title: Usefulness of the addition of beta-2-microglobulin, cystatin C and C-reactive protein to an established risk factors model to improve mortality risk prediction in patients undergoing coronary angiography.
abstract: Evidence-based therapies are available to reduce the risk for death from cardiovascular disease, yet many patients go untreated. Novel methods are needed to identify those at highest risk for cardiovascular death. In this study, the biomarkers β2-microglobulin, cystatin C, and C-reactive protein were measured at baseline in a cohort of participants who underwent coronary angiography. Adjusted Cox proportional-hazards models were used to determine whether the biomarkers predicted all-cause and cardiovascular mortality. Additionally, improvements in risk reclassification and discrimination were evaluated by calculating the net reclassification improvement, C-index, and integrated discrimination improvement with the addition of the biomarkers to a baseline model of risk factors for cardiovascular disease and death. During a median follow-up period of 5.6 years, there were 78 deaths among 470 participants. All biomarkers independently predicted future all-cause and cardiovascular mortality. A significant improvement in risk reclassification was observed for all-cause (net reclassification improvement 35.8%, p = 0.004) and cardiovascular (net reclassification improvement 61.9%, p = 0.008) mortality compared to the baseline risk factors model. Additionally, there was significantly increased risk discrimination with C-indexes of 0.777 (change in C-index 0.057, 95% confidence interval 0.016 to 0.097) and 0.826 (change in C-index 0.071, 95% confidence interval 0.010 to 0.133) for all-cause and cardiovascular mortality, respectively. Improvements in risk discrimination were further supported using the integrated discrimination improvement index. In conclusion, this study provides evidence that β2-microglobulin, cystatin C, and C-reactive protein predict mortality and improve risk reclassification and discrimination for a high-risk cohort of patients who undergo coronary angiography.
authors.affiliation: Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Kevin T
authors.initials: KT
authors.lastname: Nead
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Zhou
authors.forename: Roxanne Diaz
authors.initials: RD
authors.lastname: Caceres
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Sharp
authors.forename: Mackenzie R
authors.initials: MR
authors.lastname: Wehner
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Olin
authors.forename: John P
authors.initials: JP
authors.lastname: Cooke
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Leeper
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000401:mortality*; D017023:Coronary Angiography; D055316:Cystatin C / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D016019:Survival Analysis; D001613:beta 2-Microglobulin / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D055316:Cystatin C; D001613:beta 2-Microglobulin; D002097:C-Reactive Protein