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J Clin Hypertens (Greenwich). 2012; 14:675–679. ©2012 Wiley Periodicals, Inc.
The authors quantified the impact of hypertension on gout incidence in middle-aged white and African American men and women. The Atherosclerosis Risk in Communities Study (ARIC) was a prospective population-based cohort that recruited patients between 1987 and 1989 from 4 US communities. Using a time-dependent Cox proportional hazards model, the authors estimated the adjusted hazard ratio (HR) of incident gout by time-varying hypertension and tested for mediation by serum urate level. There were 10,872 participants among whom 45% had hypertension during follow-up; 43% were men and 21% were African American. Over 9 years, 274 (2.5%) participants developed gout (1.8% of women and 3.5% of men). The unadjusted HR of incident gout was approximately 3 times (HR, 2.87; 95% confidence interval [CI], 2.24–3.78) greater for those with hypertension. Adjusting for confounders resulted in an attenuated but still significant association between hypertension and gout (HR, 2.00; 95% CI, 1.54–2.61). Adjustment for serum urate level further attenuated but did not abrogate the association (HR, 1.36, 95% CI, 1.04–1.79). There was no evidence of effect modification by sex (P=.35), race (P=.99), or obesity at baseline (P=.82). Hypertension was independently associated with increased gout risk in middle-aged African American and white adults. Serum urate level may be a partial intermediate on the pathway between hypertension and gout.
There is a high prevalence of hypertension in the United States1 and this chronic condition is associated with morbidity and mortality.2 One condition associated with hypertension is gout, a metabolic disorder characterized by an inflammatory arthritis. Previous studies found that hypertension is associated with a 2- to 3-fold increase in the risk of gout.3–7 However, these previous studies have been limited in their ability to draw inference to broader populations. They were unable to generalize the results to the US population because these studies involved only a small number of patients with gout,7 included only men,4–7 or included only white participants.8 Many of these studies have focused on the association of a baseline history of hypertension,4–7 rather than time-varying measures of both treated and untreated hypertension. The prevalence of hypertension increases with age and thus studying a time-fixed measure of hypertension in a longitudinal cohort will misclassify participants as being normotensive. Previous studies have not adjusted for factors such as kidney function,4,6–8 which may explain part of the association of hypertension and gout. Additionally, other studies have adjusted for diuretic use when assessing the impact of hypertension.6,8 However, diuretics are first-line treatment for hypertension and thus are on the causal pathway between hypertension and gout. Adjusting for diuretic use measures the direct effect of hypertension on the incidence of gout but does not confound this association.
In this study, we addressed the previous gaps in the literature surrounding the association of hypertension and gout. We quantified the hazard of incident gout by hypertension and hypertension risk factors during 9 years of follow-up in a longitudinal population-based cohort of middle-aged adults. Additionally, we tested whether serum urate levels mediated the association of hypertension and gout.
- Top of page
- Materials and Methods
- Study Limitations
In a large prospective population-based study of middle-aged African American and white adults, patients with hypertension were at a 2-fold higher risk of developing gout. The association of hypertension and gout was independent of gout risk factors including kidney function. Additionally, our results suggest that serum urate level may be a partial mediator of hypertension and gout. Finally, hypertension increased the risk of gout regardless of sex, race, and obesity status.
We were able to extend the previous findings that hypertension was associated with gout from cohorts that were limited to men or participants of white race to a population-based cohort. The magnitude of the association, approximately a 2-fold increase in risk, was similar to previous studies.6,8 Campion and colleagues5 reported that hypertension was not associated with gout after adjusting for serum urate in men. Similarly, our results suggest that serum urate is a mediator of the association of hypertension and gout. However, we did not observe that the presence of hypertension nullified the association of African American race and gout, as was observed in a previous study.4 These differences in results may be due to the difference in the age of the cohorts, with ARIC being a study of adults at middle-age rather than at early adult life.
The biological mechanism linking hypertension and gout is thought to be through kidney function. The excretion of uric acid occurs primarily via the kidney.12 Hypertension is thought to be the cause of glomerular arteriolar damage and glomerulosclerosis. This will then lead to renal insufficiency and hyperuricemia. However, the directionality of hypertension and hyperuricemia is currently debated and it is possible that the relationship is bi-directional.13 Additionally, hypertension is a component of the metabolic syndrome, which has been associated with the development of gout.14
ARIC was a well-characterized cohort with very high response rates. This is one of the largest biracial studies of gout, which included both male and female participants with gout. Additionally, we used a broad definition of hypertension that included both measured BP and treatment. We were able to control for potential confounders of the association of hypertension and gout such as obesity, alcohol intake, and kidney function. Additionally, our results were robust to sensitivity analyses.
Acknowledgments and disclosure: The authors thank the staff and participants of the Atherosclerosis Risk in Communities Study (ARIC) study for their important contributions. ARIC is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C). Mara McAdams DeMarco was supported by a T32 training grant from the National Heart, Lung, and Blood Institute grant (5T32HL007024). The authors report no conflict of interest.