Sex-related differences among young adults with heart failure in Sweden.

BACKGROUND: Differences between the sexes among the non-elderly with heart failure (HF) have been insufficiently evaluated. This study aims to investigate sex-related differences in early-onset HF. METHODS: Patients aged 18 to 54 years who were registered from 2003 to 2014 in the Swedish Heart Failure Register were included. Each patient was matched with two controls from the Swedish Total Population Register. Data on comorbidities and outcomes were obtained through the National Patient Register and Cause of Death Register. RESULTS: We identified 3752 patients and 7425 controls. Of the patients, 971 (25.9%) were women and 2781 (74.1%) were men with a mean (standard deviation) age of 44.9 (8.4) and 46.4 (7.3) years, respectively. Men had more hypertension and ischemic heart disease, whereas women had more congenital heart disease and obesity. During the median follow-up of 4.87 years, 26.5 and 24.7 per 1000 person-years male and female patients died, compared with 3.61 and 2.01 per 1000 person-years male and female controls, respectively. The adjusted hazard ratios for all-cause mortality, compared with controls, were 4.77 (3.78-6.01) in men and 7.84 (4.85-12.7) in women (p for sex difference = 0.11). When HF was diagnosed at 30, 35, 40, and 45 years, women and men lost up to 24.6 and 24.2, 24.4 and 20.9, 20.5 and 18.3, and 20.7 and 16.5 years of life, respectively. CONCLUSION: Long-term mortality was similar between the sexes. Women lost more years of life than men.

Diverging trends for onset of acute myocardial infarction, heart failure, stroke and mortality in young males: role of changes in obesity and fitness.

BACKGROUND: As opposed to the decreasing overall rates of coronary heart disease (CHD) incidence and overall cardiovascular disease (CVD) mortality, heart failure (HF) and stroke incidence are increasing in young people, potentially due to rising rates of obesity and reduced cardiorespiratory fitness (CRF). OBJECTIVES: We investigated trends in early major CVD outcomes in a large cohort of young men. METHODS: Successive cohorts of Swedish military conscripts from 1971 to 1995 (N = 1,258,432; mean age, 18.3 years) were followed, using data from the National Inpatient and Cause of Death registries. Cox proportional hazard models were used to analyse changes in 21-year CVD event rates. RESULTS: 21-year CVD and all-cause mortality and incidence of acute myocardial infarction (AMI) decreased progressively. Compared with the cohort conscripted in 1971-1975 (reference), the hazard ratios (HRs) for the last 1991-1995 cohort were 0.50 [95% confidence interval (CI) 0.42-0.59] for CVD mortality; 0.57 (95% CI 0.54-0.60) for all-cause mortality; and 0.63 (95% CI 0.53-0.75) for AMI. In contrast, the incidence of ischaemic stroke, intracerebral haemorrhage and HF increased with HRs of 1.43 (95% CI 1.17-1.75), 1.30 (95% CI 1.01-1.68) and 1.84 (95% CI 1.47-2.30), respectively. During the period, rates of obesity increased from 1.04% to 2.61%, whilst CRF scores decreased slightly. Adjustment for these factors influenced these secular trends only moderately. CONCLUSION: Secular trends of young-onset CVD events demonstrated a marked shift from AMI and CVD mortality to HF and stroke incidence. Trends were significantly, though moderately, influenced by changing baseline BMI and CRF.

What determines continuing grey matter changes in first-episode schizophrenia and affective psychosis?

