Biomedical subjects

E Thaulow

Publications and source records attributed to E Thaulow.

At least 55 records · Page 3Linked to original sources

PubMed1998

Attenuated physical exercise capacity in smokers compared with non-smokers after coronary angioplasty despite similar luminal diameters.

AIMS: To study the impact of smoking on the change in exercise capacity in patients treated with coronary angioplasty. METHODS: Three hundred and sixty-eight men below 70 years of age eligible for percutaneous transluminal coronary angioplasty without previous coronary interventions were consecutively enrolled. Of the 334 patients (90.8%) who completed the study 77 (23.1%) were current smokers. Exercise tests were performed before percutaneous transluminal coronary angioplasty, 2 and 19 +/- 2.4 weeks after percutaneous transluminal coronary angioplasty. Coronary angiography was done in 333 patients (99.7%) (at mean 19 +/- 2.4 weeks). The angiograms were analysed quantitatively. RESULTS: There were no differences in the clinical and angiographic characteristics among the groups except for age. The non-smokers were older than the smokers (55.7 vs 52.4 years (P = 0.001)). Exercise capacity was equal before percutaneous transluminal coronary angioplasty in both groups (17.6 vs 16.5 W x min-1 x kg-1). Non-smokers had a significantly higher increase in exercise capacity than smokers from baseline to 2 weeks after percutaneous transluminal coronary angioplasty (mean difference 4.3 W x min-1 x kg-1 (95% CI: 2.3 to 6.2; P < 0.001)), and from baseline to 19 weeks after percutaneous transluminal coronary angioplasty (mean difference 3.9 W x min-1 x kg-1 (95% CI: 1.6 to 6.2; P < 0.001). CONCLUSION: A clinical benefit from percutaneous transluminal coronary angioplasty was seen in both groups as judged from exercise testing. Smokers had a substantially lower increase in exercise capacity than non-smokers, indicating an attenuated benefit from percutaneous transluminal coronary angioplasty among smokers.

Adult↗

PubMed1998

Clustering of coronary risk factors with increasing blood pressure at rest and during exercise.

BACKGROUND: The metabolic cardiovascular syndrome is the label given to the clustering of unfavourable levels of a number of coronary risk factors in subjects with high resting blood pressures. We found recently that exercise blood pressure had a strong independent prognostic value. OBJECTIVE: To search for possible similar associations between exercise blood pressure levels and coronary risk factors by studying conventional and recently acknowledged coronary risk factors. METHODS: The study population comprised 1999 healthy men aged 40-59 years. Age-adjusted coronary risk factor levels and their relation to resting and exercise blood pressures were studied. Resting blood pressure was measured after subjects had rested supine for 5 min. The exercise blood pressure used was the systolic blood pressure measured with the subject sitting on a bicycle ergometer at the end of a work load of 600 kpm/min (100 W) for 6 min. RESULTS: Besides corroborating the relation between the metabolic syndrome and resting blood pressure levels, we observed similar or even stronger associations between levels of various coronary risk factors and exercise blood pressure. We found rather strong, direct associations between exercise blood pressure and total cholesterol level, fasting triglyceride level and body mass index whereas inverse relations were found for glucose tolerance, physical fitness, pulmonary functioning and the ability to increase heart rate during exercise. Virtually all these associations had a level of statistical significance of P<0.001. CONCLUSIONS: High exercise blood pressure levels are strongly associated with unfavourable levels of a number of important coronary risk factors. A similar metabolic syndrome to that observed in subjects with high resting blood pressures therefore appears to be present in subjects with high exercise blood pressure responses. These associations may considerably amplify the independent risk of high blood pressure responses to moderate exercise.

Adult↗

PubMed1998

Aerobic endurance testing of children and adolescents--a comparison of two treadmill-protocols.

