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Biomedical subjects

C J Pepine

Publications and source records attributed to C J Pepine.

At least 91 records · Page 5Linked to original sources
PubMed1997

Potential role of angiotensin-converting enzyme inhibition in myocardial ischemia and current clinical trials.

The understanding of the atherosclerotic disease process has broadened during the past few years to include the roles of the endothelium and of tissue angiotensin-converting enzyme (ACE) as regulators of a complex interaction of events that may lead to the development of atherosclerosis and, eventually, to the occurrence of clinical ischemia-related events. Several large clinical trials using ACE inhibitors have previously demonstrated a reduced risk of morbidity and mortality in patients with coronary artery disease and left ventricular dysfunction and in patients with heart failure or who had experienced an acute myocardial infarction. The effects of ACE inhibition are now being evaluated in other ongoing or recently completed trials in patients with evidence of coronary artery disease, but who have preserved left ventricular function and do not have an acute infarction. The results of these trials can be expected to enhance further our ability to intervene in the atherosclerotic process, resulting in improved outcomes in patients with coronary artery disease.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Prognostic markers in thrombolytic therapy: looking beyond mortality.

In the era of multiple new therapies (e.g., aspirin, beta blockers, thrombolysis, angiotensin-converting enzyme inhibitors, etc.) with the potential to improve outcome, the utility of traditional methods for predicting risk for adverse outcome after acute myocardial infarction (MI) is being reevaluated. Recent data suggest that heart failure, male gender, older age, and ischemia on ambulatory electrocardiogram (ECG) monitoring are the best predictors for increased risk of death or nonfatal MI. Exercise stress testing and ejection fraction determination provide little, if any, additional prognostic information. A new, highly promising strategy is to assess the degree of resolution in ST-segment elevation on repeated ECG monitoring following thrombolytic therapy. Studies have shown that failure to achieve prespecified degrees of ST-segment resolution within the first few hours of thrombolytic therapy is a reliable indicator of risk for post-MI mortality. Emerging data are also raising the possibility that cardiac troponin-T levels can be utilized as an important prognostic marker for adverse outcome in patients who present with acute ischemic syndromes.

Age Factors↗
PubMed1996

Left ventricular, peripheral vascular, and neurohumoral responses to mental stress in normal middle-aged men and women. Reference Group for the Psychophysiological Investigations of Myocardial Ischemia (PIMI) Study.

BACKGROUND: The normal cardiovascular response to mental stress in middle-aged and older people has not been well characterized. METHODS AND RESULTS: We studied 29 individuals 45 to 73 years old (15 women, 14 men) who had no coronary risk factors, no history of coronary artery disease, and a negative exercise test. Left ventricular (LV) volumes and global and regional function were assessed by radionuclide ventriculography at rest and during two 5-minute standardized mental stress tasks (simulated public speaking and the Stroop Color-Word Test), administered in random order. A substantial sympathetic response occurred with both mental stress tests, characterized by increases in blood pressure, heart rate, rate-pressure product, cardiac index, and stroke work index and rises in plasma levels of epinephrine and norepinephrine but not beta-endorphin or cortisol. Despite this sympathetic response, LV volume increased and ejection fraction (EF) decreased secondary to an increase in afterload. The change in EF during mental stress-varied among individuals but was associated positively with changes in LV contractility and negatively with baseline EF and changes in afterload. EF decreased > 5% during mental stress in 12 individuals and > 8% in 5; 3 developed regional wall motion abnormalities. CONCLUSIONS: Mental stress in the laboratory results in a substantial sympathetic response in normal middle-aged and older men and women, but EF commonly falls because of a concomitant rise in afterload. These results provide essential age- and sex-matched reference data for studies of mental stress-induced ischemia in patients with coronary artery disease.

Aged↗
PubMed1996

Ischemic, hemodynamic, and neurohormonal responses to mental and exercise stress. Experience from the Psychophysiological Investigations of Myocardial Ischemia Study (PIMI).

