Murray A. Mittleman

Particulate Matter Air Pollution and Cardiovascular Disease An Update to the Scientific Statement From the American Heart Association

In 2004, the first American Heart Association scientific statement on “Air Pollution and Cardiovascular Disease” concluded that exposure to particulate matter (PM) air pollution contributes to cardiovascular morbidity and mortality. In the interim, numerous studies have expanded our understanding of this association and further elucidated the physiological and molecular mechanisms involved. The main objective of this updated American Heart Association scientific statement is to provide a comprehensive review of the new evidence linking PM exposure with cardiovascular disease, with a specific focus on highlighting the clinical implications for researchers and healthcare providers. The writing group also sought to provide expert consensus opinions on many aspects of the current state of science and updated suggestions for areas of future research. On the basis of the findings of this review, several new conclusions were reached, including the following: Exposure to PM <2.5 &mgr;m in diameter (PM2.5) over a few hours to weeks can trigger cardiovascular disease–related mortality and nonfatal events; longer-term exposure (eg, a few years) increases the risk for cardiovascular mortality to an even greater extent than exposures over a few days and reduces life expectancy within more highly exposed segments of the population by several months to a few years; reductions in PM levels are associated with decreases in cardiovascular mortality within a time frame as short as a few years; and many credible pathological mechanisms have been elucidated that lend biological plausibility to these findings. It is the opinion of the writing group that the overall evidence is consistent with a causal relationship between PM2.5 exposure and cardiovascular morbidity and mortality. This body of evidence has grown and been strengthened substantially since the first American Heart Association scientific statement was published. Finally, PM2.5 exposure is deemed a modifiable factor that contributes to cardiovascular morbidity and mortality.

Air pollution and cardiovascular disease: A statement for healthcare professionals from the expert panel on population and prevention science of the American Heart Association

Air pollution is a heterogeneous, complex mixture of gases, liquids, and particulate matter. Epidemiological studies have demonstrated a consistent increased risk for cardiovascular events in relation to both short- and long-term exposure to present-day concentrations of ambient particulate matter. Several plausible mechanistic pathways have been described, including enhanced coagulation/thrombosis, a propensity for arrhythmias, acute arterial vasoconstriction, systemic inflammatory responses, and the chronic promotion of atherosclerosis. The purpose of this statement is to provide healthcare professionals and regulatory agencies with a comprehensive review of the literature on air pollution and cardiovascular disease. In addition, the implications of these findings in relation to public health and regulatory policies are addressed. Practical recommendations for healthcare providers and their patients are outlined. In the final section, suggestions for future research are made to address a number of remaining scientific questions.

Increased Particulate Air Pollution and the Triggering of Myocardial Infarction

Background—Elevated concentrations of ambient particulate air pollution have been associated with increased hospital admissions for cardiovascular disease. Whether high concentrations of ambient particles can trigger the onset of acute myocardial infarction (MI), however, remains unknown. Methods and Results—We interviewed 772 patients with MI in the greater Boston area between January 1995 and May 1996 as part of the Determinants of Myocardial Infarction Onset Study. Hourly concentrations of particle mass <2.5 &mgr;m (PM2.5), carbon black, and gaseous air pollutants were measured. A case-crossover approach was used to analyze the data for evidence of triggering. The risk of MI onset increased in association with elevated concentrations of fine particles in the previous 2-hour period. In addition, a delayed response associated with 24-hour average exposure 1 day before the onset of symptoms was observed. Multivariate analyses considering both time windows jointly revealed an estimated odds ratio of 1.48 associated with an increase of 25 &mgr;g/m3 PM2.5 during a 2-hour period before the onset and an odds ratio of 1.69 for an increase of 20 &mgr;g/m3 PM2.5 in the 24-hour period 1 day before the onset (95% CIs 1.09, 2.02 and 1.13, 2.34, respectively). Conclusions—The present study suggests that elevated concentrations of fine particles in the air may transiently elevate the risk of MIs within a few hours and 1 day after exposure. Further studies in other locations are needed to clarify the importance of this potentially preventable trigger of MI.