Fifty-eight children and adolescents of both sexes, aged 8-16, were tested on a treadmill using two different protocols. The well-known Bruce-protocol has the disadvantages of steep incline and large increments at each step. A new protocol (Oslo-protocol) with less incline and smaller increments was compared to the Bruce-protocol. The results from the two protocols showed no differences with regard to peak oxygen uptake (VO2peak) or peak heart rate (HRpeak). However, the respiratory exchange ratio (R) and blood lactate concentration [La-] showed higher values when the Bruce-protocol was used. The study also indicated that the often used criteria of HRpeak, R and achievement of a plateau in VO2 to estimate VO2peak, were not reliable indicators in either protocol. When time to exhaustion was used as an estimation of aerobic endurance level, the Oslo-protocol discriminated better than the Bruce-protocol. As a conclusion, the results indicate that none of the criteria may be used as a reliable indicator of having achieved VO2peak. An experienced testleader may be essential to define when VO2peak has been reached in children. On the basis of the results from the current study, the Oslo-protocol seems suitable as a test-protocol when testing children and adolescents for VO2peak.

Adolescent↗

PubMed1997

[Catheter treatment of congenital heart defects. Arterial septal defects and open ductus arteriosus].

The results of new methods for catheter treatment of congenital heart defects are presented. Between 1989 and 1996 closure of a patent ductus arteriosus was performed in 66 instances on 63 patients, eight of which were with coils. Three patients were treated twice, one with an additional umbrella, two with coils. The overall complete closure rate for umbrellas was 75%, after two ducts, which were initially totally occluded, recanalized. In six more patients the procedure was either aborted or indication was not present. All six ducts treated with coils as the first procedure were completely closed. One of two patients who had residual leak after previous umbrella treatment achieved complete closure after subsequent coil implantation. Closure of atrial septal defects in the oval fossa was performed using the Amplatzer septal occluder in seven children. Complete closure was achieved in all of them. There have been no complications, in particular there have been no cases of embolization in any of the groups. The results seem to indicate that coil occlusion of a persistently patent duct may be at least as good as the umbrella in terms of complete closure. So far both methods have been safe, but experience with coils is limited. The closure of atrial septal defects shows encouraging results. We will continue to offer this treatment as an alternative to open heart surgery in carefully selected patients.

Adolescent↗

PubMed1997

Relationship between exercise hyperpnea, hemodynamics, and blood gases before and during glyceryl trinitrate infusion in patients with exercise-induced elevation of pulmonary artery wedge pressure.

BACKGROUND: The mechanisms underlying the excessive ventilatory response to exercise in patients with cardiac failure are still not fully understood. HYPOTHESIS: This study was undertaken to investigate the mechanisms behind exercise hyperpnea in patients with exercise-induced left ventricular dysfunction. METHODS: In 18 patients, aged 57-82 years, all with atherosclerotic lumbar aorta aneurysm and pulmonary artery wedge pressure (PAWP) > 25 mmHg during supine exercise, ventilation (V), central hemodynamics, and arterial and venous blood gases were examined during supine rest and exercise, before and during infusion of glyceryl trinitrate (GTN). RESULTS: Before GTN, exercise PAWP was 32.2 +/- 6.1 mmHg and V/V O2 was 33.8 +/- 7.7 l/l (130% of predicted). With GTN, exercise PAWP was markedly reduced to 15.3 +/- 3.8 mmHg (p < 0.001), whereas V/V O2 was only marginally reduced to 32.3 +/- 3.0 l/l (124% of predicted) (p < 0.05). Exercise physiologic dead space (VD/VT) declined from 0.31 +/- 0.16 to 0.26 +/- 0.17 (p < 0.05), while PaCO2 was reduced from 5.20 +/- 0.31 to 5.10 +/- 0.24 kPa (p < 0.05). PvO2 and cardiac output (CO), however, were unchanged below normal. CONCLUSION: The data show that exercise-induced hyperpnea was not substantially reduced by rapid normalization of PAWP and could not be related to preservation of normal PaCO2 in the presence of high VD/VT. The persistence of exercise hyperpnea and reduced PvO2 after GTN is consistent with augmented ventilatory stimuli from hypoxia-induced metabolic abnormalities in the skeletal muscles, or/and persistently reduced CO, due to changes in the integrated superior command of ventilation and circulation.

Aged↗

PubMed1997

Clinical promise of calcium antagonists in the angioplasty patient.

