| 1. |
- Nolte, I. M., et al.
(författare)
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Genetic loci associated with heart rate variability and their effects on cardiac disease risk
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)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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| 2. |
- Andersson, C, et al.
(författare)
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Triple specificity of ZnT8 autoantibodies in relation to HLA and other islet autoantibodies in childhood and adolescent type 1 diabetes
- 2013
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Ingår i: Pediatric Diabetes. - : Wiley-Blackwell. - 1399-543X .- 1399-5448. ; 14:2, s. 97-105
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Tidskriftsartikel (refereegranskat)abstract
- Andersson C, Vaziri-Sani F, Delli AJ, Lindblad B, Carlsson A, Forsander G, Ludvigsson J, Marcus C, Samuelsson U, Ivarsson SA, Lernmark A, Elding Larsson H, the BDD Study group. Triple specificity of ZnT8 autoantibodies in relation to HLA and other islet autoantibodies in childhood and adolescent type 1 diabetes. Pediatric Diabetes 2013: 14: 97-105. Objective To establish the diagnostic sensitivity of and the relationships between autoantibodies to all three Zinc transporter 8 (Zinc transporter 8 autoantibody to either one, two, or all three amino acid variants at position 325, ZnT8A) variants to human leukocyte antigen (HLA)-DQ and to autoantibodies to glutamic acid decarboxylase (GADA), insulinoma-associated protein 2 (IA-2A), and insulin (IAA). Methods We analyzed 3165 patients with type 1 diabetes (T1D) in the Better Diabetes Diagnosis study for HLA-DQ genotypes and all six autoantibodies (ZnT8RA, arginine 325 Zinc transporter 8 autoantibody; ZnT8WA, tryptophan 325 Zinc transporter 8 autoantibody; ZnT8QA, glutamine 325 Zinc transporter 8 autoantibody; GADA, IA-2A, and IAA). Results ZnT8A was found in 65% of the patients and as many as 108 of 3165 (3.4%) had 13 ZnT8A alone. None had ZnT8QA alone. Together with GADA (56%), IA-2A (73%), and IAA (33%), 93% of the T1D patients were autoantibody positive. All three ZnT8A were less frequent in children below 2 yr of age (pandlt;0.0001). All three ZnT8A were associated with DQA1-B1*X-0604 (DQ6.4) and DQA1-B1*03-0302 (DQ8). ZnT8WA and ZnT8QA were negatively associated with DQA1-B1*05-02 (DQ2). Conclusions Analysis of ZnT8A increased the diagnostic sensitivity of islet autoantibodies for T1D as only 7% remained islet autoantibody negative. The association between DQ6.4 and all three ZnT8A may be related to ZnT8 antigen presentation by the DQ6.4 heterodimer.
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| 3. |
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| 4. |
- ter Haar, C. Cato, et al.
(författare)
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Difference vectors to describe dynamics of the ST segment and the ventricular gradient in acute ischemia
- 2013
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Ingår i: Journal of Electrocardiology. - : Elsevier BV. - 1532-8430 .- 0022-0736. ; 46:4, s. 302-311
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Tidskriftsartikel (refereegranskat)abstract
- Background: The ECG is important in the diagnosis and triage of the acute coronary syndrome (ACS), especially in the hyperacute phase, the "golden hours," during which myocardial salvage possibilities are largest. An important triaging decision to be taken is whether or not a patient requires primary PCI, for which, as mentioned in the guidelines, the presence of an ST elevation (STE) pattern in the ECG is a major criterion. However, preexisting non-zero ST amplitudes (diagnostic, but also non-diagnostic) can obscure or even preclude this diagnosis. Methods: In this study, we investigated the potential diagnostic possibilities of ischemia detection by means of changes in the ST vector, Delta ST, and changes in the VG (QRST integral) vector, Delta VG. We studied the vectorcardiograms (VCGs) synthesized of the ECGs of 84 patients who underwent elective PTCA. Mean +/- SD balloon occlusion times were 260 +/- 76 s. The ECG ischemia diagnosis (ST elevation, STE, or non-ST-elevation, NSTE), magnitudes and orientations of the ST and VG vectors, and the differences Delta ST and Delta VG with the baseline ECG were measured after 3 min of balloon occlusion. Results: Planar angles between the Delta ST and Delta VG vectors were 14.9 +/- 14.0 degrees. Linear regression of Delta VG on Delta ST yielded Delta VG = 324. Delta ST (r = 0.85; P < 0.0001, Delta ST in mV). We adopted Delta ST > 0.05 mV, and the corresponding Delta VG > 16.2 mV.ms as ischemia thresholds. The classical criteria characterized the ECGs of 46/84 (55%) patients after 3 min of occlusion as STE ECGs. Combined application of the Delta ST and Delta VG criteria identified 73/84 (87%) of the patients as ischemic. Conclusion: Differential diagnosis by Delta ST and Delta VG (requiring an earlier made non-ischemic baseline ECG) could dramatically improve ECG guided detection of patients who urgently require catheter intervention. (C) 2013 Elsevier Inc. All rights reserved.
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| 5. |
- Swenne, Christine Leo, et al.
(författare)
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Peri-operative glucose control and development of surgical wound infections in patients undergoing coronary artery bypass graft
- 2005
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Ingår i: Journal of Hospital Infection. - : Elsevier BV. - 0195-6701 .- 1532-2939. ; 61:3, s. 201-212
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood glucose following coronary artery bypass graft (CABG) is associated with an increased risk of surgical wound infection (SWI). It is unclear whether hyperglycaemia, the diabetic state, the longstanding vascular effects of diabetes, or the systematic inflammatory response confers the increased vulnerability to SWI. This study was designed to examine the significance of postoperative blood glucose control as a risk factor for SWI after vein graft harvesting on the leg and sternotomy. Patients with and without diabetes had a CABG within 60 days to be eligible. The present study was part of a larger protocol investigating SWI following CABG in a total of 374 patients. Potential risk factors, duration of diabetes, pre-operative glycated haemoglobin (HbA1c) and presence of long-term complications were recorded. All patient records were reviewed retrospectively to record 10% glucose infusions during the operation, and blood glucose concentrations and insulin therapy on postoperative days 0, 1 and 2. Patients were contacted by telephone 30 and 60 days after surgery and interviewed in accordance with a questionnaire about symptoms and signs of wound infection. In the present study, it was not possible to separate the effect of diabetes as a risk factor for SWI from that of hyperglycaemia. However, in the subgroup of patients without a pre-operative diagnosis of diabetes, increased blood glucose concentrations during postoperative days 0, 1 and 2 was associated with an increased risk of mediastinitis.
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