{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T20:47:32Z","timestamp":1788814052808,"version":"build-2803163510"},"reference-count":60,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,3,30]],"date-time":"2020-03-30T00:00:00Z","timestamp":1585526400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Elevated blood homocysteine (Hcy) among middle-aged adults can increase age-related disease risk, possibly through other biochemical and hematological markers. We selected markers for hyperhomocysteinemia among middle-aged adults, studied time-dependent Hcy-marker associations and computed highly predictive indices of hyperhomocysteinemia, with cross-sectional and longitudinal validations. We used data from the National Health and Nutrition Examination Survey (NHANES III, phase 2, nmax = 4000), the NHANES 1999\u20132006 (nmax = 10,151) and pooled NHANES (cross-sectional validation). Longitudinal validation consisted of mixed-effects linear regression models (Hcy predicting markers\u2019 annual rates of change), applied to the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS, n = 227\u2013244 participants, k = 2.4 repeats\/participant, Agebase: 30\u201365 years) data. Machine learning detected nine independent markers for Hcy &gt; 14 \u00b5mol\/L (NHANES III, phase 2): older age; lower folate and B-12 status; higher serum levels of creatinine, uric acid, alkaline phosphatase, and cotinine; mean cell hemoglobin and red cell distribution widths (RDW); results replicated in the 1999\u20132006 NHANES [AUC = 0.60\u20130.80]. Indices combining binary markers increased elevated Hcy odds by 6.9\u20137.5-fold. In HANDLS, first-visit Hcy predicted annual increase in creatinine, RDW and alkaline phosphatase, with third-visit index (2013\u20132018) directly predicting Hcy (2004\u20132009). We provide evidence of the internal and external validity of indices composed of several biomarkers that are strongly associated with elevated Hcy.<\/jats:p>","DOI":"10.3390\/nu12040950","type":"journal-article","created":{"date-parts":[[2020,3,31]],"date-time":"2020-03-31T10:29:38Z","timestamp":1585650578000},"page":"950","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Biochemical and Hematological Correlates of Elevated Homocysteine in National Surveys and a Longitudinal Study of Urban Adults"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1050-4523","authenticated-orcid":false,"given":"May A.","family":"Beydoun","sequence":"first","affiliation":[{"name":"Laboratory of Epidemiology and Population Sciences, NIA\/NIH\/IRP, Baltimore, MD 21224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hind A.","family":"Beydoun","sequence":"additional","affiliation":[{"name":"Department of Research Programs, Fort Belvoir Community Hospital, Fort Belvoir, VA 22060, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter H.","family":"MacIver","sequence":"additional","affiliation":[{"name":"Laboratory of Epidemiology and Population Sciences, NIA\/NIH\/IRP, Baltimore, MD 21224, USA"},{"name":"Department of Psychology, University of Maryland Baltimore County, Catonsville, MD 21228, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharmin","family":"Hossain","sequence":"additional","affiliation":[{"name":"Laboratory of Epidemiology and Population Sciences, NIA\/NIH\/IRP, Baltimore, MD 21224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4788-8820","authenticated-orcid":false,"given":"Jose A.","family":"Canas","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Johns Hopkins Medical Institutions, Saint Petersburg, FL 33701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele K.","family":"Evans","sequence":"additional","affiliation":[{"name":"Laboratory of Epidemiology and Population Sciences, NIA\/NIH\/IRP, Baltimore, MD 21224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan B.","family":"Zonderman","sequence":"additional","affiliation":[{"name":"Laboratory of Epidemiology and Population Sciences, NIA\/NIH\/IRP, Baltimore, MD 21224, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S116","DOI":"10.1177\/15648265080292S116","article-title":"Public health significance of elevated homocysteine","volume":"29","author":"Selhub","year":"2008","journal-title":"Food Nutr. 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