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Objectives Patients with severe heart failure (HF) suffer from a high symptom burden and high mortality. European and Swedish guidelines for HF care recommend palliative care for these patients. Different models for integrated palliative care and HF care have been described in the literature. No studies were found that qualitatively evaluated these models. The purpose of this study is to describe patients' experiences of a new model of person-centred integrated HF and palliative care at home. Method Interviews were conducted with 12 patients with severe HF (New York Heart Association class III–IV) and included in the research project of Palliative advanced home caRE and heart FailurE caRe (PREFER). Qualitative content analysis was used for data analysis. Results Two themes and a total of five categories were identified. The first theme was feeling secure and safe through receiving care at home with the categories: having access to readily available care at home, being followed up continuously and having trust in the team members' ability to help. The second theme was being acknowledged as both a person and a patient, with the following two categories: being met as a person, participating in decisions about one's care and receiving help for symptoms of both HF and comorbidities. Conclusions Person-centred integrated HF and palliative care provides a secure environment and holistic care for patients with severe HF. This approach is a way to improve the care management in this population.

Introduction: Fibrinolytic factors, plasminogen activator inhibitor-1, tissue plasminogen activator, tissue plasminogen activator/plasminogen activator-complex and the haemostatic factor von Willebrand factor are known markers of cardiovascular disease. Their plasma levels are adversely affected in patients with dysglycaemia, and glucose normalization with insulin glargine might improve the levels of these factors. Methods: Prespecified Swedish substudy of the Outcome Reduction with an Initial Glargine Intervention trial (ClinicalTrials.gov number, NCT00069784). Tissue plasminogen activator activity, tissue plasminogen activator antigen, plasminogen activator inhibitor-1 antigen, tissue plasminogen activator/plasminogen activator inhibitor-1 complex and von Willebrand factor were analysed at study start, after 2 years and at the end of the study (median follow-up of 6.2 years). Results: Of 129 patients (mean age of 64 ± 7 years, females: 19%), 68 (53%) and 61 (47%) were randomized to the insulin glargine and standard care group, respectively. Allocation to insulin glargine did not significantly affect the studied fibrinolytic markers or von Willebrand factor compared to standard care. Likewise, there were no significant differences in plasminogen activator inhibitor-1, tissue plasminogen activator antigen and von Willebrand factor. During the whole study period, the within-group analysis revealed a curvilinear pattern and significant changes for tissue plasminogen activator/plasminogen activator inhibitor-1 complex, tissue plasminogen activator antigen and von Willebrand factor in the insulin glargine but not in the standard care group. Conclusion: In people with dysglycaemia and other cardiovascular risk factors, basal insulin does not improve the levels of markers of fibrinolysis or von Willebrand factor compared to standard glucose-lowering treatments., Originally included in thesis in manuscript form with title: "The effect of basal insulin glargine on the fibrinolytic system and von Willebrand factor in people with dysglycaemia and high risk for cardiovascular events : Swedish substudy of the ORIGIN trial" and authors: Aslak Rautio, Hertzel C Gerstein, Jenny Hernestål-Boman, Shun Fu Lee, Linda Garcia Mellbin, Mona Olofsson, Lars Rydén and Kurt Boman

Background We evaluated whether early measurement of soluble urokinase plasminogen activator receptor (suPAR) could predict future risk of postoperative complications in initially asymptomatic patients with mild-moderate aortic stenosis (AS) undergoing aortic valve replacement (AVR) surgery. Methods Baseline plasma suPAR levels were available in 411 patients who underwent AVR surgery during in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Cox analyses were used to evaluate suPAR in relation to all-cause mortality and the composite endpoint of postoperative complications (all-cause mortality, congestive heart failure, stroke and renal impairment) occurring in the 30-day postoperative period. Results Patients with initially higher levels of suPAR were at increased risk of postoperative mortality with a HR of 3.5 (95% CI 1.4 to 9.0, P=0.008) and postoperative complications with a HR of 2.7 (95% CI 1.5 to 5.1, P=0.002), per doubling in suPAR. After adjusting for the European System for Cardiac Operative Risk Evaluation or Society of Thoracic Surgeons risk score, suPAR remained associated with postoperative mortality with a HR 3.2 (95% CI 1.2 to 8.6, P=0.025) and 2.7 (95% CI 1.0 to 7.8, P=0.061); and postoperative complications with a HR of 2.5 (95% CI 1.3 to 5.0, P=0.007) and 2.4 (95% CI 1.2 to 4.8, P=0.011), respectively. Conclusion Higher baseline suPAR levels are associated with an increased risk for postoperative complications and mortality in patients with mild-moderate, asymptomatic AS undergoing later AVR surgery. Further validation in other subsets of AS individuals are warranted.

Objective: Chronic heart failure is a disease with high morbidity and symptom burden for patients, and it also places great demands on family members. Patients with heart failure should have access to palliative care for the purpose of improving quality of life for both patients and their families. In the PREFER randomized controlled intervention, patients with New York Heart Association classes III–IV heart failure received person-centered care with a multidisciplinary approach involving collaboration between specialists in palliative and heart failure care. The aim of the present study was to describe family members' experiences of the intervention, which integrated palliative advanced home and heart failure care. Method: This study had a qualitative descriptive design based on family member interviews. Altogether, 14 family members participated in semistructured interviews for evaluation after intervention completion. The data were analyzed by means of content analysis. Results: Family members expressed gratitude and happiness after witnessing the patient feeling better due to symptom relief and empowerment. They also felt relieved and less worried, as they were reassured that the patient was being cared for properly and that their own responsibility for care was shared with healthcare professionals. However, some family members also felt as though they were living in the shadow of severe illness, without receiving any support for themselves. Significance of results: Several benefits were found for family members from the PREFER intervention, and our results indicate the significance of integrated palliative advanced home and heart failure care. However, in order to improve this intervention, psychosocial professionals should be included on the intervention team and should contribute by paying closer attention and providing targeted support for family members.

Background and aims: Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory marker associated with cardiovascular disease. Statins lower both low-density lipoprotein (LDL)-cholesterol and C-reactive protein (CRP), resulting in improved outcomes. However, whether lipid-lowering therapy also lowers suPAR levels is unknown.& para;& para;Methods: We investigated whether treatment with Simvastatin 40 mg and Ezetimibe 10 mg lowered plasma suPAR levels in 1838 patients with mild-moderate, asymptomatic aortic stenosis, included in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study, using a pattern mixture model. A 1-year Cox analysis, adjusted for established cardiovascular risk factors, allocation to study treatment, peak aortic valve velocity and baseline suPAR, was performed to evaluate relationships between change in suPAR with all-cause mortality and the composite endpoint of major cardiovascular events (MCE) composed of ischemic cardiovascular events (ICE) and aortic valve related events (AVE).& para;& para;Results: After 4.3 years of follow-up, suPAR levels had increased by 9.2% (95% confidence interval [CI]: 7.0%-11.5%) in the placebo group, but only by 4.1% (1.9%-6.2%) in the group with lipid-lowering treatment (p<0.001). In a multivariate 1-year analysis, 1-year suPAR was strongly associated with all-cause mortality, hazard ratio (HR) = 2.05 (1.17-3.61); MCE 1.40 (1.01-1.92); and AVE 1.42 (1.02-1.99) (all p<0.042) for each doubling of suPAR; but was not associated with ICE.& para;& para;Conclusions: Simvastatin and Ezetimibe treatment impeded the progression of the time-related increase in plasma suPAR levels. Year-1 suPAR was associated with all-cause mortality, MCE, and AVE irrespective of baseline levels (SEAS study: NCT00092677). (C) 2018 Elsevier B.V. All rights reserved.

