Biochemical and Hematological Correlates of Elevated Homocysteine in National Surveys
Loading...
Links to Files
Author/Creator ORCID
Date
2020-03-30
Type of Work
Department
Program
Citation of Original Publication
May A. Beydoun et al., 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
Rights
This item is likely protected under Title 17 of the U.S. Copyright Law. Unless on a Creative Commons license, for uses protected by Copyright Law, contact the copyright holder or the author.
Attribution 4.0 International (CC BY 4.0)
Attribution 4.0 International (CC BY 4.0)
Subjects
Abstract
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.