Depending upon the definition used, restenosis occurs in 10-60% of patients who undergo percutaneous transluminal coronary angioplasty. Restenosis appears to be the result of a combination of pathophysiological processes, including elastic recoil of arterial walls, platelet deposition and thrombus formation and resultant fibro-cellular neointimal hyperplasia. A range of pharmacological interventions has been used in an attempt to reduce the rate of restenosis following angioplasty, with little success. Furthermore, many patients who undergo angioplasty still suffer from ischaemia after the procedure. Calcium antagonists, such as the long-acting dihydropyridine amlodipine, have been demonstrated to be effective in the control of both symptomatic and asymptomatic ischaemia and are, therefore, likely to be of utility for this purpose in angioplasty patients. Calcium antagonists also exhibit characteristics that may lead to a reduction in restenosis, in that they inhibit platelet aggregation, reduce vasoplasm and inhibit the action of mitogens which stimulate proliferation and migration of smooth muscle cells. The results of five trials of calcium antagonists in angioplasty patients have been individually unconvincing in terms of prevention of restenosis, only one trial demonstrated a significant effect. However, a meta-analysis of these results has demonstrated an approximately 30% reduction in the chance of restenosis in those patients treated with calcium antagonists. The Coronary Angioplasty Amlodipine in Restenosis (CAPARES) trial has been initiated to assess the impact of amlodipine upon the rate of restenosis and angina/ischaemia after the procedure.

Amlodipine↗

PubMed1997

Predictors of 7-year changes in exercise blood pressure: effects of smoking, physical fitness and pulmonary function.

BACKGROUND: The health status of 1999 apparently healthy men, aged 40-59 years, was ascertained after 16 years. We found that their systolic blood pressure during an ergometer exercise test added prognostic information beyond that from their blood pressure at rest concerning total cardiovascular mortality and mortality from myocardial infarction. OBJECTIVE: To determine predictors of the change in systolic blood pressure at rest during 7 years and of the change in the prognostically important peak exercise systolic blood pressure at 600 kilopondmetres/min during 7 years. METHODS: Predictors of the changes in blood pressures were investigated in 1393 middle-aged men who had been healthy without drug treatment for chronic disease or hypertension for 7 years. Twelve potential independent predictors were investigated. RESULTS: Previous blood pressures, age and body mass index were independent predictors and could explain 18% of the change in systolic blood pressure at rest over 7 years. For systolic blood pressure at 600 kilopondmetres/min also smoking was associated with a rise whereas a high body mass index, physical fitness and forced expiratory volume in 1 s (all P< 0.001) were associated with lower blood pressure, explaining 19% of the variability. CONCLUSIONS: Beyond a relatively strong tracking of blood pressures and the expected effect of age, smoking is associated with a 7-year rise in exercise systolic blood pressure whereas relatively higher body mass, physical fitness and pulmonary function are associated with lower exercise systolic blood pressure after 7 years in middle-aged healthy men.

Adult↗

PubMed1997

Seasonal covariation in physical fitness and blood pressure at rest and during exercise in healthy middle-aged men.

It has been suggested that seasonal changes in cardiovascular risk factors may explain simultaneous seasonal variations in cardiovascular diseases. Since systolic blood pressure (SBP) during an ergometer exercise test adds prognostic information beyond that of BP at rest we aimed to study whether SBP during exercise also demonstrates similar seasonal variation after adjustment for covariates. Blood pressures of 1574 apparently healthy men aged 40-59 years examined throughout two consecutive years showed a seasonal variation, with higher SBP during the period September-December compared with the rest of the year, 2.8 mmHg (p = 0.003) at rest and 4.2 mmHg (p < 0.001) during ergometer exercise at 600 kpm min-1. After adjustment for a parallel marked drop in physical fitness, these differences were no longer significant. Thus, the seasonal variation in SBP at rest and during exercise in apparently healthy middle-aged men may be explained by a parallel seasonal variation in physical fitness. A seasonal covariation in long-term cardiovascular mortality in the same study suggests that the parallel variation of independent risk factors is of clinical significance.

Adult↗

PubMed1997

Exercise blood pressure predicts cardiovascular death and myocardial infarction.