Observational studies indicate that low-density lipoprotein (LDL) cholesterol acts as a primary contributor to an active process leading to aortic stenosis (AS) development. However, randomized clinical trials have failed to demonstrate an effect of lipid lowering on impeding AS progression. This study explored if pretreatment LDL levels and AS severity altered the efficacy of lipid-lowering therapy. The study goal was evaluated in the analysis of surviving patients with baseline data in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial of 1,873 asymptomatic patients with mild-to-moderate AS. Serially measured peak aortic jet velocity was the primary effect estimate. Linear mixed model analysis adjusted by baseline peak jet velocity and pretreatment LDL levels was used to assess effect modifications of treatment. Data were available in 1,579 (84%) patients. In adjusted analyses, lower baseline peak aortic jet velocity and higher pretreatment LDL levels increased the effect of randomized treatment (p >= 0.04 for interaction). As such, treatment impeded progression of AS in the highest quartile of LDL among patients with mild AS at baseline (0.06 m/s per year slower progression vs placebo in peak aortic jet velocity, 95% confidence interval 0.01 to 0.11, p = 0.03), but not in the 3 other quartiles of LDL. Conversely, among patients with moderate AS, there was no detectable effect of treatment in any of the pretreatment LDL quartiles (all p In conclusion, in a non prespecified post hoc analysis, the efficacy of lipid-lowering therapy on impeding AS progression increased with higher pretreatment LDL and lower peak aortic jet velocity (SEAS study: NCT00092677).

BACKGROUND: The complex needs of people with chronic heart failure (HF) place great demands on their family members, and it is important to ask family members about their perspectives on the quality of HF care. OBJECTIVE: To describe family members' perceptions of quality of HF care in an outpatient setting. METHODS: A cross-sectional study using a short form of the Quality from Patients' Perspective (QPP) questionnaire for data collection. The items in the questionnaire measure four dimensions of quality, and each item consists of both the perceived reality of the care and its subjective importance. The study included 57 family members of patients with severe HF in NYHA class III-IV. RESULTS: Family members reported areas for quality improvements in three out of four dimensions and in dimensionless items. The lowest level of perceived reality was reported for treatment for confusion and loss of appetite. Treatment for shortness of breath, access to the apparatus and access to equipment necessary for medical care were the items with the highest subjective importance for the family members. CONCLUSION: Family members identified important areas for quality improvement in the care for patients with HF in an outpatient setting. In particular, symptom alleviation, information to patients, patient participation and access to care were identified as areas for improvements. Thus, measuring quality from the family members' perspective with the QPP might be a useful additional perspective when it comes to the planning and implementation of changes in the organisation of HF care.

OBJECTIVES: To compare the effects of the beta-blocker atenolol with the angiotensin receptor blocker (ARB) losartan on plasma tissue-type plasminogen activator (tPA) activity and mass concentration, plasminogen activator inhibitor-1 (PAI-1) activity, tPA/PAI-1 complex, and von Willebrand factor (VWF). DESIGN: A prespecified, explorative substudy in 22 patients with hypertension and left ventricular hypertrophy (LVH) performed within randomized multicenter, double-blind prospective study. RESULTS: After a median of 36 weeks of treatment, there were significant differences between the treatment groups, atenolol versus losartan, in plasma median levels of tPA mass (11.9 vs 7.3 ng/mL, P = .019), PAI-1 activity (20.7 vs 4.8 IU/mL, P = .030), and tPA/PAI-1 complex (7.1 vs 2.5 ng/mL, P = .015). In patients treated with atenolol, median levels of tPA mass (8.9-11.9 ng/mL, P = .021) and VWF (113.5%-134.3%, P = .021) increased significantly, indicating a change toward a more prothrombotic state. No significant changes occurred in the losartan group. CONCLUSION: Losartan treatment was associated with preserved fibrinolytic balance compared to a more prothrombotic fibrinolytic and hemostatic state in the atenolol group. These findings suggest different fibrinolytic and hemostatic responses to treatment in hypertensive patients with LVH.

Background: Patients with aortic stenosis (AS) often have concomitant hypertension. Antihypertensive treatment with a beta-blocker (Bbl) is frequently avoided because of fear of depression of left ventricular function. However, it remains unclear whether antihypertensive treatment with a Bbl is associated with increased risk of cardiovascular events in patients with asymptomatic mild to moderate AS. Methods and results: We did a post hoc analysis of 1873 asymptomatic patients with mild to moderate AS and preserved left ventricular ejection fraction in the SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) study. Propensity-matched Cox regression and competing risk analyses were used to assess risk ratios for all-cause mortality, sudden cardiac death, and cardiovascular death. A total of 932 (50%) patients received Bbl at baseline. During a median follow-up of 4.3 +/- 0.9 years, 545 underwent aortic valve replacement, and 205 died; of those, 101 were cardiovascular deaths, including 40 sudden cardiovascular deaths. In adjusted analyses, Bbl use was associated with lower risk of all-cause mortality (hazard ratio 0.5, 95% confidence interval 0.3-0.7, P<0.001), cardiovascular death (hazard ratio 0.4, 95% confidence interval 0.2-0.7, P<0.001), and sudden cardiac death (hazard ratio 0.2, 95% confidence interval 0.1-0.6, P=0.004). This was confirmed in competing risk analyses (all P<0.004). No interaction was detected with AS severity (all P>0.1). Conclusions: In post hoc analyses Bbl therapy did not increase the risk of all-cause mortality, sudden cardiac death, or cardiovascular death in patients with asymptomatic mild to moderate AS. A prospective study may be warranted to determine if Bbl therapy is in fact beneficial.

Background and purpose: To estimate healthcare resource utilization among patients with heart failure (HF) with preserved (HFpEF) versus reduced (HFrEF) ejection fraction using population data from two Swedish counties. Methods: Patients with HF were identified via electronic medical records (EMRs) from primary and/or secondary care in Uppsala and Västerbotten, linked via unique identifiers to data from the National Patient Register and Swedish Prescribed Drug Register. Local echocardiography data were used to identify HFpEF (defined as ejection fraction ≥50%) and HFrEF (defined as <50%). Patients aged ≥18 years with ≥2 diagnoses of HF between 01/01/2010 and 31/03/2015 and an ICD-10 diagnostic code of I50 (inclusive of all granular codes), I42.0, I42.6, I42.7, I42.9, I110, I130 or I132 in any position were included. Patients were followed from date of first diagnosis (index date) to end of study period or EMR collection, date of death or loss to follow-up for other reasons, whichever came first. Unadjusted all-cause and cardiovascular disease (CVD)-related hospitalization rates were assessed using a Cox proportional hazards model, accounting for age, sex, setting of first diagnosis (primary vs secondary care), HF phenotype and NT-proBNP level. Results: In total, 8702 patients with HF were identified. HF phenotype was known in 3167 patients; 64.6% had HFrEF, 35.4% had HFpEF. Patients with HFrEF were younger (mean±SD: 69.9±13.7 vs 74.2±12.6 years) with a lower Charlson comorbidity index (1.65 vs 1.83) than those with HFpEF. All-cause hospitalization rates were marginally lower for HFrEF than for HFpEF (mean [95% CI] proportion of patients hospitalized within 1 year of diagnosis, 72.5 [70.1–74.8]% vs 73.8 [70.7–77.0]%; hazard ratio [HR] over whole follow-up period, 0.87 [0.79–0.97], p=0.0093). The proportion of patients hospitalized was higher for those diagnosed in secondary care than in primary care, particularly within 1 year of diagnosis (1-year rate, 69.6 [68.3, Special Issue: Abstracts of the Heart Failure 2017 and the 4th World Congress on Acute Heart Failure, Paris, France, 29 April – 2 May 2017Rapid Fire 4 - Therapy and management

Background: Dietary risks today constitute the largest proportion of disability-adjusted life years (DALYs) globally and in Sweden. An increasing number of people today consume highly processed foods high in saturated fat, refined sugar and salt and low in dietary fiber, vitamins and minerals. It is important that dietary trends over time are monitored to predict changes in disease risk. Methods: In total, 15,995 individuals with two visits 10 (±1) years apart in the population-based Västerbotten Intervention Programme 1996–2014 were included. Dietary intake was captured with a 64-item food frequency questionnaire. Percent changes in intake of dietary components, Healthy Diet Score and Dietary Inflammatory Index were calculated and related to body mass index (BMI), serum cholesterol and triglyceride levels and blood pressure at the second visit in multivariable regression analyses. Results: For both sexes, on group level, proportion of energy intake (E%) from carbohydrates and sucrose decreased (largest carbohydrate decrease among 40 year-olds) and E% protein and total fat as well as saturated and poly-unsaturated fatty acids (PUFA) increased (highest protein increase among 30 year-olds and highest fat increase among 60 year-olds) over the 10-year period. Also, E% trans-fatty acids decreased. On individual basis, for both sexes decreases in intake of cholesterol and trans-fatty acids were associated with lower BMI and serum cholesterol at second visit (all P < 0.05). For men, increases in intake of whole grain and Healthy Diet Score were associated with lower BMI and serum cholesterol at second visit (all P < 0.05). Also for men, decreases in intake of trans-fatty acids and increases in Healthy Diet Score were associated with lower systolic blood pressure at second visit (P = 0.002 and P < 0.000). For women, increases in intake of PUFA and Healthy Diet Score were associated with lower BMI at second visit (P = 0.01 and P < 0.05). Surprisingly, increases i

