Elizabeth Mostofsky

Modeling the Association Between Particle Constituents of Air Pollution and Health Outcomes

There is increasing interest in evaluating the association between specific fine-particle (particles with aerodynamic diameters less than 2.5 µm; PM2.5) constituents and adverse health outcomes rather than focusing solely on the impact of total PM2.5. Because PM2.5 may be related to both constituent concentration and health outcomes, constituents that are more strongly correlated with PM2.5 may appear more closely related to adverse health outcomes than other constituents even if they are not inherently more toxic. Therefore, it is important to properly account for potential confounding by PM2.5 in these analyses. Usually, confounding is due to a factor that is distinct from the exposure and outcome. However, because constituents are a component of PM2.5, standard covariate adjustment is not appropriate. Similar considerations apply to source-apportioned concentrations and studies assessing either short-term or long-term impacts of constituents. Using data on 18 constituents and data from 1,060 patients admitted to a Boston medical center with ischemic stroke in 2003-2008, the authors illustrate several options for modeling the association between constituents and health outcomes that account for the impact of PM2.5. Although the different methods yield results with different interpretations, the relative rankings of the association between constituents and ischemic stroke were fairly consistent across models.

Habitual Coffee Consumption and Risk of Heart Failure: A Dose-Response Meta-Analysis

Background— There have been discrepant findings on the association between coffee consumption and risk of incident heart failure. Methods and Results— We conducted a systematic review and a dose-response meta-analysis of prospective studies that assessed the relationship between habitual coffee consumption and the risk of heart failure. We searched electronic databases (MEDLINE, Embase, and CINAHL) from January 1966 through December 2011, with the use of a standardized protocol. Eligible studies were prospective cohort studies that examined the association of coffee consumption with incident heart failure. Five independent prospective studies of coffee consumption and heart failure risk, including 6522 heart failure events and 140 220 participants, were included in the meta-analysis. We observed a statistically significant J-shaped relationship between coffee and heart failure. Compared with no consumption, the strongest inverse association was seen for 4 servings/day and a potentially higher risk at higher levels of consumption. There was no evidence that the relationship between coffee and heart failure risk varied by sex or by baseline history of myocardial infarction or diabetes. Conclusions— Moderate coffee consumption is inversely associated with risk of heart failure, with the largest inverse association observed for consumption of 4 servings per day.Background—There have been discrepant findings on the association between coffee consumption and risk of incident heart failure. Methods and Results—We conducted a systematic review and a dose-response meta-analysis of prospective studies that assessed the relationship between habitual coffee consumption and the risk of heart failure. We searched electronic databases (MEDLINE, Embase, and CINAHL) from January 1966 through December 2011, with the use of a standardized protocol. Eligible studies were prospective cohort studies that examined the association of coffee consumption with incident heart failure. Five independent prospective studies of coffee consumption and heart failure risk, including 6522 heart failure events and 140 220 participants, were included in the meta-analysis. We observed a statistically significant J-shaped relationship between coffee and heart failure. Compared with no consumption, the strongest inverse association was seen for 4 servings/day and a potentially higher risk at higher levels of consumption. There was no evidence that the relationship between coffee and heart failure risk varied by sex or by baseline history of myocardial infarction or diabetes. Conclusions—Moderate coffee consumption is inversely associated with risk of heart failure, with the largest inverse association observed for consumption of 4 servings per day.

