This study investigates the relationship between ambient fine particle pollution and impaired cardiac autonomic control in the elderly. Heart rate variability ( HRV ) among 56 elderly ( mean age 82 ) nonsmoking residents of a retirement center in Baltimore County, Maryland, was monitored for 4 weeks, from July 27 through August 22, 1998. The weather was seasonally mild ( 63 ± 848F mean daily temperature ) with low to moderate levels of fine particles ( PM 2.5 < 50 g / m 3 ) . Two groups of approximately 30 subjects were examined on alternate days. A spline mixed -effects model revealed a negative relationship between outdoor 24 -h average fine particulate matter ( PM 2.5 ) and high -frequency ( HF ) HRV that was consistent with our earlier Baltimore study for all but 2 days. These 2 days were the only days with significant precipitation in combination with elevated PM 2.5 . They were also unusual in that back -trajectory of their air masses was distinctly different from those on the other study days, emanating from the direction of rural Pennsylvania. Mixed -effects analysis for all 24 study days showed a small negative association of outdoor PM 2.5 with HF HRV ( À 0.03 change in log [ HF HRV ] for a 10 g / m 3 increment in PM 2.5 ) after adjustment for age, sex, cardiovascular status, trend, maximum temperature, average dew point temperature, random subject intercepts, and autocorrelated residuals. After excluding study days 4 and 5, this association was strengthened ( À 0.07 change in log [ HF HRV ] for 10 g / m 3 PM 2.5 , 95% CI À 0.13 to À 0.02 ) and was similar to that obtained in an earlier study ( À 0.12 change in log [ HF HRV ] for a 10 g / m 3 increment in outdoor PM 2.5 , 95% CI À 0.24 to À 0.00 ) [ Liao D., Cai J., Rosamond W.D., Barnes R.W., Hutchinson R.G., Whitsel E.A., Rautaharju P., and Heiss G. Cardiac autonomic function and incident coronary heart disease: a population -based case -cohort study. The ARIC Study. Atherosclerosis Risk in Communities Study. Am J Epidemiol 1997: 145 ( 8 ) : 696 ± 706 ] . Acute ( 1 to 4 h ) previous PM 2.5 exposure did not have a stronger impact than the 24 -h measure. A distributed lag model incorporating the six preceding 4 -h means also did not indicate any effect greater than that observed in the 24 -h measure. This study is consistent with earlier findings that exposures to PM 2.5 are associated with decreased HRV in the elderly.

It has been hypothesized that mutational events may be involved in the atherogenetic process and that at least a portion of atherosclerotic plaques may develop according to an initiation‐promotion process of arterial smooth muscle cells, akin to benign tumors. We conducted a study to evaluate the occurrence of oxidative DNA damage and formation of DNA adducts in human atherosclerotic lesions and to assess the relationships of these promutagenic alterations with exposure to atherogenic risk factors. Pure DNA was extracted from the tunica media (composed mainly of smooth muscle cells) of abdominal aorta fragments taken at surgery from 85 patients suffering from severe atherosclerotic lesions. DNA adducts were detected by synchronous fluorescence spectrophotometry and 32P postlabeling after enrichment of adducts with either butanol or nuclease P1. 8‐Hydroxy‐2'‐deoxyguanosine (8‐OH‐dG), a typical indicator of oxidative DNA damage, was measured by HPLC/electrochemical detection. A complete questionnaire reporting general, clinical, and laboratory characteristics was available for each patient. All 84 samples tested by 32P postlabeling were positive by displaying the presence of diagonal radioactive zones and up to 9 individual DNA adducts. Of 52 samples tested, 32 (61.5%) yielded typical positive signals at synchronous fluorescence spectrophotometry. All but one of 39 samples tested had very high levels of 8‐OH‐dG, thus showing a remarkable oxidative DNA damage. Statistically significant correlations were found between the levels of molecular biomarkers and atherogenic risk factors including age, number of currently smoked cigarettes, ratio of total‐to‐high density lipoprotein blood cholesterol, blood triglycerides, and blood pressure. The DNA alterations detected in our study may be only one component of the genetic basis of atherogenesis. Moreover, no causal role in the atherogenetic process can be inferred from our results. However, DNA alterations, including oxidative damage and adduction of reactive molecules of either endogenous or exogenous source, were systematically present in the smooth muscle cells of human atherosclerotic lesions and their intensity was significantly correlated with the occurrence of atherogenic risk factors in the patients studied.—De Flora, S., Izzotti, A., Walsh, D., Degan, P., Petrilli, G. L., Lewtas, J. Molecular epidemiology of atherosclerosis. FASEB J. 11, 1021–1031 (1997)

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