Alcohol consumption is associated with a lower incidence of acute myocardial infarction: results from a large prospective population-based study in Norway.

AIMS: Compelling evidence suggests that light-to-moderate alcohol consumption is associated with a reduced risk of acute myocardial infarction (AMI), but several issues from previous studies remain to be addressed. The aim of this study was to investigate some of these key issues related to the association between alcohol consumption and AMI risk, including the strength and shape of the association in a low-drinking setting, the roles of quantity, frequency and beverage type, the importance of confounding by medical and psychiatric conditions, and the lack of prospective data on previous drinking. METHODS: A population-based prospective cohort study of 58 827 community-dwelling individuals followed for 11.6 years was conducted. We assessed the quantity and frequency of consumption of beer, wine and spirits at baseline in 1995-1997 and the frequency of alcohol intake approximately 10 years earlier. RESULTS: A total of 2966 study participants had an AMI during the follow-up period. Light-to-moderate alcohol consumption was inversely and linearly associated with AMI risk. After adjusting for major cardiovascular disease risk factors, the hazard ratio for a one-drink increment in daily consumption was 0.72 (95% confidence interval 0.62-0.86). Accounting for former drinking or comorbidities had almost no effect on the association. Frequency of alcohol consumption was more strongly associated with lower AMI risk than overall quantity consumed. CONCLUSIONS: Light-to-moderate alcohol consumption was linearly associated with a decreased risk of AMI in a population in which abstaining from alcohol is not socially stigmatized. Our results suggest that frequent alcohol consumption is most cardioprotective and that this association is not driven by misclassification of former drinkers.

Job strain predicts recurrent events after a first acute myocardial infarction: the Stockholm Heart Epidemiology Program.

OBJECTIVES: Studies investigating the prognostic role of job stress in coronary heart disease are sparse and have inconclusive findings. We aimed (i) to investigate whether job strain predicts recurrent events after acute myocardial infarction (AMI) and if so (ii) to determine behavioural and biological factors that contribute to the explanation of this association. DESIGN: Prospective study. SETTING: Ten emergency hospitals in the larger Stockholm area, Sweden. SUBJECTS: Non-fatal AMI cases from the Stockholm Heart Epidemiology Program case-control study who were employed and younger than 65 years at the time of their hospitalization (n = 676). RESULTS: During the 8.5 year follow-up, 155 patients experienced cardiac death or non-fatal AMI; totally 96 patients died, 52 of cardiac causes. After adjustment for potential confounders, patients with high job strain had an increased risk for the combination of cardiac death and non-fatal AMI relative to those with low job strain, the hazard ratio (HR) and the 95% confidence interval (CI) being 1.73 (1.06-2.83). Results were similar for cardiac [HR (95% CI): 2.81 (1.16-6.82)] and total mortality [HR (95% CI): 1.65 (0.91-2.98)]. We found no evidence for mediation from lifestyle, sleep, lipids, glucose, inflammatory and coagulation markers on the association between job strain and the combination of cardiac death and non-fatal AMI. CONCLUSIONS: Job strain was associated with poor long-term prognosis after a first myocardial infarction. Interventions focusing on reducing stressors at the workplace or on improving coping with work stress in cardiac patients might improve their survival post-AMI.

Chocolate consumption and mortality following a first acute myocardial infarction: the Stockholm Heart Epidemiology Program.

OBJECTIVES: To assess the long-term effects of chocolate consumption amongst patients with established coronary heart disease. DESIGN: In a population-based inception cohort study, we followed 1169 non-diabetic patients hospitalized with a confirmed first acute myocardial infarction (AMI) between 1992 and 1994 in Stockholm County, Sweden, as part of the Stockholm Heart Epidemiology Program. Participants self-reported usual chocolate consumption over the preceding 12 months with a standardized questionnaire distributed during hospitalization and underwent a health examination 3 months after discharge. Participants were followed for hospitalizations and mortality with national registries for 8 years. RESULTS: Chocolate consumption had a strong inverse association with cardiac mortality. When compared with those never eating chocolate, the multivariable-adjusted hazard ratios were 0.73 (95% confidence interval, 0.41-1.31), 0.56 (0.32-0.99) and 0.34 (0.17-0.70) for those consuming chocolate less than once per month, up to once per week and twice or more per week respectively. Chocolate consumption generally had an inverse but weak association with total mortality and nonfatal outcomes. In contrast, intake of other sweets was not associated with cardiac or total mortality. CONCLUSIONS: Chocolate consumption was associated with lower cardiac mortality in a dose dependent manner in patients free of diabetes surviving their first AMI. Although our findings support increasing evidence that chocolate is a rich source of beneficial bioactive compounds, confirmation of this strong inverse relationship from other observational studies or large-scale, long-term, controlled randomized trials is needed.