BACKGROUND: Magnetic resonance imaging (MRI) studies have shown that brain abnormalities in psychosis might be progressive during the first years of illness. We sought to determine whether first-episode psychosis (FEP) subjects show progressive regional grey matter (GM) changes compared with controls, and whether those changes are associated with diagnosis, illness course or antipsychotic (AP) use. METHOD: Thirty-two subjects with first-episode schizophrenia-spectrum disorders (FESZ), 24 patients with first-episode affective psychoses (FEAP) and 34 controls recruited using a population-based design underwent structural MRI scanning at baseline and at a 5-year follow-up. Regional GM volumes were assessed with voxel-based morphometry (VBM). Patients were treated at community settings, and about half of them remained mainly untreated. RESULTS: No significant progressive changes in GM regional volumes were observed in either the FESZ or FEAP group overall. However, FESZ subjects with a non-remitting course showed GM decrements in the left superior temporal gyrus (STG) and insula relative to remitted FESZ subjects. Non-remitted FEAP subjects exhibited a GM decrease in the dorsolateral prefrontal cortex (DLPFC) bilaterally in comparison to remitted FEAP subjects. Among FESZ subjects, AP use was associated with regional GM decrements in the right insula and increments in the cerebellum. CONCLUSIONS: Our results suggest that the progression of brain abnormalities in FEP subjects is restricted to those with a poor outcome and differs between diagnosis subgroups. AP intake is associated with a different pattern of GM reductions over time.

Consequences of insecurity in emergency telephone consultations: an experimental study in medical students.

QUESTION UNDER STUDY: Handling emergency telephone consultations (ETCs) is a challenging and very important task for doctors. The aims of the study were to document insecurity in medical students during ETCs and to identify the reasons for that insecurity. We hypothesised that insecurity is associated with advising more urgent action (e.g. advice to call for an ambulance) in ETCs. METHODS: We used ETCs with simulated patients (SPs), with each student randomly allocated two of four possible cases. After the training, 137 students reported on any insecurity that they had in the various ETC phases. We analysed the reasons for insecurity using descriptive statistics. The association between the students' advice that urgent action was needed and their insecurity was analysed with Spearman rank correlation. RESULTS: Overall, 95% of the students felt insecure in at least one phase of their ETC. History taking was the phase in which students felt most insecure (63.1%), followed by the phase of analysing the information given by the patient (44.9%). Perceived insecurity was associated with more urgent advice in one case scenario (abdominal pain; correlation r = 0.46; p <0.01). The other two cases (child with fever; chest pain) also had a positive, but not statistically significant, correlation trend (p <0.12; p <0.08). CONCLUSIONS: Insecurity is highly prevalent among medical students in their ETC decision-making. ETC training in medical schools, with a focus on structured history taking and formulating discriminating questions, might help decrease insecurity in ETCs. Medical education should also teach management of insecurity.

Longitudinal follow-up of cavum septum pellucidum and adhesio interthalamica alterations in first-episode psychosis: a population-based MRI study.

BACKGROUND: Neurodevelopmental alterations have been described inconsistently in psychosis probably because of lack of standardization among studies. The aim of this study was to conduct the first longitudinal and population-based magnetic resonance imaging (MRI) evaluation of the presence and size of the cavum septum pellucidum (CSP) and adhesio interthalamica (AI) in a large sample of patients with first-episode psychosis (FEP). METHOD: FEP patients (n=122) were subdivided into schizophrenia (n=62), mood disorders (n=46) and other psychosis (n=14) groups and compared to 94 healthy next-door neighbour controls. After 13 months, 80 FEP patients and 52 controls underwent a second MRI examination. RESULTS: We found significant reductions in the AI length in schizophrenia FEP in comparison with the mood disorders and control subgroups (longer length) at the baseline assessment, and no differences in any measure of the CSP. By contrast, there was a diagnosis×time interaction for the CSP length, with a more prominent increase for this measure in the psychosis group. There was an involution of the AI length over time for all groups but no diagnosis×time interaction. CONCLUSIONS: Our findings suggest that the CSP per se may not be linked to the neurobiology of emerging psychotic disorders, although it might be related to the progression of the disease. However, the fact that the AI length was shown to be shorter at the onset of the disorder supports the neurodevelopmental model of schizophrenia and indicates that an alteration in this grey matter junction may be a risk factor for developing psychosis.

