on March 31, 2008
Published online before print March 31, 2008, doi: 10.1161/CIRCULATIONAHA.107.726067
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Submitted on July 13, 2007
From the Department of Environmental Health, Harvard School of Public Health, Boston, Mass (A.B., H.S., J.S.); Department of Environmental and Occupational Health, University of Milan and IRCCS Maggiore Hospital, Mangiagalli and Regina Elena Foundation, Milan, Italy (A.B.); Division of Nutritional Sciences, Cornell University, Ithaca, NY (P.A.C.); Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass (A.L.); Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor (S.K.P.); and VA Normative Aging Study, Veterans Affairs Boston Healthcare System and the Department of Medicine, Boston University School of Medicine, Boston, Mass (D.S., P.V.). * To whom correspondence should be addressed. E-mail: abaccare{at}hsph.harvard.edu.
Background—Particulate air pollution is associated with cardiovascular mortality and morbidity. To help identify mechanisms of action and protective/susceptibility factors, we evaluated whether the effect of particulate matter <2.5 µm in aerodynamic diameter (PM2.5) on heart rate variability was modified by dietary intakes of methyl nutrients (folate, vitamins B6 and B12, methionine) and related gene polymorphisms (C677T methylenetetrahydrofolate reductase [MTHFR] and C1420T cytoplasmic serine hydroxymethyltransferase [cSHMT]). Methods and Results—Heart rate variability and dietary data were obtained between 2000 and 2005 from 549 elderly men from the Normative Aging Study. In carriers of [CT/TT] MTHFR genotypes, the SD of normal-to-normal intervals was 17.1% (95% CI, 6.5 to 26.4; P=0.002) lower than in CC MTHFR subjects. In the same [CT/TT] MTHFR subjects, each 10-µg/m3 increase in PM2.5 in the 48 hours before the examination was associated with a further 8.8% (95% CI, 0.2 to 16.7; P=0.047) decrease in the SDNN. In [CC] cSHMT carriers, PM2.5 was associated with an 11.8% (95% CI, 1.8 to 20.8; P=0.02) decrease in SDNN. No PM2.5-SSDN association was found in subjects with either [CC] MTHFR or [CT/TT] cSHMT genotypes. The negative effects of PM2.5 were abrogated in subjects with higher intakes (above median levels) of B6, B12, or methionine. PM2.5 was negatively associated with heart rate variability in subjects with lower intakes, but no PM2.5 effect was found in the higher intake groups. Conclusion—Genetic and nutritional variations in the methionine cycle affect heart rate variability either independently or by modifying the effects of PM2.5.
Accepted on January 29, 2008
Cardiac Autonomic Dysfunction. Effects From Particulate Air Pollution and Protection by Dietary Methyl Nutrients and Metabolic Polymorphisms
Andrea Baccarelli MD, PhD*,
Key words: aging • epidemiology • heart rate • metabolism • nervous system, autonomic
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Circulation 2008 117: 1769.