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

Area of Science:

• Environmental Health
• Cardiovascular Disease Research
• Toxicology

Background:

• Lead is a toxic metal linked to increased cardiovascular disease (CVD) risk and mortality.
• Lead exposure can induce hyperhomocysteinemia (HHCy), a potential pathogenic factor for CVDs.

Purpose of the Study:

• To investigate the mediating role of homocysteine (Hcy) in the association between lead exposure and cardiovascular mortality.
• To quantify the extent to which Hcy mediates lead-induced CVD mortality.

Main Methods:

• Analysis of data from 17,915 adults in the National Health and Nutrition Examination Survey (1999-2006).
• Mortality data ascertained via National Death Index up to December 31, 2015.
• Cox proportional hazards regression and logit models used to assess associations and mediation by Hcy.

Main Results:

• Blood lead levels were strongly associated with increased CVD mortality (p-trend < 0.001).
• This association remained significant after adjusting for Hcy levels.
• Homocysteine was shown to mediate lead's effect on CVD mortality (OR 1.42; 95% CI 1.30-1.55).

Conclusions:

• Elevated homocysteine levels mediate a significant portion, nearly half, of the cardiovascular mortality associated with blood lead levels.
• This finding elucidates a critical mechanism linking environmental lead exposure to cardiovascular health outcomes.