Coping Mediates the Association Between Type D Personality and Perceived Health in Chinese Patients with Coronary Heart Disease

Background: Increasing evidence show that Type D personality is a risk factor for morbidity, mortality, and quality of life of patients with coronary vascular disease. Few studies examined coping as a potential behavioral mechanism to explain the harmful effect of Type D personality. Purpose: This study examined the association between Type D personality, coping, and perceived health among Chinese patients with coronary heart disease (CHD). Methods: One hundred seventeen CHD patients completed the assessments on Type D personality, coping, perceived severity of CHD, and morale. Results: There was no difference on severity of coronary artery stenosis between Type D and non-Type D patients. Compared to the non-Type D patients, the Type D patients perceived higher severity of CHD (5.31±2.41 versus 4.45±2.17, p<0.05) and lower morale (12.67±4.71 versus 15.00±4.43, p<0.05), and used less confrontation (16.90±5.39 versus 20.88±4.95, p<0.001) and more acceptance-resignation coping (10.16±3.50 versus 8.35±3.48, p<0.05). Mediation analyses showed that confrontation coping mediated the association between Type D personality and perceived severity of disease, and acceptance-resignation coping mediated the association between Type D personality and morale after controlling for age, gender, and clinical variables. Conclusion: The Type D patients used maladaptive coping in response to disease. These coping strategies fully mediated the association between Type D personality and perceived health. Implications for integrating coping training into the intervention for patients with a Type D personality are discussed. © 2010 The Author(s).published_or_final_versionSpringer Open Choice, 21 Feb 201

Research into the effect Of SGLT2 inhibition on left ventricular remodelling in patients with heart failure and diabetes mellitus (REFORM) trial rationale and design

Background Heart failure (HF) and diabetes (DM) are a lethal combination. The current armamentarium of anti-diabetic agents has been shown to be less efficacious and sometimes even harmful in diabetic patients with concomitant cardiovascular disease, especially HF. Sodium glucose linked co-transporter type 2 (SGLT2) inhibitors are a new class of anti-diabetic agent that has shown potentially beneficial cardiovascular effects such as pre-load and after load reduction through osmotic diuresis, blood pressure reduction, reduced arterial stiffness and weight loss. This has been supported by the recently published EMPA-REG trial which showed a striking 38 and 35 % reduction in cardiovascular death and HF hospitalisation respectively. Methods The REFORM trial is a novel, phase IV randomised, double blind, placebo controlled clinical trial that has been ongoing since March 2015. It is designed specifically to test the safety and efficacy of the SLGT2 inhibitor, dapagliflozin, on diabetic patients with known HF. We utilise cardiac-MRI, cardio-pulmonary exercise testing, body composition analysis and other tests to quantify the cardiovascular and systemic effects of dapagliflozin 10 mg once daily against standard of care over a 1 year observation period. The primary outcome is to detect the change in left ventricular (LV) end systolic and LV end diastolic volumes. The secondary outcome measures include LV ejection fraction, LV mass index, exercise tolerance, fluid status, quality of life measures and others. Conclusions This trial will be able to determine if SGLT2 inhibitor therapy produces potentially beneficial effects in patients with DM and HF, thereby replacing current medications as the drug of choice when treating patients with both DM and HF

Innate immunity and remodelling

A wide variety of cardiac disease states can induce remodelling and lead to the functional consequence of heart failure. These complex disease states involve a plethora of parallel signal transduction events, which may be associated with tissue injury or tissue repair. Innate immunity is activated in hearts injured in different ways, evident as cytokine release from the heart, activation of toll-like receptors involved in recognizing danger, and activation of the transcription factor nuclear factor kappa B. Nuclear factor kappa B regulates gene programmes involved in inflammation as well as the resolution of inflammation. The impact of this is an enigma; while cytokines, toll-like receptors, and nuclear factor kappa B appear to elicit myocardial protection in studies of preconditioning, the literature strongly indicates a detrimental role for activation of innate immunity in studies of acute ischaemia–reperfusion injury. The impact of activation of cardiac innate immunity on the long-term outcome in in vivo models of hypertrophy and remodelling is less clear, with conflicting results as to whether it is beneficial or detrimental. More research using genetically engineered mice as tools, different models of evoking remodelling, and long-term follow-up is required for us to conclude whether activation of the innate immune system is good, bad, or unimportant in chronic injury models

Left ventricular remodeling in swine after myocardial infarction: a transcriptional genomics approach

Despite the apparent appropriateness of left ventricular (LV) remodeling following myocardial infarction (MI), it poses an independent risk factor for development of heart failure. There is a paucity of studies into the molecular mechanisms of LV remodeling in large animal species. We took an unbiased molecular approach to identify candidate transcription factors (TFs) mediating the genetic reprogramming involved in post-MI LV remodeling in swine. Left ventricular tissue was collected from remote, non-infarcted myocardium, 3 weeks after MI-induction or sham-surgery. Microarray analysis identified 285 upregulated and 278 downregulated genes (FDR < 0.05). Of these differentially expressed genes, the promoter regions of the human homologs were searched for common TF binding sites (TFBS). Eighteen TFBS were overrepresented >two-fold (p < 0.01) in upregulated and 13 in downregulated genes. Left ventricular nuclear protein extracts were assayed for DNA-binding activity by protein/DNA array. Out of 345 DNA probes, 30 showed signal intensity changes >two-fold. Five TFs were identified in both TFBS and protein/DNA array analyses, which showed matching changes for COUP-TFII and glucocorticoid receptor (GR) only. Treatment of swine with the GR antagonist mifepristone after MI reduced the post-MI increase in LV mass, but LV dilation remained unaffected. Thus, using an unbiased approach to study post-MI LV remodeling in a physiologically relevant large animal model, we identified COUP-TFII and GR as potential key mediators of post-MI remodeling

