The incidence of “Silent” Coronary Heart Disease

In a group of clinically normal male executives subjected to maximal treadmill stress testing, the occurrence of ischemic st segment responses was in all cases unaccompanied by pain, while in a clinically suspect group a large proportion of those having ischemic st segment responses did not have chest pain.While a significant number of persons have no subjective sensation of pain while having ischemic st segment changes on the electrocardiograph during or after maximal treadmill exercise, occasionally atypical pain may occur during or following exercise. Maximal treadmill stress testing is useful in discovering “silent” coronary artery disease.     

Exercise ECG changes in normal women

Submaximal and/or maximal exercise was carried out by 357 women without a history of cardiovascular disease, using a bicycle ergometer and/or treadmill while monitored by a bipolar ECG lead CM₅. In 40- to 60-year-old women the incidence of an ischemic ECG pattern during or after exercise ranged from 20 to 50%. Because clinical coronary disease can be expected in less than 10% of normal women followed for 16 years, most of these ECG changes were not considered to be due to occult coronary disease. At the present time exercise ECG changes in women cannot be used with any reliability as an aid in the diagnosis of chest pain or in screening normal female populations for coronary heart disease.     

Graded Treadmill Stress Testing: Patterns of Physician Use and Abuse

Treadmill stress testing is used in assessing the condition of patients with known or suspected heart disease. We did a prospective study to clarify physician ordering and integration of the test. Ordering criteria were always complied with, although most tests were ordered for evaluation of atypical chest pain and only a few for high risk patients with known cardiac dysfunction, indicating a misplaced emphasis on the diagnostic capabilities of the test. Tests in patients with atypical chest pain and stress-induced ischemic changes were always integrated, but in 30 percent of patients with atypical pain and no stress-induced electrocardiographic changes, the tests were not used in patient management. This was often due to the misconception that negative findings on a stress test excluded coronary disease. Physicians should be alerted to this misplaced emphasis and misconception.     

Reciprocal change in ST segment in acute myocardial infarction: correlation with findings on exercise electrocardiography and coronary angiography.

The clinical relevance of reciprocal changes in the ST segment occurring at the time of acute myocardial infarction was studied prospectively in 85 consecutive uncomplicated cases. Reciprocal depression of the ST segment was defined as depression of 1 mm or more in electrocardiogram leads other than those reflecting the infarct. All patients underwent maximal, symptom limited treadmill stress testing two weeks after the infarct and coronary angiography six weeks after infarction. Forty six patients had inferior, 34 anterior, and five true posterior infarction. Of the 51 patients with reciprocal changes, 45 (88%) developed exercise induced ST segment depression in areas remote from the infarction zone. At angiography all 45 patients were shown to have stenoses greater than 70% in at least two major vessels. Four patients had negative exercise electrocardiograms and were sequently shown to have single vessel disease subtending their infarct, and the remaining two patients had a false negative treadmill test result. Of the 27 patients without reciprocal changes, 21 (78%) had negative treadmill stress test results associated with single vessel coronary disease. Five had positive stress test results and multivessel coronary disease, and one had a false negative stress test result. The remaining seven patients had ST segment elevation without Q wave formation in the reciprocal areas and were assessed separately. Of these, six had positive stress test results and multivessel coronary disease and one had a negative stress test result and single vessel coronary disease to the infarct area. Twenty one patients with anterior infarcts (62%) and 27 with inferior infarcts (59%) had reciprocal changes. No differences emerged in the relation between infarct site, reciprocal change, and presence of additional coronary disease. At follow up of the 51 patients with reciprocal changes in the ST segment 36 had become symptomatic, of whom 29 had undergone coronary artery bypass surgery. By contrast, only four of the 27 patients without reciprocal changes in the ST segment had developed symptoms, and two of these had undergone coronary revascularisation. Reciprocal ST segment depression at the time of acute myocardial infarction may identify patients with severe coronary disease who are at risk of subsequent cardiac events and appears to be as reliable as results of early postinfarction treadmill stress testing in predicting the underlying coronary anatomy. When the electrocardiogram does not show reciprocal changes treadmill testing provides valuable additional information.     

Attenuated responses to sympathoexcitation in individuals with Down syndrome.