Physical, Psychological and Chemical Triggers of Acute Cardiovascular Events Preventive Strategies

In addition to the impact of long-term stressors such as sedentary lifestyle and long-term exposure to high levels of air pollution, many studies have shown that there is an increased risk of acute cardiovascular events immediately after behavioral, psychosocial, and environmental triggers.1–8 After the landmark study documenting the increased rates of myocardial infarction (MI) related to the 1981 earthquake in Athens9 and the description of the circadian variation in the incidence of MI by Muller et al,10 various studies documented the frequency of potential triggers in the period immediately preceding MI onset. Although the observational studies examining physical, psychological, and chemical triggers of acute cardiovascular events are not without limitations, studies continue to show that short-term exposures appear to play a role in the occurrence of cardiovascular events. These triggers have been discussed in previous reviews,1–8 with a general consensus that different preventive strategies may be appropriate for particular triggers. The purpose of this review is to bring together the evidence of the association between several triggers and cardiovascular outcomes and to discuss the common underlying pathophysiology of these triggers. Rather than leading to slowly progressive atherosclerosis, triggers represent the final step in the pathophysiological process leading to cardiovascular outcomes among susceptible individuals, such as those with vulnerable atherosclerotic plaque, chronic atherosclerotic disease, disorders of the cardiac conduction system, and microvascular disease. In the presence of a vulnerable atherosclerotic plaque, chemical, physical, and psychological stressors may trigger transient vasoconstrictive and prothrombotic effects that ultimately cause plaque disruption and thrombosis. Even in the absence of an occlusive thrombus, triggers may lower the threshold for cardiac electric instability and increase cardiac sympathetic activation via centrally mediated release of catecholamines, thereby evoking primary ventricular fibrillation and sudden cardiac death.11 Figure 1 depicts several potential …

Risk of Acute Myocardial Infarction After the Death of a Significant Person in One's Life The Determinants of Myocardial Infarction Onset Study

Background— Acute psychological stress is associated with an abrupt increase in the risk of cardiovascular events. Intense grief in the days after the death of a significant person may trigger the onset of acute myocardial infarction (MI), but this relationship has not been systematically studied. Methods and Results— We conducted a case-crossover analysis of 1985 participants from the multicenter Determinants of Myocardial Infarction Onset Study interviewed during index hospitalization for an acute MI between 1989 and 1994. We compared the observed number of deaths in the days preceding MI symptom onset with its expected frequency based on each patients control information, defined as the occurrence of deaths in the period from 1 to 6 months before infarction. Among the 1985 subjects, 270 (13.6%) experienced the loss of a significant person in the prior 6 months, including 19 within 1 day of their MI. The incidence rate of acute MI onset was elevated 21.1-fold (95% confidence interval, 13.1–34.1) within 24 hours of the death of a significant person and declined steadily on each subsequent day. The absolute risk of MI within 1 week of the death of a significant person is 1 excess MI per 1394 exposed individuals at low (5%) 10-year MI risk and 1 per 320 among individuals at high (20%) 10-year risk. Conclusions— Grief over the death of a significant person was associated with an acutely increased risk of MI in the subsequent days. The impact may be greatest among individuals at high cardiovascular risk.Background— Acute psychological stress is associated with an abrupt increase in the risk of cardiovascular events. Intense grief in the days after the death of a significant person may trigger the onset of acute myocardial infarction (MI), but this relationship has not been systematically studied. Methods and Results— We conducted a case-crossover analysis of 1985 participants from the multicenter Determinants of Myocardial Infarction Onset Study interviewed during index hospitalization for an acute MI between 1989 and 1994. We compared the observed number of deaths in the days preceding MI symptom onset with its expected frequency based on each patients control information, defined as the occurrence of deaths in the period from 1 to 6 months before infarction. Among the 1985 subjects, 270 (13.6%) experienced the loss of a significant person in the prior 6 months, including 19 within 1 day of their MI. The incidence rate of acute MI onset was elevated 21.1-fold (95% confidence interval, 13.1–34.1) within 24 hours of the death of a significant person and declined steadily on each subsequent day. The absolute risk of MI within 1 week of the death of a significant person is 1 excess MI per 1394 exposed individuals at low (5%) 10-year MI risk and 1 per 320 among individuals at high (20%) 10-year risk. Conclusions— Grief over the death of a significant person was associated with an acutely increased risk of MI in the subsequent days. The impact may be greatest among individuals at high cardiovascular risk. # Clinical Perspective {#article-title-27}

