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 microm (PM(2.5)), 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 microg/m(3) PM(2.5) during a 2-hour period before the onset and an odds ratio of 1.69 for an increase of 20 microg/m(3) PM(2.5) 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 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.

Association of blood pressure with fibrinolytic potential in the Framingham offspring population.

BACKGROUND: Hypertension is an established risk factor for acute coronary events. Because fibrinolytic and hemostatic factors are also associated with cardiovascular disease, we examined the relations of systolic and diastolic blood pressures (SBP and DBP) to levels of plasminogen activator inhibitor antigen, tissue plasminogen activator antigen, fibrinogen, factor VII, von Willebrand factor, fibrinogen, and plasma viscosity in subjects of the Framingham Offspring Study. METHODS AND RESULTS: We studied 1193 men and 1459 women after the exclusion of subjects with known cardiovascular disease and those receiving anticoagulant or antihypertensive therapy. Linear regression models were used to evaluate SBP and DBP as predictors of fibrinolytic and hemostatic factor levels in separate sex models, with adjustment for age, body mass index, smoking, diabetes, total cholesterol, HDL, triglycerides, alcohol intake, and estrogen use (in women). In both sexes, levels of plasminogen activator inhibitor and tissue plasminogen activator antigen were positively related to SBP and DBP (P<0.001). Plasma viscosity was positively related to SBP (P=0.008) and DBP (P=0.001) in women only. There was no association between SBP or DBP and fibrinogen, factor VII, or von Willebrand factor in either sex. CONCLUSIONS: These data suggest that impaired fibrinolysis may play an important role in the pathogenesis of cardiovascular disease in hypertensive patients.

Platelet glycoprotein IIIa Pl(a) polymorphism, fibrinogen, and platelet aggregability: The Framingham Heart Study.

BACKGROUND: Recent data suggest that the Pl(A2) allele of the platelet glycoprotein IIIa receptor may be a genetic risk factor for cardiovascular disease. We previously reported that the Pl(A2) allele was associated with increased platelet aggregability, as indicated by lower epinephrine threshold concentrations. Paradoxically, however, it has been reported that Pl(A2)-positive platelets have reduced fibrinogen binding. Because fibrinogen mediates platelet aggregability, we hypothesized that plasma fibrinogen levels may interact with Pl(A) genotype in modulating platelet aggregability. Methods and Results-- Glycoprotein IIIa Pl(A) genotype, fibrinogen level, and platelet aggregability were ascertained in 1340 subjects enrolled into the Framingham Offspring Study. Platelet aggregability was evaluated by the Born method. Higher fibrinogen levels were associated with increased epinephrine-induced aggregation (P=0.002) and a trend for ADP-induced aggregation (P=0.07). The fibrinogen effect was genotype specific, however, in that the increase in platelet aggregability with higher fibrinogen was present for the Pl(A1/A1) genotype (P=0.0005 and P=0.03 for epinephrine- and ADP-induced aggregation, respectively) but not for the Pl(A2)-positive genotype (P>0.90). CONCLUSION: Higher fibrinogen levels were associated with increased platelet aggregability. However, the association between fibrinogen and platelet aggregability was genotype specific. This interaction may be responsible for the conflicting findings regarding Pl(A) genotype and platelet aggregability. Further study of this gene-environment interaction may provide insight into cardiovascular disease risk.

Association of fibrinogen with cardiovascular risk factors and cardiovascular disease in the Framingham Offspring Population.

BACKGROUND: Fibrinogen has been identified as an independent risk factor for cardiovascular disease and associated with traditional cardiovascular risk factors. Also, the role of elevated fibrinogen in thrombosis suggests that it may be on the causal pathway for certain risk factors to exert their effect. These associations remain incompletely characterized. Moreover, the optimal fibrinogen assay for risk stratification is uncertain. METHODS AND RESULTS: In 2632 subjects from cycle 5 of the Framingham Offspring Population, fibrinogen levels were determined with a newly developed immunoprecipitation test (American Biogenetic Sciences) and the functional Clauss method. With the immunoprecipitation method, there were significant linear trends across fibrinogen tertiles (P:<0.001) for age, body mass index, smoking, diabetes mellitus, total cholesterol, HDL cholesterol, and triglycerides in men and women. The Clauss method had significant results (P:<0.030), except for triglycerides in men. Fibrinogen levels were higher for those with compared with those without cardiovascular disease. After covariate adjustment, fibrinogen remained significantly higher in those with cardiovascular disease with the use of the immunoprecipitation test (P:=0.035 and P:=0.018 for men and women, respectively) but not with the Clauss method. CONCLUSIONS: Fibrinogen was associated with traditional cardiovascular risk factors. Elevation of fibrinogen may provide a mechanism for risk factors to exert their effect. Also, fibrinogen levels were higher among subjects with cardiovascular disease compared with those without disease. The immunoprecipitation test showed a stronger association with cardiovascular disease than the Clauss method, suggesting that it may be a useful screening tool to identify individuals at increased thrombotic risk.

