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.
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.