OBJECTIVE: A significant reduction in the incidence of cardiovascular disease, including abdominal aortic aneurysm (AAA), has been observed in the past decades. In this study, a small but geographically well defined and carefully characterized population, previously screened for AAA and risk factors, was re-examined 11 years later. The aim was to study the reduction of AAA prevalence and associated factors. METHODS: All men and women aged 65 to 75 years living in the Norsjö municipality in northern Sweden in January 2010 were invited to an ultrasound examination of the abdominal aorta, registration of body parameters and cardiovascular risk factors, and blood sampling. An AAA was defined as an infrarenal aortic diameter ≥30 mm. Results were compared with a corresponding investigation conducted in 1999 in the same region. RESULTS: A total of 602 subjects were invited, of whom 540 (90%) accepted. In 2010, the AAA prevalence was 5.7% (95% confidence interval [CI], 2.8%-8.5%) among men compared with 16.9% (95% CI, 12.3%-21.6%) in 1999 (P < .001). The corresponding figure for women was 1.1% (95% CI, 0.0%-2.4%) vs 3.5% (95% CI, 1.2%-5.8%; P = .080). A low prevalence of smoking was observed in 2010 as well as in 1999, with only 13% and 10% current smokers, respectively (P = .16). Treatment for hypertension was significantly more common in 2010 (58% vs 44%; P < .001). Statins increased in the population (34% in 2010 vs 3% in 1999; P < .001), and the lipid profile in women had improved significantly between 1999 and 2010. CONCLUSIONS: A highly significant reduction in AAA prevalence was observed during 11 years in Norsjö. Treatment for hypertension and with statins was more frequent, whereas smoking habits remained low. This indicates that smoking is not the only driver behind AAA occurrence and that lifestyle changes and treatment of cardiovascular risk factors may play an equally important role in the observed recent decline in AAA prevalence.

We tested the prognostic impact of a marker of arterial stiffness, pulse pressure/stroke volume index (PP/SVi), in patients with hypertension and left ventricular (LV) hypertrophy. We used data from 866 patients randomized to losartan or atenolol-based antihypertensive treatment, over a median of 4.8 years, in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. The association of PP/SVi with outcomes was tested in Cox regression analyses and reported as hazard ratio (HR) and 95% confidence intervals (CI). In multivariate regression, reduction of PP/SVi was independently associated with male gender, reduction in systolic blood pressure (BP) and relative wall thickness and with an increase in left ventricular ejection fraction (all p < .05). After adjusting for confounders, higher baseline PP/SVi predicted a 38% higher hazard of combined major fatal and non-fatal cardiovascular events (95% CI 1.04-1.84), and higher hazard of cardiovascular mortality (HR 2.35 (95% CI 1.59-3.48) and stroke (HR 1.45 (95% CI 1.06-1.99) (all p < .05). Higher PP/SVi also predicts higher rate of hospitalization for HF (HR 2.15 (95% CI 1.48-3.12) and a 52% higher hazard of all-cause mortality (95% CI 1.10-2.09) (both p < .05). In hypertensive patients with electrocardiographic LV hypertrophy, higher PP/SVi was associated with increased cardiovascular morbidity and mortality.

Asymmetric interventricular septum hypertrophy (ASH) has been associated with increased perioperative morbidity and mortality in patients with severe, symptomatic aortic valve stenosis (AS). Less is known about the prognostic impact of ASH during progression of AS. Clinical, echocardiographic, and outcome data from 1,691 patients with initially asymptomatic, mostly moderate AS, participating in the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) study was used. ASH was considered present if interventricular septum/posterior wall thickness ratio in end-diastole ≥1.5. The associations of ASH with hazard rate of ischemic cardiovascular events were tested in time-dependent Cox regression analyses. Based on the presence of ASH at study echocardiograms, the study population was grouped in to a no-ASH, nonpersistent ASH, persistent ASH, and new-onset ASH groups. During a median of 4.3 years of follow-up, ASH persisted or developed in 17% of patients. Persistent or new-onset ASH was characterized by higher left ventricular mass index and ejection fraction at baseline (both p <0.05) but not with female gender or hypertension. In time-varying Cox regression analyses adjusting for these confounders, persistent or new-onset ASH was associated with higher hazard rate of ischemic cardiovascular events (hazard rate 1.45; 95% confidence interval 1.09 to 1.91, p = 0.01), in particular coronary artery bypass grafting (hazard rate 1.69; 95% confidence interval 1.17 to 2.47; p = 0.006), whereas no association with increased mortality was found. In conclusion, in patients with AS without diabetes or known renal or cardiovascular disease participating in the SEAS study, persistent or new-onset ASH during progression of AS was associated with higher rate of ischemic cardiovascular events.

AIM: The purpose of this study was to describe clients and occupational therapists (OTs) experiences of a home-based programme focusing energy conservation strategies (ECS) for clients with chronic heart failure (CHF). METHODS: The programme, based on occupational therapy intervention process model (OTIPM), was led by two OTs in primary health care. Five clients' self-reported activities of daily living (ADL), fatigue, depression, goal achievements and use of ECS. Furthermore, both clients and OTs were individually interviewed. RESULTS: The clients reported mild depression, severe fatigue and both increased and decreased independence in ADL. Most goals were achieved, and multiple ECS were used. Clients perceived that they worked collaboratively with the OTs and gained professional support to enhance daily activities. The OTs experienced knowledge and structure and found benefits from the programme, but doubted the possibility of using it in clinical practice. CONCLUSIONS: This study, despite having few participants, indicates that both the OTs and the clients experienced that the specialized programme gave structure to the OTs work, provided knowledge about CHF and valuable energy conservation strategies. The programme supported the OTs in working in a more comprehensive client-centred way. However, its feasibility needs to be further evaluated.

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Background: Heart failure (HF) is a life-threatening condition and optimal handling is necessary to reduce risk of therapy failure. The impact of the duration of HF diagnosis on HF outcome has not previously been examined. The objectives of this study were (I) to evaluate the impact of patient age on clinical outcomes, (II) to evaluate the impact of duration of the HF disease on outcomes, and (III) to evaluate the impact of age and HF duration on B-type Natriuretic Peptide (BNP) concentration in a population of HF patients. Methods and results: In the UPSTEP (Use of PeptideS in Tailoring hEart failure Project) study we retrospectively evaluated how age and HF duration affected HF outcome. HF duration was divided into < 1 year, 1-5 years and > 5 years. A multivariate Cox proportional hazard regression analysis showed that HF duration influenced outcome more than age, even when adjusted for comorbidities(< 1 year versus > 5 years: HR 1.65; 95% CI 1.28-2.14; P < 0.0002) on HF mortality and hospitalisations. The influence of age on BNP showed increased BNP as age increased. However, there was a significant effect on BNP concentration when comparing HF duration of less than one year to HF duration to more than five years, even when adjusted for age. Conclusions: Patients with longer HF duration had significantly worse outcome compared to those with short HF duration, even when adjusted for patient age and comorbidities. Age did not influence outcome but had an impact on BNP concentration; however, BNP concentration increased as HF duration increased.

