Association of air pollution with increased incidence of ventricular tachyarrhythmias recorded by implanted cardioverter defibrillators.
Epidemiologic studies have demonstrated a consistent link between sudden cardiac deaths Sudden Cardiac Death Definition
Sudden cardiac death (SCD) is an unexpected death due to heart problems, which occurs within one hour from the start of any cardiac-related symptoms. SCD is sometimes called cardiac arrest. and particulate air pollution. We used implanted cardioverter defibrillator defibrillator, device that delivers an electrical shock to the heart in order to stop certain forms of rapid heart rhythm disturbances (arrhythmias). The shock changes a fibrillation to an organized rhythm or changes a very rapid and ineffective cardiac rhythm to a (ICD ICD International Classification of Diseases (of the World Health Organization); intrauterine contraceptive device.
abbr. ) records of ventricular tachyarrhythmias to assess the role of air pollution as a trigger of these potentially life-threatening events. The study cohort consisted of 203 cardiac patients with ICD devices in the Boston metropolitan area who were followed for an average of 3.1 years between 1995 and 2002. Fine particle mass and gaseous air pollution plus temperature and relative humidity relative humidity
The ratio of the amount of water vapor in the air at a specific temperature to the maximum amount that the air could hold at that temperature, expressed as a percentage. were measured on almost all days, and black carbon, sulfate sulfate, chemical compound containing the sulfate (SO4) radical. Sulfates are salts or esters of sulfuric acid, H2SO4, formed by replacing one or both of the hydrogens with a metal (e.g., sodium) or a radical (e.g., ammonium or ethyl). , and particle number The particle number, N, is the number of so called 'elementary particles' (or elementary constituents) in a thermodynamical system. The particle number is a fundamental parameter in thermodynamics and it is conjugate to the chemical potential. on a subset of days. Date, time, and intracardiac intracardiac /in·tra·car·di·ac/ (-kahr´de-ak) within the heart.
Within the heart.
within the heart. electrograms of ICD-detected arrhythmias were downloaded at the patients' regular follow-up visits (about every 3 months). Ventricular tachyarrhythmias were identified by electrophysiologist review. Risk of ventricular arrhythmias associated with air pollution was estimated with logistic regression In statistics, logistic regression is a regression model for binomially distributed response/dependent variables. It is useful for modeling the probability of an event occurring as a function of other factors. , adjusting for season, temperature, relative humidity, day of the week, patient, and a recent prior arrhythmia arrhythmia (ārĭth`mēə), disturbance in the rate or rhythm of the heartbeat. Various arrhythmias can be symptoms of serious heart disorders; however, they are usually of no medical significance except in the presence of . We found increased risks of ventricular arrhythmias associated with 2-day mean exposure for all air pollutants considered, although these associations were not statistically significant. We found statistically significant associations between air pollution and ventricular arrhythmias for episodes within 3 days of a previous arrhythmia. The associations of ventricular tachyarrhythmias with fine particle mass, carbon monoxide carbon monoxide, chemical compound, CO, a colorless, odorless, tasteless, extremely poisonous gas that is less dense than air under ordinary conditions. It is very slightly soluble in water and burns in air with a characteristic blue flame, producing carbon dioxide; , nitrogen dioxide nitrogen dioxide
A poisonous brown gas, NO2, often found in smog and automobile exhaust fumes and synthesized for use as a nitrating agent, a catalyst, and an oxidizing agent.
Noun 1. , and black carbon suggest a link with motor vehicle pollutants. The associations with sulfate suggest a link with stationary fossil fuel fossil fuel: see energy, sources of; fuel.
Any of a class of materials of biologic origin occurring within the Earth's crust that can be used as a source of energy. Fossil fuels include coal, petroleum, and natural gas. combustion sources. Key words: air pollution, arrhythmias, epidemiology, fibrillation fibrillation /fi·bril·la·tion/ (fi?bri-la´shun)
1. the quality of being made up of fibrils.
2. a small, local, involuntary, muscular contraction, due to spontaneous activation of single muscle cells or muscle , heart arrest. Environ Health Perpect 113:670-674 (2005). doi:10.1289/ehp.7767 available via http://dx.doi.org/[Online 18 February 2005]
A large number of epidemiologic studies have found an association between short-term episodes of increased particulate air pollution and cardiovascular morbidity and mortality Morbidity and Mortality can refer to:
1. suitable for respiration.
2. small enough to be inhaled.
1. Fit for breathing, as air. particulate matter particulate matter
n. Abbr. PM
Material suspended in the air in the form of minute solid particles or liquid droplets, especially when considered as an atmospheric pollutant.
Noun 1. has been specifically implicated im·pli·cate
tr.v. im·pli·cat·ed, im·pli·cat·ing, im·pli·cates
1. To involve or connect intimately or incriminatingly: evidence that implicates others in the plot.
2. in the triggering of myocardial infarction myocardial infarction: see under infarction. (D'Ippoliti et al. 2003; Peters et al. 2001), arrhythmias (Peters et al. 2000), decompensation decompensation /de·com·pen·sa·tion/ (de?kom-pen-sa´shun)
1. inability of the heart to maintain adequate circulation, marked by dyspnea, venous engorgement, and edema.
