Pre-plaque conformational changes in Alzheimer's disease-linked Aß and APP.

Reducing levels of the aggregation-prone Aß peptide that accumulates in the brain with Alzheimer's disease (AD) has been a major target of experimental therapies. An alternative approach may be to stabilize the physiological conformation of Aß. To date, the physiological state of Aß in brain remains unclear, since the available methods used to process brain tissue for determination of Aß aggregate conformation can in themselves alter the structure and/or composition of the aggregates. Here, using synchrotron-based Fourier transform infrared micro-spectroscopy, non-denaturing gel electrophoresis and conformational specific antibodies we show that the physiological conformations of Aß and amyloid precursor protein (APP) in brain of transgenic mouse models of AD are altered before formation of amyloid plaques. Furthermore, focal Aß aggregates in brain that precede amyloid plaque formation localize to synaptic terminals. These changes in the states of Aß and APP that occur prior to plaque formation may provide novel targets for AD therapy.

[Quality assurance of secondary prevention of coronary artery disease. Ongoing project offers possibilities for improved treatment]. / Kvalitetssäkring av sekundärprevention vid kranskärlssjukdom. Pågående projekt skapar möjligheter till förbättrad behandling.

Regional programs for secondary prevention of coronary artery disease have been under development for nearly a decade in Sweden. To achieve maximum adherence these programs were created in close collaboration between hospital and primary care physicians. The programs are local applications of national guidelines and aim to support compliance among both patients and physicians. In January 1998 the Swedish Society of Cardiology and the Swedish Association of General Practice launched a program for quality control and quality assurance of these initiatives. So far, 51 of 79 districts have joined the program. Patients' diaries used for risk factor registration contain 7 report cards on the management of risk factors and medication. These cards are sent to a central registry upon release from the hospital, after 3-6 months, and annually for 5 years. Results from the first year point to differences between the various districts with respect to compliance with both local programs and European guidelines. Overall, results are promising and indicate that this program is successful and leads to improved management of patients with coronary artery disease.

Comparison of calculated, measured and self-assessed intelligibility of speech in noise for hearing-aid users.

The Speech Intelligibility Index (SII) was used along with paired-comparison judgements and speech recognition scores to compare the speech intelligibility provided by two hearing-aid frequency responses in two different background noises. The purpose was to validate an SII-based procedure. Test subjects were 26 hearing-aid users representing a wide range of hearing loss configurations. One hearing-aid setting was in close agreement with the NAL-R prescription, whereas the other setting was achieved by reducing the high-frequency gain by about 10 dB compared to NAL-R. There were good overall agreements between results of the three methods. Average speech recognition scores were about 4 percentage points higher for the NAL-R frequency response, which also was subjectively judged as significantly better in terms of speech intelligibility. The SII based procedure was found to be suitable for comparing hearing-aid characteristics within subjects.

Long-term effects on cholesterol levels and the utilization of lipid-lowering drugs of a hospital-based programme for secondary prevention of coronary artery disease.

BACKGROUND: The study was designed to determine whether a 1-year hospital-based secondary prevention programme would have any long-term effects on serum lipid levels and the use of lipid-lowering drugs in patients with coronary artery disease 4 years after referral to primary care facilities for follow-up. DESIGN/METHODS: After acute myocardial infarction or coronary bypass surgery, 241 consecutive patients were randomly assigned to conventional care (CC) by the primary health care facilities or to a 1-year hospital-based secondary prevention programme (SPP) with target levels for serum cholesterol (< 5.2 mmol/l) and triglycerides (< 1.5 mmol/l). After 1 year all patients were referred to the primary care sector for a further 4-year follow-up. RESULTS: At the 1-year follow-up there was a significant decrease in serum cholesterol, LDL-cholesterol and triglyceride levels in the SPP group but no change in the CC group, and lipid-lowering drugs were used more frequently in the SPP group. These changes were maintained after 5 years. The proportion of patients achieving target serum cholesterol and triglyceride levels were larger in the SPP group. CONCLUSIONS: Initiatives regarding cholesterol lowering and drug treatment taken by specialists within a structured hospital-based SPP have long-term impact. Accordingly, drug treatment should be initiated and adjusted to adequate doses before patients are referred to primary care for follow-up.

Health care costs of heart failure: results from a randomised study of patient education.

