{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T20:38:28Z","timestamp":1776976708546,"version":"3.51.4"},"reference-count":70,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Circulating total bilirubin is known to be inversely and independently associated with future risk of cardiovascular disease. However, the relationship of circulating total bilirubin with incident hypertension is uncertain. We aimed to assess the association of total bilirubin with future hypertension risk and supplemented this with a Mendelian randomization approach to investigate any causal relevance to the association.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Plasma total bilirubin levels were measured at baseline in the\n              <jats:styled-content style=\"fixed-case\">PREVEND (Prevention of Renal and Vascular End\u2010Stage Disease)<\/jats:styled-content>\n              prospective study of 3989 men and women without hypertension. Hazard ratios (95% confidence intervals) of total bilirubin with incident hypertension were assessed. New\u2010onset hypertension was recorded in 1206 participants during a median follow\u2010up of 10.7\u00a0years. Baseline total bilirubin was approximately log\u2010linearly associated with hypertension risk. Age\u2010 and sex\u2010adjusted\n              <jats:styled-content style=\"fixed-case\">hazard ratio<\/jats:styled-content>\n              for hypertension per 1\u2010SD increase in log\n              <jats:sub>e<\/jats:sub>\n              total bilirubin was 0.86 (0.81\u20130.92;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001), which was attenuated to 0.94 (0.88\u20130.99;\n              <jats:italic>P<\/jats:italic>\n              =0.040) after further adjustment for established risk factors and other potential confounders. The association was marginally significant on further adjustment for high\u2010sensitivity C\u2010reactive protein (0.94; 0.88\u20131.00;\n              <jats:italic>P<\/jats:italic>\n              =0.067). A genetic variant at the\n              <jats:styled-content style=\"fixed-case\">UGT<\/jats:styled-content>\n              1A1*28 locus consistently shown to be strongly associated with circulating bilirubin levels\u2014rs6742078\u2014was not significantly associated with blood pressure or hypertension (\n              <jats:italic>P<\/jats:italic>\n              &gt;0.05 for all), arguing against a strong causal association of circulating bilirubin with blood pressure.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">The weak and inverse association of circulating total bilirubin with future hypertension risk may be driven by biases such as unmeasured confounding and\/or reverse causation. Further evaluation is warranted.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.117.006503","type":"journal-article","created":{"date-parts":[[2017,11,14]],"date-time":"2017-11-14T01:10:24Z","timestamp":1510621824000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":34,"title":["Circulating Total Bilirubin and Future Risk of Hypertension in the General Population: The Prevention of Renal and Vascular End\u2010Stage Disease (PREVEND) Prospective Study and a Mendelian Randomization Approach"],"prefix":"10.1161","volume":"6","author":[{"given":"Setor K.","family":"Kunutsor","sequence":"first","affiliation":[{"name":"Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lyanne M.","family":"Kieneker","sequence":"additional","affiliation":[{"name":"Department of Nephrology Medicine, University of Groningen and 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