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Biomedical subjects

Lars Køber

Publications and source records attributed to Lars Køber.

At least 55 records · Page 3Linked to original sources
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

Hyperinsulinaemia is associated with increased long-term mortality following acute myocardial infarction in non-diabetic patients.

AIMS: To study the impact of disturbances in glucose metabolism on total mortality in non-diabetic patients with acute myocardial infarction. METHODS AND RESULTS: Four hundred and ninety four patients with a verified myocardial infarction and no history of diabetes were studied. The study population comprised a subgroup of patients screened for participation in the Trandolapril Cardiac Evaluation (TRACE) study. At baseline, fasting insulin, fasting glucose, glycosylated haemoglobin (HbA1c), and urinary albumin excretion were measured. Survival status was determined after 6-8 years. Patients with hyperinsulinaemia were more obese and more frequently suffered from hypertension, previous myocardial infarction and congestive heart failure. In a univariate regression analysis, values in the upper quartile of insulin, glucose, HbA1c, and urinary albumin were associated with an excess mortality risk (RR=1.8 (1.2-2.7), p=0.002; RR=1.6 (1.2-2.1), p=0.001; RR= 1.9 (1.3-2.9), p=0.001; RR=1.6 (1.2-2.1), p=0.02 respectively). However, only a high insulin level remained significant in a multivariable analysis (RR=1.54 (1.03-2.31), p=0.04) including baseline variables, left ventricular systolic function and in-hospital complications. CONCLUSIONS: High fasting plasma insulin is an independent risk factor of all-cause mortality in non-diabetic patients with acute myocardial infarction. This justifies future intervention studies aiming at reducing insulin resistance and using fasting insulin as the target variable.

Aged↗
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

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

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↗
PubMed2004

A benefit-risk assessment of class III antiarrhythmic agents.

The prevalence of arrhythmia in the population is increasing as more people survive for longer with cardiovascular disease. It was once thought that antiarrhythmic therapy could save life, however, it is now evident that antiarrhythmic therapy should be administrated with the purpose of symptomatic relief. Since many patients experience a decrease in physical performance as well as a diminished quality of life during arrhythmia there is still a need for antiarrhythmic drug therapy. The development of new antiarrhythmic agents has changed the focus from class I to class III agents since it became evident that with class I drug therapy the prevalence of mortality is considerably higher. This review focuses on the benefits and risks of known and newer class III antiarrhythmic agents. The benefits discussed include the ability to maintain sinus rhythm in persistent atrial fibrillation patients, and reducing the need for implantable cardioverter defibrillator shock/antitachycardia therapy, since no class III antiarrhythmic agents have proven survival benefit. The risks discussed mainly focus on pro-arrhythmia as torsade de pointes ventricular tachycardia.

Amiodarone↗
PubMed2003

Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both.

BACKGROUND: Angiotensin-converting-enzyme (ACE) inhibitors such as captopril reduce mortality and cardiovascular morbidity among patients with myocardial infarction complicated by left ventricular systolic dysfunction, heart failure, or both. In a double-blind trial, we compared the effect of the angiotensin-receptor blocker valsartan, the ACE inhibitor captopril, and the combination of the two on mortality in this population of patients. METHODS: Patients receiving conventional therapy were randomly assigned, 0.5 to 10 days after acute myocardial infarction, to additional therapy with valsartan (4909 patients), valsartan plus captopril (4885 patients), or captopril (4909 patients). The primary end point was death from any cause. RESULTS: During a median follow-up of 24.7 months, 979 patients in the valsartan group died, as did 941 patients in the valsartan-and-captopril group and 958 patients in the captopril group (hazard ratio in the valsartan group as compared with the captopril group, 1.00; 97.5 percent confidence interval, 0.90 to 1.11; P=0.98; hazard ratio in the valsartan-and-captopril group as compared with the captopril group, 0.98; 97.5 percent confidence interval, 0.89 to 1.09; P=0.73). The upper limit of the one-sided 97.5 percent confidence interval for the comparison of the valsartan group with the captopril group was within the prespecified margin for noninferiority with regard to mortality (P=0.004) and with regard to the composite end point of fatal and nonfatal cardiovascular events (P<0.001). The valsartan-and-captopril group had the most drug-related adverse events. With monotherapy, hypotension and renal dysfunction were more common in the valsartan group, and cough, rash, and taste disturbance were more common in the captopril group. CONCLUSIONS: Valsartan is as effective as captopril in patients who are at high risk for cardiovascular events after myocardial infarction. Combining valsartan with captopril increased the rate of adverse events without improving survival.