Longitudinal brain volumetric changes during one year in non-elderly healthy adults: a voxel-based morphometry study

Previous cross-sectional magnetic resonance imaging (MRI) studies of healthy aging in young adults have indicated the presence of significant inverse correlations between age and gray matter volumes, although not homogeneously across all brain regions. However, such cross-sectional studies have important limitations and there is a scarcity of detailed longitudinal MRI studies with repeated measures obtained in the same individuals in order to investigate regional gray matter changes during short periods of time in non-elderly healthy adults. In the present study, 52 healthy young adults aged 18 to 50 years (27 males and 25 females) were followed with repeated MRI acquisitions over approximately 15 months. Gray matter volumes were compared between the two times using voxel-based morphometry, with the prediction that volume changes would be detectable in the frontal lobe, temporal neocortex and hippocampus. Voxel-wise analyses showed significant (P < 0.05, family-wise error corrected) relative volume reductions of gray matter in two small foci located in the right orbitofrontal cortex and left hippocampus. Separate comparisons for males and females showed bilateral gray matter relative reductions in the orbitofrontal cortex over time only in males. We conclude that, in non-elderly healthy adults, subtle gray matter volume alterations are detectable after short periods of time. This underscores the dynamic nature of gray matter changes in the brain during adult life, with regional volume reductions being detectable in brain regions that are relevant to cognitive and emotional processes.

Longitudinal brain volumetric changes during one year in non-elderly healthy adults: a voxel-based morphometry study.

Previous cross-sectional magnetic resonance imaging (MRI) studies of healthy aging in young adults have indicated the presence of significant inverse correlations between age and gray matter volumes, although not homogeneously across all brain regions. However, such cross-sectional studies have important limitations and there is a scarcity of detailed longitudinal MRI studies with repeated measures obtained in the same individuals in order to investigate regional gray matter changes during short periods of time in non-elderly healthy adults. In the present study, 52 healthy young adults aged 18 to 50 years (27 males and 25 females) were followed with repeated MRI acquisitions over approximately 15 months. Gray matter volumes were compared between the two times using voxel-based morphometry, with the prediction that volume changes would be detectable in the frontal lobe, temporal neocortex and hippocampus. Voxel-wise analyses showed significant (P < 0.05, family-wise error corrected) relative volume reductions of gray matter in two small foci located in the right orbitofrontal cortex and left hippocampus. Separate comparisons for males and females showed bilateral gray matter relative reductions in the orbitofrontal cortex over time only in males. We conclude that, in non-elderly healthy adults, subtle gray matter volume alterations are detectable after short periods of time. This underscores the dynamic nature of gray matter changes in the brain during adult life, with regional volume reductions being detectable in brain regions that are relevant to cognitive and emotional processes.

Lack of progression of brain abnormalities in first-episode psychosis: a longitudinal magnetic resonance imaging study.

BACKGROUND: Some neuroimaging studies have supported the hypothesis of progressive brain changes after a first episode of psychosis. We aimed to determine whether (i) first-episode psychosis patients would exhibit more pronounced brain volumetric changes than controls over time and (ii) illness course/treatment would relate to those changes. METHOD: Longitudinal regional grey matter volume and ventricle:brain ratio differences between 39 patients with first-episode psychosis (including schizophrenia and schizophreniform disorder) and 52 non-psychotic controls enrolled in a population-based case-control study. RESULTS: While there was no longitudinal difference in ventricle:brain ratios between first-episode psychosis subjects and controls, patients exhibited grey matter volume changes, indicating a reversible course in the superior temporal cortex and hippocampus compared with controls. A remitting course was related to reversal of baseline temporal grey matter deficits. CONCLUSIONS: Our findings do not support the hypothesis of brain changes indicating a progressive course in the initial phase of psychosis. Rather, some brain volume abnormalities may be reversible, possibly associated with a better illness course.

Intestinal paracellular permeability is not affected in chronic congestive heart failure.

