Diuretic use, increased serum urate levels, and risk of incident gout in a population-based study of adults with hypertension: The Atherosclerosis Risk in Communities cohort study

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Abstract

Objective To quantify the role of diuretic use in gout development in an adult population with hypertension. Methods The Atherosclerosis Risk in Communities study, a prospective population-based cohort from 4 US communities, consisted of 4 visits over a 9-year period. Participants were included in this analysis if they answered a query about gout, were free of gout at baseline, and had hypertension (defined as taking medication to treat hypertension or having blood pressure of ≥140/90 mm Hg). Trained interviewers recorded use of antihypertensive drugs. Incident gout was defined as self-reported onset of gout after baseline. Using a time-dependent Cox proportional hazards model, we estimated hazard ratios (HRs; with 95% confidence intervals [95% CIs]) for incident gout by time-varying diuretic use, both adjusted for confounders and tested for mediation by serum urate level. Results There were 5,789 participants with hypertension; 37% were treated with a diuretic. Use of any diuretic (HR 1.48 [95% CI 1.11, 1.98]), a thiazide diuretic (HR 1.44 [95% CI 1.00, 2.10]), or a loop diuretic (HR 2.31 [95% CI 1.36, 3.91]) was associated with incident gout as compared with not using any diuretic, not using a thiazide diuretic, or not using a loop diuretic, respectively. After adjusting for serum urate level, the association between diuretic use and gout was null. Use of antihypertensive medication other than diuretic agents was associated with decreased gout risk (adjusted HR 0.64 [95% CI 0.49, 0.86]) compared to untreated hypertension. The longitudinal change in serum urate levels was 0.72 mg/dl (95% CI 0.57, 0.87) higher in those who began treatment with a diuretic than in those who did not (P <0.001). Conclusion Thiazide and loop diuretics were associated with increased gout risk, an association mediated by a change in serum urate levels.

Original languageEnglish (US)
Pages (from-to)121-129
Number of pages9
JournalArthritis and Rheumatism
Volume64
Issue number1
DOIs
StatePublished - Jan 2012

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Gout
Uric Acid
Diuretics
Atherosclerosis
Cohort Studies
Hypertension
Serum
Population
Confidence Intervals
Sodium Potassium Chloride Symporter Inhibitors
Sodium Chloride Symporter Inhibitors
Antihypertensive Agents
Proportional Hazards Models
Prospective Studies
Interviews
Blood Pressure

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology
  • Pharmacology (medical)

Cite this

@article{ff53d8eb1df548589ea84c3ae2260ce9,
title = "Diuretic use, increased serum urate levels, and risk of incident gout in a population-based study of adults with hypertension: The Atherosclerosis Risk in Communities cohort study",
abstract = "Objective To quantify the role of diuretic use in gout development in an adult population with hypertension. Methods The Atherosclerosis Risk in Communities study, a prospective population-based cohort from 4 US communities, consisted of 4 visits over a 9-year period. Participants were included in this analysis if they answered a query about gout, were free of gout at baseline, and had hypertension (defined as taking medication to treat hypertension or having blood pressure of ≥140/90 mm Hg). Trained interviewers recorded use of antihypertensive drugs. Incident gout was defined as self-reported onset of gout after baseline. Using a time-dependent Cox proportional hazards model, we estimated hazard ratios (HRs; with 95{\%} confidence intervals [95{\%} CIs]) for incident gout by time-varying diuretic use, both adjusted for confounders and tested for mediation by serum urate level. Results There were 5,789 participants with hypertension; 37{\%} were treated with a diuretic. Use of any diuretic (HR 1.48 [95{\%} CI 1.11, 1.98]), a thiazide diuretic (HR 1.44 [95{\%} CI 1.00, 2.10]), or a loop diuretic (HR 2.31 [95{\%} CI 1.36, 3.91]) was associated with incident gout as compared with not using any diuretic, not using a thiazide diuretic, or not using a loop diuretic, respectively. After adjusting for serum urate level, the association between diuretic use and gout was null. Use of antihypertensive medication other than diuretic agents was associated with decreased gout risk (adjusted HR 0.64 [95{\%} CI 0.49, 0.86]) compared to untreated hypertension. The longitudinal change in serum urate levels was 0.72 mg/dl (95{\%} CI 0.57, 0.87) higher in those who began treatment with a diuretic than in those who did not (P <0.001). Conclusion Thiazide and loop diuretics were associated with increased gout risk, an association mediated by a change in serum urate levels.",
author = "{McAdams Demarco}, {Mara Ann} and Maynard, {Janet W.} and Alan Baer and Allan Gelber and Young, {J Hunter} and Alvaro Alonso and Josef Coresh",
year = "2012",
month = "1",
doi = "10.1002/art.33315",
language = "English (US)",
volume = "64",
pages = "121--129",
journal = "Arthritis and Rheumatology",
issn = "2326-5191",
publisher = "John Wiley and Sons Ltd",
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T1 - Diuretic use, increased serum urate levels, and risk of incident gout in a population-based study of adults with hypertension

