Interaction Between Air Pollution and Genetic Predisposition to Blood Pressure and LDL-C on Cardiovascular Events

Area of Science:

• Environmental Health
• Cardiovascular Genetics
• Epidemiology

Background:

• Particulate matter ≤2.5μm (PM2.5) is a significant global environmental risk factor for cardiovascular disease.
• Genetic predisposition to factors like high LDL cholesterol and blood pressure influences cardiovascular risk.
• Understanding gene-environment interactions is crucial for personalized cardiovascular risk assessment.

Purpose of the Study:

• To investigate the impact of PM2.5 air pollution on cardiovascular risk.
• To examine the interaction between PM2.5 exposure and genetic predisposition to LDL cholesterol and systolic blood pressure.
• To assess how PM2.5 modifies cardiovascular risk in individuals with varying genetic risk scores.

Main Methods:

• A Mendelian Randomization (MR) study utilizing UK Biobank data (n=412,446) over 13.85 years.
• Polygenic Risk Scores (PRS) for LDL-C and SBP were used as instrumental variables for MACE.
• Survival regression, causal inference, and machine learning models assessed PM2.5 interactions with genetic and clinical risk factors.

Main Results:

• A significant negative interaction was found between PM2.5 and PRS for both SBP and LDL-C concerning MACE incidence.
• Increased genetic risk for SBP and LDL-C was associated with a reduced relative risk of MACE at higher PM2.5 levels.
• Absolute cardiovascular risk remained highest in high-PRS groups across all PM2.5 exposure levels.

Conclusions:

• Individuals with higher genetic risk for SBP and LDL-C face the greatest absolute cardiovascular risk when exposed to air pollution.
• PM2.5 exposure may attenuate the relative risk of MACE in genetically susceptible individuals, possibly due to high baseline risk.
• Findings support a significant gene-environment interaction between air pollution and genetically influenced cardiovascular risk factors.