{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T05:16:49Z","timestamp":1792819009715,"version":"4.5.0"},"reference-count":24,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,3,29]],"date-time":"2017-03-29T00:00:00Z","timestamp":1490745600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000980","name":"Arthritis Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000980","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis Care &amp; Research"],"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Obesity is strongly associated with incident gout risk, but its association with the risk of recurrent gout attacks has been null or weak, constituting an obesity paradox. We sought to demonstrate and overcome the methodologic issues associated with the obesity paradox for risk of recurrent gout attacks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using the Multiple Risk Factor Intervention Trial database, we decomposed the total effect of obesity into its direct and indirect (i.e., mediated) effects using marginal structural models. We also estimated the total effect of body mass index (BMI) change from baseline among incident gout patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 11,816 gout\u2010free subjects at baseline, we documented 408 incident gout cases, with 132 developing recurrent gout attacks over a 7\u2010year followup period. The adjusted odds ratio (OR) for incident gout among obese individuals was 2.6, whereas that for recurrent gout attacks among gout patients was 0.98 (i.e., the obesity paradox). These ORs correlated well with the ORs for the indirect and direct effects of obesity on the risk of recurrent gout attacks (2.83 and 0.98, respectively). Compared with no BMI change, the OR of increasing versus decreasing &gt;5% of baseline BMI was 0.61 and 1.60 for recurrent gout attacks, respectively (<jats:italic>P<\/jats:italic> for trend\u2009&lt;\u20090.01), suggesting a dose\u2010response association.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The obesity paradox for the risk of recurrent gout attacks is explained by the absence of the direct effect, which is often measured in conventional analyses and misinterpreted as the intended total effect of interest. In contrast, the BMI change analysis correctly estimated the intended total effect of BMI, and revealed a dose\u2010response relationship.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acr.22954","type":"journal-article","created":{"date-parts":[[2016,6,22]],"date-time":"2016-06-22T19:12:26Z","timestamp":1466622746000},"page":"561-566","source":"Crossref","is-referenced-by-count":38,"title":["Obesity Paradox in Recurrent Attacks of Gout in Observational Studies: Clarification and Remedy"],"prefix":"10.1002","volume":"69","author":[{"given":"Uyen\u2010Sa D. T.","family":"Nguyen","sequence":"first","affiliation":[{"name":"University of Massachusetts Medical School, Worcester, and Boston University School of Medicine Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Boston University School of Medicine Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong","family":"Louie\u2010Gao","sequence":"additional","affiliation":[{"name":"Boston University School of Medicine Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingbo","family":"Niu","sequence":"additional","affiliation":[{"name":"Boston University School of Medicine Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David T.","family":"Felson","sequence":"additional","affiliation":[{"name":"Boston University School of Medicine Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8488-5170","authenticated-orcid":false,"given":"Michael P.","family":"LaValley","sequence":"additional","affiliation":[{"name":"Boston University School of Public Health Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyon K.","family":"Choi","sequence":"additional","affiliation":[{"name":"Boston University School of Medicine, Massachusetts General Hospital, and Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,3,29]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keq256"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rdc.2014.01.001"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.165.7.742"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2006.04.006"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3272"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2014.36"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.20287"},{"key":"e_1_2_6_9_1","first-page":"116","article-title":"Unrecognized myocardial infarction: experience in the Multiple Risk Factor Intervention Trial (MRFIT)","volume":"75","author":"Grimm RH","year":"1987","journal-title":"Circulation"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1982.03330120059033"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-2456(87)90006-7"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091-7435(81)90058-X"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4684-3285-5_33"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38171"},{"key":"e_1_2_6_15_1","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1001\/archinte.1997.00440340060005","article-title":"Gout and risk for subsequent coronary heart disease: the Meharry\u2010Hopkins Study","volume":"157","author":"Gelber AC","year":"1997","journal-title":"Arch Intern Med"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ken305"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22014"},{"key":"e_1_2_6_18_1","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1001\/jama.1982.03330120023025","article-title":"Risk factor changes and mortality results: Multiple Risk Factor Intervention Trial Research Group","volume":"248","author":"Multiple Risk Factor Intervention Trial","year":"1982","journal-title":"JAMA"},{"key":"e_1_2_6_19_1","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1001\/jama.1997.03540310093041","article-title":"The Multiple Risk Factor Intervention Trial (MRFIT): a return to a landmark trial","volume":"277","author":"Gotto AM","year":"1997","journal-title":"JAMA"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4780091214"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwr525"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.139899"},{"key":"e_1_2_6_23_1","first-page":"255","article-title":"Studies on the impaired metabolism of uric acid in obese subjects: marked reduction of renal urate excretion and its improvement by a low\u2010calorie diet","volume":"10","author":"Yamashita S","year":"1986","journal-title":"Int J Obes"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.59.7.539"},{"key":"e_1_2_6_25_1","first-page":"104","article-title":"Frequency and predictors of inappropriate management of recurrent gout attacks in a longitudinal study","volume":"33","author":"Neogi T","year":"2006","journal-title":"J Rheumatol"}],"container-title":["Arthritis Care &amp; 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