Physical activity assessment by accelerometry in people with heart failure

Background: International guidelines for physical activity recommend at least 150 min per week of moderate-to-vigorous physical activity (MVPA) for adults, including those with cardiac disease. There is yet to be consensus on the most appropriate way to categorise raw accelerometer data into behaviourally relevant metrics such as intensity, especially in chronic disease populations. Therefore the aim of this study was to estimate acceleration values corresponding to inactivity and MVPA during daily living activities of patients with heart failure (HF), via calibration with oxygen consumption (VO2) and to compare these values to previously published, commonly applied PA intensity thresholds which are based on healthy adults. Methods: Twenty-two adults with HF (mean age 71 ± 14 years) undertook a range of daily living activities (including laying down, sitting, standing and walking) whilst measuring PA via wrist- and hip-worn accelerometers and VO2 via indirect calorimetry. Raw accelerometer output was used to compute PA in units of milligravity (mg). Energy expenditure across each of the activities was converted into measured METs (VO2/resting metabolic rate) and standard METs (VO2/3.5 ml/kg/min). PA energy costs were also compared with predicted METs in the compendium of physical activities. Location specific activity intensity thresholds were established via multilevel mixed effects linear regression and receiver operator characteristic curve analysis. A leave-one-out method was used to cross-validate the thresholds. Results: Accelerometer values corresponding with intensity thresholds for inactivity ( 50% lower than previously published intensity thresholds for both wrists and waist accelerometers (inactivity: 16.7 to 18.6 mg versus 45.8 mg; MVPA: 43.1 to 49.0 mg versus 93.2 to 100 mg). Measured METs were higher than both standard METs (34-35%) and predicted METs (45-105%) across all standing and walking activities. Conclusion: HF specific accelerometer intensity thresholds for inactivity and MVPA are lower than previously published thresholds based on healthy adults, due to lower resting metabolic rate and greater energy expenditure during daily living activities for HF patients. Trial registration: Clinical trials.gov NCT03659877, retrospectively registered on September 6th 2018.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.This study was undertaken as part of a PhD, which was funded by a University of Exeter Postgraduate Studentship Grant. The funders were not involved in design of the study, data collection, analysis, and interpretation of data, and in writing the manuscript.published version, accepted versio

Primary skeletal muscle myoblasts from chronic heart failure patients exhibit loss of anti-inflammatory and proliferative activity

BACKGROUND: Peripheral skeletal muscle wasting is a common finding with adverse effects in chronic heart failure (HF). Whereas its clinical relevance is beyond doubt, the underlying pathophysiological mechanisms are not yet fully elucidated. We aimed to introduce and characterize the primary culture of skeletal muscle cells from individual HF patients as a supportive model to study this muscle loss. METHODS AND RESULTS: Primary myoblast and myotubes cultures were successfully propagated from the m. vastus lateralis of 6 HF patients with reduced ejection fraction (HFrEF; LVEF <45 %) and 6 age and gender-matched healthy donors. HFrEF cultures were not different from healthy donors in terms of morphology, such as myoblast size, shape and actin microfilament. Differentiation and fusion indexes were identical between groups. Myoblast proliferation in logarithmic growth phase, however, was attenuated in the HFrEF group (p = 0.032). In addition, HFrEF myoblasts are characterized by a reduced TNFR2 expression and IL-6 secretion (p = 0.017 and p = 0.016; respectively). CONCLUSION: Biopsy derived primary skeletal muscle myoblasts of HFrEF patients produce similar morphological and myogenic differentiation responses as myoblasts of healthy donors, though demonstrate loss of anti-inflammatory and proliferative activity

Molecular and cellular mechanisms of skeletal muscle atrophy: an update

Skeletal muscle atrophy is defined as a decrease in muscle mass and occurs when protein degradation exceeds protein synthesis. Potential triggers of muscle wasting are long-term immobilization, malnutrition, severe burns, aging as well as various serious and often chronic diseases, such as chronic heart failure, obstructive lung disease, renal failure, AIDS, sepsis, immune disorders, cancer and dystrophies. Interestingly, a cooperation between several pathophysiological factors, including inappropriately adapted anabolic (e.g. growth hormone, insulin-like growth factor 1) and catabolic proteins (e.g. tumor necrosis factor alpha, myostatin), may tip the balance towards muscle-specific protein degradation through activation of the proteasomal and autophagic systems or the apoptotic pathway. Based on the current literature, we present an overview of the molecular and cellular mechanisms that contribute to muscle wasting. We also focus on the multi-facetted therapeutic approach that is currently employed to prevent the development of muscle wasting and to counteract its progression. This approach includes adequate nutritional support, implementation of exercise training and possible pharmacological compounds