N-terminal proBNP and mortality in hospitalised patients with heart failure and preserved vs. reduced systolic function: data from the prospective Copenhagen Hospital Heart Failure Study (CHHF).

UNLABELLED: Preserved systolic function among heart failure patients is a common finding, a fact that has only recently been fully appreciated. The aim of the present study was to examine the value of NT-proBNP to predict mortality in relation to established risk factors among consecutively hospitalised heart failure patients and secondly to characterise patients in relation to preserved and reduced systolic function. MATERIAL: At the time of admission 2230 consecutively hospitalised patients had their cardiac status evaluated through determinations of NT-proBNP, echocardiography, clinical examination and medical history. Follow-up was performed 1 year later in all patients. RESULTS: 161 patients fulfilled strict diagnostic criteria for heart failure (HF). In this subgroup of patients 1-year mortality was approximately 30% and significantly higher as compared to the remaining non-heart failure population (approx. 16%). Using univariate analysis left ventricular ejection fraction (LVEF), New York Heart Association classification (NYHA) and plasma levels of NT-proBNP all predicted mortality independently. However, regardless of systolic function, age and NYHA class, risk-stratification was provided by measurements of NT-proBNP. Having measured plasma levels of NT-proBNP, LVEF did not provide any additional prognostic information on mortality among heart failure patients (multivariate analysis). CONCLUSION: The results show that independent of LVEF, measurements of NT-proBNP add additional prognostic information. It is concluded that NT-proBNP is a strong predictor of 1-year mortality in consecutively hospitalised patients with heart failure with preserved as well as reduced systolic function.

Effect of the serotonin receptor agonist, buspirone, on immune function in HIV-infected individuals: a six-month randomized, double-blind, placebo-controlled trial.

PURPOSE: Previous studies have shown that agents modulating the cAMP/PKA pathway have a beneficial effect on immune reconstitution in HIV-infected individuals. Here we evaluate the effect of buspirone on immune function as measured by CD4 and CD8 T-cell counts, CD4/CD8 T-cell ratio, HIV viral load, and response to pokeweed mitogen (PWM) in antiretroviral naive HIV-1-infected individuals. METHOD: Twenty-three HIV-infected patients with CD4 T-cell counts above 300 per microL were enrolled in a 6-month double-blinded placebo controlled trial. No patients received antiretroviral therapy during the study. Blood samples were drawn prior to treatment, after 1 week, 1 month, 3 months, and 6 months, and as a follow-up sample 1 month after completion of study. RESULTS: A significant decrease in CD8+ T-cell counts (p =.02) and an increase in CD4/CD8 ratio (p =.0003) in buspirone-treated patients compared to placebo-treated patients was observed. There were no significant differences in CD4 T-cell counts, HIV viral load, or proliferative response to PWM between those receiving placebo and those receiving buspirone. CONCLUSION: Buspirone treatment leads to significant changes in CD8 T-cell count and in CD4/CD8 ratio. Thus, agents affecting the adenosine 3', 5'-cyclic monophosphate/protein kinase A type 1 (cAMP/PKA-1) pathway may be candidates for positive immune modulation in patients with HIV-1 infection.

The serum level of soluble urokinase receptor is elevated in tuberculosis patients and predicts mortality during treatment: a community study from Guinea-Bissau.

