Risk Of Acute Cardiac Events Research Articles

Reduction in Observation Unit Length of Stay With Coronary Computed Tomography Angiography Depends on Time of Emergency Department Presentation

Prior studies demonstrating shorter length of stay (LOS) from coronary computed tomography angiography (CCTA) relative to stress testing in emergency department (ED) patients have not considered time of patient presentation. The objectives of this study were to determine whether low-risk chest pain patients receiving stress testing or CCTA have differences in ED plus observation unit (OU) LOS and if there are disparities in testing modality use, based on the time of patient presentation to the ED. The authors examined a cohort of low-risk chest pain patients evaluated in an ED-based OU using prospective and retrospective OU registry data. During the study period, stress testing and CCTA were both available from 08:00 to 17:00 hours. CCTA was not available on weekends, and therefore only subjects presenting on weekdays were included. Cox regression analysis was used to model the effect of testing modality (stress testing vs. CCTA) on OU LOS. Separate models were fit based on time of patient presentation to the ED using 4-hour blocks beginning at midnight. The primary independent variable was testing modality: stress testing or CCTA. Age, sex, and race were included as covariates. Logistic regression was used to model testing modality choice by time period adjusted for age, sex, and race. Over the study period, 841 subjects presented Monday through Friday. Median LOS was 18.0 hours (interquartile range [IQR] = 11.7 to 22.9 hours). Objective cardiac testing was completed in 788 of 841 (94%) patients, with 496 (63%) receiving stress testing and 292 (37%) receiving CCTA. After age, race, and sex were adjusted for, patients presenting between 08:00 and 11:59 hours not only had a shorter LOS associated with CCTA (p < 0.0001), but also had a greater likelihood of being tested by CCTA (p = 0.001). None of the other time periods had significant differences in LOS or testing modality choice for CCTA relative to stress testing. In an OU setting with weekday and standard business hours CCTA availability, CCTA testing was associated with shorter LOS among low-risk chest pain patients only in patients presenting to the ED between 08:00 and 11:59 hours. That time period was also associated with a greater likelihood of being tested by CCTA, suggesting that ED providers may have intuited the inability of CCTA to shorten LOS during other times.

Lymphocyte Subpopulations in Lymph Nodes and Peripheral Blood: A Comparison between Patients with Stable Angina and Acute Coronary Syndrome

ObjectiveAtherosclerosis is characterized by a chronic inflammatory response involving activated T cells and impairment of natural killer (NK) cells. An increased T cell activity has been associated with plaque instability and risk of acute cardiac events. Lymphocyte analyses in blood are widely used to evaluate the immune status. However, peripheral blood contains only a minor proportion of lymphocytes. In this study, we hypothesized that thoracic lymph nodes from patients with stable angina (SA) and acute coronary syndrome (ACS) might add information to peripheral blood analyses.MethodsPeripheral blood and lymph nodes were collected during coronary by-pass surgery in 13 patients with SA and 13 patients with ACS. Lymphocyte subpopulations were assessed by flow cytometry using antibodies against CD3, CD4, CD8, CD19, CD16/56, CD25, Foxp3, CD69, HLA-DR, IL-18 receptor (R) and CCR4.ResultsLymph nodes revealed a lymphocyte subpopulation profile substantially differing from that in blood including a higher proportion of B cells, lower proportions of CD8+ T cells and NK cells and a 2-fold higher CD4/CD8 ratio. CD4+CD69+ cells as well as Foxp3+ regulatory T cells were markedly enriched in lymph nodes (p<0.001) while T helper 1-like (CD4+IL-18R+) cells were more frequent in blood (p<0.001). The only significant differences between ACS and SA patients involved NK cells that were reduced in the ACS group. However, despite being reduced, the NK cell fraction in ACS patients contained a significantly higher proportion of IL-18R+ cells compared with SA patients (p<0.05).ConclusionThere were several differences in lymphocyte subpopulations between blood and lymph nodes. However, the lymphocyte perturbations in peripheral blood of ACS patients compared with SA patients were not mirrored in lymph nodes. The findings indicate that lymph node analyses in multivessel coronary artery disease may not reveal any major changes in the immune response that are not detectable in blood.

