Genetics in heart failure:where are we headed?

Heart failure is a complex disease with many precipitating factors. Novel insights into the genetic background of heart failure have boosted new areas of research that gave rise to the concept of genetic predisposition for heart failure. Various genetic defects and variances have been identified and subsequently linked to the onset of or progression to heart failure. Nevertheless, our understanding of the genetic basis for heart failure is incomplete because we lack knowledge of the functionality of genetic variances. We also do not understand the impact of genetic variances in noncoding DNA because of logistic problems in performing whole-genome scans and difficulties in statistical evaluation of large amounts of data generated by the genetic boom. It is expected that in the future we will be able to overcome these problems and apply the knowledge gained by genetic analyses to target and optimize treatment.</p

Diabetes, Glycemic Control, and New-Onset Heart Failure in Patients With Stable Coronary Artery Disease: Data from the Heart and Soul Study

OBJECTIVE Diabetes is a predictor of both coronary artery disease (CAD) and heart failure. It is unknown to what extent the association between diabetes and heart failure is influenced by other risk factors for heart failure. RESEARCH DESIGN AND METHODS We evaluated the association of diabetes and A1C with incident heart failure in outpatients with stable CAD and no history of heart failure (average follow-up 4.1 years). RESULTS Of 839 participants, 200 had diabetes (23.8%). Compared with patients who did not have diabetes, those with diabetes had an increased risk of heart failure (hazard ratio [HR] 2.17 [95% CI 1.37-3.44]). Adjustment for risk factors for CAD (age, sex, race, smoking, physical inactivity, obesity, blood pressure, and LDL cholesterol), interim myocardial infarction, and myocardial ischemia did not alter the strength of the association between diabetes and heart failure. After inclusion also of other risk factors for heart failure (left ventricular ejection fraction, diastolic dysfunction, and C-reactive protein) and medication use, diabetes remained an independent predictor of heart failure (HR 3.34 [95% CI 1.65-6.76]; P = 0.001). Each 1% increase in A1C concentration was associated with a 36% increased HR of heart failure hospitalization (HR 1.36 [95% CI 1.17-1.58]). CONCLUSIONS In patients with stable CAD who are free from heart failure at baseline, diabetes and glycemic control are independent risk factors for new-onset heart failure. The mechanisms by which diabetes and hyperglycemia lead to heart failure deserve further study, as the association is independent of baseline functional assessment of ischemia, systolic and diastolic function, and interim myocardial infarction

Atherosclerosis in the circle of Willis: Spatial differences in composition and in distribution of plaques

AbstractBackground and aimsIntracranial atherosclerosis is one of the main causes of ischemic stroke. However, the characteristics of intracranial arteries and atherosclerosis have rarely been studied. Therefore, we systematically investigated atherosclerotic changes in all arteries of the Circle of Willis (CoW).MethodsSixty-seven CoWs obtained at autopsy from randomly chosen hospital patients (mean age, 67.3 ± 12.5 years), of which a total of 1220 segments were collected from 22 sites. Atherosclerotic plaques were classified according to the revised American Heart Association classification and were related to local vessel characteristics, such as the presence of an external and internal elastic lamina and the elastic fibre density of the media.Results181 out of the 1220 segments had advanced plaques (15%), which were mainly observed in large arteries such as the internal carotid, middle cerebral, basilar and vertebral artery. Only 11 out of 1220 segments (1%) showed complicated plaques (p < 0.001). Six of these were intraplaque hemorrhages (IPH) and observed only in patients who had cardiovascular-related events (p = 0.015). The frequency of characteristics such as the external elastic lamina and a high elastin fibre density in the media was most often associated with the vertebral artery. Only 3% (n = 33) of the CoW arteries contained calcification (p < 0.001), which were mostly observed in the vertebral artery (n = 13, 12%).ConclusionsAdvanced atherosclerotic plaques in the CoW are relatively scarce and mainly located in the 4 large arteries, and mostly characterized by an early and stable phenotype, a low calcific burden, and a low frequency of IPH

Predictive value of plasma galectin-3 levels in heart failure with reduced and preserved ejection fraction

Aims. Galectin-3 is an emerging biomarker which has been studied in relatively small heart failure (HF) cohorts with predominantly systolic HF. We studied the prognostic value of base-line galectin-3 in a large HF cohort, with preserved and reduced left ventricular ejection fraction (LVEF), and compared this to other biomarkers. Methods. We studied 592 HF patients who had been hospitalized for HF and were followed for 18 months. The primary end-point was a composite of all-cause mortality and HF hospitalization. Results. A doubling of galectin-3 levels was associated with a hazard ratio (HR) of 1.97 (1.62-2.42) for the primary outcome (P <0.001). After correction for age, gender, BNP, eGFR, and diabetes the HR was 1.38 (1.07-1.78; P = 0.015). Galectin-3 levels were correlated with higher IL-6 and CRP levels (P <0.002). Changes of galectin-3 levels after 6 months did not add prognostic information to the base-line value (n = 291); however, combining plasma galectin-3 and BNP levels increased prognostic value over either biomarker alone (ROC analysis, P <0.05). The predictive value of galectin-3 was stronger in patients with preserved LVEF (n = 114) compared to patients with reduced LVEF (P <0.001). Conclusions. Galectin-3 is an independent marker for outcome in HF and appears to be particularly useful in HF patients with preserved LVEF

