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| 2. |
- Backman, Helena, et al.
(författare)
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Decreased COPD prevalence in Sweden after decades of decrease in smoking
- 2020
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Ingår i: Respiratory Research. - : Springer Nature. - 1465-9921 .- 1465-993X. ; 21
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundCOPD has increased in prevalence worldwide over several decades until the first decade after the millennium shift. Evidence from a few recent population studies indicate that the prevalence may be levelling or even decreasing in some areas in Europe. Since the 1970s, a substantial and ongoing decrease in smoking prevalence has been observed in several European countries including Sweden. The aim of the current study was to estimate the prevalence, characteristics and risk factors for COPD in the Swedish general population. A further aim was to estimate the prevalence trend of COPD in Northern Sweden from 1994 to 2009.MethodsTwo large random population samples were invited to spirometry with bronchodilator testing and structured interviews in 2009–2012, one in south-western and one in northern Sweden, n = 1839 participants in total. The results from northern Sweden were compared to a study performed 15 years earlier in the same area and age-span. The diagnosis of COPD required both chronic airway obstruction (CAO) and the presence of respiratory symptoms, in line with the GOLD documents since 2017. CAO was defined as post-bronchodilator FEV1/FVC < 0.70, with sensitivity analyses based on the FEV1/FVC < lower limit of normal (LLN) criterion.ResultsBased on the fixed ratio definition, the prevalence of COPD was 7.0% (men 8.3%; women 5.8%) in 2009–2012. The prevalence of moderate to severe (GOLD ≥ 2) COPD was 3.5%. The LLN based results were about 30% lower. Smoking, occupational exposures, and older age were risk factors for COPD, whereof smoking was the most dominating risk factor. In northern Sweden the prevalence of COPD, particularly moderate to severe COPD, decreased significantly from 1994 to 2009, and the decrease followed a decrease in smoking.ConclusionsThe prevalence of COPD has decreased in Sweden, and the prevalence of moderate to severe COPD was particularly low. The decrease follows a major decrease in smoking prevalence over several decades, but smoking remained the dominating risk factor for COPD.
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| 3. |
- Cederstrom, S., et al.
(författare)
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New candidate genes for ST-elevation myocardial infarction
- 2020
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 287:1, s. 66-77
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Tidskriftsartikel (refereegranskat)abstract
- Background Despite extensive research in atherosclerosis, the mechanisms of coronary atherothrombosis in ST-elevation myocardial infarction (STEMI) patients are undetermined. Objectives Our aim was to find candidate genes involved in STEMI by analysing leucocyte gene expression in STEMI patients, without the influence of secondary inflammation from innate immunity, which was assumed to be a consequence rather than the cause of coronary atherothrombosis. Methods Fifty-one patients were included at coronary angiography because of STEMI. Arterial blood was sampled in the acute phase (P1), at 24-48 h (P2) and at 3 months (P3). Leucocyte RNA was isolated and gene expression analysis was performed by Affymetrix Human Transcriptome Array 2.0. By omission of up- or downregulated genes at P2, secondary changes from innate immunity were excluded. Genes differentially expressed in P1 when compared to the convalescent sample in P3 were determined as genes involved in STEMI. Results Three genes were upregulated at P1 compared to P3; ABCG1 (P = 5.81 x 10(-5)), RAB20 (P = 3.69 x 10(-5)) and TMEM2 (P = 7.75 x 10(-6)) whilst four were downregulated; ACVR1 (P = 9.01 x 10(-5)), NFATC2IP (P = 8.86 x 10(-5)), SUN1 (P = 3.87 x 10(-5)) and TTC9C (P = 7.18 x 10(-6)). These genes were also highly expressed in carotid atherosclerotic plaques. Conclusions We found seven genes involved in STEMI. The study is unique regarding the blood sampling in the acute phase and omission of secondary expressed genes from innate immunity. However, the results need to be replicated by future studies.
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| 5. |
- Karadimou, G, et al.