ASSOCIATIONS BETWEEN OZONE EXPOSURE AND DYSFUNCTOIN OF CARDIAC AUTONOMIC NERVOUS SYSTEM IN HEALTHY ELDERLY SUBJECTS

Background and Aims: Previous studies have provided strong evidences that elevated levels of ambient ozone (O3) are associated with the increased cardiovascular mortality and morbidity. The dysfunction of cardiac autonomic nervous system (ANS), indicated by the disturbed heart rate variability (HRV) indices, is the major contributor to the triggering of electro-physiologic diseases. Heterogeneous associations between O3 exposures within several hours and HRV in subjects with compromised health status are reported in some previous studies. No studies, however, have focused on the effect of several minutes O3 exposure on healthy elderly subjects. Methods: Real time ambient O3 concentration and HRV indices of 20 healthy elderly subjects were measured continuously and concurrently by 5-min segment in winter, Beijing. Mixed linear model was used to evaluate the associations between ambient 5-min average O3 and concurrent 5-min HRV frequency indices adjusting for the time-variant variables (temperature and relative humidity) and subject characteristics. Results: Elevated ambient O3 exposure was associated with decreased High Frequency (HF) (•=-0.00213, p =0.024) and increased low-frequency/high-frequency ratio (LFHFR) (•=0.00177, p =0.016) in healthy elderly subjects. Conclusions: We conclude that ambient O3 exposures within several minutes may exert predominance of cardiac sympathetic nervous activity, which may increase the risk for acute cardiac events.

Exercise-Induced Cardiac Troponin Release: Real-Life Clinical Confusion

Exercise training represents a successful and powerful strategy to prevent future cardiovascular disease. Paradoxically, performance of exercise is also associated with an increased risk of acute cardiac events. Accordingly, patients may present to hospital with cardiac symptoms following a bout of unaccustomed physical effort (e.g. exercise). Current guidelines for the identification of an acute myocardial infarction (AMI) importantly depend on the presence of cardiac troponin as a highly sensitive marker of cardiac damage. However, a number of studies have reported elevated cardiac troponin levels in asymptomatic, healthy subjects after endurance exercise (such as a marathon, prolonged cycling or prolonged walking). These observations indicate that elevated cardiac troponin levels can be the result of cardiac ischemia, and subsequent necrosis, but also may be related to strenuous exercise. In this paper, we present three different clinical cases of post-exercise elevations in cardiac troponins, each with a distinct clinical presentation. These case studies emphasize that a detailed assessment of all symptoms and a thorough patient-history are prerequisite for accurate interpretation of a positive cardiac troponin test following exercise.

Oestradiol supplement minimises coronary occlusion-induced myocardial infarction and ventricular dysfunction in oophorectomised female rats

BackgroundEndogenous oestrogen deficiency after menopause is associated with high risk of acute cardiac events and the protection of exogenous oestrogen supplements remains uncertain. This study investigates whether oestrogen therapy protects the heart from ischemic injury in oophorectomised rats. MethodsSexually mature female Sprague–Dawley rats (6 for each group) with bilateral oophorectomy underwent selective ligation (occlusion) of left coronary artery for 4weeks. 17β-oestradiol (E2) supplements (10μg, i.m., every other day) were started before (preventive-therapeutic supplement) or after coronary occlusion (therapeutic supplement). ResultsIn oophorectomised rats plasma levels of E2 declined from 1301±80 to 196±48pmol/L (p<0.01) and cardiac expression of oestrogen receptors (ER) decreased by ∼60%. E2 supplements recovered the ER expression. Selective ligation of left coronary led myocardial infarction in the left ventricle, with an increase in plasma cardiac troponin I (cTn-I), decrease in systolic blood pressure (SBP), and reduction of left ventricular pressures. Preventive-therapeutic but not therapeutic E2 supplement reduced cTn-I levels (from 21.9±2.0 to 6.0±0.3ng/mL, p<0.01), minimised infarction (from 37.0±1.2% to 18.1±2.3%, p<0.05), increased SBP (from 82±4.2 to 97±4.4mm Hg, p<0.05), and improved left ventricular end pressures in the oophorectomised rats following coronary occlusion. ConclusionPostmenopausal (ooporectomised) oestrogen supplement commenced before establishment of myocardial ischemia minimises myocardial infarction and ventricular dysfunction following the coronary artery occlusion. Cellular and molecular mechanisms underlying the cardiac protection of oestrogen therapy remain unclear, in which activation of cardiac ER expression and increasing in circulating CD90+ stem cells may be involved.