This study evaluated blood pressure and heart rate responses to exercise and nonexercise tasks as indexes of autonomic function in subjects with and without Down syndrome (DS). Twenty-four subjects (12 with and 12 without DS) completed maximal treadmill exercise, isometric handgrip (30% of maximum), and cold pressor tests, with heart rate and blood pressure measurements. Maximal heart rate and heart rate and blood pressure responses to the isometric handgrip and cold pressor tests were reduced in subjects with DS (P < 0.05). Both early (first 30 s) and late (last 30 s) responses were reduced. Obesity did not appear to influence the results, as both obese and normal-weight subjects with DS exhibited similar responses, and controlling for body mass index did not alter the results between controls and subjects with DS. Individuals with DS, without congenital heart disease, exhibit reduced heart rate and blood pressure responses to isometric handgrip exercise and cold pressor testing, consistent with autonomic dysfunction. Autonomic dysfunction may partially explain chronotropic incompetence observed during maximal treadmill exercise in individuals with DS.     

Early exercise testing and coronary angiography after uncomplicated myocardial infarction.

In a prospective study 61 patients aged 55 years or less with uncomplicated myocardial infarction underwent treadmill stress testing at two weeks and coronary angiography at six weeks after infarction. Of the 44 patients who had a positive stress test, 43 had additional severe coronary artery disease confirmed by coronary angiography. Of the 17 patients who had a negative stress test for additional disease, coronary angiography identified only single-vessel disease in the infarct area in 15. The sensitivity of the stress test was 95% and the specificity 94%, though the number of patients in the study was small. Thus, exercise testing has considerable potential for the early identification of multiple-vessel disease in patients with uncomplicated myocardial infarction.     

A review of the postulated mechanisms concerning the association of Helicobacter pylori with ischemic heart disease

Since its discovery, Helicobacter pylori has been implicated in the pathogenesis of several diseases, both digestive and extradigestive. Interestingly, the majority of the extradigestive-related literature is focused on two vascular manifestations: stroke and ischemic heart disease. Potential mechanisms for the establishment of a H. pylori-induced ischemic heart disease have been proposed with regard to chronic inflammation, molecular mimicry, oxidative modifications, endothelial dysfunction, direct effect of the microorganism on atherosclerotic plaques as well as changes regarding traditional or novel risk factors for ischemic heart disease or even platelet-H. pylori interactions. A positive link between H. pylori infection and ischemic heart disease has been suggested by a series of studies focusing on epidemiologic evidence, dyslipidemic alterations, upregulation of inflammatory markers or homocysteine levels, induction of hypercoagulability, oxidation of low-density lipoprotein, causation of impaired endothelial function, detection of H. pylori DNA in atherosclerotic plaques, and participation of certain antigens and antibodies in a cross-reactivity model. There are studies, however, which investigated the relationship between H. pylori and ischemic heart disease with regard to the same parameters and failed to confirm the suggested positive association. Further studies in the direction of interaction between H. pylori and the host's genotype as well as a quest for evidence towards novel risk factors for ischemic heart disease such as oxidative stress, vascular remodeling, vascular calcification, or vasomotor activity, may reveal a field of great interest, thus contributing to the determination of new potential mechanisms.     

Cardiovascular responses to a high-volume continuous circuit resistance training protocol

The purpose of this investigation was to determine the level of cardiovascular stress elicited by continuous and prolonged circuit resistance training (CRT). Each of the 11 men who volunteered as a subject were tested to determine oxygen consumption and heart rate responses to a submaximal and maximal treadmill protocol and a CRT session consisting of 10 exercises and 10 repetitions at 40% of 1 repetition maximum (1RM) for each station with 4.6 circuits performed. The physiological stress of the CRT in this study was evident by the sustained heart rate of more than 70% of maximum for 16.6 minutes, with the last 12 minutes at more than 80%. Despite the large anaerobic component in CRT, Vo(2) was sustained at 50% or more of maximum for the final 12 minutes. Treadmill running, involving large muscle groups, increased Vo(2) more rapidly than CRT, where alternating larger and smaller muscle groups were used. In addition, at the same Vo(2) heart rate differed significantly between the 2 modes of activity. Heart rate in CRT was higher (at 165) than the heart rate of 150 found during treadmill running at the same 50% Vo(2). Such workouts may be used in a training cycle in classical linear periodization or in a nonlinear program day targeting local muscular endurance under intense cardiorespiratory conditions, which may help individuals develop enhanced toleration of physiological environments where high cardiovascular demands and higher lactate concentrations are present.     

