORE and short-term MACE risk (p value for interaction=0.967). Furthermore, in the age groups of 41-50 years, 51-60 years and 61-70 years, lifetime risk was significantly elevated in the high-risk group compared with the low-risk group.

Conclusion: We have developed a ceramide-based risk stratification tool (CERT SCORE) that demonstrates robust predictive value for identifying high-risk MACE patients among CAD patients. This tool offers considerable clinical utility for guiding patient management and informing therapeutic decisions.

Keywords
Angina Pectoris; Cardiac Epidemiology; Cardiovascular Disease; Coronary heart disease; Ischaemic heart disease.
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