Risk of Acute Myocardial Infarction After the Death of a Significant Person in One's Life

Background— Acute psychological stress is associated with an abrupt increase in the risk of cardiovascular events. Intense grief in the days after the death of a significant person may trigger the onset of acute myocardial infarction (MI), but this relationship has not been systematically studied. Methods and Results— We conducted a case-crossover analysis of 1985 participants from the multicenter Determinants of Myocardial Infarction Onset Study interviewed during index hospitalization for an acute MI between 1989 and 1994. We compared the observed number of deaths in the days preceding MI symptom onset with its expected frequency based on each patients control information, defined as the occurrence of deaths in the period from 1 to 6 months before infarction. Among the 1985 subjects, 270 (13.6%) experienced the loss of a significant person in the prior 6 months, including 19 within 1 day of their MI. The incidence rate of acute MI onset was elevated 21.1-fold (95% confidence interval, 13.1–34.1) within 24 hours of the death of a significant person and declined steadily on each subsequent day. The absolute risk of MI within 1 week of the death of a significant person is 1 excess MI per 1394 exposed individuals at low (5%) 10-year MI risk and 1 per 320 among individuals at high (20%) 10-year risk. Conclusions— Grief over the death of a significant person was associated with an acutely increased risk of MI in the subsequent days. The impact may be greatest among individuals at high cardiovascular risk.Background— Acute psychological stress is associated with an abrupt increase in the risk of cardiovascular events. Intense grief in the days after the death of a significant person may trigger the onset of acute myocardial infarction (MI), but this relationship has not been systematically studied. Methods and Results— We conducted a case-crossover analysis of 1985 participants from the multicenter Determinants of Myocardial Infarction Onset Study interviewed during index hospitalization for an acute MI between 1989 and 1994. We compared the observed number of deaths in the days preceding MI symptom onset with its expected frequency based on each patients control information, defined as the occurrence of deaths in the period from 1 to 6 months before infarction. Among the 1985 subjects, 270 (13.6%) experienced the loss of a significant person in the prior 6 months, including 19 within 1 day of their MI. The incidence rate of acute MI onset was elevated 21.1-fold (95% confidence interval, 13.1–34.1) within 24 hours of the death of a significant person and declined steadily on each subsequent day. The absolute risk of MI within 1 week of the death of a significant person is 1 excess MI per 1394 exposed individuals at low (5%) 10-year MI risk and 1 per 320 among individuals at high (20%) 10-year risk. Conclusions— Grief over the death of a significant person was associated with an acutely increased risk of MI in the subsequent days. The impact may be greatest among individuals at high cardiovascular risk. # Clinical Perspective {#article-title-27}

Outbursts of anger as a trigger of acute cardiovascular events: a systematic review and meta-analysis

AIM Short-term psychological stress is associated with an immediate physiological response and may be associated with a transiently higher risk of cardiovascular events. The aim of this study was to determine whether brief episodes of anger trigger the onset of acute myocardial infarction (MI), acute coronary syndromes (ACS), ischaemic and haemorrhagic stroke, and ventricular arrhythmia. METHODS AND RESULTS We performed a systematic review of studies evaluating whether outbursts of anger are associated with the short-term risk of heart attacks, strokes, and disturbances in cardiac rhythm that occur in everyday life. We performed a literature search of the CINAHL, Embase, PubMed, and PsycINFO databases from January 1966 to June 2013 and reviewed the reference lists of retrieved articles and included meeting abstracts and unpublished results from experts in the field. Incidence rate ratios and 95% confidence intervals were calculated with inverse-variance-weighted random-effect models. The systematic review included nine independent case-crossover studies of anger outbursts and MI/ACS (four studies), ischaemic stroke (two studies), ruptured intracranial aneurysm (one study), and ventricular arrhythmia (two studies). There was evidence of substantial heterogeneity between the studies (I(2) = 92.5% for MI/ACS and 89.8% for ischaemic stroke). Despite the heterogeneity, all studies found that, compared with other times, there was a higher rate of cardiovascular events in the 2h following outbursts of anger. CONCLUSION There is a higher risk of cardiovascular events shortly after outbursts of anger.

