Biomedical subjects

Christian Torp-Pedersen

Publications and source records attributed to Christian Torp-Pedersen.

At least 19 recordsLinked to original sources

PubMed2006

Atrial fibrillation, ischaemic heart disease, and the risk of death in patients with heart failure.

AIMS: Atrial fibrillation (AF) is a risk factor for death in patients with a myocardial infarction, but highly variable results are reported in patients with heart failure. We studied the prognostic impact of AF in heart failure patients with and without ischaemic heart disease. METHODS AND RESULTS: During a period of 2 years, 3587 patients admitted to hospital because of heart failure were included in this study. All patients were examined by echocardiography and the presence of AF was recorded. Follow-up was available for 8 years. Twenty four percent of those discharged alive from hospital had AF. After 4 and 8 years of follow-up, mortality was higher in patients with AF than in patients without, 56 vs. 52% and 77 vs. 73%, respectively. Cox multivariable regression analysis showed a small but significant importance of AF for long-term mortality [hazard ratio (HR) 1.12, 95% confidence limits (CI), 1.02-1.23, P=0.018]. There was a significant interaction between the importance of AF and the presence of ischaemic heart disease (P=0.034). In patients with AF at the time of discharge and ischaemic heart disease, HR was 1.25 (95% CI: 1.09-1.42) and P<0.001; in patients with AF at discharge and without ischaemic heart disease, HR was 1.01 (95% CI: 0.88-1.16) and P=0.88. CONCLUSION: AF is associated with increased risk of death only in patients with ischaemic heart disease. This finding may explain the variable results of studies of the prognosis associated with AF in heart failure.

Aged↗

PubMed2006

A systematic review: effect of angiotensin converting enzyme inhibition on left ventricular volumes and ejection fraction in patients with a myocardial infarction and in patients with left ventricular dysfunction.

BACKGROUND AND AIM: To summarize and quantify results of echocardiographic studies examining the effect of angiotensin converting enzyme (ACE) inhibition on left ventricular remodelling in patients with acute myocardial infarction (MI) and in patients with left ventricular systolic dysfunction (LVSD). METHODS: Systematic review of the literature and meta-analysis of eligible studies providing data on end-diastolic and end-systolic volumes and left ventricular ejection fraction (LVEF) were performed. RESULTS: Data from 16 eligible studies were meta-analysed. The results of studies including patients with MI and preserved LVEF (>45%) showed no significant benefit of ACE inhibition. Results of studies/subgroups with mean LVEF < or =45% demonstrated significant differences in diastolic and systolic volumes of 3.0 (0.1, 6.0) ml and 2.25 (0.04, 4.4) ml in short-term (4-14 weeks) follow-up in favour of ACE inhibitor, p=0.041 and p=0.046 respectively. In the long-term (6-12 months) follow-up, the differences in diastolic and systolic volumes were 4.2 (0.98, 7.4) ml and 3.3 (0.9, 5.8) ml in favour of ACE inhibitor, p=0.01 and p=0.007 respectively. LVEF improved in both short and long-term follow-up, p=0.034 and p=0.021, respectively. CONCLUSION: Chronic use of ACE inhibition has a small but sustained and beneficial effect on remodelling in patients with myocardial infarction and patients with chronic left ventricular dysfunction.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2006

Risk of death or reinfarction associated with the use of selective cyclooxygenase-2 inhibitors and nonselective nonsteroidal antiinflammatory drugs after acute myocardial infarction.