Background: To explore the relationships between anaemia or iron deficiency (ID) and symptoms, quality of life (QoL), morbidity, and mortality. Methods: A post-hoc, non-prespecified, explorative substudy of the prospective randomized PREFER trial. One centre study of outpatients with severe HF and palliative need managed with advanced home care. Associations between anaemia, ID, and the Edmonton Symptom Assessment Scale (ESAS), Euro QoL (EQ-5D), Kansas City Cardiomyopathy Questions (KCCQ) were examined only at baseline but at 6months for morbidity and mortality. Results: Seventy-two patients (51 males, 21 females), aged 79.2±9.1years. Thirty-nine patients (54%) had anaemia and 34 had ID (47%). Anaemia was correlated to depression (r=0.37; p=0.001), anxiety (r=0.25; p=0.04), and reduced well-being (r=0.26; p=0.03) in the ESAS; mobility (r=0.33; p=0.005), pain/discomfort (r=0.27; p=0.02), and visual analogue scale of health state (r=-0.28; p=0.02) in the EQ-5D; and physical limitation (r=-0.27; p=0.02), symptom stability; (r=-0.43; p<0.001); (r=-0.25; p=0.033), social limitation;(r=-0.26; p=0.03), overall summary score; (r=-0.24, p=0.046) and clinical summary score; (r=-0.27; p=0.02) in the KCCQ. ID did not correlate to any assessment item. Anaemia was univariably associated with any hospitalization (OR: 3.0; CI: 1.05-8.50, p=0.04), but not to mortality. ID was not significantly associated with any hospitalization or mortality. Conclusion: Anaemia, but not ID, was associated although weakly with symptoms and QoL in patients with advanced HF and palliative home care.

BACKGROUND: Heart failure is a serious condition with high mortality and a high symptom burden. Most patients with heart failure will be taken care of in primary care but the knowledge of how the quality of care is perceived by patients with heart failure is limited. OBJECTIVE: The aim was to explore how patients with heart failure report quality of care, in an outpatient setting. METHODS: Seventy-one patients with a confirmed diagnosis of heart failure and who were cared for in an outpatient setting were included in this cross-sectional study. Quality of care was assessed with a short form of the Quality from the Patient's Perspective questionnaire. The items measured four dimensions, and each item consists of both perceived reality of the received care and its subjective importance. RESULTS: Inadequate quality was identified in three out of four dimensions and in items without dimension affiliation. In total, inadequate quality was identified in 19 out of 25 items. Patients reported the highest level of perceived reality in 'my family member was treated well' and the lowest perceived reality in 'effective treatment for loss of appetite'. Effective treatment for shortness of breath was of the highest subjective importance for the patients. CONCLUSION: Important areas for improvement in the quality of care for patients with heart failure in an outpatient setting were identified, such as symptom alleviation, information, participation and access to care.

Objective In Sweden, previous favourable trends in blood cholesterol levels have recently levelled off or even increased in some age groups since 2003, potentially reflecting changing fashions and attitudes towards dietary saturated fatty acids (SFA). We aimed to examine the potential effect of different SFA intake on future coronary heart disease (CHD) mortality in 2025. Methods We compared the effect on future CHD mortality of two different scenarios for fat intake a) daily SFA intake decreasing to 10 energy percent (E%), and b) daily SFA intake rising to 20 E %. We assumed that there would be moderate improvements in smoking (5%), salt intake (1g/day) and physical inactivity (5% decrease) to continue recent, positive trends. Results In the baseline scenario which assumed that recent mortality declines continue, approximately 5,975 CHD deaths might occur in year 2025. Anticipated improvements in smoking, dietary salt intake and physical activity, would result in some 380 (-6.4%) fewer deaths (235 in men and 145 in women). In combination with a mean SFA daily intake of 10 E%, a total of 810 (-14%) fewer deaths would occur in 2025 (535 in men and 275 in women). If the overall consumption of SFA rose to 20 E%, the expected mortality decline would be wiped out and approximately 20 (0.3%) additional deaths might occur. Conclusion CHD mortality may increase as a result of unfavourable trends in diets rich in saturated fats resulting in increases in blood cholesterol levels. These could cancel out the favourable trends in salt intake, smoking and physical activity.

Objectives: To compare the acute effects of uninterrupted sitting with sitting interrupted by brief bouts of light-intensity walking on self-reported fatigue, cognition, neuroendocrine biomarkers and cardiometabolic risk markers in overweight/obese adults. Design: Randomised two-condition crossover trial. Setting: Laboratory study conducted in Melbourne, Australia. Participants: 19 overweight/obese adults (45–75 years). Interventions: After an initial 2 h period seated, participants consumed a meal-replacement beverage and completed (on 2 days separated by a 6-day washout period) each condition over the next 5 h: uninterrupted sitting (sedentary condition) or sitting with 3 min bouts of light-intensity walking every 30 min (active condition). Primary outcome measures: Self-reported fatigue, executive function and episodic memory at 0 h, 4 h and 7 h. Secondary outcome measures: Neuroendocrine biomarkers and cardiometabolic risk markers (blood collections at 0 h, 4 h and 7 h, blood pressure and heart rate measured hourly and interstitial glucose measured using a continuous glucose monitoring system). Results: During the active condition, fatigue levels were lower at 4 h (−13.32 (95% CI −23.48 to −3.16)) and at 7 h (−10.73 (95% CI −20.89 to −0.58)) compared to the sedentary condition. Heart rate was higher at 4 h (4.47 (95% CI 8.37 to 0.58)) and at 7 h (4.32 (95% CI 8.21 to 0.42)) during the active condition compared to the sedentary condition. There were no significant differences between conditions by time for other variables. In the sedentary condition, changes in fatigue scores over time correlated with a decrease in heart rate and plasma dihydroxyphenylalanine (DOPA) and an increase in plasma dihydroxyphenylglycol (DHPG). Conclusions: Interrupting prolonged sitting with light-intensity walking breaks may be an effective fatigue countermeasure acutely. Fatigue levels corresponded with the heart rate and neuroendocrine biomarker changes in uninterrupted sitting in t

Background: Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory marker associated with subclinical cardiovascular damage and cardiovascular events. Whether suPAR is of prognostic value in asymptomatic patients with aortic stenosis (AS) remains unknown. Methods: Plasma suPAR levels were measured in 1503 patients with a mean age of 68 years who were recruited in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Cox regression analysis was performed to evaluate associations between suPAR and the composite end points of ischemic cardiovascular events (ICEs), aortic valve events (AVEs), cardiovascular and all-cause mortality after adjusting for traditional cardiovascular risk factors, and allocation to treatment. Results: The multivariate adjusted hazard ratio (HR) (95% confidence interval [CI]) per unit log2 ng/mL increase in suPAR was HR, 1.5; 95% CI, 1.2-1.9; P = 0.002 for ICEs; HR, 1.2; 95% CI, 0.9-1.5; P = 0.071) for AVEs; HR, 2.0; 95% CI, 1.2-3.3; P = 0.007) for cardiovascular mortality, and HR, 2.0; 95% CI, 1.4-2.9; P < 0.001 for all-cause mortality. Conclusions: In patients with mild-moderate AS, suPAR is independently associated with the incidence of ICEs, cardiovascular mortality, and all-cause mortality., Introduction: Le récepteur soluble de l’activateur du plasminogène de l’urokinase (suPAR, soluble urokinase plasminogen activator receptor) est un marqueur de l’inflammation associé aux lésions cardiovasculaires subcliniques et aux événements cardiovasculaires. Or, on ignore encore si le suPAR a une valeur pronostique chez les patients présentant une sténose aortique asymptomatique. Méthodes: La concentration plasmatique du suPAR a été mesurée chez 1503 patients âgés en moyenne de 68 ans et recrutés parmi les participants à l’étude SEAS (Simvastatin andEzetimibe inAorticStenosis). Une analyse selon le modèle de régression de Cox a été réalisée afin d’évaluer les associations entre le suPAR et les paramètres d’évaluation composites regroupant les événements cardiovasculaires ischémiques, les événements liés à la valve aortique, la mortalité cardiovasculaire et la mortalité de toutes causes, après ajustement en fonction des facteurs de risque cardiovasculaire classiques et du traitement attribué. Résultats: Le rapport des risques instantanés (RRI) multivarié et corrigé (intervalle de confiance [IC] à 95 %) par unité (log2 ng/ml) d’augmentation du suPAR était de 1,5 (IC à 95 % : 1,2-1,9; p = 0,002) pour les événements cardiovasculaires ischémiques; RRI de 1,2 (IC à 95 % : 0,9-1,5; p = 0,071) pour les événements liés à la valvule aortique; RRI de 2,0 (IC à 95 % : 1,2-3,3; p = 0,007) pour la mortalité cardiovasculaire; et RRI de 2,0 (IC à 95 % : 1,4-2,9; p < 0,001) pour la mortalité de toutes causes. Conclusions: Chez les patients présentant une sténose aortique légère ou modérée, le suPAR est associé de façon indépendante à l’incidence d’événements cardiovasculaires ischémiques, de mortalité cardiovasculaire et de mortalité de toutes causes.