OBJECTIVE: To investigate whether the exercise systolic blood pressure predicts cardiovascular morbidity and mortality and in particular myocardial infarction beyond that prediction provided by the casual blood pressure at rest and independently of other cardiovascular risk factors. METHODS: We performed an average 16-year follow-up of 1999 middle-aged healthy men. RESULTS: We found that the systolic blood pressure during 6 min on a moderate load during a bicycle ergometer exercise test was a stronger predictor of total cardiovascular mortality and of morbidity and mortality from myocardial infarction than was the blood pressure of the subjects at rest. Furthermore, an early rise in systolic blood pressure during exercise seems to add prognostic information only when the systolic blood pressure of the subject at rest is elevated mildly (>/= 140 mmHg). Subjects whose systolic blood pressure increased to >/= 200 mmHg had a more than twofold greater risk of dying from cardiovascular causes and from myocardial infarction in particular within 16 years than did normotensives and men whose systolic blood pressure was >/= 140 mmHg when they were at rest whose systolic blood pressure did not increase to a similar extent, after we had adjusted for differences in age and a rather large number of traditional risk factors for cardiovascular disease. CONCLUSION: We suggest that systolic blood pressures recorded during standardized ergometer exercise testing may help one to distinguish between severe and less severe cases of hypertension among middle-aged men.

Journal Article↗

PubMed1996

Hemodynamic time course of acute and chronic isosorbide dinitrate treatment at rest and during exercise in patients with stable ischemic heart disease.

HYPOTHESIS: The study was undertaken to establish differences between venous and arterial isosorbide dinitrate (ISDN) effects during acute and chronic treatment, hemodynamics at rest, and during supine exercise. METHODS: These effects were assessed invasively in 16 patients with stable ischemic heart disease before and at hourly intervals for 4 h after administration of peroral 30 mg ISDN. Eight patients were previously untreated (acute group), and eight were treated with 30 mg ISDN asymmetrically b.i.d. for two weeks (chronic group). RESULTS: Prior to ISDN administration, right atrial, mean pulmonary artery, pulmonary artery wedge, and mean arterial pressure (RAP, MPAP, PAWP, and MAP) rose from normal resting to pathologic values during exercise. One h after ISDN administration, all exercise pressures were normalized (p < 0.001). During the following 3 h, exercise RAP rose similarly in both groups (p < 0.01), while MPAP rose particularly in the chronic group (p < 0.001). Exercise PAWP and MAP, however, remained low in the acute group, but increased markedly in the chronic group (p < 0.01), particularly from the third to the fourth hour after ISDN. CONCLUSION: The daily, asymmetric administration of 30 mg ISDN b.i.d. maintained beneficial, anti-ischemic effects for 2 to 3 h after a morning dose of the drug, but thereafter attenuation of the effects occurred in the arteries but not in the veins.

Exercise Test↗

PubMed1996

Serum N-terminal proatrial natriuretic factor in children with congenital heart disease.

An objective and simple method of establishing and grading heart failure in children is needed. The N-terminal of the atrial natriuretic factor prohormone, called proANF, is stable in vitro, relatively easy to measure and has been demonstrated as a clinically useful marker of heart failure in adults. We measured proANF in 62 children with congenital heart disease and in 62 age-matched controls, in order to examine the relationship of proANF to different clinical and haemodynamic parameters. Echo Doppler cardiography was performed in all children, and 29 also underwent cardiac catheterization. The children were classified for volume and pressure load in each cardiac chamber, for shunt size and for signs of heart failure. In paediatric patients without cardiac or renal disease, median proANF was 384 pmol.l(-1). In children with congenital heart disease, median proANF was 904 (200-5320) pmol.l(-1) (P < 0.001). The three groups with the highest proANF levels were children with documented high atrial pressure (median proANF 1885 pmol.l(-1)), a large left to right shunt (median proANF 1565 pmol.l-(1)) and moderate or severe heart failure (median proANF 1305 pmol.l(-1)). Furthermore, the proANF level correlated negatively with age and glomerular filtration rate. We conclude that elevation of the proANF level is related to atrial pressures, heart failure and a high pulmonary to systemic flow ratio. These findings make proANF a potential new diagnostic tool in heart disease in children.

Adolescent↗

PubMed1996

Exercise blood pressure predicts mortality from myocardial infarction.

