Wissenschaftszentrum Umwelt

Background and Objective: Exposure to ambient particles has been shown to be responsible for cardiovascular effects, especially in elderly with cardiovascular disease. The study assessed the association between deceleration capacity (DC) as well as heart rate variability (HRV) and ambient particulate matter (PM) in patients with coronary artery disease (CAD). Methods: A prospective study with up to 12 repeated measurements was conducted in Erfurt, Germany, between October 2000 and April 2001 in 56 patients with physician-diagnosed ischemic heart disease, stable angina pectoris or prior myocardial infarction at an age of at least 50 years. Twenty-minute ECG recordings were obtained every two weeks and 24-hour ECG recordings every four weeks. Exposure to PM (size range from 10 nm to 2.5 μm), and elemental (EC) and organic (OC) carbon was measured. Additive mixed models were used to analyze the association between PM and ECG recordings. Results: The short-term recordings showed decrements in the high-frequency component of HRV as well as in RMSSD (root-mean-square of successive differences of NN intervals) in association with increments in EC and OC 0-23 hours prior to the recordings. The long-term recordings revealed decreased RMSSD and pNN50 (% of adjacent NN intervals that differed more than 50 ms) in association with EC and OC 24-47 hours prior to the recordings. In addition, highly significant effects were found for DC which decreased in association with PM 2.5 , EC and OC concurrent with the ECG recordings as well as with a lag of up to 47 hours. Conclusions: The analysis showed significant effects of ambient particulate air pollution on DC and HRV parameters reflecting parasympathetic modulation of the heart in patients with CAD. An air pollution-related decrease in parasympathetic tone as well as impaired heart rate deceleration capacity may contribute to an increased risk for cardiac morbidity and sudden cardiac death in vulnerable populations.

Rationale: Ambient particulate matter has been associated with systemic inflammation indicated by blood markers such as fibrinogen, implicated in promoting atherothrombosis. Objective: This study evaluated whether single nucleotide polymorphisms (SNPs) within the fibrinogen genes modified the relationship between ambient particles and plasma fibrinogen. Methods: In 854 myocardial infarction survivors from five European cities plasma fibrinogen levels were determined repeatedly (N=5082). City-specific analyses were conducted to assess the impact of particulate matter on fibrinogen levels applying additive mixed models adjusting for patient characteristics, time trend and weather. City-specific estimates were pooled using meta-analysis methodology. Measurements and Main Results: Seven SNPs in the FGA and FGB genes shown to be associated with differences in fibrinogen levels were selected. Promoter SNPs within FGA and FGB were associated with modifications of the relationship between 5-day averages of particulate matter with an aerodynamic diameter below 10 µm (PM 10) and plasma fibrinogen levels. The PM 10-fibrinogen relationship for subjects with the homozygous minor allele genotype of FGB rs1800790 compared to subjects homozygous for the major allele was eightfold higher (p-value for the interaction 0.037). Conclusions: The data suggest that susceptibility to ambient particulate matter may be partly genetically determined by polymorphisms that alter early physiological responses such as transcription of fibrinogen. Subjects with variants of these frequent SNPs may have increased risks not only due to constitutionally higher fibrinogen concentrations, but also due to an augmented response to environmental inflammatory stimuli such as ambient particulate matter.

Background: C-reactive protein (CRP), a sensitive marker of the acute-phase response, has been associated with future cardiovascular endpoints independently of other risk factors. A joint analysis of the role of risk factors in predicting mean concentrations and variation of high-sensitivity CRP (hsCRP) in serum has not been carried out previously. Methods: We used data from 1003 myocardial infarction (MI) survivors who had hsCRP measured monthly up to 8 times and multivariate mixed effects statistical models to study the role of time-variant and -invariant factors on the geometric mean of and the intraindividual variation in hsCRP concentrations. Results: Patients with ≥6.5% glycosylated hemoglobin (HbA1c) had 26.2% higher hsCRP concentrations (95% CI, 7.2%–48.6%) and 20.7% greater variation in hsCRP values (P = 0.0034) than patients with lower baseline Hb A1c values (<6.5%). Similar but less pronounced differences were seen in patients with a self-reported diagnosis of type 2 d...

