Malcolm Maclure

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.

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.

Triggering of Myocardial Infarction by Cocaine

BACKGROUND Cocaine has been implicated as a trigger of acute myocardial infarction in patients with and those without underlying coronary atherosclerosis. However, the magnitude of the increase in risk of acute myocardial infarction immediately after cocaine use remains unknown. METHODS AND RESULTS In the Determinants of Myocardial Infarction Onset Study, we interviewed 3946 patients (1282 women) with acute myocardial infarction an average of 4 days after infarction onset. Data were collected on the use of cocaine and other potential triggers of myocardial infarction. We compared the reported use of cocaine in the hour preceding the onset of myocardial infarction symptoms with its expected frequency by using self-matched control data based on the case-crossover study design. Of the 3946 patients interviewed, 38 (1%) reported cocaine use in the prior year and 9 reported use within the 60 minutes preceding the onset of infarction symptoms. Compared with nonusers, cocaine users were more likely to be male (87% vs 67%, P=0.01), current cigarette smokers (84% vs 32%, P<0.001), younger (44+/-8 vs 61+/-13 years, P<0.001), and minority group members (63% vs 11%, P<0.001). The risk of myocardial infarction onset was elevated 23.7 times over baseline (95% CI 8.5 to 66.3) in the 60 minutes after cocaine use. The elevated risk rapidly decreased thereafter. CONCLUSIONS Cocaine use is associated with a large abrupt and transient increase in the risk of acute myocardial infarction in patients who are otherwise at relatively low risk. This finding suggests that studying the pathophysiological changes produced by cocaine may provide insights into the mechanisms by which myocardial infarction is triggered by other stressors.

Increased onset of sudden cardiac death in the first three hours after awakening.

A circadian variation of sudden cardiac death has been documented, but its relation to individual time of awakening and possible triggering events has not been studied in the general population. By monitoring of mortality records in 4 cities and towns in Massachusetts, 148 potential cases of sudden cardiac death were identified. In 94 cases, the informants listed on the death certificates were contacted, the diagnosis of sudden cardiac death was established, and a telephone interview was completed within a mean of 19 days (range 8 to 28) after the death. The time of day of all 94 cases of sudden cardiac death (mean age 61 +/- 9 years, 74% men) demonstrated a circadian variation (p less than 0.05) with a peak from 9:00 A.M. to 12:00 noon. An analysis of time of death adjusted for individual wake-times of the decedents demonstrated an increased onset of sudden cardiac death during the initial 3-hour interval after awakening with a relative risk of 2.6 (95% confidence interval 1.6, 4.2) compared with other times of the day. The increased risk of sudden cardiac death soon after awakening suggests specific triggering factors or mechanisms that are particularly likely to occur during this time. The narrowing of the time interval during which the risk of sudden cardiac death is increased should facilitate the study of possible pathogenetic mechanisms and triggering factors of the disease and may aid in the design of more effective preventive strategies.

Sudden cardiac death. Support for a role of triggering in causation.

Epidemiological studies have identified associations between time of day and risk of sudden cardiac death. The marked peak in the occurrence of sudden cardiac death after awakening suggests that the disease is triggered by changes that occur during this time period. Increased sympathetic stimulation is a likely cause of such triggering. In the light of the circadian variation of sudden cardiac death and the evidence linking physical activity or mental stress (both associated with activation of the sympathetic nervous system) to the disease, the role of potential triggering events should be investigated. Controlled studies are needed to determine the relative risk of activities that may trigger sudden cardiac death. Since such studies must rely on witnesses (or resuscitated patients), data quality must be closely scrutinized, and studies using case-control and case-crossover designs are needed. The epidemiological and pathophysiological data reviewed in the present article suggest a number of pathways through which activities may trigger sudden cardiac death. Different extrinsic stimuli may cause similar physiological changes that subsequently lead to acute pathological events, a decrease in the ventricular fibrillation threshold through a direct myocardial effect, or a harmful effect on the conduction system. Myocardial ischemia induced by plaque rupture and thrombosis may lead directly to myocardial electric instability. The presence of chronic structural abnormalities of the myocardial tissue or the conduction system may further lower the threshold for electric instability and ventricular fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)

Tea Consumption and Mortality After Acute Myocardial Infarction

Background—Some studies have suggested that tea consumption may be associated with lower mortality among individuals with cardiovascular disease, but the effects of tea consumption on mortality after acute myocardial infarction are unknown. Methods and Results—As part of the Determinants of Myocardial Infarction Onset Study, we performed a prospective cohort study of 1900 patients hospitalized with a confirmed acute myocardial infarction between 1989 and 1994, with a median follow-up of 3.8 years. Trained interviewers assessed self-reported usual weekly caffeinated tea consumption during the year before infarction with a standardized questionnaire. We compared long-term mortality according to tea consumption using Cox proportional hazards regression. Of the 1900 patients, 1019 consumed no tea (nondrinkers), 615 consumed <14 cups per week (moderate tea drinkers), and 266 consumed 14 or more cups per week (heavy tea drinkers). Compared with nondrinkers, age- and sex-adjusted mortality was lower among moderate tea drinkers (hazard ratio, 0.69; 95% CI, 0.53 to 0.89) and heavy tea drinkers (hazard ratio, 0.61; 95% CI, 0.42 to 0.86). Additional adjustment for clinical and sociodemographic characteristics did not appreciably alter this association (hazard ratio, 0.72; 95% CI, 0.55 to 0.94 for moderate tea drinkers; hazard ratio, 0.56; 95% CI, 0.37 to 0.84 for heavy tea drinkers). The association of tea and mortality was similar for total and cardiovascular mortality. Conclusions—Self-reported tea consumption in the year before acute myocardial infarction is associated with lower mortality after infarction.