(författare)
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TLR7 Expression Is Associated with M2 Macrophage Subset in Calcific Aortic Valve Stenosis
- 2020
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 9:7
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Tidskriftsartikel (refereegranskat)abstract
- Calcific aortic valve stenosis (CAVS) is a common age-related disease characterized by active calcification of the leaflets of the aortic valve. How innate immune cells are involved in disease pathogenesis is not clear. In this study we investigate the role of the pattern recognition receptor Toll-like receptor 7 (TLR7) in CAVS, especially in relation to macrophage subtype. Human aortic valves were used for mRNA expression analysis, immunofluorescence staining, or ex vivo tissue assays. Response to TLR7 agonist in primary macrophages and valvular interstitial cells (VICs) were investigated in vitro. In the aortic valve, TLR7 correlated with M2 macrophage markers on mRNA levels. Expression was higher in the calcified part compared with the intermediate and healthy parts. TLR7+ cells were co-stained with M2-type macrophage receptors CD163 and CD206. Ex vivo stimulation of valve tissue with the TLR7 ligand imiquimod significantly increased secretion of IL-10, TNF-α, and GM-CSF. Primary macrophages responded to imiquimod with increased secretion of IL-10 while isolated VICs did not respond. In summary, in human aortic valves TLR7 expression is associated with M2 macrophages markers. Ex vivo tissue challenge with TLR7 ligand led to secretion of immunomodulatory cytokine IL-10. These results connect TLR7 activation in CAVS to reduced inflammation and improved clearance.
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| 6. |
- Myrberg, Tomi, et al.
(författare)
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Restrictive spirometry versus restrictive lung function using the GLI reference values
- 2022
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Ingår i: Clinical Physiology and Functional Imaging. - : Wiley. - 1475-0961 .- 1475-097X. ; 42:3, s. 181-189
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Tidskriftsartikel (refereegranskat)abstract
- Background: Restrictive lung function may indicate various underlying diseases. The aim of this study was to evaluate the accuracy of different restrictive spirometry patterns (RSPs) to identify restrictive lung function (total lung capacity [TLC] < lower limit of normal [LLN]) according to reference values by the Global Lung Function Initiative (GLI) in a wide age-ranged, general population sample. Methods: A general population sample (n = 607, age 23–72 years, smokers 18.8%) with proper dynamic spirometry and TLC measurements, was included. Accuracy of two main categories of RSP to identify TLC < LLN were evaluated: traditional RSPs (definition 1: FVC < 80% of predicted and FEV1/FVC ≥ 0.7 and definition 2: FVC < LLN and FEV1/FVC ≥ LLN) and RSPs defined by Youden's method (definition 3: FVC < 85.5% of predicted and FEV1/FVC ≥ LLN and definition 4: FVC Z-score < −1.0 and FEV1/FVC ≥ LLN). Results: The prevalence of restrictive lung function (TLC < LLN) was 5.3%. The most accurate cut-offs for FVC to identify TLC < LLN were 85.5% for FVC% of predicted, and −1.0 for FVC Z-score. The traditional RSP definitions 1 and 2 had higher specificity (95.0% and 96.9%) but substantially lower sensitivity compared to RSP definitions 3 and 4. Conclusion: Based on the GLI reference values, the RSP definition FVC < LLN and FEV1/FVC ≥ LLN yielded the highest specificity and may appropriately be used to rule out restrictive lung function. The RSP definition with the most favourable trade-off between sensitivity and specificity, FVC < 85.5% of predicted and FEV1/FVC ≥ LLN, may serve as an alternative with higher sensitivity for screening. © 2022 The Authors. Clinical Physiology and Functional Imaging published by John Wiley & Sons Ltd on behalf of Scandinavian Society of Clinical Physiology and Nuclear Medicine.
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| 7. |
- Rykaczewska, Urszula, et al.