BACKGROUND: In chronic heart failure (CHF) it has been proposed that a dysfunction of the gastrointestinal barrier could lead to translocation of endotoxin into the systemic circulation. A secondary inflammatory reaction, observed as increased levels of cytokines, could negatively affect cardiac function. The aims of this paper were therefore to determine whether patients with CHF have a disturbed mucosal barrier and whether it was possible to detect endotoxin in venous blood. METHODS: Nineteen stable patients with CHF (New York Heart Association II-III, EF40% and earlier hospitalisation for heart failure) were investigated. Twenty healthy subjects (HS group) and 25 patients, who were admitted for bone marrow transplantation (BMT group), served as controls. Gastrointestinal permeability was assessed by a (51)Cr-EDTA absorption test. RESULTS: Eleven patients with and eight without peripheral oedema were included. Median age was 76.5 years. Intestinal permeability was 1.82+/-1.96% in the CHF patients and 1.54+/-.59% and 1.9+/-.9% in HS and BMT groups, respectively (p=0.4 and p=0.7, CHF vs HS and BMT, respectively). No difference was found between patients with and without oedema and endotoxins were below the detection limit in all patients. DISCUSSION: This study does not support the hypothesis that patients with CHF have a dysfunctional gastrointestinal barrier, at least as assessed by the (51)Cr-EDTA resorbtion test.

[Better treatment of heart failure by measurements of natriuretic peptides. There are still remaining problems when it comes to the interpretation of measurement levels]. / Bättre behandling av hjärtsvikt med mätning av natriuretiska peptider. Tolkningen av mätvärdena bereder dock fortfarande problem.

The heart is increasingly being recognised as a major endocrine organ involved in haemodynamic homeostasis. Natriuretic peptides, i.e. atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), affect renal, adrenal and central nervous system functions as well as vessel tonus and permeability thus causing decreased preload and afterload. Natriuretic peptides, BNP in particular, are independent risk factors for morbidity and mortality. They also have high negative predictive values for cardiac insufficiency indicating high diagnostic sensitivity for heart failure in outpatient practice. Monitoring of therapy for heart failure may be improved if BNP measurement is used in conjunction with clinical assessment. However, several problems remain to be solved, such as optimal decision limits in relation to sex and age for the assessment of heart failure.

Skeletal muscle characteristics, muscle strength and thigh muscle area in patients before and after cardiac transplantation.

BACKGROUND: Patients with chronic heart failure demonstrate several skeletal muscle abnormalities. The underlying mechanisms are unclear. After cardiac transplantation, cardiac function is restored, but exercise capacity is still impaired. AIM: To evaluate the influence of cardiac transplantation on skeletal muscle fibre composition, fibre area and capillarization as well as muscle enzymes, lactate, thigh muscle area and strength. METHODS: Ten patients were longitudinally investigated before, 1-3 and 6-9 months after transplantation. Ten healthy individuals served as controls. A biopsy from the lateral vastus muscle was obtained and the thigh muscle area was measured with computed tomography. Muscle strength in the knee extensors and exercise capacity were also evaluated. RESULTS: Muscle lactate was elevated in patients vs. controls (3.6+/-3.0 vs. 1.5+/-0.7 mmol/kg wet wt., P=0.037), and decreased to normal (1.4+/-0.3 mmol/kg wet wt., P=0.038) after transplantation. Citrate synthase activity was decreased in patients (5.6+/-1.5 micromol/g wet wt./min) vs. controls (8.1+/-1.6 micromol/g wet wt./min, P=0.0018), and did not change post transplantation. Patients had decreased number of capillaries in contact with each fibre vs. controls (2.6+/-0.5 vs. 3.5+/-1.0, P=0.039) which persisted post transplantation. Exercise capacity increased after transplantation (74+/-22 vs. 118+/-26 W, P=0.0002), whereas muscle strength did not improve significantly. CONCLUSION: The persisting intrinsic abnormalities in skeletal muscle after cardiac transplantation may contribute to the impaired exercise capacity observed in cardiac transplant recipients.

