| 1. |
- Friberg, Leif, et al.
(författare)
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High prevalence of atrial fibrillation among patients with ischemic stroke
- 2014
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Ingår i: Stroke. - 0039-2499 .- 1524-4628. ; 45:9, s. 2599-
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose-Atrial fibrillation (AF) is a common cause of devastating but potentially preventable stroke. Estimates of the prevalence of AF among patients with stroke vary considerably because of difficulties in detection of intermittent, silent AF. Better recognition of AF in this patient group may help to identify and offer protection to individuals at risk. Our aim was to determine the nationwide prevalence of AF among patients with ischemic stroke, as well as their use of oral anticoagulation. Methods-Cross-sectional study of unselected patients in cross-linked nationwide Swedish health registers. All 94 083 patients with a diagnosis of ischemic stroke in the nationwide stroke register Riks-Stroke between 2005 and 2010 were studied. Information about previously diagnosed AF, and comorbidity, was obtained from the nationwide Patient Register and cross-referenced with the national Drug Register containing data on all dispensed pharmacological prescriptions in Sweden. Results-Combination of data from Riks-Stroke and from the Patient Register showed that 31 428 (33.4%) patients with ischemic stroke had previously known, or newly diagnosed, AF. Of those, only 16.2% had received warfarin in a pharmacy within 6 months before stroke onset. After hospital discharge, only 35.0% of the survivors received warfarin within the first 3 months after discharge. The likelihood for underlying AF was strongly correlated to the CHA(2)DS(2)-VASC score, which is a point based scheme for assessment of stroke risk in AF but which also predicts likelihood of AF. In this scheme points are given for age, previous stroke or transient ischemic attack, hypertension, heart failure, diabetes, vascular disease and female sex. Conclusions-Access to nationwide register data shows that AF is more common among patients with ischemic stroke than those previously reported. Few patients with stroke and AF had anticoagulant treatment before the event, and few got it after the event. CHA(2)DS(2)-VASc could be a useful monitoring tool to intensify efforts to diagnose AF among patients with cryptogenic stroke.
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| 2. |
- Irewall, Anna-Lotta, 1987-
(författare)
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Recurrent events and secondary prevention after acute cerebrovascular disease
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background Patients who experience a stroke or transient ischemic attack (TIA) are at high risk of recurrent stroke, but little is known about temporal trends in unselected populations. Reports of low adherence to recommended treatments indicate a need for enhanced secondary preventive follow-up to achieve the full potential of evidence-based treatments. In addition, socioeconomic factors have been associated with poor health outcomes in a variety of contexts. Therefore, it is important to assess the implementation and results of secondary prevention in different socioeconomic groups.Aims The aims of this thesis were to assess temporal trends in ischemic stroke recurrence and evaluate the implementation and results of a nurse-led, telephone-based follow-up program to improve blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) levels after stroke/TIA.Methods In study I, we collected baseline data for unique patients with an ischemic stroke event between 1998 and 2009 (n=196 765) from the Swedish Stroke Register (Riksstroke). Recurrent ischemic stroke events within 1 year were collected from the Swedish National Inpatient Register (IPR) and the cumulative incidence was compared between four time periods using the Kaplan-Meier survival analysis and the logrank test. Implementation (study II) and 1-year results (study III-IV) for the secondary preventive follow-up were studied in the NAILED (Nurse-based Age-independent Intervention to Limit Evolution of Disease) study. Between 1 Jan 2010 and 31 Dec 2013, the baseline characteristics of consecutive patients admitted to Östersund Hospital for acute stroke or TIA were collected prospectively (n=1776). Consenting patients in a condition permitting telephone-based follow-up were randomized to nurse-led, telephone-based follow-up or follow-up according to usual care. Follow-up was cunducted at 1 and 12 months after discharge and the intervention included BP and LDL-C measurements, titration of medication, and lifestyle counseling. In study II, we analyzed factors associated with non-participation in the randomized phase of the NAILED study, including association with education level. In addition, we compared the 1-year prognosis in terms of cumulative survival between participants and non-participants. In study III, we compared differences in BP and LDL-C levels between the intervention and control groups during the first year of follow-up and, in study IV, in relation to level of education (low, ≤10 years; high, >10 years).Results The cumulative 1-year incidence of recurrent ischemic stroke decreased from 15.0% to 12.0%. Among surviving stroke and TIA patients, 53.1% were included for randomization, 35.7% were excluded mainly due to physical or cognitive disability, and 11.2% declined participation in the randomized phase. A low level of education was independently associated with exclusion, as well as the patient’s decision to