Apparently healthy men (n=1999, 40 to 59 years old) were investigated from 1972 through 1975 to determine whether systolic blood pressure during bicycle ergometer exercise predicts morbidity and mortality from myocardial infarction beyond that of casual blood pressure taken after 5 minutes of supine rest. During a follow-up of 31 984 patient-years (average, 16 years), 235 subjects had myocardial infarctions, of which 143 were nonfatal and 92 were fatal. Exercise blood pressure was more strongly related than casual blood pressure to both morbidity and mortality from myocardial infarction. Among 520 men with casual systolic blood pressure = 140 mm Hg, 304 increased their systolic blood pressure to > or = 200 mm Hg during 6 minutes of exercise at an initial workload of 600 kpm/min. These 304 men had an excessive risk of myocardial infarction (18.8% versus 9.5% among the 1294 men with casual blood pressure < 140 mm Hg and exercise blood pressure < 200 mm Hg; P < .001). As many as 58% of those with myocardial infarction in this group died, compared with 33% (range, 26% to 35%) for all other groups (P=.0011), including those with casual blood pressure > or = 140 mm Hg and exercise blood pressure < 200 mm Hg. Thus, exercise blood pressure is a stronger predictor than casual blood pressure of morbidity and mortality from myocardial infarction, and an early rise in systolic blood pressure during exercise adds prognostic information about mortality from myocardial infarction among otherwise healthy middle-aged men with mildly elevated casual blood pressure. We suggest that blood pressure taken during standardized exercise testing may distinguish between severe and less severe hypertension.

Adult↗

PubMed1995

Long term effects of smoking on physical fitness and lung function: a longitudinal study of 1393 middle aged Norwegian men for seven years.

OBJECTIVE: To study association between smoking habits and long term decline in physical fitness and lung function in middle aged men who remained healthy. DESIGN: Baseline and follow up measurements performed during 1972-5 and 1980-2 respectively. SETTING: National University Hospital of Oslo, Norway. SUBJECTS: 1393 men aged 40-59 at baseline who were all healthy at baseline and at follow up. MAIN OUTCOME MEASURES: Forced expiratory volume in one second and physical fitness (defined as total work done during a symptom limited bicycle ergometer test divided by body weight. RESULTS: Initial fitness was substantially lower among 347 persistent smokers than among 791 persistent non-smokers (1349 J/kg v 1618 J/kg), as was initial forced expiratory volume (3341 ml v 3638 ml). Mean (95% confidence interval) decline in fitness over 7.2 years was 217 (185 to 249) J/kg among smokers compared with 86 (59 to 113) J/kg among non-smokers (P < 0.001). Corresponding declines in forced expiratory volume were 271 (226 to 316) ml in smokers and 116 (85 to 147) ml in non-smokers (P < 0.001). Differences between smokers and non-smokers remained practically unchanged after adjustment for age and level of physical activity. Changes in fitness and forced expiratory volume among 199 men who had stopped smoking mimicked the findings for persistent non-smokers, and 56 men who started smoking presented findings close to those of persistent smokers. CONCLUSION: Decline in physical fitness and lung function among healthy middle aged men was considerably greater among smokers than among non-smokers and could not be explained by differences in age and physical activity.

Adult↗

PubMed1995

Early hemodynamic effects at rest with acute and chronic isosorbide dinitrate treatment in patients with ischemic heart disease.

Asymmetric dosage regimens are used to circumvent development of nitrate tolerance and are believed to restore totally the hemodynamic responsiveness to an acute dosage of nitrates. This study assessed invasively the hemodynamics during supine rest before and for 50 min after peroral 30 mg isosorbide dinitrate (ISDN) in 16 patients with stable ischemic heart disease; 8 previously untreated patients (NT group) and 8 patients treated asymmetrically b.i.d. with 30 mg ISDN for 14 days prior to the invasive investigation (T group). Before initiation of treatment, both groups had identical mean arterial pressure (MAP) and heart rate (HR). On the day of invasive investigation, before intake of ISDN, MAP was higher in the T group but unchanged in the NT group. After the intake of ISDN, right atrial pressure (RAP), mean pulmonary arterial pressure, and pulmonary arterial wedge pressure declined markedly within 10 to 15 min in both groups, while MAP showed a more protracted decline, reaching a new level only after 25 to 30 min. In the NT group, HR accelerated markedly and remained elevated throughout the observation period, whereas in the T group HR showed no significant alteration after ISDN intake. At the end of the observation period, the cardiac index (CI) was definitely reduced in the NT group, but remained unchanged in the T group, while the systemic vascular resistance index was unchanged in the former and was clearly reduced in the latter. It is concluded that the fall in MAP in the NT group was solely due to a fall in CI, and that the decline in RAP and venous return in the NT group induced neurohumoral reflexes leading to a rise in HR and prevention of arterial dilation, whereas in the T group, already influenced by chronic treatment, such acute counterregulatory responses were markedly attenuated or absent.

