Abstract

Objective To determine the independent associations of antihypertensive drugs with the risk of incident gout among people with hypertension.
Design Nested case-control study.
Setting UK general practice database, 2000-7.
Participants All incident cases of gout (n=24,768) among adults aged 20-79 and a random sample of 50,000 matched controls.
Main outcome measure Relative risk of incident gout associated with use of antihypertensive drugs.
Results After adjusting for age, sex, body mass index, visits to the general practitioner, alcohol intake, and pertinent drugs and comorbidities, the multivariate relative risks of incident gout associated with current use of antihypertensive drugs among those with hypertension (n=29,138) were 0.87 (95% confidence interval 0.82 to 0.93) for calcium channel blockers, 0.81 (0.70 to 0.94) for losartan, 2.36 (2.21 to 2.52) for diuretics, 1.48 (1.40 to 1.57) for β blockers, 1.24 (1.17 to 1.32) for angiotensin converting enzyme inhibitors, and 1.29 (1.16 to 1.43) for non-losartan angiotensin II receptor blockers. Similar results were obtained among those without hypertension. The multivariate relative risks for the duration of use of calcium channel blockers among those with hypertension were 1.02 for less than one year, 0.88 for 1-1.9 years, and 0.75 for two or more years and for use of losartan they were 0.98, 0.87, and 0.71, respectively (both P<0.05 for trend).
Conclusions Compatible with their urate lowering properties, calcium channel blockers and losartan are associated with a lower risk of incident gout among people with hypertension. By contrast, diuretics, β blockers, angiotensin converting enzyme inhibitors, and non-losartan angiotensin II receptor blockers are associated with an increased risk of gout.

Introduction

Hypertension is one of the most common comorbidities of gout. According to the latest estimates from the US National Health and Nutrition Examination Survey (2007-8), 74% of patients with gout have hypertension,^[1] which corresponds to 6.1 million adults in the United States alone. This substantial burden of comorbidity possibly stems from copathogenesis of the two conditions or renal changes in hypertension leading to decreased urate excretion. Studies have shown that the presence of hypertension is independently associated with the risk of incident gout^[2] through reduced renal blood flow with increased renal and systemic vascular resistance and decreased renal excretion of urate.^[3-6]

Certain antihypertensive drugs also increase the levels of serum uric acid and thus may contribute to the risk of gout. For example, in addition to the well known entities of diuretic induced hyperuricaemia and gout,^[3,7,8] the use of β blockers has been shown to increase levels of serum uric acid in short-term trials.^[8,9] However, calcium channel blockers and losartan have been found to lower serum uric acid levels,^[10-16] carrying the potential to lower the risk of gout. To date, however, no study has investigated the relation between various antihypertensive agents and the risk of gout. To address these issues, we analysed a cohort of 24,768 people with newly diagnosed gout and 50,000 matched controls from the health improvement network database.

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