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Carlsson, Axel C
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Publications (10 of 68) Show all publications
Carlsson, A. C., Ruge, T., Kjøller, E., Hilden, J., Kolmos, H. J., Sajadieh, A., . . . Ärnlöv, J. (2018). 10-Year Associations between Tumor Necrosis Factor Receptors 1 and 2 and Cardiovascular Events in Patients with Stable Coronary Heart Disease: A CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) Trial Substudy.. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, 7(9), Article ID e008299.
Open this publication in new window or tab >>10-Year Associations between Tumor Necrosis Factor Receptors 1 and 2 and Cardiovascular Events in Patients with Stable Coronary Heart Disease: A CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) Trial Substudy.
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2018 (English)In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 9, article id e008299Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: We aimed to assess the associations and predictive powers between the soluble receptors for tumor necrosis factor (TNF)-α (TNFR1 and TNFR2) and cardiovascular outcomes in patients with stable coronary heart disease.

METHODS AND RESULTS: CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) is a randomized clinical trial comparing clarithromycin with placebo in patients with stable coronary heart disease. The primary outcome was a composite of nonfatal acute myocardial infarction, unstable angina pectoris, cerebrovascular disease, and all-cause mortality. Patients were followed up for 10 years; discovery sample, those assigned placebo (1204 events in n=1998); and replication sample, those assigned clarithromycin (1220 events in n=1979). We used Cox regression adjusted for C-reactive protein level, established cardiovascular risk factors, kidney function, and cardiovascular drugs. After adjustments, higher serum levels of TNFR1 and TNFR2 were associated with the composite outcome in the discovery sample (hazard ratio per SD increase, 1.13; 95% confidence interval, 1.05-1.22; P=0.001 for TNFR1; hazard ratio, 1.16; 95% confidence interval, 1.08-1.24; P<0.001 for TNFR2). The associations were similar in the replication sample. The associations with the composite outcome were mainly driven by acute myocardial infarction, cardiovascular mortality, and noncardiovascular mortality. The addition of TNFR1 and TNFR2 to established cardiovascular risk factors improved prediction only modestly (<1%).

CONCLUSIONS: Increased concentrations of circulating TNFR1 and TNFR2 were associated with increased risks of cardiovascular events and mortality in patients with stable coronary heart disease. Yet, the utility of measuring TNFR1 and TNFR2 to improve risk prediction in these patients appears limited.

CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00121550.

Keywords
cohort study, coronary atherosclerosis, tumor necrosis factor‐α
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-349365 (URN)10.1161/JAHA.117.008299 (DOI)000432332800014 ()29686027 (PubMedID)
Funder
Swedish Research CouncilMarianne and Marcus Wallenberg FoundationSwedish Heart Lung Foundation
Available from: 2018-04-26 Created: 2018-04-26 Last updated: 2018-07-27Bibliographically approved
Wändell, P., Carlsson, A. C., Holzmann, M. J., Ärnlöv, J., Sundquist, J. & Sundquist, K. (2018). Associations between relevant cardiovascular pharmacotherapies and incident heart failure in patients with atrial fibrillation: a cohort study in primary care. Journal of Hypertension, 36(9), 1929-1935
Open this publication in new window or tab >>Associations between relevant cardiovascular pharmacotherapies and incident heart failure in patients with atrial fibrillation: a cohort study in primary care
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2018 (English)In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 36, no 9, p. 1929-1935Article in journal (Refereed) Published
Abstract [en]

Objective: To study association between relevant cardiovascular pharmacotherapy and incident congestive heart failure (CHF) in patients with atrial fibrillation treated in primary health care.

Methods: Study population included all adults (n=7975) aged 45 years and older diagnosed with atrial fibrillation at 75 primary care centers in Sweden between 2001 and 2007. Outcome was defined as a first diagnosis of CHF post-atrial fibrillation diagnosis. Association between CHF and treatment with relevant cardiovascular pharmacotherapies (beta blockers, calcium blockers, digitalis, diuretics, RAS blockers, and statins) was explored using Cox regression analysis with hazard ratios and 95% CIs. Adjustments were made for age, sociodemographic variables, and comorbid conditions (with or without cardiovascular disorders).