Effects of a stress management program on vital exhaustion and depression in women with coronary heart disease: a randomized controlled intervention study.

OBJECTIVES: Psychosocial factors, including depression and vital exhaustion (VE) are associated with adverse outcome in coronary heart disease (CHD). Women with CHD are poor responders to psychosocial treatment and knowledge regarding which treatment modality works in them is limited. This randomized controlled clinical study evaluated the effect of a 1-year stress management program, aimed at reducing symptoms of depression and VE in CHD women. DESIGN: Patients were 247 women, < or =75 years, recruited consecutively after a cardiac event and randomly assigned to either stress management (20 2-h sessions) and medical care by a cardiologist, or to obtaining usual health care as controls. Measurements at; baseline (6-8 weeks after randomization), 10 weeks (after 10 intervention sessions), 1 year (end of intervention) and 1-2 years follow-up. RESULTS: For VE, intention to treat analysis showed effects for time (P < 0.001) and time x treatment interaction (P = 0.005), reflecting that both groups improved over time, and that the decrease of VE was more pronounced in the intervention group. However, the level of VE was higher in the intervention group than amongst controls at baseline, 22.7 vs. 19.4 (P = 0.036) but it did not differ later. The change in depressive symptoms did not differ between the groups. CONCLUSIONS: CHD women attending our program experienced a more pronounced decrease in VE than controls. However, as they had higher baseline levels, due to regression towards the mean we cannot attribute the decrease in VE to the intervention. Whether the program has long-term beneficial effects needs to be evaluated.

Wine drinking is associated with increased heart rate variability in women with coronary heart disease.

OBJECTIVE: To test the hypothesis that alcohol consumption is positively related to heart rate variability (HRV) in women with coronary heart disease (CHD) and therefore that cardiac autonomic activity is potentially implicated in the mediation of the favourable effects of moderate drinking. DESIGN, SETTINGS, AND PATIENTS: Cross sectional study of female patients who survived hospitalisation for acute myocardial infarction or underwent a revascularisation procedure, percutaneous transluminal coronary angioplasty, or coronary artery bypass grafting. MAIN OUTCOME MEASURES: Ambulatory 24 hour ECG was recorded during normal activities. The mean of the standard deviations of all normal to normal intervals for all five minute segments of the entire recording (SDNNI) and the following frequency domain parameters were assessed: total power, high frequency power, low frequency power, and very low frequency power. A standardised questionnaire evaluated self reported consumption of individual alcoholic beverage types: beer, wine, and spirits. Other clinical characteristics, such as age, body mass index, smoking habits, history of diabetes mellitus, menopausal status, educational status, and treatment, were also assessed. RESULTS: Wine intake was associated with increased HRV in both time and frequency domains independently of other clinical covariates (for example, ln SDNNI was 3.89 among wine drinkers v 3.59 among wine non-drinkers in the multivariate model; p = 0.014). In contrast, consumption of beer and spirits and the total amount of alcohol consumed did not relate significantly to any of the HRV parameters. CONCLUSION: Intake of wine, but not of spirits or beer, is positively and independently associated with HRV in women with CHD. These results may contribute to the understanding of the complex relation between alcohol consumption and CHD.

Inflammatory markers and heart rate variability in women with coronary heart disease.

