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Lipid and endothelial related genes, ambient particulate matter, and heart rate variability --the VA Normative Aging Study
  1. Cizao Ren1,
  2. Andrea Baccarelli2,
  3. Elissa Wilker3,
  4. Helen Suh1,
  5. David Sparrow4,
  6. Pantel Vokonas4,
  7. Robert Wright5,
  8. Joel Schwartz1
  1. 1 Exposure, Epidemiology and Risk Program, Harvard School of Public Health, United States;
  2. 2 Center of Molecular and Genetic Epidemiology, University of Milan, Italy;
  3. 3 Environmental and Occupational Medicine and Epidemiology Program, Harvard School of Public Health, United States;
  4. 4 Veterans Affairs Boston Healthcare System & the Dept of Medicine, Boston Univ School of Medicine, United States;
  5. 5 Department of Environmental Health, Harvard School of Public Health, United States
  1. E-mail: rencizao{at}


Background: Many studies have shown that exposures to air pollution are associated with cardiovascular events although the mechanism remains to be clarified. To identify whether exposures to ambient particles act on autonomic function via the lipid/endothelial metabolism pathway, we evaluated whether the effects of particulate matter < 2.5 µm in aerodynamic diameter (PM2.5) on heart rate variability (HRV) were modified by gene polymorphisms related to those pathways.

Methods: We used HRV and gene data from the Normative Aging Study and PM2.5 from a monitor located a kilometer from the examination site. We fitted a mixed model to investigate the associations between PM2.5 and repeated measurements of HRV by gene polymorphisms of apolipoprotein E (APOE), lipoprotein lipase (LPL) and vascular endothelial growth factor (VEGF) adjusting for potential confounders chosen a priori.

Results: A 10-µg/m³ increase of PM2.5 in the two days before the examination was associated with 3.8% [95% confidence interval (CI): 0.2%, 7.4%], 7.8% [95 CI: 0.4%, 15.3%] and 10.6% [95% CI: 1.8 %, 19.4%] decreases of the standard deviation of normal-to-normal intervals, the low frequency and the high frequency, respectively. Overall, carriers of wild type APOE, LPL and VEGF genes had stronger effects of particles on HRV compared to those with hetero- or homozygous types. Variations of LPL-N291S, LPL-D9N and APOE-G113C significantly modified effects of PM2.5 on HRV.

Conclusion: Associations between PM2.5 and HRV were modified by gene polymorphisms of APOE, LPL and VEGF and biological metabolism remains to be identified.

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