Background: Among the numerous emerging biomarkers, high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) have received widespread interest, and a large database has been accumulated on their potential role as predictors of cardiovascular risk. The concentrations of inflammatory biomarkers, however, are influenced, among other things, by physiological variation, which is the natural within-individual variation occurring over time. Implementation of hsCRP and IL-6 measurement into clinical practice requires data on the reliability of such measurements. Methods: We serially measured hsCRP and IL-6 concentrations in up to 6 blood samples taken at monthly intervals from 200 post–myocardial infarction patients who participated in the AIRGENE study. Results: The mean (SD) of the ln-transformed plasma concentrations (in milligrams per liter for hsCRP and nanograms per liter for IL-6) for all participants over all samples was 0.16 (1.04) for hsCRP and 0.76 (0.57) for IL-6, wi...

Most epidemiological studies have shown an elevated risk for cardiovascular events associated with exposure to fine particulate matter (PM) (de Hartog 2003; de Hartog et al. 2009; Peters et al. 2001, 2004; Schwartz 1997). PM has been associated with increased risks of myocardial infarction (MI), stroke, arrhythmia, and heart failure within hours to days of exposure in susceptible individuals. In addition, air pollutants have been linked with intermediate outcomes that may reflect mecha nistic links, including endothelial dysfunction and vasoconstriction, increased blood pressure (BP), prothrombotic and coagulant changes, systemic inflammatory and oxidative stress responses, autonomic imbalance and arrhythmias, and the progression of atherosclerosis (Brook et al. 2010). Lipoprotein-associated phospholipase A 2 (Lp-PLA2), a member of the phospholipase superfamily, is an enzyme produced by monocytes and macrophages, T cells, and mast cells. Oxidized low-density lipoprotein (LDL) within the subendothelial space is converted by Lp-PLA2 into oxidized free fatty acids and lysophoshatidylcholine (Macphee et al. 1999; Zalewski and Macphee 2005). These products trigger an inflammatory cascade by stimulating the expression of adhesion molecules and the release of cytokines by endothelial cells and plaque-based macrophages, which recruit more monocytes into the subendothelial space where they become activated and differentiate into macrophages. The fact that Lp-PLA2 is produced locally within atherosclerotic lesions itself likely accounts for its high specificity for vascular as opposed to systematic inflammation (Lerman and McConnell 2008). Plasma Lp-PLA2 levels are not affected by systemic inflammatory diseases such as rheumatoid arthritis, osteoarthritis, or chronic obstructive pulmonary disease (Lerman and McConnell 2008). Plasma Lp-PLA2 is bound mainly to LDL. Epidemiological studies have found consistent and statistically significant positive associations between Lp-PLA2 mass or activity and coronary artery disease and stroke (Anderson 2008; Gorelick 2008; Koenig and Khuseyinova 2009; Koenig et al. 2009). Lp-PLA2 is a marker of cardiovascular risk independent of and in addition to traditional risk factors [Lp-PLA(2) Studies Collaboration et al. 2010], and Lp-PLA2 may be directly involved in the causal pathway of plaque inflammation and the formation of rupture-prone plaques (Lerman and McConnell 2008). This study was performed to investigate whether exposure to ambient particulate and gaseous air pollutants is associated with a systemic increase in Lp-PLA2 levels, consistent with our hypothesis that Lp-PLA2 may be a potential mediator in the pathway between air pollution and cardiovascular disease. Materials and Methods Study design and study population. A prospective longitudinal study of post-MI patients was conducted in Augsburg, Germany, and two adjacent counties (a total of 300,000 inhabits were living in the three counties at the time of the study) as part of a study on Air Pollution and Inflammatory Response in Myocardial Infarction Survivors: Gene-Environment Interaction in a High Risk Group (AIRGENE) (Peters et al. 2007). Up to six repeated clinical examinations were scheduled every 4-6 weeks between May 2003 and March 2004 in six European cities (Athens,