Results: During a mean of 5.7 years (SD 2.3) of follow-up, totally 1552 patients (19.5%; 803 women and 749 men) had a recorded CHF diagnosis. Thiazides (hazard ratio 0.74, 95% CI 0.65-0.84), vessel-active calcium channel blockers (hazard ratio 0.76, 95% CI 0.67-0.86), and nonselective beta blockers (hazard ratio 0.84, 95% CI 0.72-0.98), with specifically sotalol representing 80% of nonselective beta blockers (hazard ratio 0.81, 95% CI 0.69-0.97), were associated with lower CHF risk in fully adjusted models. Loop diuretics (hazard ratio 1.41, 95% CI 1.25-1.57) were associated with a higher risk. Findings for thiazides and vessel-active channel blockers were consistent in the tested subgroups.

Conclusion: In this clinical setting, we found that thiazides, vessel-active calcium channel blockers, and nonselective beta blockers (specifically sotalol) were associated with a lower risk of incident CHF among patients with atrial fibrillation. The findings of the present study need to be confirmed in other settings.

Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS, 2018
Keywords
atrial fibrillation, congestive heart failure, drug treatment, sex
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-362473 (URN)10.1097/HJH.0000000000001813 (DOI)000442250500023 ()29870433 (PubMedID)
Funder
Swedish Research CouncilForte, Swedish Research Council for Health, Working Life and Welfare
Available from: 2018-10-05 Created: 2018-10-05 Last updated: 2018-10-05Bibliographically approved
Wallen, E. F., Ljunggren, G., Carlsson, A. C., Pettersson, D. & Wändell, P. (2018). High prevalence of diabetes mellitus, hypertension and obesity among persons with a recorded diagnosis of intellectual disability or autism spectrum disorder. Journal of Intellectual Disability Research, 62(4), 269-280
Open this publication in new window or tab >>High prevalence of diabetes mellitus, hypertension and obesity among persons with a recorded diagnosis of intellectual disability or autism spectrum disorder
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2018 (English)In: Journal of Intellectual Disability Research, ISSN 0964-2633, E-ISSN 1365-2788, Vol. 62, no 4, p. 269-280Article in journal (Refereed) Published
Abstract [en]

Background: Obesity and lack of physical activity are frequently reported in persons with intellectual disability (ID) or autism spectrum disorder (ASD). We hypothesised a higher prevalence of diabetes and hypertension in this population.

Method: We used administrative data for all primary and specialist outpatient and inpatient healthcare consultations for people with at least one recorded diagnosis of diabetes mellitus, hypertension or obesity from 1998 to 2015. Data were drawn from the central administrative database for Stockholm County, Sweden. It was not possible to separate data for type 1 and type 2 diabetes. We stratified 26988 individuals with IDs or ASD into three groups, with Down syndrome treated separately, and compared these groups with 1996140 people from the general population.

Results: Compared with the general population, men and women with ID/ASD had 1.6-3.4-fold higher age-adjusted odds of having a registered diagnosis of obesity or diabetes mellitus, with the exception of diabetes among men with Down syndrome. A registered diagnosis of hypertension was only more common among men with ID/ASD than in the general population.

Conclusions: Diabetes and blood pressure health screening, along with efforts to prevent development of obesity already in childhood, are necessary for individuals with IDs and ASD. We believe that there is a need for adapted community-based health promotion programmes to ensure more equitable health for these populations.

Place, publisher, year, edition, pages
WILEY, 2018
Keywords
autism spectrum disorder, diabetes mellitus, down syndrome, hypertension, intellectual disability, prevalence studies
National Category
Psychiatry
Identifiers
urn:nbn:se:uu:diva-350734 (URN)10.1111/jir.12462 (DOI)000427123900001 ()29280230 (PubMedID)
Available from: 2018-05-16 Created: 2018-05-16 Last updated: 2018-05-16Bibliographically approved
Carlsson, A. C., Jansson, J.-H., Söderberg, S., Ruge, T., Larsson, A. & Ärnlöv, J. (2018). Levels of soluble tumor necrosis factor receptor 1 and 2, gender, and risk of myocardial infarction in Northern Sweden. Atherosclerosis, 272, 41-46
Open this publication in new window or tab >>Levels of soluble tumor necrosis factor receptor 1 and 2, gender, and risk of myocardial infarction in Northern Sweden
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2018 (English)In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 272, p. 41-46Article in journal (Refereed) Published
Abstract [en]

BACKGROUND AND AIMS:

Soluble receptors for tumor necrosis factor alpha (sTNFR1 and sTNFR2) have been associated with cardiovascular diseases, and some evidence points towards a difference in associated risk between men and women. We aimed to study the association between sTNFR1 and sTNFR2 and incident myocardial infarctions (MI) and to explore the influence of established cardiovascular risk factors in men and women.