BACKGROUND: The pathophysiology of mental stress-induced myocardial ischemia, which occurs at lower heart rates than during physical stress, is not well understood. METHODS AND RESULTS: The Psychophysiological Investigations of Myocardial Ischemia Study (PIMI) evaluated the physiological and neuroendocrine functioning in unmedicated patients with stable coronary artery disease and exercise-induced ischemia. Hemodynamic and neurohormonal responses to bicycle exercise, public speaking, and the Stroop test were measured by radionuclide ventriculography, ECG, and blood pressure and catecholamine monitoring. With mental stress, there were increases in heart rate, systolic blood pressure, cardiac output, and systemic vascular resistance that were correlated with increases in plasma epinephrine. During exercise, systemic vascular resistance fell, and there was no relationship between the hemodynamic changes and epinephrine levels. The fall in ejection fraction was greater with mental stress than exercise. During mental stress, the changes in ejection fraction were inversely correlated with the changes in systemic vascular resistance. Evidence for myocardial ischemia was present in 92% of patients during bicycle exercise and in 58% of patients during mental stress. Greater increases in plasma epinephrine and norepinephrine occurred with ischemia during exercise, and greater increases in systemic vascular resistance occurred with ischemia during mental stress. CONCLUSIONS: Mental stress-induced myocardial ischemia is associated with a significant increase in systemic vascular resistance and a relatively minor increase in heart rate and rate-pressure product compared with ischemia induced by exercise. These hemodynamic responses to mental stress can be mediated by the adrenal secretion of epinephrine. The pathophysiological mechanism involved are important in the understanding of the etiology of myocardial ischemia and perhaps in the selection of appropriate anti-ischemic therapy.

Adult↗
PubMed1996

Asymptomatic Cardiac Ischemia Pilot (ACIP) Study. Relationship between exercise-induced and ambulatory ischemia in patients with stable coronary disease.

BACKGROUND: We investigated whether the presence and frequency of asymptomatic ischemic episodes recorded during ambulatory ECG (AECG) monitoring could be predicted on the basis of clinical characteristics or exercise treadmill test (ETT) performance in patients with stable coronary disease and whether the estimate of ischemia severity was similar between the AECG and ETT. METHODS AND RESULTS: Patients screened for the Asymptomatic Cardiac Ischemia Pilot (ACIP) study were selected for the current analysis if data were available from 48-hour AECG monitoring as well as from an ETT during which the patient developed > or = 1-mm ST-segment depression. Exercise ECG data were available for 143 of the 910 patients without ischemic episodes and for 659 of the 910 patients with ischemic episodes during AECG monitoring. Angina was more frequent among patients with ambulatory ischemic episodes than among patients without such ischemia (P < .001). Patients with AECG ischemia had a consistently more marked ischemic response on the ETT than patients without AECG ischemia; patients likely to have AECG ischemia could be predicted on the basis of ETT performance characteristics. However, the correlation coefficients between the severity of ischemia estimated by ETT and by AECG were small. CONCLUSIONS: There are significant relations between ischemia detected by AECG monitoring and by ETT, but the relations are limited, indicating that the two tests are not redundant to characterize coronary patients. A larger study investigating the prognostic significance of the ischemia identified by each modality, with follow-up for clinical events, will be necessary to determine the most appropriate methods to evaluate patients with stable coronary disease.

Coronary Disease↗
PubMed1996

Effects of A1 adenosine receptor agonism using N6-cyclohexyl-2'-O-methyladenosine in patients with left ventricular dysfunction.

BACKGROUND: The role of adenosine as a neuromodulator in heart failure was studied with the use of a selective adenosine A1 receptor agonist, N6-cyclohexyl-2'-O-methyladenosine (SDZ-WAG 994). METHODS AND RESULTS: Fifty patients with heart failure symptoms and moderate left ventricular systolic dysfunction had a balloon flotation catheter inserted. Patients received placebo or a single oral dose of either 1, 2, or 5 mg SDZ-WAG 994. After baseline measurements were obtained, hemodynamic and electrophysiological recordings were repeated at 30-minute intervals for the next 4 hours, then every 6 hours for the next 24 hours. Blood samples for norepinephrine, epinephrine, aldosterone, atrial natriuretic peptide, and plasma renin activity were drawn at baseline and 2 hours after drug administration. A adenosine receptor agonism produced no important effects on systemic, right atrial, pulmonary artery, or pulmonary capillary wedge pressures; cardiac index; respiratory rate; or heart rate. The PR interval (a reflection of A1 receptor-mediated activity) increased significantly in a stepwise fashion. At the 5-mg dose of SDZ-WAG 994, significant increases in atrial natriuretic peptide (216 +/- 137 to 407 +/- 146 pg/mL) and norepinephrine (477 +/- 243 to 618 +/- 237 pg/mL) levels were noted. CONCLUSIONS: A1 adenosine receptor agonism with SDZ-WAG 994 resulted in no significant hemodynamic changes at rest in this subset of patients with left ventricular dysfunction. An increase in the PR interval and atrial natriuretic peptide level, consistent with adenosine A1 receptor-mediated activity, was observed. In addition, an increase in the norepinephrine level was observed, suggesting a role for adenosine as a peripheral nervous system neuromodulator.