T2 - The Atherosclerosis Risk in Communities cohort study

AU - McAdams Demarco, Mara Ann

AU - Maynard, Janet W.

AU - Baer, Alan

AU - Gelber, Allan

AU - Young, J Hunter

AU - Alonso, Alvaro

AU - Coresh, Josef

PY - 2012/1

Y1 - 2012/1

N2 - Objective To quantify the role of diuretic use in gout development in an adult population with hypertension. Methods The Atherosclerosis Risk in Communities study, a prospective population-based cohort from 4 US communities, consisted of 4 visits over a 9-year period. Participants were included in this analysis if they answered a query about gout, were free of gout at baseline, and had hypertension (defined as taking medication to treat hypertension or having blood pressure of ≥140/90 mm Hg). Trained interviewers recorded use of antihypertensive drugs. Incident gout was defined as self-reported onset of gout after baseline. Using a time-dependent Cox proportional hazards model, we estimated hazard ratios (HRs; with 95% confidence intervals [95% CIs]) for incident gout by time-varying diuretic use, both adjusted for confounders and tested for mediation by serum urate level. Results There were 5,789 participants with hypertension; 37% were treated with a diuretic. Use of any diuretic (HR 1.48 [95% CI 1.11, 1.98]), a thiazide diuretic (HR 1.44 [95% CI 1.00, 2.10]), or a loop diuretic (HR 2.31 [95% CI 1.36, 3.91]) was associated with incident gout as compared with not using any diuretic, not using a thiazide diuretic, or not using a loop diuretic, respectively. After adjusting for serum urate level, the association between diuretic use and gout was null. Use of antihypertensive medication other than diuretic agents was associated with decreased gout risk (adjusted HR 0.64 [95% CI 0.49, 0.86]) compared to untreated hypertension. The longitudinal change in serum urate levels was 0.72 mg/dl (95% CI 0.57, 0.87) higher in those who began treatment with a diuretic than in those who did not (P <0.001). Conclusion Thiazide and loop diuretics were associated with increased gout risk, an association mediated by a change in serum urate levels.

AB - Objective To quantify the role of diuretic use in gout development in an adult population with hypertension. Methods The Atherosclerosis Risk in Communities study, a prospective population-based cohort from 4 US communities, consisted of 4 visits over a 9-year period. Participants were included in this analysis if they answered a query about gout, were free of gout at baseline, and had hypertension (defined as taking medication to treat hypertension or having blood pressure of ≥140/90 mm Hg). Trained interviewers recorded use of antihypertensive drugs. Incident gout was defined as self-reported onset of gout after baseline. Using a time-dependent Cox proportional hazards model, we estimated hazard ratios (HRs; with 95% confidence intervals [95% CIs]) for incident gout by time-varying diuretic use, both adjusted for confounders and tested for mediation by serum urate level. Results There were 5,789 participants with hypertension; 37% were treated with a diuretic. Use of any diuretic (HR 1.48 [95% CI 1.11, 1.98]), a thiazide diuretic (HR 1.44 [95% CI 1.00, 2.10]), or a loop diuretic (HR 2.31 [95% CI 1.36, 3.91]) was associated with incident gout as compared with not using any diuretic, not using a thiazide diuretic, or not using a loop diuretic, respectively. After adjusting for serum urate level, the association between diuretic use and gout was null. Use of antihypertensive medication other than diuretic agents was associated with decreased gout risk (adjusted HR 0.64 [95% CI 0.49, 0.86]) compared to untreated hypertension. The longitudinal change in serum urate levels was 0.72 mg/dl (95% CI 0.57, 0.87) higher in those who began treatment with a diuretic than in those who did not (P <0.001). Conclusion Thiazide and loop diuretics were associated with increased gout risk, an association mediated by a change in serum urate levels.

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