Triggering of acute myocardial infarction by heavy physical exertion. Protection against triggering by regular exertion. Determinants of Myocardial Infarction Onset Study Investigators

BACKGROUND Despite anecdotal evidence suggesting that heavy physical exertion can trigger the onset of acute myocardial infarction, there have been no controlled studies of the risk of myocardial infarction during and after heavy exertion, the length of time between heavy exertion and the onset of symptoms (induction time), and whether the risk can be modified by regular physical exertion. To address these questions, we collected data from patients with confirmed myocardial infarction on their activities one hour before the onset of myocardial infarction and during control periods. METHODS Interviews with 1228 patients conducted an average of four days after myocardial infarction provided data on their usual annual frequency of physical activity and the time, type, and intensity of physical exertion in the 26 hours before the onset of myocardial infarction. We compared the observed frequency of heavy exertion (6 or more metabolic equivalents) with the expected values using two types of self-matched analyses based on a new case-crossover study design. The low frequency of heavy exertion during the control periods was validated by data from a population-based control group of 218 subjects. RESULTS Of the patients, 4.4 percent reported heavy exertion within one hour before the onset of myocardial infarction. The estimated relative risk of myocardial infarction in the hour after heavy physical exertion, as compared with less strenuous physical exertion or none, was 5.9 (95 percent confidence interval, 4.6 to 7.7), Among people who usually exercised less than one, one to two, three to four, or five or more times per week, the respective relative risks were 107 (95 percent confidence interval, 67 to 171), 19.4 (9.9 to 38.1), 8.6 (3.6 to 20.5), and 2.4 (1.5 to 3.7). Thus, increasing levels of habitual physical activity were associated with progressively lower relative risks. The induction time from heavy exertion to the onset of myocardial infarction was less than one hour, and symptoms usually began during the activity. CONCLUSIONS Heavy physical exertion can trigger the onset of acute myocardial infarction, particularly in people who are habitually sedentary. Improved understanding of the mechanisms by which heavy physical exertion triggers the onset of myocardial infarction and the manner in which regular exertion protects against it would facilitate the design of new preventive approaches.

Triggering of Acute Myocardial Infarction Onset by Episodes of Anger

BACKGROUND Many anecdotes and several uncontrolled case series have suggested that emotionally stressful events, and more specifically, anger, immediately precede and appear to trigger the onset of acute myocardial infarction. However, controlled studies to determine the relative risk of myocardial infarction after episodes of anger have not been reported. METHODS AND RESULTS We interviewed 1623 patients (501 women) an average of 4 days after myocardial infarction. The interview identified the time, place, and quality of myocardial infarction pain and other symptoms, the estimated usual frequency of anger during the previous year, and the intensity and timing of anger and other potentially triggering factors during the 26 hours before the onset of myocardial infarction. Anger was assessed by the onset anger scale, a single-item, seven-level, self-report scale, and the state anger subscale of the State-Trait Personality Inventory. Occurrence of anger in the 2 hours preceding the onset of myocardial infarction was compared with its expected frequency using two types of self-matched control data based on the case-crossover study design. The onset anger scale identified 39 patients with episodes of anger in the 2 hours before the onset of myocardial infarction. The relative risk of myocardial infarction in the 2 hours after an episode of anger was 2.3 (95% confidence interval, 1.7 to 3.2). The state anger subscale corroborated these findings with a relative risk of 1.9 (95% confidence interval, 1.3 to 2.7). Regular users of aspirin had a significantly lower relative risk (1.4; 95% confidence interval, 0.8 to 2.6) than nonusers (2.9; 95% confidence interval, 2.0 to 4.1) (P < .05). CONCLUSIONS Episodes of anger are capable of triggering the onset of acute myocardial infarction, but aspirin may reduce this risk. A better understanding of the manner in which external events trigger the onset of acute cardiovascular events may lead to innovative preventive strategies aimed at severing the link between these external stressors and their pathological consequences.