Adenosine↗
PubMed1996

Angiotensin-converting enzyme inhibition with quinapril improves endothelial vasomotor dysfunction in patients with coronary artery disease. The TREND (Trial on Reversing ENdothelial Dysfunction) Study.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors may exert some of their benefits in the therapy of hypertension, congestive heart failure, and acute myocardial infarction by their improvement of endothelial dysfunction. TREND (Trial on Reversing ENdothelial Dysfunction) investigated whether quinapril might improve endothelial dysfunction in normotensive patients with coronary artery disease and no heart failure, cardiomyopathy, or major lipid abnormalities so that confounding variables that affect endothelial dysfunction could be minimized. METHODS AND RESULTS: Using a double-blind, randomized, placebo-controlled design, we measured the effects of quinapril (40 mg daily) on coronary artery diameter responses to acetylcholine using quantitative coronary angiography. The primary response variable was the net change in the acetylcholine-provoked constriction of target segments between the baseline (prerandomization) and 6-month follow-up angiograms. The constrictive responses to acetylcholine were comparable in the placebo (n = 54) and quinapril (n = 51) groups at baseline. After 6 months, only the quinapril group showed significant net improvement in response to incremental concentrations of acetylcholine (4.5 +/- 3.0% [mean +/- SEM] versus -0.1 +/- 2.8% at 10(-6) mol/L and 12.1 +/- 3.0% versus -0.8 +/- 2.9% at 10(-4) mol/L, quinapril versus placebo, respectively; overall P = .002). CONCLUSIONS: TREND shows that ACE inhibition with quinapril improved endothelial dysfunction in patients who were normotensive and who did not have severe hyperlipidemia or evidence of heart failure. These benefits of ACE inhibition are likely due to attenuation of the contractile effects and superoxide-generating effects of angiotensin II and to enhancement of endothelial cell release of nitric oxide secondary to diminished breakdown of bradykinin.

Acetylcholine↗
PubMed1996

What does it mean to improve prognosis of patients with coronary artery disease?

When improvement in prognosis of patients with coronary artery disease is the goal, the physician must be knowledgeable about the patient-related factors and the fact that therapies influence prognosis in such patients. Further, the clinician must be very specific in choice of therapeutic agents directed toward improvement of prognosis, and this process must include prescriptions of appropriate formulation and dosage.

Cardiovascular Agents↗
PubMed1996

Relation of patient characteristics to cardiac ischemia during daily life activity (an Asymptomatic Cardiac Ischemia Pilot Data Bank Study).

Cardiac ischemia during daily life activities, detected by ambulatory electrocardiographic (AECG) monitoring has been associated with increased risk for adverse outcomes. Because daily life ischemia is usually asymptomatic, prevalence and descriptive data of patients with asymptomatic cardiac ischemia (ACI) are not well defined. Accordingly, patients screened for the Asymptomatic Cardiac Ischemia Pilot (ACIP) trial by 48-hour AECG monitoring were investigated to identify factors associated with ACI. A total of 1,820 patients with ischemia on a screening stress test and/or known or suspected coronary artery disease underwent AECG monitoring. Their mean age was 61 years, range 33 to 89; 83% were men and 81% were white. On AECG monitoring, ACI occurred in 897 patients (49%). There was a modest trend (p = 0.04) between increasing age and ACI prevalence. Increased risk for ACI was observed in patients reporting angina 6 weeks before screening (odds ratio 1.38, 99% confidence interval 1.08 to 1.77, p = 0.0008). There was a positive association between increases in heart rate during daily life and ACI prevalence (p < 0.0001). No daily, monthly, or seasonal variation in ACI prevalence was found, although ACI was more prevalent in northern than southern sites. In this group of clinically stable patients, selected on the basis of high risk for coronary artery disease, the prevalence of ACI was higher than expected from previous reports. Several readily available clinical characteristics (i.e., advanced age, recent angina, increased heart rate change with daily activity) were associated with significantly increased probability of ACI.