Aged↗
PubMed2003

Tumor necrosis factor-alpha inhibits insulin's stimulating effect on glucose uptake and endothelium-dependent vasodilation in humans.

BACKGROUND: Inflammatory mechanisms could be involved in the pathogenesis of both insulin resistance and atherosclerosis. Therefore, we aimed at examining whether the proinflammatory cytokine tumor necrosis factor (TNF)-alpha inhibits insulin-stimulated glucose uptake and insulin-stimulated endothelial function in humans. METHODS AND RESULTS: Healthy, lean male volunteers were studied. On each study day, 3 acetylcholine (ACh) or sodium nitroprusside (SNP) dose-response studies were performed by infusion into the brachial artery. Before and during the last 2 dose-response studies, insulin and/or TNF-alpha were coinfused. During infusion of insulin alone for 20 minutes, forearm glucose uptake increased by 220+/-44%. This increase was completely inhibited during coinfusion of TNF-alpha (started 10 min before insulin) with a more pronounced inhibition of glucose extraction than of blood flow. Furthermore, TNF-alpha inhibited the ACh forearm blood flow response (P<0.001), and this inhibition was larger during insulin infusion (P=0.01) but not further increased by NG-monomethyl-L-arginine acetate (P=0.2). Insulin potentiated the SNP response less than the ACh response and the effect of TNF-alpha was smaller (P<0.001); TNF-alpha had no effect on the SNP response without insulin infusion. Thus, TNF-alpha inhibition of the combined response to insulin and ACh was likely mediated through inhibition of NO production. CONCLUSIONS: These results support the concept that TNF-alpha could play a role in the development of insulin resistance in humans, both in muscle and in vascular tissue.

Acetylcholine↗
PubMed2003

Prognostic importance of complete atrioventricular block complicating acute myocardial infarction.

Third-degree atrioventricular block after acute myocardial infarction is considered to have prognostic importance. However, its importance in conjunction with thrombolytic therapy and its relation to left ventricular function remains uncertain. This report also outlines an important distinction between atrioventricular block in the setting of anterior and inferior wall acute myocardial infarction, with profound clinical and prognostic implications.

Aged↗
PubMed2003

Tetrahydrobiopterin restores endothelial dysfunction induced by an oral glucose challenge in healthy subjects.

An oral glucose challenge causes transient impairment of endothelial function, probably because of increased oxidative stress. During oxidative stress, endothelial nitric oxide (NO) synthase (eNOS) becomes uncoupled because of decreased bioavailability of tetrahydrobiopterin (BH4), an essential cofactor of eNOS. Therefore, we examined whether an acute supplement of BH4 could restore endothelial dysfunction induced by an oral glucose challenge. Healthy subjects were examined in 53 experiments. Forearm blood flow was measured by venous occlusion plethysmography. Dose-response studies were obtained during intra-arterial infusion of serotonin to elicit endothelium-dependent, NO-specific vasodilation and during sodium nitroprusside (SNP) infusion to elicit endothelium-independent vasodilation. Subjects were examined before (fasting) and 1 and 2 h after an oral glucose challenge (75 g) with serotonin (n = 10) and SNP (n = 8). On different days (6R)-5,6,7,8-tetrahydro-l-biopterin dihydrochloride (6R-BH4; n = 10), the active cofactor of eNOS or its stereoisomer (6S)-5,6,7,8-tetrahydro-l-biopterin sulfate (6S-BH4; n = 10), which is inactive as a cofactor, was added 10 min (500 microg/min) before and during the 1-h postchallenge serotonin dose-response study. In vitro studies showed that 6R-BH4 and 6S-BH4 were equipotent antioxidants. Serotonin response was reduced by 24 +/- 7% (at the highest dose) at 1 h postchallenge compared with fasting (P = 0.001) and was restored 2 h postchallenge. The reduction was reversed by the administration of 6R-BH4 but not by 6S-BH4. SNP responses were slightly increased 1 and 2 h postchallenge (increased by 15 +/- 13% at third dose 2 h postchallenge, P = 0.0001). An oral glucose challenge causes transient, NO-specific, endothelial dysfunction, which may be reversed by BH4. Transient postprandial endothelial dysfunction may be partly explained by reduced bioavailability of BH4 and NO.

Administration, Oral↗