OBJECTIVE: To investigate whether the serum level of soluble urokinase plasminogen activator receptor (suPAR) carries prognostic information in individuals infected with Mycobacterium tuberculosis. DESIGN: suPAR was measured by ELISA in 262 individuals at the time of enrolment into a cohort based on suspicion of active tuberculosis and in 101 individuals after 8 months of follow-up. RESULTS: The suPAR levels were elevated in patients with active TB compared to TB-negative individuals (P < 0.001). suPAR levels were highest in patients positive for TB on direct microscopy (n = 84, median suPAR 3.17 ng/ml, P < 0.001), followed by patients negative on direct microscopy but culture positive (n = 35, median suPAR 2.41 ng/ml, P = 0.005) and by patients diagnosed on clinical grounds (n = 63, median suPAR 2.13 ng/ml, P = 0.06) compared to 64 TB-negative individuals (median suPAR 1.73 ng/ml). During the 8-month treatment period, 23 TB cases died. In a multivariate Cox model controlling for HIV status, age, sex, CD4 count and type of TB diagnosis, the mortality increase per ng suPAR was 1.25 (95%CI 1.12-1.40). After treatment, suPAR levels had decreased to the levels of TB-negative individuals. CONCLUSIONS: suPAR levels are elevated in TB patients and associated with mortality. Furthermore, suPAR may be a potential marker of treatment efficacy.

[Joggers live longer]. / Motionslöpare lever längre.

In all 4,658 men, 20-79 years of age, with no prior myocardial infarction, attended two examinations. Jogging status was self-reported based on the question "Are you a jogger?" The study shows that regular jogging is not associated with increased mortality in men, as the joggers had significantly lower mortality than non-joggers. The lower mortality of joggers could be an effect of the physical training, but it could also be due to selection or a combination of both. On the other hand, numerous studies within the fields of epidemiology, work-physiology, psychology and biochemistry have all pointed toward a beneficial effect of physical activity on health, but the optimal intensity, frequency and duration of physical activity has yet to be established.

[Joggers live longer. The Osterbro study]. / Motionsløbere lever laengere. østerbroundersøgelsen.

INTRODUCTION: Jogging is one of the most popular forms of vigorous exercise, but its effect on longevity has not been documented. METHOD: This analysis comprise a random sample of 4658 men aged 20-79 years with no prior myocardial infarction, who participated in the first (1976-1978) and second (1981-1983) examination of the Copenhagen City Heart Study. They were entered in the mortality analysis at the second examination and were followed up until 30 November 1998. The influence of jogging on time to death was analysed by Cox regression, with age as the time axis. In addition to jogging, the model included diabetes, smoking, household income, education, and alcohol consumption as potential confounding variables, and systolic blood pressure, total cholesterol, HDL cholesterol, and BMI as intermediate variables. RESULTS: At the first examination, 217 men (4.7%) reported active jogging. Of these, 96 (2.1%) were still joggers five years later. Overall, 4335 men were non-joggers at both examinations. A significant effect of jogging was found only for the group that were joggers at both examinations, relative risk 0.37 (95% confidence interval, 0.19 to 0.71; p = 0.003). DISCUSSION: We have found that regular joggers have a significantly lower mortality than have non-joggers. This could also be due to other lifestyle factors, but numerous studies have pointed towards a beneficial effect of physical activity on health. The optimal intensity, frequency, and duration of physical activity has yet to be established.

[The course of pulmonary function in adults with asthma. The Osterbro study]. / Forløb af lungefunktion hos voksne med asthma. Osterbroundersøgelsen.

We studied the course of forced expiratory volume in one second (FEV1) in adults with self-reported asthma using data from a longitudinal epidemiological study of the general population, The Copenhagen City Heart Study. The study was conducted over a period of 15 years with three measurements of lung function. The data base consisted of 17,506 men and women including 1.095 participants with asthma. The unadjusted FEV1 decline in subjects with asthma was 38 ml/year compared to 22 ml/year in nonasthmatics. Similarly, the statistical analysis showed that the FEV1 normalised by height (FEV1/height2) was significantly poorer in subjects with asthma compared to nonasthmatics (p < 0.001). Smoking contributed significantly to lung function decline regardless of asthma status (p < 0.001). In a sample of the general population, adults with self-reported asthma have a significantly faster decline of ventilatory function than nonasthmatics.

[Changed working plans can improve medical training]. / En aendret arbejdstilrettelaeggelse kan medføre en forbedret laegeuddannelse.