Activities of Daily Living↗
PubMed1996

Comparison of subgroups assigned to medical regimens used to suppress cardiac ischemia (the Asymptomatic Cardiac Ischemia Pilot [ACIP] Study).

This report focuses on the subset of 235 patients from the Asymptomatic Cardiac Ischemia Pilot (ACIP) study receiving randomly assigned medical therapy to treat angina and suppress ischemia detected on ambulatory electrocardiography: 121 patients received the sequence of atenolol and nifedipine, and 114 diltiazem and isosorbide dinitrate. After 12 weeks of therapy, the primary end point (absence of ambulatory electrocardiographic (ECG) ischemia and no clinical events) was reached in 47% of atenolol/nifedipine- versus 31% of diltiazem/isosorbide dinitrate-treated patients (adjusted p = 0.03). A trend to increased exercise time to ST depression was seen in the atenolol and nifedipine versus diltiazem and isosorbide dinitrate regimens (median treadmill duration 5.8 vs 4.8 minutes; p = 0.04). However, when adjusted for baseline imbalances in ambulatory ECG ischemia, the 2 medical combinations were similar in suppression of ambulatory ECG ischemia. In both medication regimens, an association between mean heart rate and ischemia on ambulatory electrocardiography after 12 weeks of treatment was observed so that patients on either regimen with a mean heart rate > 80 beats/min had ischemia detectable almost twice as often as those with a mean heart rate < 70 beats/min (p < 0.001).

Angina Pectoris↗
PubMed1996

Ongoing clinical trials of angiotensin-converting enzyme inhibitors for treatment of coronary artery disease in patients with preserved left ventricular function.

At present there is considerable activity in the area of prevention of atherosclerosis-related events using angiotensin-converting enzyme inhibitors. Large trials have demonstrated significant reduction in cardiovascular morbidity and mortality with long-term use of angiotensin-converting enzyme inhibitors in patients with left ventricular dysfunction, heart failure or acute myocardial infarction. Reductions in acute ischemic events (e.g., myocardial infarction, unstable angina and need for early revascularization) were independent of ejection fraction and were greater than would be expected from the small reduction in blood pressure that occurred, suggesting that other patients with coronary artery disease may benefit from angiotensin-converting enzyme inhibitor therapy. This hypothesis is being tested in multiple double-blind, randomized, controlled clinical trials with durations of follow-up of 3 to 5 years that will involve approximately 30,000 patients. The trials vary with respect to patient population (e.g., normotensive vs. hypertensive, normolipidemic vs. hyperlipidemic, with vs. without diabetes mellitus), angiotensin-converting enzyme inhibitor used and outcome measures. When available, the results of these clinical trials could have very important implications for the role of long-term angiotensin-converting enzyme inhibitor therapy for preventing or delaying the development of atherosclerosis-related ischemic events.

Adolescent↗
PubMed1995

Circadian variation in coronary tone in patients with stable angina. Protective role of the endothelium.

BACKGROUND: Coronary endothelium plays a key role in the regulation of coronary tone, platelet adhesion, and aggregation, which are important factors in triggering acute cardiovascular events. However, its role in modulating the effects of circadian variations on coronary tone is not known. METHODS AND RESULTS: Responses of 72 nonstenotic coronary segments to acetylcholine and nitroglycerin were measured in 12 patients with chronic stable angina at 6 AM and 1 PM. After baseline angiography, three infusions of acetylcholine (10(-6), 10(-5), and 10(-4) mol/L) were administered selectively into the left coronary artery, followed by nitroglycerin. Diameters (in millimeters) of proximal, middle, and distal segments were measured by quantitative techniques. Forty-seven segments showed a constrictor response to acetylcholine (group 1, dysfunctional endothelium), and 25 other segments showed a dilator response (group 2, normally functioning endothelium). In group 1, the constrictor response to acetylcholine was significantly greater in the morning than in the afternoon (23 +/- 3% and 10 +/- 1%, mean +/- SEM, respectively; P < .001), and the dilator response to nitroglycerin was also significantly greater in the morning than in the afternoon (19 +/- 2% and 11 +/- 2%; P < .01). In group 2, the dilator response to acetylcholine did not differ significantly between the morning and afternoon (22 +/- 3% and 17 +/- 2%, respectively; P = NS), and the dilator response to nitroglycerin was also similar at both times of the day (30 +/- 3% and 28 +/- 4%, respectively; P = NS). CONCLUSIONS: Coronary segments with dysfunctional endothelium exhibit an early morning exaggeration in vasomotor activity, whereas segments with normally functioning endothelium do not show circadian variations. This suggests a potential protective role for the endothelium in modulating variations in coronary tone that may contribute to increased incidence of cardiovascular events in the early morning hours.