BACKGROUND: The selective cyclooxygenase-2 (COX-2) inhibitors and other nonselective nonsteroidal antiinflammatory drugs (NSAIDs) have been associated with increased cardiovascular risk, but the risk in patients with established cardiovascular disease is unknown. We analyzed the risk of rehospitalization for acute myocardial infarction (MI) and death related to the use of NSAIDs including selective COX-2 inhibitors in patients with prior MI. METHODS AND RESULTS: All patients with first-time MI between 1995 and 2002 as well as all prescription claims for NSAIDs after discharge were identified from nationwide Danish administrative registers. The risk of death and rehospitalization for MI associated with the use of selective COX-2 inhibitors and nonselective NSAIDs was studied with the use of multivariable proportional hazards models and case-crossover analysis. A total of 58 432 patients were discharged alive and included in the study; 9773 experienced rehospitalization for MI, and 16 573 died. A total of 5.2% of patients received rofecoxib, 4.3% celecoxib, 17.5% ibuprofen, 10.6% diclofenac, and 12.7% other NSAIDs. For any use of rofecoxib, celecoxib, ibuprofen, diclofenac, and other NSAIDs, the hazard ratios and 95% confidence intervals for death were 2.80 (2.41 to 3.25; for rofecoxib), 2.57 (2.15 to 3.08; for celecoxib), 1.50 (1.36 to 1.67; for ibuprofen), 2.40 (2.09 to 2.80; for diclofenac), and 1.29 (1.16 to 1.43; for other NSAIDS); there were dose-related increases in risk of death for all of the drugs. There were trends for increased risk of rehospitalization for MI associated with the use of both the selective COX-2 inhibitors and the nonselective NSAIDs. CONCLUSIONS: Selective COX-2 inhibitors in all dosages and nonselective NSAIDs in high dosages increase mortality in patients with previous MI and should therefore be used with particular caution in these patients.

Aged↗

PubMed2006

Impact of implantable defibrillators and resynchronization therapy on outcome in patients with left ventricular dysfunction--a meta-analysis.

BACKGROUND: The clinical benefits of cardiac resynchronization therapy (CRT) and primary prophylactic implantable cardioverter defibrillator (ICD) in patients with left ventricular systolic dysfunction (LVSD) are debated. OBJECTIVE: To evaluate by a meta-analysis the effect of CRT and prophylactic ICD therapy in patients with LVSD. METHODS: Eligible trials evaluating the effect of CRT vs. no-CRT, ICD vs. no-ICD and adding ICD to CRT vs. no-ICD were selected and meta-analyzed. The outcomes were: all cause mortality, cardiac mortality, hospitalization for heart failure and change in exercise tolerance and New York Heart Association class. RESULTS: Implantation of CRT reduced all cause mortality odds ratio (OR) = 0.73 (0.60-0.89) p = 0.002 and hospitalization for heart failure OR = 0.60 (0.45, 0.80) p = 0.001, increased peak oxygen consumption by 1.77 (0.32-3.22) ml/kg/min p = 0.017 and improved New York Heart Association class by at least one class with OR = 1.52 (1.30, 1.77) p < 0.0001. Implantation of ICD reduced all-cause mortality OR = 0.75 (0.59-0.96) p = 0.025 and cardiac mortality OR = 0.63 (0.48, 0.82) p = 0.001. Adding ICD to CRT reduced all cause mortality OR = 0.69 (0.53-0.91) p = 0.008. CONCLUSION: Selective patients with LVSD benefit from CRT, ICD or both. Further investigations are necessary to clarify which patients benefit most from a single or combined device implantation.

Defibrillators, Implantable↗

PubMed2006

Anaemia is an independent predictor of mortality in patients with left ventricular systolic dysfunction following acute myocardial infarction.

BACKGROUND: In patients with chronic heart failure (HF), mortality is inversely related to haemoglobin (hgb) concentration. We investigated the prognostic importance of anaemia in patients with acute myocardial infarction (AMI) and left ventricular systolic dysfunction (LVSD) with and without HF. METHODS AND RESULTS: We studied 1731 patients with AMI and left ventricular ejection fraction </=35% from the TRAndolapril Cardiac Evaluation (TRACE) study. Mild anaemia (110 g/L</=hgb<120 g/L in women and 120 g/L</=hgb<130 g/L in men) was present in 264 patients (15%), 114 (7%) had moderate (100 g/L</=hgb<110 g/L in women and 110 g/L</=hgb<120 g/L in men) and 59 (3%) had severe (hgb <100 g/L in women and <110 g/L in men) anaemia. According to the WHO criteria (hgb </=120 g/L in women and <130 g/L in men), 25% had anaemia. Anaemia was associated with increasing age, higher serum creatinine, lower body mass index, history of chronic HF, and worse NYHA class. In multivariable analyses including other prognostic factors only severe anaemia was associated with increased mortality, hazard ratio 1.59 (1.20-2.11). Anaemia was of prognostic importance in patients with HF, but not without HF. In HF patients the hazard ratios were 1.73 (1.26-2.36), 1.20 (0.93-1.56) and 1.05 (0.88-1.25) for severe, moderate and mild anaemia, respectively. CONCLUSION: Anaemia is an independent predictor of mortality in patients with AMI and LVSD, but prognostic importance of anaemia is confined to the first year following AMI. The increased risk is driven by patients with severe anaemia and HF.