Aged↗

PubMed1995

Heart rate increase and maximal heart rate during exercise as predictors of cardiovascular mortality: a 16-year follow-up study of 1960 healthy men.

BACKGROUND: Resting heart rate is directly associated and maximal exercise-induced heart rate inversely associated with cardiovascular mortality, and therefore their difference might contain prognostic information from both variables. The comparative long-term prognostic values of maximal exercise-induced heart rate and of the difference between it and resting heart rate were studied in apparently healthy middle-aged men. METHODS: Resting heart rate and maximal exercise-induced heart rate were measured, and their difference calculated, in 1960 apparently healthy men aged 40-59 years, and mortality was recorded over a period of 16 years. Conventional coronary risk factors were assessed at baseline. RESULTS: Both the difference between the two heart rates and the maximal exercise-induced heart rate were strongly, independently and inversely associated with cardiovascular mortality after adjustment for age, smoking, systolic blood pressure, lung function, glucose tolerance, serum cholesterol level, serum triglycerides level, physical fitness and exercise ECG findings. The adjusted relative risk of cardiovascular death in heart-rate difference quartiles 3 and 4 compared with that in quartile 1 (the lowest heart-rate difference quartile) was 0.54 (95% confidence interval 0.33-0.86; P = 0.009). The corresponding value for maximal exercise-induced heart rate was 0.56 (95% confidence interval 0.34-0.89; P = 0.018). Within the lowest heart-rate difference quartile, but not within the lowest maximal exercise-induced heart rate quartile, a further, strong, negative gradient in cardiovascular mortality was observed. In the high working capacity range, low heart-rate difference but not low maximal exercise-induced heart rate predicted very high cardiovascular disease mortality. Heart-rate difference and maximal exercise-induced heart rate were also inversely associated with non-cardiovascular disease mortality. CONCLUSIONS: Both heart-rate difference and maximal exercise-induced heart rate were strong, graded, long-term predictors of cardiovascular mortality among apparently healthy middle-aged men, independent of age, physical fitness and conventional coronary risk factors. However, low heart-rate difference was a better predictor than low maximal exercise-induced heart rate for recognizing individuals who were at particularly high risk of dying prematurely from cardiovascular diseases.

Adult↗

PubMed1995

Evaluation and quality-of-life assessment of amlodipine and enalapril in patients with hypertension.

In this multicentre, double-blind trial in 461 patients with essential hypertension, amlodipine (5-10 mg once daily) and enalapril (10-40 mg once daily) were compared in terms of quality of life, efficacy and tolerability after 1 year of treatment (part 1). In part 2, 177 patients successfully treated with amlodipine in part 1 continued in an open evaluation of efficacy and safety of antihypertensive treatment with amlodipine for a further 2 years. In part 1, both drugs were similarly effective in lowering blood pressure (BP) (although significantly more enalapril patients required a diuretic) while maintaining quality of life. Apart from class-typical effects, such as oedema for calcium antagonists and cough for angiotensin-converting enzyme inhibitors, both drugs were equally well tolerated, with few adverse effects of clinical significance. Only a few patients (eight amlodipine (4%), nine enalapril (4%)) were withdrawn from the trial because of drug-related adverse events, demonstrating that the tolerability was good. Neutral to slightly beneficial effects were found in blood lipid concentrations after treatment with amlodipine. The BP reduction seen in the amlodipine patients after part 1 was maintained during part 2. Also, blood lipids and safety variables remained virtually constant. It is concluded that, at similar BP reduction, quality of life is equally well maintained on amlodipine and enalapril therapy. Thus, amlodipine compares favourably with enalapril as an effective and well-tolerated anti-hypertensive agent over the first year. Additionally, amlodipine patients evaluated over a 2-year extension maintained good BP control and the drug was well tolerated.