2. of heart failure patients (Morris and Naumova 1998; Schwartz and Morris 1995; Wellenius et al., in press), and the exacerbation of myocardial ischemia myocardial ischemia,
n a loss of oxygen to the heart muscle caused by blockage of the coronary arteries or their branches.
myocardial ischemia (Pekkanen et al. 2002; Wellenius et al. 2003). Particulate-related changes in autonomic nervous system autonomic nervous system: see nervous system.
autonomic nervous system
Part of the nervous system that is not under conscious control and that regulates the internal organs. It includes the sympathetic, parasympathetic, and enteric nervous systems. activity, as assessed by heart rate variability Heart rate variability (HRV) is a measure of variations in the heart rate. It is usually calculated by analysing the time series of beat-to-beat intervals from ECG or arterial pressure tracings. , have been observed in both experimental animal studies (Godleski et al. 2000) and human panel studies (Creason et al. 2001; Gold et al. 2000; Liao et al. 1999, 2004; Pope et al. 1999), suggesting sympathetic activation or vagal vagal /va·gal/ (va´gal) pertaining to the vagus nerve.
Of or relating to the vagus nerve.
pertaining to the vagus nerve. suppression after particulate air pollution exposure. Such changes in autonomic tone may increase the risk of ventricular arrhythmias in vulnerable patients (Huikuri et al. 2001). Ventricular tachyarrhythmias, primarily ventricular tachycardia Ventricular Tachycardia Definition
Ventricular tachycardia (V-tach) is a rapid heart beat that originates in one of the lower chambers (the ventricles) of the heart. and ventricular fibrillation ventricular fibrillation
Uncoordinated contraction of the muscle fibres of the heart's ventricles (see arrhythmia). Causes include heart attack, electric shock, anoxia, abnormally high potassium or low calcium in the blood, and digitalis or epinephrine poisoning ( , are common precursors to sudden cardiac death (Bayes de Luna et al. 1989; Myerburg et al. 1992).
Implanted cardioverter defibrillators (ICDs) passively monitor for ventricular tachyarrhythmias that, if not terminated, could be life threatening. On detecting such an arrhythmia, the ICD can apply cardiac pacing or cardioverter shock to restore normal rhythms. The ICD also records the date and time of arrhythmias plus intracardiac electrograms immediately before and during these events. In a pilot study of 100 Boston area ICD patients with follow-up for up to 3 years, we found increased risk of an ICD therapeutic discharge on days after elevated air pollution concentrations (Peters et al. 2000). In this pilot study, we did not collect data on patient characteristics or medication. However, we did find stronger air pollution associations among patients with frequent ICD discharges.
This study was designed to confirm the pilot study observations. In a larger sample of ICD patients in Boston with longer follow-up, we identified ventricular tachyarrhythmias by review of ICD-recorded electrograms. We assessed the association between community air pollution and ventricular tachyarrhythmias using time-series methods. We also evaluated modification of the air pollution association by patient medical conditions See carpal tunnel syndrome, computer vision syndrome, dry eyes and deep vein thrombosis. , antiarrhythmic antiarrhythmic /an·ti·ar·rhyth·mic/ (-ah-rith´mik)
1. preventing or alleviating cardiac arrhythmias.
2. an agent that so acts.
adj. medications, and recent arrhythmias.
Materials and Methods
Arrhythmias. We examined the effects of air pollution on incidence of tachyarrhythmias in ICD patients clinically followed between July 1995 and July 2002 at the Tufts New England New England, name applied to the region comprising six states of the NE United States—Maine, New Hampshire, Vermont, Massachusetts, Rhode Island, and Connecticut. The region is thought to have been so named by Capt. Medical Center (Dockery et al., in press). The source population consisted of patients implanted with third-generation Guidant ICDs (Cardiac Pacemakers, Inc., St. Paul St. Paul
as a missionary he fearlessly confronts the “perils of waters, of robbers, in the city, in the wilderness.” [N.T.: II Cor. 11:26]
See : Bravery , MN) at the New England Medical Center Cardiac Electrophysiology Cardiac electrophysiology is the science of the mechanisms, functions, and performance of the electrical activities of specific regions of the heart. This term is usually used in describing studies of such phenomena by invasive (intracardiac) recording of spontaneous activity as and Pacemaker Laboratory between June 1995 and 31 December 1999. All patients met the American College of Cardiology The American College of Cardiology (ACC) is a nonprofit medical association established in 1949 to educate, research and influence health care public policy. The president for the 2006–2007 year is Steven E. Nissen.  The organization has 39 chapters in the U.S. and the American Heart Association American Heart Association (AHA),
n.pr a national voluntary health agency that has the goal of increasing public and medical awareness of cardiovascular diseases and stroke, and thereby reducing the number of associated deaths and disabilities. guidelines for ICD implantation (Gregoratos et al. 1998). We excluded patients residing in ZIP codes > 40 km (25 miles) from the air monitoring site at the Harvard School of Public Health The Harvard School of Public Health is (colloquially, HSPH) is one of the professional graduate schools of Harvard University. Located in Longwood Area of the Boston, Massachusetts neighborhood of Mission Hill, next to Harvard Medical School and Cambridge, Massachusetts, . Patient characteristics before implant (including age, sex, race and ethnicity, residential ZIP code, implant date, device model, diagnoses at implant, and physiologic measurements before implant) were abstracted from patient records. Prescribed medications were abstracted from clinical records at each follow-up visit.