Angiotensin-converting enzyme gene expression in skeletal muscle in patients with chronic heart failure.

BACKGROUND: Skeletal muscle factors may influence functional limitation in patients with heart failure. The renin-angiotensin system is activated in chronic heart failure. Treatment with angiotensin-converting enzyme (ACE) inhibitors improve symptoms and prognosis. The goal of this study was to quantify and localize skeletal muscle ACE-mRNA in patients with chronic heart failure and in control subjects, and to elucidate skeletal muscle fiber area and capillary density. METHODS AND RESULTS: Biopsies from the lateral vastus muscle were taken from 9 patients before and after treatment with enalapril and in 10 control subjects. ACE-mRNA was quantified with reverse transcription polymerase chain reaction. Immunohistochemistry was used to localize ACE within skeletal muscle. No difference in ACE-mRNA transcripts between patients and control subjects was detected, nor did ACE gene expression change after treatment with enalapril. The number of ACE-mRNA transcripts was related to muscle fiber area, whereas an inverse relationship between the number of ACE transcripts and capillary density was found. ACE was detected in the endothelial cells of capillaries in skeletal muscle. CONCLUSION: ACE is expressed in skeletal muscle and is confined to endothelial cells. The close relationship between capillary density and number of ACE transcripts indicate that activation of the renin-angiotensin system has an impact on capillary growth.

Muscular performance in heart failure.

BACKGROUND: Some of the major symptoms in patients with chronic heart failure are muscle weakness and fatigue. However, not much is known about muscle performance in these patients compared to healthy controls. METHODS AND RESULTS: Activity level, gait speed, hand grip strength, muscle performance of the knee extensors and flexors along with the plantar and dorsal flexors of the foot were evaluated. Muscle biopsies from the lateral vastus lateralis were taken. Sixteen patients in New York Heart Association class II or III were tested and compared to 112 reference subjects. Compared to the reference subjects, there was a reduction in activity level, gait speed, isometric and isokinetic peak torque for knee extension at different velocities, hand grip strength, peak torque for plantar and dorsal flexion of the ankle and isometric and isokinetic endurance for the knee extension. Recovery was faster. There were small differences in fiber composition. 3-Hydroxy-acylCoA-dehydrogenase and citrate synthase were lower, and lactate dehydrogenase was increased. CONCLUSIONS: Muscle performance is affected in terms of both strength and endurance, which might affect performance in everyday activities. The more pronounced reduction in hand grip compared to the other muscles tested could be an indication of intrinsic abnormalities in the skeletal muscle.

Skeletal muscle alterations in patients with chronic heart failure.

AIMS: To investigate skeletal muscle in patients with chronic heart failure and controls, and relate skeletal muscle variables to functional class, exercise capacity, central haemodynamics, muscle strength and medical treatment. METHODS: Biopsy from the lateral vastus muscle was obtained in 43 patients and 20 controls. Right sided heart catheterization was performed in 19 patients and maximal exercise testing in 26 patients. In nine patients muscle strength was measured. Patients had higher lactate levels, higher lactate dehydrogenase activity, and lower oxidative enzymes activity than controls. In patients, the percentage of type I fibres and capillarization were decreased while the percentage of type II B fibres were increased. Lactate dehydrogenase activity correlated with exercise capacity, muscle strength and right atrial pressure. Digoxin-treated patients had significantly lower oxidative enzyme activity than patients without digoxin treatment. CONCLUSION: Patients with chronic heart failure have several skeletal muscle abnormalities. Central haemodynamics and medical treatment may, in addition to inactivity, be important in skeletal muscle changes.

Skeletal muscle changes in patients with chronic heart failure before and after treatment with enalapril.

