Serum uric acid and risk for cardiovascular disease and death: the Framingham Heart Study
B F Culleton1, M G Larson, W B Kannel
1National Heart, Lung, and Blood Institute's Framingham Heart Study, Massachusetts 01702, USA.
Insights
Elevated serum uric acid is not a direct cause of heart disease or death. Its apparent link is likely due to other associated risk factors, particularly diuretic use in women.
Area of Science:
- Cardiovascular epidemiology
- Metabolic health research
Background:
- Hyperuricemia is linked to cardiovascular disease (CVD) and mortality.
- The independent role of uric acid in CVD risk is not fully understood.
Purpose of the Study:
- To investigate the association between serum uric acid levels and incident coronary heart disease (CHD).
- To examine the relationship between serum uric acid and cardiovascular disease (CVD) mortality.
- To assess the link between serum uric acid and all-cause mortality.
Main Methods:
- A community-based, prospective observational study of 6763 participants from the Framingham Heart Study.
- Serum uric acid levels were measured at baseline (1971-1976).
- Event rates were analyzed by sex-specific uric acid quintiles over 117,376 person-years of follow-up.
Main Results:
- In men, elevated uric acid was not associated with adverse outcomes after age adjustment.
- In women, uric acid predicted incident CHD, CVD death, and all-cause mortality (P < 0.05).
- These associations in women disappeared after adjusting for CVD risk factors; diuretic use was identified as a key confounder.
Conclusions:
- Serum uric acid does not appear to have a causal role in the development of CHD, CVD death, or all-cause mortality.
- The observed association between uric acid and adverse outcomes is likely explained by its correlation with other risk factors.
- Diuretic use may confound the relationship between uric acid and cardiovascular outcomes.
Background:
Hyperuricemia is associated with risk for cardiovascular disease and death. However, the role of uric acid independent of established risk factors is uncertain.
Objective:
To examine the relation of serum uric acid level to incident coronary heart disease, death from cardiovascular disease, and death from all causes.
Design:
Community-based, prospective observational study.
Setting:
Framingham, Massachusetts.
Patients:
6763 Framingham Heart Study participants (mean age, 47 years).
Measurements:
Serum uricacid level at baseline (1971 to 1976); event rates per 1000 person-years by sex-specific uric acid quintile.
Results:
During 117,376 person-years of follow-up, 617 coronary heart disease events, 429 cardiovascular disease deaths, and 1460 deaths from all causes occurred. In men, after adjustment for age, elevated serum uric acid level was not associated with increased risk for an adverse outcome. In women, after adjustment for age, uric acid level was predictive of coronary heart disease (P = 0.002), death from cardiovascular disease (P = 0.009), and death from all causes (P = 0.03). After additional adjustment for cardiovascular disease risk factors, uric acid level was no longer associated with coronary heart disease, death from cardiovascular disease, or death from all causes. In a stepwise Cox model, diuretic use was identified as the covariate responsible for rendering serum uric acid a statistically nonsignificant predictor of outcomes.
Conclusions:
These findings indicate that uric acid does not have a causal role in the development of coronary heart disease, death from cardiovascular disease, or death from all causes. Any apparent association with these outcomes is probably due to the association of uric acid level with other risk factors.
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