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Multiple Cardiac Biomarkers to Improve Prediction of Cardiovascular Events: Findings from the Generation Scotland
Paul Welsh1, Dorien M Kimenai2, Anoop S V Shah3
1School of Cardiovascular & Metabolic Health, University of Glasgow, Glasgow, United Kingdom.
Insights
A combined biomarker approach using growth differentiation factor-15 (GDF-15), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and cardiac troponin I (cTnI) improved cardiovascular risk prediction. This sex-specific strategy offers refined estimates for primary prevention.
Area of Science:
- Cardiology
- Biomarker Research
- Preventive Medicine
Background:
- Single cardiac biomarkers have limited success in improving cardiovascular risk prediction for primary prevention.
- The utility of a combined, sex-specific biomarker approach remains unclear.
Purpose of the Study:
- To evaluate a sex-specific, combined cardiac biomarker strategy for enhancing cardiovascular risk prediction.
- To determine if combinations of biomarkers offer superior risk stratification compared to individual markers or existing models.
Main Methods:
- Utilized data from the Generation Scotland Scottish Family Health Study (N=18,383).
- Measured NT-proBNP, GDF-15, cTnI, cTnT, and CRP using automated immunoassays.
- Employed sex-specific Cox models incorporating SCORE2 risk factors to assess biomarker additions for major adverse cardiovascular events (MACE).
Main Results:
- Combined models including GDF-15, NT-proBNP, and cTnI demonstrated the most significant improvements in risk prediction discrimination for women.
- For men, combinations of NT-proBNP with GDF-15 or CRP also enhanced risk prediction.
- Individual biomarkers showed varying degrees of improvement, with GDF-15 for women and NT-proBNP for men yielding the greatest single-marker benefit.
Conclusions:
- A combined biomarker approach, specifically utilizing GDF-15, NT-proBNP, and cTnI, effectively refines cardiovascular risk estimates.
- This sex-specific strategy holds promise for improving primary prevention strategies by providing more accurate risk stratification.
Background:
Many studies have investigated whether single cardiac biomarkers improve cardiovascular risk prediction for primary prevention but whether a combined approach could further improve risk prediction is unclear. We aimed to test a sex-specific, combined cardiac biomarker approach for cardiovascular risk prediction.
Methods:
In the Generation Scotland Scottish Family Health Study, N-terminal pro-B-type natriuretic peptide (NT-proBNP), growth differentiation factor-15 (GDF-15), cardiac troponin I (cTnI), cardiac troponin T (cTnT), and C-reactive protein (CRP) were measured in stored serum using automated immunoassays. Sex-specific Cox models that included SCORE2 risk factors evaluated addition of single and combined biomarkers for prediction of major adverse cardiovascular events (MACE). Combined biomarker models were compared to a baseline model that included SCORE2 risk factors.
Results:
The study population comprised 18 383 individuals (58.9% women, median age of 48 years [25th-75th percentile, 35-58 years]). During the median follow up of 11.6 (25th-75th percentile, 10.8-13.0) years, MACE occurred in 942 (5.1%) individuals. The greatest increase in discrimination with addition of individual biomarkers to the base model was for women GDF-15 and for men NT-proBNP (change in c-index: + 0.010 for women and +0.005 for men). For women, combined biomarker models that included GDF-15 and NT-proBNP (+0.012) or GDF-15 and cTnI (+0.013), but not CRP or cTnT, further improved discrimination. For men, combined biomarker models that included NT-proBNP and GDF-15 (+0.007), NT-proBNP and cTnI (+0.006), or NT-proBNP and CRP (+0.008), but not cTnT, further improved discrimination.
Conclusions:
A combined biomarker approach, particularly the use of GDF-15, NT-proBNP and cTnI, further refined cardiovascular risk estimates.
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