BACKGROUND: Heart failure is a serious syndrome with a bad prognosis. Hospitalisation is common and readmittance rate is high; factors which influence the cost of care and treatment. Only scarce data on detailed patient materials regarding health care costs are known. AIMS: To describe in detail the health care costs for heart failure patients. METHODS: Costs for patients (n=108) who completed a randomised education trial were studied for 6 months after hospital discharge. Costs for hospital stay, out-patient visits, diagnostic tests and procedures, laboratory analyses and drug treatment were calculated. Official unit prices list used to reimburse providers of cross-boundary health services and prices for drugs in the Swedish Drug Compendium were employed. RESULTS: The total cost for a heart failure patient was approximately 20000 SEK (2564 US$, 7.80 SEK=1 US$) for 6 months. There was a 27-fold variation between patients. There was no relation between age or sex and cost. In decreasing order cost for hospitalisation was followed by costs for out-patient visits, diagnostic tests and procedures, laboratory analyses and drugs. CONCLUSION: Hospitalisation was the largest part of the total cost and there was a large inter-individual variation. Efforts to reduce the economic burden should be focused on hospitalisation. Due to skewed distribution, individual data must be considered in the analysis of the efforts.

Health-related quality of life in elderly patients with heart failure.

OBJECTIVE: To assess health-related quality of life (HRQL) in elderly patients with congestive heart failure (CHF) and correlate these to clinical and demographic variables. PATIENTS AND METHODS: HRQL was evaluated in 191 patients with CHF, aged 65-84 years, using a self-administered questionnaire including the Nottingham Health Profile (NHP), Quality of Life Questionnaire in Heart Failure and Patients' Global Self-Assessment. RESULTS: HRQL was more impaired in women than to men (p < 0.05), New York Heart Association functional class correlated to HRQL (p < 0.01) and HRQL, as assessed by NHP, was impaired in CHF patients compared to a previously evaluated, age and sex matched, normal reference population. CONCLUSION: Measurement of HRQL in heart failure patients provides important information in addition to a clinical evaluation, and inclusion of HRQL assessments in clinical practice is feasible and warranted. Specific intervention should be aimed at improving HRQL in those most severely affected.

Alcohol consumption and disability pension among middle-aged men.

PURPOSE: To analyze the relation between alcohol consumption and the risk of disability pension among middle-aged men. METHODS: In the mid-seventies, complete birth-year cohorts of middle-aged male residents in Malmö, Sweden, were invited to participate in a general health survey. The 3751 men with complete data who constituted the cohort in this study were followed for 11 years. Alcohol consumption was estimated from the scores obtained from a test designed to identify subjects with alcohol related problems. RESULTS: Of the 498 men granted disability pension during follow-up, 48 stated to be teetotalers. The cumulative incidence of disability pension among teetotalers was 19%, whereas, it was 12% and 16%, respectively, among men with low and high alcohol consumption. The adjusted relative risk (RR) for acquiring a disability pension (using the group with low alcohol consumption as reference) was 1.8 among abstainers and 1.3 among men with high alcohol consumption. CONCLUSIONS: Alcohol overconsumption, as well as teetotalism, showed a positive relation to disability pension, and a moderate alcohol intake was found to be beneficial with respect to the risk of future disability pension.

Left atrioventricular plane displacement is related to both systolic and diastolic left ventricular performance in patients with chronic heart failure.

AIMS: Left atrioventricular plane displacement is proposed to reflect left ventricular systolic function and is strongly related to prognosis in patients with heart failure. Left atrioventricular plane displacement is a different measure of left ventricular function compared to ejection fraction, and the factors influencing left atrioventricular plane displacement are insufficiently characterized. We wanted to assess any relationship between left atrioventricular plane displacement and left ventricular diastolic performance. METHODS AND RESULTS: Left ventricular diastolic filling, left atrioventricular plane displacement, and fractional shortening were assessed by echocardiography/Doppler in 54 patients with chronic heart failure (age 64 +/- 7 years). Left atrioventricular plane displacement correlated significantly with Doppler variables of left ventricular filling, in particular the inverse logarithm of early transmitral flow deceleration time; log-1 Edt (r = -0.61, P < 0.0001, n = 54). Left atrioventricular plane displacement also correlated with fractional shortening (r = 0.49, P < 0.001, n = 50). However, fractional shortening did not correlate with any Doppler variable. Log-1 Edt, fractional shortening, age, heart rate, left ventricular and atrial size, and degree of mitral regurgitation were included in a multiple regression analysis. Only log-1 Edt (P = 0.001) and fractional shortening (P = 0.03) correlated independently with left atrioventricular plane displacement. Among patients with similar fractional shortening, those with more compromised diastolic performance had lower left atrioventricular plane displacement. CONCLUSION: Left atrioventricular plane displacement was related to both systolic and diastolic left ventricular performance, which may explain some of the discrepancies between left atrioventricular plane displacement and ejection fraction.