Sexual Function in Men Older Than 50 Years of Age: Results from the Health Professionals Follow-up Study

Context We know little about age-specific prevalence and correlates of sexual function among U.S. men. Contribution Among 31 742 male health care professionals, 74% younger than 59 years of age and 10% older than 80 years of age rated sexual function as good or very good. Moderate or big problems were identified by 12%, 22%, and 30% of those younger than 59 years of age, 60 to 69 years of age, and older than 69 years of age, respectively. Increasing age after age 50 years, inactive lifestyle, obesity, and multiple medical conditions and medications were associated with worse function. Implications These cross-sectional analyses show that sexual dysfunction is common, particularly among older men. The Editors For decades, diminished sexual function has been taken for granted as a natural part of the aging process. The strong relationship between erectile dysfunction and aging has been demonstrated in observational studies dating back to 1948 (1). For many men, decreases in sexual function are also associated with decrements in quality of life (2-4). With recent advances in treatment and with the growing body of epidemiologic research on the cause of the problem, many cases of erectile dysfunction can be treated and some possibly prevented. The aim of our study was to describe the prevalence and correlates of male sexual function in the four decades of life after 50 years of age. We also estimated the effect of previous erectile function, comorbid conditions, and modifiable risk factors in an effort to examine the causes of age-related erectile dysfunction. Methods Participants The Health Professionals Follow-up Study (HPFS) is a cohort of male dentists, optometrists, osteopaths, podiatrists, pharmacists, and veterinarians in the United States who responded to a mailed questionnaire in 1986. The response rate for the original survey was 32%. Follow-up questionnaires are mailed every 2 years (5). At the time of the 2000 questionnaire, 43 235 men, age 53 to 90 years, were alive and actively participating in the study. We mailed the questionnaire up to four times to nonrespondents and received 34 282 responses (response rate, 79%). Erectile dysfunction among patients with prostate cancer is commonly associated with therapy rather than with the systemic causes thought to account for most other cases of the disorder. Therefore, we excluded from the primary analyses men who reported a prostate cancer diagnosis, which was later confirmed through medical record review, at any date before the assessment of erectile function (n = 2540). Men with missing responses to the primary outcome variable were also excluded from the relative risk analysis (n = 2514). These men tended to be older and have higher prevalence of chronic disease than participants in the present study. Outcome Measures Sexual Function and Dysfunction In 2000, participants were asked to rate their ability in the previous 3 months, without treatment, to have and maintain an erection adequate for intercourse. Response options included very poor, poor, fair, good, and very good. Men with poor or very poor ability were considered to have erectile dysfunction, the primary outcome in these analyses. Additional measures of sexual function, such as desire, ability to reach orgasm, and usual quality of erections, are items modified from the University of California, Los Angeles (UCLA), Prostate Cancer Index (6, 7). In 2000, participants were not queried about the frequency of or opportunities for intercourse; psychosocial function; partner discord; or heterosexual, homosexual, or bisexual preferences. Age and Other Independent Variables Age during the month when the 2000 questionnaire was returned was calculated from the date of birth ascertained on the 1986 baseline questionnaire. In age-adjusted analyses, 5-year age categories were used. Every 2 years, participants were asked to report their smoking status and the average number of cigarettes smoked per day in the previous year. Men who did not smoke before 1986 and did not report smoking during follow-up were considered never-smokers. Men who reported smoking in the past but were not smoking at the time of the 2000 questionnaire were considered past smokers. Men who reported smoking on the 2000 questionnaire were considered current smokers. Because alcohol intake is assessed every 4 years (8), our most recent measure was taken from the 1998 questionnaire. Men reported average consumption of beer, wine, and spirits in the previous year. Response categories ranged from never to six or more servings per day. One serving was equivalent to one glass, can, or bottle of beer; one 4-oz glass of wine; or one measure of spirits. Alcohol content per serving was estimated as 12.8 g for beer, 11.0 g for wine, and 14.0 g for spirits. We calculated intake for each beverage type and summed all values to determine the average total daily alcohol consumption. We assessed