Incident Chronic Heart Failure Research Articles

MyD88 in myeloid cells promotes angiotensin II-induced vascular inflammation and is associated with all-cause mortality and incident heart failure in humans with arterial hypertension

Abstract Background Angiotensin II (AngII) causes hypertension and promotes vascular accumulation of inflammatory cells. We aimed to determine how myeloid factor of differentiation 88 (MyD88) contributes to vascular dysfunction and arterial hypertension in mice and humans. Methods Male C57BL/6 as well as MyD88-/-, LysMCre/wtMyD88LSL/LSL, LysMCre/wt, TLR2-/-, TLR4-/-, TLR7-/- and TLR9-/- were investigated in the AngII-model of hypertension (1 mg/kg/d for 7days). Biodata analyses were performed in the Gutenberg-Health Study (GHS), a population based cohort. In addition, we performed computational analyses of known hypertension-related genes from genome-wide association studies (GWAS) to investigate whether they preferentially interact with MyD88 in the human protein network. Results MyD88 deficiency attenuated AngII-induced blood pressure increase and endothelial dysfunction in conductance and resistance vessels. Vascular mRNA expression levels of vcam-1, nos2, nox2 were decreased in AngII-infused MyD88-/- mice compared to C57BL/6 controls. Flow cytometric analyses revealed that AngII-induced aortic accumulation of CD11b+Ly6Chi inflammatory monocytes was significantly dampened in MyD88-/- mice. AngII increased mRNA expression of cd62L, cd68 and ccl2, which was blocked in MyD88-/- mice, indicating a role of MyD88 for myeloid cell activation and differentiation. Additionally, aortic interferon-g+ NK cells and mRNA levels of interleukin-12 and interleukin-1b were reduced in AngII-treated MyD88-/- mice. Bone marrow transfer experiments demonstrated a vasoprotective effect of MyD88 deficiency in bone marrow-derived cells, and selective expression of MyD88 in LysMCre/wtMyD88LSL/LSL mice restored AngII-induced pathology, revealing that myelomonocytic cells drives vascular dysfunction in a MyD88-dependent manner. Furthermore, data from 1,274 individuals in the GHS indicated, that MyD88 mRNA expression was associated with all cause mortality and incident chronic heart failure after a median follow-up of 11.6 years. Computational analysis of the human protein interaction network demonstrated that MyD88 is significantly connected to proteins encoded by genetic loci associated with blood pressure traits in multiple GWAS. Conclusion We provide evidence, that MyD88 expressed by myelomonocytic cells promotes AngII-induced vascular dysfunction and arterial hypertension. MyD88 might be used as an inflammatory diagnostic marker for the risk of death in hypertensive patients.

Weakness Is Associated with Time to Incident Chronic Heart Failure in Aging Americans.

Handgrip strength is considered a biomarker of nutritional status and strength capacity, which are both linked to heart complications. However, it is not well understood how weakness, as measured by handgrip strength, factors into common heart conditions seen in aging adults such as chronic heart failure (CHF). The purpose of this study was to determine the association between weakness and incident CHF for aging Americans. Longitudinal-Panel. Physical measures were completed during enhanced face-to-face interviews. The core interview was typically conducted over the telephone. Data from 17,431 adults aged at least 50 years who identified as Black or White, completed interviews without a proxy, and participated in at least one wave of the 2006-2014 waves of the Health and Retirement Study were included. Handgrip strength was measured with a hand-held dynamometer. Healthcare provider diagnosed CHF was self-reported at each wave. Sex- and race-specific maximal handgrip strength cut-points were used for determining weakness (Black men: <40-kilograms, Black women: <31-kilograms, White men: <35-kilograms, White women: <22-kilograms). A covariate-adjusted Cox model analyzed the association between weakness and incident CHF. Of those included, 5,397 (31.0%) were weak and 327 (1.9%) developed CHF during the mean follow-up of 4.7±2.7 years. Those who were weak had a 35% higher risk (hazard ratio: 1.35; 95% confidence interval: 1.05, 1.74) of developing CHF, compared to those who were not-weak. Measures of handgrip strength should be utilized by healthcare providers for assessing age-related weakness, nutritional status, and CHF risk. Likewise, interventions aiming to prevent or treat CHF in aging adults should incorporate measures of handgrip strength for helping to determine efficacy of intervention programs.