Sudden cardiac death, genes, and arrhythmogenesis : consideration of new population and mechanistic approaches from a national heart, lung, and blood institute workshop, part I.

Malignant ventricular arrhythmias are the leading mechanism of death in patients with acute and chronic cardiac pathologies. The extent to which inherited mutations and polymorphic variation in genes determining arrhythmogenic mechanisms affect these patients remains unknown, but based on recent population studies, this risk appears significant, deserving much greater investigation. This report summarizes a National Heart, Lung, and Blood Institute workshop that considered sources of genetic variation that may contribute to sudden cardiac death in common cardiac diseases. Evidence on arrhythmogenic mechanisms in recent population studies suggests a significant portion of the risk of sudden cardiac death in such broad populations may be unrelated to traditional risk factors for predisposing conditions such as atherosclerosis, hypertension, and diabetes and instead may involve unrecognized genetic and environmental interactions that influence arrhythmic susceptibility more directly. Additional population and genetic studies directed at discovering the sources of inherited molecular risk that are most directly linked to arrhythmia initiation and propagation, in addition to studies on previously well-described risk factors, would appear to have considerable potential for reducing premature cardiovascular mortality.

Sudden cardiac death, genes, and arrhythmogenesis: consideration of new population and mechanistic approaches from a National Heart, Lung, and Blood Institute workshop, Part II.

This is Part II of a 2-part article dealing with malignant ventricular arrhythmias, which are the leading mechanism of death in common cardiac diseases. Genetic population studies directed at discovering common proximal sources of inherited molecular risk most directly linked to arrhythmia initiation and propagation would appear to have considerable potential in helping reduce cardiovascular mortality.

Alcohol consumption and hemostatic factors: analysis of the Framingham Offspring cohort.

BACKGROUND: Moderate alcohol consumers have lower rates of cardiovascular disease than abstainers. One proposed mechanism is a beneficial effect on hemostatic parameters, but previous studies have provided conflicting results. METHODS AND RESULTS: We measured levels of fibrinogen, plasma viscosity, von Willebrand factor, factor VII, plasminogen activator inhibitor antigen-1, and tissue plasminogen activator antigen in a cross-sectional analysis of 3223 adults free of cardiovascular disease enrolled in the Framingham Offspring Study. We assessed their alcohol consumption with a standardized questionnaire. Light-to-moderate alcohol consumption was associated with lower levels of fibrinogen, plasma viscosity, von Willebrand factor, and factor VII. This association was most pronounced for consumers of 3 to 7 drinks weekly for viscosity and 7 to 21 drinks weekly for the other hemostatic measures. Alcohol intake of 7 to 21 drinks weekly or more was associated with impaired fibrinolytic potential, reflected by higher levels of plasminogen activator inhibitor antigen-1 and tissue plasminogen activator antigen. Wine drinkers had lower plasminogen activator inhibitor antigen-1 levels than other drinkers, particularly at 3 to 21 drinks weekly, but beverage type did not otherwise consistently affect the results. CONCLUSIONS: Light-to-moderate alcohol consumption is associated with lower levels of coagulatory factors, but higher intake is associated with impaired fibrinolytic potential. These findings are consistent with the hypothesis that a balance between hemostatic and fibrinolytic activity may contribute to the complex relation of alcohol use with coronary heart disease.

Coronary artery thrombosis: historical aspects.