Acute Disease↗

PubMed2006

A comparison of the effects of carvedilol and metoprolol on well-being, morbidity, and mortality (the "patient journey") in patients with heart failure: a report from the Carvedilol Or Metoprolol European Trial (COMET).

OBJECTIVES: This study was designed to investigate the loss of well-being, in terms of life-years, overall and in patients randomized to metoprolol versus carvedilol in the Carvedilol Or Metoprolol European Trial (COMET). BACKGROUND: The ultimate objectives of treating patients with heart failure are to relieve suffering and prolong life. Although the effect of treatment on mortality is usually described in trials, the effects on patient well-being throughout the trials' courses are rarely reported. METHODS: A total of 3,029 patients randomized in the COMET study were included in the analysis. "Patient journey" was calculated by adjusting days alive and out of hospital over four years using a five-point score completed by the patient every four months, adjusted according to the need for intensification of diuretic therapy. Scores ranged from 0% (dead or hospitalized) to 100% (feeling very well). RESULTS: Over 48 months, 17% of all days were lost through death, 1% through hospitalization, 23% through impaired well-being, and 2% through the need for intensified therapy. Compared with metoprolol, carvedilol was associated with fewer days lost to death, with no increase in days lost due to impaired well-being or days in hospital. The "patient journey" score improved from a mean of 54.8% (SD 26.0) to 57.4% (SD 26.3%) (p < 0.0068). CONCLUSIONS: Despite treatment with beta-blockers, heart failure remains associated with a marked reduction in well-being and survival. Loss of quality-adjusted life-years through death and poor well-being seemed of similar magnitude over four years, and both were much larger than the loss that could be attributed to hospitalization.

Adrenergic beta-Antagonists↗

PubMed2006

Prognostic value of aortic pulse wave velocity as index of arterial stiffness in the general population.

BACKGROUND: Few population studies addressed the prognostic significance of aortic pulse wave velocity (APWV) above and beyond other cardiovascular risk factors. METHODS AND RESULTS: We studied a sex- and age-stratified random sample of 1678 Danes aged 40 to 70 years. We used Cox regression to investigate the prognostic value of APWV, office pulse pressure (PP), and 24-hour ambulatory PP while adjusting for mean arterial pressure (MAP) and other covariates. Over a median follow-up of 9.4 years, the incidence of fatal and nonfatal cardiovascular end points, cardiovascular mortality, and fatal and nonfatal coronary heart disease amounted to 154, 62, and 101 cases, respectively. We adjusted for sex, age, body mass index, MAP measured in the office (conventional PP and APWV) or by ambulatory monitoring (24-hour PP), smoking, and alcohol intake. With these adjustments, APWV maintained its prognostic significance in relation to each end point (P<0.05), whereas office and 24-hour PP lost their predictive value (P>0.19), except for office PP in relation to coronary heart disease (P=0.02). For each 1-SD increment in APWV (3.4 m/s), the risk of an event increased by 16% to 20%. In sensitivity analyses, APWV still predicted all cardiovascular events after standardization to a heart rate of 60 beats per minute, after adjustment for 24-hour MAP instead of office MAP, and/or after additional adjustment for the ratio of total to HDL serum cholesterol and diabetes mellitus at baseline. CONCLUSIONS: In a general Danish population, APWV predicted a composite of cardiovascular outcomes above and beyond traditional cardiovascular risk factors, including 24-hour MAP.

Adult↗

PubMed2006

Metabolic syndrome, low-density lipoprotein cholesterol, and risk of cardiovascular disease: a population-based study.