INTRODUCTION: The quality of clinical medical training in Denmark has been closely debated and criticised in recent years. Reorganisation of the daily working plans is one of the recommendations for improvement. METHOD: In the Department of Gastrointestinal Surgery, we made changes in the daily working plans in order to improve supervision and training. These changes included firmer attachment of the young residents to specialised medical teams in the department and the creation of more supervised working situations. The morning rounds were done by all the senior and junior doctors in the team together, which meant that the rounds could be completed in half-an-hour and consequently more senior doctors were available for supervision during the rest of the day. This was adopted by the outpatient clinic, the endoscopy unit, and the operating rooms, where activities did not start until after the rounds. RESULTS: The changes led to a considerable increase in the number of working situations with supervision. Assessment by a questionnaire showed that residents also found significant improvements in supervision during all clinical activities. Overall satisfaction with the department and working conditions increased. CONCLUSION: Many different aspects must be considered if clinical medical training is to improve. One key factor is a thorough revision of the daily working plans, so as to establish as many supervised teaching situations as possible.

Copenhagen City Heart Study: longitudinal analysis of ventilatory capacity in diabetic and nondiabetic adults.

The natural history of lung function in diabetes is unknown due to the lack of longitudinal observations. The decline of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) was studied over 15 yrs in the 17,506 adult participants of The Copenhagen City Heart Study, which included 266 individuals with diabetes. Multiple linear regression and a mixed-effects model were used, taking into account correlation between repeated measurements and adjusting for relevant confounders. In both sexes, FEV1 and FVC were consistently lower in diabetic individuals, compared with healthy individuals, with an average reduction of approximately 8% of the predicted value. Longitudinal analyses showed that the decline of FEV1 and FVC in diabetic individuals was similar to that observed in nondiabetic subjects. It was concluded that although diabetic subjects have, on average, a lower forced expiratory volume in one second and forced vital capacity than individuals without diabetes, this deficit seems not to be progressive in the long term. These observations may be of importance with regard to diabetes treatment with inhaled pulmonary insulin, which is likely to become available within a few years.

Prenatal detection of chromosome aneuploidies by fluorescence in situ hybridization: experience with 2000 uncultured amniotic fluid samples in a prospective preclinical trial.

Successful rapid prenatal detection of selected numerical chromosome abnormalities by using fluorescence in situ hybridization (FISH) on uncultured amniotic fluid samples has been described by Klinger et al. (1992) and Ward et al. (1993, 1997). Using essentially the same FISH protocol and identical probes specific for chromosomes 21, 18, 13, X, and Y, we prospectively compared the results of FISH and conventional cytogenetics on 2000 amniotic fluid cell samples. The 1-day FISH assay yielded discrete differences in the signal profiles between cytogenetically disomic, i.e., normal, and trisomic samples. Due to intermittent absent Y-signals, the assay differentiated less well between samples with cytogenetically normal and abnormal sex chromosome complements. The assay efficiency, and thus the clinical utility, was affected by (1) unsuccessful hybridizations (7 per cent of all hybridizations), (2) hybridizations with less than 50 scorable nuclei (19 per cent of all hybridizations), and (3) visibly contaminated samples with possible maternal cell contamination (14 per cent of all samples). As a result, we were not able to reproduce the results of Klinger et al. (1992) and Ward et al. (1993, 1997).

Prolonged signal-averaged P wave duration after elective cardioversion increases the risk of recurrent atrial fibrillation.