Hindlimb unloading results in loss of circadian control of heart rate and increased incidence of spontaneous ventricular arrhythmias

Hindlimb unloading (HU) in rats, a model of cardiovascular deconditioning, has been found to result in cardiac sympathovagal imbalance. Previous data indicate that derangement in circadian control of heart rate may lead to increased risk for acute cardiac events via alterations in autonomic function. We hypothesized that attenuated circadian control of HR and increased incidence of spontaneous premature ventricular complexes (PVC) would occur over the course of 10–14 days of HU vs casted control (CC) condition. Radiotelemetry probes for electrocardiographic analysis were implanted in male, Sprague‐Dawley rats 10 days prior to manipulations. Data were collected for 5 consecutive minutes at the top of each hour, separated into light and dark cycles and statistically compared. Circadian differences in HR in CC (n=4) and HU (n=6) rats were similar and significantly different over 48h of baseline and 72h of HU adaptation. While loss of this difference and tachycardia occurred initially in both groups, HR and circadian control returned to baseline levels by 6 days in CC rats but not in HU rats. In addition, 27 spontaneous PVCs and one run of salvo were observed in a subset of HU rats (n=3) as compared to only 4 spontaneous PVCs in a subset of CC (n=2) rats. These data indicate that deconditioning leads to loss of circadian control of HR and increased incidence of ventricular arrhythmias, likely due to autonomic dysfunction.

Sleep-disordered breathing and cardiac autonomic modulation in children

Objectives To investigate the adverse cardiac autonomic effects of sleep-disordered breathing (SDB) in a large population-based sample and a clinical sample of children. Methods Subjects included a population-based sample of 700 and a clinically diagnosed sample of 43 SDB children. SDB was defined based on an apnea hypopnea index (AHI) ⩾ 1 during one night of polysomnography. Cardiac autonomic modulation was measured by heart rate variability (HRV) analysis of the beat-to-beat RR interval data collected during polysomnography. Results The mean (SD) age was 112 (21) months, with 49% male and 25% non-white. About 73.0% had AHI < 1 (no SDB), 25.8% had 1–5 AHI (mild SDB), and 1.2% had ⩾5 AHI (moderate SDB). Among individuals with moderate SDB in the population-based sample and the clinically diagnosed SDB patients, the mean (SE) of HRV-high frequency power (HF) was significantly lower compared to children without SDB [6.00 (0.32) and 6.24 (0.14), respectively, vs. 6.68 (0.04) ms 2, p < 0.05 and p < 0.01, respectively], whereas the low frequency power to high frequency power ratio (LF/HF) was significantly higher [1.62 (0.20) and 1.74 (0.09), respectively, vs. 0.99 (0.02), both p < 0.01)]. Conclusions SDB in healthy young children and in clinical patients is significantly associated with impaired cardiac autonomic modulation, i.e., sympathetic overflow and weaker parasympathetic modulation, which may contribute to increased risk of acute cardiac events in persons with SDB, even before reaching the “high risk age.”

Plasma cystatin C for prediction of 1-year cardiac events in Mediterranean patients with non-ST elevation acute coronary syndrome

ObjectiveEvaluation of renal function (RF) is important for management of patients with non-ST elevation acute coronary syndrome (NSTE-ACS). Cystatin C, a sensitive marker of RF, appears to be also a marker of cardiovascular risk. Little is known regarding its predictive role in NSTE-ACS patients. MethodsWe assessed 525 patients taking part in the “Systemic Inflammation Evaluation in patients with NSTE-ACS” (SIESTA) study. Patients were subdivided in quartiles according to cystatin C plasma concentrations (mg/L), i.e., Q1<0.81; Q2=0.81–0.92; Q3=0.93–1.10; Q4≥1.11. Glomerular filtration rate (eGFR) was estimated using the modification of diet in renal disease (MDRD) equation. The study end-point was the composite of cardiac death, non-fatal myocardial infarction and unstable angina at 1-year follow up. ResultsFew patients (0.8%) had severely impaired RF (MDRD<30ml/min/1.73m2). 157 patients reached (30%) the study end-point. Patients in Q3 and Q4 showed a higher cumulative probability of cardiac events compared to patients in the lowest quartile. On multivariable analysis, patients in Q3 and Q4 had an increased incidence of cardiac events (adjusted HR=1.57 95%CI 1.04–2.49; p=0.036). Patients with TIMI risk score ≥3 or in-hospital heart failure were also at higher risk for acute cardiac events. Conventional markers of RF, i.e., serum creatinine and eGRF, were not predictors for the study end-point. ConclusionsIncreased levels of cystatin C were an independent predictor of cardiac events at 1-year follow up in this contemporary series of Mediterranean patients with NSTE-ACS.

