Reduced heart rate variability (HRV), a marker of poor cardiac autonomic function, has been associated with air pollution, especially fine particulate matter < 2.5 μm in aerodynamic diameter ( ...PM2.5). We examined the relationship between HRV standard deviation of normal-to-normal intervals (SDNN), power in high frequency (HF) and low frequency (LF), and LF:HF ratio and ambient air pollutants in 497 men from the Normative Aging Study in greater Boston, Massachusetts, seen between November 2000 and October 2003. We examined 4-hr, 24-hr, and 48-hr moving averages of air pollution ( PM2.5, particle number concentration, black carbon, ozone, nitrogen dioxide, sulfur dioxide, carbon monoxide). Controlling for potential confounders, HF decreased 20.8% 95% confidence interval (CI), 4.6-34.2% and LF:HF ratio increased 18.6% (95% CI, 4.1-35.2%) per SD (8 μ g/ m3) increase in 48-hr PM2.5. LF was reduced by 11.5% (95% CI, 0.4-21.3%) per SD (13 ppb) increment in 4-hr O3. The associations between HRV and PM2.5and O3were stronger in people with ischemic heart disease (IHD) and hypertension. The associations observed between SDNN and LF and PM2.5were stronger in people with diabetes. People using calcium-channel blockers and beta-blockers had lower associations between O3and PM2.5with LF. No effect modification by other cardiac medications was found. Exposures to PM2.5and O3are associated with decreased HRV, and history of IHD, hypertension, and diabetes may confer susceptibility to autonomic dysfunction by air pollution.
Exposure to particulate air pollution has been related to increased hospitalization and death, particularly from cardiovascular disease. Lower blood DNA methylation content is found in processes ...related to cardiovascular outcomes, such as oxidative stress, aging, and atherosclerosis.
We evaluated whether particulate pollution modifies DNA methylation in heavily methylated sequences with high representation throughout the human genome.
We measured DNA methylation of long interspersed nucleotide element (LINE)-1 and Alu repetitive elements by quantitative polymerase chain reaction-pyrosequencing of 1,097 blood samples from 718 elderly participants in the Boston area Normative Aging Study. We used covariate-adjusted mixed models to account for within-subject correlation in repeated measures. We estimated the effects on DNA methylation of ambient particulate pollutants (black carbon, particulate matter with aerodynamic diameter < or = 2.5 microm PM2.5, or sulfate) in multiple time windows (4 h to 7 d) before the examination. We estimated standardized regression coefficients (beta) expressing the fraction of a standard deviation change in DNA methylation associated with a standard deviation increase in exposure.
Repetitive element DNA methylation varied in association with time-related variables, such as day of the week and season. LINE-1 methylation decreased after recent exposure to higher black carbon (beta = -0.11; 95% confidence interval CI, -0.18 to -0.04; P = 0.002) and PM2.5 (beta = -0.13; 95% CI, -0.19 to -0.06; P < 0.001 for the 7-d moving average). In two-pollutant models, only black carbon, a tracer of traffic particles, was significantly associated with LINE-1 methylation (beta = -0.09; 95% CI, -0.17 to -0.01; P = 0.03). No association was found with Alu methylation (P > 0.12).
We found decreased repeated-element methylation after exposure to traffic particles. Whether decreased methylation mediates exposure-related health effects remains to be determined.
Several studies have suggested an increased risk of fatal coronary heart disease (CHD) among patients with panic disorder, phobic anxiety, and other anxiety disorders. We prospectively examined this ...association in the Normative Aging Study.
An anxiety symptoms scale was constructed out of five items from the Cornell Medical Index, which was administered to the cohort at baseline. During 32 years of follow-up, we observed 402 cases of incident coronary heart disease (137 cases of nonfatal myocardial infarction, 134 cases of angina pectoris, and 131 cases of fatal CHD: made up of 26 cases of sudden cardiac death and 105 cases of nonsudden death). A nested case-control design (involving 1869 control subjects who remained free of diagnosed CHD) was used to assess the association between anxiety and risk of CHD. Compared with men reporting no symptoms of anxiety, men reporting two or more anxiety symptoms had elevated risks of fatal CHD (age-adjusted odds ratio OR = 3.20, 95% confidence interval CI: 1.27 to 8.09), and sudden death (age-adjusted OR = 5.73, 95% CI: 1.26 to 26.1). The multivariate OR after adjusting for a range of potential confounding variables was 1.94 (95% CI: 0.70-5.41) for fatal CHD and 4.46 (95% CI: 0.92-21.6) for sudden death. No excess risks were found for nonfatal myocardial infarction or angina.
These data suggest an association between anxiety and fatal coronary heart disease, in particular, sudden cardiac death.