Background: Epidemiological studies have shown that ambient particulate matter (PM) and changes in air temperature are associated with increased cardiopulmonary events. oBjective: We hypothesized that patients with previous myocardial infarction (MI) experience changes in heart rate (HR) and repolarization parameters, such as Bazett-corrected QT interval (QTc), and T-wave amplitude (Tamp), in association with increases in air pollution and temperature changes. Methods: Between May 2003 and February 2004, 67 MI survivors from the Augsburg KORA-MI registry repeatedly sent 16 sec electrocardiograms (ECGs) with a personal transmitter (Viapac) via telephone to the Philips Monitoring Center, where ECG parameters were immediately analyzed. Meteorological data and air pollutants were acquired from fixed monitoring sites on an hourly basis. Additive mixed models were used for analysis. Effect modification by patient characteristics was investigated. results: The analysis of the 1,745 ECGs revealed an increased HR associated with interquartile range (IQR) increases in PM levels among participants not using beta-adrenergic receptor blockers and among those with body mass index ≥ 30 kg/m 2. We observed a 24-to 47-hr lagged QTc prolongation [0.5% change (95% confidence interval, 0.0-1.0%)] in association with IQR increases in levels of PM ≤ 2.5 µm in aerodynamic diameter, especially in patients with one [0.6% (0.1-1.0%)] or two [1.2% (0.4-2.1%)] minor alleles of the nuclear factor (erythroid-derived 2)-like 2 (NFE2L2) single-nucleotide polymorphism rs2364725. Positive immediate (0-23 hr) and inverse delayed (48-71 hr up to 96-119 hr) associations were evident between PM and Tamp. We detected an inverse U-shaped association between temperature and Tamp, with a maximum Tamp at 5°C. conclusions: Increased air pollution levels and temperature changes may lead to changes in HR and repolarization parameters that may be precursors of cardiac problems.

Research | Article Evidence from epidemiologic studies indicates that ambient particulate air pollution and air pollution episodes lead to increased cardiovascular hospital admissions and mortality (Pope 2000; Schwartz 1994). Although the relative effects of particulate air pollution are greater for respiratory than for cardiovascular mortality, the absolute number of deaths attributable to particulate air pollution is much higher for cardiovascular than for respiratory deaths (Dockery 2001; Frampton 2001). Cardiac rhythm disorders are the leading cause of hospital admissions for cardiovascular diseases in the United States. More Materials and Methods Study population. A prospective panel study was conducted in patients with coronary artery disease who participated in 12 subsequent clinical exams between 16 October 2000 and 27 April 2001 in Erfurt, a city of 200,000 inhabitants in East Germany. Subjects were required to be male, at least 50 years of age, and have doctor-diagnosed coronary artery disease confirmed by a typical history of angina pectoris or by prior myocardial infarction. Exclusion criteria were as follows: current smokers; patients with pacemakers; patients with recent (< 3 months) myocardial infarction, recent bypass surgery or coronary angioplasty, bundle-branch blocks, or type 1 diabetes; and patients on anticoagulation therapy (warfarin derivatives). Sixtyone coronary artery disease patients were recruited from a large clinical practice of a local cardiologist to participate in the study, and 56 patients remained for the analyses. Three patients with intermittent bundlebranch blocks and one patient with sinus arrhythmia were excluded, and one patient did not participate. Data on health status, pulmonary and cardiac symptoms, medication, and smoking history were obtained at baseline and during follow-up visits. All subjects signed a written consent, and the study protocol was approved by the German ethics commission, Bayerische Landesaerztekammer.

BACKGROUND: Numerous studies have found that ambient air pollution has been associated with cardiovascular disease exacerbation. OBJECTIVES: Given previous findings, we hypothesized that particulate air pollution might induce systemic inflammation in myocardial infarction (MI) survivors, contributing to an increased vulnerability to elevated concentrations of ambient particles. METHODS: A prospective longitudinal study of 1,003 MI survivors was performed in six European cities between May 2003 and July 2004. We compared repeated measurements of interleukin 6 (IL-6), fibrinogen, and C-reactive protein (CRP) with concurrent levels of air pollution. We collected hourly data on particle number concentrations (PNC), mass concentrations of particulate matter (PM) < 10 µm (PM 10) and < 2.5 µm (PM 2.5), gaseous pollutants, and meteorologic data at central monitoring sites in each city. City-specific confounder models were built for each blood marker separately, adjusting for meteorology and time-varying and time-invariant covariates. Data were analyzed with mixed-effects models. RESULTS: Pooled results show an increase in IL-6 when concentrations of PNC were elevated 12-17 hr before blood withdrawal [percent change of geometric mean, 2.7; 95% confidence interval (CI), 1.0-4.6]. Five day cumulative exposure to PM 10 was associated with increased fibrinogen concentrations (percent change of arithmetic mean, 0.6; 95% CI, 0.1-1.1). Results remained stable for smokers, diabetics, and patients with heart failure. No consistent associations were found for CRP. CONCLUSIONS: Results indicate an immediate response to PNC on the IL-6 level, possibly leading to the production of acute-phase proteins, as seen in increased fibrinogen levels. This might provide a link between air pollution and adverse cardiac events.