abstain from randomization. Excluded patients had a more than 12-times higher risk of death within 1 year than patients who were randomized. After 1 year of follow-up, the mean systolic BP, diastolic BP, and LDL-C levels were 3.3 mmHg (95% CI 0.3 to 6.3), 2.3 mmHg (95% CI 0.5 to 4.2), and 0.3 mmol/L (95% CI 0.1 to 0.4) lower in the intervention group than among controls. Among participants with values above the treatment goal at baseline, the differences in systolic BP and LDL-C levels were more pronounced (8.0 mmHg, 95% CI 4.0 to 12.1; 0.6 mmol/L, 95% CI 0.4 to 0.9). In the intervention group, participants with a low level of education achieved similar or larger improvements in BP and LDL-C than participants with a high level of education. In the control group, BP remained unaltered and the LDL-C levels increased among participants with a low level of education.Conclusion The 1-year risk of ischemic stroke recurrence decreased in Sweden between 1998 and 2010. Nurse-led, telephone-based secondary preventive follow-up is feasible in just over half of the survivors of acute stroke and TIA and achieve better than usual care in terms of BP and LDL-C levels, and equality in BP improvements across groups defined by education level. However, a large proportion of stroke survivors are in a general condition precluding this form of follow-up, and their prognosis in terms of 1-year survival is poor. Patients with a low education level are over-represented within this group and among patients declining randomization for secondary preventive follow-up.
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| 3. |
- Johansson, Elias, 1984-
(författare)
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Carotid stenosis
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Carotid stenosis is one of several causes of ischemic stroke and entails a high risk of ischemic stroke recurrence. Removal of a carotid stenosis by carotid endarterectomy results in a risk reduction for ischemic stroke, but the magnitude of risk reduction depends on several factors. If the delay between the last symptom and carotid endarterectomy is less than 2 weeks, the absolute risk reduction is >10%, regardless of age, sex, or if the degree of carotid stenosis is 50–69% or 70–99%. Thus, speed is the key. However, if many patients suffers an ischemic stroke recurrence within the first 2 weeks of the presenting event, an additional benefit is likely be obtained if carotid endarterectomy is performed even earlier than within 2 week after the presenting event. Carotid endarterectomy for asymptomatic carotid stenoses carries a small risk reduction for stroke. Screening for asymptomatic carotid stenosis requires a prevalence of >5% in the examined population, i.e., higher than in the general population; however, directed screening in groups with a prevalence of >5% is beneficial. The aims of this thesis were to investigate the length of the delay to carotid endarterectomy, determine the risk of recurrent stroke before carotid endarterectomy, and determine if a calcification in the area of the carotid arteries seen on dental panoramic radiographs is a valid selection method for directed ultrasound screening to detect asymptomatic carotid stenosis. Consecutive patients with a symptomatic carotid stenosis who underwent a preoperative evaluation aimed at carotid endarterectomy at Umeå Stroke Centre between January 1, 2004–March 31, 2006 (n=275) were collected retrospectively and between August 1, 2007–December 31, 2009 (n=230) prospectively. In addition, 117 consecutive persons, all preliminarily eligible for asymptomatic carotid endarterectomy and with a calcification in the area of the carotid arteries seen on panoramic radiographs, were prospectively examined with carotid ultrasound. The median delay between the presenting event and carotid endarterectomy was 11.7 weeks in the first half year of 2004, dropped to 6.9 weeks in the first quarter year of 2006, and had dropped to 3.6 weeks in the second half year of 2009. The risk of ipsilateral ischemic stroke recurrence was 4.8% within 2 days, 7.9% within 1 week, and 11.2% within 2 weeks of the presenting event. For patients with a stroke or transient ischemic attack as the presenting event, this risk was 6.0% within 2 days, 9.7% within 1 week, and 14.3% within 2 weeks of the presenting event. For the 10 patients with a near-occlusion, the risk of ipsilateral ischemic stroke recurrence was 50% at 4 weeks after the presenting event. Among the 117 persons with a calcification in the area of the carotid arteries seen on panoramic radiographs, eight had a 50–99% carotid stenosis, equalling a prevalence of 6.8% (not statistically significantly over the pre-specified 5% threshold). Among men, the prevalence of 50–99% carotid stenosis was 12.5%, which was statistically significantly over the pre-specified 5% threshold. In conclusion: The delay to carotid endarterectomy was longer than 2 weeks. Additional benefit is likely to be gained by performing carotid endarterectomy within a few days of the presenting event instead of at 2 weeks because many patients suffer a stroke recurrence within a few days; speed is indeed the key. The finding that near-occlusion entails an early high risk of stroke recurrence stands in sharp contrast to previous studies; one possible explaination is that this was a high-risk period missed in previous studies. The incidental finding of a calcification in the area of the carotid arteries on a panoramic radiograph is a valid indication for carotid ultrasound screening in men who are otherwise eligible for asymptomatic carotid endarterectomy.