Date, time, and intracardiac electrograms of all detected arrhythmias were downloaded from the ICD records collected at the patients' regular clinical follow-up visits (on average, every 89 days). Patients contributed person-time to the follow-up between ICD implantation and their last clinical follow-up visit at the New England Medical Center before July 2002. We excluded the first 14 days after implantation, periods when the patient was a hospital inpatient, and periods between clinical visits when the patient was not followed up at the New England Medical Center. Subjects who died or who were lost to follow-up were censored at their last clinical follow-up.
The intracardiac electrograms for each ICD-detected arrhythmia were reviewed by an electrophysiologist (M.S.L.) blinded to air pollution levels. Ventricular tachyarrhythmias were identified based on atrial-ventricular dysynchrony, onset interval, stability, morphology of the tachycardia tachycardia: see arrhythmia.
Heart rate over 100 (as high as 240) beats per minute. When it is a normal response to exercise or stress, it is no danger to healthy people, but when it originates elsewhere, it is an arrhythmia. , and response to therapy. We excluded sinus tachycardias, arrhythmias originating outside the ventricle ventricle /ven·tri·cle/ (ven´tri-k'l) a small cavity or chamber, as in the brain or heart.ventric´ular
ventricle of Arantius the rhomboid fossa, especially its lower end. (e.g., atrial tachycardia atrial tachycardia Cardiology Tachycardia triggered by a focus in the atrium, which beats at 160 to 190 bpm. See Atrial fibrillation, Atrial flutter. , atrial fibrillation atrial fibrillation
Irregular rhythm (arrhythmia) of contraction of the atria (upper heart chambers). The most common major arrhythmia, it may result as a consequence of increased fibrous tissue in the aging heart, of heart disease, or in association with severe infection. , atrial flutter atrial flutter
Rapid regular atrial contractions occurring usually at rates between 250 and 400 per minute and often producing saw-tooth waves in an electrocardiogram. Also called auricular flutter. , sinus tachycardia), and noise or over-sensing events. An episode day was defined as one or more ventricular arrhythmic ar·rhyth·mic
Lacking rhythm or regularity of rhythm. events on a given calendar day.
Data collection and preliminary analyses have been described previously (Dockery et al., in press). The Harvard School of Public Health Human Studies Committee and the New England Medical Center Institutional Review Board approved this retrospective record review.
Air pollution. Ambient concentrations of gaseous air pollutants were measured by the Massachusetts Department of Environmental Protection between 1995 and 2002 at six sites for ozone, nitrogen dioxide, and/or sulfur dioxide sulfur dioxide, chemical compound, SO2, a colorless gas with a pungent, suffocating odor. It is readily soluble in cold water, sparingly soluble in hot water, and soluble in alcohol, acetic acid, and sulfuric acid. and four sites for carbon monoxide in the Boston metropolitan area. We calculated the average air pollution concentration across the reporting air pollution monitoring stations for each hour accounting for differences in the annual mean and the standardized deviations of each monitor (Schwartz 2000). The daily mean was then calculated from the 24-hr specific average concentrations across the monitors.
Fine particulate (< 2.5 [micro]m aerodynamic diameter Drug particles for pulmonary delivery are typically characterized by aerodynamic diameter rather than geometric diameter. The velocity at which the drug settles is proportional to the aerodynamic diameter, da. ) matter (P[M.sub.2.5]) concentrations were measured (model 1400A tapered element oscillating os·cil·late
intr.v. os·cil·lat·ed, os·cil·lat·ing, os·cil·lates
1. To swing back and forth with a steady, uninterrupted rhythm.
2. microbalance mi·cro·bal·ance
A balance designed to weigh very small loads, up to 0.1 gram.
Noun 1. microbalance - balance for weighing very small objects
balance - a scale for weighing; depends on pull of gravity ; Rupprecht and Patashnick, East Greenbush East Greenbush is the name the following places in the United States of America:
The hourly surface observations from the National Weather Service at Logan Airport in East Boston were extracted from climatic records (Earth-Info, Inc., Boulder, CO). Daily minimum temperature and mean relative humidity were calculated from the hourly observations.
Statistical analyses. Following the analytic methods used in the pilot study (Peters et al. 2000), we assessed the association of arrhythmias with air pollution using time-series methods. We merged the patient-specific record of days on study and ICD-detected ventricular arrhythmias with the daily mean air pollution and weather measurements. The association of arrhythmic episode-days with air pollution was analyzed by logistic regression using generalized estimating equations (Diggle 1988; Zeger et al. 1988) with random effects Random effects can refer to:
COSINE - Cooperation for Open Systems Interconnection Networking in Europe. A EUREKA project. terms with periods of one, one-half, one-third, and one-quarter year, quadratic functions of minimum temperature and mean humidity, indicators for day of the week, and an indicator for a previous arrhythmia within 3 days.