A cold shock response triggering acute myocardial infarction

Acute risk factors are activities and events that suddenly and transiently increase the risk of acute cardiac events, as reported recently in International Journal of Cardiology. It has already been reported that sudden submersion in cold water may provoke myocardial infarction in both subjects with atherosclerotic coronary disease and young people with angiographically normal coronary arteries. We report a case of an acute myocardial infarction triggered by sudden exposure to cold air temperature extreme in a young person with acutely occluded proximal part of the left anterior descending coronary artery and normal other coronary arteries who had extreme obesity and cigarette smoking as cardiovascular risk factors. Our report indicates that the sudden cold exposure and the resulting cold shock response may provoke acute myocardial infarction in young susceptible patients.

“The Rust of Life”: Impact of Anxiety on Cardiac Patients

Anxiety has both functionally appropriate and inappropriate consequences. Among patients with cardiac disease, anxiety can be functionally appropriate when it prompts an individual to quickly seek treatment for acute cardiac signs and symptoms. But anxiety may have medical or psychological consequences when it is persistent or severe, including difficulty adhering to prescribed treatments and making recommended lifestyle changes, adoption of or failure to change risky behaviors, increased risk for acute cardiac events, and increased risk for in-hospital complications after admission for acute coronary syndrome. Yet, because anxiety is a universal emotion that is managed without consequence by many people, its importance is often ignored by healthcare providers. The impact of psychosocial (with a major emphasis on anxiety) and behavioral variables on biological outcomes was examined systematically. The research included (1) examination and comparison of the intensity of anxiety in international samples of various critically, acutely, and chronically ill cardiac patients; (2) determination of differences between men and women in the expression of anxiety; (3) investigation of factors predictive of anxiety levels, including perceived control; (4) studies of healthcare providers' knowledge of anxiety assessment and providers' practices in assessing and managing anxiety; and (5) determination of the impact of anxiety on clinical outcomes in cardiac patients. The goal of this program of research is to improve patients' outcomes on a widespread basis by placing anxiety in the forefront of clinical cardiac practice.

Recommendations for participation in competitive sport and leisure-time physical activity in individuals with cardiomyopathies, myocarditis and pericarditis

Several relatively uncommon, but important cardiovascular diseases are associated with increased risk for acute cardiac events during exercise (including sudden death), such as hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC) and myo-pericarditis. Practising cardiologists are frequently asked to advise on exercise programmes and sport participation in young individuals with these cardiovascular diseases. Indeed, many asymptomatic (or mildly symptomatic) patients with cardiomyopathies aspire to a physically active lifestyle to take advantage of the many documented benefits of exercise. While recommendations dictating the participation in competitive sport for athletes with cardiomyopathies and myo-pericarditis have recently been published as a consensus document of the European Society of Cardiology, no European guidelines have addressed the possible participation of patients with cardiomyopathies in recreational and amateur sport activities. The present document is intended to offer a comprehensive overview to practising cardiologists and sport physicians of the recommendations governing safe participation in different types of competitive sport, as well as the participation in a variety of recreational physical activities and amateur sports in individuals with cardiomyopathies and myo-pericarditis. These recommendations, based largely on the experience and insights of the expert panel appointed by the European Society of Cardiology, include the most up-to-date information concerning regular exercise and sports activity in patients with cardiomyopathies and myo-pericarditis.

2006 Katharine A. Lembright Award—“The Thin Stream of Fear Trickling Through the Mind”: Impact of Anxiety in Cardiac Patients