Background: To investigate whether B-type natriuretic peptide (NP)-guided treatment of heart failure (HF) patients improved their health related quality of life (Hr-QoL) compared to routine HF treatment, and whether changes in Hr-QoL differed depending on whether the patient was a responder to NP-guided therapy or not. Methods: A secondary analysis of the UPSTEP-study, a Scandinavian multicentre study using a prospective, randomized, open, blinded evaluation design on patients with HF with New York Heart Association (NYHA) class II-IV. NP-guiding was aimed to reduce BNP < 150 ng/L if < 75 years or BNP < 300 ng/L if > 75 years. A responder was defined as a patient with a BNP < 300 ng/L and/or a decrease in BNP of at least 40 % in week 16 compared to study start. Short form-36 (SF-36) was used to measure Hr-QoL. At the study start, 258 patients presented evaluable SF-36 questionnaires, 131 in the BNP group and 127 in the control group. At the study end 100 patients in the NP-guided group and 98 in the control group, presenting data from both the study start and the study end. Results: There were no significant differences in Hr-QoL between NP-guided HF treatment and control group; however significant improvements could be seen in four of the eight domains in the NP-guided group, whereas in the control group improvements could be seen in six of the domains. Among the responders improvements could be noted in four domains whereas in the non-responders improvements could be seen in only one domain evaluating within group changes. Conclusions: Improved Hr-QoL could be demonstrated in several of the domains in both the NP-guided and the control group. In the responder group within group analyses showed more increased Hr-QoL compared to the non-responder group. However, all groups demonstrated increase in Hr-QoL.

Background/Purpose: Heart failure (HF) is the most common cause of hospitalization at medical clinics for patients older than 65 years. Purpose: To study the prognostic value of biomarkers, comorbidities, and verified HF diagnosis for all-cause and cardiovascular hospitalizations. Methods: Between 2000 and 2003, 170 patients with HF symptoms according to their general practitioners were recruited and referred for echocardiography, biomarker measures and a final cardiology consultation. HF diagnosis was based on the general practitioner's prespecified HF record, echocardiography, and hospital records. Records from the departments of medicine and surgery were used to identify hospitalizations. This is a 10-year longitudinal observational primary healthcare center study. Results: During 10 years, 136 (80%) patients had 660 and 207 all-cause and cardiovascular hospitalizations, respectively. In multivariable logistic regression, age [ odds ratio (OR) = 1.1, 95% confidence interval (CI) = 1.01-1.15] and underlying heart disease (OR = 3.5, 95% CI = 1.00-11.89) significantly predicted all-cause hospitalization. Age (OR = 1.1, 95% CI = 1.01-1.12), underlying heart disease (OR = 3.4, 95% CI = 1.041-1.40), and N-terminal of prohormone brain natriuretic peptide >= 800 ng/L (OR = 4.3, 95% CI = 1.5-12.50) significantly predicted cardiovascular hospitalizations. In Cox regression analysis, overall HF (HR = 1.8, 95% CI = 1.06-2.94) significantly predicted time to first all-cause hospitalizations while no variable independently predicted time to first cardiovascular hospitalization. Conclusion: In patients with HF symptoms managed in primary healthcare, age, and underlying heart diseases predicted all-cause hospitalizations. N-terminal of prohormone brain natriuretic peptide added independent prognostic information for cardiovascular hospitalizations.

BACKGROUND: A previous cross-sectional study suggested that tissue plasminogen activator-activity might be an early marker of asymptomatic lower extremity arterial disease, but the long-term relationship is unknown. SUBJECTS AND METHODS: This study included 96 diabetic (48 type 1/48 type 2) and 62 non-diabetic subjects aged 30-70 years without previously known lower extremity arterial disease (age: 50.3 ± 9.3 years, gender: M/W 47.5/52.5% and body mass index: 26.6 ± 4.5 kg/m(2)). The relationships between asymptomatic lower extremity arterial disease and fibrinolytic markers (tissue plasminogen activator-activity, tissue plasminogen activator-mass, plasminogen activator inhibitor-1 activity) at baseline and after 10 years were assessed by logistic regression analysis adjusting for age, hypertension, statin treatment, HbA1c, triglycerides and low-density lipoprotein cholesterol as fixed covariates. RESULTS: The tissue plasminogen activator-activity at baseline and at the 10-year follow-up significantly predicted the presence of sign(s) of lower extremity arterial disease (odds ratio = 1.78, 95% confidence interval: 1.02-3.10, p = 0.043 and odds ratio = 1.78, 95% confidence interval: 1.12-2.23, p = 0.014, respectively). In addition, tissue plasminogen activator-mass at the 10-year follow-up was associated with signs of lower extremity arterial disease (odds ratio = 1.07, 95% confidence interval: 1.00-1.15, p = 0.046). Baseline age, hypertension and HbA1c were independently associated with sign(s) of lower extremity arterial disease at 10 years (odds ratio = 1.09, 95% confidence interval: 1.04-1.14, p = < 0.001; odds ratio = 3.68, 95% confidence interval: 1.67-8.12, p = 0.001 and odds ratio = 1.54, 95% confidence interval: 1.21-1.95, p = < 0.001, respectively). CONCLUSION: This long-term study supports previous findings of a significant association between asymptomatic lower extremity arterial disease and tissue plasminogen activator-activity. Thus, tissue plasmi

Background: Evidence for treating hypertension in patients with asymptomatic aortic valve stenosis is scarce. We used data from the SEAS trial (Simvastatin Ezetimibe in Aortic Stenosis) to assess what blood pressure (BP) would be optimal. METHODS: A total of 1767 patients with asymptomatic aortic stenosis and no manifest atherosclerotic disease were analyzed. Outcomes were all-cause mortality, cardiovascular death, heart failure, stroke, myocardial infarction, and aortic valve replacement. BP was analyzed in Cox models as the cumulative average of serially measured BP and a time-varying covariate. RESULTS: The incidence of all-cause mortality was highest for average follow-up systolic BP >= 160 mm Hg (4.3 per 100 person-years; 95% confidence interval [CI], 3.1-6.0) and lowest for average systolic BP of 120 to 139 mm Hg (2.0 per 100 person-years; 95% CI, 1.6-2.6). In multivariable analysis, all-cause mortality was associated with average systolic BP < 120 mm Hg (hazard ratio [HR], 3.4; 95% CI, 1.9-6.1), diastolic BP >= 90 mm Hg (HR, 1.8; 95% CI, 1.1-2.9), and pulse pressure < 50 mm Hg (HR, 1.8; 95% CI, 1.1-2.9), with systolic BP of 120 to 139 mm Hg, diastolic BP of 70 to 79 mm Hg, and pulse pressure of 60 to 69 mm Hg taken as reference. Low systolic and diastolic BPs increased risk in patients with moderate aortic stenosis. With a time-varying systolic BP from 130 to 139 mm Hg used as reference, mortality was increased for systolic BP >= 160 mm Hg (HR, 1.7; P=0.033) and BP of 120 to 129 mm Hg (HR, 1.6; P= 0.039). CONCLUSIONS: Optimal BP seems to be systolic BP of 130 to 139 mm Hg and diastolic BP of 70 to 90 mm Hg in these patients with asymptomatic aortic stenosis and no manifest atherosclerotic disease or diabetes mellitus.