There is intense scientific interest in the possibility that the acute administration of a fibrinolytic agent might be of benefit to patients with acute myocardial infarction. This hypothesis, which will soon be tested in a major trial by the National Heart, Lung, and Blood Institute, has emerged from a confluence of advances in three areas: increased knowledge about the role of thrombosis in myocardial infarction, the development of fibrinolytic agents and the recognition that ischemic myocardial tissue might be salvaged from necrosis by timely reperfusion. Examination of the manner in which these areas of knowledge developed and interacted not only illuminates our path to this specific therapeutic possibility, but also demonstrates the indirect and stuttering manner in which important new ideas often evolve.

Triggers, acute risk factors and vulnerable plaques: the lexicon of a new frontier.

A neglected area of cardiovascular research--study of the mechanisms of acute disease onset-is receiving increased attention. The new interest is based on the undisputed findings that onset of myocardial infarction and sudden cardiac death are more likely soon after awakening, indicating that activities of the patient frequently trigger the diseases. Triggering may occur when stressors produce hemodynamic, vasoconstrictive and prothrombotic forces--acute risk factors--that, in the presence of a vulnerable atherosclerotic plaque, cause plaque disruption and thrombosis. Triggering research may clarify mechanisms and suggest measures to sever the linkage between a potential trigger and its pathologic consequence.

Similar results of percutaneous transluminal coronary angioplasty for women and men with postmyocardial infarction ischemia.

OBJECTIVES: The purpose of this study was to determine whether there are gender differences in the outcome of percutaneous transluminal coronary angioplasty performed for postmyocardial infarction ischemia. BACKGROUND: Although women have a higher mortality rate after myocardial infarction than that of men, they are less frequently referred for coronary angioplasty (and coronary artery bypass graft surgery) than are men, possibly because of expectations of a worse procedural outcome. METHODS: We analyzed the morbidity and mortality at coronary angioplasty and during a mean follow-up period of 34.4 months for women and 34.2 months for men in 505 consecutive patients (164 women and 341 men) with postmyocardial infarction ischemia between 1981 and 1989. RESULTS: Compared with men, women had similar procedural success rates (89.6% and 91.2%, respectively), need for coronary artery bypass surgery (3.7% and 2.6%) and mortality rates at coronary angioplasty (0.6% and 0.9%). During the follow-up period, there were no significant gender differences in the requirement for coronary artery bypass surgery (3.6% and 4%), repeat angioplasty (18.7% and 17.3%), reinfarction (5.8% and 6%) and death (3.6% and 3.7%) or the combined end points of all four events (26.6% and 26.6%). Women had significantly more recurrent angina than did men (54% vs. 42.5%, p < 0.01), even though the extent of coronary artery disease and frequency of incomplete revascularization were similar in men and women. CONCLUSIONS: The procedural outcome of coronary angioplasty for postmyocardial infarction ischemia is similar in women and men. Long-term follow-up is also similar except that women experience an increased incidence of recurrent angina, an outcome also reported after bypass surgery. Therefore, concerns over the safety of coronary angioplasty in women should not adversely influence decisions concerning referral of women for coronary angioplasty after myocardial infarction complicated by ischemia.

A perspective on the potential problems with aspirin as an antithrombotic agent: a comparison of studies in an animal model with clinical trials.

Aspirin is the most widely prescribed agent to reduce the platelet-mediated contributions to atherosclerosis, coronary thrombosis and restenosis after angioplasty. While aspirin treatment has led to significant reductions in morbidity and mortality in many clinical trials, there are several scenarios in which aspirin may fail to provide a full antithrombotic benefit. The cyclic flow model of experimental coronary thrombosis suggests that elevations of plasma catecholamines, high shear forces acting on the platelets in the stenosed lumen and the presence of multiple, input stimuli can activate platelets through different mechanisms that may lead to thrombosis despite aspirin therapy. Aspirin therapy is limited because it only blocks some of the input stimuli, leaving aspirin-independent pathways through which coronary thrombosis can be precipitated. These include thrombin and thrombogenic arterial wall substrates such as tissue factor. New agents that block the adenosine diphosphate (ADP) receptor, or regulate platelet free cytosolic calcium, such as direct nitric oxide donors, may be more potent overall than aspirin. Agents that block the platelet integrin GPIIb-IIIa receptor inhibit the binding of fibrinogen to platelets regardless of which input stimuli activate the platelet and, thus, as demonstrated in the cyclic flow model, would be much more potent than aspirin as an antithrombotic agent. The cyclic flow model has been useful in predicting which agents are likely to be of benefit in clinical trials.