Context: The aerosol components responsible for the adverse health effects of the exposure to particulate matter (PM) have not been conclusively identified, and there is especially little information on the role of particulate organic compounds (POC). Objective: This study evaluated the role of PM and POC with regard to daily symptoms. Methods: One hundred and fifty-three myocardial infarction survivors from Augsburg, Germany, recorded daily occurrence of different symptoms in winter 2003/2004. Ambient concentrations of PM with a diameter <2.5 μm (PM 2.5), particle number concentration (PNC), PM 2.5-bound hopanes, and polycyclic aromatic hydrocarbons (PAH) were quantified. Data were analyzed using generalized estimating equations adjusting for meteorological and other time-variant confounders. Results: The odds for avoidance of physically demanding activities due to heart problems increased immediately associated with most POC measures (e.g. 5% per 1.08 ng/m 3 increase in benzo[a]pyrene, 95%-confidence interval (CI):1-9%) and tended to a delayed decrease. After a 2-day delayed decrease associated with hopanes, the odds for shortness of breath increased consistently after 3 days with almost all POC measures (e.g. 4% per 0.21 ng/m 3 increase in 17α(H), 21β(H)-hopane, CI: 1-8%). The odds for heart palpitations marginally increased immediately in association with PNC (8% per 8146 cm-3 increase in PNC, CI: 0-16%). Conclusions: The study showed an association between PM, particle-bound POC, and daily symptoms. The organic compounds may be causally related with cardiovascular health or act rather as indicators for traffic-and combustionrelated particles.

Given the accumulating evidence that people with underlying heart disease are a particularly vulnerable group for triggers like changing meteorological parameters, the objective of this longitudinal study was to analyze the influence of weather parameters on blood pressure, arrhythmia and ischemia in cardiovascular patients. A panel study with repeated measurements was conducted in a rehabilitation clinic in Timmendorfer Strand (Baltic Sea, Germany) with 872 cardiovascular patients. Heart rate, blood pressure and electrocardiography changes were measured during repeated bicycle ergometries. Generalized Estimating Equations were used for regression analyses of immediate, delayed and cumulative influences of the daily measured meteorological data. For men, a decrease in air temperature and in water vapor pressure doubled the risk of ST-segment depression during ergometry [odds ratio (OR) for 1 day delay: 1.88 (1.24; 2.83) for air temperature] with a delay of 1-2 days. For women, an increase of their heart rate before the start of the ergometry [same day: 4.36 beats/min (0.99; 7.74) for air temperature] and a 2-to 3-fold higher risk for ventricular ectopic beats [1 day delay: OR 2.43 (1.17; 5.05) for air temperature] was observed with an increase in temperature and water vapor pressure in almost all analyzed time-windows. The study indicates that meteorological parameters can induce changes in heart function which may lead to adverse cardiovascular events especially in susceptible, diseased individuals. The observed effect on ST-segment depression could be a link between the association of weather changes and cardiovascular morbidity and mortality.

Objectives Changes in air temperature are associated with an increase in cardiovascular events, but the role of procoagulant and proinflammatory blood markers is still poorly understood. The authors investigated the association between air temperature and fibrinogen, plasminogen activator inhibitor type 1, interleukin-6 and high-sensitivity C reactive protein in two potentially susceptible groups. Methods This prospective panel study was conducted between March 2007 and December 2008 in Augsburg, Germany. The study population comprised 187 participants with type 2 diabetes mellitus or impaired glucose tolerance and 87 participants with genetic polymorphisms on the detoxification and inflammation pathways. Overall, 1766 repeated blood measurements were collected. Hourly meteorology data were available from a central measurement site. The association between temperature and blood markers was analysed with additive mixed models. Results For type 2 diabetes mellitus and impaired glucose tolerance participants, the authors observed immediate, lagged and cumulative increases in fibrinogen (range of percentage changes in geometric mean: 0.6%e0.8%) and plasminogen activator inhibitor type 1 (6.0%e10.1%) in association with a 58C temperature decrement. Participants with a body mass index above 30 kg/m 2 as well as females showed particularly strong fibrinogen effects. In participants with the special genetic background, 58C decreases in the 5-day average of temperature led to a change of 8.0% (95% CI 0.5% to 16.2%) in interleukin-6 and of À8.4% (95% CI À15.8% to À0.3%) in high-sensitivity C reactive protein, the latter driven by physically active individuals. Conclusions The authors observed different temperature effects on blood markers in two potentially susceptible groups probably indicating varying underlying biological mechanisms. This study results might provide a link between temperature and cardiovascular events.