Acetylcholine↗
PubMed1995

Asymptomatic Cardiac Ischemia Pilot (ACIP) Study. Improvement of cardiac ischemia at 1 year after PTCA and CABG.

BACKGROUND: Cardiac ischemia on the ambulatory ECG (AECG) and/or on the exercise treadmill test (ETT) is associated with an increased risk of adverse outcome. Myocardial revascularization more often suppresses cardiac ischemia than does medical management alone. However, few studies have compared the effects of percutaneous transluminal coronary angioplasty (PTCA) with those of coronary artery bypass grafting (CABG) on cardiac ischemia and clinical outcome. METHODS AND RESULTS: A total of 558 patients were randomly assigned to one of three treatment strategies in the Asymptomatic Cardiac Ischemia Pilot (ACIP) study: angina-guided medical strategy (n = 184), ischemia-guided medical strategy (n = 182), or revascularization (n = 192). In patients assigned to revascularization, the choice of the procedure, PTCA or CABG, was made by the clinical unit staff and patient based on a coronary angiogram usually performed within 2 months of enrollment. CABG was selected in 78 patients and PTCA in 92 patients. At 12 weeks, ischemia on the AECG was suppressed in 70% of CABG patients versus 46% of PTCA patients (P = .002). Ischemia on the ETT was no longer present in 46% versus 23% of the patients, respectively (P = .005). Angina, within 4 weeks of the follow-up visit, was absent in 90% versus 68%, respectively (P = .001). These clinical variables remained improved in both groups at 1 year. Clinical events (myocardial infarction or repeat revascularization) occurred in 1 CABG patient versus 7 PTCA patients at 12 weeks, and in 1 versus 16 patients, respectively, at 12 months (P < .001). CONCLUSIONS: Ischemia on the AECG and ETT and angina were relieved in many patients after both procedures; however, CABG was superior to PTCA, and it was associated with a lower incidence of clinical events at 1 year. These results suggest that more complete revascularization relates to better clinical outcome. However, a large trial is needed to confirm these results.

Angina Pectoris↗
PubMed1995

Time-series analysis of long-term ambulatory myocardial ischemia: effects of beta-adrenergic and calcium channel blockade.

We have previously demonstrated the utility of time-series analysis applied to 72-hour ambulatory electrocardiographic data in patients with coronary artery disease. The present investigation applied time-series analysis to long-term (120-hour) ambulatory electrocardiographic data to determine the minimal period of monitoring needed (1) to detect periodicity of ischemia-related variables in ambulatory patients, (2) to describe auto-correlation and cross-correlation functions for heart rate and ischemia, and (3) to describe the effects of beta-adrenergic and calcium channel blockade on circadian characteristics and coupling of heart rate and ischemia. A double-blind crossover design was used to obtain 120-hour recordings during placebo, atenolol (200 mg/day), and diltiazem (360 mg/day) administration. During all three treatment periods, distinct circadian variation of heart rate was documented by autocorrelation and Fourier analysis. Ischemia did not exhibit clear periodicity as indexed by autocorrelation in any period; however, it was coupled to heart rate in all treatment periods as reflected in cross-correlation analysis. Although diltiazem did not quantitatively alter the circadian characteristics of heart rate or ischemia, atenolol produced a shift in the coupling between remaining ischemia and heart rate in time. Significant autocorrelation was detected for all treatment periods after 72 hours of monitoring, suggesting that 72 hours is the minimum amount of time needed for analysis of ambulatory electrocardiographic data in patients with coronary artery disease.

Atenolol↗