| 1. |
- Ay, Hakan, et al.
(författare)
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Pathogenic Ischemic Stroke Phenotypes in the NINDS-Stroke Genetics Network
- 2014
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Ingår i: Stroke. - 0039-2499. ; 45:12, s. 3589-3596
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: NINDS (National Institute of Neurological Disorders and Stroke)-SiGN (Stroke Genetics Network) is an international consortium of ischemic stroke studies that aims to generate high-quality phenotype data to identify the genetic basis of pathogenic stroke subtypes. This analysis characterizes the etiopathogenetic basis of ischemic stroke and reliability of stroke classification in the consortium. METHODS: Fifty-two trained and certified adjudicators determined both phenotypic (abnormal test findings categorized in major pathogenic groups without weighting toward the most likely cause) and causative ischemic stroke subtypes in 16954 subjects with imaging-confirmed ischemic stroke from 12 US studies and 11 studies from 8 European countries using the web-based Causative Classification of Stroke System. Classification reliability was assessed with blinded readjudication of 1509 randomly selected cases. RESULTS: The distribution of pathogenic categories varied by study, age, sex, and race (P<0.001 for each). Overall, only 40% to 54% of cases with a given major ischemic stroke pathogenesis (phenotypic subtype) were classified into the same final causative category with high confidence. There was good agreement for both causative (κ 0.72; 95% confidence interval, 0.69-0.75) and phenotypic classifications (κ 0.73; 95% confidence interval, 0.70-0.75). CONCLUSIONS: This study demonstrates that pathogenic subtypes can be determined with good reliability in studies that include investigators with different expertise and background, institutions with different stroke evaluation protocols and geographic location, and patient populations with different epidemiological characteristics. The discordance between phenotypic and causative stroke subtypes highlights the fact that the presence of an abnormality in a patient with stroke does not necessarily mean that it is the cause of stroke.
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| 2. |
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| 3. |
- Engström, Gunnar, et al.
(författare)
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The Swedish CArdioPulmonary BioImage Study : objectives and design
- 2015
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 278:6, s. 645-659
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Tidskriftsartikel (refereegranskat)abstract
- Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.
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| 4. |
- Engström, Karin, et al.
(författare)
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Hazards with electrocautery-induced decomposition of fatty acids - in view of lipid embolization
- 2010
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Ingår i: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 44:5, s. 307-312
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. Electrocautery is an appreciated surgical tool, which however, generates immense heat and fat-tissue melting. In cardiac surgery, liquefied fat collects on the surface of blood in the pericardial cavity and becomes aspirated by the heart-lung machine for aortic recycling. Deposits seen in the brain microcirculation after surgery are caused by lipid embolism. This study investigates lipid chemistry, whether heat from electrocautery generates fatty-acid fragmentation and decomposition. Design. Pericardial fat tissue was sampled from cardiac-surgery patients and from piglets. The human tissue was exposed to electrocautery, or to fixed temperatures in an in vitro model. Fatty-acid decomposition was explored by solid-phase microextraction gas chromatography and the distribution of fatty acids was measured. Results. Fatty-acid decomposition demonstrated a temperature-effect relationship (p=0.007). At 350 degrees C the proportion of polyunsaturated fatty acids became heavily reduced or were abolished (p=0.016). Electrocautery resulted in similar changes. Conclusions. Electrocautery induces a profound fatty-acid fragmentation to form short-chained compounds. The chemical and toxic nature of these compounds remains to be determined, including their clinical implications at blood recycling in cardiac surgery.
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| 5. |
- Johansson, Bengt, et al.
(författare)
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Evaluation of hyaluronan and calcifications in stenotic and regurgitant aortic valves.
- 2011
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Ingår i: European Journal of Cardio-Thoracic Surgery. - : Elsevier. - 1010-7940 .- 1873-734X. ; 39:1, s. 27-32
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Hyaluronan (HA) is a major component of the interstitium and has been observed in normal heart valves. The function of HA in heart valves is unknown but contribution to biomechanical function has been proposed. The purpose of this investigation was to study the distribution of HA in relation to calcifications in diseased human aortic valves. Methods: Human aortic valves were collected at aortic valve replacement, of whom nine patients had regurgitation and 13 stenotic disease. The valves were decalcified and stained for the visualisation of HA. The specimens were macroscopically evaluated for magnitude of calcification using image analysis. The microscopic amount and distribution of HA and calcifications were semiquantitatively evaluated using histochemistry. Results: The overall HA staining showed an inverse relationship against the magnitude of observed valve calcifications (p<0.001) and type of disease (p=0.014). Multiple-group comparison revealed regionally reduced HA staining in diffuse and heavy calcified regions inside the valve (both p<0.001) compared with normal-structured parts of the valve. HA was concentrated on the ventricular side of the valve (p=0.002). Conclusions: The content of HA was reduced in calcified aortic valves and had a heterogeneous distribution, potentially contributing to poor valve function. HA may also be involved in the pathophysiological process in degenerative aortic stenosis.