PURPOSE: Both heart rate variability (HRV) and inflammatory markers are carrying prognostic information in coronary heart disease (CHD), however, we know of no studies examining their relation in CHD. The aim of this study, therefore, was to assess the association between HRV and inflammatory activity, as reflected by the levels of interleukin-6 (IL-6), IL-1 receptor antagonist (IL-1ra) and C-reactive protein (CRP). SUBJECTS AND METHODS: Consecutive women patients who survived hospitalization for acute myocardial infarction, and/or underwent a percutaneous transluminal coronary angioplasty or a coronary artery bypass grafting were included and evaluated in a stable condition 1 year after the index events. An ambulatory 24-h ECG was recorded during normal activities. SDNN index (mean of the standard deviations of all normal to normal intervals for all 5-min segments of the entire recording) and the following frequency domain parameters were assessed: total power, high frequency (HF) power, low frequency (LF) power and very low frequency (VLF) power. Levels of high-sensitivity CRP were measured by nephelometry, IL-6 and IL-1ra concentrations were determined by enzyme immunoassay. RESULTS: Levels of IL-6 showed an inverse relation with HRV measures even after controlling for potential confounding factors. The P-values were 0.02, 0.04, 0.01, 0.03, 0.18 for the multivariate association with SDDN index, total power, VLF power, LF power and HF power respectively. In contrast, the inverse relationship between HRV measures and CRP or IL-1ra levels were weak and nonsignificant. Correlation coefficients for the relationship between IL-6 and HRV measures were both uni- and multivariately higher than for the relationship between HRV measures and any other factors evaluated in this study. CONCLUSION: Concentration of IL-6 showed a negative, independent association with HRV in women with CHD. Thus, increased inflammatory activity, as reflected by IL-6 levels, may represent a new auxiliary mechanism linking decreased HRV to poor prognosis in CHD.

Association between increased levels of reverse triiodothyronine and mortality after acute myocardial infarction.

PURPOSE: The thyroid hormone system may be downregulated temporarily in patients who are severely ill. This "euthyroid sick syndrome" may be an adaptive response to conserve energy. However, thyroid hormone also has beneficial effects on the cardiovascular system, such as improving cardiac function, reducing systemic vascular resistance, and lowering serum cholesterol levels. We investigated whether thyroid hormone levels obtained at the time of myocardial infarction are associated with subsequent mortality. PATIENTS AND METHODS: Serum levels of thyroid hormones (triiodothyronine [T3], reverse T3, free thyroxine [T4], and thyroid-stimulating hormone) were measured in 331 consecutive patients with acute myocardial infarction (mean age [+/- SD], 68 +/- 12 years), from samples obtained at the time of admission. RESULTS: Fifty-three patients (16%) died within 1 year. Ten percent (16 of 165) of patients with reverse T3 levels (an inactive metabolite) >0.41 nmol/L (the median value) died within the first week after myocardial infarction, compared with none of the 166 patients with lower levels (P <0.0004). After 1 year, the corresponding figures were 24% (40 of 165) versus 7.8% (13 of 166; P <0.0001). Reverse T3 levels >0.41 nmol/L were associated with an increased risk of 1-year mortality (hazard ratio = 3.0; 95% confidence interval: 1.4 to 6.3; P = 0.005), independent of age, previous myocardial infarction, prior angina, heart failure, serum creatinine level, and peak serum creatine kinase-MB fraction levels. CONCLUSION: Determination of reverse T3 levels may be a valuable and simple aid to improve identification of patients with myocardial infarction who are at high risk of subsequent mortality.

Growth hormone and insulin-like growth factor-1 in acute myocardial infarction.

BACKGROUND: Growth hormone therapy after myocardial infarction improves cardiac function and survival in animals. Beneficial effects in humans are reported from studies where patients with idiopathic dilated cardiomyopathy were treated with growth hormone. We have studied the role of the endogenous growth hormone system in myocardial infarction. METHODS AND RESULTS: Fifty-two consecutive patients with acute myocardial infarction were studied during the first 5 days and at follow-up 6 and 12 weeks later. The time from chest pain onset was used in the analyses. The mean growth hormone level within the first 6 h was nearly three times higher (1.1 +/- 0.2 microg. l(-1)) than on the third day (0.4 +/- 0.05 microg. l(-1), P < 0.0002). It remained higher in patients with higher levels of cardiac enzymes, impaired left ventricular function and intense inflammatory response. Insulin-like growth factor-1 (IGF-1) declined slowly but remained within the normal range throughout the whole study period. Patients who died within 2 years had higher levels of growth hormone and lower levels of IGF-1, indicating growth hormone resistance. Endogenous levels of growth hormone or IGF-1 did not correlate with improvement in left ventricular function at 6 weeks. CONCLUSIONS: The growth hormone axis is stimulated early in acute myocardial infarction, particularly in patients with more severe cardiac damage. Whether treatment with growth hormone can be beneficial for patients with heart failure after myocardial infarction remains to be investigated.

