Serum uric acid and the risk of mortality during 23 years follow-up in the Scottish Heart Health Extended Cohort Study

Abstract

Background: Elevated uric acid is a prevalent condition with controversial health consequences. Observational studies disagree with regard to the relationship of uric acid with mortality, and with factors modifying this relationship.

Objective: We examined the association of serum uric acid with mortality in 15,083 participants in the Scottish Heart Health Extended Cohort (SHHEC) Study.

Methods: Serum uric acid was measured at study enrollment. Death was ascertained using both the Scottish death register and record linkage.

Results: During a median follow-up of 23 years, there were 3980 deaths. In Cox proportional hazards models with sexes combined, those in the highest fifth of uric acid had significantly greater mortality (HR 1.18, 95% CI: 1.06, 1.31) compared with the second fifth, after adjustment for traditional cardiovascular risk factors. This relationship was modified by sex (P-interaction=0.002) with adjusted HRs of 1.69 (95% CI: 1.40, 2.04) and 0.99 (95% CI: 0.86, 1.14) in women and men, respectively. Compared with the second fifth, the highest fifth of uric acid was most associated with kidney-related death (HR: 2.08, 95% CI: 1.31, 3.32).

Conclusion: Elevated uric acid is associated with earlier mortality, especially in women. Future studies should evaluate mechanisms for these interactions and explore the strong association with renal-related mortality.

Keywords: Cancer; Cardiovascular disease; Cohort; Hyperuricemia; Kidney disease; Mortality; Scottish Heart Health Extended Cohort (SHHEC); Uric acid.

Figure 1

Adjusted hazard ratios (solid line) from restricted cubic spline models for mortality, using overall fifths of baseline uric acid. Gray shading represents the 95% confidence intervals. The models were expressed relative to the 40^th percentile with knots specified at the 20^th, 40^th, 60^th, and 80^th percentiles and were adjusted for age, sex, systolic blood pressure, diastolic blood pressure, blood pressure medication use, systolic blood pressure & medication use interaction, smoking status, number of cigarettes per day among smokers, total cholesterol, high density lipoprotein cholesterol, body mass index, baseline diabetes status, daily alcohol use, and the Scottish Index of Multiple Deprivation. The plots were truncated at the 0.5^th and 99.5^th percentiles. The hazard ratios are shown on a natural log scale. Vertical lines depict male (M) and female (F) cutpoints for hyperuricemia.

Figure 2

Forest plot portraying the hazard ratio and 95% confidence interval of mortality, comparing participants with hyperuricemia (>416.36 μmol/L in men and >356.88 μmol/L in women) to participants without hyperuricemia. All strata were adjusted for age, sex, systolic blood pressure, diastolic blood pressure, blood pressure medication use, systolic blood pressure & medication use interaction, smoking status, number of cigarettes per day among smokers, total cholesterol, high density lipoprotein cholesterol, body mass index, baseline diabetes status, daily alcohol use, and the Scottish Index of Multiple Deprivation (SIMD). P-values comparing strata were determined using interaction terms.