We sought to examine the relative contribution to cardiovascular risk of the metabolic syndrome (MS) compared with that of a high LDL cholesterol level in a population-based study of 2493 men and women, age 41-72 years, without major cardiovascular diseases at baseline. MS was defined according to the National Cholesterol Education Program criteria. The study population was subdivided into four groups on the basis of presence (prevalence: 15%) or absence of MS (85%) and presence (15%) or absence of high LDL cholesterol (85%) defined as a level >5.02 mmol/L or </=5.02 mmol/L. After 9.5 years, 233 had a cardiovascular endpoint (cardiovascular death, ischemic heart disease, and stroke). In proportional-hazard models, adjusting for age, sex, and smoking, and with subjects without MS and LDL cholesterol </=5.02 mmol/L as reference (73%), the relative risk of an endpoint (95% CI) was 1.49 (1.04-2.13) in participants without MS and LDL cholesterol >5.02 mmol/L (12%), 1.80 (1.26-2.57) in subjects with MS and LDL cholesterol </=5.02 mmol/L (12%) and 3.21 (1.99-5.17) in participants with both MS and LDL cholesterol >5.02 mmol/L (3%). In a general population, MS was associated with a cardiovascular risk comparable with that of a high LDL cholesterol level.

Adult↗

PubMed2006

Long-term compliance with beta-blockers, angiotensin-converting enzyme inhibitors, and statins after acute myocardial infarction.

AIMS: To study initiation, dosages, and compliance with beta-blockers, angiotensin-converting enzyme (ACE)-inhibitors, and statins in patients after acute myocardial infarction (AMI) and to identify likely targets for improvement. METHODS AND RESULTS: Patients admitted with first AMI between 1995 and 2002 were identified by linking nationwide administrative registers. A total of 55 315 patients survived 30 days after discharge and were included; 58.3% received beta-blockers, 29.1% ACE-inhibitors, and 33.5% statins. After 1, 3, and 5 years, 78, 64, and 58% of survivors who had started therapy were still receiving beta-blockers, 86, 78, and 74% were receiving ACE-inhibitors, and 85, 80, and 82% were receiving statins, respectively. Increased age and female sex were associated with improved compliance. The dosages prescribed were generally 50% or less of the dosages used in clinical trials, and dosages did not increase during the observation period. Patients who did not start treatment shortly after discharge had a low probability of starting treatment later. CONCLUSION: The main problem with underuse of recommended treatment after AMI is that treatment is not initiated at an appropriate dosage shortly after AMI. A focused effort in the immediate post-infarction period would appear to provide long-term benefit.

Adrenergic beta-Antagonists↗

PubMed2006

Ambulatory blood pressure monitoring and risk of cardiovascular disease: a population based study.

BACKGROUND: Information on the relationship between ambulatory blood pressure (BP) and cardiovascular disease in the general population is sparse. METHODS: Prospective study of a random sample of 1700 Danish men and women, aged 41 to 72 years, without major cardiovascular diseases. At baseline, ambulatory BP, office BP, and other risk factors were recorded. The end point was a combined end point consisting of cardiovascular mortality, ischemic heart disease, and stroke. RESULTS: After a mean follow-up of 9.5 years, 156 end points were recorded. In multivariate models, the relative risk (95% confidence interval) associated with increments of 10/5 mmHg of systolic/diastolic ambulatory BP were 1.35 (1.21-1.50) and 1.27 (1.16-1.39). The corresponding figures for office BP were 1.18 (1.09-1.29) and 1.11 (1.03-1.19). Compared with normotension (office BP <140/90 mm Hg; daytime BP <135/85 mm Hg) the relative risks associated with isolated office hypertension (office BP >/=140/90 mm Hg; daytime BP <135/85 mm Hg), isolated ambulatory hypertension (office BP <140/90 mm Hg; daytime BP >/=135/85 mm Hg), and sustained hypertension (office BP >/=140/90 mm Hg; daytime BP >/=135/85 mm Hg) were 0.66 (0.30-1.44), 1.52 (0.91-2.54), and 2.10 (1.45-3.06), respectively. A blunted BP decrease at night was a risk factor (P = .02) in subjects with daytime ambulatory hypertension, but not in subjects with daytime ambulatory normotension (P = .13). CONCLUSIONS: Ambulatory BP provided prognostic information about cardiovascular disease better than office BP. Isolated office hypertension was not a risk factor and isolated ambulatory hypertension tended to be associated with increased risk. A blunted BP decrease at night was a risk factor in subjects with daytime ambulatory hypertension.

Adult↗

PubMed2006

Beat-to-beat QT dynamics in paroxysmal atrial fibrillation.

