{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T18:51:52Z","timestamp":1777661512739,"version":"3.51.4"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"19","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2020,10,6]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p xml:lang=\"en\">Serum bilirubin is inversely associated with cardiovascular risk. Atazanavir, an HIV protease inhibitor that competitively inhibits bilirubin conjugation, provides a unique opportunity to examine whether selectively increasing bilirubin is cardioprotective. We sought to determine whether patients receiving atazanavir manifest a reduced risk of cardiovascular disease compared with those receiving darunavir, an HIV protease inhibitor that does not increase serum bilirubin.<\/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              This was a retrospective cohort study of 1020 patients with HIV. The main outcome was time to myocardial infarction or ischemic stroke. Mean follow\u2010up was 6.6\u00b13.4\u00a0years, with 516 receiving atazanavir and 504 darunavir. Atazanavir patients exhibited significantly higher serum total bilirubin (1.7 versus 0.4\u00a0mg\/dL;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001) and longer mean time to ischemic event (10.2 versus 9.4\u00a0years;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001). On Cox regression, atazanavir treatment (hazard ratio [HR], 0.38; 95% CI, 0.21\u20130.71;\n              <jats:italic>P<\/jats:italic>\n              =0.002) and serum bilirubin (HR, 0.60; 95% CI, 0.41\u20130.89;\n              <jats:italic>P<\/jats:italic>\n              =0.011) were independently associated with a lower risk of an ischemic event. Notably, when atazanavir and bilirubin were included together in the Cox regression model, atazanavir lost significance (HR, 0.55; 95% CI, 0.24\u20131.29;\n              <jats:italic>P<\/jats:italic>\n              =0.169) consistent with bilirubin being an intermediate variable on the causal pathway between atazanavir and its effect on cardiovascular disease. Patients on atazanavir also had a significantly lower risk of developing new cardiovascular disease (HR, 0.53; 95% CI, 0.33\u20130.86;\n              <jats:italic>P<\/jats:italic>\n              =0.010) and longer mean time to death (12.2 versus 10.8 years;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p xml:lang=\"en\">Patients with HIV on atazanavir manifest a decreased risk of cardiovascular disease when compared with those on darunavir, an effect that appears to be mediated by serum bilirubin.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.120.016310","type":"journal-article","created":{"date-parts":[[2020,9,15]],"date-time":"2020-09-15T09:14:31Z","timestamp":1600161271000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":17,"title":["Association Between Atazanavir\u2010Induced Hyperbilirubinemia and Cardiovascular Disease in Patients Infected with HIV"],"prefix":"10.1161","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0836-811X","authenticated-orcid":false,"given":"Michael","family":"Li","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Endoscopy Brigham &amp; Women\u2019s Hospital Boston MA"},{"name":"Harvard Medical School Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1709-8230","authenticated-orcid":false,"given":"Walter W.","family":"Chan","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Endoscopy Brigham &amp; Women\u2019s Hospital Boston MA"},{"name":"Harvard Medical School Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen D.","family":"Zucker","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Endoscopy Brigham &amp; Women\u2019s Hospital Boston MA"},{"name":"Harvard Medical School Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.113.6.1776"},{"key":"e_1_3_1_3_2","article-title":"Bilirubin acts as an endogenous regulator of inflammation by disrupting adhesion molecule-mediated leukocyte migration","volume":"3","author":"Vogel ME","year":"2016","unstructured":"Vogel ME, Zucker SD. 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