Serum Urate and Incident Cardiovascular Disease: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

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. CARDIA recruited 5115 black and white individuals...

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Bibliographic Details
Published in:PloS one 2015-09, Vol.10 (9), p.e0138067-e0138067
Main Authors: Wang, Huifen, Jacobs, Jr, David R, Gaffo, Angelo L, Gross, Myron D, Goff, Jr, David C, Carr, J Jeffrey
Format: Article
Language:English
Subjects:
Abnormalities
Adolescent
Adult
Adults
Aging
Analysis
Atherosclerosis
Biomarkers
Biomarkers - blood
Cardiovascular disease
Cardiovascular diseases
Cardiovascular Diseases - blood
Cardiovascular Diseases - epidemiology
Cohort Studies
Confidence intervals
Coronary artery
Coronary Artery Disease - blood
Coronary Artery Disease - epidemiology
Coronary Vessels - pathology
Demographics
Development and progression
Epidemiology
Exercise
Exploration
Female
Gender
Hazards
Health aspects
Health risk assessment
Health risks
Humans
Hyperuricemia
Incidence
Male
Mathematical models
Medical records
Patient outcomes
Predictions
Quartiles
Risk analysis
Risk Factors
Statistical analysis
Uric acid
Uric Acid - blood
Young Adult
Young adults
Youth
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Summary: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. 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. 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). 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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0138067