Increasing levels of restriction in pharmacoepidemiologic database studies of elderly and comparison with randomized trial results

Background:The goal of restricting study populations is to make patients more homogeneous regarding potential confounding factors and treatment effects and thereby achieve less biased effect estimates. Objectives:This article describes increasing levels of restrictions for use in pharmacoepidemiology and examines to what extent they change rate ratio estimates and reduce bias in a study of statin treatment and 1-year mortality. Methods:The study cohort was drawn from a population of seniors age 65 years and older enrolled in both Medicare and the Pennsylvania Pharmaceutical Assistance Contract for the Elderly (PACE) between 1995 and 2002. We identified all users of statins during the study period and assessed the time until death within 1 year. The following progressive restrictions were applied: (1) study incident drug users only, (2) choose a comparison group most similar to the intervention group, (3) exclude patients with contraindications, (4) exclude patients with low adherence, and (5) restrict to specific high-risk/low-risk subgroups represented in randomized trails (RCTs). Results:The basic cohort comprised 122,406 statin users, who were on average 78 years old and predominantly white (93%) and showed an unadjusted rate ratio of 0.32 for statin users. When all 5 restrictions were applied (N = 11,673), the unadjusted rate ratio had increased to 0.72. Multivariable Cox regression adjusted rate ratios increased from 0.62 [95% confidence interval (CI), 0.58–0.66] to 0.79 (95% CI, 0.60–1.03). However, after the first 3 restrictions the effect size changed little. The final estimate is similar to that obtained as a pooled estimate of 3 pravastatin RCTs in patients age 65 years and older. We argue that restrictions 1 through 4 compromised generalizability little. Conclusions:In our example of a large database study, restricting to incident drug users, similar comparison groups, patients without contraindication, and to adherent patients was a practical strategy, which limited the effect of confounding, as these approaches yield results closer to those seen in RCTs.

A case-control study of diet and risk of renal adenocarcinoma.

We examined dietary and other risk factors for renal adenocarcinoma in a case-control study of 203 incident and 207 prevalent cases and 605 neighborhood controls. Using unconditional logistic regression to control selection biases identified in an adjunct study. we tound exposure odds ratios (OR) similar to those from other studies: 1.9 (with a 95% confidence interval (c1) from 0.8 to 4.4) for smoking 2 packs of cigarettes per day; 3.8 (95% CI: 0.78–18) for 3 or more packs per day; 1.7 (95% CI: 0.9–3.2) for women and 1.7 (95% CI: 1.1–2.8) for men in the highest quintile of relative weight (kg); 2.0 (95% C1: 1.3–3.1) for northeastern European ancestry; and 2.3(95% CI: 1.34.1) for history of kidney stones. Incident cases consumed more meats and fewer vegetables than controls: the age-sex-education-adlusted OR for average intake of 85 g (302) of beef per day was 3.4 (95% CI: 1.67.2). Inverse associations were seen for most vegetables. Dietary animal protein, animal fat, and saturated fat, with and without energy adlustment, were weakly associated with disease in unconditional and conditional logistic regressions. Priorhypotheses concerning intake of cholesterol, beta-carotene, preformed vitamin A, and cruciferous vegetables were n o t corrobo

Binge Drinking and Mortality After Acute Myocardial Infarction

Background— Moderate drinkers have a lower risk of mortality after myocardial infarction (MI). Although binge drinking has been associated with a higher risk of MI in some studies, its relation to prognosis after MI is uncertain. Methods and Results— In a prospective, inception cohort study conducted at 45 US hospitals, 1935 patients hospitalized with a confirmed MI between 1989 and 1994 underwent detailed personal interviews. Patients reported their usual frequency of binge drinking of beer, wine, and liquor, defined as intake of 3 or more drinks within 1 to 2 hours, and were followed up for mortality for a median of 3.8 years. Of 1919 eligible patients, 250 (94% men) reported binge drinking during the prior year, and a total of 318 patients died during follow-up. Binge drinkers had a 2-fold higher risk of mortality than drinkers who did not binge (hazard ratio, 2.0; 95% confidence interval, 1.3 to 3.0). A comparison of 192 binge drinkers and 192 other patients matched on propensity scores yielded a similar result. The association between binge drinking and total mortality tended to be similar among patients whose usual alcohol intake was light or heavier and for binge drinkers who consumed beer, wine, or liquor. Usual alcohol intake was inversely associated with mortality, but binge drinking completely attenuated this relation. Conclusions— Our results suggest that alcohol consumption may be linked to potential hazards among patients who survive acute MI. Although moderate intake has been associated with lower mortality, binge drinking, even among light drinkers, appears to be associated with 2-fold higher mortality.