Objective To investigate relations between inflammation and aortic valve stenosis (AS) by measuring high-sensitivity C-reactive protein, at baseline (hsCRP(0)) and after 1year (hsCRP(1)) and exploring associations with aortic valve replacement (AVR). Design We examined 1423 patients from the Simvastatin and Ezetimibe in Aortic Stenosis study. Results During first year of treatment, hsCRP was reduced both in patients later receiving AVR (2.3 [0.9-4.9] to 1.8 [0.8-5.4] mg/l, p<0.001) and not receiving AVR (1.90 [0.90-4.10] to 1.3 [0.6-2.9] mg/l, p<0.001). In Cox-regression analyses, hsCRP(1) predicted later AVR (HR=1.17, p<0.001) independently of hsCRP(0) (HR=0.96, p=0.33), aortic valve area (AVA) and other risk factors. A higher rate of AVR was observed in the group with high hsCRP(0) and an increase during the first year (AVR(highCRP0CRP1inc)=47.3% versus AVR(highCRP0CRP1dec)=27.5%, p<0.01). The prognostic benefit of a 1-year reduction in hsCRP was larger in patients with high versus low hsCRP(0) eliminating the difference in incidence of AVR between high versus low hsCRP(0) (AVR(highCRP0CRP1dec)=27.5% versus AVR(lowCRP0CRP1dec)=25.8%, p=0.66) in patients with reduced hsCRP during the first year. Conclusions High hsCRP(1) or an increase in hsCRP during the first year of follow-up predicted later AVR independently of AVA, age, gender and other risk factors, although no significant improvement in C-statistics was observed.

Background: Previous economic studies of person-centered palliative home care have been conducted mainly among patients with cancer. Studies on cost-effectiveness of advanced home care for patients with severe heart failure are lacking when a diagnosis of heart failure is the only main disease as the inclusion criterion. Aim: To assess the cost-effectiveness of a new concept of care called person-centered integrated heart failure and palliative home care. Design: A randomized controlled trial was conducted from January 2011 to 2013 at a center in Sweden. Data collection included cost estimates for health care and the patients’ responses to the EQ-5D quality of life instrument. Setting/participants: Patients with chronic and severe heart failure were randomly assigned to an intervention (n = 36) or control (n = 36) group. The intervention group received the Palliative Advanced Home Care and Heart Failure Care intervention over 6 months. The control group received the same care that is usually provided by a primary health care center or heart failure clinic at the hospital. Results: EQ-5D data indicated that the intervention resulted in a gain of 0.25 quality-adjusted life years, and cost analysis showed a significant cost reduction with the Palliative Advanced Home Care and Heart Failure Care intervention. Even if costs for staffing are higher than usual care, this is more than made up for by the reduced need for hospital-based care. This intervention made it possible for the county council to use €50,000 for other needs. Conclusion: The Palliative Advanced Home Care and Heart Failure Care working mode saves financial resources and should be regarded as very cost-effective., Special Issue.

Introduction: Muscle sample collection can introduce variation in any measured variable due to inter- and intramuscle variation. We investigated the variation in gene expression and fiber type composition after repeated biopsy sampling from the vastus lateralis muscle. Methods: Six subjects donated 3 tissue samples each. One hour after baseline sampling from 1 vastus lateralis muscle, samples from both vastus lateralis muscles were obtained. Results: The fiber type composition differed between biopsies taken from the same leg. There were no within-subject differences in gene expression between the 3 biopsies. Multivariate analysis supports a model in which gene expression differs significantly between individuals but is not affected by repeated muscle biopsy sampling from the same subject. Conclusion: One vastus lateralis muscle sample per subject is sufficient to establish a reliable baseline for comparing gene expression representing selected pathways over time within the same individual.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia. NT-proBNP is a fragment of the prohormone brain natriuretic peptide. Previous studies indicate that increased levels of NT-proBNP are associated with higher recurrence rates of AF after electrical cardioversion. Our null hypothesis was that NT-proBNP does not predict recurrence of AF after restoration of sinus rhythm. METHODS: We performed a hypothesis generating study within a double-blinded, placebo-controlled, randomized, prospective multicentre study of the effects of atorvastatin on recurrence of AF after electrical cardioversion. 199 patients with persistent AF and an indication for cardioversion were included in the present substudy. NT-proBNP was assessed prior to cardioversion. Cardioversion was performed according to local standard clinical practice on an elective outpatient basis. Patients were followed-up one month after cardioversion. RESULTS: 181 patients had a successful cardioversion and 91 of the study group remained in sinus rhythm at day 30. Recurrence of AF was observed in 108 patients at day 30. An optimal cutpoint for NT-proBNP at 500 ng/L predicted recurrence of AF after cardioversion (OR 2.94; 95% CI 1.30-6.63). In multivariate analysis adjusting for age, sex, hypertension, and treatment group strengthened the results (OR 3,56; 95% CI 1,44-8,81). When analysing the ROC curve of NT-proBNP in baseline and atrial fibrillation at day 30 the result was 0.57. CONCLUSION: NT-proBNP levels are a predictor of recurrence of AF 30 days after cardioversion. ROC curves indicates that the practical value of NT-proBNP for the individual patient is limited.

AIMS: To assess the prognostic importance of high-sensitive C reactive protein (hsCRP) in patients with mild to moderate aortic valve stenosis during placebo or simvastatin/ezetimibe treatment in Simvastatin and Ezetimibe in Aortic Stenosis (SEAS). METHODS AND RESULTS: In 1620 SEAS patients, we measured lipids and hsCRP at baseline and after 1 year of treatment and registered during 4 years of follow-up major cardiovascular events (MCE) composed of ischaemic cardiovascular events (ICE) and aortic valve-related events (AVE). Simvastatin/ezetimibe reduced low-density lipoprotein cholesterol (3.49 (2.94 to 4.15) to 1.32 (1.02 to 1.69) vs 3.46 (2.92 to 4.08) to 3.34 (2.81 to 3.92) mmol/L) and hsCRP (2.1 (0.9 to 4.1) to 1.2 (0.6 to 2.4) vs 2.2 (0.9 to 4.9) to 1.8 (0.85 to 4.35) mg/L, all p<0.05) during the first year of treatment. In multivariable Cox regression analysis adjusting for traditional risk factors and baseline hsCRP, ICE was associated with a 1-year increase of hsCRP (HR=1.19 (95% CI 1.12 to 1.25), p<0.001) but not with active treatment (HRTreatment=0.86 (0.67 to 1.13), p=0.28). Patients in the top quartile of baseline hsCRP versus the rest were associated with a higher risk of MCE (HR=1.34(1.09 to 1.64), p=0.02). The prognostic benefit of reduction in hsCRP after 1 year was significantly larger (p<0.01 for interaction) in patients with high versus low baseline hsCRP; hence, a reduction in hsCRP abolished the difference in incidence of MCE between high versus low baseline hsCRP in patients with reduced hsCRP (31.1 vs 31.9%, NS) in contrast to patients with increased hsCRP. CONCLUSIONS: The treatment-associated reduction in ICE was in part related to a reduction in hsCRP but not in lipids. hsCRP reduction was associated with less MCE, especially in patients with high baseline hsCRP. TRIAL REGISTRATION: NCT00092677.

OBJECTIVE: Women with severe aortic valve stenosis (AS) have better LV systolic function and more concentric LV geometry than their male counterparts. However, sex differences in cardiovascular (CV) outcome during progression of AS have not been reported from a longitudinal prospective study. METHODS: Doppler echocardiography and CV events were recorded during a median of 4.0 years in 979 men and 632 women aged 28-86 (mean 67±10) years in the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) study. LV systolic function was assessed by EF and midwall shortening (MWS). Study outcomes were AS-related events, ischaemic CV events and total mortality. RESULTS: The annular cumulative incidence of AS events, ischaemic CV events and death was 8.1%, 3.4% and 2.8% in women, and 8.9%, 4.4% and 2.4% in men, respectively. Women and men had similar AS progression rate whether measured by peak jet velocity, mean gradient or valve area. In multivariate analyses, female sex independently predicted less reduction in LV MWS and EF during follow-up (both p<0.05). In time-varying Cox analyses, women had a 40% lower rate of ischaemic CV events (95% CI 21% to 54%), in particular, more than 50% lower rate of stroke and coronary artery bypass grafting, and a 31% lower all-cause mortality (95% CI 1% to 51%), independent of active study treatment, age and hypertension, as well as time-varying valve area, low systolic function and abnormal LV geometry. AS event rate did not differ by sex. CONCLUSIONS: In the SEAS study, women and men had similar rates of AS progression and AS-related events. However, women had lower total mortality and ischaemic CV event rate than men independent of confounders. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT00092677.

