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Biomedical subjects

Christian Torp-Pedersen

Publications and source records attributed to Christian Torp-Pedersen.

At least 55 records · Page 3Linked to original sources
PubMed2005

New antiarrhythmic agents for atrial fibrillation and atrial flutter.

Atrial fibrillation is the most common sustained cardiac arrhythmia and is a frequent reason for antiarrhythmic therapy. Existing antiarrhythmic drugs have important side effects and presently the therapy to maintain sinus rhythm is not superior to a strategy of controlling excessive heart rate. This review summarises current strategies to improve antiarrhythmic therapy for atrial fibrillation. The most important strategies are: i) to develop drugs without proarrhythmic effects--development of drugs devoid of QT prolonging potential is the main strategy; ii) multiple channel-blocking drugs--inspired by the efficacy of amiodarone, several drugs are being developed that have similar electrophysiological properties as amiodarone, but without the extracardiac side effects; iii) drugs that act exclusively in the atria--the atria contain specific potassium channels, and several drugs that act only on these channels are in development; and iv) antiarrhythmic therapy without effects on ion channels--inhibition of the renin-angiotensin system and steroid therapy has been shown to have some effect in the treatment of atrial fibrillation. Many drugs are in development and the therapeutic scenario for treatment of atrial fibrillation may change quickly.

Animals↗
PubMed2004

The long-term impact of the angiotensin-converting enzyme inhibitor trandolapril on mortality and hospital admissions in patients with left ventricular dysfunction after a myocardial infarction: follow-up to 12 years.

AIMS: To investigate the long-term benefits of treatment with angiotensin-converting enzyme (ACE)-inhibitors in patients with myocardial infarction (MI) and left ventricular dysfunction (LVD). METHODS AND RESULTS: In the trandolapril cardiac evaluation (TRACE) study, 1749 patients with LVD (ejection fraction< or =35%) were randomized to trandolapril (n=876) or placebo (n=873) 3-7 days post-MI. Enrolment lasted from 1990 to 1994; on-treatment follow-up ranged from 2 to 4 years. At study closure, all patients were recommended continued ACE-inhibitor use. National registries were used to track deaths and hospitalizations until 2002. Mortality was analysed with Cox proportional hazard models and hospitalization with Poisson regression models (models adjusted for observation time). Over 10-12 years of follow-up, a total of 1283 deaths and 9220 hospitalizations were registered. Compared with the placebo group, the trandolapril group had a significantly reduced risk of all-cause mortality (relative risk 0.89, 95% CI 0.80-0.99, P=0.03), all-cause hospitalizations (rate ratio 0.92, 95% CI 0.88-0.96, P<0.001), and cardiovascular hospitalizations (rate ratio 0.95, 95% CI 0.91-1.00, P=0.047), including congestive heart failure hospitalizations (rate ratio 0.85, 95% CI 0.77-0.93, P<0.001). CONCLUSION: In patients with LVD, use of trandolapril shortly after an MI for 2-4 years has long-term benefits. The beneficial effect on mortality and hospitalization rates is maintained for at least 10-12 years.

Aged↗
PubMed2004

Effect of obesity and being overweight on long-term mortality in congestive heart failure: influence of left ventricular systolic function.

AIMS: Previous studies have suggested that a high body mass index (BMI) is associated with an improved outcome in congestive heart failure (CHF). However, the studies addressing this problem have not included enough patients with non-systolic heart failure to evaluate how left ventricular systolic function interacts with obesity on prognosis in CHF. The aim of this study was to evaluate how BMI influences mortality in patients hospitalized with CHF, and to address in particular whether the effect of BMI is influenced by left ventricular (LV) systolic function. METHODS AND RESULTS: Retrospective analysis of baseline and survival data for 4700 hospitalized CHF patients for whom BMI was available. LV systolic function, as assessed by wall motion index was available for 95% of the patients. Follow-up time ranged from 5 to 8 years. In the total population, the risk of death decreased steadily with increasing BMI from the underweight to the obese. Compared with normal weight, and adjusted for sex and age, risk ratios (RR) and 95% confidence limits were: underweight 1.56 (1.33-1.84), overweight 0.90 (0.83-0.97), obese 0.77 (0.70-0.86). Being underweight conferred a greater risk in CHF patients with normal systolic function [RR 1.66 (1.29-2.14), compared with normal weight] than in patients with reduced systolic function [RR 1.11 (0.87-1.42), P for interaction 0.03]. In patients with systolic dysfunction, obesity was associated with increased risk compared with normal weight [RR 1.21 (1.01-1.45)]. CONCLUSION: Increasing BMI in CHF is associated with a lower mortality, but the influence is complex and depends on left ventricular systolic function. Hence, in patients with systolic dysfunction obesity may indicate an increased risk.

