Aggregate Risk Score Based on Markers of Inflammation, Cell Stress, and Coagulation Is an Independent Predictor of Adverse Cardiovascular Outcomes
ABSTRACT 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.
- SourceAvailable from: Abdul Wahab Hritani
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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 . Subjects were classified as current or non-smokers. "
ABSTRACT: Objective: Stromal derived factor-1α/CXCL12 is a chemoattractant responsible for homing of progenitor cells to ischemic tissues. We aimed to investigate the association of plasma CXCL12 with long-term cardiovascular outcomes in patients with coronary artery disease (CAD). Methods: 785 patients aged: 63 ± 12 undergoing coronary angiography were independently enrolled into discovery (N = 186) and replication (N = 599) cohorts. Baseline levels of plasma CXCL12 were measured using Quantikine CXCL12 ELISA assay (R&D systems). Patients were followed for cardiovascular death and/or myocardial infarction (MI) for a mean of 2.6 yrs. Cox proportional hazard was used to determine independent predictors of cardiovascular death/MI. Results: The incidence of cardiovascular death/MI was 13% (N = 99). High CXCL12 level based on best discriminatory threshold derived from the ROC analysis predicted risk of cardiovascular death/MI (HR = 4.81, p = 1 × 10(-6)) independent of traditional risk factors in the pooled cohort. Addition of CXCL12 to a baseline model was associated with a significant improvement in c-statistic (AUC: 0.67-0.73, p = 0.03). Addition of CXCL12 was associated with correct risk reclassification of 40% of events and 10.5% of non-events. Similarly for the outcome of cardiovascular death, the addition of the CXCL12 to the baseline model was associated with correct reclassification of 20.7% of events and 9% of non-events. These results were replicated in two independent cohorts. Conclusion: Plasma CXCL12 level is a strong independent predictor of adverse cardiovascular outcomes in patients with CAD and improves risk reclassification. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.Atherosclerosis 10/2014; 238(1):113-118. DOI:10.1016/j.atherosclerosis.2014.10.094 · 3.97 Impact Factor
- Journal of the American College of Cardiology 05/2013; 62(4). DOI:10.1016/j.jacc.2013.04.029 · 15.34 Impact Factor
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ABSTRACT: Progression to major acute cardiovascular events often is triggered by an atherosclerotic plaque complicated by rupture or erosion, namely the vulnerable plaque. Early and secure identification of these plaques would allow the development of individualized therapeutic and pharmacological strategies, applied in a timely manner. Imaging methods have a huge potential in detecting and monitoring the evolution of vulnerable plaque. Even though there are multiple invasive and noninvasive techniques, clinical application is for now a matter of choosing the relevant imaging feature for the prognosis, the methodo-logy of study and the target population.09/2013; 8(4):309-314.