To evaluate if enalapril treatment can influence skeletal muscle metabolism and histology we investigated 26 patients with congestive heart failure and 20 normal subjects. The patients were treated with enalapril for 3 months in addition to diuretics and digitalis. Biopsies from the lateral vastus muscle were taken before and after treatment. Citrate synthetase, 3-hydroxyacyl-CoA dehydrogenase and phosphorylase activities were significantly decreased in the patients compared with controls. The number of capillaries per fibre and the number of capillaries surrounding each fibre were significantly decreased among patients. After 3 months of enalapril treatment functional class improved significantly. The lactate dehydrogenase activity increased whereas the oxidative enzymes did not change significantly. The type I, II and II A fibre areas increased significantly after enalapril treatment. We conclude that patients with chronic heart failure have decreased activity of oxidative enzymes and of phosphorylase in skeletal muscle. They also have decreased capillarization in skeletal muscle. These changes were not influenced by enalapril treatment. The increase in muscle fibre area seen after enalapril treatment could be due to increased physical activity. The cause of increased muscle lactate dehydrogenase activity after enalapril treatment needs further investigation.

Skeletal muscle metabolism during exercise in patients with chronic heart failure.

OBJECTIVE: To investigate the metabolic response of skeletal muscle to exercise in patients with chronic heart failure and determine its relation to central haemodynamic variables. SETTING: University hospital in Sweden. PARTICIPANTS: 16 patients in New York Heart Association class II-III and 10 healthy controls. MAIN OUTCOME MEASURES: Skeletal muscle biopsies were obtained from the quadriceps muscle at rest and at submaximal and maximal exercise. Right sided heart catheterisation was performed in eight patients. RESULTS: The patients had lower maximal oxygen consumption than the control group (13.2 (2.9) v 26.8 (4.4) ml/kg/min, P < 0.001). They had reduced activities of citrate synthetase (P < 0.05) and 3-hydroxyacyl-CoA dehydrogenase (P < 0.05) compared with the controls. At maximal exercise adenosine triphosphate (P < 0.05), creatine phosphate (P < 0.01), and glycogen (P < 0.01) were higher whereas glucose (P < 0.001) and lactate (P < 0.06) were lower in the patients than in the controls. Citrate synthetase correlated inversely with skeletal muscle lactate at submaximal exercise (r = -0.90, P < 0.003). No correlations between haemodynamic variables and skeletal muscle glycogen, glycolytic intermediates, and adenosine nucleotides during exercise were found. CONCLUSION: Neither skeletal muscle energy compounds nor lactate accumulation were limiting factors for exercise capacity in patients with chronic heart failure. The decreased activity of oxidative enzymes may have contributed to the earlier onset of anaerobic metabolism, but haemodynamic variables seemed to be of lesser importance for skeletal muscle metabolism during exercise.

Skeletal muscle fiber composition and capillarization in patients with chronic heart failure: relation to exercise capacity and central hemodynamics.

Patients with chronic heart failure have structural and metabolic changes in skeletal muscle, which may be of importance for symptomatology. The origin of these changes are still unknown. The relationship between fiber composition and capillarization in skeletal muscle with exercise capacity and central hemodynamic variables was examined. Biopsies from the lateral vastus muscle were taken in 12 patients with chronic heart failure. Samples from eight normal subjects served as control samples. All patients underwent maximal exercise tests. Central hemodynamic variables were measured during exercise in five patients. The patients had a higher percentage of type II B fibers (P = .03) and fewer capillaries per fiber (P = .02) than the controls subjects. VO2 max correlated with the percentage of type I fibers, whereas the correlation with the type II A fibers was inverse. Cardiac index and pulmonary capillary wedge pressure at submaximal and maximal exercise were related to fiber type composition and relative fiber areas. Skeletal muscle fiber type composition and capillarization was changed in patients with chronic heart failure. These changes might influence exercise capacity. There were relationships between central hemodynamic variables and skeletal muscle changes. What the cause and effects were need further investigation.