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| 4. |
- Johansson, Kristina, 1986-
(författare)
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Biomarkers and risk of intracerebral hemorrhage : population-based studies in northern Sweden
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundIntracerebral hemorrhage (ICH) is a disease associated with a high morbidity and mortality and treatment options for the condition are limited. Even though an ICH event usually comes as a surprise to the affected individual, pathogenetic processes often have occurred before the sudden ICH event and may have preceded disease onset by years. It is possible that individuals at increased risk of ICH could be identified using biomarkers, for example markers of hemostasis and fibrinolysis. Even if these biomarkers are not part of the causal chain, they could be used as risk indicators to better define high-risk groups. Another approach could be to measure already established risk markers for ICH, such as self-reported alcohol consumption, using a blood biomarker. That could increase measurement reliability and consequently the accuracy of the estimates of ICH risk.AimsThe aim of this thesis was to investigate potential biomarkers and risk of ICH. Specific aims were to evaluate the associations between factor XII, D-dimer, von Willebrand factor (VWF), ABO blood groups with focus on blood group O, phosphatidylethanol (PEth), and risk of ICH.MethodsIn our first study, aiming to investigate the association between factor XII and risk of hemorrhagic stroke, we followed participants of the health examination northern Sweden MONItoring trends and determinants in CArdiovascular disease (MONICA) performed in 1994 as a cohort until 2011. Factor XII concentrations were measured in blood samples drawn at the baseline health examination where the participants also answered a questionnaire regarding lifestyle factors and medical history. Diagnosis codes from the National Patient Register and the Swedish Cause of Death Register were used to find cases of hemorrhagic stroke, defined as ICH or subarachnoid hemorrhage. In the subsequent studies, the associations between biomarkers (factor XII, D-dimer, VWF, ABO blood groups, and PEth) and risk of ICH were investigated using a matched, nested case-referent design including individuals that had participated in the Västerbotten Intervention Programme, the MONICA and the Mammography Screening Project in 1985–2007. The participants donated blood samples at baseline for future research which were stored at -80 degrees C until biomarker analyses. The majority of the participants also underwent a baseline health examination including a questionnaire. First-ever ICH diagnoses during the study period 1985–2007 were validated using medical records and autopsy reports. To each case, two referents were matched for age, sex, geographical region, health examination date and health examination setting. ResultsIn the cohort study of the association between factor XII concentrations and risk of hemorrhagic stroke, 1,852 participants were included among which 30 experienced a hemorrhagic stroke event. There was an association between high factor XII and risk of hemorrhagic stroke in a multivariable model (hazard ratio 1.51; 95% confidence interval [CI] 1.03–2.21 per standard deviation [SD] of factor XII). In the case-referent study of the association between factor XII and risk of ICH, 70 cases with ICH and 137 matched referents were included. We found no association between factor XII and risk of ICH in a multivariable model (odds ratio [OR] 1.06; 95% CI 0.57–1.97 per SD of factor XII). The study of the association between D-dimer and risk of ICH included 141 cases and 255 matched referents. We found an association between D-dimer and risk of ICH in a multivariable model (OR 1.36; 95% CI 1.05–1.77 per SD of D-dimer). When stratifying the analysis for time between blood sampling and ICH event in tertiles, the association remained significant in the cases with the shortest time between blood sampling and ICH event in a multivariable model (OR 1.78; 95% CI 1.05–3.05 per SD of D-dimer). The study investigating the association between VWF and risk of ICH included 139 cases and 276 referents. We found no association between VWF and risk of ICH in a multivariable model (OR 0.85; 95% CI 0.54–1.34 per SD of VWF). In the analysis investigating the associations between ABO blood groups and risk of ICH, 162 cases and 317 referents were included. We found no association between blood group O compared to non-O blood groups and risk of ICH (OR 0.96; 95% CI 0.65–1.42). In the study of the association between PEth concentrations and risk of ICH, 97 cases and 180 referents were included. There was an association between PEth concentrations > 0.30 µmol/L compared to < 0.01 µmol/L and risk of ICH in a multivariable model (OR 4.64; 95% CI 1.49–14.40).ConclusionsHigh concentrations of D-dimer and PEth are associated with an increased risk of ICH. Our conclusion of the two studies investigating the association between factor XII and risk of hemorrhagic stroke and ICH respectively is that there is no association between factor XII and risk of ICH. We found no association between VWF or blood group O and risk of ICH.