Chocolate Intake and Incidence of Heart Failure: A Population-Based, Prospective Study of Middle-Aged and Elderly Women

Background—Randomized clinical trials have shown that chocolate intake reduces systolic and diastolic blood pressure, and observational studies have found an inverse association between chocolate intake and cardiovascular disease. The aim of this study was to investigate the association between chocolate intake and incidence of heart failure (HF). Methods and Results—We conducted a prospective cohort study of 31 823 women aged 48 to 83 years without baseline diabetes or a history of HF or myocardial infarction who were participants in the Swedish Mammography Cohort. In addition to answering health and lifestyle questions, participants completed a food-frequency questionnaire. Women were followed from January 1, 1998, through December 31, 2006, for HF hospitalization or death through the Swedish inpatient and cause-of-death registers. Over 9 years of follow-up, 419 women were hospitalized for incident HF (n=379) or died of HF (n=40). Compared with no regular chocolate intake, the multivariable-adjusted rate ratio of HF was 0.74 (95% CI, 0.58 to 0.95) for women consuming 1 to 3 servings of chocolate per month, 0.68 (95% CI, 0.50 to 0.93) for those consuming 1 to 2 servings per week, 1.09 (95% CI, 0.74 to 1.62) for those consuming 3 to 6 servings per week, and 1.23 (95% CI, 0.73 to 2.08) for those consuming ≥1 servings per day (P=0.0005 for quadratic trend). Conclusions—In this population, moderate habitual chocolate intake was associated with a lower rate of HF hospitalization or death, but the protective association was not observed with intake of ≥1 servings per day.Background— Randomized clinical trials have shown that chocolate intake reduces systolic and diastolic blood pressure, and observational studies have found an inverse association between chocolate intake and cardiovascular disease. The aim of this study was to investigate the association between chocolate intake and incidence of heart failure (HF). Methods and Results— We conducted a prospective cohort study of 31 823 women aged 48 to 83 years without baseline diabetes or a history of HF or myocardial infarction who were participants in the Swedish Mammography Cohort. In addition to answering health and lifestyle questions, participants completed a food-frequency questionnaire. Women were followed from January 1, 1998, through December 31, 2006, for HF hospitalization or death through the Swedish inpatient and cause-of-death registers. Over 9 years of follow-up, 419 women were hospitalized for incident HF (n=379) or died of HF (n=40). Compared with no regular chocolate intake, the multivariable-adjusted rate ratio of HF was 0.74 (95% CI, 0.58 to 0.95) for women consuming 1 to 3 servings of chocolate per month, 0.68 (95% CI, 0.50 to 0.93) for those consuming 1 to 2 servings per week, 1.09 (95% CI, 0.74 to 1.62) for those consuming 3 to 6 servings per week, and 1.23 (95% CI, 0.73 to 2.08) for those consuming ≥1 servings per day ( P =0.0005 for quadratic trend). Conclusions— In this population, moderate habitual chocolate intake was associated with a lower rate of HF hospitalization or death, but the protective association was not observed with intake of ≥1 servings per day.