Anxiety has both functionally appropriate and pathological consequences. Among people with cardiac disease, anxiety can be functionally appropriate when it triggers an individual to quickly seek treatment for acute cardiac symptoms. Anxiety, however, may have pathological consequences when it is persistent or severe. These consequences may include the following: difficulty adhering to prescribed treatments and making recommended lifestyle changes; adoption of or failure to change risky behaviors; increased risk for acute cardiac events; and increased risk for in-hospital complications after admission for acute coronary syndrome. Nevertheless, because anxiety is a universal emotion that is managed without consequence by many people, its significance is often ignored by healthcare providers. The purpose of this presentation is to describe findings from a biobehavioral program of research in which the impact of psychosocial (with a major emphasis on anxiety) and behavioral variables on biological outcomes has been systematically examined. In this program of research we have (1) examined and compared the intensity of anxiety in international samples of various cardiac patient groups; (2) determined gender differences in the expression of anxiety; (3) investigated factors predicting anxiety levels, including perceived control; (4) studied healthcare providers’ knowledge of anxiety assessment and their practices with regard to the assessment and management of anxiety; (5) determined the impact of anxiety on clinical outcomes in cardiac patients and elucidated mechanisms for the linkage; and (6) tested interventions to decrease anxiety and improve morbidity and mortality. We hope to improve patient outcomes on a widespread basis by placing anxiety in the forefront of clinical cardiac practice.

Early Time to Benefit with Intensive Statin Treatment: Could It Be the Pleiotropic Effects?

Acute coronary syndrome (ACS) is associated with a number of abnormalities in inflammation, endothelial function, and coagulation, all of which appear to be modulated by statins. We examined the time to benefit of different statin regimens in the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) trial and other ACS trials that compared statin therapies in patients with ACS. In PROVE IT-TIMI 22, apparent clinical benefit was observed as early as 30 days, with significant reduction in all-cause mortality, myocardial infarction, unstable angina requiring rehospitalization, revascularization performed 30 days postrandomization, or stroke observed as early as 4 months. In PROVE IT-TIMI 22, atorvastatin 80 mg lowered both low-density lipoprotein (LDL) cholesterol and C-reactive protein (CRP) at 30 days and 4 months to a greater extent than pravastatin 40 mg. Those who achieved the lowest LDL and the lowest CRP levels at 30 days after ACS had the lowest risk of acute cardiac events. The very early benefits of statin therapy appeared to be correlated with CRP reductions, which may relate to the intensity of the pleiotropic effects of statins.

Update on using coronary calcium screening by computed tomography to measure risk for coronary heart disease

Coronary artery disease (CAD) is the number one killer of adults in the United States, claiming one-half million deaths annually. Early detection and prevention strategies clearly remain a top priority for health care providers in order to reduce the high mortality rate of heart disease. As an unequivocal reflection of arteriosclerosis, coronary arterial calcium (CAC) may provide a means to qualitatively assess the overall disease severity and likewise serve as a means to assess risk for CHD. It is known that patients with heavy calcium burdens have more advanced CAD, a concomitantly a higher likelihood of coronary stenoses, and a concomitant higher risk for acute cardiac events. Computed tomography has been shown to be an accurate, non-invasive method to quantify coronary calcification burden in patients. Evidence shows that calcium measurements by CT correlate well with histological plaque analyses, and that CAC measurements accurately reflect disease severity and can be useful to assess individual risk for CHD. The purpose of this article is to summarize the currently available evidence that has attempted to validate CAC screening as a screening exam and risk predictor for coronary heart disease.

Deletion polymorphism in the alpha2B-adrenergic receptor gene is associated with flow-mediated dilatation of the brachial artery.

A deletion variant of the alpha(2B)-adrenergic receptor (alpha(2B)-AR) has been associated with an increased risk of acute cardiac events in middle-aged men. Our aim was to determine the possible associations between the alpha(2B)-AR gene deletion variant and indicators of subclinical atherosclerosis in the brachial and carotid arteries. A total of 148 middle-aged men participating in an epidemiological twin study on risk factors for subclinical coronary heart disease were genotyped using PCR. Flow-mediated dilatation (FMD) of the brachial artery, carotid artery compliance and carotid intima-media thickness were measured using high-resolution ultrasound. FMD was 6.2+/-5.0% in subjects with the I/I (insertion/insertion) genotype, 5.5+/-4.1% in the I/D (insertion/deletion) group and 4.1+/-3.8% in the D/D (deletion/deletion) group ( P =0.03 for trend). In multivariate regression analysis controlling for age, presence of hypertension, smoking, use of angiotensin-converting enzyme inhibitors and plasma levels of low-density lipoprotein cholesterol and lipoprotein (a), the association between the alpha(2B)-AR genotype and FMD remained significant ( P =0.04 for trend). The alpha(2B)-AR genotype was not associated with intima-media thickness or carotid artery compliance. These findings indicate that subjects homozygous for the deletion allele of alpha(2B)-AR appear to have an increased risk of impaired endothelial function, which may provide an explanation for the previously observed increased risk of myocardial infarction in male subjects with this genotype. It is not known whether the association of the alpha(2B)-AR polymorphism with endothelial function is direct, or is mediated via altered sympathetic activation.