We considered mean air pollution concentrations on the same day and lags of 1, 2, and 3 days. The lag structure of the data was estimated by evaluating each lag day (0 to 3) separately and jointly in an unconstrained distributed lag model (Pope and Schwartz 1996). We have found consistently elevated (although not statistically significant) risk estimates associated with air pollution concentrations on the day of (lag 0) and the day before (lag 1) the arrhythmia (Dockery et al., in press). Therefore, in this article we report only the effects of 2-day running mean air pollution concentrations.
We explored potential modification of the air pollution associations in multivariate logistic regression including interactions between air pollution and indicators of patient characteristics. Patients were stratified stratified /strat·i·fied/ (strat´i-fid) formed or arranged in layers.
Arranged in the form of layers or strata. by reported ejection fraction ejection fraction
The blood present in the ventricle at the end of diastole and expelled during the contraction of the heart.
Ejection fraction before implantation ([less than or equal to] 35% vs. > 35%), prior myocardial infarction, and the diagnosis of coronary artery disease coronary artery disease, condition that results when the coronary arteries are narrowed or occluded, most commonly by atherosclerotic deposits of fibrous and fatty tissue. before implantation (not sufficient numbers of patients for specific analyses of other cardiac diagnoses). We assessed modification of the air pollution associations by usual prescribed medications (reported at more than half of clinical follow-ups) grouped as beta-blockers, digoxin digoxin: see digitalis. , and other antiarrhythmics (amiodarone, sotalol, mexilitine, and quinidine quinidine (kwĭn`ĭdēn'), heart muscle relaxant used to maintain regular heart rhythm patterns. It is an alkaloid chemically similar to quinine and, like quinine, occurs naturally in some species of cinchona trees. ). The strongest predictor of a ventricular arrhythmia was an arrhythmia in the previous 3 days. Therefore, in addition to controlling for prior arrhythmias, we assessed the modification of the air pollution association by a prior ventricular arrhythmia.
We present odds ratios (ORs) and 95% confidence intervals (CIs) based on an interquartile range In descriptive statistics, the interquartile range (IQR), also called the midspread, middle fifty and middle of the #s, is a measure of statistical dispersion, being equal to the difference between the third and first quartiles. (25th percentile-75th percentile) increase in each air pollution concentration, p-Values are reported for the effects of air pollution and for the interactions of air pollution with posited effect modifiers. We characterize p-values < 0.05 as statistically significant, and p-values < 0.10 as marginally significant. For air pollutants and subgroups of events with statistically significant associations, we examined the risk of arrhythmias versus quintiles Quintiles Transnational Corp. is a contract research organization which serves the pharmaceutical, biotechnology and healthcare industries. History
Quintiles was founded in 1982 by Dennis Gillings and as of 2007 it has 18,000 employees. of air pollution concentration.
Patient population. A total of 307 patients had Guidant ICDs implanted at the New England Medical Center between June 1995 and the end of 1999. There were 203 patients followed up with residential ZIP codes within 40 km (25 miles) of the ambient air pollution monitoring site at the Harvard School of Public Health. These ICD patients had a total of 635 person-years (pyr) of follow-up or an average of 3.1 years per subject.
There were 933 ICD-detected tachyarrhythmias (separated by at least 60 min), of which 798 (86%) were ventricular (63 ventricular fibrillation, 25 nonsustained ventricular fibrillation, 622 ventricular tachycardia, and 88 nonsustained ventricular tachycardia). We restricted analysis to the 670 ventricular episode days (one or more ventricular arrhythmias on a calendar day), average of 1.06 episode days/pyr, among 84 (41%) patients.
Patients were predominantly men (75%) with an average age at implantation of 64 years (range, 19-90 years). The rate of ventricular episode days per person-year was higher among men (1.22/pyr) compared with women (0.62/pyr), and increased with age at implantation. Eighty-three percent of the patients were reported to be white, 3% African American African American Multiculture A person having origins in any of the black racial groups of Africa. See Race. , 5% Hispanic, 3% Asian, and 7% of undetermined or unknown race/ethnicity.
Among the patients reported to have had a myocardial infarction before ICD implantation, the rate of ventricular arrhythmias (1.73/pyr) was almost three times the rate among the patients without a prior myocardial infarction (0.61/pyr). The patients with low ejection fraction ([less than or equal to] 35%) before implantation had a rate of ventricular episodes (1.48/pyr) approximately three times larger than that of patients with ejection fraction > 35% (0.45/pyr).