Coffee and acute ischemic stroke onset The Stroke Onset Study

Objective: Prior research suggests an acutely elevated risk of myocardial infarction and sudden cardiac death in the hour after coffee intake. However, the risk of ischemic stroke associated with transient exposure to coffee remains unclear. We hypothesized that caffeine intake is associated with a transiently increased risk of ischemic stroke. Methods: In this multicenter case-crossover study, we interviewed 390 subjects (209 men, 181 women) between January 2001 and November 2006 a median of 3 days after acute ischemic stroke. Each subjects coffee consumption in the hour before stroke symptoms was compared with his or her usual frequency of consumption in the prior year. Results: Of the 390 subjects, 304 (78%) drank coffee in the prior year, 232 within 24 hours and 35 within 1 hour of stroke onset. The relative risk (RR) of stroke in the hour after consuming coffee was 2.0 (95% confidence interval [CI], 1.4–2.8; p < 0.001). There was no apparent increase in risk in the hour following consumption of caffeinated tea (RR = 0.9, 95% CI 0.4–2.0; p = 0.85) or cola (RR = 1.0, 95% CI 0.4–2.4; p = 0.95). The association between ischemic stroke in the hour after coffee consumption was only apparent among those consuming ≤1 cup per day but not for patients who consumed coffee more regularly (p for trend = 0.002). Relative risks remained similar when the sample was restricted to those who were not simultaneously exposed to other potential triggers and the results remained significant after stratifying by time of day. Conclusion: Coffee consumption transiently increases the risk of ischemic stroke onset, particularly among infrequent drinkers.

Alcohol and Acute Ischemic Stroke Onset The Stroke Onset Study

Background and Purpose— Previous research suggests that regular heavy alcohol consumption increases the risk for ischemic stroke, whereas frequent light to moderate alcohol intake may decrease the risk. However, the risk of ischemic stroke associated with transient exposure to alcohol remains unclear. In this study, we used a case–crossover approach to test the hypothesis that alcohol consumption affects the acute risk of ischemic stroke, to determine the length of time between alcohol intake and the onset of symptoms (induction time), and to examine whether the risk varies by the type of alcohol. Methods— In this multicenter study, we interviewed 390 patients (209 men, 181 women) between January 2001 and November 2006 (median 3 days after stroke). Alcohol consumption in the hour before stroke symptoms was compared with its expected frequency based on the usual frequency of alcohol consumption over the prior year. Results— Of the 390 patients, 248 (64%) reported alcohol consumption in the prior year, 104 within 24 hours and 14 within 1 hour of stroke onset. The relative risk of stroke in the hour after consuming alcohol was 2.3 (95% CI, 1.4 to 4.0; P=0.002). The relative risks were similar for different types of alcoholic beverages and when the sample was restricted to those who were not simultaneously exposed to other potential triggers. Conclusions— The risk of stroke onset is transiently elevated in the hour after alcohol ingestion.

Alcohol and Immediate Risk of Cardiovascular Events: A Systematic Review and Dose-Response Meta-Analysis

Background— Although considerable research describes the cardiovascular effects of habitual moderate and heavy alcohol consumption, the immediate risks following alcohol intake have not been well characterized. Based on its physiological effects, alcohol may have markedly different effects on immediate and long-term risk. Methods and Results— We searched CINAHL, Embase, and PubMed from inception to March 12, 2015, supplemented with manual screening for observational studies assessing the association between alcohol intake and cardiovascular events in the following hours and days. We calculated pooled relative risks and 95% confidence intervals for the association between alcohol intake and myocardial infarction, ischemic stroke, and hemorrhagic stroke using DerSimonian and Laird random-effects models to model any alcohol intake or dose–response relationships of alcohol intake and cardiovascular events. Among 1056 citations and 37 full-text articles reviewed, 23 studies (29 457 participants) were included. Moderate alcohol consumption was associated with an immediately higher cardiovascular risk that was attenuated after 24 hours, and even protective for myocardial infarction and hemorrhagic stroke (≈2–4 drinks: relative risk=30% lower risk) and protective against ischemic stroke within 1 week (≈6 drinks: 19% lower risk). In contrast, heavy alcohol drinking was associated with higher cardiovascular risk in the following day (≈6–9 drinks: relative risk=1.3–2.3) and week (≈19–30 drinks: relative risk=2.25–6.2). Conclusions— There appears to be a consistent finding of an immediately higher cardiovascular risk following any alcohol consumption, but, by 24 hours, only heavy alcohol intake conferred continued risk.