Effects of systematic education on heart failure patients' knowledge after 6 months. A randomised, controlled trial.

BACKGROUND: Many procedures for patient education are introduced in clinical practice without proper evaluation in randomised trials. AIMS: To compare systematic nurse and pharmacist led education including an interactive Kodak Photo-CD Portfolio technique with conventional information regarding heart failure patients' knowledge. METHODS: One hundred and thirty heart failure patients discharged from hospital were randomised to receive either conventional information or additional structured education with a follow-up of 6 months. Difference in knowledge was tested by questionnaire after 6 months. RESULTS: At the end of the study there was a significant difference in the intervention group (n = 50) compared to the control group (n = 58) regarding knowledge as tested by a questionnaire. Of maximal 28 points the intervention group attained 17.2 points (mean) and the control group 14.3 points (mean), 95% confidence interval for difference 1.0-4.7 points (P = 0.0051). CONCLUSIONS: Two to 3 hours of systematic education improved heart failure patients' knowledge on essential issues. High age does not preclude the introduction of a new technique for patient education.

Non-compliance and knowledge of prescribed medication in elderly patients with heart failure.

AIMS: To determine the extent of non-compliance to prescribed medication in elderly patients with heart failure and to determine to what extent patients recall information given regarding their medication. METHODS AND RESULTS: Non-compliance and knowledge of prescribed medication was studied in 22 elderly heart failure patients [mean age 79 +/- 6 (range 70-97); 14 (64%) male], using in-depth interviews performed 30 days after having been prescribed medication. All patients received standardised verbal and written information regarding their medication. Only 12 (55%) patients could correctly name what medication had been prescribed, 11 (50%) were unable to state the prescribed doses and 14 (64%) could not account for when the medication was to be taken, i.e. at what time of day and when in relation to meals the medication was to be taken. In the overall assessment six (27%) patients were found non-compliant and 16 (73%) patients were considered as possibly being compliant with their prescribed medication. CONCLUSIONS: Non-compliance was common in elderly heart failure patients, as were shortcomings in patients knowledge regarding prescribed medication, despite efforts to give adequate information. There exists a need for alternative strategies to improve compliance in these patients.

Exercise training in heart failure improves quality of life and exercise capacity.

AIMS: Benefit from exercise training in heart failure has mainly been shown in men with ischaemic disease. We aimed to examine the effects of exercise training in heart failure patients < or = 75 years old of both sexes and with various aetiology. METHODS AND RESULTS: Fifty-four patients with stable mild-to-moderate heart failure were randomized to exercise or control, and 49 completed the study (49% > or = 65 years; 29% women; 24% non-ischaemic aetiology; training, n = 22; controls, n = 27). The exercise programme consisted of bicycle training at 80% of maximal intensity over a period of 4 months. Improvements vs controls were found regarding maximal exercise capacity (6 +/- 12 vs -4 +/- 12% [mean +/- SD], P < 0.01) and global quality-of-life (2 [1] vs 0 [1] units [median ¿inter-quartile range¿], P < 0.01), but not regarding maximal oxygen consumption or the dyspnoea-fatigue index. All of these four variables significantly improved in men with ischaemic aetiology compared with controls (n = 11). However, none of these variables improved in women with ischaemic aetiology (n = 5), or in patients with non-ischaemic aetiology (n = 6). The training response was independent of age, left ventricular systolic function, and maximal oxygen consumption. No training-related adverse effects were reported. CONCLUSION: Supervised exercise training was safe and beneficial in heart failure patients < or = 75 years, especially in men with ischaemic aetiology. The effects of exercise training in women and patients with non-ischaemic aetiology should be further examined.

Cost effective management programme for heart failure reduces hospitalisation.

OBJECTIVE: To study the effects of a management programme on hospitalisation and health care costs one year after admission for heart failure. DESIGN: Prospective, randomised trial. SETTING: University hospital with a primary catchment area of 250,000 inhabitants. PATIENTS: 190 patients (aged 65-84 years, 52.3% men) hospitalised because of heart failure. INTERVENTION: Two types of patient management were compared. The intervention group received education on heart failure and self management, with follow up at an easy access, nurse directed outpatient clinic for one year after discharge. The control group was managed according to routine clinical practice. MAIN OUTCOME MEASURES: Time to readmission, days in hospital, and health care costs during one year. RESULTS: The one year survival rate was 71.8% (n = 79) in the control group and 70.0% (n = 56) in the intervention group (NS). The mean time to readmission was longer in the intervention group than in the control group (141 (87) v 106 (101); p < 0.05) and number of days in hospital tended to be fewer (4.2 (7.8) v 8.2 (14.3); p = 0.07). There was a trend towards a mean annual reduction in health care costs per patient of US$1300 (US $1 = SEK 7.76) in the intervention group compared with costs in the controls (US$3594 v 2294; p = 0.07). CONCLUSIONS: A management programme for patients with heart failure discharged after hospitalisation reduces health care costs and the need for readmission.