OBJECTIVE: To assess the risk of atrial fibrillation (AF) recurrence after elective cardioversion of AF in relation to the signal-averaged P wave duration (SAPWD), clinical characteristics of the patient, and the duration of the AF disease. DESIGN: We studied 131 consecutive patients (88 men, 43 women), median age 67 years (range 29-87 years), after elective cardioversion of AF into sinus rhythm. The SAPWD was measured on inclusion, and the follow-up period was 1 month. Recurrent AF within the first month after cardioversion was regarded as endpoint. RESULTS: AF recurred in 73 patients (56%). Multiple logistic regression analysis showed that prolonged SAPWD above 160 ms was the only significant risk factor for recurrent AF, OR=2.22 (95% CI 1.07-4.60), p=0.03. There was no significant effect of age, diagnosed hypertension, diagnosed congestive heart failure, dilated left atrium, or long duration of AF on the risk of AF relapse. CONCLUSION: Prolonged SAPWD above 160 ms is a risk factor for recurrent AF after elective cardioversion of persistent AF.

A 15-year follow-up study of ventilatory function in adults with asthma.

BACKGROUND: Although the prevalence of asthma and morbidity related to asthma are increasing, little is known about the natural history of lung function in adults with this disease. METHODS: We used data from a longitudinal epidemiologic study of the general population in a Danish city, the Copenhagen City Heart Study, to analyze changes over time in the forced expiratory volume in one second (FEV1) in adults with self-reported asthma and adults without asthma. The study was conducted between 1976 and 1994; for each patient, three measurements of lung function were obtained over a 15-year period. The final data set consisted of measurements from 17,506 subjects (8136 men and 9370 women), of whom 1095 had asthma. RESULTS: Among subjects who participated in all three evaluations, the unadjusted decline in FEV1 among subjects with asthma was 38 ml per year, as compared with 22 ml per year in those without asthma. The decline in FEV1 normalized for height (FEV1 divided by the square of the height in meters) was greater among the subjects with asthma than among those without the disease (P<0.001). Among both men and women, and among both smokers and nonsmokers, subjects with asthma had greater declines in FEV1 over time than those without asthma (P<0.001). At the age of 60 years, a 175-cm-tall nonsmoking man without asthma had an average FEV1 of 3.05 liters, as compared with 1.99 liters for a man of similar age and height who smoked and had asthma. CONCLUSIONS: In a sample of the general population, people who identified themselves as having asthma had substantially greater declines in FEV1 over time than those who did not.

Exogenous female sex steroid hormones and risk of asthma and asthma-like symptoms: a cross sectional study of the general population.

BACKGROUND: Recent evidence suggests a role for hormonal factors in the aetiology of asthma. METHODS: Data from a large study of women selected from the general population were used to relate treatment with oral hormonal contraceptives (OCP) and postmenopausal hormone replacement therapy (HRT) to the following asthma indicators: self-reported asthma, wheezing, cough at exertion, and use of medication for asthma. The study sample comprised 1536 premenopausal and 3016 postmenopausal women who participated in the third round of the Copenhagen City Heart Study in 1991-4. A total of 377 women were taking OCP (24.5% of premenopausal women) and 458 were on HRT (15.2% of postmenopausal women). RESULTS: In premenopausal women 4.8% reported having asthma. The prevalence of self-reported asthma, wheeze, use of asthma medication, and cough at exertion was not significantly related to use of OCP. In postmenopausal women the prevalence of self-reported asthma was 6.2%. A weak but consistent association was observed between HRT and self-reported asthma (OR 1.42 (95% CI 0.95 to 2.12)), wheeze (OR 1.29 (95% CI 1.02 to 1.64)), cough at exertion (OR 1.34 (95% CI 1.01 to 1.77)), and use of asthma medication (OR 1.45 (95% CI 0.97 to 2.18)). CONCLUSIONS: In this study of the general population no relationship was found between the use of OCP and asthma. Although an association was observed between HRT and asthma and asthma-like symptoms, this was relatively weak and it is concluded that there is no necessity to change present prescription practice.

Randomised study of risk of fetal loss related to early amniocentesis versus chorionic villus sampling.