Aged↗
PubMed2004

Influence of diabetes and diabetes-gender interaction on the risk of death in patients hospitalized with congestive heart failure.

OBJECTIVES: The purpose of this study was to investigate the influence of diabetes on long-term mortality in a large cohort of patients hospitalized with heart failure (HF). BACKGROUND: Diabetes is common in HF patients, but information on the prognostic effect of diabetes is sparse. METHODS: The study is an analysis of survival data comprising 5,491 patients consecutively hospitalized with new or worsening HF and screened for entry into the Danish Investigations of Arrhythmia and Mortality on Dofetilide (DIAMOND). Screening, which included obtaining an echocardiogram in 95% of the patients, took place at Danish hospitals between 1993 and 1995. The follow-up time was five to eight years. RESULTS: A history of diabetes was found in 900 patients (16%), 41% of whom were female. Among the diabetic patients, 755 (84%) died during follow-up, compared with 3,200 (70%) among the non-diabetic patients, resulting in a risk ratio (RR) of death in diabetic patients of 1.5 (95% confidence interval [CI] 1.4 to 1.6, p < 0.0001). In a multivariate analysis, the RR of death in diabetic patients was 1.5 (CI 1.3 to 1.76, p < 0.0001), but a significant interaction between diabetes and gender was found. Diabetes increased the mortality risk more in women than in men, with the RR for diabetic men being 1.4 (95% CI 1.3 to 1.6, p < 0.0001) and 1.7 for diabetic women (95% CI 1.4 to 1.9, p < 0.0001). The effect of diabetes on mortality was similar in patients with depressed and normal left ventricular systolic function. CONCLUSIONS: Diabetes is a potent, independent risk factor for mortality in patients hospitalized with HF. The excess risk in diabetic patients appears to be particularly prominent in females.

Aged↗
PubMed2004

Importance of a history of hypertension for the prognosis after acute myocardial infarction--for the Bucindolol Evaluation in Acute myocardial infarction Trial (BEAT) study group.

BACKGROUND: Arterial hypertension is a major risk factor for cardiovascular events. The prognosis for hypertensive patients after acute myocardial infarction (MI) is uncertain because of the sparse and somewhat contradictionary data. HYPOTHESIS: Our study aimed to investigate the importance of hypertension to prognosis after an MI in patients receiving contemporary medical therapy. METHODS: We performed a retrospective study using a large register from the Bucindolol Evaluation in Acute myocardial infarction Trial (BEAT). The register comprised 3,326 patients admitted between June 1998 and August 1999 with an enzyme-verified MI to 33 Danish coronary care units. Hypertension was considered present when a previous diagnosis of hypertension was accompanied by relevant medical therapy. Survival information for all patients was obtained in January 2002. RESULTS: Of the 3,326 patients studied, 825 were hypertensive. Overall, 28.4% had died by January 2002. The unadjusted hazard ratio associated with hypertension was 1.2 (95% confidence limit [CI] 1.1-1.4, p = 0.004). Hypertensive patients were older, and after adjustment for age the hazard ratio associated with hypertension was 1.04 (CI 0.9-1.2, p = 0.6). Adjustment for further covariates did not change the result. CONCLUSION: Our study showed that after an acute MI the survival rate of patients with and without a history of hypertension was identical when they received contemporary medical therapy.

Adult↗
PubMed2004

Female sex is associated with a better long-term survival in patients hospitalized with congestive heart failure.

AIMS: Results of previous studies on the influence of gender on prognosis in heart failure have been conflicting and most studies have been conducted in selected populations. The aim of this study was determine whether mortality risk in women and men hospitalized with congestive heart failure is different. METHODS AND RESULTS: Survival analysis of 5491 consecutive patients admitted with congestive heart failure to 34 Danish hospitals between 1993-1996. Follow-up time was 5-8 years. Forty percent of the patients were female. Females were older, had less evidence of ischaemic heart disease and their left ventricular systolic function was preserved to a greater extent than in males. Men were more often treated with ACE inhibitors. During the follow-up period 1569 women (72%) and 2386 (72%) of the men died. When the age difference between men and women was adjusted for, male gender was associated with an increased risk of death (RR 1.25 (1.17-1.34)) and the increased risk was confirmed in a multivariate model containing several covariates. CONCLUSIONS: In patients hospitalized with congestive heart failure male gender is an independent predictor of mortality. Female heart failure patients may be under-treated with ACE inhibitors.

Aged↗
PubMed2004

Effect of age on short and long-term mortality in patients admitted to hospital with congestive heart failure.