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| 6. |
- Jönsson, Karl, et al.
(författare)
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Glomerular filtration rate in patients with atrial fibrillation on warfarin treatment: A subgroup analysis from the AURICULA registry in Sweden.
- 2011
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Ingår i: Thrombosis Research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 128:4, s. 341-345
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Numerous associations between chronic kidney disease (CKD) and atrial fibrillation (AF) have been reported and patients with CKD on anticoagulation therapy have an increased risk of bleeding. Currently, new anticoagulant agents are emerging in clinical practice, some of which are excreted by the kidneys. The proportion of AF patients on anticoagulant treatment with reduced renal function is, however, unknown. MATERIALS AND METHODS: Using AURICULA, a Swedish registry for anticoagulation, estimated glomerular filtration rate (eGFR) was investigated in AF patients on warfarin treatment (n=2,603). The study group was compared with a healthy sample from the population (n=2,261). Two different creatinine prediction equations were used for calculating eGFR: the Lund-Malmö (LM) and MDRD Study equation. RESULTS: The fraction of AF patients with eGFR <30 and <45ml/min/1.73m(2) were 8.1% and 22.9% with the LM and 4.3% and 16.3% with the MDRD equation, respectively, and significantly higher than corresponding values in the reference population. GFR decreased with increasing age, where 11.4% and 5.6% of AF patients aged≥75years had eGFR <30ml/min/1.73m(2) according to the LM and MDRD equations, respectively. CONCLUSIONS: Severe renal impairment is common among AF patients on anticoagulant treatment with warfarin, especially at higher ages. Monitoring of renal function should be implemented in clinical practice for AF patients treated with new anticoagulants eliminated by the kidneys.
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| 7. |
- Lövkvist, Håkan, et al.
(författare)
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A large-sample assessment of possible association between ischaemic stroke and rs12188950 in the PDE4D gene
- 2012
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 20:7, s. 783-789
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Tidskriftsartikel (refereegranskat)abstract
- Previous reports have shown ambiguous findings regarding the possible associations between ischaemic stroke (IS) and single nucleotide polymorphisms (SNPs) in the phosphodiesterase 4D (PDE4D) gene region. The SNP rs12188950 (or SNP45) has often been studied in this context. We performed a multi-centre study involving a large sample of 2599 IS patients and 2093 control subjects from the south and west regions of Sweden to replicate previous studies regarding IS risk and rs12188950. Subjects from Lund Stroke Register (LSR), Malmo Diet and Cancer Study (MDC) and Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) were enroled. Subgroups of participants with hypertension and participants <55 years of age, as well as the TOAST subgroups large vessel disease, small vessel disease and cardioembolism, were also assessed. Univariate odds ratios (ORs) and ORs controlling for hypertension, diabetes and current smoking were calculated. We additionally performed a meta-analysis including 10 500 patients and 10 102 control subjects from 17 publications (including the present study). When assessing pooled data from LSR, MDC and SAHLSIS we obtained no association between IS and rs12188950 for all participants (OR=0.93; 95% confidence interval (CI): 0.83-1.05). Significant associations were not found for hypertensive participants or participants with age <55, or when separately evaluating patients from the three different TOAST subgroups. The meta-analysis showed no significant overall estimate (OR=0.96; 95% CI: 0.89-1.04) with significant heterogeneity for random effect (P=0.042). No effect from rs12188950 on IS was found from either our pooled multi-centre data or the performed meta-analysis. We did not find any association between the examined subgroups and rs12188950 either. European Journal of Human Genetics (2012) 20, 783-789; doi: 10.1038/ejhg.2012.4; published online 25 January 2012
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| 8. |
- Lövkvist, Håkan, et al.
(författare)
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Are 25 SNPs from the CARDIoGRAM study associated with ischaemic stroke?