BACKGROUND: Several cohort studies have shown the feasibility of early amniocentesis (between 11 and 13 weeks of gestation) as an alternative to chorionic villus sampling (CVS) for karyotyping, but the only completed randomised study of fetal safety showed a significant fetal-loss risk related to first-trimester amniocentesis. We assessed fetal safety in early amniocentesis and CVS. METHODS: We assessed early amniocentesis at 11-13 weeks gestational age compared with the fetal risk associated with CVS at 10-12 weeks. 1160 pregnant women were randomly assigned one procedure (581 early amniocentesis, 579 CVS) after a baseline ultrasound examination at 10 weeks' gestation and were followed up until birth. Total fetal loss and neonatal morbidity were the primary outcome measures. Sampling success and pregnancy complications were secondary outcomes. We used a filter to increase the cell yield in the early amniotic-fluid samples. CVS was transabdominal. FINDINGS: We found a significantly increased occurrence of talipes equinovarus in the early amniocentesis group (p < 0.01), the risk of which was associated with sampling at the earliest gestational ages and with temporary leakage of amniotic fluid after sampling. Therefore, the trial was stopped early, which reduced the power of the safety study. 4.8% (27) of fetuses in the CVS group and 5.4% (30) in the early amniocentesis group were lost after randomisation (p = 0.66). More detailed survival analysis did not show any significant differences in fetal loss rates. Leakage of amniotic fluid after sampling occurred significantly more frequently after early amniocentesis than after CVS (p < 0.001), but we found no other major differences in pregnancy complications. Significantly more CVS than early amniocentesis procedures were repeated or failed to produce a karyotype (p < 0.01). INTERPRETATION: Even though the numbers were small, we found an association between early amniocentesis and talipes equinovarus. We believe this association to be true, since it supports a trend in a similar randomised study. Our results show that early amniocentesis, when done with the filter technique, is associated with an abortion risk similar to CVS, although the limited size of our study population reduced the strength of this conclusion.

NT-proBNP: a new diagnostic screening tool to differentiate between patients with normal and reduced left ventricular systolic function.

OBJECTIVE: To evaluate whether measurements of N-terminal pro-brain natriuretic peptide (NT-proBNP) can be used to differentiate patients with normal and reduced left ventricular ejection fraction (LVEF) in an unselected consecutive group of hospital inpatients. SETTING: City general hospital, Copenhagen, Denmark. PATIENTS AND DESIGN: During a 10 month period 2230 admissions to a city general hospital (80% of targeted patients) had an echocardiographic evaluation of left ventricular function, a comprehensive clinical evaluation, and blood analysis of N-terminal-pro-brain natriuretic peptide (NT-proBNP) within 24 hours of admission. Exclusions resulted from lack of informed consent or failure to obtain the required evaluations before death or discharge from hospital. Echocardiography was unsatisfactory in 37 patients, so the final number studied was 2193. RESULTS: A raised NT-proBNP (>or= 357 pmol/l) identified patients with an LVEF of 40% was more than 97%. This probability rapidly decreased to 70% as the measured NT-proBNP increased to 150% of the predicted value. CONCLUSIONS: A single measurement of NT-proBNP at the time of hospital admission provides important information about LVEF in unselected patients.

Prenatal detection of chromosome aneuploidies in uncultured chorionic villus samples by FISH.

We developed a 1-d FISH assay for detection of numerical chromosome abnormalities in uncultured chorionic villus samples (CVS). Probes specific for chromosomes 13, 18, 21, X, and Y were used to determine ploidy by analysis of signal number in hybridized nuclei. Aneuploidy detection using this assay was directly compared with the results obtained by conventional cytogenetic analysis in a consecutive, clinical study of 2,709 CVS and placental samples. The FISH assay yielded discrete differences in the signal profiles between cytogenetically normal and abnormal samples. On the basis of these results, we generated FISH-assay cutoff values that discriminated between karyotypically normal and aneuploid samples. Samples with mosaicism and a single sample with possible heritable small chromosome X probe target were exceptions and showed poor agreement between FISH results and conventional cytogenetics. We conclude that the FISH assay may act as a more accurate and less labor-demanding alternative to "direct" CVS analysis.