BACKGROUND: QT dynamics parameters are used only in sinus rhythm. However, because many patients with paroxysmal atrial fibrillation undergo antiarrhythmic treatment that changes QT, developing methods for measuring QT dynamics during atrial fibrillation is important. OBJECTIVES: The purpose of this study was to evaluate whether QT dynamics in atrial fibrillation can be measured more reliably if additional RR intervals are included in the QT calculation. METHODS: QT and RR intervals were measured in 15 patients with atrial fibrillation and sinus rhythm on the same 24-hour Holter recording. Full QT adaptation is not instantaneous but lags behind over several beats. To correct for this lag, we adapted a weighted average method using five successive RR intervals. Linear regression was performed on (QT, RR) and (QT, RR(modified)) pairs. Variability ratio (standard deviation of all QT intervals/standard deviation of all RR intervals) and modified variability ratio (standard deviation of all QT intervals/modified standard deviation of all RR intervals) were calculated. RESULTS: QT-RR slope was reduced in atrial fibrillation compared with sinus rhythm (0.076 +/- 0.009 vs 0.113 +/- 0.0013, P = .0005). When correcting for lag, using the QT-RR(modified) slope, the slope in atrial fibrillation became similar to the slope in sinus rhythm (0.126 +/- 0.013 vs 0.126 +/- 0.013, P = .9547). The variability ratio was reduced in atrial fibrillation compared with sinus rhythm (0.175 +/- 0.017 vs 0.240 +/- 0.031, P = .009), but when correcting for the lag, the modified variability ratio was similar in atrial fibrillation and sinus rhythm (0.262 +/- 0.029 vs 0.267 +/- 0.038, P = .80). CONCLUSION: The results of this study demonstrate that QT dynamics can be measured reliably in atrial fibrillation using 24-hour Holter recordings.

Action Potentials↗

PubMed2006

Ambulatory arterial stiffness index predicts stroke in a general population.

OBJECTIVE: The ambulatory arterial stiffness index (AASI) can be computed from individual 24-h blood pressure recordings. METHODS: We investigated the prognostic value of AASI and 24-h pulse pressure in a random sample of 1829 Danes, aged 40-70 years. We adjusted for sex, age, body mass index, mean arterial pressure, smoking, diabetes, ratio of total to high-density lipoprotein cholesterol, and history of cardiovascular disease with Cox regression. RESULTS: Over a median follow-up of 9.4 years, incidences of fatal and nonfatal endpoints were 40 for stroke, 150 for coronary heart disease, and 212 for cardiovascular events. In fully adjusted models, the hazard ratios associated with 1 SD increase (0.14 U) in the AASI were 1.62 (95% confidence interval, 1.14-2.28; P = 0.007) for stroke, 0.96 (0.80-1.14; P = 0.62) for coronary heart disease, and 1.06 (0.91-1.23; P = 0.49) for cardiovascular events. None of these ratios reached significance for pulse pressure (P > 0.47). The AASI still predicted stroke after excluding individuals with previous cardiovascular disease or after adjustment for systolic and/or diastolic blood pressure instead of mean arterial pressure. CONCLUSIONS: In a randomly recruited European population, the AASI was a strong predictor of stroke, beyond traditional cardiovascular risk factors, including the mean arterial pressure and pulse pressure.

Adult↗

PubMed2006

Prevalence and characteristics of impaired glucose metabolism in patients referred to comprehensive cardiac rehabilitation: the DANSUK study.

BACKGROUND: Lifestyle and pharmacological interventions can delay the progression of impaired glucose tolerance (IGT) to type 2 diabetes (T2DM), and there is growing evidence that earlier detection of T2DM and intensified risk factor management may result in improved cardiovascular morbidity and mortality. We studied the prevalence of impaired glucose metabolism (T2DM, IGT and impaired fasting glucose; IFG) in patients referred to cardiac rehabilitation, and further studied whether we could identify groups in which an oral glucose tolerance test (OGTT) need not be performed. METHODS: As part of a cardiac rehabilitation trial, 201 patients participated. Patients without a diagnosis of T2DM (N=159) underwent an OGTT 3 months after inclusion. RESULTS: Forty-two patients (21%) had known T2DM at enrolment. Based on the OGTT, 26 patients (13%) had unrecognized T2DM, 36 (18%) had IGT and 19 (9%) were diagnosed with isolated IFG according to the World Health Organization definition. Using fasting plasma glucose alone, 19% of the patients with unrecognized T2DM and two-thirds of patients with IGT would be misclassified. Using IFG as a means to detect IGT showed a sensitivity of only 33% and a positive predictive value of 39%. CONCLUSION: More than 60% of the patients (123/201) referred to cardiac rehabilitation had impaired glucose metabolism and 18% of the screened patients (29/159) would be misclassified if an OGTT was omitted. IFG and IGT did not identify the same patients or the same cardiovascular risk profile. An OGTT test should therefore be considered a constituent part of routine care management in cardiac rehabilitation settings.

