Association of cardiac biomarkers with long-term cardiovascular events in a community cohort

Abstract

Introduction: We hypothesized that combining biomarkers of atherosclerotic cardiovascular disease (ASCVD) would improve prediction of ASCVD events in a primary prevention cohort.

Materials and methods

The study assessed major adverse cardiac events (MACE) (myocardial infarction, coronary artery bypass graft, percutaneous intervention, stroke, and death. Cox proportional hazards models assessed apolipoprotein AI (ApoA1), apolipoprotein B (ApoB), ceramide score, cystatin C, galectin-3 (Gal3), LDL-C, Non-HDL-C, total cholesterol (TC), N-terminal B-type natriuretic peptide (NT proBNP), high-sensitivity cardiac troponin (HscTnI) and soluble interleukin 1 receptor-like 1. In adjusted models, Ceramide score was defined by from N-palmitoyl-sphingosine [Cer(16:0)], N-stearoyl-sphingosine [Cer(18:0)], N-nervonoyl-sphingosine [Cer(24:1)] and N-lignoceroyl-sphingosine [Cer(24:0)]. Multi-biomarker models were compared with C-statistics and Integrated Discrimination Index (IDI).

Results

A total of 1131 patients were included. Adjusted NT proBNP per 1 SD resulted in a 31% increased risk of MACE/death (HR = 1.31) and a 31% increased risk for stroke/MI (HR = 1.31). Adjusted Ceramide per 1 SD showed a 13% increased risk of MACE/death (HR = 1.13) and a 29% increased risk for stroke/MI (HR = 1.29). These markers added to clinical factors for both MACE/death (p = 0.003) and stroke/MI (p = 0.034). HscTnI was not a predictor of outcomes when added to the models.

Discussion

Ceramide score and NT proBNP improve the prediction of MACE and stroke/MI in a community primary prevention cohort.

Clinical significance

In a community cohort, where a wide range of biomarkers were evaluated, Ceramide score provided additive value over traditional cardiac risk factors alone for predicting stroke/MI. NT ProBNP provided additive value in prediction of MACE/death. Other biomarkers failed to improve the discrimination of these models.

Keywords:

• Ceramide score
• coronary artery disease
• N-Terminal proBNP

Acknowledgements

The authors report there are no additional acknowledgements to report.

Author contributions

Churchill – primary author.

Gochanour – statistics for data analysis and manuscript review.

Scott – statistics for data analysis and manuscript review.

Vasile – concept and initial drafting of the manuscript. Involved in the analytical validation of the ceramide assay and manuscript review.

Rodeheffer – originator of the PAVID concept. He wrote the initial grant and enrolled the patients and manuscript review.

Meeusen – Involved in the analytical validation of the ceramide assay and manuscript review.

Jaffe – original concept, funding, senior author with final say over the manuscript. Originator of licensing and then developing the ceramide assay at Mayo Clinic, Rochester.

Disclosure statement

Dr. Jaffe has or presently consults for most of the major diagnostic ­companies and has over time consulted for most of the companies that market the assays used in this study. All other authors have no declarations of interest to report.

Data availability

The data that support the findings of this study are available from the corresponding author, ASJ, upon reasonable request.

Additional information

Funding

This work did not receive funding support by a grant or other agency. All financial support was provided internally by the Mayo Clinic Department of Cardiovascular Diseases.