The most common preimplantation diagnosis Preimplantation diagnosis is the act of checking an ovum, zygote, or blastocyst for defects or diseases by cytogenetics before implanting into a womb. Preimplantation diagnosis takes place before prenatal diagnosis, which refers to a checking for defects in a fetus or embryo that was coronary artery disease (70%) followed by cardiomyopathy Cardiomyopathy Definition
Cardiomyopathy is a chronic disease of the heart muscle (myocardium), in which the muscle is abnormally enlarged, thickened, and/or stiffened. (36%). Nine patients (4%) were classified as having primary electrical disease, and four of these had ventricular arrhythmic events. Four patients (2%) had long QT syndrome The long QT syndrome (LQTS) is a heart condition associated with prolongation of repolarisation (recovery) following depolarisation (excitation) of the cardiac ventricles. It is associated with syncope (fainting) and sudden death due to ventricular arrhythmias. (a congenital disorder congenital disorder
A large group of disorders arising during development that cause abnormality of the human body. Most are due to genetic factors such as inherited or spontaneous mutations, whereas others are caused by environmental influences during pregnancy such as characterized by prolongation of the QT interval QT interval
the portion of an electrocardiogram between the onset of the Q wave and the end of the T wave, representing the total time for ventricular depolarization and repolarization. on the electrocardiogram electrocardiogram /elec·tro·car·dio·gram/ (-kahr´de-o-gram?) a graphic tracing of the variations in electrical potential caused by the excitation of the heart muscle and detected at the body surface. ), but only one of these had an event during follow-up. Patients with coronary artery disease had the highest rates of detected ventricular arrhythmias (1.30/pyr) compared with those with other diagnoses (0.50/pyr).
Eighty-nine percent of these patients were prescribed antiarrhythmic medications. The rates of ventricular arrhythmic episode days was higher among those prescribed digoxin (1.68/pyr) or other antiarrhythmics (1.45/pyr) than among those prescribed beta-blockers (0.92/pyr) or no regular antiarrhythmic medication (0.88/pyr).
Approximately one-quarter (164) of the 670 ventricular arrhythmias followed a previous ventricular arrhythmia within 3 days. We found that having a prior arrhythmia (within 3 days) was a very strong predictor for a subsequent arrhythmia (OR = 7.2; 95% CI, 5.9-8.9).
Air pollution. P[M.sub.2.5] was measured on 2,005 (79%) of the follow-up days and BC on 1,533 (60%) days (Table 1). Particulate S[O.sub.4] measurements were limited to 908 (36%) days, and PN to 772 (30%) days. Daily P[M.sub.2.5] was strongly correlated with S[O.sub.4] (Pearson correlation r = 0.74) and BC (r = 0.67), but only weakly correlated (r = -0.13) with PN.
The gaseous pollutants were measured on essentially all follow-up days (Table 1). Daily CO and N[O.sub.2], both indicators of motor vehicle emissions, were highly correlated with each other (r = 0.61), positively correlated (r > 0.4) with BC, P[M.sub.2.5], and S[O.sub.2], but negatively correlated with [O.sub.3].
Air pollution association. We found positive associations between ventricular arrhythmic episode days and mean air pollution on the same and previous days, but none of these associations approached statistical significance (Table 2).
We did not find consistent increased susceptibility to the effects of air pollution on risk of ventricular arrhythmias based on patient characteristics. We found marginally significant (p < 0.10) interaction of the associations with CO with ejection fraction (stronger with low ejection fraction), preimplantation diagnosis of coronary artery disease (weaker with coronary artery disease), and prior myocardial infarction (weaker with prior myocardial infarction), and of the associations with N[O.sub.2] with prior myocardial infarction (stronger with prior myocardial infarction). No other interactions approached statistical significance. We saw no evidence that any of the prescribed drugs modified the associations of ventricular arrhythmias with air pollution.
The interaction of a prior ventricular atrhythmia with air pollution was statistically significant for P[M.sub.2.5], BC, N[O.sub.2], S[O.sub.2], and CO and marginally significant for S[O.sub.4] (Table 3). For ventricular arrhythmias within 3 days of a prior event (Table 3), we found statistically significant positive associations with P[M.sub.2.5], BC, N[O.sub.2], CO, and S[O.sub.2], marginally significant associations with S[O.sub.4], but no associations with [O.sub.3] or PN. For ventricular arrhythmias more than 3 days after a previous ventricular arrhythmia, we found no associations with any air pollutants (Table 3). We assessed the risk of ventricular arrhythmias stratified by a prior ventricular tachyarrhythmia tachyarrhythmia /tachy·ar·rhyth·mia/ (tak?e-ah-rith´me-ah) any disturbance of the heart rhythm in which the heart rate is abnormally increased.
n. versus quintiles of air pollution (Figure 1). We found generally increasing risk with increasing quintiles of P[M.sub.2.5], BC, and CO and weaker suggestions of an exposure response with N[O.sub.2], S[O.sub.2], and [O.sub.3].
[FIGURE 1 OMITTED]
In this study of 203 New England Medical Center ICD patients living in the Boston metropolitan area with up to 7 years of follow-up, we found the risk of any ICD-detected ventricular tachyarrhythmia was positively but not significantly associated with increased exposure to air pollution on the days before the arrhythmia (Table 2). We found statistically significant associations of air pollution with increased risk of ventricular arrhythmias among patients with an arthythmia within the previous 3 days. These findings suggest that air pollution may provoke ventricular tachyarrhythmias only in the presence of acutely predisposing conditions that increase ventricular electrical instability. We did not find consistent indications that the air pollution associations with ventricular arrhythmias were modified by indicators of chronically impaired cardiac function, including a prior myocardial infarction, a diagnosis of coronary artery disease, or an ejection fraction < 35%, or by prescribed antiarrhythmic medications.