Aged↗

PubMed2006

The reliability of echocardiographic left ventricular wall motion index to identify high-risk patients for multicenter studies.

OBJECTIVE: To study whether the use of echocardiographic left ventricular (LV) wall motion index (WMI) is a dependable parameter for identifying patients with LV dysfunction to be enrolled in multicenter trials. METHODS: Videotaped echocardiographic examinations from 200 randomly selected patients that were screened for inclusion into the DIAMOND-CHF and DIAMOND-MI trials were reevaluated by an external expert echocardiographer. WMI was calculated using the 16-segment LV model. RESULTS: The external echocardiographer systematically found lower values of WMI than the core laboratory. The average difference in WMI was 0.18 (SD: 0.33) in the DIAMOND-CHF trial and 0.09 (SD: 0.33) in the DIAMOND-MI trial. The difference in WMI exceeded 0.33 in 34% of the patients in both trials. The cutoff value for inclusion into the DIAMOND trials was WMI < or = 1.2. There was an agreement on WMI dichotomized to below or above 1.2 in 82% of the patients in both trials (kappa coefficient 0.66 for the DIAMOND-CHF and 0.55 for the DIAMOND-MI). CONCLUSIONS: Despite substantial interlaboratory variation in WMI in individual patients and a systematic lower WMI score by the external echocardiographer there was an acceptable overall agreement for identifying patients with severe impairment of LV function. This not only underscores the value of LV-WMI as a useful tool for selecting high-risk patients to be included in multicenter studies but also serves to warn against the use of rigid cutoff values for WMI in the treatment of individual patients.

Anti-Arrhythmia Agents↗

PubMed2006

Mortality after acute myocardial infarction according to income and education.

OBJECTIVE: To study how income and educational level influence mortality after acute myocardial infarction (AMI). DESIGN AND SETTING: Prospective analysis using individual level linkage of registries in Denmark. PARTICIPANTS: All patients 30-74 years old hospitalised for the first time with AMI in Denmark in 1995-2002. MAIN OUTCOME MEASURES: Relative risk (RR) of 30 day mortality and long term mortality (31 days until 31 December 2003) associated with income (adjusted for education) or educational level (adjusted for income) and further adjusted for sex, age, civil status, and comorbidity. RESULTS: The study identified 21 391 patients 30-64 years old and 16 169 patients 65-74 years old. The 30 day mortality was 7.0% among patients 30-64 years old and 15.9% among those 65-74 years old. Among patients surviving the first 30 days, the long term mortality was 9.9% and 28.3%, respectively. The adjusted RR of 30 day mortality and long term mortality among younger patients with low compared with high income was 1.54 (95% confidence interval 1.36 to 1.79) and 1.65 (1.45 to 1.85), respectively. The RR of 30 day and long term mortality among younger patients with low compared with high education was 1.24 (1.03 to 1.50) and 1.33 (1.11 to 1.59), respectively. The RR of 30 day and long term mortality among older patients with low compared with high income was 1.27 (1.15 to 1.41) and 1.38 (1.27 to 1.50), respectively. Older high and low education patients did not differ in mortality. CONCLUSION: This study shows that both educational level and income substantially and independently affect mortality after AMI, indicating that each indicator has specific effects on mortality and that these indicators are not interchangeable.

Acute Disease↗

PubMed2006

Bosentan: a review of its use in pulmonary arterial hypertension and systemic sclerosis.