Objectives. B-type natriuretic peptide (BNP) levels predict prognosis and outcome in heart failure (HF) patients. To evaluate the optimal cut-off level of BNP to predict death, need for hospitalization, and worsening HF, and also to determine the optimal time to apply the chosen cut-off value. Design. In a sub-study from the Use of PeptideS in Tailoring hEart failure Project or UPSTEP study where tailoring treatment of HF by BNP level was evaluated, we assessed the change in percentage between levels of BNP at study start versus a specific week (2, 6, 10, 16, 24, 36, or 48) during the follow-up period. Results. The optimum cut-off percentage levels were obtained using a Cox proportional regression analysis of death, hospitalization, and worsening HF. A decrease in BNP by less than 40% in week 16 compared with study start and/or a BNP > 300 ng/L presented the highest hazard ratio (HR) for a non-responder to reach a combined endpoint (HR: 2.43; 95% confidence interval or CI: 1.61-3.65; p < 0.00003). This definition gave a 78% risk reduction of cardiovascular (CV) mortality (p > 0.0005) and an 89% risk reduction of HF mortality (p > 0.004), and reduced risk of CV and HF hospitalization for the responders. Conclusions. Patients with a decrease in BNP of more than 40% compared with that at study start and/or a BNP level below 300 ng/L at week 16 had a significantly reduced risk of CV and HF mortality and hospitalization.

OBJECTIVE: To evaluate the impact of the Västerbotten Intervention Programme (VIP) by comparing all eligible individuals (target group impact) according to the intention-to-treat principle and VIP participants with the general Swedish population. DESIGN: Dynamic cohort study. SETTING/PARTICIPANTS: All individuals aged 40, 50 or 60 years, residing in Västerbotten County, Sweden, between 1990 and 2006 (N=101 918) were followed from their first opportunity to participate in the VIP until age 75, study end point or prior death. INTERVENTION: The VIP is a systematic, long-term, county-wide cardiovascular disease (CVD) intervention that is performed within the primary healthcare setting and combines individual and population approaches. The core component is a health dialogue based on a physical examination and a comprehensive questionnaire at the ages of 40, 50 and 60 years. PRIMARY OUTCOMES: All-cause and CVD mortality. RESULTS: For the target group, there were 5646 deaths observed over 1 054 607 person-years. Compared to Sweden at large, the standardised all-cause mortality ratio was 90.6% (95% CI 88.2% to 93.0%): for women 87.9% (95% CI 84.1% to 91.7%) and for men 92.2% (95% CI 89.2% to 95.3%). For CVD, the ratio was 95.0% (95% CI 90.7% to 99.4%): for women 90.4% (95% CI 82.6% to 98.7%) and for men 96.8% (95% CI 91.7 to 102.0). For participants, subject to further impact as well as selection, when compared to Sweden at large, the standardised all-cause mortality ratio was 66.3% (95% CI 63.7% to 69.0%), whereas the CVD ratio was 68.9% (95% CI 64.2% to 73.9%). For the target group as well as for the participants, standardised mortality ratios for all-cause mortality were reduced within all educational strata. CONCLUSIONS: The study suggests that the VIP model of CVD prevention is able to impact on all-cause and cardiovascular mortality when evaluated according to the intention-to-treat principle.

Background/purpose: There is a lack of long-term follow-up studies for elderly patients with heart failure (HF) in primary health care. There is conflicting information on prognostic differences between systolic or diastolic HF in elderly patients. Our aims were, first, to study the association between overall HF or types of HF and all-cause and cardiovascular mortality, and second, to explore the impact of N-terminal prohormone of brain natriuretic peptide (NTproBNP) and comorbidities. Methods: A longitudinal, prognostic, observational primary health care study with 10 years of follow-up comparing an elderly patient population with HF (systolic and/or diastolic HF) to patients without HF was conducted. HF was diagnosed with echocardiography according to the European Society of Cardi- ology guidelines. Results: Seventy-seven of 144 patients (102 women and 42 men; mean age, 77 years) had systolic and/or diastolic HF and were compared with 67 patients without HF (Reference group). During the 10-year follow-up, 71 (49%) patients died (women, 68%; men, 32%). In univariate Cox regression analysis, sig- nificant associations were found for overall HF [hazard ratio (HR), 1.86; 95% confidence interval (CI), 1.15 e3.01], isolated systolic HF (HR, 1.95; 95% CI, 1.06e3.61), and combined (systolic and diastolic) HF (HR, 3.28; 95% CI, 1.74e6.14) with all-cause mortality, but not for isolated diastolic HF. Similar results were found for cardiovascular mortality. In multivariate analysis, age (HR, 1.11; 95% CI, 1.06e1.17), kidney dysfunction (HR, 1.91; 95% CI, 1.11e3.29), smoking (HR, 3.70; 95% CI, 2.02e6.77), and NTproBNP (HR, 1.01; 95% CI, 1.00e1.02) significantly predicted all-cause mortality, but not any type of HF. Conclusion: Patients diagnosed with systolic HF had a worse prognosis for mortality compared to the reference group, but in patients with diastolic HF the prognosis for mortality was similar with that in the reference group. NTproBNP was a valuable prognostic facto

Recent American College of Cardiology/American Heart Association guidelines on statin initiation on the basis of total atherosclerotic cardiovascular disease risk argue that the preventive effect of statins on cardiovascular events outweigh the side effects, although this is controversial. Studies indicate a possible effect of statin therapy on reducing risk of lens opacities. However, the results are conflicting. The Simvastatin and Ezetimibe in Aortic Stenosis study (NCT00092677) enrolled 1,873 patients with asymptomatic aortic stenosis and no history of diabetes, coronary heart disease, or other serious co-morbidities were randomized (1:1) to double-blind 40 mg simvastatin plus 10 mg ezetimibe versus placebo. The primary end point in this substudy was incident cataract. Univariate and multivariate Cox models were used to analyze: (1) if the active treatment reduced the risk of the primary end point and (2) if time-varying low-density lipoproteins (LDL) cholesterol lowering (annually assessed) was associated with less incident cataract per se. During an average follow-up of 4.3 years, 65 patients (3.5%) developed cataract. Mean age at baseline was 68 years and 39% were women. In Cox multivariate analysis adjusted for age, gender, prednisolone treatment, smoking, baseline LDL cholesterol and high sensitivity C-reactive protein; simvastatin plus ezetimibe versus placebo was associated with 44% lower risk of cataract development (hazard ratio 0.56, 95% confidence interval 0.33 to 0.96, p = 0.034). In a parallel analysis substituting time-varying LDL-cholesterol with randomized treatment, lower intreatment LDL-cholesterol was in itself associated with lower risk of incident cataract (hazard ratio 0.78 per 1 mmol/ml lower total cholesterol, 95% confidence interval 0.64 to 0.93, p = 0.008). In conclusion, randomized treatment with simvastatin plus ezetimibe was associated with a 44% lower risk of incident cataract development. This effect should perhaps be considered in

Background: Digoxin is widely used for rate control of atrial fibrillation. However, recent studies have reported conflicting results on the association of digoxin with mortality when used in patients with atrial fibrillation. Moreover, the relationship of digoxin use to mortality in hypertensive patients with atrial fibrillation has not been examined. Methods and results: All-cause mortality was examined in relation to in-treatment digoxin use in 937 hypertensive patients with ECG left ventricular hypertrophy in atrial fibrillation at baseline (n = 134) or who developed atrial fibrillation during follow-up (n = 803), randomly assigned to losartan or atenolol-based treatment, in post-hoc analysis of a substudy of the Losartan Intervention For Endpoint Reduction in hypertension (LIFE) trial. During 4.7 ± 1.1 years of mean follow-up, 167 patients died (17.8%) and 372 (39.7%) were treated with digoxin. In univariate Cox analyses, in-treatment digoxin use, entered as a time-varying covariate, was associated with a 61% higher risk of dying (hazard ratio 1.61, 95% confidence interval 1.18–2.19, P = 0.003). After adjusting for other univariate predictors of death in this population, including age, diabetes, history of ischemic heart disease, stroke, or heart failure, baseline Cornell product, QRS duration, heart rate, serum glucose, creatinine and high-density lipoprotein cholesterol, and a propensity score for digoxin use entered as standard covariates, and for in-treatment heart rate, pulse pressure, and Sokolow–Lyon voltage treated as time-varying covariates, digoxin use was no longer a significant predictor of mortality (hazard ratio 1.04, 95% confidence interval 0.73–1.48, P = 0.839). Conclusion: In hypertensive patients with ECG left ventricular hypertrophy with existing or new atrial fibrillation, digoxin use is not associated with a significantly increased risk of all-cause mortality after adjusting for other independent predictors of death and for the factors asso