These results are broadly consistent with those of previously published studies of air pollution associations with tachyarrhythmias leading to ICD therapeutic discharge. In this study, we found significantly increased risk of ventricular arrhythmias with P[M.sub.2.5], BC, CO, N[O.sub.2], and S[O.sub.2] among patients with a recent prior ventricular arrhythmia. In the pilot study (Peters et al. 2000); ICD patients in Boston with frequent (> 10) discharges during follow-up had an exposure related increase in ICD discharge associated with P[M.sub.2.5], BC, CO, and N[O.sub.2].
A recent study assessed the association of air pollution in Vancouver, British Columbia British Columbia, province (2001 pop. 3,907,738), 366,255 sq mi (948,600 sq km), including 6,976 sq mi (18,068 sq km) of water surface, W Canada. Geography
, Canada, with ICD discharges among 50 patients with an average of 2.2 years of follow-up (Rich et al. 2004; Vedal et al. 2004). In crude analyses, the rate of ICD discharge increased with quartiles of N[O.sub.2] and CO concentration on the same day (Vedal et al. 2004). However, there were no statistically significant positive associations with ICD discharge with N[O.sub.2] or CO after adjusting for temporal patterns and numerous weather parameters. The lack of significant associations may be caused by overcontrol of some variables, as these investigators suggest.
Both of these previously reported studies (Peters et al. 2000; Vedal et al. 2004) focused on ICD therapeutic discharge without characterization or validation of the underlying arrhythmia. Of the almost 2,000 arrhythmias identified and recorded by the ICD devices in this study, 8% were classified as oversensing, 4% were sinus tachycardias, 18% were supraventricular arrhythmias, and 70% were ventricular arrhythmias. Thus, 30% of the ICD-detected arrhythmias were not the potentially life-threatening ventricular tachyarrhythmias defined as the primary outcome for this study.
An important question in these analyses is the appropriate exposure averaging time and the lag between exposure and cardiac arrhythmia cardiac arrhythmia
See cardiac dysrhythmia.
An irregular heart rate or rhythm.
Mentioned in: Holter Monitoring, Stress Test
cardiac arrhythmia . In the pilot study, we found associations with air pollutants 2 days before the arrhythmias and with the 5-day mean air pollution (Peters et al. 2000). In this study, ventricular arrhythmias were positively associated with ambient air pollution on the same and the previous calendar days. Temporality tem·po·ral·i·ty
n. pl. tem·po·ral·i·ties
1. The condition of being temporal or bounded in time.
2. temporalities Temporal possessions, especially of the Church or clergy.
Noun 1. would require that air pollution exposure precede the arrhythmia. This temporal association is clearly true for associations with air pollution on the previous day, but mean air pollution on the same calendar day would include hours after as well as before the detected arrhythmia. Using the pollutant concentrations from the specific 24 hr preceding the arrhythmia would likely provide a better estimate of each subject's exposure and allow investigation of exposures in the hours before the arrhythmia.
For these patients living in eastern Massachusetts, air pollution exposure was estimated based on a single or a small number of monitors in the Boston metropolitan area. This would lead to misclassification of air pollution exposure, but this misclassification would be independent of the risk for ventricular arrhythmias. Such nondifferential misclassification of exposure produces an attenuated Attenuated
Alive but weakened; an attenuated microorganism can no longer produce disease.
Mentioned in: Tuberculin Skin Test
having undergone a process of attenuation. estimate of associations (and larger CIs) in epidemiologic studies assuming linear associations. If these observations are true, then studies with improved estimation of subject specific air pollution exposures would be expected to find stronger, more statistically significant associations.
We found associations with CO, N[O.sub.2], BC, and P[M.sub.2.5]. These four pollutants had high day-to-day correlations with each other and were strongly correlated with S[O.sub.2]. It would not be possible to differentiate the independent effects of these pollutants. Nevertheless, the associations with these specific pollutants are consistent with an effect from air pollution from motor vehicle sources.
Animal studies in Boston have suggested that changes in indicators of cardiac function are specifically associated with motor vehicle pollution (Clarke et al. 2000). Analysis of daily mortality in Boston and five other cities suggested that motor vehicle pollution was more strongly related to cardiovascular mortality than to respiratory mortality (Laden et al. 2000). Cardiovascular emergency department visits in Atlanta, Georgia, were significantly associated with these same markers of motor vehicle air pollution N[O.sub.2], CO, P[M.sub.2.5], BC, and fine particle organic carbon (Metzger et al. 2004). For Atlanta emergency department visits for dysrhythmias, positive associations were found for these same motor vehicle pollutants, although these associations were not statistically significant because of the smaller number of events.
