Biomedical subjects
Publications and source records attributed to C J Pepine.
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OBJECTIVES: The purpose of this study was to determine whether endurance exercise training could buffer neuroendocrine activity in chronic heart failure patients. BACKGROUND: Neuroendocrine activation is associated with poor long-term prognosis in heart failure. There is growing consensus that exercise may be beneficial by altering the clinical course of heart failure, but the mechanisms responsible for exercise-induced benefits are unclear. METHODS: Nineteen heart failure patients (ischemic disease; New York Heart Association [NYHA] class II or III) were randomly assigned to either a training group or to a control group. Exercise training consisted of supervised walking three times a week for 16 weeks at 40% to 70% of peak oxygen uptake. Medications were unchanged. Neurohormones were measured at study entry and after 16 weeks. RESULTS: The training group (n = 10; age = 61 +/- 6 years; EF = 30 +/- 6%) and control group (n = 9; age = 62 +/- 7 years; EF = 29 +/- 7%) did not differ in clinical findings at study entry. Resting levels of angiotensin II, aldosterone, vasopressin and atrial natriuretic peptide in the training and control groups did not differ at study entry (5.6 +/- 1.3 pg/ml; 158 +/- 38 pg/ml; 6.1 +/- 2.0 pg/ml; 37 +/- 8 pg/ml training group vs. 4.8 +/- 1.2; 146 +/- 23; 4.9 +/- 1.1; 35 +/- 10 control group). Peak exercise levels of angiotensin II, aldosterone, vasopressin and atrial natriuretic peptide in the exercise and control groups did not differ at study entry. After 16 weeks, rest and peak exercise hormone levels were unchanged in control patients. Peak exercise neurohormone levels were unchanged in the training group, but resting levels were significantly (p < 0.001) reduced (angiotensin -26%; aldosterone -32%; vasopressin -30%; atrial natriuretic peptide -27%). CONCLUSIONS: Our data indicate that 16 weeks of endurance exercise training modified resting neuroendocrine hyperactivity in heart failure patients. Reduction in circulating neurohormones may have a beneficial impact on long-term prognosis.
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Our study evaluated the influence of smoking status on coronary endothelial function in normotensive patients with coronary artery disease who received placebo or the angiotensin-converting enzyme inhibitor quinapril in the TREND study (Trial on Reversing Endothelial Dysfunction). In this retrospective analysis of data from the previously published study, patients were classified as either smokers (n = 23) or nonsmokers (n = 82). Patients underwent coronary angiography at baseline and again after 6-month follow-up. The primary response variable was the net change in acetylcholine-induced diameter of the target coronary artery segments (n = 105) between the baseline and 6-month follow-up angiograms. The secondary response variables were based on analysis of all segments (n = 300) and the mean diameter responses of target and all segments at 6 months. At baseline, coronary artery vasomotor responses were similar in smokers and nonsmokers in the placebo and quinapril groups. There was a significant improvement in the primary response variable for both smokers (P = 0.008) and nonsmokers (P = 0.047) randomized to quinapril compared with placebo. At 6-month follow-up, nonsmokers in the placebo group showed no significant change in the mean vasoconstrictor responses (8.3% vs. 8.0% at acetylcholine 10(-4) mol/L), whereas nonsmokers in the quinapril-treated group showed significantly less vasoconstriction (2.7% vs. 13.2%; P = 0.003). Among smokers in the placebo group, vasoconstriction increased nonsignificantly (21.7% vs. 17.2% at baseline) but decreased significantly in the quinapril group (0.5% vs. 17.9%; P = 0.002). These results indicate that ACE inhibition improves the coronary vasomotor response in both smokers and nonsmokers, but that smokers apparently derive greater benefit.
BACKGROUND: Antiplatelet agents are widely recognized for their efficacy in reducing the occurrence of vascular events in patients with atherothrombotic disease. Aspirin is currently considered to be the "reference standard" antiplatelet agent and is recommended by the American Heart Association for use in patients with a wide range of manifestations of cardiovascular disease on the basis of its high benefit-to-risk and benefit-to-cost ratios. Recently, clopidogrel (Plavix, Bristol-Myers Squibb Co), another antiplatelet agent, was approved by the Food and Drug Administration for many of the same indications as aspirin. SUMMARY OF REVIEW: Because physicians will be faced with deciding whether to switch from the well-established practice of recommending aspirin for use in patients with atherothrombotic disease, both aspirin and clopidogrel are compared with respect to the primary factors that influence such decisions (ie, their relative efficacy, safety, cost, and convenience of use). CONCLUSIONS: Based on the available evidence, aspirin is preferred for the majority of stroke or myocardial infarction patients at risk of recurrent atherothrombotic events. Clopidogrel may, however, provide valuable therapeutic benefit over aspirin in patients with peripheral arterial disease and in stroke or myocardial infarction patients for whom aspirin treatment is contraindicated or for whom aspirin fails to achieve the desired therapeutic effect.
