Aggregate Risk Score Based on Markers of Inflammation, Cell Stress, and Coagulation Is an Independent Predictor of Adverse Cardiovascular Outcomes

Emory University School of Medicine, Department of Medicine, Division of Cardiology. Atlanta, GA.
Journal of the American College of Cardiology (Impact Factor: 16.5). 05/2013; 62(4). DOI: 10.1016/j.jacc.2013.03.072
Source: PubMed


OBJECTIVE: To determine an aggregate, pathway- specific risk score for enhanced prediction of death and myocardial infarction (MI). BACKGROUND: Activation of inflammatory, coagulation, and cellular stress pathways contribute to atherosclerotic plaque rupture. We hypothesized that an aggregate risk score comprised of biomarkers involved in these different pathways--high sensitivity C-reactive protein (CRP), fibrin degradation products (FDP), and heat shock protein 70 (HSP70) levels--would be a powerful predictor of death and MI. METHODS: Serum levels of CRP, FDP and HSP70 were measured in 3,415 consecutive patients with suspected or confirmed CAD undergoing cardiac catheterization. Survival analyses were performed with models adjusted for established risk factors. RESULTS: Median follow-up was 2.3 years. Hazard ratios (HRs) for all-cause death and MI based on cut-points were as follows: for CRP ≥3.0 mg/L, HR=1.61HSP70 >0.625 ng/mL, HR= 2.26; and FDP ≥1.0 μg/ml, HR=1.62 (p <0.0001 for all). An aggregate biomarker score between 0 and 3 was calculated based on these cut-points. Compared to the group with 0 score, HRs for all-cause death and MI were 1.83, 3.46, and 4.99 for those with scores of 1, 2, and 3, respectively (p for each: <0.001). Annual event rates were 16.3% for the 4.2% of subjects with a score of 3 compared to 2.4% in 36.4% subjects with a score of 0. The C-Statistic and Net Reclassification improved (p<0.0001) with the addition of the biomarker score. CONCLUSIONS: An aggregate score based on serum levels of CRP, FDP and HSP70 is a predictor of future risk of death and MI in patients with suspected or known CAD.

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Available from: Ravi Prasad Avati Nanjundappa, Aug 25, 2015
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    • "The replication cohort was a nested study within the Emory Cardiovascular Biobank with subjects enrolled between years 2008e2011. Demographics, medical, and behavioral characteristics as well as risk factor prevalence were documented as previously described [10]. Subjects were classified as current or non-smokers. "
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    • "Clinical characteristics and behavioral factors were obtained using a comprehensive questionnaire and were confirmed by electronic chart review. Risk factor prevalence was determined by physician diagnosis and/or treatment of hypertension, hyperlipidemia, and diabetes and detailed medication history was obtained [15]. Prevalent myocardial infarction (MI) at the time of enrollment was diagnosed using standard universal criteria. "
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    • "The scores improved accuracy of clinical algorithms for global cardiovascular risk prediction that reclassified subjects at intermediate-risk into higher- or lower-risk categories. Another score based on serum levels of CRP, fibrin degradation products, and heat shock protein 70 as predictors of future risk of death and myocardial infarction in patients with suspected or known CHD followed in 2013 [34]. "
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