IL-6 and IL-1 receptor antagonist in stable angina pectoris and relation of IL-6 to clinical findings in acute myocardial infarction.

OBJECTIVES: To determine if increased inflammatory activity, as reflected by interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1ra) levels, is present in patients with stable angina pectoris and if IL-6 levels on admission to the coronary care unit in patients with acute myocardial infarction (AMI) are related to heart failure and fever response. SUBJECTS AND METHODS: We studied 28 patients with stable angina pectoris enrolled for coronary angiography, and compared them with sex- and age-matched controls. Thirty-four patients with AMI were studied and samples for determination of IL-6 levels were taken on admission within 36 h of onset of symptoms. IL-6 and IL-1ra were determined in serum by enzyme immunoassay. RESULTS: Levels of IL-6 and IL-1ra were higher in patients with stable angina pectoris than in controls (mean 4.6 +/- 3.6 vs. 3.0 +/- 2.9 ng L-1, P < 0.03, and 774 +/- 509 vs. 490 +/- 511 ng L-1, P < 0.01, respectively). IL-6 and IL-1ra levels were not related to angiographic findings. IL-6 levels were high in patients with AMI (38.9 +/- 75.6 ng L-1). Patients with prolonged fever (duration > 4 days) had higher IL-6 levels (94.7 +/- 138.2 vs. 21.7 +/- 29.7 ng L-1, P < 0.05). IL-6 levels were not related to heart failure. CONCLUSIONS: Our results indicate that increased inflammatory activity is present not only in acute coronary syndromes, but also in a chronic form of ischaemic heart disease, giving further evidence for a central role of inflammatory processes in coronary artery disease. With regard to AMI, we found increased inflammatory activity in patients with prolonged fever.

Outlook after acute myocardial infarction in the very elderly compared with that in patients aged 65 to 75 years.

Little is known concerning late outcome and prognostic factors after acute myocardial infarction in the very elderly (greater than 75 years of age). Accordingly, this study compared the clinical course and mortality rate for up to 1 year in a large multicenter data base that included 702 patients greater than 75 years of age (mean +/- SD 81 +/- 4 years), with a less elderly subset of 1,321 patients between 65 and 75 years of age (mean 70 +/- 3 years). The postdischarge 1 year cardiac mortality rate was 17.6% for those greater than 75 years of age compared with 12.0% for patients between 65 and 75 years of age (p less than 0.01). There were differences in the prevalence of several factors, including female gender, history of angina pectoris, history of congestive heart failure, smoking habits and incidence of congestive heart failure during hospitalization. Multivariate analyses of predictors of cardiac death in hospital survivors selected different factors as important in the two age subgroups; age was selected in the 65 to 75 year age group but was not an independent predictor in the very elderly. The survival curves beginning at day 10 for patients 65 to 75 and in those greater than 75 years old were similar for up to 90 days but diverged later. In the very elderly, 63% of late cardiac deaths were sudden or due to new myocardial infarction, similar to the causes of 67% of deaths in the younger age group.(ABSTRACT TRUNCATED AT 250 WORDS)

Early determination of serum lipids and apolipoproteins in acute myocardial infarction: possibility for immediate intervention.

Early identification of elevated cholesterol in patients with acute myocardial infarction (MI) is of interest as secondary prevention can then be initiated when patients are highly motivated. However, since the lipid pattern changes during acute MI, screening for lipid disturbances is often not performed until 6 months later. We prospectively studied lipid and apolipoprotein levels during acute MI and 3 and 6 months later in 123 consecutive acute MI patients, mean age 64 +/- 10 (SD) years, who were admitted within 24 h from onset of symptoms, mean delay 5.5 h. Blood was taken at admission to the Coronary Care Unit (CCU), the first morning in the CCU, at hospital discharge and at 3 and 6 months follow-up. Patients were fasted overnight except at admission, and no specific dietary advice was given. Total serum cholesterol, triglycerides, and apolipoprotein (apo) A-I concentrations did not differ significantly (1-3%) between CCU admission and the 3 and 6 months control. During the subsequent hospital period, lipid concentrations generally decreased and at discharge were 15-25% below those at 6 months follow-up (P less than 0.001). The highest correlations between immediate CCU determination and 6 months follow-up were obtained for cholesterol (r = +0.71) and apo B (r = +0.67). Thus, lipid levels obtained early at CCU admission in acute MI patients are representative of the patient's baseline levels which are in contrast to those registered later during hospital stay. This information could be used to identify patients for early intervention.