Effect of treadmill exercise testing on serum enzymes and the resting electrocardiogram.

Fifty-three adult male patients with chest pain underwent treadmill exercise stress testing according to the Bruce protocol. The resting 12-lead electrocardiogram (ECG) and serum concentrations of glutamic oxaloacetic transaminase, lactic dehydrogenase creatine phosphokinase and alpha-hydroxybutyrate dehydrogenase were evaluated before, and at 1 and 20 hours after exercise. Twenty-eight subjects (53 percent) had a normal test result, 10 (19 percent) had ischemic ST -segment changes and anginal pain, and 15 (28 percent) were considered to have equivocal results because of an abnormal baseline ECG or the concurrent administration of cardioactive medication. In contrast to earlier reports, no significant changes in the serum enzyme values were seen in any of the three groups orin any individual subject, nor were ECG changes detected after recovery from exercise. The diagnostic evaluation of the exercise ECG must depend upon the demonstration of ischemic ST -segment changes and not upon changes in concentrations of serum enzymes.     

Sudden death during ambulatory monitoring.

Three patients with ischaemic heart disease died suddenly while being monitored with an ambulatory tape recorder. Two had terminal ventricular fibrillation initiated by paired bidirectional ventricular ectopic beats against a background of scattered ectopic activity; both had had ventricular tachycardia during routine treadmill exercise testing in the week before death. The third patient developed bizarre ventricular complexes followed by asystole. Sudden death may be due to ventricular fibrillation initiated by paired ventricular ectopic beats with changing morphology, or asystole following bizarre ventricular complexes. Exercise testing may have an important predictive value.     

Therapeutic potential of vitamin E against myocardial ischemic-reperfusion injury.

Myocardial ischemia is a disease process characterized by reduced coronary flow such that the supply of nutritive blood to heart muscle (myocardium) is insufficient for normal myocardial aerobic metabolism. Prompt reestablishment of coronary flow by invasive and noninvasive clinical procedures is the most direct and effective means of limiting myocardial damage in ischemic heart disease patients, although reperfusion carries with it an injury component which may reflect, at least to some degree, the toxic effects of partially reduced oxygen species and their participation in degenerative cellular processes such as membrane lipid peroxidation. Vitamin E, a lipophilic, chain-breaking antioxidant, is a prominent membrane constituent in heart muscle, where it modulates/regulates various aspects of heart muscle-cell metabolism and function. Vitamin E's beneficial effects against experimentally induced oxidative damage to the heart, along with inverse epidemiological correlations between plasma vitamin E level and either anginal pain or mortality due to ischemic heart disease, suggest that vitamin E might have protective and therapeutic roles against myocardial ischemic-reperfusion injury. Laboratory investigations aimed at addressing this possibility have demonstrated that vitamin E supplementation protects isolated hearts against ischemic-reperfusion injury, and relatively more inconsistent and limited data document cardioprotective effects of vitamin E in some animal models of myocardial ischemia-reperfusion, especially when administered prior to the ischemic period. Clinical attempts to establish whether vitamin E has therapeutic benefit in ischemic heart disease patients remain inconclusive, having relied upon a variety of nonuniformly controlled protocols and a single, rather subjective endpoint (anginal pain). Consequently, although laboratory data constitute a conceptual context for and indirect support of the idea that vitamin E could be a cardioprotectant against ischemic-reperfusion injury, compelling clinical evidence regarding vitamin E's therapeutic potential in the ischemic heart-disease patient is lacking. Elective coronary revascularization would appear to provide an attractive clinical setting for evaluating the therapeutic efficacy of vitamin E in the context of cardiac ischemia-reperfusion. Further biochemical work would still be required to define how vitamin E exerts any cardioprotective effect observed in these patients.     