Modifiers of timing and possible triggers of acute myocardial infarction in the Thrombolysis in Myocardial Infarction Phase II (TIMI II) Study Group.

OBJECTIVES: The aim of this study was to provide insight into the mechanism of acute myocardial infarction by determining the modifiers of timing and possible triggers of onset of infarction. BACKGROUND: A higher frequency of onset of acute myocardial infarction has been reported in the morning with a peak in the 1st 3 h after awakening. This observation suggests that the onset of infarction may be triggered by activity in the morning and at other times of the day. METHODS: The clinical history of the 3,339 patients entered into the Thrombolysis in Myocardial Infarction phase II study was analyzed to determine characteristics predicting a higher frequency of infarction between 6 AM and noon, and onset of infarction during exertion. RESULTS: A higher proportion (34.4%) of infarctions began in the morning (6 AM to noon) compared with other times of the day. Characteristics independently predicting a higher frequency between 6 AM to noon were no beta-adrenergic blocking agent use in the 24 h before infarction, no discomfort other than the index pain in the preceding 48 h, occurrence of the infarction on a weekday and no history of current smoking. In 18.7% of patients, infarction occurred during moderate or marked physical activity. Independent predictors of exertion-related infarction included male gender, no history of current smoking, white race, no use of calcium channel blocking agents or nitrates in the preceding 24 h, the absence of either chest pain at rest in the 3 weeks before infarction or any pain in the preceding 48 h, the absence of new onset angina and the presence of exertional pain in the preceding 3 weeks. Compared with patients whose infarction occurred at rest or during mild activity, those with exertion-related infarction had fewer coronary vessels with > or = 60% stenosis (p = 0.002) and were more likely to have an occluded infarct-related vessel after thrombolytic therapy (p = 0.01). CONCLUSIONS: Further study of the timing and activity at onset of infarction may provide insight into the pathophysiologic mechanisms causing acute myocardial infarction and provide clues to preventive measures.

The in-hospital development of cardiogenic shock after myocardial infarction: incidence, predictors of occurrence, outcome and prognostic factors. The MILIS Study Group.

The incidence, outcome and predictors of the in-hospital development of cardiogenic shock and its prognostic significance were analyzed in 845 patients presenting with acute myocardial infarction. Cardiogenic shock developed after hospitalization in 60 patients (7.1%). In half of these patients, cardiogenic shock developed at least 24 h after hospital admission. The in-hospital mortality rate was greater than 15 times higher for patients with cardiogenic shock than for patients without shock (65.0% versus 4.3%, respectively, p less than 0.001). Enzymatic evidence of infarct extension occurred in 23.3% of the patients with shock compared with 7.4% of those without shock (p less than 0.0001). Multivariate analysis indicated that independent predictors for the in-hospital development of cardiogenic shock were age greater than 65 years (p = 0.007), left ventricular ejection fraction on hospital admission less than 35% (p = 0.007), large infarct as estimated from serial enzyme determinations (that is, peak creatine kinase-MB isoenzyme greater than 160 IU/liter (p = 0.008), history of diabetes mellitus (p = 0.011) and previous myocardial infarction (p = 0.012). Patients with three, four or five of these risk factors had a 17.9%, 33.7% or 54.4% probability, respectively, of developing cardiogenic shock after hospital admission. Left ventricular function, as reflected by left ventricular ejection fraction (p = 0.04) and severity of left ventricular wall motion abnormality (p = 0.04), was the most important determinant of in-hospital mortality in the patients with cardiogenic shock.

Sequential combination thrombolytic therapy for acute myocardial infarction: results of the Pro-Urokinase and t-PA Enhancement of Thrombolysis (PATENT) Trial.