AIMS: To describe the association between age and risk factors in patients hospitalised with congestive heart failure (CHF) and to determine the effect of age on mortality. METHODS AND RESULTS: Consecutive patients admitted to 34 hospitals with CHF during a period of 2 years were registered. Mean age was 71.7+/-10.2 years, 60% were male and 63% were in NYHA class III-IV. Moderate to severe left ventricular (LV) systolic dysfunction was present in 41%. Short and long-term survival status was obtained after 30 days and 5-8 years, respectively. Older patients less frequently had LV systolic dysfunction, were under treated with ACE-inhibitors and were more often female. The prevalence of hypertension, diabetes and ischaemic heart disease increased with age, until the oldest age group (>80 years). Age was an independent predictor of short-term mortality (risk ratio (RR) per 10-year increase was 1.23 (95% CI 1.04-1.47)). Advancing age significantly increased long-term mortality (RR 1.55 (1.50-1.61)). Age interacted with the LV ejection fraction (P = 0.003). In patients with LV systolic dysfunction, the RR per 10-year increase was 1.29 (1.19-1.39) whereas in patients with preserved systolic function the RR was 1.57 (1.43-1.72, multivariate analyses). CONCLUSION: The clinical characteristics of CHF patients vary considerably with age. Elderly patients hospitalised with CHF face a very grave prognosis, particularly if their heart failure symptoms are caused by LV systolic dysfunction.

Age Factors↗
PubMed2004

Importance of chronic obstructive pulmonary disease for prognosis and diagnosis of congestive heart failure in patients with acute myocardial infarction.

AIMS: To evaluate the importance of chronic obstructive pulmonary disease for prognosis and diagnosis of congestive heart failure in patients with acute myocardial infarction. METHOD AND RESULTS: Prospective registration of 6669 consecutive patients admitted with infarction and screened for a randomised controlled trial. A history of COPD was present in 765 (11.5%) patients. Thirty-day and 5-year survival in patients with chronic obstructive pulmonary disease was 86.3 and 42.9%. In patients without pulmonary disease the figures were 87.7 and 57.5%, respectively, giving a relative risk of 1.49 (1.35-1.65). In multivariate analysis the relative risk was 1.15 (1.04-1.28). The prevalence of congestive heart failure was 65.9% in patients with chronic obstructive pulmonary disease and 52.0% in patients without. This difference was most distinct in patients with normal or only slightly decreased left ventricular systolic function. In patients without congestive heart failure, chronic obstructive pulmonary disease was of prognostic importance [RR=1.44 (1.17-1.78)], but not in patients with congestive heart failure [RR=1.09 (0.96-1.23)]. CONCLUSION: Chronic obstructive pulmonary disease is a predictor of long-term mortality in patients with acute myocardial infarction without congestive heart failure, but is also a confounding factor for the diagnosis of congestive heart failure.

Aged↗
PubMed2004

A meta-analysis of the effect of angiotensin-converting enzyme inhibitors on functional capacity in patients with symptomatic left ventricular systolic dysfunction.

AIM: To determine by meta-analysis whether angiotensin-converting enzyme (ACE) inhibitors improve exercise tolerance in patients with symptomatic left ventricular systolic dysfunction (LVSD). METHODS AND RESULTS: After literature search 13 multi-centre double blind parallel group trials that evaluated the effect of ACE inhibitors vs. placebo on exercise duration were selected. Ninety-four percent of patients were in New York Heart Association class II-IV. The studies were combined using the Cochrane meta-analysis program (Review manager version 4.1). Analyses according to treatment period, exercise protocols and publication periods were performed. Treatment with ACE inhibitor over 4-12 weeks resulted in a beneficial effect on exercise duration (P=0.003 and P=0.0008 for 4- and 12-weeks treatment, respectively), but the magnitude of improvements did not exceed 30 s corresponding to only 5% compared with placebo. CONCLUSION: In addition to the pronounced effect on mortality and morbidity in patients with symptomatic LVSD, ACE inhibitors have improving effect on functional capacity measured as exercise tolerance time.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

Prehospital delay in acute coronary syndrome--an analysis of the components of delay.

BACKGROUND: Prompt hospital admission is essential when treating acute coronary syndrome. Delay prior to admission is unnecessarily long. Therefore, a thorough scrutiny of the influence of characteristics, circumstantial and subjective variables on elements of prehospital delay among patients admitted with acute coronary syndrome is warranted. METHODS: A structured interview was conducted on 250 consecutive patients admitted alive with acute coronary syndrome. RESULTS: Median prehospital, decision, physician and transportation delays were 107, 74, 25 and 22 min, respectively. Women (n=77) had more frequently atypical symptoms and increased prehospital delay caused by prolonged physician and transportation delay. Physician delay among women and men were 69 and 16 min, respectively. Patients with prior myocardial infarction had reduced prehospital delay, which was caused by shorter decision and physician delay; whereas patients with prior mechanical revascularisation or typical symptoms had prolonged prehospital delay due to long decision delay. When symptoms were interpreted as cardiac the decision and prehospital delay were reduced. CONCLUSION: The medical profession underestimates the risk of acute coronary syndrome among women, and thereby contributes to unnecessary long delay to treatment. The patient's prior experience and interpretation has a significant influence on behaviour.

