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| 3. |
- Reid, Sarah, et al.
(författare)
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High genetic risk score is associated with early disease onset, damage accrual and decreased survival in systemic lupus erythematosus
- 2020
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 79:3, s. 363-369
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To investigate associations between a high genetic disease risk and disease severity in patients with systemic lupus erythematosus (SLE).METHODS: Patients with SLE (n=1001, discovery cohort and n=5524, replication cohort) and healthy controls (n=2802 and n=9859) were genotyped using a 200K Immunochip single nucleotide polymorphism array. A genetic risk score (GRS) was assigned to each individual based on 57 SLE risk loci.RESULTS: SLE was more prevalent in the high, compared with the low, GRS-quartile (OR 12.32 (9.53 to 15.71), p=7.9×10-86 and OR 7.48 (6.73 to 8.32), p=2.2×10-304 for the discovery and the replication cohorts, respectively). In the discovery cohort, patients in the high GRS-quartile had a 6-year earlier mean disease onset (HR 1.47 (1.22 to 1.75), p=4.3×10-5), displayed higher prevalence of damage accrual (OR 1.47 (1.06 to 2.04), p=2.0×10-2), renal disorder (OR 2.22 (1.50 to 3.27), p=5.9×10-5), anti-dsDNA (OR 1.83 (1.19 to 2.81), p=6.1×10-3), end-stage renal disease (ESRD) (OR 5.58 (1.50 to 20.79), p=1.0×10-2), proliferative nephritis (OR 2.42 (1.30 to 4.49), p=5.1×10-3), anti-cardiolipin-IgG (OR 1.89 (1.13 to 3.18), p=1.6×10-2), anti-β2-glycoprotein-I-IgG (OR 2.29 (1.29 to 4.06), p=4.8×10-3) and positive lupus anticoagulant test (OR 2.12 (1.16 to 3.89), p=1.5×10-2) compared with patients in the low GRS-quartile. Survival analysis showed earlier onset of the first organ damage (HR 1.51 (1.04 to 2.25), p=3.7×10-2), first cardiovascular event (HR 1.65 (1.03 to 2.64), p=2.6×10-2), nephritis (HR 2.53 (1.72 to 3.71), p=9.6×10-7), ESRD (HR 6.78 (1.78 to 26.86), p=6.5×10-3) and decreased overall survival (HR 1.83 (1.02 to 3.30), p=4.3×10-2) in high to low quartile comparison.CONCLUSIONS: A high GRS is associated with increased risk of organ damage, renal dysfunction and all-cause mortality. Our results indicate that genetic profiling may be useful for predicting outcomes in patients with SLE.
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- Stockfelt, Marit, et al.
(författare)
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Activated low-density granulocytes in peripheral and intervillous blood and neutrophil inflammation in placentas from SLE pregnancies
- 2021
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Ingår i: Lupus Science and Medicine. - : BMJ. - 2053-8790. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective Women with SLE face an increased risk of adverse pregnancy outcomes compared with healthy women, but the underlying immunological mechanisms are unknown. Given the recognised association of neutrophil activation with SLE pathogenesis, we examined whether there is increased neutrophil activation and inflammation in blood and placenta in SLE relative to healthy pregnancy. Methods At delivery, peripheral blood, maternal-derived intervillous blood and placentas were collected from 12 SLE and 10 healthy control pregnancies. The proportion of low-density granulocytes (LDGs) and the activation status of LDG and normal-density granulocytes were examined with flow cytometry. The chemokines CXCL8 and CXCL1 were quantified with a cytometric bead-based assay and interferon alpha (IFNα) protein levels with a Simoa method. IFNα-stimulated maternal-derived decidual stromal cells were examined for CXCL8 gene expression with qPCR. A pathologist, blinded to the patient background, examined all placentas. Results Women with SLE had significantly higher proportions of LDG in peripheral blood compared with controls (p=0.02), and LDG in both peripheral and intervillous blood were more activated in SLE relative to healthy pregnancies (peripheral blood: p=0.002 and intervillous blood: p=0.05). There were higher levels of CXCL8 and CXCL1 in intervillous compared with peripheral blood in women with SLE (p=0.004 and p=<0.0001, respectively) but not in controls. In SLE pregnancy, IFNα was detectable in 6 out of 10 intervillous blood samples but only in one control. Stimulation with IFNα upregulated CXCL8 gene expression in decidual stromal cells from both SLE and healthy pregnancy. Histological chorioamnionitis was present in 6 out of 12 placentas from women with SLE and in 1 out of 10 controls. Conclusions In women with SLE, locally produced chemokines in the placenta are increased and may attract and activate neutrophils. This in turn could contribute to placental inflammation and dysfunction and increased risk of placenta-related pregnancy complications.
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- Andersson, Tobias, 1976, et al.
(författare)
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Country of birth and mortality risk in hypertension with and without diabetes: the Swedish primary care cardiovascular database.
