Multi-ethnic genome-wide association study for atrial fibrillation

Atrial fibrillation (AF) affects more than 33 million individuals worldwide and has a complex heritability. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF

Związek między stężeniem adiponektyny w surowicy i zwapnieniowym zwężeniem zastawki aortalnej

Background: Adiponectin, an adipose tissue derived cytokine, is known to have antiatherogenic and anti-inflammatory effectson endothelial cells and macrophages. Calcific aortic valve disease has a similar physiopathology to atherosclerosis.Aim: To investigate the relationship between adiponectin and calcific aortic valve disease.Methods: The study group consisted of 58 patients with calcific aortic stenosis and 24 healthy controls. Aortic stenosis patientswere divided into three groups according to their valvular areas: mild (n = 11), moderate (n = 25), and severe (n = 22).Serum adiponectin levels and other biochemical parameters were measured.Results: The aortic stenosis and control group were similar in terms of age, gender and cardiovascular risk factors. Adiponectinmedian values did not differ significantly between two groups (2.19 μg/mL [1.43–3.18], 1.79 μg/mL [1.34–3.42] aorticstenosis and control group, respectively; p = 0.7). Aortic stenosis patients were divided into three groups according to theirvalvular area as mild, moderate and severe. There were no differences when we compared adiponectin levels among thosegroups (mild: 2.10 μg/mL [1.47–3.31], moderate: 2.13 μg/mL [1.44–2.91], severe: 2.65 μg/mL [1.28–3.43]; p = 0.67). Age(r = 0.26, p = 0.045) and aspartate aminotransferase (r = 0.28, p = 0.04) had positive correlations with adiponectin; whilewhite blood cell count (r = –0.32, p = 0.015), fasting blood glucose (r = –0.29, p = 0.03), haemoglobin (r = –0.27, p = 0.04)and triglyceride levels (r = –0.41, p = 0.002) had negative correlations.Conclusions: In our study, we did not find a relationship between adiponectin levels and calcific aortic valve disease.Wstęp: Adiponektyna, cytokina produkowana przez tkankę tłuszczową, ma działanie przeciwmiażdżycowe i przeciwzapalnew stosunku do komórek śródbłonka i makrofagów. Zwapnienie zastawki aorty ma podobny patomechanizm jak miażdżyca.Cel: Celem niniejszej pracy było zbadanie zależności między stężeniem adiponektyny a stopniem zwapnieniowego zwężeniaaorty.Metody: Do badania włączono 58 chorych ze zwapnieniowym zwężeniem aorty i 24 zdrowe osoby stanowiące grupę kontrolną.Chorych ze stenozą aortalną podzielono na 3 grupy w zależności od stopnia zwężenia: osoby z łagodnym (n = 11),umiarkowanym (25) i ciężkim (n = 22) zwężeniem zastawki aortalnej. U wszystkich uczestników badania zmierzono stężenieadiponektyny w surowicy oraz inne parametry biochemiczne.Wyniki: Rozkład wieku, płci i czynników ryzyka sercowo-naczyniowego był podobny w grupie ze stenozą aortalną i w grupiekontrolnej. Porównanie mediany stężenia adiponektyny również nie wykazało istotnej różnicy między grupami [odpowiednio2,19 μg/ml (1,43–3,18); 1,79 μg/ml (1,34–3,42); p = 0,7]. Chorych ze stenozą aortalną podzielono na trzy grupy — z lekkim,umiarkowanym lub ciężkim zwężeniem — w zależności od pola powierzchni ujścia zastawki. Nie stwierdzono różnic, porównującstężenia adiponektyny w tych trzech grupach [łagodne zwężenie: 2,10 μg/ml (1,47–3,31), umiarkowane: 2,13 μg/ml(1,44–2,91), ciężkie: 2,65 μg/ml (1,28–3,43); p = 0,67]. Wiek (r = 0,26; p = 0,045) i stężenie aminotransferazy asparaginianowej(r = 0,28; p = 0,04) korelowały dodatnio ze stężeniem adiponektyny, natomiast w przypadku liczby krwinekbiałych (r = –0,32; p = 0,015), glikemii na czczo (r = –0,29; p = 0,03) oraz stężenia hemoglobiny (r = –0,27; p = 0,04)i triglicerydów (r = –0,41; p = 0,002) wykazano korelację ujemną.Wnioski: W niniejszym badaniu nie wykazano związku stężenia adiponektyny z zwapnieniowym zwężeniem aorty ani zestopniem zwężenia

Which is the best for the warfarin monitoring: Following up by fixed or variable physician?

OBJECTIVE: Warfarin therapy has some difficulties in terms of close monitoring and dosage. This study aims to evaluate the effect of same-fixed versus different-variable physician-based monitoring of warfarin therapy on treatment quality and clinical end-points. METHODS: A total of 625 consecutive patients requiring warfarin treatment were enrolled at seven centers. INR values of the patients measured at each visit and registered to hospital database were recorded. Time in therapeutic range (TTR) was calculated using linear interpolation method (Rosendaal’s method). A TTR value of ≥65% was considered as effective warfarin treatment. If a patient was evaluated by the same-fixed physician at each INR visit, was categorized into the same-physician (SP) group. In contrast, if a patient was evaluated by different-variable physicians at each INR visit, was categorized into variable physician (VP) group. Enrolled patients were followed up for bleeding and embolic events. RESULTS: One hundred and fifty-six patients (24.9%) were followed by SP group, 469 (75.1%) patients were followed by VP group. Median TTR value of the VP group was lower than that of SP group (56.2% vs. 65.1%, respectively, p=0.009). During median 25.5 months (9–36) of follow-up, minor bleeding, major bleeding and cerebral embolic event rates were higher in VP group compared to SP group (p<0.001, p=0.023, p<0.001, respectively). In multivariate analysis, INR monitoring by VP group was found to be an independent predictor of increased risk of bleeding events (OR 2.55, 95% CI 1.64–3.96, p<0.001) and embolism (OR 3.42, 95% CI 1.66–7.04, p=0.001). CONCLUSION: INR monitoring by same physician was associated with better TTR and lower rates of adverse events during follow-up. Hence, it is worth encouraging an SP-based outpatient follow-up system at least for where warfarin therapy is the only choice