title: Homocysteine and reclassification of cardiovascular disease risk.
abstract: OBJECTIVE
  The purpose of this study was to examine whether adding homocysteine (Hcy) to a model based on traditional cardiovascular disease (CVD) risk factors improves risk classification.
  
  
  BACKGROUND
  Data on using Hcy to reclassify individuals in various risk categories beyond traditional approaches have not been adequately scrutinized.
  
  
  METHODS
  We performed a post hoc analysis of the MESA (Multi-Ethnic Study of Atherosclerosis) and NHANES III (National Health and Nutrition Examination Survey III) datasets. Hcy was used to predict composite CVD and hard coronary heart disease (CHD) events in the MESA study and CVD and CHD mortality in the NHANES III survey using adjusted Cox-proportional hazard analysis. Reclassification of CHD events was performed using a net reclassification improvement (NRI) index with a Framingham risk score (FRS) model with and without Hcy.
  
  
  RESULTS
  Hcy level (>15 μmol/l) significantly predicted CVD (adjusted hazard ratio [aHR]: 1.79, 95% confidence intervals [CI]: 1.19 to 1.95; p = 0.006) and CHD events (aHR: 2.22, 95% CI: 1.20 to 4.09; p = 0.01) in the MESA trial and CVD (aHR: 2.72, 95% CI: 2.01 to 3.68; p < 0.001) and CHD mortality (aHR: 2.61, 95% CI: 1.83 to 3.73; p < 0.001) in the NHANES III, after adjustments for traditional risk factors and C-reactive protein. The level of Hcy, when added to FRS, significantly reclassified 12.9% and 18.3% of the overall and 21.2% and 19.2% of the intermediate-risk population from the MESA and NHANES cohorts, respectively. The categoryless NRI also showed significant reclassification in both MESA (NRI: 0.35, 95% CI: 0.17 to 0.53; p < 0.001) and NHANES III (NRI: 0.57, 95% CI: 0.43 to 0.71; p < 0.001) datasets.
  
  
  CONCLUSIONS
  From these 2 disparate population cohorts, we found that addition of Hcy level to FRS significantly improved risk prediction, especially in individuals at intermediate risk for CHD events.
authors.affiliation: Division of Cardiology, Wayne State University, Detroit Medical Center, Detroit, MI 48201, USA.
authors.forename: Vikas
authors.initials: V
authors.lastname: Veeranna
authors.forename: Sandip K
authors.initials: SK
authors.lastname: Zalawadiya
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Niraj
authors.forename: Jyotiranjan
authors.initials: J
authors.lastname: Pradhan
authors.forename: Brian
authors.initials: B
authors.lastname: Ference
authors.forename: Robert C
authors.initials: RC
authors.lastname: Burack
authors.forename: Sony
authors.initials: S
authors.lastname: Jacob
authors.forename: Luis
authors.initials: L
authors.lastname: Afonso
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology*; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009749:Nutrition Surveys; D018570:Risk Assessment / Q000379:methods; D014481:United States / Q000453:epidemiology
chemical_list: D006710:Homocysteine