The 6-minute walk: a new measure of exercise capacity in patients with chronic heart failure

Cycle and treadmill exercise tests are unsuitable for elderly, frail and severely limited patients with heart failure and may not reflect capacity to undertake day-to-day activities. Walking tests have proved useful as measures of outcome for patients with chronic lung disease. To investigate the potential value of the 6-minute walk as an objective measure of exercise capacity in patients with chronic heart failure, the test was administered six times over 12 weeks to 18 patients with chronic heart failure and 25 with chronic lung disease. The subjects also underwent cycle ergometer testing, and their functional status was evaluated by means of conventional measures. The walking test proved highly acceptable to the patients, and stable, reproducible results were achieved after the first two walks. The results correlated with the conventional measures of functional status and exercise capacity. The authors conclude that the 6-minute walk is a useful measure of functional exercise capacity and a suitable measure of outcome for clinical trials in patients with chronic heart failure.     

Changes in the Cardiovascular Function in Healthy Subjects and Patients with Ischemic Heart Disease during Sleep

The purpose of this study was to investigate the autonomic regulation of the cardiovascular system during sleep in health and disease. The examination included 396 subjects: 29 healthy subjects and 367 patients with ischemic heart disease, of whom 149 had left-ventricular failure and 214 hypertension. Sleep quality and the presence of obstructive sleep apnea syndrome were evaluated by polysomnography; the character of autonomic regulation of cardiac rhythm and hemodynamics was determined by computerized testing during night sleep and an active orthostatic test immediately before and after sleep. The results permitted the authors to conclude that autonomic regulation may be restored to various degrees in health and disease, depending on the pathology level. The sleep quality influenced the restoration of hemodynamics more than that of the cardiac rhythm, mainly when obstructive sleep apnea syndrome was present.     

ADF/cofilin and actin dynamics in disease

ADF/cofilins are key regulators of actin dynamics in normal cells. Recent findings suggest that, under cellular stress, the wild-type proteins might form complexes with actin that can alter cell function. Owing to their rapid formation, these complexes might initiate or aid in the progression of diseases as diverse as Alzheimer's disease and ischemic kidney disease. Although evidence for their involvement in diseases other than Alzheimer's and ischemic kidney disease is tenuous, recent studies suggest that altered production, regulation or localization of these proteins might lead to cognitive impairment, inflammation, infertility, immune deficiencies and other pathophysiological defects.     

Ischemic heart disease without anginal pain]

Prolonged ECG-recording with Holter's technique facilitated detection of heart ischemic episodes without accompanying anginal pain. It is estimated that ischemic heart disease without anginal pain involves about 20% of all patients with IHD, and the episodes of heart ischemia with and without anginal pain occur in 30% of these patients. A course of ischemic heart disease without anginal pain may be due to decreased sensitivity to pain stimuli caused by the lesions to sensory afferent nerves or by the increased serum endorphins. The majority of experiments has shown that asymptomatic ischemic heart disease increases the risk of sudden death. It may be explained by increased physical exercise attempted by these patients and not compliance with anti-sclerotic therapeutical and preventive measures. The treatment of asymptomatic ischemic heart disease is similar to that in symptomatic froms of this diseases.     

Hierarchy of individual calibration levels for heart rate and accelerometry to measure physical activity.

Combining accelerometry with heart rate (HR) monitoring may improve precision of physical activity measurement. Considerable variation exists in the relationships between physical activity intensity (PAI) and HR and accelerometry, which may be reduced by individual calibration. However, individual calibration limits feasibility of these techniques in population studies, and less burdensome, yet valid, methods of calibration are required. We aimed to evaluate the precision of different individual calibration procedures against a reference calibration procedure: a ramped treadmill walking-running test with continuous measurement of PAI by indirect calorimetry in 26 women and 25 men [mean (SD): 35 (9) yr, 1.69 (0.10) m, 70 (14) kg]. Acceleration (along the longitudinal axis of the trunk) and HR were measured simultaneously. Alternative calibration procedures included treadmill testing without calorimetry, submaximal step and walk tests with and without calorimetry, and nonexercise calibration using sleeping HR and gender. Reference accelerometry and HR models explained >95% of the between-individual variance in PAI (P < 0.001). This fraction dropped to 73 and 81%, respectively, for accelerometry and HR models calibrated with treadmill tests without calorimetry. Step-test calibration captured 62-64% (accelerometry) and 68% (HR) of the variance between individuals. Corresponding values were 63-76% and 59-61% for walk-test calibration. There was only little benefit of including calorimetry during step and walk calibration for HR models. Nonexercise calibration procedures explained 54% (accelerometry) and 30% (HR) of the between-individual variance. In conclusion, a substantial proportion of the between-individual variance in relationships between PAI, accelerometry, and HR is captured with simple calibration procedures, feasible for use in epidemiological studies.     