(författare)
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PCSK6 Is a Key Protease in the Control of Smooth Muscle Cell Function in Vascular Remodeling
- 2020
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Ingår i: Circulation Research. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-7330 .- 1524-4571. ; 126:5, s. 571-585
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: PCSKs (Proprotein convertase subtilisins/kexins) are a protease family with unknown functions in vasculature. Previously, we demonstrated PCSK6 upregulation in human atherosclerotic plaques associated with smooth muscle cells (SMCs), inflammation, extracellular matrix remodeling, and mitogens. Objective: Here, we applied a systems biology approach to gain deeper insights into the PCSK6 role in normal and diseased vessel wall. Methods and Results: Genetic analyses revealed association of intronic PCSK6 variant rs1531817 with maximum internal carotid intima-media thickness progression in high-cardiovascular risk subjects. This variant was linked with PCSK6 mRNA expression in healthy aortas and plaques but also with overall plaque SMA+ cell content and pericyte fraction. Increased PCSK6 expression was found in several independent human cohorts comparing atherosclerotic lesions versus healthy arteries, using transcriptomic and proteomic datasets. By immunohistochemistry, PCSK6 was localized to fibrous cap SMA+ cells and neovessels in plaques. In human, rat, and mouse intimal hyperplasia, PCSK6 was expressed by proliferating SMA+ cells and upregulated after 5 days in rat carotid balloon injury model, with positive correlation to PDGFB (platelet-derived growth factor subunit B) and MMP (matrix metalloprotease) 2/MMP14. Here, PCSK6 was shown to colocalize and cointeract with MMP2/MMP14 by in situ proximity ligation assay. Microarrays of carotid arteries from Pcsk6(-/-) versus control mice revealed suppression of contractile SMC markers, extracellular matrix remodeling enzymes, and cytokines/receptors. Pcsk6(-/-) mice showed reduced intimal hyperplasia response upon carotid ligation in vivo, accompanied by decreased MMP14 activation and impaired SMC outgrowth from aortic rings ex vivo. PCSK6 silencing in human SMCs in vitro leads to downregulation of contractile markers and increase in MMP2 expression. Conversely, PCSK6 overexpression increased PDGFBB (platelet-derived growth factor BB)-induced cell proliferation and particularly migration. Conclusions: PCSK6 is a novel protease that induces SMC migration in response to PDGFB, mechanistically via modulation of contractile markers and MMP14 activation. This study establishes PCSK6 as a key regulator of SMC function in vascular remodeling.
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| 8. |
- Vaz, Juan, et al.
(författare)
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Incidence, aetiology and related comorbidities of cirrhosis: a Swedish population-based cohort study
- 2020
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Ingår i: Bmc Gastroenterology. - : Springer Science and Business Media LLC. - 1471-230X. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The incidence of cirrhosis for individuals in Sweden has previously been reported as stable/low among European countries. However, Swedish population-based studies are scarce and none of them included data from the most recent decade (2010-2019). We aimed to describe the incidence and aetiology of cirrhosis in the Halland region from 2011 to 2018, and to describe the severity and prevalence of liver-related complications and other primary comorbidities at the time of cirrhosis diagnosis. Methods We conducted a retrospective cohort study of all patients with cirrhosis in Halland, which has a population of 310,000 inhabitants. Medical records and histopathology registries were reviewed. Results A total of 598 patients with cirrhosis were identified. The age-standardised incidence was estimated at 23.2 per 100,000 person-years (95% CI 21.3-25.1), 30.5 (95% CI 27.5-33.8) for men and 16.4 (95% CI 14.3-18.7) for women. When stratified by age, the highest incidence rates were registered at age 60-69 years. Men had a higher incidence rate for most age groups when compared to women. The most common aetiology was alcohol (50.5%), followed by cryptogenic cirrhosis (14.5%), hepatitis C (13.4%), and non-alcoholic fatty liver disease (5.7%). Most patients had at least one liver-related complication at diagnosis (68%). The most common comorbidities at diagnosis were arterial hypertension (33%), type 2 diabetes (29%) and obesity (24%). Conclusions Based on previous Swedish studies, our results indicate that the incidence of cirrhosis in Sweden might be considerably higher than previously reported. It is uncertain if the incidence of cirrhosis has previously been underestimated or if an actual increment has occurred during the course of the most recent decade. The increased incidence rates of cirrhosis reported in Halland are multifactorial and most likely related to higher incidence rates among the elderly. Pre-obesity and obesity are common in cirrhosis and non-alcoholic fatty liver disease has become an important cause of cirrhosis in Halland.
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| 9. |
- Vaz, Juan, et al.