OBJECTIVES: The present study was designed to test the efficacy and safety of a sequential combination of recombinant tissue-type plasminogen activator (rt-PA) and pro-urokinase in patients with acute myocardial infarction. BACKGROUND: Efforts continue to identify a thrombolytic regimen that induces rapid, complete and sustained coronary artery patency in acute myocardial infarction. The two endogenous plasminogen activators rt-PA and pro-urokinase have been shown experimentally to induce fibrinolysis by sequential and complementary mechanisms. As a result, certain combinations of these activators have been found to be synergistic in vitro and in vivo. METHODS: In a multicenter observational study with core facilities for angiographic and laboratory analysis, 101 patients with acute myocardial infarction were enrolled and given a low dose bolus of rt-PA (5 to 10 mg) followed by a 90-min infusion of pro-urokinase (40 mg/h). All patients received intravenous heparin and oral aspirin. Coronary angiography was performed in all patients at 90 min. RESULTS: Angiography at 90 min showed the infarct-related artery to be patent (Thrombolysis in Myocardial Infarction [TIMI] grade 2 or 3 flow) in 77% of patients, and 60% achieved TIMI grade 3 flow. At one center, angiography was repeated at 24 h to detect a possible reocclusion. All 28 patients with a patent infarct-related artery at 90 min had patency at 24 h (82% achieved TIMI grade 3 flow). Treatment was well tolerated, with bleeding complications essentially confined to arterial puncture site hematomas. There was only one in-hospital death. CONCLUSIONS: A sequential combination of low dose rt-PA and reduced-dose pro-urokinase produced a high TIMI 3 patency rate, was well tolerated and was associated with a low reocclusion rate.

Prevention by nifedipine of cold pressor-induced decrease in left ventricular ejection fraction.

To examine the effects of nifedipine on changes in ventricular function produced by cold, the cold pressor test was administered to eight patients with angiographically documented coronary artery disease. Radionuclide ventriculograms were obtained at baseline and during the cold pressor stimulus both before and after administration of nifedipine, 10 mg buccally; thus, four serial radionuclide ventriculograms were obtained per patient. The cold pressor stimulus did not produce any significant difference in the mean (+/- standard deviation) peak rate-pressure product during the control or nifedipine test (10,900 +/- 3,390 versus 10,600 +/- 3,700). However, the increase in systolic blood pressure (p = 0.05) and the peak systolic blood pressure achieved (p less than 0.001) were greater during the control (134 +/- 19 to 160 +/- 25 mm Hg) than during the nifedipine (125 +/- 18 to 145 +/- 21 mm Hg) cold pressor test. The mean global left ventricular ejection fraction decreased during the control cold pressor test from a baseline value of 0.60 +/- 0.08 to 0.52 +/- 0.08 (p = 0.004). After nifedipine, this variable did not change during the repeat cold pressor test (0.63 +/- 0.09) compared with the repeat baseline value (0.63 +/- 0.11). Therefore, the difference in left ventricular ejection fraction response during control versus nifedipine cold pressor testing was highly significant (p less than 0.0001). In patients with obstructive coronary artery disease, nifedipine abolished the decrease in left ventricular ejection fraction observed during the control cold pressor test and may be of value to protect patients from cold-induced left ventricular dysfunction. The mechanism may be a combination of coronary artery vasodilation and systolic unloading of the left ventricle.

Effects of therapy with nifedipine GITS or atenolol on mental stress-induced ischemic left ventricular dysfunction.

OBJECTIVES: We sought to determine the effect of nifedipine gastrointestinal therapeutic system (GITS) or atenolol on ischemic left ventricular dysfunction induced by mental stress. BACKGROUND: The efficacy of conventional antianginal therapy in preventing myocardial ischemia induced by mental stress is unknown. METHODS: Nifedipine GITS, atenolol and placebo were administered to 15 subjects with stable angina in a double-blind crossover trial. Subjects underwent a series of mental stressors at the end of each treatment. Radionuclide ventriculography was performed at baseline and at peak mental stress. Other measured variables included time to ischemia on exercise treadmill testing, ischemia on 48-h ambulatory electrocardiogram (ECG) monitoring, and resting and mental stress-induced levels of plasma catecholamines, tissue plasminogen activator antigen, plasminogen activator inhibitor-1 and platelet aggregability. RESULTS: Mental stress resulted in a significant increase in plasma epinephrine and norepinephrine levels during each treatment phase. Atenolol therapy was associated with lower baseline and postmental stress rate-pressure product compared with nifedipine or placebo. Therapy with either nifedipine GITS or atenolol prevented the development of wall-motion abnormalities and the decline in regional ejection fraction (EF) in the segment with the largest deterioration in wall motion during placebo therapy. Both medications prevented the decrease in global EF in subjects who demonstrated at least a 5% fall in global EF on placebo therapy. No therapy exerted a statistically significant benefit on exercise performance or frequency of ischemia during ambulatory ECG monitoring. CONCLUSIONS: Both nifedipine GITS and atenolol are effective at preventing mental stress-induced wall-motion abnormalities, although the mechanisms may be different.