Predictors for repeated hyperkalemia and potassium trajectories in high-risk patients - A population-based cohort study.

Understanding predictors and trajectories of increased potassium may inform testing and treatment of hyperkalemia. We examined predictors for repeated hyperkalemia among patients after first-time renin angiotensin system inhibitor (RASi) prescription, chronic kidney disease (CKD), or chronic heart failure (CHF); and we also examined potassium trajectories in these patients after their first hyperkalemia event. We used Danish population-based registries to identify all patients with first-time RASi prescription, incident CKD, or incident CHF (2000–2012). For patients with a first hyperkalemia event, potassium trajectories over the following 6 months were examined. The predictors associated with repeated hyperkalemia were assessed, with repeated hyperkalemia defined as a potassium test >5.0 mmol/L after the first event within 6 months. Overall 262,375 first-time RASi users, 157,283 incident CKD patients, and 14,600 incident CHF patients were included. Of patients with a first hyperkalemia event, repeated hyperkalemia within 6 months occurred in 37% of RASi users, 40% with CKD, and 49% of patients with CHF. Predictors included severe hyperkalemia, low eGFR, diabetes, and spironolactone use. In all cohorts, the median potassium levels declined over 2–4 weeks after a hyperkalemia event for the first time, but reverted to levels higher than before the initial hyperkalemia event in those who had repeated hyperkalemia. Following hyperkalemia, discontinuation of RASi and spironolactone was common in the RASi and CHF cohorts. Repeated hyperkalemia was common among the explored cohorts. The first hyperkalemia event was an indicator of increased median potassium levels. Predictors may identify patients likely to benefit from intensified monitoring and intervention.

High Serum Concentrations of Uric Acid: Clinical and Prognostic Significance in Chronic Heart Failure

The article is devoted to the value of asymptomatic hyperuricemia in patients with chronic heart failure (CHF). The review summarizes results of a number of epidemiological reports that have increasingly linked elevated serum uric acid with an increased risk of incident CHF and adverse outcomes in CHF patients. Pharmacological and non-pharmacological approaches to influencing disturbances of uric acid metabolism are discussed.

0446: Impact of body mass index on prognosis in systolic heart failure patients: Moroccan profile

Higher body mass index (BMI) is associated with incident chronic heart failure (CHF) but it is paradoxically associated with better prognosis. The objective of the study was to analyze the relationship between body mass index and HF in a Moroccan profil. We enrolled 685 patients admitted to the Therapeutic Unit of Chronic Heart Failure (TUHF) from 2006 to 2013 as follow: under-weight (BMI <18.5kg/m 2 , n=35), normal (18.5 ≤BMI<25, n=349), overweight (25≤BMI <30, n=200) and obese (BMI ≥30, n=101) and compared the results from their clinical data, laboratory tests and echocardiography. The prevalence of obesity and overweight in CHF were 15 and 29% respectively. Obese group had a higher prevalence of obesity-related comorbidity (hypertension: p=0.0001, diabetes mellitus: p=0.0001 and dyslipidemia: p=0.001). Age, Ischemic heart disease, strock attack, stage NYHA, heart rate, hospitaliszation rate for cardiac decompensation, left right ventricular systolic function did not differ among the groups. However male sex, anemia and diastolic dysfunction were higher in the underweight group than in the other groups (p<0.0001 and p=0.03 respectively). High body mass index (overweigh and obesity) was frequent in chronic heart failure and it was not predictor of cardiac decompensations and hospitalizations. Furthermore, lower BMI was associated with diastolic dysfunction.

Mean HbA1c and mortality in diabetic individuals with heart failure: a population cohort study.