- 2021
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Ingår i: Journal of hypertension. - 1473-5598. ; 39:6, s. 1155-1162
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Tidskriftsartikel (refereegranskat)abstract
- Hypertension and diabetes are common and are both associated with high cardiovascular morbidity and mortality. We aimed to investigate associations between mortality risk and country of birth among hypertensive individuals in primary care with and without concomitant diabetes, which has not been studied previously. In addition, we aimed to study the corresponding risks of myocardial infarction and ischemic stroke.This observational cohort study of 62557 individuals with hypertension diagnosed 2001-2008 in the Swedish Primary Care Cardiovascular Database assessed mortality by the Swedish Cause of Death Register, and myocardial infarction and ischemic stroke by the National Patient Register. Cox regression models were used to estimate study outcome hazard ratios by country of birth and time updated diabetes status, with adjustments for multiple confounders.During follow-up time without diabetes using Swedish-born as reference, adjusted mortality hazard ratios per country of birth category were Finland: 1.26 (95% confidence interval 1.15-1.38), high-income European countries: 0.84 (0.74-0.95), low-income European countries: 0.84 (0.71-1.00) and non-European countries: 0.65 (0.56-0.76). The corresponding adjusted mortality hazard ratios during follow-up time with diabetes were high-income European countries: 0.78 (0.63-0.98), low-income European countries: 0.74 (0.57-0.96) and non-European countries: 0.56 (0.44-0.71). During follow-up without diabetes, the corresponding adjusted hazard ratio of myocardial infarction was increased for Finland: 1.16 (1.01-1.34), whereas the results for ischemic stroke were inconclusive.In Sweden, hypertensive immigrants (with the exception for Finnish-born) with and without diabetes have a mortality advantage, as compared to Swedish-born.
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- Andersson, Tobias, 1976, et al.
(författare)
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The impact of diabetes, education and income on mortality and cardiovascular events in hypertensive patients: A cohort study from the Swedish Primary Care Cardiovascular Database (SPCCD).
- 2020
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 15:8
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Tidskriftsartikel (refereegranskat)abstract
- In this study we aimed to estimate the effect of diabetes, educational level and income on the risk of mortality and cardiovascular events in primary care patients with hypertension.We followed 62,557 individuals with hypertension diagnosed 2001-2008, in the Swedish Primary Care Cardiovascular Database. Study outcomes were death, myocardial infarction, and ischemic stroke, assessed using national registers until 2012. Cox regression models were used to estimate adjusted hazard ratios of outcomes according to diabetes status, educational level, and income.During follow-up, 13,231 individuals died, 9981 were diagnosed with diabetes, 4431 with myocardial infarction, and 4433 with ischemic stroke. Hazard ratios (95% confidence intervals) for diabetes versus no diabetes: mortality 1.57 (1.50-1.65), myocardial infarction 1.24 (1.14-1.34), and ischemic stroke 1.17 (1.07-1.27). Hazard ratios for diabetes and ≤9 years of school versus no diabetes and >12 years of school: mortality 1.56 (1.41-1.73), myocardial infarction 1.36 (1.17-1.59), and ischemic stroke 1.27 (1.08-1.50). Hazard ratios for diabetes and income in the lowest fifth group versus no diabetes and income in the highest fifth group: mortality 3.82 (3.36-4.34), myocardial infarction 2.00 (1.66-2.42), and ischemic stroke 1.91 (1.58-2.31).Diabetes combined with low income was associated with substantial excess risk of mortality, myocardial infarction and ischemic stroke among primary care patients with hypertension.
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- Andersson, Ulrika, et al.
(författare)
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Patients and Professionals as Partners in Hypertension Care: Qualitative Substudy of a Randomized Controlled Trial Using an Interactive Web-Based System Via Mobile Phone
- 2021
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Ingår i: Journal of Medical Internet Research. - : JMIR Publications Inc.. - 1438-8871. ; 23:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: The use of technology has the potential to support the patient´s active participation regarding treatment of hypertension. This might lead to changes in the roles of the patient and health care professional and affect the partnership between them. Objective: The aim of this qualitative study was to explore the partnership between patients and health care professionals and the roles of patients and professionals in hypertension management when using an interactive web-based system for self-management of hypertension via the patient’s own mobile phone. Methods: Focus group interviews were conducted with 22 patients and 15 professionals participating in a randomized controlled trial in Sweden aimed at lowering blood pressure (BP) using an interactive web-based system via mobile phones. The interviews were audiorecorded and transcribed and analyzed using thematic analysis. Results: Three themes were identified: the technology, the patient, and the professional. The technology enabled documentation of BP treatment, mainly for sharing knowledge between the patient and the professional. The patients gained increased knowledge of BP values and their relation to daily activities and treatment. They were able to narrate about their BP treatment and take a greater responsibility, inspired by new insights and motivation for lifestyle changes. Based on the patient’s understanding of hypertension, professionals could use the system as an educational tool and some found new ways of communicating BP treatment with patients. Some reservations were raised about using the system, that it might be too time-consuming to function in clinical practice and that too much measuring could result in stress for the patient and an increased workload for the professionals. In addition, not all professionals and patients had adopted the instructions regarding the use of the system, resulting in less realization of its potential. Conclusions: The use of the system led to the patients taking on a more active role in their BP treatment, becoming more of an expert of their BP. When using the system as intended, the professionals experienced it as a useful resource for communication regarding BP and lifestyle. Patients and professionals described a consultation on more equal grounds. The use of technology in hypertension management can promote a constructive and person-centered partnership between patient and professional. However, implementation of a new way of working should bring benefits and not be considered a burden for the professionals. To establish a successful partnership, both the patient and the professional need to be motivated toward a new way of working.
