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- Ashar, Foram N., et al.
(author)
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A comprehensive evaluation of the genetic architecture of sudden cardiac arrest
- 2018
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In: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 39:44, s. 3961-
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Journal article (peer-reviewed)abstract
- Aims: Sudden cardiac arrest (SCA) accounts for 10% of adult mortality in Western populations. We aim to identify potential loci associated with SCA and to identify risk factors causally associated with SCA.Methods and results: We carried out a large genome-wide association study (GWAS) for SCA (n = 3939 cases, 25 989 non-cases) to examine common variation genome-wide and in candidate arrhythmia genes. We also exploited Mendelian randomization (MR) methods using cross-trait multi-variant genetic risk score associations (GRSA) to assess causal relationships of 18 risk factors with SCA. No variants were associated with SCA at genome-wide significance, nor were common variants in candidate arrhythmia genes associated with SCA at nominal significance. Using cross-trait GRSA, we established genetic correlation between SCA and (i) coronary artery disease (CAD) and traditional CAD risk factors (blood pressure, lipids, and diabetes), (ii) height and BMI, and (iii) electrical instability traits (QT and atrial fibrillation), suggesting aetiologic roles for these traits in SCA risk.Conclusions: Our findings show that a comprehensive approach to the genetic architecture of SCA can shed light on the determinants of a complex life-threatening condition with multiple influencing factors in the general population. The results of this genetic analysis, both positive and negative findings, have implications for evaluating the genetic architecture of patients with a family history of SCA, and for efforts to prevent SCA in high-risk populations and the general community.
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| 2. |
- Kiguchi, Tekeyuki, et al.
(author)
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Out-of-hospital cardiac arrest across the World : First report from the International Liaison Committee on Resuscitation (ILCOR).
- 2020
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In: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 152, s. 39-49
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Journal article (peer-reviewed)abstract
- BACKGROUND: Since development of the Utstein style recommendations for the uniform reporting of cardiac arrest, increasing numbers of national and regional out-of-hospital cardiac arrest (OHCA) registries have been established worldwide. The International Liaison Committee on Resuscitation (ILCOR) created the Research and Registries Working Group and aimed to systematically report data collected from these registries.METHODS: We conducted two surveys of voluntarily participating national and regional registries. The first survey aimed to identify which core elements of the current Utstein style for OHCA were collected by each registry. The second survey collected descriptive summary data from each registry. We chose the data collected for the second survey based on the availability of core elements identified by the first survey.RESULTS: Seven national and four regional registries were included in the first survey and nine national and seven regional registries in the second survey. The estimated annual incidence of emergency medical services (EMS)-treated OHCA was 30.0-97.1 individuals per 100,000 population. The combined data showed the median age varied from 64 to 79 years and more than half were male in all 16 registries. The provision of bystander cardiopulmonary resuscitation (CPR) and bystander automated external defibrillator (AED) use was 19.1-79.0% in all registries and 2.0-37.4% among 11 registries, respectively. Survival to hospital discharge or 30-day survival after EMS-treated OHCA was 3.1-20.4% across all registries. Favorable neurological outcome at hospital discharge or 30 days after EMS-treated OHCA was 2.8-18.2%. Survival to hospital discharge or 30-day survival after bystander-witnessed shockable OHCA ranged from 11.7% to 47.4% and favorable neurological outcome from 9.9% to 33.3%.CONCLUSION: This report from ILCOR describes data on systems of care and outcomes following OHCA from nine national and seven regional registries across the world. We found variation in reported survival outcomes and other core elements of the current Utstein style recommendations for OHCA across nations and regions.
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| 3. |
- Nolte, I. M., et al.
(author)
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Genetic loci associated with heart rate variability and their effects on cardiac disease risk
- 2017
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Journal article (peer-reviewed)abstract
- Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (-0.74 < r(g) < -0.55) and blood pressure (-0.35 < r(g) < -0.20). These findings provide clinically relevant biological insight into heritable variation in vagal heart rhythm regulation, with a key role for genetic variants (GNG11, RGS6) that influence G-protein heterotrimer action in GIRK-channel induced pacemaker membrane hyperpolarization.
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