Pleomorphic carcinoma of the thyroid.

The Canadian Home Fitness Test (CHFT) and the Bruce treadmill test were performed by 230 men aged 45 to 69 years. Because of inaccuracies in the counting of heart rates, less was known about the fitness of the men after testing than before. In addition, inaccuracies in the test record and design were uncovered. A more accurate estimate of fitness could be obtained when the subjects'' own rating of exertional intensity was substituted for heart rate counting. The CHFT is a marketing tool of Health and Welfare Canada that may be useful in selling fitness, but as a measure of fitness in Canadian homes it is likely to be misleading.     

Age Related Bioenergetics Profiles in Isolated Rat Cardiomyocytes Using Extracellular Flux Analyses

Mitochondrial dysfunction is increasingly recognized and studied as a mediator of heart disease. Extracellular flux analysis (XF) has emerged as a powerful tool to investigate cellular bioenergetics in the context of cardiac health and disease, however its use and interpretation requires improved understanding of the normal metabolic differences in cardiomyocytes (CM) at various stages of maturation. This study standardized XF analyses methods (mitochondrial stress test, glycolytic stress test and palmitate oxidation test) and established age related differences in bioenergetics profiles of healthy CMs at newborn (NB1), weaning (3WK), adult (10WK) and aged (12–18MO) time points. Findings show that immature CMs demonstrate a more robust and sustained glycolytic capacity and a relative inability to oxidize fatty acids when compared to older CMs. The study also highlights the need to recognize the contribution of CO₂ from the Krebs cycle as well as lactate from anaerobic glycolysis to the proton production rate before interpreting glycolytic capacity in CMs. Overall, this study demonstrates that caution should be taken to assure that translatable developmental time points are used to investigate mitochondrial dysfunction as a cause of cardiac disease. Specifically, XF analysis of newborn CMs should be reserved to study fetal/neonatal disease and older CMs (≥10 weeks) should be used to investigate adult disease pathogenesis. Knowledge gained will aid in improved investigation of developmentally programmed heart disease and stress the importance of discerning maturational differences in bioenergetics when developing mitochondrial targeted preventative and therapeutic strategies for cardiac disease.     

Contribution of the PI 3-kinase/Akt survival pathway toward osmotic preconditioning

Osmolytes are rapidly lost from the ischemic heart, an effect thought to benefit the heart by reducing the osmotic load. However, the observation that chronic lowering of one of the prominent osmolytes, taurine, is more beneficial to the ischemic heart than acute taurine loss suggests that osmotic stress may benefit the ischemic heart through multiple mechanisms. The present study examines the possibility that chronic osmotic stress preconditions the heart in part by stimulating a cardioprotective, osmotic-linked signaling pathway. Hyperosmotic stress was produced by treating rat neonatal cardiomyocytes during the pre-hypoxic period with either the taurine depleting agent, beta-alanine (5 mM), or with medium containing 25 mM mannitol. The cells were then subjected to chemical hypoxia in medium containing 3 mM Amytal and 10 mM deoxyglucose but lacking beta-alanine and mannitol. Cells that had been pretreated with either 5 mM beta-alanine or 25 mM mannitol exhibited resistance against hypoxia-induced apoptosis and necrosis. Associated with the osmotically preconditioned state was the activation of Akt and the inactivation of the pro-apoptotic factor, Bad, both events blocked by the inhibition of PI 3-kinase. However, preconditioning the cardiomyocyte with mannitol had no effect on the generation of free radicals during the hypoxic period. Osmotic stress also promoted the upregulation of the anti-apoptotic factor, Bcl-2. Since inhibition of PI 3-kinase with Wortmannin also prevents osmotic-mediated cardioprotection, we conclude that hyperosmotic-mediated activation of the PI 3-kinase/Akt pathway contributes to osmotic preconditioning.