physical activity on the 2000 questionnaire using a previously validated questionnaire (9). This instrument consists of 10 questions about the average time per week that participants spent doing the following activities in the previous year: walking to work or for exercise; jogging; running; bicycling; lap swimming; tennis; squash or racquetball; calisthenics or rowing, stair, or ski machine; weightlifting or weight machine; and heavy outdoor work. Response options included 13 categories ranging from none to 40 or more hours per week. We also asked the number of stair flights climbed daily and usual walking pace. Metabolic equivalents (METs) were assigned for each type of exercise, and MET hours per week were calculated on the basis of the amount of time participants spent doing each activity. Television viewing time was measured in a similar format. With the same 13 response options, participants were asked to report the amount of time they spent sitting or lying down while watching television. Body size was assessed by using self-reported height and weight (10). Body mass index was calculated as kg/m2. On each HPFS questionnaire, participants are asked to report health conditions diagnosed by a physician in the previous 2 years, as well as current medications. Self-reported hypertension and hypercholesterolemia were not further verified, but reports of diabetes, heart disease, stroke, prostate cancer, and other cancer were verified through supplemental questionnaires, medical records, or both. Current medications were measured by using drug class categories, such as -blockers and tricyclic antidepressants. In each category, the two most popular drugs were listed as examples. We also asked about supplemental use of dehydroepiandrosterone and St. Johns wort. As mentioned earlier, we asked participants to rate their ability to have and maintain erections without treatment. Therefore, we did not control for erectile dysfunction treatments in these analyses. Statistical Analysis We conducted a cross-sectional analysis of erectile dysfunction. Age-stratified frequencies of demographic characteristics, health behaviors, chronic conditions, and many aspects of sexual function are presented. We also present prevalence rates of erectile dysfunction in 5-year age strata. Using the MantelHaenszel statistic to estimate adjusted relative risks (11), we examined the association of erectile dysfunction with age, health behaviors, and comorbid conditions. Unlike logistic regression, the MantelHaenszel procedure estimates the relative risk directly and does not require the rare-disease assumption for the odds ratio to estimate the relative risk. Compatible tests for trend of ordered categorical variables were conducted by using the median values of each variable category. Role of the Funding Sources The National Institutes of Health provided funding for HPFS general follow-up. Pfizer, Inc., provided funding for the examination of causes of sexual function. One of the coauthors, Dr. Glasser, is employed by Pfizer, Inc. The first and last authors made all final decisions regarding the design, conduct, and reporting of the study and the decision to submit the manuscript for publication. Results This group of 31 742 health professionals with no known history of prostate cancer ranged in age from 53 to 90 years at the time of the 2000 questionnaire. As shown in Table 1, men in the oldest age group were less likely to be married, smoke, or engage in physical activity and were more likely than younger men to have comorbid conditions. Table 2 provides unadjusted frequencies and mean ratings for many aspects of sexual function. There is a clear, linear, age-related decline for nearly all of the variables assessed. For instance, mean overall sexual function was equivalent to good (mean overall score, 4.1) in the youngest men and declined steadily to poor (mean overall score, 1.8) in the oldest group. When men with prostate cancer were excluded, the age-standardized prevalence of erectile dysfunction in the previous 3 months was 33%. Table 1. Demographic Characteristics, Health Behaviors, and Comorbid Conditions for 31 742 Health Professionals without Prostate Cancer by Age Group Table 2. Sexual Function in 31 742 Health Professionals without Prostate Cancer by Age Group Fewer than 2% of men who reported erection problems said that their first difficulty occurred before age 40 years, and only 4% said that it occurred between age 40 to 49 years. After age 50 years, the percentage of men who had experienced their first problems with erection increased sharply26% in men age 50 to 59 years and 40% in men age 60 to 69 years. The prevalence of erectile dysfunction increased with increasing age. Participants with prostate cancer (2109 for whom data on erectile dysfunction were available) were excluded from all other analyses; however, prevalence of erectile dysfunction in these participants is presented in the Figure because of the stark contrast to the prevalence in other men. Men who remained