The effect of diabetes mellitus on prognosis and serial left ventricular function after acute myocardial infarction: contribution of both coronary disease and diastolic left ventricular dysfunction to the adverse prognosis. The MILIS Study Group.

Patients with diabetes mellitus experience a more adverse outcome after acute myocardial infarction compared with nondiabetic patients, although the mechanisms responsible for these findings are not clear. From the Multicenter Investigation of the Limitation of Infarct Size (MILIS) study, the course of acute infarction in 85 diabetic patients was compared with that in 415 nondiabetic patients, all of whom had serial assessments of left ventricular function. The diabetic patients experienced a more complicated in-hospital and postdischarge course than did the nondiabetic patients, including a higher incidence of postinfarction angina, infarct extension, heart failure and death, despite the development of a smaller infarct size and similar levels of left ventricular ejection fraction. Although diabetic patients had a worse profile of cardiovascular risk factors at the time of the index infarction, the increased incidence of adverse outcomes among them persisted despite adjustment for these baseline imbalances. Diabetic women had a poor baseline risk profile compared with the other groups categorized by gender and diabetic status, and experienced an almost twofold increase in cardiac mortality despite development of the smallest infarct size during the index event. The duration of diabetes and the use of insulin at the time of the index infarction were associated with a better in-hospital mortality rate, but the duration of diabetes did not exert a major influence on the outcome of the diabetic patients. The factors responsible for the increased incidence of adverse outcomes among diabetic patients may be related to an acceleration of the atherosclerotic process, diastolic left ventricular dysfunction associated with diabetic cardiomyopathy or other unidentified unfavorable processes.

Prognostic implications of an early peak in plasma MB creatine kinase in patients with acute myocardial infarction.

To determine the prognostic implications of an early peak in plasma MB creatine kinase (MB CK) in patients with acute myocardial infarction who were not treated with an acute intervention, 342 patients with myocardial infarction confirmed by MB CK were retrospectively studied. The patients were classified into those with an early peak MB CK (less than or equal to 15 hours after the onset of symptoms, n = 84) and those with a late peak MB CK (greater than 15 hours after the onset of symptoms, n = 258). Patients with an early peak MB CK were slightly older, were more frequently female and had a higher incidence of prior myocardial infarction, congestive heart failure and arrhythmias compared with patients with a late peak MB CK. Patients with an early peak MB CK more frequently presented with ST segment depression (23 versus 11%, p less than 0.01), with anterior location of ischemia or infarction (71 versus 52%, p less than 0.01) and with a lower mean left ventricular ejection fraction (41.4 versus 47.4%, p less than 0.01). Despite more extensive left ventricular dysfunction at initial presentation, patients with an early peak MB CK had a smaller mean MB CK infarct size index (12.6 versus 18.9 g-Eq/m2, p less than 0.01), with no difference in the incidence of in-hospital complications, including death. The early left ventricular dysfunction improved in the patients with an early peak MB CK, evidenced by a 4.5% increase in ejection fraction from admission to 10 days after infarction, whereas the ejection fraction did not improve in patients with a late peak MB CK. However, the patients with an early peaking MB CK had myocardium in jeopardy as reflected by a higher incidence of ST segment depression and a decrement in the global left ventricular ejection fraction with exercise. The 4 year life table estimate for the rate of recurrent myocardial infarction after hospital discharge was higher in patients with an early peak MB CK (33 versus 22%, p less than 0.05), with an even more striking difference in the 4 year estimate for the rate of fatal recurrent infarction (20 versus 8%, p less than 0.001). The 4 year mortality estimate was markedly higher in hospital survivors with an early peak MB CK than in those with a late peak (47 versus 19%, p less than 0.0001) and, even after adjustment for differences in baseline characteristics, the residual excess mortality in those with an early peak was still significant (p less than 0.02).(ABSTRACT TRUNCATED AT 400 WORDS)