Worry is an important component of anxiety, which recent work suggests is related to increased incidence of coronary heart disease (CHD). Chronic worry has also been associated with decreased heart ...rate variability. We hypothesized that high levels of worry may increase CHD risk.
We examined prospectively the relationship of worry with CHD incidence in the Normative Aging Study, an ongoing cohort of older men. In 1975, 1759 men free of diagnosed CHD completed a Worries Scale, indicating the extent to which they worried about each of five worry domains: social conditions, health, financial, self-definition, and aging. During 20 years of follow-up, 323 cases of incident CHD occurred: 113 cases of nonfatal myocardial infarction (MI); 86 cases of fatal CHD; and 124 cases of angina pectoris. Worry about social conditions was the domain most strongly associated with incident CHD. Compared with men reporting the lowest levels of social conditions worry, men reporting the highest levels had multivariate adjusted relative risks of 2.41 (95% CI, 1.40 to 4.13) for nonfatal MI and 1.48 (95% CI, 0.99 to 2.20) for total CHD (nonfatal MI and fatal CHD). A dose-response relation was found between level of worry and both nonfatal MI (P for trend, .002) and total CHD (P for trend, .04).
These results suggest that high levels of worry in specific domains may increase the risk of CHD in older men.
Increasing evidence supports an association between symptomatic depression and the risk of coronary heart disease (CHD), although no single study has compared multiple depression scales. We ...hypothesized that higher levels of symptomatic depression assessed from different depression scales were associated with the risk of CHD. We examined this relation in the Normative Aging Study, a prospective cohort of older men. A total of 1,305 men free of diagnosed CHD in 1986 completed the revised Minnesota Multiphasic Personality Inventory (MMPI-2). We categorized scores for the MMPI-2 D, MMPI-2 DEP, and Symptom Checklist-90 (SCL-90) depression scales. During an average 7.0 years of follow-up, 110 cases of incident CHD occurred, including 30 cases of nonfatal myocardial infarction, 20 cases of fatal CHD, and 60 cases of angina pectoris. Compared with men reporting the lowest level of depression, men in the highest level of depression had multivariate-adjusted relative risks of incident CHD (total CHD and angina) of 1.46 (95% confidence interval 0.83 to 2.57), 2.07 (95% confidence interval 1.13 to 3.81), and 1.73 (95% confidence interval 0.97 to 3.10) for the MMPI-2 D, MMPI-2 DEP, and SCL-90 scales, respectively. Similar RRs were obtained for each CHD subtype according to each depression scale. We found strong dose-response relations between level of depression measured by the MMPI-2 DEP scale and incidence of both angina pectoris (p value for trend, 0.039) and CHD (p value for trend, 0.016). Among older men, symptomatic depression measured by any of 3 depression scales may be positively associated with the risk of CHD.
Background: Ozone (O3) exposure is known to cause oxidative stress. This study investigated the acute effects of O3 on lung function in the elderly, a suspected risk group. It then investigated ...whether genetic polymorphisms of antioxidant genes (heme oxygenase-1 (HMOX1) and glutathione S-transferase pi (GSTP1)) modified these associations. Methods: 1100 elderly men from the Normative Aging Study were examined whose lung function (forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1)) was measured every 3 years from 1995 to 2005. The study genotyped the GSTP1 Ile105Val and Ala114Val polymorphisms and the (GT)n repeat polymorphism in the HMOX1 promoter, classifying repeats as short (n<25) or long (n⩾25). Ambient O3 was measured continuously at locations in the Greater Boston area. Mixed linear models were used, adjusting for known confounders. Results: A 15 ppb increase in O3 during the previous 48 h was associated with a 1.25% decrease in FEV1 (95% CI: −1.96% to −0.54%). This estimated effect was worsened with either the presence of a long (GT)n repeat in HMOX1 (−1.38%, 95% CI: −2.11% to −0.65%) or the presence of an allele coding for Val105 in GSTP1 (−1.69%, 95% CI: −2.63% to −0.75%). A stronger estimated effect of O3 on FEV1 was found in subjects carrying both the GSTP1 105Val variant and the HMOX1 long (GT)n repeat (−1.94%, 95% CI: −2.89% to −0.98%). Similar associations were also found between FVC and O3 exposure. Conclusions: Our results suggest that O3 has an acute effect on lung function in the elderly, and the effects may be modified by the presence of specific polymorphisms in antioxidant genes.