Introduction: Increased levels of interleukin 6 (IL-6), a marker for systemic inflammation, have been associated with cardiovascular morbidity and mortality. Materials and Methods: We investigated the influence of IL6 gene polymorphisms on mean level and variability of plasma IL-6 in a population of myocardial infarction survivors recruited in six European cities as part of the AIRGENE study. DNA from each individual was collected and genotyped for eight functional and tagging single nucleotide polymorphisms (SNPs) in the IL6 gene. Results: We analyzed 946 subjects with 5520 repeated plasma samples for IL-6 levels. For four IL6 SNPs in high linkage disequilibrium, heterozygous and homozygous minor allele genotypes were associated with an increase in mean plasma IL-6 levels. SNP rs1800795 was associated with a 6.3% increase in IL-6 (95% confidence interval [CI] 1.7-11,2%) For these SNPs, we found that genotypes associated with higher IL-6 levels also tended to be associated to higher between-individual variability of IL-6 levels on the log-scale than other genotypes. Variability over time within individuals varied little by genotype. Conclusions: We found four genetic polymorphisms in the IL6 gene associated with mean level and variability of plasma IL-6 between individuals in myocardial infarction survivors.

Plasma fibrinogen is an acute phase protein playing an important role in the blood coagulation cascade having strong associations with smoking, alcohol consumption and body mass index (BMI). Genome-wide association studies (GWAS) have identified a variety of gene regions associated with elevated plasma fibrinogen concentrations. However, little is yet known about how associations between environmental factors and fibrinogen might be modified by genetic variation. Therefore, we conducted large-scale meta-analyses of genome-wide interaction studies to identify possible interactions of genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentration. The present study included 80,607 subjects of European ancestry from 22 studies. Genome-wide interaction analyses were performed separately in each study for about 2.6 million single nucleotide polymorphisms (SNPs) across the 22 autosomal chromosomes. For each SNP and risk factor, we performed a linear regression...

Background: Growing evidence indicates that ambient air pollution is associated with exacerbation of chronic diseases like chronic pulmonary disease. A prospective panel study was conducted to investigate short-term changes of blood markers of inflammation and coagulation in response to daily changes in air pollution in Erfurt, Germany. 12 clinical visits were scheduled and blood parameters were measured in 38 male patients with chronic pulmonary disease during winter 2001/2002. Additive mixed models with random patient intercept were applied, adjusting for trend, weekday, and meteorological parameters. Hourly data on ultrafine particles (UFP, 0.01-0.1 μm), accumulation mode particles (ACP, 0.1-1.0 μm), PM 10 (particulate matter <10 μm in diameter), elemental (EC) and organic carbon (OC), gaseous pollutants (nitrogen monoxide [NO], nitrogen dioxide [NO 2 ], carbon monoxide [CO], and sulphur dioxide [SO 2 ]) were collected at a central monitoring site and meteorological data were received from an official network. For each person and visit the individual 24-hour average of pollutants immediately preceding the blood withdrawal (lag 0) up to day 5 (lag1-4) and 5-day running means were calculated. Results: Increased levels of fibrinogen were observed for an increase in one interquartile range of UFP, PM 10 , EC, OC, CO, and NO revealing the strongest effect for lag 3. E-selectin increased in association with ACP and PM 10 with a delay of one day. The ACP effect was also seen with the 5day-mean. The pattern found for D-dimer was inconsistent. Prothrombin fragment 1+2 decreased with lag 4 consistently for all particulate pollutants. Von Willebrand factor antigen (vWF) showed a consistent decrease in association with almost all air pollutants with all lags except for lag 0. No

Epidemiological studies on health effects of air pollution have consistently shown adverse cardiovascular effects. Toxicological studies have provided evidence for thrombogenic effects of particles.A prospective panel study in a susceptible population was conducted in Erfurt, Germany, to study the effects of daily changes in ambient particles on various blood cells and soluble CD40ligand (sCD40L, also known as CD154), a marker for platelet activation that can cause increased coagulation and inflammation. Blood cells and plasma sCD40L levels were repeatedly measured in 57 male patients with coronary heart disease (CHD) during winter 2000/2001. Fixed effects linear regression models were applied, adjusting for trend, weekday and meteorological parameters.Hourly data on ultrafine particles (UFP, number concentration of particles from 0.01 to 0.1 microm), mass concentration of particles less than 10 and 2.5 microm in diameter (PM10, PM2.5), accumulation mode particle counts (AP, 0.1-1.0...

