title: Serum Urate and Incident Cardiovascular Disease: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.
abstract: OBJECTIVE
  There is controversy about whether serum urate (sUA) predicts future cardiovascular disease (CVD) independently of classical risk factors, and the age at which any prediction starts. We studied the sUA-CVD association among generally healthy adults.
  
  
  METHODS
  CARDIA recruited 5115 black and white individuals aged 18-30 years in 1985-1986 (year-0). Fatal and nonfatal CVD events by year 27 (n = 164) were ascertained during annual contacts and classified using medical records. The association with sUA (year-0, 10, 15 and 20) was modeled using Cox proportional hazards regression, pooling over gender-specific quartiles.
  
  
  RESULTS
  Mean sUA concentration was higher in men than women, but increased over time in both genders. Those with elevated sUA had worse metabolic profiles that substantially deteriorated over time. Adjusting for demographic and lifestyle factors (the minimal model), baseline sUA concentration was positively associated with incident CVD (hazard ratio (HR) per mg/dL = 1.21; 95% confidence interval: 1.05, 1.39; P = 0.005). This positive association attenuated to nonsignificance in the full model accounting simultaneously for classical CVD risk factors (HR = 1.09; 0.94, 1.27; P = 0.24). Both the minimal and full models appeared to show stronger associations (than year-0 sUA) between year-10 sUA and incident CVD (HR = 1.27 and 1.12, respectively), but sUA was not statistically significant in the full model. Despite fewer events, year-15 sUA showed a significant sUA-CVD association pattern, with minimal model association magnitude comparable to year-10, and remained significant in the full model (HR = 1.19; 1.02, 1.40; P = 0.03). Hyperuricemia at year-15 strongly predicted CVD risk (HR = 2.11; 1.34, 3.33; P = 0.001), with some attenuation in the full model (HR = 1.68; P = 0.04).
  
  
  CONCLUSIONS
  sUA may be an early biomarker for CVD in adults entering middle age. The prediction of CVD by sUA appeared to strengthen with aging. The potential complex relation of sUA with deterioration of a cluster of metabolic abnormalities warrants future exploration.
authors.affiliation: Nutritional Epidemiology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, United States of America.
authors.forename: Huifen
authors.initials: H
authors.lastname: Wang
authors.affiliation: Division of Epidemiology and Community Health, School of Public Health, University of Minnesota-Twin Cities, Minneapolis, MN, United States of America.
authors.forename: David R
authors.initials: DR
authors.lastname: Jacobs
authors.affiliation: Division of Rheumatology, University of Alabama at Birmingham, Birmingham, AL, United States of America.
authors.forename: Angelo L
authors.initials: AL
authors.lastname: Gaffo
authors.affiliation: Laboratory of Medicine and Pathology, University of Minnesota-Twin Cities, Minneapolis, MN, United States of America.
authors.forename: Myron D
authors.initials: MD
authors.lastname: Gross
authors.affiliation: Colorado School of Public Health, University of Colorado Denver, Aurora, CO, United States of America.
authors.forename: David C
authors.initials: DC
authors.lastname: Goff
authors.affiliation: Department of Radiology, Vanderbilt University Medical Center, Nashville, TN, United States of America.
authors.forename: J Jeffrey
authors.initials: JJ
authors.lastname: Carr
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology*; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000097:blood / Q000453:epidemiology*; D003331:Coronary Vessels / Q000473:pathology; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D012307:Risk Factors; D014527:Uric Acid / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D014527:Uric Acid