Adult↗

PubMed1994

Amlodipine reduces transient myocardial ischemia in patients with coronary artery disease: double-blind Circadian Anti-Ischemia Program in Europe (CAPE Trial).

OBJECTIVES: This study was carried out to determine the effect of the once-daily calcium channel blocking agent amlodipine (half-life 35 to 50 h) on the circadian pattern of myocardial ischemia in patients with chronic stable angina. BACKGROUND: Myocardial ischemia during normal daily life, both symptomatic and asymptomatic, has been associated with increased risk of cardiovascular morbidity and mortality, and the circadian pattern parallels that for myocardial infarction and sudden death. METHODS: The Circadian Anti-Ischemia Program in Europe (CAPE) was a large, 10-week international (63 sites), double-blind, parallel study. After a 2-week, single-blind placebo phase, during which stable doses of antianginal treatment were maintained (beta-adrenergic blocking agents in 65% of patients), patients with chronic stable angina with at least three attacks of angina per week, with at least four ischemic episodes or > or = 20 min of ST segment depression in 48 h of Holter monitoring, were randomized to receive treatment with either 5 mg/day of amlodipine or placebo (2:1 randomization). The dose was increased to 10 mg/day after 4 weeks. During week 7 of treatment, 48-h ambulatory ECG monitoring was repeated. RESULTS: Three hundred fifteen of 1,160 patients screened were eligible, and 250 had complete evaluable data. Compared with placebo, amlodipine significantly reduced both the frequency of ST segment depression episodes (60% for amlodipine vs. 44% for placebo, p = 0.025) and total integrated ST ischemic area (62% mm-min vs. 50% mm-min, p = 0.042). Amlodipine reduced ischemia over the 24 h with the intrinsic circadian pattern maintained. In addition, diary data showed a significant reduction in angina (70% for amlodipine vs. 44% for placebo, p = 0.0001) and in nitroglycerin consumption (67% vs. 22%, respectively, p = 0.0006). Amlodipine and placebo demonstrated similar safety profiles (adverse events 17.3% for amlodipine and 13.3% for placebo; discontinuation rates due to adverse events were 2% vs. 4.4%, respectively). CONCLUSIONS: Once-daily amlodipine, when added to background treatment, significantly reduced both symptomatic and asymptomatic ischemic events over 24 h in patients with chronic stable angina.

Adult↗

PubMed1994

Influence of glyceryl trinitrate on venous and arterial effects of chronic, asymmetric isosorbide dinitrate treatment in patients with ischemic heart disease.

Asymmetric dosage regimes have been introduced to circumvent development of nitrate tolerance. This study assessed invasively the hemodynamics during supine rest and exercise before and after 4 weeks treatment with 30 mg isosorbide dinitrate (ISDN) or placebo asymmetrically b.i.d. in 14 randomized patients with stable ischemic heart disease in a double-blinded study. An intravenous infusion of glyceryl trinitrate (GTN) was used to assess possible nitrate tolerance. During the initial, medication-free exercise all patients had increased pulmonary arterial wedge pressure (PAWP) 31.4 +/- 5.56 mmHg (mean +/- SD), showing impaired left ventricular function, while mean arterial pressures (MAP) rose from 112 +/- 16.3 mmHg at rest to 141 +/- 15.9 mmHg during exercise. After 4 weeks ISDN treatment, mean exercise PAWP and MAP, 3 h after morning dose, were reduced to 22.4 +/- 7.09 mmHg and 127 +/- 18.2 mmHg, respectively. Before the ISDN treatment, GTN reduced exercise PAWP to 13.9 +/- 5.27 mmHg and MAP to 119 +/- 11.2 mmHg, whereas after 4 weeks ISDN treatment, the addition of GTN did not reduce exercise PAWP and MAP to the same low levels. Thus, the applied ISDN regimen improved the hemodynamics, but induced a definite, partial nitrate tolerance.

Aged↗