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- Bager, Johan-Emil, et al.
(författare)
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Blood pressure levels and risk of haemorrhagic stroke in patients with atrial fibrillation and oral anticoagulants: results from The Swedish Primary Care Cardiovascular Database of Skaraborg.
- 2021
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Ingår i: Journal of hypertension. - 1473-5598. ; 39:8, s. 1670-1677
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Tidskriftsartikel (refereegranskat)abstract
- To assess the risk of haemorrhagic stroke at different baseline SBP levels in a primary care population with hypertension, atrial fibrillation and newly initiated oral anticoagulants (OACs).We identified 3972 patients with hypertension, atrial fibrillation and newly initiated OAC in The Swedish Primary Care Cardiovascular Database of Skaraborg. Patients were followed from 1 January 2006 until a first event of haemorrhagic stroke, death, cessation of OAC or 31 December 2016. We analysed the association between continuous SBP and haemorrhagic stroke with a multivariable Cox regression model and plotted the hazard ratio as a function of SBP with a restricted cubic spline with 130mmHg as reference.There were 40 cases of haemorrhagic stroke during follow-up. Baseline SBP in the 145-180mmHg range was associated with a more than doubled risk of haemorrhagic stroke, compared with a SBP of 130mmHg.In this cohort of primary care patients with hypertension and atrial fibrillation, we found that baseline SBP in the 145-180mmHg range, prior to initiation of OAC, was associated with a more than doubled risk of haemorrhagic stroke, as compared with an SBP of 130mmHg. This suggests that lowering SBP to below 145mmHg, prior to initiation of OAC, may decrease the risk of haemorrhagic stroke in patients with hypertension and atrial fibrillation.
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| 9. |
- Bager, Johan-Emil, et al.
(författare)
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Hypertension: sex-related differences in drug treatment, prevalence and blood pressure control in primary care.
- 2023
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Ingår i: Journal of human hypertension. - : Springer Science and Business Media LLC. - 1476-5527. ; 37, s. 662-670
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Forskningsöversikt (refereegranskat)abstract
- Antihypertensive treatment is equally beneficial for reducing cardiovascular risk in both men and women. Despite this, the drug treatment, prevalence and control of hypertension differ between men and women. Men and women respond differently, particularly with respect to the risk of adverse events, to many antihypertensive drugs. Certain antihypertensive drugs may also be especially beneficial in the setting of certain comorbidities - of both cardiovascular and extracardiac nature - which also differ between men and women. Furthermore, hypertension in pregnancy can pose a considerable therapeutic challenge for women and their physicians in primary care. In addition, data from population-based studies and from real-world data are inconsistent regarding whether men or women attain hypertension-related goals to a higher degree. In population-based studies, women with hypertension have higher rates of treatment and controlled blood pressure than men, whereas real-world, primary-care data instead show better blood pressure control in men. Men and women are also treated with different antihypertensive drugs: women use more thiazide diuretics and men use more angiotensin-enzyme inhibitors and calcium-channel blockers. This narrative review explores these sex-related differences with guidance from current literature. It also features original data from a large, Swedish primary-care register, which showed that blood pressure control was better in women than men until they reached their late sixties, after which the situation was reversed. This age-related decrease in blood pressure control in women was not, however, accompanied by a proportional increase in use of antihypertensive drugs and female sex was a significant predictor of less intensive antihypertensive treatment.
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- Bengtsson, Eva, et al.
(författare)
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CD163+ macrophages are associated with a vulnerable plaque phenotype in human carotid plaques
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Macrophages are a functionally heterogeneous group of immune cells abundant in atherosclerotic plaques. Macrophages expressing CD163 are associated with intraplaque hemorrhage and have previously been considered atheroprotective. However, in a recent study CD163-deficient atherosclerotic ApoE−/− mice exhibited smaller and less complex plaques, suggesting a proatherogenic role of CD163. Previous smaller studies on CD163+ macrophages and plaque stability in humans have yielded diverging results. Here we assessed the association of CD163+ cells to plaque vulnerability in a large cohort of human carotid plaques. CD163 protein expression was analyzed by immunohistochemistry in 200 human carotid plaques removed by endarterectomy from 103 patients with and 93 patients without cerebrovascular symptoms. Furthermore, CD163 mRNA expression was analyzed in 66 of the plaques. Both protein and mRNA expression of CD163 was higher in plaques from symptomatic patients and in plaques with high vulnerability index. CD163+ macrophages were primarily found in shoulder regions and in the center of the plaques. The present data show that CD163 is associated with increased plaque vulnerability in human carotid plaques, supporting the notion that CD163+ macrophages could contribute to clinical events.
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