Bosentan (Tracleer), an orally administered dual endothelin (ET)(A) and ET(B) receptor antagonist, is indicated in the treatment of pulmonary arterial hypertension (PAH). The efficacy of oral bosentan 125 mg twice daily in improving exercise capacity has been demonstrated in well designed trials in adult patients with idiopathic PAH or PAH associated with connective tissue disease or congenital systemic-to-pulmonary shunts, and in other trials in patients with idiopathic PAH or PAH associated with congenital heart disease or HIV infection. The beneficial effects of first-line bosentan treatment may be maintained for up to 1 year in patients with idiopathic PAH or PAH associated with connective tissue disease. Despite the potential for treatment-related teratogenicity and hepatotoxicity, long-term data indicate that bosentan is generally well tolerated at the approved dosages. Although well designed trials are required to establish the efficacy of bosentan versus or in combination with other specific PAH therapies, especially sildenafil, the convenient oral administration and lack of serious injection-related adverse effects may render bosentan preferable to other PAH therapies. Preliminary data indicate that bosentan may be effective in pediatric PAH patients, although randomized trials are required. Furthermore, bosentan may be a useful option for the prevention of digital ulcer development in patients with systemic sclerosis. Thus, in accordance with current clinical guidelines, bosentan is a convenient, effective, and generally well tolerated agent for use in the first-line treatment of class III PAH or second-line treatment of class IV PAH.

Antihypertensive Agents↗

PubMed2005

Effect of beta-blocker therapy on functional status in patients with heart failure--a meta-analysis.

BACKGROUND: The results of randomised control trials (RCTs) evaluating the effect of beta-blockers on functional status in patients with chronic heart failure are conflicting. AIM: To perform a systematic review and meta-analysis of RCTs evaluating the effect of beta-blockers on New York Heart Association (NYHA) classification and exercise tolerance in chronic heart failure. METHODS AND RESULTS: We selected 28 RCTs evaluating beta-blocker versus placebo in addition to ACE inhibitor therapy. Combined results of 23 RCTs showed that beta-blockers improved NYHA class by at least one class with odds ratio (OR) 1.80 (1.33-2.43) p<0.0001. Meta-analysis of 10 RCTs showed a significant prolongation of exercise time by 44.19 (6.62-81.75) s p=0.021. Combining 8 RCTs evaluating the maximal peak oxygen uptake and 9 RCTs evaluating 6-min walk distance showed that beta-blockers had no significant effect compared with placebo, p=0.484, and p=0.730, respectively. Combined results of the 23 RCTs showed significant reducing effect on all cause mortality with OR=0.69 (0.59-0.82) p<0.0001. CONCLUSION: Chronic use of a beta-blocker in conjunction with ACE inhibitor therapy improves dyspnoea and prolongs exercise tolerance time, but has no significant effect on 6-min walk test or maximal oxygen uptake in patients with heart failure.

Adrenergic beta-Antagonists↗

PubMed2005

Quinapril treatment increases insulin-stimulated endothelial function and adiponectin gene expression in patients with type 2 diabetes.

OBJECTIVE: Angiotensin-converting enzyme inhibitors reduce cardiovascular mortality and improve endothelial function in type 2 diabetic patients. We hypothesized that 2 months of quinapril treatment would improve insulin-stimulated endothelial function and glucose uptake in type 2 diabetic subjects and simultaneously increase the expression of genes that are pertinent for endothelial function and metabolism. METHODS: Twenty-four type 2 diabetic subjects were randomized to receive 2 months of quinapril 20 mg daily or no treatment in an open parallel study. Endothelium-dependent and -independent vasodilation was studied during serotonin or sodium nitroprusside infusion in the diabetic patients and in 15 healthy subjects. Endothelial function, insulin-stimulated endothelial function, and insulin-stimulated glucose uptake were measured before and after quinapril treatment. Blood flow was measured by venous occlusion plethysmography. Gene expression was measured by real-time PCR. RESULTS: Quinapril treatment increased insulin-stimulated endothelial function in the type 2 diabetic subjects (P = 0.005), whereas forearm glucose uptake was unchanged. Endothelial function was also increased by quinapril (P = 0.001). Systolic and diastolic blood pressures were reduced by quinapril (P < 0.001). Quinapril increased adiponectin gene expression in vascular tissue obtained from sc adipose biopsies. CONCLUSIONS: Quinapril treatment increases insulin-stimulated endothelial function in patients with type 2 diabetes. Increased vascular adiponectin gene expression may contribute to this beneficial effect.

Adiponectin↗