First myocardial infarction: age and ejection fraction identify a low-risk group.

This study examines patients with a first myocardial infarction (MI) (about 70% of the population, n = 2089), and identifies factors associated with 1-year cardiac mortality in patients discharged alive. With the use of multivarate analysis of variables observed at hospital discharge in patients with a first MI, age was the most important predictor, followed by left ventricular ejection fraction (LVEF) (determined in 56%) and other variables. Based on this finding, age subsets (less than or equal to 50, 51 to 70, greater than 70 years) were related to LVEF groups (less than or equal to 0.40, 0.41 to 0.50, greater than 0.50). Patients with a first MI who were less than 50 years of age with LVEF greater than 0.40 and patients between 51 and 70 years of age with LVEF greater than 0.50 had a very low risk for 1-year cardiac death, 1.2 +/- 1.1% (95% confidence interval). Such patients comprised 47% of individuals with a first MI having an LVEF determination. Mortality in the remaining patients less than 70 years was 7.4 +/- 3.5%. Mortality for patients greater than 70 years was high, 22.2 +/- 6.6%. Thus with LVEF as the only predischarge test, a sizable low risk group can be identified among patients with a first MI.

Influence on prognosis and morbidity of left ventricular ejection fraction with and without signs of left ventricular failure after acute myocardial infarction.

The left ventricular (LV) ejection fraction (EF) is known to be an independent predictor of late prognosis after acute myocardial infarction. Despite a previous report that early heart failure (evidenced only by advanced pulmonary rales in the hospital) can predict prognosis in the absence of severe depression of the LVEF at hospital discharge, the potentially strong influence of various measures of in-hospital heart failure on the predictive ability of LVEF has not been generally appreciated. Accordingly, in 972 patients with acute myocardial infarction the effect on late mortality of the presence or absence in-hospital of both clinical and radiographic signs of LV failure in subgroups of patients with normal, moderately or severely depressed LVEF was examined and measured close to hospital discharge. Patients were divided into 3 groups according to LVEF: group I LVEF less than or equal to 40, n = 265; group II LVEF 0.41 to 0.50, n = 241 and group III LVEF greater than or equal to 0.51, n = 466. When clinical signs of LV failure were present at any time during the coronary care unit period, the 1-year mortality rate after hospital discharge in groups I, II and III was 26, 19 and 8%, compared with 12% (p less than 0.01), 6% (p less than 0.01) and 3% (p less than 0.02), respectively, when signs of LV failure were absent.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of exercise training on spatial R-wave amplitude in patients with coronary artery disease.

To evaluate the influence of an exercise program on spatial and left precordial R-wave amplitude among patients with coronary artery disease, computerized electrocardiogram (ECG) data were acquired during maximal treadmill testing before and after 1 yr in 89 patients randomized to either exercise (n = 40) or control (n = 49) groups. Spatial and lateral R-wave amplitudes were derived from the orthogonal Frank (XYZ) lead system. The exercise group significantly increased maximal O2 consumption (0.17 l/min), whereas controls decreased significantly (0.12 l/min, P less than 0.01 between groups). No significant changes in electrocardiographic R-wave voltage measurements occurred within or between groups during the year. It is concluded that exercise training does not result in increases in R-wave voltage in patients with coronary artery disease.

Left ventricular volume during supine exercise: importance of myocardial scar in patients with coronary heart disease.

Existing studies suggest that exercise-induced ischemia produces an increase in left ventricular end-diastolic volume; however, all of these studies have included patients with previous myocardial infarction. To test whether the end-diastolic volume response to exercise is related to the extent of myocardial scar, the results of gated radionuclide supine exercise tests performed on 130 subjects were reviewed. The patient group comprised 130 subjects were reviewed. The patient group comprised 130 men aged 35 to 65 years (mean +/- SD 52 +/- 5) with documented coronary heart disease. The extent of myocardial ischemia and scar formation was assessed by stress electrocardiography and thallium-201 scintigraphy. Patients were classified into three groups on the basis of left ventricular end-diastolic volume response at peak exercise: group 1 (n = 72) had an increase of end-diastolic volume greater than 10%, group 2 (n = 41) had a change in end-diastolic volume less than 10% and group 3 (n = 17) had a decrease in end-diastolic volume greater than 10% (n = 17). At rest there was no significant difference among groups in heart rate, systolic blood pressure, end-diastolic (EDVrest) or end-systolic volumes or ejection fraction (p greater than 0.05); however, at peak exercise the end-systolic volume response was significantly greater for group 1 (p less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial perfusion changes following 1 year of exercise training assessed by thallium-201 circumferential count profiles.