We cannot exclude the possible role of sulfur oxides, which are generally considered to be indicators of air pollution from power plants and other stationary fossil fuel combustion sources. In this analysis, we found associations of ventricular tachyarrhythmias in subjects with a recent event associated with S[O.sub.2] (p = 0.013) and with S[O.sub.4] (p = 0.06). The positive, marginally significant associations with S[O.sub.4] are notable because S[O.sub.4] data were available only on a limited number of days (37%) compared with S[O.sub.2] and the other gaseous pollutants. Particulate S[O.sub.4] concentrations in Boston largely reflect secondary particles formed during long-range transport. Gaseous S[O.sub.2] concentrations reflect local sulfur emissions and were most highly correlated with motor vehicle pollutants.
A major advantage of the ICD data is the passive monitoring of cardiac tachyarrhythmias. Nevertheless, ICD-detected ventricular arrhythmias were rare events in this follow-up, and the small number of subjects with multiple ICD-detected arrhythmias is a limitation. These patients clearly represent a highly selected cohort of special interest, because their previous history of cardiovascular disease Cardiovascular disease
Disease that affects the heart and blood vessels.
Mentioned in: Lipoproteins Test
cardiovascular disease might make them particularly sensitive to the effects of air pollution episodes. The observed associations of ventricular tachyarrhythmias with particulate air pollution in these subjects are large compared with previous studies. In a mortality time-series analysis Time-series analysis
Assessment of relationships between two or among more variables over periods of time. in Boston and five other cities (Schwartz et al. 1996), each increase of 10 [micro]g/[m.sup.3] in the 2-day mean P[M.sub.2.5] was associated with a 2% increase in the risk of cardiovascular mortality. For Boston ICD patients (Table 2), the observed associations imply an 11% (95% CI, -9 to 35%) increased risk of potentially fatal ventricular arrhythmias when scaled to the same 10 [micro]g/[m.sup.3] in the 2-day mean P[M.sub.2.5] concentrations. Thus, the ICD patients had a risk of potentially life-threatening ventricular tachyarrhythmias associated with fine particles that was more than five times the risk of cardiovascular death in the general population. Among those at the highest risk--those with a recent prior ventricular arrhythmia--the increased risk of a new ventricular tachyarrhythmia was 97% (95% CI, 46-165%) associated with each 10-[micro]g/[m.sup.3] increase in P[M.sub.2.5].
We found that ventricular tachyarrhythmias among patients with ICDs increased with air pollution on the same and previous days, but these associations did not reach statistical significance. However, among patients with a recent tachyarrhythmia, the increased risk of a follow-up ventricular tachyarrhythmia associated with air pollution was large and statistically significant. These observations suggest that air pollution may act in combination with a cardiac electrical instability to increase the risk for ventricular tachyarrhythmias. Among such acutely vulnerable ICD patients, there was an exposure response with P[M.sub.2.5], BC, N[O.sub.2], CO, and S[O.sub.2], which we interpret as indicators of mobile source pollution, and also evidence of an association with S[O.sub.4], which we interpret as an indicator of power plant and other stationary fossil fuel combustion sources.
ICDs have proven to be highly effective in reducing the risk of death in patients with high risk of cardiac arrhythmias. The passive monitoring of arrhythmias by these devices has provided a rich resource for understanding the role of air pollution episodes as potential triggers of these events.
Some counts of observations (Tables 1 and 2) and the interquartile range of S[O.sub.4] (Tables 1, 2, and 3) were for 1-day rather than 2-day mean in the original manuscript published online. They have been corrected here.
