{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T17:05:12Z","timestamp":1773767112840,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T00:00:00Z","timestamp":1724112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>The relationship between \u03b1\u2010Klotho (\u03b1K) and mortality is controversial and has not been examined in a large, diverse cohort. We investigated the association between serum \u03b1K protein levels with all\u2010cause and cause\u2010specific mortality in a cohort representative of the US population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used National Health and Nutrition Examination Survey (NHANES) data from 2007 to 2016. A nonlinear association between mortality and \u03b1K levels as a quadratic variable were examined using Cox proportional hazard models and competing risk models. Multivariable models were adjusted for age, gender, race, hypertension, diabetes, smoking, alcohol use, physical activity, body mass index (BMI), serum cholesterol, estimated glomerular filtration rate, highest educational status attained and family income to poverty threshold ratio.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of the 13\u2009749 participants, 1569 (11%) died, 7092 (52%) were female, and 5918 (43%) were Caucasian. The mean (SD) of age was 58 (11) years, BMI 29.7 (6.7) kg\/m<jats:sup>2<\/jats:sup>, and \u03b1K was 0.85 (0.31) ng\/mL. In the adjusted Cox proportional hazards model with quadratic \u03b1K, we found a U\u2010shaped relationship between all\u2010cause mortality and \u03b1K levels (continuous \u03b1K hazard ratio [HR]\u2009=\u20090.56, 95% confidence interval [CI]: 0.37, 0.85; <jats:italic>P<\/jats:italic>\u2009=\u2009.007; squared\u2010\u03b1K HR\u2009=\u20091.25, 95% CI: 1.11, 1.41; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). A similar U\u2010shaped relationship was noted between \u03b1K and cancer mortality in the adjusted Cox proportional hazards model (continuous \u03b1K HR\u2009=\u20090.45, 95% CI: 0.19, 1.06; <jats:italic>P<\/jats:italic>\u2009=\u20090.07; squared \u03b1K HR\u2009=\u20091.32, 95% CI: 1.07, 1.61; <jats:italic>P<\/jats:italic>\u2009=\u20090.009). No relationship was present with cardiovascular or other\u2010cause mortality.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In this large diverse cohort, we report a U\u2010shaped relationship between \u03b1K with all\u2010cause and cancer mortality. Further research to elucidate the underlying biological mechanism of these relationships is needed.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.16217","type":"journal-article","created":{"date-parts":[[2024,8,21]],"date-time":"2024-08-21T23:25:20Z","timestamp":1724282720000},"page":"3277-3285","source":"Crossref","is-referenced-by-count":1,"title":["The relationship between serum \u03b1\u2010Klotho with all\u2010cause and cause\u2010specific mortality"],"prefix":"10.1111","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5901-2987","authenticated-orcid":false,"given":"Nargiza","family":"Sadr","sequence":"first","affiliation":[{"name":"Department of Medicine Eastern Virginia Medical School  Norfolk Virginia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cynthia J.","family":"Avila","sequence":"additional","affiliation":[{"name":"EVMS School of Health Professions Macon &amp; Joan Brock Virginia Health Sciences Old Domion University  Norfolk Virginia 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