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| 5. |
- Kilpeläinen, Tuomas O, et al.
(författare)
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Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
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| 6. |
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| 7. |
- Lindgren, Christer, et al.
(författare)
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A 3-Year Clinical Follow-up of Implants Placed in Two Different Biomaterials Used for Sinus Augmentation
- 2012
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Ingår i: International Journal of Oral & Maxillofacial Implants. - : Quintessence Publishing. - 0882-2786 .- 1942-4434. ; 27:5, s. 1151-1162
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The aims of the present study were to compare a novel biphasic calcium phosphate (BCP) with deproteinized bovine bone (DBB) for maxillary sinus floor augmentation in a split-mouth design and to perform a clinical follow-up of dental implants placed in the augmented sinuses. Materials and Methods: Partially or completely edentulous patients requiring bilateral sinus augmentation were included in the study. The patients were randomized for augmentation with BCP (test) and DBB (control) in the contralateral side. Eight months after grafting, dental implants were placed. After 3 years of graft healing, core biopsy specimens were obtained from the grafted areas for histologic and histomorphometric analyses. After 3 years of functional implant loading, implant survival/success rates and clinical indices were assessed and radiographic examination and resonance frequency analysis were performed. Results: Nine completely edentulous patients and two partially edentulous patients (mean age, 67 years) who required bilateral sinus augmentation were included in the study, and 62 implants were placed. The mean values for the area of newly formed bone in the retrieved specimens were 29% +/- 14.3% and 32% +/- 18.0% for BCP and DBB, respectively; the percentage of graft particles in contact with bone was 38% +/- 10.9% in the BCP group and 44% +/- 12.1% in the DBB group (no statistical significant differences between groups). The mean values for the area of BCP particles and DBB particles were 20% +/- 7.5% and 24% +/- 13.5%, respectively (difference not significant). One dental implant was lost from each group, resulting in an overall implant survival rate of 96.8% after 3 years of loading. Conclusion: After 3 years, a similar amount of newly formed bone was present regardless of the biomaterial used. The choice of biomaterial did not seem to influence implant survival rates.
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| 8. |
- Lindgren, Christer, et al.
(författare)
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A Prospective 1-Year Clinical and Radiographic Study of Implants Placed after Maxillary Sinus Floor Augmentation with Synthetic Biphasic Calcium Phosphate or Deproteinized Bovine Bone
- 2012
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Ingår i: Clinical Implant Dentistry and Related Research. - Malden : Wiley. - 1523-0899 .- 1708-8208. ; 14:1, s. 41-50
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Tidskriftsartikel (refereegranskat)abstract
- Background: The technique of using bone grafts or different biomaterials for augmentation of the maxillary sinus prior to implant placement is well accepted by clinicians. However, clinical documentation of some bone substitutes is still lacking. Purpose: This prospective study was designed to evaluate the success rate of implants placed after maxillary sinus augmentation with a novel synthetic biphasic calcium phosphate (BCP) or deproteinized bovine bone (DBB), the latter acting as control. Material and Methods: Nine edentulous patients and two partially edentulous patients with a mean age of 67 years with a bilateral need for sinus augmentation, <5 mm residual bone in the floor of the sinus and a crestal width ≥4 mm, were included in the study. After bilateral elevation of the Schneiderian membrane, all patients were randomized for augmentation with synthetic BCP in one side and DBB in the contralateral side. After 8 months of graft healing, 62 implants with an SLActive surface were placed. Implant survival, graft resorption, plaque index, bleeding on probing, sulcus bleeding index, probing pocket depth, and implant success rate were evaluated after 1 year of functional loading. Results: After a mean of 118 days, all patients received their fixed prosthetic constructions. One implant was lost in each biomaterial, giving an overall survival rate of 96.8%. Success rates for implants placed in BCP and DBB were 91.7 and 95.7%, respectively. No significant difference in marginal bone loss was found around implants placed in BCP, DBB, or residual bone, respectively. The mean graft resorption was 0.43 mm (BCP) and 0.29 mm (DBB). Conclusion: In this limited study, implant success rate was not dependent on the biomaterial used for maxillary sinus augmentation. Similar results were found after 1 year of functional loading for implants placed after sinus augmentation using BCP or DBB.
