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Open Access 17-01-2024 | Research

Blood Homocysteine Levels Mediate the Association Between Blood Lead Levels and Cardiovascular Mortality

Authors: Sapha Shibeeb, Atiyeh Abdallah, Zumin Shi

Published in: Cardiovascular Toxicology | Issue 1/2024

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Abstract

Lead is a heavy, toxic metal and its exposure to humans can lead to increased risk of cardiovascular disease development and mortality. Lead exposure has been shown to induce hyperhomocysteinemia (HHCy) which may be a major pathogenic risk for the risk of CVDs. The aim of this study was to investigate whether homocysteine (Hcy) mediates the effect of lead on cardiovascular mortality. A total of 17,915 adults aged ≥ 20 who participated in the National Health and Nutrition Examination Survey (1999 to 2006). Information on mortality was ascertained via probabilistic matching to the death certificates from the National Death Index recorded up to December 31, 2015. Cox proportional hazards regression was performed to assess the association between blood lead levels and mortality. Mediation via Hcy was examined using a logit model. During a mean follow-up of 11.6 years, the incidences of CVD mortality were 0.73, 2.18, 3.03 and 4.94 per 1000 person-years across quarterlies of blood lead levels from low to high. Following multivariable adjustment, blood lead levels were strongly associated with CVD mortality in all mortality models (p-trend < 0.001). This association remained statistically significant after further adjusting for quartiles of homocysteine (model 3; HR 1.38 (95% CI 1.01—1.89) p-trend < 0.001). Furthermore, blood lead levels increased the odds of CVD mortality via homocysteine (indirect effect) (OR 1.42 (95% CI 1.30—1.55)), demonstrating the mediatory effect of homocysteine. This the first study that demonstrates that increased homocysteine mediates nearly half of CVD mortality related to blood lead levels.
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Metadata
Title
Blood Homocysteine Levels Mediate the Association Between Blood Lead Levels and Cardiovascular Mortality
Authors
Sapha Shibeeb
Atiyeh Abdallah
Zumin Shi
Publication date
17-01-2024
Publisher
Springer US
Published in
Cardiovascular Toxicology / Issue 1/2024
Print ISSN: 1530-7905
Electronic ISSN: 1559-0259
DOI
https://doi.org/10.1007/s12012-023-09819-0

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