Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

Differences in classification of COPD patients into risk groups A-D: a cross-sectional study

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease proposed in 2011 a new system to classify chronic obstructive pulmonary disease (COPD) patients into risk groups A-D, which considers symptoms and future exacerbation risk to grade disease severity. The aim of this study was to investigate the agreement between COPD risk group classifications using COPD assessment test (CAT) or modified Medical Research Council (mMRC) and severity grades or past-year exacerbations. Furthermore, physical activity across risk groups was examined. METHODS: 87 patients with stable COPD were classified into risk groups A-D. CAT and mMRC were completed. Severity grades I-IV were determined using spirometry and the number of past-year exacerbations was recorded. To test the interrater agreement, Cohen’s Kappa was calculated. Daily physical activity was measured by the SenseWear Mini armband. RESULTS: Using CAT, 65.5% of patients were in high-symptom groups (B and D). With mMRC, only 37.9% were in B and D. Using severity grades, 20.7% of patients were in high-exacerbation risk groups (C and D). With past-year exacerbations, 9.2% were in C and D. Interrater agreement between CAT and mMRC (κ = 0.21) and between severity grades and past-year exacerbations (κ = 0.31) was fair. Daily steps were reduced in risk groups B and C + D compared to A (p < 0.01), using either classification. CONCLUSIONS: When classifying COPD patients into risk groups A-D, the use of CAT or mMRC and severity grades or past-year exacerbations does not provide equal results. Daily steps decreased with increasing COPD risk groups