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Biomarkers to predict recurrent cardiovascular disease: the Heart and Soul Study
Michael G Shlipak1, Joachim H Ix, Kirsten Bibbins-Domingo
1Section of General Internal Medicine, San Francisco VA Medical Center, San Francisco, Calif, USA. Michael.shlipak@ucsf.edu
Insights
Biomarkers like N-terminal prohormone brain natriuretic peptide (Nt-proBNP), albuminuria, and C-reactive protein (CRP) significantly improve cardiovascular event prediction in patients with existing coronary artery disease. These markers reflect hemodynamic stress, kidney damage, and inflammation.
Area of Science:
- Cardiology
- Biomarker Research
- Preventive Medicine
Background:
- Current cardiovascular risk algorithms are suboptimal for predicting outcomes in patients with established coronary artery disease.
- There is a need for improved risk stratification tools in this high-risk population.
Purpose of the Study:
- To evaluate the predictive value of six biomarkers for cardiovascular events in individuals with pre-existing coronary artery disease.
- To determine if these biomarkers enhance risk prediction beyond traditional factors.
Main Methods:
- The Heart and Soul Study cohort (979 participants with coronary artery disease) was analyzed.
- Associations between N-terminal prohormone brain natriuretic peptide (Nt-proBNP), cystatin C, albuminuria, C-reactive protein (CRP), interleukin-6, and fibrinogen with cardiovascular events were examined.
- Multivariate analyses adjusted for demographic, lifestyle, clinical, and treatment variables.
Main Results:
- Five biomarkers (Nt-proBNP, cystatin C, albuminuria, CRP, interleukin-6) were individually associated with increased cardiovascular risk.
- Nt-proBNP, albuminuria, and CRP remained significant predictors after multivariable adjustment.
- Adding these three biomarkers to clinical predictors significantly improved the area under the receiver operator curve from 0.73 to 0.77.
Conclusions:
- Biomarkers reflecting hemodynamic stress (Nt-proBNP), kidney damage (albuminuria), and inflammation (CRP) significantly enhance cardiovascular event risk prediction in patients with established coronary artery disease.
- These findings support the integration of these biomarkers into risk assessment strategies for secondary prevention.
Purpose:
The study purpose was to evaluate the ability of 6 biomarkers to improve the prediction of cardiovascular events among persons with established coronary artery disease.
Background:
Cardiovascular risk algorithms are designed to predict the initial onset of coronary artery disease but are less effective in persons with preexisting coronary artery disease.
Methods:
We examined the association of N-terminal prohormone brain natriuretic peptide (Nt-proBNP), cystatin C, albuminuria, C-reactive protein (CRP), interleukin-6, and fibrinogen with cardiovascular events in 979 Heart and Soul Study participants with coronary artery disease after adjusting for demographic, lifestyle, and behavior variables; cardiovascular risk factors; cardiovascular disease severity; medication use; and left ventricular ejection fraction. The outcome was a composite of stroke, myocardial infarction, and coronary heart disease death during an average of 3.5 years of follow-up.
Results:
During follow-up, 142 participants (15%) developed cardiovascular events. The highest quartiles (vs lower 3 quartiles) of 5 biomarkers were individually associated with cardiovascular risk after multivariate analysis: Nt-proBNP hazard ratio (HR)=2.13 (95% confidence interval [CI], 1.43-3.18); cystatin C HR=1.72 (95% CI, 1.10-2.70); albuminuria HR=1.71 (95% CI, 1.15-2.54); CRP HR=2.00 (95% CI, 1.40-2.85); and interleukin-6 HR=1.76 (95% CI, 1.22-2.53). When all biomarkers were included in the multivariable analysis, only Nt-proBNP, albuminuria, and CRP remained significant predictors of events: HR=1.88 (95% CI, 1.23-2.85), HR=1.63 (95% CI, 1.09-2.43), and HR=1.82 (95% CI, 1.24-2.67), respectively. The area under the receiver operator curve for clinical predictors alone was 0.73 (95% CI, 0.68-0.78); adding Nt-proBNP, albuminuria, and CRP significantly increased the area under the receiver operator curve to 0.77 (95% CI, 0.73-0.82, P<.005).
Conclusion:
Among persons with prevalent coronary artery disease, biomarkers reflecting hemodynamic stress, kidney damage, and inflammation added significant risk discrimination for cardiovascular events.
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