Controversy exists regarding the importance of glycaemic control in patients with type 2 diabetes mellitus (T2DM) and chronic heart failure (CHF) based on conflicting reports using single baseline glycosyated haemoglobin (HbA1c ). Using the time-weighted mean of serial HbA1c measurements has been found to be a better predictor of diabetic complications as it reflects the glycaemic burden for that individual over time. We therefore sought to confirm this in a large cohort of patients with T2DM and incident CHF. A time-weighted mean HbA1c was calculated using all HbA1c measurements following CHF diagnosis. Patients were grouped into five categories of HbA1c (≤6.0%, 6.1-7.0%, 7.1-8.0%, 8.1-9.0%, and >9.0%). The relationship between time-weighted mean HbA1c and all-cause death after CHF diagnosis was assessed. A total of 1447 patients with T2DM met the study criteria. During a median follow-up of 2.8 years, there were 826 (57.1%) deaths, with a crude death rate of 155 deaths per 1000 person-years [95% confidence interval (CI) 144-166]. A Cox regression model, adjusted for all significant predictors, with the middle HbA1c category (7.1-8.0%) as the reference, showed a U-shaped relationship between HbA1c and outcome [HbA1c <6.0%, hazard ratio (HR) 2.5, 95% CI 1.8-3.4; HbA1c 6.1-7.0%, HR 1.4, 95% 1.1-1.7; HbA1c 8.1-9.0%, HR 1.3, 95% CI 1.0-1.6; and HbA1c >9.0%, HR 1.8, 95% CI 1.4-2.3]. Further analysis revealed a protective effect of insulin sensitizers (i.e. metformin) (HR 0.7, 95% CI 0.61-0.93) but not other drug classes. In patients with T2DM and CHF, our study shows a U-shaped relationship between HbA1c and mortality, with the lowest risk in patients with modest glycaemic control (HbA1c 7.1-8.0%) and those treated with insulin sensitizers.

Supervivencia de pacientes ambulatorios con insuficiencia cardiaca crónica del área mediterránea. Un estudio de base poblacional

Introduction and objectivesScarce research has been performed in ambulatory patients with chronic heart failure in the Mediterranean area. Our aim was to describe survival trends in our target population and the impact of prognostic factors. MethodsWe carried out a population-based retrospective cohort study in Catalonia (north-east Spain) of 5659 ambulatory patients (60% women; mean age 77 [10] years) with incident chronic heart failure. Eligible patients were selected from the electronic patient records of primary care practices from 2005 and were followed-up until 2007. ResultsDuring the follow-up period deaths occurred in 950 patients (16.8%). Survival after the onset of chronic heart failure at 1, 2, and 3 years was 90%, 80%, 69%, respectively. No significant differences in survival were found between men and women (P=.13). Cox proportional hazard modelling confirmed an increased risk of death with older age (hazard ratio=1.06; 95% confidence interval, 1.06-1.07), diabetes mellitus (hazard ratio=1.53; 95% confidence interval, 1.33-1.76), chronic kidney disease (hazard ratio=1.73; 95% confidence interval, 1.45-2.05), and ischemic heart disease (hazard ratio=1.18; 95% confidence interval, 1.02-1.36). Hypertension (hazard ratio=0,73; 95% confidence interval, 0,64-0,84) had a protective effect. ConclusionsService planning and prevention programs should take into consideration the relatively high survival rates found in our area and the effect of prognostic factors that can help to identify high risk patients.Full English text available from:www.revespcardiol.org/en

Survival in Mediterranean Ambulatory Patients With Chronic Heart Failure. A Population-based Study