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Explore the source record for details and available documents.
In the United States alone, it is estimated that 60 million people have hypertension, the estimate varying according to whether hypertension is defined as a blood pressure of >140/90 mm Hg or, as has emerged from the Sixth Joint National Commission on Hypertension (JNC VI) consensus conference, of >130/90 mm Hg. Coronary artery disease frequently accompanies hypertension. In our studies of >5,000 patients with coronary artery disease, half had hypertension. The reasons are numerous. Hypertension is a major risk factor for CAD. The incidence of both conditions increases with age, so that the majority of individuals >65 years of age with coronary artery disease probably also have hypertension. Some authorities predict that, due to the increasing size of the elderly population, there will be a doubling in the prevalence of both coronary artery disease and hypertension in the next century. This is of vital concern to all clinicians. This article reviews some of the prevalence and population trends in coronary artery disease and hypertension, and some of the pathogenic mechanisms involved, as well the results of some current outcome trials.
The objectives of this study were to compare and contrast indicators of ischemia in a well-characterized group of 196 patients with coronary artery disease, documented angiographically or by verified history of myocardial infarction, and a positive exercise test result. Myocardial ischemia occurs frequently in response to everyday stressors in patients with coronary artery disease. The Psychophysiological Interventions in Myocardial Ischemia study provides a unique opportunity to study neuroendocrine and psychological manifestations of ischemia. Patients with exercise-induced ischemia underwent exercise radionuclide ventriculography and electrocardiographic monitoring and 2 laboratory mental stressors (Speech and Stroop) after being withdrawn from cardiac medications. In addition, 48-hour ambulatory electrocardiograms were recorded during routine daily activities. Patients with a history of angina within the past 3 months reported angina during the bicycle or treadmill test with a much higher frequency than patients without such an anginal history (77% vs 26%). Ejection fraction (EF) responses to the Stroop test were abnormal in 48% of patients with an abnormal EF response to the Speech task, versus 17% in patients with a normal EF response (p <0.01). Seventy-six percent of patients had an abnormal EF response to bicycle exercise. Three indicators of ischemia (ST-segment depression, wall motion abnormality, and EF response) were compared during the same laboratory stressor and across different types of stress tests. Presence of the 3 indicators was only moderately associated during exercise, and only weak or nonsignificant associations occurred among the presence of the 3 ischemic markers during mental stress. Occurrence of the same ischemic markers was moderately associated between the 2 mental stress tasks, but few associations were found between the occurrence of the same ischemic marker during exercise and mental stress. There is a marked heterogeneity of responses to psychological and exercise stress testing using electrocardiography, ambulatory electrocardiography, or radionuclide criteria for ischemia during stress. The heterogeneity may be related to differences in the magnitude or types of physiologic responses provoked and to differences in the sensitivity and specificity of the different tests used to identify ischemia.
BACKGROUND: Non-Q-wave myocardial infarction is usually managed according to an "invasive" strategy (i.e., one of routine coronary angiography followed by myocardial revascularization). METHODS: We randomly assigned 920 patients to either "invasive" management (462 patients) or "conservative" management, defined as medical therapy and noninvasive testing, with subsequent invasive management if indicated by the development of spontaneous or inducible ischemia (458 patients), within 72 hours of the onset of a non-Q-wave infarction. Death or nonfatal infarction made up the combined primary end point. RESULTS: During an average follow-up of 23 months, 152 events (80 deaths and 72 nonfatal infarctions) occurred in 138 patients who had been randomly assigned to the invasive strategy, and 139 events (59 deaths and 80 nonfatal infarctions) in 123 patients assigned to the conservative strategy (P=0.35). Patients assigned to the invasive strategy had worse clinical outcomes during the first year of follow-up. The number of patients with one of the components of the primary end point (death or nonfatal myocardial infarction) and the number who died were significantly higher in the invasive-strategy group at hospital discharge (36 vs. 15 patients, P=0.004, for the primary end point; 21 vs. 6, P=0.007, for death), at one month (48 vs. 26, P=0.012; 23 vs. 9, P=0.021), and at one year (111 vs. 85, P=0.05; 58 vs. 36, P= 0.025). Overall mortality during follow-up did not differ significantly between patients assigned to the conservative-strategy group and those assigned to the invasive-strategy group (hazard ratio, 0.72; 95 percent confidence interval, 0.51 to 1.01). CONCLUSIONS: Most patients with non-Q-wave myocardial infarction do not benefit from routine, early invasive management consisting of coronary angiography and revascularization. A conservative, ischemia-guided initial approach is both safe and effective.
