October 1, 2025BMJ OpenOpen Access

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

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Why the study?

To develop a CERT SCORE using odd-chain and even-chain ceramide species and evaluate its association with short-term and lifetime cardiovascular risk in CAD patients.

Does a high CERT SCORE predict increased risk of MACE in patients with coronary atherosclerotic heart disease?

Structured PICO

Does a high CERT SCORE predict increased risk of MACE in patients with coronary atherosclerotic heart disease?

Population

Patients with coronary atherosclerotic heart disease (CAD) defined as having at least one coronary artery stenosis of ≥50% as assessed by coronary angiography or CT angiography, from Beijing Anzhen Hospital.

Intervention

High-risk CERT SCORE (score 7-12) based on ceramide species (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))

Comparator

Low-risk CERT SCORE (score 0-6)

Outcome

Major adverse cardiac events (MACE) including all-cause death, myocardial infarction, heart failure, cerebral infarction and readmissioncomposite

A novel ceramide-based risk score (CERT SCORE) effectively stratifies short-term and lifetime risk of MACE in patients with coronary atherosclerotic heart disease.

Implication

Ceramide-based CERT score may refine CV risk stratification in CAD; leaves open prospective validation before clinical adoption.

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.