Introduction and objectivesScarce research has been performed in ambulatory patients with chronic heart failure in the Mediterranean area. Our aim was to describe survival trends in our target population and the impact of prognostic factors. MethodsWe carried out a population-based retrospective cohort study in Catalonia (north-east Spain) of 5659 ambulatory patients (60% women; mean age 77 [10] years) with incident chronic heart failure. Eligible patients were selected from the electronic patient records of primary care practices from 2005 and were followed-up until 2007. ResultsDuring the follow-up period deaths occurred in 950 patients (16.8%). Survival after the onset of chronic heart failure at 1, 2, and 3 years was 90%, 80%, 69%, respectively. No significant differences in survival were found between men and women (P=.13). Cox proportional hazard modelling confirmed an increased risk of death with older age (hazard ratio=1.06; 95% confidence interval, 1.06-1.07), diabetes mellitus (hazard ratio=1.53; 95% confidence interval, 1.33-1.76), chronic kidney disease (hazard ratio=1.73; 95% confidence interval, 1.45-2.05), and ischemic heart disease (hazard ratio=1.18; 95% confidence interval, 1.02-1.36). Hypertension (hazard ratio=0.73; 95% confidence interval, 0.64-0.84) had a protective effect. ConclusionsService planning and prevention programs should take into consideration the relatively high survival rates found in our area and the effect of prognostic factors that can help to identify high risk patients.

009 ADHERENCE TO HEART FAILURE THERAPY AND OUTCOME: A POPULATION BASED STUDY

Background Improvements in medical therapy for chronic heart failure (CHF) have resulted in an increase in the number of drugs which patients have to take. As CHF patients are often elderly with multiple comorbid conditions, the resulting polypharmacy could potentially lead to non-adherence to medications. The aim of this study was to determine the prevalence of non-adherence among CHF patients and to determine if non-adherence is associated with a poor outcome. Methods We conducted a 10 year retrospective longitudinal cohort study of CHF patients from Tayside in Scotland (population of 450 000) that were started on the angiotensin-converting enzyme (ACE) inhibitor, ramipril, after their incident CHF hospitalisation utilising our established record linkage database linking dispensed prescriptions to other datasets covering socioeconomic status, age, gender, hospital admissions and mortality data. To be included, patients with incident CHF hospitalisation had to have survived their index hospitalisation and completed a month of medication and have not switched to an angiotensin receptor blocker. Adherence was calculated as Proportion of Days Covered, with Results 702 eligible patients (mean age, 75.5±11.3 years) entered into the analysis. 35.9% (mean age, 78.1±11.3 years, 58.7% male) of the cohort were non-adherent and 64.1% (mean age, 74.1±11.1 years, 66.7% male) were considered adherent. Factors associated with non-adherence were male gender, old age (>81 years old), presence of ischaemic heart disease (IHD), chronic pulmonary obstructive disease (COPD) and chronic kidney disease (CKD). Non-adherence was associated with increased number of repeated hospitalisation (p=0.042) and was an independent predictor of all-cause mortality (risk ratio 1.58, 95% CI 1.29 to 1.95, p Conclusions Non-adherence to ACE inhibitor therapy was highly prevalent among CHF patients. Male patients, advanced age, presence of IHD, COPD and CKD are associated with non-adherence. Non-adherence was associated with an increase in the number of repeated hospitalisation and is a predictor of all-cause mortality.