Acute Disease↗
PubMed2004

A description of the clinical characteristics at baseline of patients recruited into the Carvedilol or Metoprolol European Trial (COMET).

BACKGROUND & AIMS: The COMET trial was a prospective, double-blind, randomised trial comparing carvedilol, a comprehensive adrenergic receptor antagonist, with metoprolol, a beta-1-selective agent in patients with heart failure and left ventricular systolic dysfunction. The trial showed a reduction in mortality with carvedilol that was consistent across subgroups. The purpose of this report is to describe in greater detail the heterogeneity of this population at baseline with particular reference to the impact of symptomatic severity, age and gender on patient characteristics. METHODS: A descriptive report using data entered in the COMET study data-base. RESULTS: The characteristics of the population studied were similar to those reported in previous trials of beta-blockers. Almost all patients were receiving diuretics and ACE inhibitors with few patients taking angiotensin receptor blockers. As expected, older patients had more co-morbidity. Older patients and women reported worse symptoms and poorer well-being despite similar ventricular dimensions and systolic dysfunction. NT-proBNP was higher in patients with more severe symptoms and older patients but not in women, although differences in NT-proBNP may have been confounded by differences in renal function. CONCLUSION: Age and gender, as well as the severity of cardiac dysfunction, appear to have an important effect on the severity of heart failure symptoms and patient 'well-being'. This could have important implications for the relationship between symptoms and prognosis and therefore the way in which patients are selected for clinical trials and the goals of treatment. This will be the subject of further analyses.

Adrenergic beta-Antagonists↗
PubMed2004

Methods of assessing the functional status of patients with left ventricular systolic dysfunction in interventional studies: can brain natriuretic peptide measurement be used as surrogate for the traditional methods?

AIM: To review whether brain natriuretic peptides (BNP) can be used as a surrogate for the traditional methods of assessing functional status in interventional studies of patients with left ventricular systolic dysfunction (LVSD). METHODS AND RESULTS: The traditional methods for assessing functional status including New York Heart Association (NYHA) class, exercise intolerance and quality of life were reviewed in relation to BNP measurements in patients with LVSD. A meta-analysis of four studies evaluating BNP levels versus exercise peak oxygen uptake or 6-minute walking distance showed a significant correlation, but a low R-value of -0.59. Studies using BNP levels for optimisation of heart failure therapy showed conflicting results concerning the correlation between the functional improvement and changes in BNP levels. Conflicting results were also found concerning the utility of BNP levels as a surrogate to predict efficacy of the various anti-congestive therapies on heart failure outcome. CONCLUSION: The results of the studies examining BNP measurement as a surrogate for functional status and drug efficacy in patients with LVSD are conflicting. Further studies are necessary to settle the place of BNP measurement as surrogate marker for exercise tolerance, NYHA classification and in assessing efficacy of different interventions in the clinical trials.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

Vascular insulin response is preserved in non-diabetic patients with coronary artery disease, despite endothelial dysfunction.

BACKGROUND: Patients with coronary artery disease (CAD) are often insulin resistant, a state that predisposes to increased atherosclerosis. Recently, it was suggested that a "vascular insulin resistance" could explain this association, causing endothelial dysfunction and hence atherosclerosis. We therefore studied the vascular insulin response in patients with CAD. MATERIALS AND METHODS: Nine non-diabetic patients with documented CAD and 31 lean healthy controls were examined. Forearm blood flow was measured by venous occlusion plethysmography. Dose-response studies of acetylcholine (ACh) and sodium nitroprusside (SNP) elicited endothelium-dependent and -independent vasodilation and were repeated during intra-arterial insulin infusion. RESULTS: Patients were insulin resistant as determined by HOMA index. Insulin infusion resulted in high physiological levels of insulin in the forearm without systemic effects. Patients had a reduced ACh response but insulin infusion increased the ACh response equally in patients and controls (a mean increase of 74+/-37 vs 57+/-24%, patients vs controls, p=0.12). A minor increase of the SNP response was also noted during insulin infusion. CONCLUSION: Vascular insulin response is intact in non-diabetic CAD patients in spite of insulin resistance and endothelial dysfunction.

Acetylcholine↗