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The present study aimed to elucidate whether the plasma levels of IS can predict the occurrence of cardiovascular events in patients with chronic heart failure (CHF) and investigate which causes of CHF leading to cardiovascular events are highly influenced by plasma IS levels. We measured the plasma IS levels in 165 patients with CHF [valvular disease: 78, dilated cardiomyopathy: 29, hypertrophic cardiomyopathy (HCM): 25 and others: 33] admitted to our hospital in 2012, and we followed up these patients for more than 5\u00a0years (the median follow-up period: 5.3\u00a0years). We measured the plasma IS level in 165 patients with CHF, and Kaplan\u2013Meier analyses showed that high plasma IS levels (\u2265\u20090.79\u00a0\u00b5g\/mL, the median value) could predict the occurrence of cardiovascular events, i.e., cardiovascular death or rehospitalization due to the worsening of CHF. The sub-analyses showed that the high IS level could predict cardiovascular events in patients with CHF due to HCM and that the plasma IS levels were closely associated with left ventricular (LV) dimension, LV systolic dysfunction, and plasma B-type natriuretic peptide levels, rather than LV diastolic dysfunction. Plasma IS level predicts cardiovascular events in patients with CHF, especially those with HCM along with cardiac dysfunction. Besides, IS may become a proper biomarker to predict cardiovascular events in patients with CHF.<\/jats:p>","DOI":"10.1038\/s41598-020-73633-9","type":"journal-article","created":{"date-parts":[[2020,10,5]],"date-time":"2020-10-05T06:05:05Z","timestamp":1601877905000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Plasma indoxyl sulfate levels predict cardiovascular events in patients with mild chronic heart failure"],"prefix":"10.1038","volume":"10","author":[{"given":"Miki","family":"Imazu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Fukuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideaki","family":"Kanzaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Amaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Hasegawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Takahama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuro","family":"Hitsumoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Tsukamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshisuke","family":"Morita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Kitakaze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,10,5]]},"reference":[{"issue":"Suppl 1","key":"73633_CR1","first-page":"S93","volume":"60","author":"DS Silverberg","year":"2003","unstructured":"Silverberg, D. 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Takahama reports grants from Banyu Life Science Foundation International, grants from The Bayer Scholarship for Cardiovascular Research. M. Amaki reports grants from Japan Heart Foundation\/Bayer Yakuhin Research Grant Abroad, non-financial support from Abbott Vascular Japan, non-financial support from Takeda. T. Hasegawa reports personal fees from Takeda, Daiichi-Sankyo, Otsuka, Bayer, Tanabe-Mitsubishi, Abbott Vascular Japan, Shionogi. T. Morita reports grants from LSI medicine, AMNOS company, UNITIKA and TED company. M. M. Kitakaze reports grants from Japanese government, grants from Japan Heart Foundation, grants from Japan Cardiovascular Research Foundation, grants and personal fees from Takeda, Astellas, Sanofi, Pfizer, Novartis, Boehringer-Ingerheim, Mitsubishi-Tanabe, Kyowa-Hakko-Kirin, Abott, and Otsuka; personal fees from Daiichi-Sankyo, Ono, Bayer, from Kowa, Dainihon-Sumitomo, Sawai, MSD, Calpis, Shionogi, AstraZeneca, Asahikasei Med., Novo Nordisk, Fuji-film RI, and Japan Medical Data; grants from Nihon Kohden. The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"16528"}}