Prospective cohort studies suggest that phobic anxiety is a strong risk factor for fatal coronary artery disease, in particular, sudden cardiac death. It has also been established that reduced heart ...rate (HR) variability can identify patients at high risk for subsequent sudden cardiac death. We therefore hypothesized that persons with symptoms of phobic anxiety may exhibit reduced HR variability. We tested our hypothesis in 581 men, aged 47 to 86 years, enrolled in the Normative Aging Study who were free of coronary artery disease and diabetes. Symptoms of anxiety were assessed using the Crown-Crisp index, an instrument that has been demonstrated in previous prospective studies to strongly predict risk of sudden cardiac death. HR variability was measured under standardized conditions, with paced deep breathing (6 breaths/1 min). Two measures of HR variability were used: the SD of HR and the maximal minus minimal HR over 1 minute. Men reporting higher levels of phobic anxiety had a higher resting HR (p = 0.025 for linear trend). After adjusting for age, mean HR, and body mass index in analyses of covariance, men reporting higher levels of phobic anxiety had lower HR variability, whether measured by the SD of HR (p = 0.03 for linear trend), or maximal minus minimal HR (p = 0.03 for linear trend). These data suggest that phobic anxiety is associated with altered cardiac autonomic control, and hence increased risk of sudden cardiac death.
Air pollution by particulate matter (PM) has been associated with cardiovascular deaths, although the mechanism of action is unclear. One proposed pathway is through disturbances of the autonomic ...control of the heart.
We tested the hypothesis that such disturbances are mediated by PM increasing oxidative stress by examining the association between PM and the high-frequency (HF) component of heart rate variability as modified by the presence or absence of the allele for glutathione-S-transferase M1 (GSTM1) and the use of statins, obesity, high neutrophil counts, higher blood pressure, and older age.
We examined the association between particles less than 2.5 microM in aerodiameter (PM2.5) and HF in 497 participants in the Normative Aging Study, using linear regression controlling for covariates.
A 10-microg/m3 increase in PM2.5 during the 48 h before HF measurement was associated with a 34% decrease in HF, 95% confidence interval (-9%, -52%), in subjects without the allele, but had no effect in subjects with GSTM1 present. Among GSTM1-null subjects, the use of statins eliminated the effect of PM2.5. Obesity and high neutrophil counts also worsened the PM effects with or without GSTM1.
The effects of PM2.5 on HF appear to be mediated by reactive oxygen species. This may be a key pathway for the adverse effects of combustion particles.
It is our central hypothesis that periodontal diseases, which are chronic Gram-negative infections, represent a previously unrecognized risk factor for atherosclerosis and thromboembolic events. ...Previous studies have demonstrated an association between periodontal disease severity and risk of coronary heart disease and stroke. We hypothesize that this association may be due to an underlying inflammatory response trait, which places an individual at high risk for developing both periodontal disease and atherosclerosis. We further suggest that periodontal disease, once established, provides a biological burden of endotoxin (lipopolysaccharide) and inflammatory cytokines (especially TxA2, IL-1 beta, PGE2, and TNF-alpha) which serve to initiate and exacerbate atherogenesis and thromboembolic events. A cohort study was conducted using combined data from the Normative Aging Study and the Dental Longitudinal Study sponsored by the United States Department of Veterans Affairs. Mean bone loss scores and worst probing pocket depth scores per tooth were measured on 1,147 men during 1968 to 1971. Information gathered during follow-up examinations showed that 207 men developed coronary heart disease (CHD), 59 died of CHD, and 40 had strokes. Incidence odds ratios adjusted for established cardiovascular risk factors were 1.5, 1.9, and 2.8 for bone loss and total CHD, fatal CHD, and stroke, respectively. Levels of bone loss and cumulative incidence of total CHD and fatal CHD indicated a biologic gradient between severity of exposure and occurrence of disease.
Background: Lead exposure has been associated with higher blood pressure, hypertension, electrocardiogram abnormalities, and increased mortality from circulatory causes. Objective: We assessed the ...association between bone lead-a more accurate biomarker of chronic lead exposure than blood lead-and risk for future ischemic heart disease (IHD). Methods: In a prospective cohort study (VA Normative Aging Study), 837 men who underwent blood or bone lead measurements at baseline were followed-up for an ischemic heart disease event between 1 September 1991 and 31 December 2001. IHD was defined as either a diagnosis of myocardial infarction or angina pectoris that was confirmed by a cardiologist. Events of fatal myocardial infarction were assessed from death certificates. Results: An IHD event occurred in 83 cases (70 nonfatal and 13 fatal). The mean blood, tibia, and patella lead levels were higher in IHD cases than in noncases. In multivariate Cox-proportional hazards models, one standard deviation increase in blood lead level was associated with a 1.27 (95% confidence interval, 1.01-1.59) fold greater risk for ischemic heart disease. Similarly, a one standard deviation increase in patella and tibia lead levels was associated with greater risk for IHD (hazard ratio for patella lead = 1.29; 95% confidence interval, 1.02-1.62). Conclusions: Men with increased blood and bone lead levels were at increased risk for future IHD. Although the pathogenesis of IHD is multifactorial, lead exposure may be one of the risk factors.
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