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Serum Urate and Incident Cardiovascular Disease: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Huifen Wang1, David R Jacobs2, Angelo L Gaffo3
1Nutritional Epidemiology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, United States of America.
Insights
Serum urate (sUA) may predict cardiovascular disease (CVD) risk in adults. This association strengthens with age, suggesting sUA is an early biomarker for CVD development.
Area of Science:
- Cardiovascular Disease Research
- Metabolic Health Studies
- Biomarker Discovery
Background:
- Controversy exists regarding serum urate (sUA) as an independent predictor of cardiovascular disease (CVD).
- The age at which sUA might predict CVD is also debated.
- Understanding sUA's role in generally healthy adults is crucial.
Purpose of the Study:
- To investigate the association between serum urate (sUA) and incident cardiovascular disease (CVD).
- To determine if sUA predicts CVD independently of established risk factors.
- To explore how this association changes with age.
Main Methods:
- The study analyzed 5115 participants aged 18-30 years over 27 years.
- Serum urate levels were measured at multiple time points (baseline, years 10, 15, 20).
- Cox proportional hazards regression modeled the sUA-CVD association, adjusting for various factors.
Main Results:
- Baseline sUA was associated with CVD risk, but this attenuated after adjusting for classical risk factors.
- Associations between sUA at year 10 and CVD were observed but not statistically significant in the full model.
- Serum urate at year 15 showed a significant association with CVD, even after adjusting for risk factors.
- Hyperuricemia at year 15 strongly predicted CVD risk.
Conclusions:
- Serum urate may serve as an early biomarker for cardiovascular disease in adults approaching middle age.
- The predictive power of sUA for CVD appears to increase with age.
- Further research is needed to understand the complex relationship between sUA, metabolic abnormalities, and CVD.
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.
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