We assessed plasma volume changes at peak exercise in 17 nonedematous men with chronic congestive heart failure due to coronary artery disease. Our findings suggest that acute exercise is associated with transient decreases in plasma and blood volume in these patients, similar in magnitude to those reported for healthy adults at peak exercise.
BACKGROUND: Patients with ambulatory electrocardiographic (AECG) ST-segment depression and critical coronary narrowing are known to be at increased risk for adverse outcome, but little is known about patients with AECG ST-segment depression without critical coronary narrowing. HYPOTHESIS: The objectives of this study were to characterize the coronary angiographic pathology in patients with AECG ST-segment depression but without critical (< 50% diameter stenosis) coronary narrowing and to compare demographic and clinical findings in these patients with those enrolled in the Asymptomatic Cardiac Ischemia Pilot Study with AECG ST-segment depression and critical (> or = 50% diameter stenosis) coronary narrowing. METHODS: Coronary angiograms from patients with AECG ST-segment depression were reviewed in a central laboratory and quantitative measurement of percent stenosis was performed. Clinical and angiographic comparisons were made between patients with and without critical coronary narrowing. RESULTS: Patients without critical coronary narrowing (n = 64) were younger (p = 0.02), less likely to be male (p < 0.001) or to have risk factors for coronary atherosclerosis or a history of myocardial infarction (p < 0.001), and had fewer ischemic episodes per 24 h on the screening AECG (p = 0.02) than patients with critical coronary narrowing (n = 441). Of patients without critical narrowing, one half had angiographic evidence for coronary artery disease (> or = 20% stenosis) and 60% had an ejection fraction > 70%. CONCLUSIONS: Patients with AECG ST-segment depression without critical coronary narrowing are heterogeneous, with half having measurable coronary artery disease. Demographically and clinically, they appear to be different than patients with AECG ST-segment depression with critical coronary narrowing.
BACKGROUND AND HYPOTHESIS: Successful recruitment strategies for ischemic heart disease (IHD) clinical trials must identify high yield sources and efficient methods for selecting patients likely to have coronary artery disease (CAD) and ischemia, but such information is lacking. METHODS: Data from the recently completed Asymptomatic Cardiac Ischemia Pilot (ACIP) Trial were used as a model contemporary CAD/IHD trial to determine the relative patient yields, within a specific time frame, for various recruitment sources. RESULTS: Over 15 months, a total of 88,881 patient records was screened at 10 sites. The highest yield source was found by screening records of patients directly referred by a physician for possible study entry. This source accounted for 595 of 814 or 73% of potential patients and for 30% of patients eventually randomized. The largest volume of potential patients was observed from coronary angiographic laboratory record screening, and this source accounted for 39% (n = 7.542) of potential patients and for 24% of those randomized. The exercise electrocardiography (ECG) laboratory patient records yielded only 16% (5,340/33,784) of potential patients and 35% of patients randomized, but this source required considerably more time and resources for screening. CONCLUSION: Considering that time and resources for screening are fixed by budget in any trial, there is a need to balance high volume-moderate yield sources with low volume-high yield sources in order to optimize recruitment in future larger scale trials, and these data provide information and direction to focus such screening efforts.
