title: Comparative value of coronary artery calcium and multiple blood biomarkers for prognostication of cardiovascular events.
abstract: The value of coronary artery calcium (CAC) scoring versus multiple biomarkers in increasing risk prediction for cardiovascular disease (CVD) remains unknown. The study group consisted of 1,286 asymptomatic participants (mean ± SD 59 ± 8 years old) with no known coronary heart disease. Mean follow-up time was 4.1 ± 0.4 years with the primary outcome of combined CVD (cardiac death, myocardial infarction, stroke, and late target vessel revascularization). CAC was calculated by the method of Agatston. Biomarkers measured were C-reactive protein, interleukin-6, myeloperoxidase, B-type natriuretic peptide, and plasminogen activator-1. During follow-up 35 participants developed CVD events including cardiac deaths (6%), myocardial infarction (23%), strokes (17%), and late revascularizations (54%). In Cox proportional-hazards models adjusted for Framingham Risk Score (FRS), presence of log CAC beyond FRS was associated with increased hazards for CVD events (hazard ratio 1.7, 95% confidence interval [CI] 1.4 to 2.0, p <0.001). Multiple biomarkers score was also associated with increased risk beyond FRS (hazard ratio 2.1, p = 0.02) per 1-U increase in score; however, the c-statistic did not increase significantly (0.75, 95% CI 0.68 to 0.84, p = 0.32). The c-statistic increased when log CAC was incorporated into FRS without or with multiple biomarkers score (c-statistic 0.84, p = 0.003 and p = 0.008 respectively). Addition of CAC to risk factors showed significant reclassification (net reclassification improvement 0.35 (95% CI 0.11 to 0.58, p = 0.007; integrated discrimination index 0.076, p = 0.0001), whereas addition of multiple biomarkers score did not show significant reclassification. In conclusion, in this study of asymptomatic subjects without known CVD, addition of CAC but not biomarkers substantially improved risk reclassification for future CVD events beyond traditional risk factors.
authors.affiliation: Department of Imaging, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Jamal S
authors.initials: JS
authors.lastname: Rana
authors.forename: Heidi
authors.initials: H
authors.lastname: Gransar
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Wong
authors.forename: Leslee
authors.initials: L
authors.lastname: Shaw
authors.forename: Michael
authors.initials: M
authors.lastname: Pencina
authors.forename: Khurram
authors.initials: K
authors.lastname: Nasir
authors.forename: Alan
authors.initials: A
authors.lastname: Rozanski
authors.forename: Sean W
authors.initials: SW
authors.lastname: Hayes
authors.forename: Louise E
authors.initials: LE
authors.lastname: Thomson
authors.forename: John D
authors.initials: JD
authors.lastname: Friedman
authors.forename: James K
authors.initials: JK
authors.lastname: Min
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Berman
mesh_terms: D015415:Biomarkers / Q000097:blood*; D002114:Calcinosis / Q000097:blood / Q000000981:diagnostic imaging / Q000453:epidemiology*; D002118:Calcium / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology*; D017023:Coronary Angiography; D003331:Coronary Vessels / Q000378:metabolism*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D011795:Surveys and Questionnaires; D014057:Tomography, X-Ray Computed; D014481:United States / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D002118:Calcium