Acknowledging Patient Heterogeneity in Economic Evaluation A Systematic Literature Review

Background and Objective Patient heterogeneity is the part of variability that can be explained by certain patient characteristics (e.g. age, disease stage). Population reimbursement decisions that acknowledge patient heterogeneity could potentially save money and increase population health. To date, however, economic evaluations pay only limited attention to patient heterogeneity. The objective of the present paper is to provide a comprehensive overview of the current knowledge regarding patient heterogeneity within economic evaluation of healthcare programmes. Methods A systematic literature review was performed to identify methodological papers on the topic of patient heterogeneity in economic evaluation. Data were obtained using a keyword search of the PubMed database and manual searches. Handbooks were also included. Relevant data were extracted regarding potential sources of patient heterogeneity, in which of the input parameters of an economic evaluation these occur, methods to acknowledge patient heterogeneity and specific concerns associated with this acknowledgement. Results A total of 20 articles and five handbooks were included. The relevant sources of patient heterogeneity (demographics, preferences and clinical characteristics) and the input parameters where they occurred (baseline risk, treatment effect, health state utility and resource utilization) were combined in a framework. Methods were derived for the design, analysis and presentation phases of an economic evaluation. Concerns related mainly to the danger of false-positive results and equity issues. Conclusion By systematically reviewing current knowledge regarding patient heterogeneity within economic evaluations of healthcare programmes, we provide guidance for future economic evaluations. Guidance is provided on which sources of patient heterogeneity to consider, how to acknowledge them in economic evaluation and potential concerns. The improved acknowledgement of patient heterogeneity in future economic evaluations may well improve the efficiency of healthcare

The attitude of Belgian social insurance physicians towards evidence-based practice and clinical practice guidelines

<p>Abstract</p> <p>Background</p> <p>Evidence-based medicine has broadened its scope and is starting to reach insurance medicine. Although still in its initial stages, physicians in the area of insurance medicine should keep up-to-date with the evidence on various diseases in order to correctly assess disability and to give appropriate advice about health care reimbursement. In order to explore future opportunities of evidence-based medicine to improve daily insurance medicine, there is a need for qualitative studies to better understand insurance physicians' perceptions of EBM. The present study was designed to identify the attitude of insurance physicians towards evidence-based medicine and clinical practice guidelines, and to determine their ability to access, retrieve and appraise the health evidence and the barriers for applying evidence to practice.</p> <p>Methods</p> <p>A cross-sectional survey study was carried out among all Dutch-speaking insurance physicians employed at one of the six Belgian social insurance sickness funds and at the National Institute of Disability and Health care Insurance (n = 224). Chi-square tests were used to compare nominal and ordinal variables. Student's t-tests, ANOVA, Mann-Whitney and Kruskal-Wallis were used to compare means of continuous variables for different groups.</p> <p>Results</p> <p>The response rate was 48.7%. The majority of respondents were positive towards evidence-based medicine and clinical practice guidelines. Their knowledge of EBM was rather poor. Perceived barriers for applying evidence to practice were mainly time and lack of EBM skills.</p> <p>Conclusion</p> <p>Although the majority of physicians were positive towards EBM and welcomed more guidelines, the use of evidence and clinical practice guidelines in insurance medicine is low at present. It is in the first place important to eradicate the perceived inertia which limits the use of EBM and to further investigate the EBM principles in the context of insurance medicine. Available high-quality evidence-based resources (at the moment mainly originating from other medical fields) need to be structured in a way that is useful for insurance physicians and global access to this information needs to be ensured.</p

Polarization-independent filters for luminescent solar concentrators

The efficiency of luminescent solar concentrators could be enhanced by use of wavelength-selective filters, reducing the amount of luminescent light lost. To accomplish this, polarization-independent filters with reflectivity >97% were made by combining layers of cholesteric liquid crystals, either a right- with a left-handed layer, or two right-handed layers with a half-lambda waveplate. Normal cholesteric filters have a reflection bandwidth which is narrower than the spectral and angular range of the luminescent emission. The reflection band is broadened from 80 to 200 nm by employing a pitch gradient in the cholesteric layer. The measured transmission bands compare well with calculations

Особенности личности страдающих гашишной зависимостью мужчин

Рассмотрен личностный профиль мужчин, страдающих гашишной зависимостью. Показано, что длительное употребление наркотика ведет к формированию шизотипической личности.The personality profile of men with hashish addiction is described. Prolonged use of drugs is shown to cause formation of schizothymic personality