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Lipid and endothelium-related genes, ambient particulate matter, and heart rate variability—the VA Normative Aging Study
  1. C Ren1,
  2. A Baccarelli2,
  3. E Wilker3,
  4. H Suh1,
  5. D Sparrow4,
  6. P Vokonas4,
  7. R Wright5,
  8. J Schwartz1
  1. 1
    Exposure, Epidemiology, and Risk Program, Harvard School of Public Health, Boston, Massachusetts, USA
  2. 2
    Center of Molecular and Genetic Epidemiology, Department of Environmental and Occupational Health, Maggiore Hospital Policlinico, Mangiagalli and Regina Elena IRCCS Foundation, University of Milan, Italy
  3. 3
    Environmental and Occupational Medicine and Epidemiology Program, Harvard School of Public Health, Boston, Massachusetts, USA
  4. 4
    VA Normative Aging Study, Veterans Affairs Boston Healthcare System and the Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA
  5. 5
    Department of Pediatrics, Children’s Hospital, Boston and Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA
  1. Correspondence to Dr C Ren, Exposure, Epidemiology, and Risk Program, Harvard School of Public Health, Landmark Center West, Suite 415, 401 Park Dr, Boston, MA 02215, USA; cren{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, whether 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 were evaluated.

Methods: HRV and gene data from the Normative Aging Study and PM2.5 from a monitor located a kilometre from the examination site were used. A mixed model was fitted 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 in PM2.5 in the 2 days before the examination was associated with 3.8% (95% CI 0.2% to 7.4%), 7.8% (95 CI 0.4% to 15.3%) and 10.6% (95% CI 1.8% to 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 than 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; the biological metabolism remains to be identified.

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  • ▸ Supplementary material is published online only at

  • Funding This study was supported by the U.S. Environmental Protection Agency grants EPA R827353 and R832416; National Institute of Environmental Health Sciences (NIEHS) grants RO1-ES015172, ES00002, PO1_ES008925, ES05257, P42-ES05947, ES-014663 and ES10798. The VA Normative Aging Study is supported by the Cooperative Studies Program/Epidemiology Research and Information Center of the U.S. Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center, Boston, Massachusetts.

  • Competing interests None declared.

  • Provenance and Peer review Not commissioned; externally peer reviewed.

  • Ethics approval Harvard University.