In the Losartan Intervention for End Point Reduction in Hypertension (LIFE) study, 4.8 years' losartan- versus atenolol-based antihypertensive treatment reduced left ventricular hypertrophy and cardiovascular end points, including cardiovascular death and stroke. However, there was no difference in myocardial infarction (MI), possibly related to greater reduction in myocardial oxygen demand by atenolol-based treatment. Myocardial oxygen demand was assessed indirectly by the left ventricular massxwall stressxheart rate (triple product) in 905 LIFE participants. The triple product was included as time-varying covariate in Cox models assessing predictors of the LIFE primary composite end point (cardiovascular death, MI, or stroke), its individual components, and all-cause mortality. At baseline, the triple product in both treatment groups was, compared with normal adults, elevated in 70% of patients. During randomized treatment, the triple product was reduced more by atenolol, with prevalences of elevated triple product of 39% versus 51% on losartan (both P0.001). In Cox regression analyses adjusting for age, smoking, diabetes mellitus, and prior stroke, MI, and heart failure, 1 SD lower triple product was associated with 23% (95% confidence interval 13%-32%) fewer composite end points, 31% (18%-41%) less cardiovascular mortality, 30% (15%-41%) lower MI, and 22% (11%-33%) lower all-cause mortality (all P0.001), without association with stroke (P=0.34). Although losartan-based therapy reduced ventricular mass more, greater heart rate reduction with atenolol resulted in larger reduction of the triple product. Lower triple product during antihypertensive treatment was strongly, independently associated with lower rates of the LIFE primary composite end point, cardiovascular death, and MI, but not stroke.

Background: An elevated resting heart rate (RHR) may be an early sign of cardiac failure, but its prognostic value during watchful waiting in asymptomatic aortic stenosis (AS) is largely unknown. Methods: RHR was determined by annual ECGs in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study of asymptomatic mild-to-moderate AS patients. Primary endpoint in this substudy was major cardiovascular events (MCEs) and secondary outcomes its individual components. Multivariable Cox-models using serially-measured RHR were used to examine the prognostic impact of RHR per se. Results: 1563 patients were followed for a mean of 4.3 years (6751 patient-years of follow-up), 553 (35%) MCEs occurred, 10% (n = 151) died, including 75 cardiovascular deaths. In multivariable analysis, baseline RHR was independently associated with MCEs (HR 1.1 per 10 min(-1) faster, 95% CI: 1.0-1.3) and cardiovascular mortality (HR 1.3 per 10 min(-1) faster, 95% CI: 1.0-1.7, both p <= 0.03). Updating RHR with annual in-study reexaminations, time-varying RHR was highly associated with excess MCEs (HR 1.1 per 10 min(-1) faster, 95% CI: 1.1-1.3) and cardiovascular mortality (HR 1.4 per 10 min(-1) faster, 95% CI: 1.2-1.7, both p <= 0.006). The association of RHR with MCEs and cardiovascular mortality was not dependent on atrial fibrillation status (both p >= 0.06 for interaction). Conclusions: RHR is independently associated with MCEs and cardiovascular death in asymptomatic AS (Clinicaltrials.gov; unique identifier NCT00092677).

Background Pruritus (itching) can be a distressing symptom, and previous research suggests that it is common in patients with chronic heart failure (CHF). Objectives The primary aim was to examine the prevalence of itching in patients with CHF and to compare this first to that among patients with coronary artery disease (CAD) and second to that of a normal Swedish population. The study also explored characteristics and possible causes of pruritus in patients with CHF. Methods In this cross-sectional prevalence study, a questionnaire was sent to 130 patients with CHF and to 130 with CAD. A total of 85 patients with CHF (65.4%) and 82 with CAD (63.1%) participated. Data were also compared with those of a previous study examining symptoms in a normal Swedish population. Results The prevalence of itching at some point during the last 3 months was 40.0% in patients with CHF and 23.2% in patients with CAD (P = 0.019). This difference was not significant after adjusting for sex, age and medication. Patients with CHF described their pruritus as more disturbing than patients with CAD. In addition, 13.6% of patients with CHF and 3.8% of persons in the normal population experienced itching every week without any rash (P = 0.001). Conclusions Pruritus is common and sometimes disturbing in patients with CHF and warrants clinical attention. Medication should be considered as a cause of itching and may explain differences in the prevalence between patients with CHF and those with CAD. However, other causes of itching in patients with CHF should be explored in prospective studies.

The effects of resistance training on mitochondrial biogenesis and oxidative capacity in skeletal muscle are not fully characterized, and even less is known about alterations in adipose tissue. We aimed to investigate adaptations in oxidative metabolism in skeletal muscle and adipose tissue after 8 weeks of heavy resistance training in apparently healthy young men. Expression of genes linked to oxidative metabolism in the skeletal muscle and adipose tissue was assessed before and after the training program. Body composition, peak oxygen uptake (VO2 peak), fat oxidation, activity of mitochondrial enzyme in muscle, and serum adiponectin levels were also determined before and after resistance training. In muscle, the expression of the genes AdipoR1 and COX4 increased after resistance training (9 and 13 %, respectively), whereas the expression levels of the genes PGC-1 alpha, SIRT1, TFAM, CPT1b, and FNDC5 did not change. In adipose tissue, the expression of the genes SIRT1 and CPT1b decreased after training (20 and 23 %, respectively). There was an increase in lean mass (from 59.7 +/- A 6.1 to 61.9 +/- A 6.2 kg), VO2 peak (from 49.7 +/- A 5.5 to 56.3 +/- A 5.0 ml/kg/min), and fat oxidation (from 6.8 +/- A 2.1 to 9.1 +/- A 2.7 mg/kg fat-free mass/min) after training, whereas serum adiponectin levels decreased significantly and enzyme activity of citrate synthase and 3-hydroxyacyl-CoA dehydrogenase did not change. Despite significant increases in VO2 peak, fat oxidation, and lean mass following resistance training, the total effect on gene expression and enzyme activity linked to oxidative metabolism was moderate.

Objectives: Previous studies have shown that biomarkers in blood plasma can predict bleeding complications during anticoagulant treatment as well as thromboembolic events and may improve existing risk stratification schemes in patients on or considered for oral anticoagulant treatment. The aim of this study was to investigate if levels of D-dimer, tissue plasminogen activator (tPA) and its complex with plasminogen inhibitor type 1 (tPA/PAI-1 complex) can predict major bleedings, cardiovascular events and all-cause mortality in patients with warfarin treatment. Design and methods: In a longitudinal cohort study, 719 patients on oral anticoagulant treatment were followed for a total of 3001 treatment years. Major bleeding, stroke, arterial emboli, myocardial infarction and death were recorded and classified. Blood samples collected at baseline were analyzed for D-dimer, tPA, and tPA/PAI-1 complex. Results: In multivariate Cox regression analysis, high levels of D-dimer were associated with major bleeding (HR 1.27 per SD; 95% CI: 1.01-1.60), cardiovascular events (HR 1.23 per SD; 95% CI: 1.05-1.45) and all-cause mortality (HR 1.25 per SD; 95% CI: 1.06-1.47). Neither tPA nor the tPA/PAI-1 complex was associated with major bleeding, cardiovascular events or all-cause mortality. Conclusion: We conclude that high levels of D-dimer predict major bleeding, cardiovascular events and all-cause mortality during warfarin treatment. (C) 2014 The Canadian Society of Clinical Chemists.