Background Transient ischemia in stable coronary disease peaks in the morning, reflecting increased myocardial oxygen demand and coronary vasomotor tone after waking. In acute coronary syndromes, however, ischemia may result from transient thrombus formation or coronary spasm at the site of a ruptured plaque. We report on the pathophysiological mechanisms underlying transient ischemia in acute coronary syndromes despite optimal therapy, on the basis of analysis of heart rate changes preceding ischemia and its circadian variation. Methods and Results Two hundred fifty-six patients with unstable angina or non–Q-wave myocardial infarction underwent continuous ST-segment monitoring for 48 hours while receiving maximal medical therapy. All ischemic episodes were characterized by their timing, duration, association with pain, and heart rate changes before the onset of ischemia. During 10 629 hours of monitoring, 44 patients (17.2%) had 176 episodes of transient ischemia. The mean heart rate at onset of ischemia was 68±12.8 bpm, and >55% of ischemic episodes were not preceded by a significant increase in heart rate. Ischemic activity had a single nocturnal peak, with 64% of all episodes occurring between 10 pm and 8 am , this nocturnal preponderance being evident for episodes with or without a preceding increase in heart rate. The characteristics and timing of transient ischemia were similar in unstable angina and non–Q-wave myocardial infarction, but transient ischemia was more frequent (27.3% versus 15.1%; P <.05) and prolonged (median, 20 versus 13.5 minutes; P <.01) in non–Q-wave myocardial infarction. Conclusions In acute coronary syndromes, transient ischemia has a low threshold, occurs predominantly without an increase in myocardial oxygen demand, and is present mainly at night rather than in the morning. These findings in patients receiving maximal medical therapy suggest significant pathophysiological differences underlying transient ischemia compared with stable coronary disease.

Many studies have confirmed a peak in the onset of acute myocardial infarction, sudden cardiac death and ischemic activity in the morning waking hours in patients with coronary artery disease. Factors potentially relevant to this observed surge in activity include marked increases in heart rate, blood pressure, catecholamine release, coronary artery tone and platelet aggregability, and a trough in the fibrinolytic state at this time. 1 Various studies have shown that β-adrenergic blockade is effective in blunting particularly the morning surge in ischemic activity,2,3 onset of acute myocardial infarction, 4 and sudden cardiac death5; however, despite the powerful coronary vasodilating and afterload-reducing properties of calcium antagonists, they have not been shown to alter the morning surge in ischemia2,6 (except in high doses7), or the morning peak in onset of myocardial infarction.4 Although the recently published nifedipine Gastrointestinal Therapeutic System (GITS) study showed an overall modification of the circadian pattern of ischemia with nifedipine GITS as monotherapy, there appeared to be no difference in circadian patterns during such active therapy and subsequent placebo withdrawal.8 It is possible that previous studies of calcium antagonists without either a 24-hour profile or chronotropic control have resulted in (1) the morning waking period being “unprotected” regarding efficacious plasma levels of drug on waking, and/or (2) an absence of modification of the heart rate response to increasing and commencing activity, a mechanism by which β blockers may, at least partially, exert their effects.

With the increased interest shown in the area of arcadian variations in physiologic parameters and cardiovascular disease processes in recent years, it has been demonstrated that there are distinct circadian rhythms in cardiovascular events, with a surge in ischemia,1 onset of acute myocardial infarction2 and sudden cardiac death3 in the morning waking hours, and a trough in such events at night. Such peaks in ischemia and onset of acute myocardial infarction are particularly related to actual time of waking and commencing activities. Because there are surges in heart rate (HR) and systolic blood pressure (BP) in the morning waking hours,4 and because β-adrenergic blocking agents blunt the morning peaks in HR,5 in addition to those of ischemia,5 onset of acute myocardial infarction2 and sudden cardiac death,6 it has been suggested that activation of the sympathetic adrenergic system may play an important role in the increased cardiovascular event rate in the period soon after waking and commencing activities. We have assessed HR and BP responses before, during and after an afternoon siesta in apparently normal subjects, and compared the changes with those recorded on waking and commencing activities in the morning to establish whether the morning waking hours are particularly associated with increases in the determinants of myocardial oxygen demand, or whether this response is reproducible after any period of “sleep”.

Long-term continuous pulmonary artery pressure monitoring was used to investigate pressure changes during different types of exercise and normal daily activities in patients with chronic heart failure. Nine men (mean age 55 years) with treated chronic heart failure underwent continuous pulmonary artery pressure measurement with use of a micromanometer-tipped catheter with in vivo calibration and frequency-modulated recording.

Accepted for publication 24 January 1996 Abstract Objective-To determine the diagnostic value of the exercise tolerance test (ETT) in women presenting with chest pain. Design-Prospective study of all women presenting to a centre with chest pain between 1987 and 1993 who were assessed by an ETT and coronary angiography. Setting-The outpatient clinic of one consultant cardiologist in a tertiary referral centre. Patients-Alil women referred to this outpatient clinic with chest pain were screened. For inclusion, patients had to perform ETT and undergo coronary angiography. Of the 347 referred during this period, 142 were excluded because they were unable to perform ETT or because of Q waves or other abnormalities on their resting electrocardiogram. Results-Overall the sensitivity of the ETT was 68% and the specificity was 61%, with a positive predictive value of 0-61 and a negative predictive value of 0-68. There were 42 false positive and 31 false negative ETT results (36% of the study group). The predictive value of a negative test was higher in younger women (< 52 years) than in the older group () 52 years) (P = 0.004), but the positive predictive value in the two groups was not significantly different. The predictive value of a negative test was also higher in those with two or fewer risk factors than in those with three or more risk factors (P = 0.001). The negative predictive value for those women above 52 years with three or more risk factors (24% of the study group) was only 0 25. Lack of chest pain during ETT was associated with a higher negative predictive value in the younger group than in the older women (P