Particulate Air Pollution, Oxidative Stress Genes, and Heart Rate Variability in an Elderly Cohort

Abstract

Background and objectivesWe have previously shown that reduced defenses against oxidative stress due to glutathione S-transferase M1 (GSTM1) deletion modify the effects of PM2.5 (fine-particulate air pollution of < 2.5 μm in aerodynamic diameter) on heart rate variability (HRV) in a cross-sectional analysis of the Normative Aging Study, an elderly cohort. We have extended this to include a longitudinal analysis with more subjects and examination of the GT short tandem repeat polymorphism in the heme oxygenase-1 (HMOX-1) promoter.MethodsHRV measurements were taken on 539 subjects. Linear mixed effects models were fit for the logarithm of HRV metrics—including standard deviation of normal-to-normal intervals (SDNN), high frequency (HF), and low frequency (LF)—and PM2.5 concentrations in the 48 hr preceding HRV measurement, controlling for confounders and a random subject effect.ResultsPM2.5 was significantly associated with SDNN (p = 0.04) and HF (p = 0.03) in all subjects. There was no association in subjects with GSTM1, whereas there was a significant association with SDNN, HF, and LF in subjects with the deletion. Similarly, there was no association with any HRV measure in subjects with the short repeat variant of HMOX-1, and significant associations in subjects with any long repeat. We found a significant three-way interaction of PM2.5 with GSTM1 and HMOX-1 determining SDNN (p = 0.008), HF (p = 0.01) and LF (p = 0.04). In subjects with the GSTM1 deletion and the HMOX-1 long repeat, SDNN decreased by 13% [95% confidence interval (CI), −21% to −4%], HF decreased by 28% (95% CI, −43% to −9%), and LF decreased by 20% (95% CI, −35% to −3%) per 10 μg/m3 increase in PM.ConclusionsOxidative stress is an important pathway for the autonomic effects of particles.

Particulate Matter Air Pollution and Cardiovascular Disease

“…207,243,244 Additional findings suggest protective effects of statins, dietary antioxidants, and B vitamins, as well as omega-3 polyunsaturated fatty acids. 205,207,215,243,244 These results suggest that pathways that reduce endogenous oxidative stress have a protective effect that mitigates reductions in HRV due to ambient PM exposure.…”

GST polymorphisms and early-onset coronary artery disease in young South African Indians

“…10 Others found an association of GSTM1 0/0 with heart failure. 11,12 Black carbon and particulate matter exposure was shown to be associated with increased intracellular and vascular cell adhesion molecules, which promoted atherosclerosis; this association was modified by the presence of the GSTM1 polymorphism. 13 GSTP1 and GSTM1 polymorphisms have been associated with the biomarker of oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine and increased susceptibility to smoking-related CAD.…”

Pretreatment with Antioxidants Augments the Acute Arterial Vasoconstriction Caused by Diesel Exhaust Inhalation

“…The results in human particulate air pollution exposure studies have been more mixed. Two studies in an older cohort in Mexico with metabolic syndrome showed attenuation of the acute PM effect on heart rate variability after long-term supplementation with fish oil (33,34). In a controlled exposure experiment to ozone, Samet and colleagues (35) showed a smaller decrement in lung function after supplementation with a cocktail of AA, a-tocopherol, and vegetables.…”