S.), which measures PSD from 500 nm-10 µm. The subsystems overlap at certain size ranges. We merged the final PSD into 3 nm-10 µm as our final data set. Particle mass concentration of PM 2.5 and PM 10 was measured by two independent Tapered Element Oscillating Microbalances (TEOM, model 1400ab, Thermo Fisher Scientific Inc., Waltham, MA, U.S.). For further details see (Pitz et al. 2008a). Particle density for PM 2.5 (ρ2.5) and PM 10 (ρ10) was calculated as the ratio of the mass concentration and the corresponding volume concentration, assuming that particles were spherically shaped. For details see (Pitz et al. 2008b).

OBJECTIVE: To investigate the relationship between breast-feeding and obesity in childhood. DESIGN: Systematic review and meta-analysis of published epidemiological studies (cohort, case-control or cross-sectional studies) comparing early feeding-mode and adjusting for potential confounding factors. Electronic databases were searched and reference lists of relevant articles were checked. Calculations of pooled estimates were conducted in fixed-and random-effects models. Heterogeneity was tested by Q-test. Publication bias was assessed from funnel plots and by a linear regression method. OUTCOME MEASURES: Odds ratio (OR) for obesity in childhood defined as body mass index (BMI) percentiles. RESULTS: Nine studies with more than 69 000 participants met the inclusion criteria. The meta-analysis showed that breastfeeding reduced the risk of obesity in childhood significantly. The adjusted odds ratio was 0.78, 95% CI (0.71, 0.85) in the fixed model. The assumption of homogeneity of results of the included studies could not be refuted (Q-test for heterogeneity, P40.3), stratified analyses showed no differences regarding different study types, age groups, definition of breast-feeding or obesity and number of confounding factors adjusted for. A dose-dependent effect of breast-feeding duration on the prevalence of obesity was reported in four studies. Funnel plot regression gave no indication of publication bias. CONCLUSION: Breast-feeding seems to have a small but consistent protective effect against obesity in children.

Background: Epidemiological studies have demonstrated associations between noise exposure and cardiovascular events. However, there have been few studies of possible underlying mechanisms. oBjectives: We examined the association between individual daytime noise exposure and heart rate variability (HRV). Methods: In a prospective panel study in Augsburg, Germany (March 2007-December 2008), 110 individuals participated in 326 electrocardiogram recordings with a mean duration of 6 hr. Five-minute averages of heart rate (HR) and HRV parameters were determined. Individual noise exposure was measured as A-weighted equivalent continuous sound pressure levels (L eq). Effects were estimated using additive mixed models adjusted for long-and short-term time trends and physical activity. Due to nonlinear exposure-response functions, we performed piecewise linear analyses with a cutoff point at 65 dB(A). results: Concurrent increases of 5dB(A) in L eq < 65dB(A) were associated with increases in HR (percent change of mean value: 1.48%; 95% CI: 1.37, 1.60%) and the ratio of low-frequency (LF) to high-frequency (HF) power (4.89%; 95% CI: 3.48, 6.32%), and with decreases in LF (-3.77%; 95% CI:-5.49,-2.02%) and HF (-8.56%; 95% CI:-10.31,-6.78%) power. Standard deviation of normal-to-normal intervals (SDNN) was positively associated with concurrent noise < 65dB(A) (5.74%; 95% CI: 5.13, 6.36) but negatively associated with noise lagged by 5-15 min (-0.53% to-0.69%). Associations with cardiac function were less pronounced for noise ≥ 65dB(A), with some in opposite directions from associations with noise < 65dB(A). Concurrent associations were modified by sex and age. conclusions: Individual daytime noise exposure was associated with immediate changes in HRV, suggesting a possible mechanism linking noise to cardiovascular risk. Noise at lower levels may have health consequences beyond those resulting from "fight-or-flight" responses to high levels of noise.