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Article

Biochemical and Hematological Correlates of Elevated Homocysteine in National Surveys and a Longitudinal Study of Urban Adults

1
Laboratory of Epidemiology and Population Sciences, NIA/NIH/IRP, Baltimore, MD 21224, USA
2
Department of Research Programs, Fort Belvoir Community Hospital, Fort Belvoir, VA 22060, USA
3
Department of Psychology, University of Maryland Baltimore County, Catonsville, MD 21228, USA
4
Department of Pediatrics, Johns Hopkins Medical Institutions, Saint Petersburg, FL 33701, USA
*
Author to whom correspondence should be addressed.
M.A.B. had full access to the data used in this manuscript and completed all the statistical analyses.
Co-senior authors.
Nutrients 2020, 12(4), 950; https://doi.org/10.3390/nu12040950
Received: 12 March 2020 / Revised: 25 March 2020 / Accepted: 26 March 2020 / Published: 30 March 2020
(This article belongs to the Special Issue Nutrition Status and Health)
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 1999–2006 (nmax = 10,151) and pooled NHANES (cross-sectional validation). Longitudinal validation consisted of mixed-effects linear regression models (Hcy predicting markers’ annual rates of change), applied to the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS, n = 227–244 participants, k = 2.4 repeats/participant, Agebase: 30–65 years) data. Machine learning detected nine independent markers for Hcy > 14 µmol/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 1999–2006 NHANES [AUC = 0.60–0.80]. Indices combining binary markers increased elevated Hcy odds by 6.9–7.5-fold. In HANDLS, first-visit Hcy predicted annual increase in creatinine, RDW and alkaline phosphatase, with third-visit index (2013–2018) directly predicting Hcy (2004–2009). We provide evidence of the internal and external validity of indices composed of several biomarkers that are strongly associated with elevated Hcy. View Full-Text
Keywords: homocysteine; hematological indices; biochemical indices; inflammation; predictive models; aging homocysteine; hematological indices; biochemical indices; inflammation; predictive models; aging
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MDPI and ACS Style

Beydoun, M.A.; Beydoun, H.A.; MacIver, P.H.; Hossain, S.; Canas, J.A.; Evans, M.K.; Zonderman, A.B. Biochemical and Hematological Correlates of Elevated Homocysteine in National Surveys and a Longitudinal Study of Urban Adults. Nutrients 2020, 12, 950. https://doi.org/10.3390/nu12040950

AMA Style

Beydoun MA, Beydoun HA, MacIver PH, Hossain S, Canas JA, Evans MK, Zonderman AB. Biochemical and Hematological Correlates of Elevated Homocysteine in National Surveys and a Longitudinal Study of Urban Adults. Nutrients. 2020; 12(4):950. https://doi.org/10.3390/nu12040950

Chicago/Turabian Style

Beydoun, May A.; Beydoun, Hind A.; MacIver, Peter H.; Hossain, Sharmin; Canas, Jose A.; Evans, Michele K.; Zonderman, Alan B. 2020. "Biochemical and Hematological Correlates of Elevated Homocysteine in National Surveys and a Longitudinal Study of Urban Adults" Nutrients 12, no. 4: 950. https://doi.org/10.3390/nu12040950

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