| 1. |
- Andreasen, Laura, et al.
(författare)
-
Brugada syndrome-associated genetic loci are associated with J-point elevation and an increased risk of cardiac arrest
- 2018
-
Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 9:JUL
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: A previous genome-wide association study found three genetic loci, rs9388451, rs10428132, and rs11708996, to increase the risk of Brugada Syndrome (BrS). Since the effect of these loci in the general population is unknown, we aimed to investigate the effect on electrocardiogram (ECG) parameters and outcomes in the general population. Materials and Methods: A cohort of 6,161 individuals (median age 45 [interquartile range (IQR) 40-50] years, 49% males), with available digital ECGs, was genotyped and subsequently followed for a median period of 13 [IQR 12.6-13.4] years. Data on outcomes were collected from Danish administrative healthcare registries. Furthermore, ~400,000 persons from UK Biobank were investigated for associations between the three loci and cardiac arrest/ventricular fibrillation (VF). Results: Homozygote carriers of the C allele in rs6800541 intronic to SCN10A had a significantly larger J-point elevation (JPE) compared with wildtype carriers (11 vs. 6 μV, P < 0.001). There was an additive effect of carrying multiple BrS-associated risk alleles with an increased JPE in lead V1. None of the BrS-associated genetic loci predisposed to syncope, atrial fibrillation, or total mortality in the general Danish population. The rs9388451 genetic locus adjacent to the HEY2 gene was associated with cardiac arrest/VF in an analysis using the UK Biobank study (odds ratio = 1.13 (95% confidence interval: 1.08-1.18), P = 0.006). Conclusions: BrS-associated risk alleles increase the JPE in lead V1 in an additive manner, but was not associated with increased mortality or syncope in the general population of Denmark. However, the HEY2 risk allele increased the risk of cardiac arrest/VF in the larger population study of UK Biobank indicating an important role of this common genetic locus.
|
|
| 2. |
- Skov, Morten W., et al.
(författare)
-
Risk prediction of atrial fibrillation based on electrocardiographic interatrial block
- 2018
-
Ingår i: Journal of the American Heart Association. - 2047-9980. ; 7:11
-
Tidskriftsartikel (refereegranskat)abstract
- Background--The electrocardiographic interatrial block (IAB) has been associated with atrial fibrillation (AF). We aimed to test whether IAB can improve risk prediction of AF for the individual person. Methods and Results--Digital ECGs of 152 759 primary care patients aged 50 to 90 years were collected from 2001 to 2011. We identified individuals with P-wave ≥120 ms and the presence of none, 1, 2, or 3 biphasic P-waves in inferior leads. Data on comorbidity, medication, and outcomes were obtained from nationwide registries. We observed a dose-response relationship between the number of biphasic P-waves in inferior leads and the hazard of AF during follow-up. Discrimination of the 10-year outcome of AF, measured by time-dependent area under the curve, was increased by 1.09% (95% confidence interval 0.43-1.74%) for individuals with cardiovascular disease at baseline (CVD) and 1.01% (95% confidence interval 0.40-1.62%) for individuals without CVD, when IAB was added to a conventional risk model for AF. The highest effect of IAB on the absolute risk of AF was observed in individuals aged 60 to 70 years with CVD. In this subgroup, the 10-year risk of AF was 50% in those with advanced IAB compared with 10% in those with a normal P-wave. In general, individuals with advanced IAB and no CVD had a higher risk of AF than patients with CVD and no IAB. Conclusions--IAB improves risk prediction of AF when added to a conventional risk model. Clinicians may consider monitoring patients with IAB more closely for the occurrence of AF, especially for high-risk subgroups.
|
|