Exercise and Acute Cardiovascular Events: Placing the Risks Into Perspective: A Scientific Statement From the American Heart Association Council on Nutrition, Physical Activity, and Metabolism and the Council on Clinical Cardiology

Habitual physical activity reduces coronary heart disease events, but vigorous activity can also acutely and transiently increase the risk of sudden cardiac death and acute myocardial infarction in susceptible persons. This scientific statement discusses the potential cardiovascular complications of exercise, their pathological substrate, and their incidence and suggests strategies to reduce these complications. Exercise-associated acute cardiac events generally occur in individuals with structural cardiac disease. Hereditary or congenital cardiovascular abnormalities are predominantly responsible for cardiac events among young individuals, whereas atherosclerotic disease is primarily responsible for these events in adults. The absolute rate of exercise-related sudden cardiac death varies with the prevalence of disease in the study population. The incidence of both acute myocardial infarction and sudden death is greatest in the habitually least physically active individuals. No strategies have been adequately studied to evaluate their ability to reduce exercise-related acute cardiovascular events. Maintaining physical fitness through regular physical activity may help to reduce events because a disproportionate number of events occur in least physically active subjects performing unaccustomed physical activity. Other strategies, such as screening patients before participation in exercise, excluding high-risk patients from certain activities, promptly evaluating possible prodromal symptoms, training fitness personnel for emergencies, and encouraging patients to avoid high-risk activities, appear prudent but have not been systematically evaluated.

Air pollution and incidence of cardiac arrhythmia.

Air pollution episodes have been associated with increased cardiovascular hospital admissions and mortality in time-series studies. We tested the hypothesis that patients with implanted cardioverter defibrillators experience potentially life-threatening arrhythmias after such air pollution episodes. We compared defibrillator discharge interventions among 100 patients with such devices in eastern Massachusetts, according to variations in concentrations of particulate matter, black carbon, and gaseous air pollutants that were measured daily for the years 1995 through 1997. A 26-ppb increase in nitrogen dioxide was associated with increased defibrillator interventions 2 days later (odds ratio = 1.8; 95% confidence interval = 1.1-2.9). Patients with ten or more interventions experienced increased arrhythmias in association with nitrogen dioxide, carbon monoxide, black carbon, and fine particle mass. These results suggest that elevated levels air pollutants are associated with potentially life-threatening arrhythmia leading to therapeutic interventions by an implanted cardioverter defibrillator.

Meta-Analysis of the Morning Excess of Acute Myocardial Infarction and Sudden Cardiac Death

To evaluate the impact of elimination of the morning peak of cardiovascular events, we performed a meta-analysis of studies of circadian variation of myocardial infarction and sudden cardiac death. The impact would be significant because approximately 1 of every 11 acute myocardial infarctions and 1 of every 15 sudden cardiac deaths are attributable to the morning excess incidence.

Triggering Myocardial Infarction by Marijuana

Background—Marijuana use in the age group prone to coronary artery disease is higher than it was in the past. Smoking marijuana is known to have hemodynamic consequences, including a dose-dependent increase in heart rate, supine hypertension, and postural hypotension; however, whether it can trigger the onset of myocardial infarction is unknown. Methods and Results—In the Determinants of Myocardial Infarction Onset Study, we interviewed 3882 patients (1258 women) with acute myocardial infarction an average of 4 days after infarction onset. We used the case-crossover study design to compare the reported use of marijuana in the hour preceding symptoms of myocardial infarction onset to its expected frequency using self-matched control data. Of the 3882 patients, 124 (3.2%) reported smoking marijuana in the prior year, 37 within 24 hours and 9 within 1 hour of myocardial infarction symptoms. Compared with nonusers, marijuana users were more likely to be men (94% versus 67%, P <0.001), current cigarette smokers (68% versus 32%, P <0.001), and obese (43% versus 32%, P =0.008). They were less likely to have a history of angina (12% versus 25%, P <0.001) or hypertension (30% versus 44%, P =0.002). The risk of myocardial infarction onset was elevated 4.8 times over baseline (95% confidence interval, 2.4 to 9.5) in the 60 minutes after marijuana use. The elevated risk rapidly decreased thereafter. Conclusions—Smoking marijuana is a rare trigger of acute myocardial infarction. Understanding the mechanism through which marijuana causes infarction may provide insight into the triggering of myocardial infarction by this and other, more common stressors.