Table 1. Distribution of the 2-day mean air pollutants averaged across multiple sites in Boston, and weather data: 11 July 1995 to 11 July 2002. Percentile Air pollutant No. 25th 50th 75th 95th P[M.sub.2.5]([micro]g/ [m.sup.3]) 2,005 7.5 10.3 14.4 23.3 BC ([micro]g/[m.sup.3]) 1,533 0.66 0.98 1.39 2.25 S[O.sub.4] ([micro]g/ [m.sup.3]) 908 1.76 2.55 3.80 7.18 PN ([10.sup,3]/[cm.sup.3]) 772 20.6 29.3 39.8 50.7 N[O.sub.2](ppb) 2,556 18.9 22.7 26.6 33.6 CO (ppm) 2,558 0.53 0.80 1.02 1.37 S[O.sub.2](ppb) 2,558 3.3 4.9 7.4 12.8 [O.sub.3] (ppb) 2,548 15.7 22.9 31.1 42.1 Minimum temperature ([degrees]C) 2,553 0.6 7.2 14.4 20.6 Relative humidity (%) 2,549 56.7 69.0 81.5 94.3 Table 2. Estimated ORs (95% CIs) for an interquartile range increase in 2-day mean air pollution. No. of Interquartile days range increase P[M.sup.2.5] 2,005 6.9 [micro]g/[m.sup.3] BC 1,533 0.74 [micro]g/[m.sup.3] S[O.sub.4] 908 2.04 [micro]g/[m.sup.3] PN 772 19,120/[cm.sup.3] N[O.sub.2] 2,556 7.7 ppb CO 2,558 0.48 ppm S[O.sub.2] 2,558 4.0 ppb [O.sub.3] 2,548 15 ppb OR (95% CI) p-Value P[M.sup.2.5] 1.08 (0.96-1.22) 0.21 BC 1.11 (0.95-1.28) 0.18 S[O.sub.4] 1.05 (0.92-1.20) 0.48 PN 1.14 (0.87-1.50) 0.35 N[O.sub.2] 1.07 (0.97-1.18) 0.19 CO 1.14 (0.95-1.29) 0.28 S[O.sub.2] 1.04 (0.94-1.14) 0.28 [O.sub.3] 1.09 (0.93-1.29) 0.28 Table 3. Association of interquartile range increase in 2-day mean air pollution with ventricular arrhythmias stratified by a recent arrhythmia (within 3 days). Air pollutant (IQR increase) > 3 Days P[M.sub.2.5] (6.9 [micro]g/[m.sup.3]) 0.98 (0.86-1.12) p = 0.73 BC (0.74 [micro]g/[m.sup.3]) 1.02 (0.83-1.24) p = 0.86 S[O.sub.4] (2.04 [micro]g/[m.sup.3]) 1.03 (0.87-1.22) p = 0.73 PN (19,120/[cm.sup.3]) 1.17 (0.82-1.66) p = 0.38 N[O.sub.2] (7.7 ppb) 1.02 (0.90-1.16) p = 0.78 CO (0.48 ppm) 1.04 (0.83-1.29) p = 0.75 S[O.sub.2] (4 ppb) 0.98 (0.87-1.11) p = 0.78 [O.sub.3] (15 ppb) 1.14 (0.92-1.40) p = 0.24 p-Value for Air pollutant (IOR increase) < 3 Days interaction P[M.sub.2.5] (6.9 [micro]g/[m.sup.3]) 1.60 (1.30-1.96) <0.001 p < 0.001 BC (0.74 [micro]g/[m.sup.3]) 1.74 (1.28-2.37) 0.003 p < 0.001 S[O.sub.4] (2.04 [micro]g/[m.sup.3]) 1.19 (0.99-1.43) 0.066 p = 0.060 PN (19,120/[cm.sup.3]) 1.11 (0.71-1.75) 0.86 p = 0.65 N[O.sub.2] (7.7 ppb) 1.34 (1.05-1.71) 0.050 p = 0.018 CO (0.48 ppm) 1.65 (1.17-2.33) 0.016 p = 0.005 S[O.sub.2] (4 ppb) 1.30 (1.06-1.61) 0.006 p = 0.013 [O.sub.3] (15 ppb) 1.01 (0.76-1.35) 0.44 p = 0.94
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Douglas W. Dockery, (1,2) Heike Luttmann-Gibson, (1) David Q. Rich, (1) Mark S. Link, (3) Murray A. Mittleman, (4,5) Diane R. Gold, (1,2) Petros Koutrakis, (1) Joel D. Schwartz, (1,2) and Richard L. Verrier (1,5)
(1) Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA; (2) Channing Laboratory, Brigham and Women's Hospital Brigham and Women's Hospital (BWH) is a hospital in the Longwood Area of the Boston, Massachusetts neighborhood of Mission Hill. With Massachusetts General Hospital, it is one of the two founding members of Partners HealthCare. and Harvard Medical School Harvard Medical School (HMS) is one of the graduate schools of Harvard University. It is a prestigious American medical school located in the Longwood Medical Area of the Mission Hill neighborhood of Boston, Massachusetts. , Boston, Massachusetts, USA; (3) New England Medical Center, Tufts University, Boston, Massachusetts, USA; (4) Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA; (5) Beth Israel Deaconess Medical Center Both an international and regional referral center, Beth Israel Deaconess Medical Center (BIDMC) in Boston, Massachusetts is a major teaching hospital of Harvard Medical School. It was formed out of the 1996 merger of Beth Israel Hospital (founded in 1916) and and Harvard Medical School, Boston, Massachusetts, USA
Address correspondence to D.W. Dockery, Exposure, Epidemiology and Risk Program, Department of Environmental Health, Harvard School of Public Health, Landmark Center, Room 415D West, P.O. Box 15677, 401 Park Dr., Boston, MA 02215 USA. Telephone: (617) 384-8740. Fax: (617) 384-8745. E-mail: firstname.lastname@example.org
We thank the data abstracters, including J. Baliff, C. Freed, C. Hu, R. Hulefeld, and L. McClelland.
The Health Effects Institute (grant 98-14) and the National Institute of Environmental Health Sciences The National Institute of Environmental Health Sciences (NIEHS) is one of 27 Institutes and Centers of the National Institutes of Health (NIH),which is a component of the Department of Health and Human Services (DHHS). The Director of the NIEHS is Dr. David A. Schwartz. (ES-09825 and ES-00002) funded this study. Particulate air pollution measurements were supported in part by the U.S. Environmental Protection Agency Environmental Protection Agency (EPA), independent agency of the U.S. government, with headquarters in Washington, D.C. It was established in 1970 to reduce and control air and water pollution, noise pollution, and radiation and to ensure the safe handling and (grant R827353).
The authors declare they have no competing financial interests.
Received 17 November 2004; accepted 14 February 2005.