Relative Risk of Sudden Cardiac Death During Marathon Running

C a 6-fold increase in the absolute incidence of exercise-related sudden cardiac death in middle-aged men compared with younger men, Thompson's 1 conclusion that vigorous physical activity transiently increases the risk of acute cardiac events agrees with relative risk analysis for a triggering effect of myocardial infarction during exercise. 2 3 Expressed as sudden cardiac death risk per person-hour, the reported rate of 1 per 50 000 marathon runners 4 represents a 5-fold increase over the average hourly incidence per person-hour. This translates into 1 death per 200 000 person-hours of competition compared with 1 sudden cardiac death per million person-hours among middle-aged men. 5 The data are finally coming in on the issue of how much exercise might be too much. The cardiovascular benefit of training for middle-aged male marathon runners may be offset by a 5-fold increase in the odds ratio for acute cardiac events during competition. At

Can the risk for acute cardiac events in acute coronary syndrome be indicated by platelet membrane activation marker P-selectin?

P-selectin, an adhesion molecule of the selectin family, is expressed on the surface of activated thrombocytes by thrombin. The aim of the present study was to assess the predictive value of P-selectin (estimated by flow cytometric assay) for acute cardiac events in acute coronary syndrome. The study consisted of 48 patients with acute coronary syndrome and 30 healthy control subjects. After immediate fixation with 1% paraformaldehyde, 50 microliters of this aliquot was incubated with phycoerythrin-CD62-related antigen, and then measured by flow cytometry. The short-term clinical course of the patients was compared with their P-selectin values. The average P-selectin values in the 30 healthy volunteers was 0.11 +/- 0.20% (range, 0.0-0.5%). Significant differences were observed between acute cardiac events in patients with unstable angina and high P-selectin values and those with normal P-selectin values (chi 2 = 4.3; P < 0.05). Moreover, the angina patients who experienced acute cardiac events had significantly elevated P-selectin values (2.1 +/- 2.3%) compared with patients who did not experience acute cardiac events (0.3 +/- 0.4%, P < 0.05). The P-selectin values were elevated in seven out of 24 patients who suffered acute myocardial infarction. Seven of the 14 patients with acute coronary syndromes and high P-selectin values required urgent percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG), or both, otherwise they developed extension of the infarction. However, only five of the 34 patients with normal P-selectin values required urgent PTCA or CABG. Significant differences were observed in acute cardiac events between the high P-selectin and normal P-selectin groups (chi 2 = 4.8, P < 0.05). High P-selectin values indicate activation of platelets and the risk of acute cardiac events in patients with acute coronary syndrome.

Enhanced transcardiac I-norepinephrine response during cold pressor test in obstructive coronary artery disease

An increase in cardiac sympathetic activity can enhance coronary vasomotor tone and lower the ventricular fibrillation threshold. We compared the transcardiac I-norepinephrine responses during cold pressor test of 20 patients with normal coronary arteries with those of 23 patients with obstructive coronary artery disease. Baseline hemodynamic data did not differ in the 2 patient groups except for left ventricular end-diastolic pressures; mean values (± standard deviation ¦SD¦) were 10 ± 3.7 and 15 ± 4.5 mm Hg in patients with normal and abnormal coronary arteries (p < 0.01). Baseline I-norepinephrine contents averaged 295 ± 152 (normal coronary arteries) and 250 ± 134 pg/ml (coronary artery disease) in the arterial blood, and 273 ± 152 and 250 ±115 pg/ml, respectively, in the coronary sinus blood. Hemodynamic responses during cold stimulus were similar in both groups. Also, cold pressor-induced increases in arterial and coronary sinus I-norepinephrine contents were balanced in patients with normal coronary arteries, averaging 19 ± 30 and 17 ± 37%, respectively. In patients with coronary artery disease, however, a 26 ± 58% increase in arterial I-norepinephrine contents was associated with a 58 ± 62% increase in coronary sinus I-norepinephrine contents (p < 0.02), suggesting myocardial I-norepinephrine net release. It is concluded that transcardiac I-norepinephrine responses during cold stimulus are enhanced in patients with obstructive coronary artery disease. This response to a relatively mild sympathetic stress, reproducible by a variety of analogous stressful situations during daily life, could present an increased risk for acute cardiac events.