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| 9. |
- Lindgren, Christer, et al.
(författare)
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Clinical histology of microimplants placed in two different biomaterials.
- 2009
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Ingår i: The International journal of oral & maxillofacial implants. - Hanover Park : Quintessence Publishing. - 0882-2786 .- 1942-4434. ; 24:6, s. 1093-100
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: This randomized, controlled study was designed to compare bone formation around microimplants with a sandblasted, acid-etched surface placed at the time of maxillary sinus floor augmentation with a synthetic biphasic calcium phosphate (BCP) or deproteinized bovine bone (DBB). MATERIALS AND METHODS: Nine completely edentulous patients and two partially edentulous patients (six women, five men) with a mean age of 67 years (range, 50 to 79 years) requiring bilateral sinus augmentation were included in the study. The patients were randomized for augmentation with BCP (test) in one side and DBB (control) in the contralateral side. At the time of augmentation, one microimplant on each side was placed vertically from the top of the alveolar crest, penetrating the residual bone and the grafting material. After 8 months of graft healing, at the time of ordinary implant placement, all 22 microimplants were retrieved with a surrounding bone core for histologic analyses. RESULTS: The bone-to-implant contact in the BCP group was 64.6% +/- 9.0%, versus 55.0% +/- 16.0% for the DBB group. The difference was not significant. The corresponding values for the area of newly formed bone in the biopsies were 41.1% +/- 9.8% and 41.6% +/- 14.0% for BCP and DBB, respectively. There were significantly more DBB particles in contact with newly formed bone than BCP particles (87.9 +/- 18.2% versus 53.9 +/- 26.1%; Wilcoxon rank sum test; P = .007). CONCLUSION: In this randomized, controlled clinical trial, new bone formation and bone-to-implant contact around microimplants with a sandblasted, acid-etched surface was found to be equivalent between sinuses augmented with BCP or DBB. Significantly more DBB particles than BCP particles were in contact with newly formed bone, but the clinical relevance of this has yet to be established.
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| 10. |
- Lindgren, Helena, 1969-, et al.
(författare)
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Distinct roles of reactive nitrogen and oxygen species to control infection with the facultative intracellular bacterium Francisella tularensis.
- 2004
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Ingår i: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 72:12, s. 7172-7182
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Tidskriftsartikel (refereegranskat)abstract
- Reactive nitrogen species (RNS) and reactive oxygen species (ROS) are important mediators of the bactericidal host response. We investigated the contribution of these two mediators to the control of infection with the facultative intracellular bacterium Francisella tularensis. When intradermally infected with the live vaccine strain F. tularensis LVS, mice deficient in production of RNS (iNOS(-/-) mice) or in production of ROS by the phagocyte oxidase (p47(phox-/-) mice) showed compromised resistance to infection. The 50% lethal dose (LD(50)) for iNOS(-/-) mice was <20 CFU, and the LD(50) for p47(phox-/-) mice was 4,400 CFU, compared to an LD(50) of >500,000 CFU for wild-type mice. The iNOS(-/-) mice survived for 26.4 +/- 1.8 days, and the p47(phox-/-) mice survived for 10.1 +/- 1.3 days. During the course of infection, the serum levels of gamma interferon (IFN-gamma) and interleukin-6 were higher in iNOS(-/-) and p47(phox-/-) mice than in wild-type mice. Histological examination of livers of iNOS(-/-) mice revealed severe liver pathology. Splenocytes obtained 5 weeks after primary infection from antibiotic-treated iNOS(-/-) mice showed an in vitro recall response that was similar in magnitude and greater secretion of IFN-gamma compared to cells obtained from wild-type mice. In summary, mice lacking expression of RNS or ROS showed extreme susceptibility to infection with F. tularensis LVS. The roles of RNS and ROS seemed to be distinct since mice deficient in production of ROS showed dissemination of infection and died during the early phase of infection, whereas RNS deficiency led to severe liver pathology and a contracted course of infection.
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