The effect of exercise training on myocardial perfusion was assessed using initial and 1-year thallium-201 (Tl-201) exercise studies in 56 patients with stable coronary artery disease (CAD). Subjects had been randomized into a trained group participating in supervised exercise three times per week and a control group. Indices (non-dimensional units) based on computer-analyzed circumferential count profile from nine regions of the heart, assessed in three projections, were used to eliminate observer bias and more accurately quantitate Tl-201 distribution and 4-hour washout. There was serial improvement of the global distribution count profiles in 21 of 27 (77.8%) of the trained and in 9 of 29 (31.0%) of the control subjects (p less than 0.001). The mean interval change in global initial distribution over the year period was 5 +/- 13 (mean +/- SD) in the trained and -6 +/- 14 in the control groups (p less than 0.003). The mean initial distribution of the trained group had improvement in all nine regions (significant in three), while the control group showed mean improvement in only one of nine regions. Additionally, the trained group showed improvement in the mean washout in five of nine regions (significant in three), while no mean regional washout improvement occurred in the control group. Thus, in this group of patients with stable CAD, exercise training resulted in apparently improved cardiac perfusion evidenced by enhance Tl-201 uptake and washout.

Limitations and advantages of the ejection fraction for defining high risk after acute myocardial infarction.

Left ventricular (LV) ejection fraction (EF) is known to be related to prognosis after acute myocardial infarction (AMI), but its role alone and in combination with other factors in the definition of a high-risk group has not been adequately specified. Several recent multicenter studies emphasize that LVEF together with features of ventricular ectopic activity during ambulatory electrocardiography define a group at high risk for death for up to 3 years. However, these high-risk groups comprised only a small fraction of the population (less than 7.5%) and failed to include 75% or more (less than 25% specificity) of observed events. In our study, LVEF was determined close to the time of hospital discharge in 750 patients with AMI enrolled in a collaborative study. Used alone, an LVEF of less than 0.45 best defined a high-risk group (39% of the population) yielding 62% sensitivity and 64% specificity for total cardiac mortality by 1 year; it was 77% sensitive for sudden death alone. In a multivariate analysis together with other factors, LVEF was an independent predictor, but other markers of LV dysfunction entered before LVEF with similar sensitivity for total cardiac deaths, but with increased specificity (75%). When an LVEF of less than 0.45 was used together with the presence of complex arrhythmias to define a high-risk group (19% of the population), sensitivity decreased to 39% and specificity increased to 84%. Thus, LVEF is a simple and effective alternative to multivariate analysis for risk assessment after AMI.(ABSTRACT TRUNCATED AT 250 WORDS)

Computer analysis of exercise-induced changes in QRS duration in patients with angina pectoris and in normal subjects.

Exercise-induced changes in QRS duration were assessed in 25 normal subjects and in 17 patients with stable ischemic heart disease. None had bundle branch block or were taking medications, and all patients had angina pectoris induced during the test. QRS duration and ST60 amplitude were measured by computer during rest while standing, at a heart rate of 100 to 110 bpm during exercise, at peak heart rate for the angina patients (mean of 127 bpm), and at the corresponding matched heart rate and peak heart rate for the normals (mean of 174 bpm). As heart rate increased, the patients showed significant ST60 depression. In normal subjects, the QRS duration tended to increase initially but at the matched heart rate level and at peak heart rate it decreased significantly compared to rest (p less than 0.01). The QRS duration in the angina patients increased significantly at the heart rate level of 100 to 110 bpm (p less than 0.05). Of the eight patients who reached a peak heart rate above 127 bpm, six (75%) during that period further increased QRS duration compared to three (12%) of the 25 normal subjects (p less than 0.001). We conclude that a consistent increase in QRS duration during exercise, although subtle, may be a marker of ischemia and consequently a potential diagnostic tool.