- 2013
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Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101. ; 20:9, s. 1284-1291
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: The Coronary Artery Disease Genome-Wide Replication and Meta-Analysis Study (CARDIoGRAM) reported 25 single-nucleotide polymorphisms (SNPs) on 15 chromosomes to be associated with coronary artery disease (CAD) risk. Because common vascular risk factors are shared between CAD and ischaemic stroke (IS), these SNPs may also be related to IS overall or one or more of its pathogenetic subtypes. Methods: We performed a candidate gene study comprising 3986 patients with IS and 2459 control subjects. The 25 CAD-associated SNPs reported by CARDIoGRAM were examined by allelic association analysis including logistic regression. Weighted and unweighted genetic risk scores (GRSs) were also compiled and likewise analysed against IS. We furthermore considered the IS main subtypes large-vessel disease (LVD), small-vessel disease and cardioembolic stroke [according to Trial of Org 10172 in Acute Stroke Treatment (TOAST)] separately. Results: SNP rs4977574 on chromosome 9p21.3 was associated with overall IS [odds ratio (OR) = 1.12; 95% confidence interval (CI): 1.04-1.20; P = 0.002] as well as LVD (OR = 1.36; 95% CI: 1.13-1.64; P = 0.001). No other SNP was significantly associated with IS or any of its main subtypes. Analogously, the GRSs did not show any noticeable effect. Conclusions: Besides the previously reported association with SNPs on chromosome 9p21, this study did not detect any significant association between IS and CAD-susceptible genetic variants. Also, GRSs compiled from these variants did not predict IS or any pathogenetic IS subtype, despite a total sample size of 6445 participants.
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| 9. |
- Aaltonen, H. Laura, et al.
(författare)
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Airspace dimension assessment with nanoparticles as a proposed biomarker for emphysema
- 2021
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Ingår i: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 76:10, s. 1040-1043
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Tidskriftsartikel (refereegranskat)abstract
- Airspace dimension assessment with nanoparticles (AiDA) is a novel method to measure distal airspace radius non-invasively. In this study, AiDA radii were measured in 618 individuals from the population-based Swedish CArdiopulmonary BioImaging Study, SCAPIS. Subjects with emphysema detected by computed tomography were compared to non-emphysematous subjects. The 47 individuals with mainly mild-to-moderate visually detected emphysema had significantly larger AiDA radii, compared with non-emphysematous subjects (326±48 μm vs 291±36 μm); OR for emphysema per 10 μm: 1.22 (1.13-1.30, p<0.0001). Emphysema according to CT densitometry was similarly associated with larger radii compared with non-emphysematous CT examinations (316±41 μm vs 291 μm±26 μm); OR per 10 μm: 1.16 (1.08-1.24, p<0.0001). The results are in line with comparable studies. The results show that AiDA is a potential biomarker for emphysema in individuals in the general population.
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| 10. |
- Abdollahpur, Mostafa, et al.
(författare)
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A subspace projection approach to quantify respiratory variations in the f-wave frequency trend
- 2022
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Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: The autonomic nervous system (ANS) is known as a potent modulator of the initiation and perpetuation of atrial fibrillation (AF), hence information about ANS activity during AF may improve treatment strategy. Respiratory induced ANS variation in the f-waves of the ECG may provide such information. Objective: This paper proposes a novel approach for improved estimation of such respiratory induced variations and investigates the impact of deep breathing on the f-wave frequency in AF patients. Methods: A harmonic model is fitted to the f-wave signal to estimate a high-resolution f-wave frequency trend, and an orthogonal subspace projection approach is employed to quantify variations in the frequency trend that are linearly related to respiration using an ECG-derived respiration signal. The performance of the proposed approach is evaluated and compared to that of a previously proposed bandpass filtering approach using simulated f-wave signals. Further, the proposed approach is applied to analyze ECG data recorded for 5 min during baseline and 1 min deep breathing from 28 AF patients from the Swedish cardiopulmonary bioimage study (SCAPIS). Results: The simulation results show that the estimates of respiratory variations obtained using the proposed approach are more accurate than estimates obtained using the previous approach. Results from the analysis of SCAPIS data show no significant differences between baseline and deep breathing in heart rate (75.5 ± 22.9 vs. 74 ± 22.3) bpm, atrial fibrillation rate (6.93 ± 1.18 vs. 6.94 ± 0.66) Hz and respiratory f-wave frequency variations (0.130 ± 0.042 vs. 0.130 ± 0.034) Hz. However, individual variations are large with changes in heart rate and atrial fibrillatory rate in response to deep breathing ranging from -9% to +5% and -8% to +6%, respectively and there is a weak correlation between changes in heart rate and changes in atrial fibrillatory rate ( r = 0.38, p < 0.03). Conclusion: Respiratory induced f-wave frequency variations were observed at baseline and during deep breathing. No significant changes in the magnitude of these variations in response to deep breathing was observed in the present study population.
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