(författare)
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Socioeconomic and marital status among liver cirrhosis patients and associations with mortality: a population-based cohort study in Sweden
- 2020
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Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe importance of socioeconomic status for survival in cirrhosis patients is more or less pronounced within different populations, most likely due to cultural and regional differences combined with dissimilarities in healthcare system organisation and accessibility. Our aim was to study the survival of patients with cirrhosis in a population-based Swedish cohort, using available data on marital status, employment status, and occupational skill level.MethodsWe conducted a retrospective cohort study of 582 patients diagnosed with cirrhosis in the Region of Halland (total population 310,000) between 2011 and 2018. Medical and histopathologic data, obtained from registries, were reviewed. Cox regression models were used to estimate associations between survival and marital status (married, never married, previously married), employment status (employed, pensioner, disability retired, unemployed), and occupational skill level (low-skilled: level I; medium-skilled: level II; medium-high skilled: level III; professionals: level IV); adjusting for sex, age, aetiology, Model for End-stage Liver Disease (MELD) score, Child-Pugh class, and comorbidities.ResultsAlcohol was the most common aetiology (51%). Most patients were male (63%) and the median age was 66years. Occupational skill level was associated with the severity of cirrhosis at diagnosis and the prevalence of Child-Pugh C gradually increased from professionals through low-skilled. The mean survival for professionals (6.39years, 95% CI 5.54-7.23) was higher than for low-skilled (3.00years, 95% CI 2.33-3.67) and medium-skilled (4.04years, 95% CI 3.64-4.45). The calculated hazard ratios in the multivariate analysis were higher for low-skilled (3.43, 95% CI 1.89-6.23) and medium-skilled (2.48, 95% CI 1.48-4.12), compared to professionals. When aggregated, low- and medium-skilled groups also had poorer mean survival (3.79years, 95% CI 3.44-4.14; vs 5.64years, 95% CI 5.00-6.28) and higher hazard ratios (1.85, 95% CI 1.32-2.61) compared to the aggregated medium-high skilled and professional groups. Marital and employment status were not statistically significant predictors of mortality in the multivariate analysis.ConclusionsOccupational skill level was strongly associated with mean survival and mortality risk. Poorer prognosis among patients with low and medium occupational skill level could not be explained by differences in sex, age, marital status, employment status, MELD score, Child-Pugh class, or comorbidity.
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| 10. |
- Vaz, Juan, et al.
(författare)
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Targeting population groups with heavier burden of hepatocellular carcinoma incidence: A nationwide descriptive epidemiological study in Sweden
- 2022
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 151:2, s. 229-239
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Tidskriftsartikel (refereegranskat)abstract
- Contemporary European studies examining associations between socioeconomic status and hepatocellular carcinoma (HCC) incidence are scarce. We aimed to target population groups with a heavier burden of HCC by assessing associations of individual-level sociodemographic variables and neighbourhood deprivation with all-stage and stage-specific HCC incidence rates (IR). Patient and population data stratified by calendar year (2012-2018), sex, age (5-year groups), household income (low, medium and high), country of birth (Nordic, non-Nordic) and neighbourhood deprivation (national quintiles Q1-Q5) were retrieved from Swedish registers. HCC stages were defined by Barcelona Clinic Liver Cancer stages 0 to A (early-stage) and B to D (late-stage). IR (per 100 000 person-years) were estimated by Poisson regression models. Men had four times higher IR than women. IRs increased markedly with lower household income as well as with neighbourhood deprivation. Seven times higher IR was observed among people with a low household income living in the most deprived neighbourhoods (IR 3.90, 95% confidence interval [CI] 3.28-4.64) compared to people with a high household income living in the least deprived neighbourhoods (IR 0.58, 95% CI 0.46-0.74). The gradient across income categories was more pronounced for late-stage than early-stage HCC. IR reached 30 (per 100 000 person-years) for people in the age span 60 to 79 years with low income and 20 for 60 to 79 year old people living in the most deprived neighbourhoods (regardless of income). Men with low household income and/or living in the most deprived neighbourhoods might be considered as primary targets in studies evaluating the cost-effectiveness of screening for early-stage HCC detection.
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