BACKGROUND: Cigarette smoking is a major risk factor for developing coronary artery disease and is associated with increased coronary morbidity and mortality in patients with established atherosclerosis. This report describes the influence of smoking on coronary endothelial function in normotensive patients with coronary artery disease, but without left ventricular dysfunction, severe hypercholesterolemia, or insulin-dependent diabetes mellitus. METHODS: Placebo-treated patients (n = 54) from a larger study assessing coronary endothelial function were classified at baseline as smokers or nonsmokers for this subgroup analysis. Patients underwent coronary angiography at baseline and again after 6-month follow-up. RESULTS: At baseline, there was a trend for a greater decrease in target segment diameter (n = 54) in smokers compared with nonsmokers (-17.2 +/- 5.3% vs. -8.0 +/- 2.5%, acetylcholine 10(-4) mol/l). All measured coronary artery segments (n = 202) showed similar responses (-7.3 +/- 2.7% vs. -3.8 +/- 1.3%, acetylcholine 10(-4) mmol/l, for smokers vs. nonsmokers, respectively). After 6 months, smokers showed an even greater vasoconstrictor response to acetylcholine whereas nonsmokers did not (-21.7 +/- 5.3% vs. -8.3 +/- 2.5%, acetylcholine 10(-4) mmol/l). The vasodilatory response to nitroglycerin was similar in smokers and nonsmokers. CONCLUSIONS: In current smokers, a marked decline in endothelium-dependent vasomotor response was observed over a 6-month period.
BACKGROUND: Several reports have questioned the lack of safety data on calcium antagonists as a drug class. Because this drug class is heterogeneous, unique features of certain calcium antagonists may set them apart in terms of safety and efficacy. HYPOTHESIS: With in excess of 7,000 person-years of observation from randomized clinical trials, verapamil was selected to evaluate whether there was evidence of harm in patients with cardiovascular disease. METHODS: MEDLINE search of English-language articles, Science Citation Index, Current Contents, manual review of cited references, pharmaceutical files, and investigator correspondence was performed. Independent review of 66 articles identified 14 randomized, parallel-group studies for inclusion. Independent, duplicate assessments were made of patient outcomes and trial characteristics (including study design, treatment dosage and schedule, duration of treatment, inclusion criteria, and sample size). Standard meta-analytic techniques were employed for analysis and interpretation of results. RESULTS: Based on over 4,000 person-years of observation, patients with acute myocardial infarction (MI) treated with verapamil had a decreased risk of nonfatal reinfarction compared with placebo (relative risk 0.79; 2-sided 95% confidence interval 0.65.0.97; p = 0.024). Verapamil had no significant effect on overall mortality compared with placebo (relative risk ranged from 0.93; 2-sided 95% confidence interval 0.78, 1.10; p = 0.40 to 0.86; 2-sided 95% confidence interval 0.71, 1.04; p = 0.13) depending on rules used to include or exclude patients from the pooling process. For the combined outcome of death or reinfarction, verapamil use was associated with a decreased risk compared with placebo (relative risk 0.82; 2-sided 95% confidence interval 0.70, 0.97; p = 0.016). In patients with angina involving a wide spectrum of disease severity, data were limited to 2,900 person-years of observation, and verapamil use did not appear to be associated with an apparent effect on mortality or MI. Data available from randomized studies of verapamil in patients with hypertension were too limited to reach conclusions (50 person-years of observation, with no deaths or MIs reported). Subgroups of hypertensive patients in two of the largest post-MI studies and the largest angina study, involving over 600 patients, yielded little useful added information. CONCLUSIONS: In patients with MI, the risks of both nonfatal reinfarction and the combined outcome of death or nonfatal MI were reduced over intermediate-term follow-up among patients treated with verapamil compared with controls (p = 0.024 and p = 0.016, respectively). In patients with angina, no evidence for harm was noted, but in hypertension the data were too limited to draw conclusions. These findings support the need to distinguish among different calcium antagonist compounds and to emphasize the need for more data in patients with hypertension.
Endothelial dysfunction is increasingly recognized as an early event in the pathogenesis of cardiovascular disease. This observation is consistent with the growing appreciation of the role of endothelium in maintaining cardiovascular health. Endothelial dysfunction and coronary artery disease are both linked to hypertension, hypercholesterolemia, diabetes mellitus, and cigarette smoking. Modification of these conditions improves both endothelial function and coronary artery disease outcomes. Dietary and lifestyle modifications and antioxidant vitamin supplementation have a beneficial effect on endothelial function, as do angiotensin-converting enzyme inhibitors and lipid-lowering agents. Future studies will determine whether interventions that specifically target endothelial dysfunction can reduce rates of clinical disease.
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