016 THE GENETICS OF GLYCAEMIC CONTROL AND HEART FAILURE ARE INTER-TWINED

<h3>Background</h3> Hyperglycaemia is associated with increased risk of cardiovascular events in diabetic individuals. The relationship between glycaemic control and the development of chronic heart failure (CHF) is undefined and may have a genetic component. In this study, we aim to assess the relationship between glycaemic control and the development of CHF and examine whether genes predicting glycosylated haemoglobin levels also predicted time to development of CHF. <h3>Methods</h3> This study was carried out in the Go-DARTS population of Tayside, Scotland, using demographic, echocardiographic and prescribing data maintained by the University of Dundee. CHF incidence, determined during the study period October 1999 to August 2011, was identified by either the presence of a hospital discharge code for CHF or echocardiogram showing left ventricular systolic dysfunction and prescription of a loop diuretic. CHF cases and non-CHF controls were matched for gender and age at diabetes diagnosis. Development of CHF was modelled using conditional logistic regression using updated mean HbA1c during the study period, using age, gender and duration of diabetes as covariates. Proportional hazard regression analysis was used to determine whether published single nucleotide polymorphisms (SNPs) associated with glycaemic control predicted time to development of CHF in this population. <h3>Results</h3> Out of 8890 diabetic individuals, 759 developed CHF during the study period (mean age at diagnosis 74.2±9.6 years, 60.6% males). The adjusted OR for developing CHF in those with updated mean HbA1C greater than 6.9 was 2.14 (95% CI 1.64 to 2.8, p&lt;0.01). Three SNPs previously associated with glycaemic control predicted time to CHF development rs6474359 (p=1.67×10–4, HR 1.90, 95% CI 1.36 to 2.67), rs7800094 (p=9.46×10–3, HR 1.23, 95% CI 1.05 to 1.45) and rs10885122 (p=0.02, HR 1.34, 95% CI 1.05 to 1.70). <h3>Conclusions</h3> These data suggest that glycaemic control is an independent risk factor for incident CHF in individuals with T2DM. Since SNPs associated with glycaemic control were also associated with CHF development this increased risk may have a genetic component.

011 HbA1c and mortality in diabetic individuals with heart failure: an observational cohort study

Background Controversy exists regarding the importance of glycaemic control in patients with type 2 diabetes mellitus (T2DM) and chronic heart failure (CHF) based on conflicting reports that had used a single baseline HbA1c. Objective To examine the relationship between the mean of all HbA1c measures after CHF diagnosis and outcome in a large cohort of T2DM patients with incident CHF. Design Retrospective, observational cohort study. Setting Tayside, Scotland. Patients T2DM patients with incident CHF between 1993 and 2010. Measurement A weighted mean HbA1c was calculated using all available HbA1c measures following CHF diagnosis and patients were grouped into five categories of HbA1c (≤6%, >6–≤7%, >7–≤8%, >8–≤9% and >9%). We subsequently compared diet and drug treated populations. The relationship between mean HbA1c and all-cause deaths after CHF diagnosis was assessed. Results 795 patients with T2DM met study criteria. Median follow-up of 3.8 years saw 491 (61.8%) deaths. Cox regression model, adjusted for all other significant predictors, with the middle HbA1c category (>7–≤8%) as the reference, showed a U shaped relationship between HbA1c and outcome. (<6% [HR 95% CI 1.78 (1.26 to 2.52)]; >6–≤7% [1.29 (1.01 to 1.66)] and >9% [1.38 (1.03 to 1.84)]. We found a similar relationship in the drug treated sub-group. However in the diet only group, low HbA1c was associated with the lowest risk of death (≤7% [0.17 (0.07 to 0.39)]). Conclusions In patients with T2DM and CHF, our observational study shows that in drug treated patients there was a U shaped relationship between HbA1c and mortality with the lowest mortality risk in patients with modest glycaemic control (HbA1c, >7–≤9%). However in diet treated patients, lower HbA1c was associated with lower mortality risk.

Effect of Metformin on Mortality in Patients With Heart Failure and Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (DM) plus chronic heart failure (CHF) is a common but lethal combination and therapeutic options are limited. Metformin is perceived as being relatively contraindicated in this context, although mounting evidence indicates that it may be beneficial. This study was carried out to investigate the use of metformin therapy for treating patients with DM and CHF in a large population-based cohort study. The Health Informatics Centre-dispensed prescribing database for the population of Tayside, Scotland (population ∼400,000) was linked to the Diabetes Audit and Research in Tayside Scotland (DARTS) information system. Patients with DM and incident CHF from 1994 to 2003 receiving oral hypoglycemic agents but not insulin were identified. Cox regression was used to assess differences in all-cause mortality rates between patients prescribed metformin and patients prescribed sulfonylureas with adjustment for co-morbidities and other therapies. Four hundred twenty-two study subjects (mean ± SD 75.4 ± 0.5 years of age, 46.2% women) were identified: metformin monotherapy (n = 68, mean age 75.5 ± 1.1 years, 48.5% women), sulfonylurea monotherapy (n = 217, mean age 76.7 ± 0.7 years, 45.2% women), and combination (n = 137, mean age, 73.4 ± 0.7 years, 46.7% women). Fewer deaths occurred in metformin users, alone or in combination with sulfonylureas, compared to the sulfonylurea monotherapy cohort at 1 year (0.59, 95% confidence interval 0.36 to 0.96) and over long-term follow up (0.67, 95% confidence interval 0.51 to 0.88). In conclusion, this large observational data suggest that metformin may be beneficial in patients with CHF and DM. These findings need to be verified by a prospective clinical trial.