Socioeconomic inequalities and disability pension in middle-aged men.

BACKGROUND: The issue of inequalities in health has generated much discussion and socioeconomic status is considered an important variable in studies of health. It is frequently used in epidemiological studies, either as a possible risk factor or a confounder and the aim of this study was to analyse the relation between socioeconomic status and risk of disability pension. METHODS: Five complete birth year cohorts of middle-aged male residents in Malmo were invited to a health survey and 5782 with complete data constituted the cohort in this prospective study. Each subject was followed for approximately 11 years and nationwide Swedish data registers were used for surveillance. RESULTS: Among the 715 men (12%), granted disability pension during follow-up, three groups were distinguished. The cumulative incidence of disability pension among blue collar workers was 17% and among lower and higher level white collar workers, 11% and 6% respectively. With simultaneous adjustment for biological risk factors and job conditions, the relative risk for being granted a disability pension (using higher level white collar workers as reference) was 2.5 among blue collar workers and 1.6 among lower level white collar workers. CONCLUSIONS: Socioeconomic status, as defined by occupation, is a risk factor for being granted disability pension even after adjusting for work conditions and other risk factors for disease.

Left ventricular atrioventricular plane displacement: an echocardiographic technique for rapid assessment of prognosis in heart failure.

OBJECTIVE: To assess the prognostic value of atrioventricular plane displacement in heart failure patients. DESIGN: Patients were followed prospectively for one year after atrioventricular plane displacement determination. SETTING: Malmö University Hospital, with a primary catchment area of 250,000 inhabitants. PATIENTS: 181 patients with a clinical diagnosis of heart failure; age 75.7 (SD 5.2) years, duration of heart failure 2.7 (5.7) years; 100 men, 81 women. MAIN OUTCOME MEASURES: Mortality in relation to atrioventricular plane displacement. RESULTS: Total mortality was 22.7% (41/181), and was highly significantly (P = 0.001) related to atrioventricular plane displacement. Mortality within prospectively defined categories of displacement was: > or = 10.0 mm, 0% (0/19); 8.2 to 9.9 mm, 10.3% (3/29); 6.4 to 8.1 mm, 19.4% (12/62); and < 6.4 mm, 36.6% (26/71). The groups were similar in age, sex, angiotensin converting enzyme inhibitor and beta blocker treatment, and cause and duration of heart failure. CONCLUSIONS: Mortality in heart failure is strongly related to atrioventricular plane displacement.

Quality of life in patients with ischaemic heart disease: a prospective controlled study.

OBJECTIVES: To assess quality of life in patients after acute myocardial infarction (AMI), coronary artery by-pass grafting surgery (CABG) and percutaneous transluminal coronary angioplasty (PTCA) as compared with healthy controls. DESIGN: Self-administered questionnaires were completed 1 month and 1 year after the event. SETTING: Department of Cardiology, University Hospital, Malmö, Sweden; 1989-1992. SUBJECTS: 296 AMI, 99 CABG, 18 PTCA patients and 88 randomly selected healthy controls were included; 349 patients completed the entire programme. MAIN OUTCOME MEASURES: Quality of life in the dimensions of perceived general health, thoracic pain, breathlessness, feeling of arrhythmia, anxiety, depression, self-esteem, experience of social life and sex life. RESULTS: Patients differed from controls in both psychological and somatic aspects of QL after 1 month. Furthermore, 1 month after the event AMI patients experienced more anxiety (P = 0.001) than CABG patients, whilst CABG patients experienced a poorer sex life (P < 0.001) than AMI patients. One year after the event patients differed from controls primarily in somatic symptoms: no significant differences were found across patient groups. Patients who sought emergency out-patient care during the follow-up year for clinically diagnosed angina pectoris or cardiac incompensation had reported higher levels of thoracic pain (P < 0.001) and breathlessness (P < 0.001) at 1 month follow-up than patients who did not seek such care. CONCLUSIONS: Quality of life is considerably affected in patients following a cardiac event, especially during the initial recovery phase. Although substantial improvement in quality of life occurs over time, the persistence of residual distress at 1-year follow-up is a challenge for clinicians concerned with the full rehabilitation of the cardiac patient.

Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project.

CONTEXT: Elevated plasma homocysteine is a known risk factor for atherosclerotic vascular disease, but the strength of the relationship and the interaction of plasma homocysteine with other risk factors are unclear. OBJECTIVE: To establish the magnitude of the vascular disease risk associated with an increased plasma homocysteine level and to examine interaction effects between elevated plasma homocysteine level and conventional risk factors. DESIGN: Case-control study. SETTING: Nineteen centers in 9 European countries. PATIENTS: A total of 750 cases of atherosclerotic vascular disease (cardiac, cerebral, and peripheral) and 800 controls of both sexes younger than 60 years. MEASUREMENTS: Plasma total homocysteine was measured while subjects were fasting and after a standardized methionine-loading test, which involves the administration of 100 mg of methionine per kilogram and stresses the metabolic pathway responsible for the irreversible degradation of homocysteine. Plasma cobalamin, pyridoxal 5'-phosphate, red blood cell folate, serum cholesterol, smoking, and blood pressure were also measured. RESULTS: The relative risk for vascular disease in the top fifth compared with the bottom four fifths of the control fasting total homocysteine distribution was 2.2 (95% confidence interval, 1.6-2.9). Methionine loading identified an additional 27% of at-risk cases. A dose-response effect was noted between total homocysteine level and risk. The risk was similar to and independent of that of other risk factors, but interaction effects were noted between homocysteine and these risk factors; for both sexes combined, an increased fasting homocysteine level showed a more than multiplicative effect on risk in smokers and in hypertensive subjects. Red blood cell folate, cobalamin, and pyridoxal phosphate, all of which modulate homocysteine metabolism, were inversely related to total homocysteine levels. Compared with nonusers of vitamin supplements, the small number of subjects taking such vitamins appeared to have a substantially lower risk of vascular disease, a proportion of which was attributable to lower plasma homocysteine levels. CONCLUSIONS: An increased plasma total homocysteine level confers an independent risk of vascular disease similar to that of smoking or hyperlipidemia. It powerfully increases the risk associated with smoking and hypertension. It is time to undertake randomized controlled trials of the effect of vitamins that reduce plasma homocysteine levels on vascular disease risk.

Influence of coronary nursing management follow up on lifestyle after acute myocardial infarction.

OBJECTIVE: To examine the ability of a secondary prevention programme to improve the lifestyle in myocardial infarction patients aged 50-70 years. DESIGN: Habitual physical activity, food habits, and smoking habits were assessed from questionnaires at admission to hospital and at the one year follow up. Initially, all patients were invited to join an exercise programme and were informed about cardiovascular risk factors. Four weeks after discharge from the hospital, 87 patients were randomised to follow up at the coronary prevention unit by a special trained nurse (the intervention group), and 81 to follow up by their general practitioners (the usual care group). After randomisation, the intervention group was educated about the effects of smoking cessation, dietary management, and regular physical activity. The intervention group also participated in a physical training programme two to three times weekly for 10-12 weeks. MAIN RESULTS: 89% of the patients referred to the intervention group improved their food habits compared with 62% of the patients referred to the usual care group (P = 0.008). Furthermore, 50% of the smokers referred to the intervention group stopped smoking compared to 29% in the usual care group (P = 0.09). Changes in physical activity did not differ between the groups. CONCLUSIONS: This secondary prevention programme based on a nurse rehabilitator was successful in improving food habits in patients with acute myocardial infarction. Initiating the smoking cessation programme during the hospital stay followed by repeated counselling during follow up might have improved the results. The exercise programme had no advantage in supporting physical activity compared to usual care.

Simplified echocardiography in the diagnosis of heart failure.

Echocardiography is essential in the diagnosis of heart failure, but insufficient resources limit its use. We compared swift (five minutes) simplified echocardiography, using elementary equipment, with standard echocardiography (45 minutes), using advanced equipment. Visual semi-quantification of cardiac dimensions, valvular stenosis, and left ventricular ejection fraction (LVEF) was performed in 100 consecutive patients with suspected or known heart failure. Agreement between simplified and standard echocardiography was 78-89% regarding semi-quantification of cardiac dimensions, and 95-98% for valvular stenosis (present/not present). Sensitivity and specificity for simplified echocardiography to identify patients with LVEF < 0.40 was 86 and 89%, respectively. Simplified echocardiography using elementary equipment could be an alternative to standard echocardiography in the diagnosis of heart failure. The cost and time saved by using simplified echocardiography allows for more patients to be examined, which should be weighed against its accuracy.