Hyperuricemia and incident hypertension: a systematic review and meta-analysis

Abstract

Objective: A novel rodent model and a recent randomized trial of hyperuricemic adolescents with hypertension suggest a pathogenetic role of uric acid in hypertension, but it remains unknown whether these findings would be applicable to adult populations where the larger disease burden exists. We conducted a systematic review and meta-analysis to determine if hyperuricemia was associated with incident hypertension, particularly in various demographic subgroups.

Methods: We searched major electronic databases using medical subject headings and keywords without language restrictions (through April 2010). We included prospective cohort studies with data on incident hypertension related to serum uric acid levels. Data abstraction was conducted in duplicate. We analyzed age, sex, and race subgroups.

Results: A total of 18 prospective cohort studies representing data from 55,607 participants were included. Hyperuricemia was associated with an increased risk for incident hypertension (adjusted risk ratio [RR] 1.41, 95% confidence interval [95% CI] 1.23-1.58). For a 1 mg/dl increase in uric acid level, the pooled RR for incident hypertension after adjusting for potential confounding was 1.13 (95% CI 1.06-1.20). These effects were significantly larger in younger study populations (P = 0.02) and tended to be larger in women (P = 0.059). Two studies suggested that the effect may also be larger among African American individuals. Furthermore, later publication year and US-based studies were significantly associated with a lower effect estimate (P values <0.02).

Conclusion: Hyperuricemia is associated with an increased risk for incident hypertension, independent of traditional hypertension risk factors. This risk appears more pronounced in younger individuals and women.

Figure 1

Study selection flow diagram.

Figure 2

Random-effects analysis of adjusted risk ratios of hyperuricemia associated with incident hypertension.

Figure 3

Random effects determined meta-regression line (β1= −0.026, p=0.02) of reported unadjusted risk ratios versus mean study age in 11 studies. Bubble size represents sample size.

Figure 4

Random-effects analysis of gender-specific adjusted risk ratios of hyperuricemia associated with incident hypertension.

Figure 5

Funnel plot for publication bias in 11 studies reporting adjusted risk ratios of hyperuricemia associated with incident hypertension. Dashed lines indicate 95% confidence intervals. SE: standard error, RR: risk ratio.