Consultation with cardiologists for persons with new-onset chronic heart failure: A population-based study

It is recommended that persons recently diagnosed with heart failure consult with a specialist in heart failure. To determine whether patients who were diagnosed with new-onset chronic heart failure (CHF) by a noncardiologist consulted with a cardiologist, and identify the factors associated with delayed consultation. Physician reimbursement administrative data were obtained for all adults with suspected new-onset CHF in the year 2000 in Quebec, defined operationally as a physician visit for CHF (based on the International Classification of Diseases, 9th Revision diagnostic codes), with no previous physician visit code for CHF in the preceding three years. Among those first diagnosed by a noncardiologist, Cox regression modelling was used to identify patient and physician characteristics associated with time to cardiology consultation. Of the 13,523 persons coded as having incident CHF, 54.9% consulted a cardiologist within the next 2.5 to 3.5 years, and 67.4% were seen by an internist or cardiologist. Older patients, women, and those with lower comorbidity and socioeconomic status had significantly longer times to cardiology consultation. The data suggest that many patients with suspected new-onset CHF do not receive prompt cardiology care, as stipulated by current recommendations. Equity of access for women and those with lower socioeconomic status appears to be problematic.

Abdominal Obesity Is an Independent Risk Factor for Chronic Heart Failure in Older People

To examine whether total and abdominal adiposity are risk factors for the development of chronic heart failure (CHF) in older men and women. Prospective, longitudinal cohort: The Health, Aging and Body Composition study. Memphis, Tennessee, and Pittsburgh, Pennsylvania, metropolitan areas. Three thousand seventy-five well-functioning community-dwelling older adults aged 70 to 79. Body composition using dual energy X-ray absorptiometry, visceral adipose tissue area using computed tomography, adjudicated CHF. Of the remaining (640 participants excluded from original group of 3,075) 2,435 participants (1,081 men, 1,354 women) without coronary heart disease or CHF at baseline, there were 166 confirmed diagnoses of CHF during the median+/-standard deviation (SD) follow-up of 6.1+/-1.4 years. After adjustment for age, race, sex, site, education, smoking, and chronic obstructive pulmonary disorder, all adiposity variables (body mass index (BMI), adipose tissue mass, percentage body fat, waist-to-thigh ratio, waist circumference, and visceral and subcutaneous abdominal adipose tissue) were significant predictors of the development of CHF. In a model that included waist circumference and BMI, waist circumference was associated with incident CHF (hazard ratio (HR)=1.27, 95% confidence interval (CI)=1.04-1.54 per SD increase, P=.02), but BMI was not (HR=1.08, 95% CI=0.86-1.35). When waist circumference and percentage fat were included together, both variables were significant predictors of CHF (waist: HR=1.17, 95% CI=1.00-1.36 per SD increase, P=.05; percentage fat: HR=1.47, 95% CI=1.16-1.87 per SD increase, P=.002). Stepwise adjustment for inflammation, hypertension, insulin resistance, and diabetes mellitus did not decrease the relative risk of a greater waist circumference for the development of CHF (all HR=1.27-1.32, 95% CI=1.02-1.61 per SD increase). Abdominal body fat distribution may be a stronger risk factor for CHF than overall obesity.