METHODS:

We conducted a nested case control study in three large Swedish cohorts, including 533 myocardial infarction cases, and 1003 age-, sex- and cohort-matched controls. Odds ratios (OR) with 95% confidence intervals (CI) were calculated.

RESULTS:

An association between circulating sTNFR1 and sTNFR2 and an increased risk for MI was found when comparing cases and controls. The odds ratios were significant after adjustment for established cardiovascular risk factors and C-reactive protein in women (OR 1.44, 95% CI 1.08-1.93 for TNFR1, and 1.61, 95% CI 1.11-2.34 for TNFR2), but was abolished in men. Women with a combination of elevated CRP and values in the upper quartile of TNFR1 or TNFR2 had a 5-fold higher risk of myocardial infarction versus those with normal CRP and values in the lower three quartiles of TNFR1 or TNFR2.

CONCLUSIONS:

As the risk estimates for TNFR1 and TNFR2 were higher and remained significant after adjustments for established cardiovascular risk factors in women but not in men, a potential role for TNFR1 and TNFR2 in identifying women with a higher MI risk is possible. The future clinical role of TNFR1 and TNFR2 in combination with CRP to identify high risk patients for coronary heart disease has yet to be determined.

Keywords
All-cause mortality, CRP, Community based cohort, Cytokines, Inflammation, Oxidative stress, Tumor necrosis factor
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-349227 (URN)10.1016/j.atherosclerosis.2018.03.020 (DOI)000430383800007 ()29547707 (PubMedID)
Funder
Swedish Research CouncilSwedish Heart Lung FoundationMarianne and Marcus Wallenberg Foundation
Available from: 2018-04-23 Created: 2018-04-23 Last updated: 2018-06-19Bibliographically approved
Wändell, P., Carlsson, A. C., Holzmann, M. J., Ärnlöv, J., Sundquist, J. & Sundquist, K. (2018). Mortality in patients with atrial fibrillation and common co-morbidities - a cohort study in primary care. Annals of Medicine, 50(2), 156-163
Open this publication in new window or tab >>Mortality in patients with atrial fibrillation and common co-morbidities - a cohort study in primary care
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2018 (English)In: Annals of Medicine, ISSN 0785-3890, E-ISSN 1365-2060, Vol. 50, no 2, p. 156-163Article in journal (Refereed) Published
Abstract [en]

Objective: To study the association between cardiovascular co-morbidities and mortality risk in primary care patients with atrial fibrillation.

Methods: The study population included all adults (n=12,283) >= 45 years diagnosed with AF at 75 primary care centres in Sweden between 2001 and 2007. The outcome was mortality (until 2010) and data were explored for co-morbidities using Cox regression with hazard ratios (HRs). Analyses were performed stratified by sex and by age-group (45-64, 65-74 and >= 75 years of age) with adjustment for age, socio-economic factors and relevant co-morbidities.

Results: During a mean of 5.8 years (standard deviation 2.4) of follow-up, 3954 (32%) patients died (1971 (35%) women, and 1983 (30%) men). High HRs were found for congestive heart disease (CHF) and cerebrovascular diseases for all age-groups among men and women (except for the 45-64 year old women); for coronary heart disease among the oldest men; for diabetes among the 65-74 year old men and the 45-64 year old women. Low HRs were found for hypertension among women >= 75 years of age.

Conclusions: In this clinical setting, CHF and cerebrovascular diseases were consistently associated with mortality in all age-groups. The possible protective effect by hypertension among elderly women should be interpreted with caution.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2018
Keywords
Coronary heart disease, cerebrovascular disease, depression, congestive heart failure, gender, hypertension, diabetes
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-347261 (URN)10.1080/07853890.2017.1407036 (DOI)000424417900007 ()29172794 (PubMedID)
Funder
Swedish Research CouncilForte, Swedish Research Council for Health, Working Life and Welfare
Available from: 2018-04-03 Created: 2018-04-03 Last updated: 2018-04-03Bibliographically approved
Nowak, C., Carlsson, A. C., Östgren, C. J., Nyström, F. H., Alam, M., Feldreich, T., . . . Ärnlöv, J. (2018). Multiplex proteomics for prediction of major cardiovascular events in type 2 diabetes. Diabetologia, 61(8), 1748-1757
Open this publication in new window or tab >>Multiplex proteomics for prediction of major cardiovascular events in type 2 diabetes
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2018 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, no 8, p. 1748-1757Article in journal (Refereed) Published
Abstract [en]

Aims/hypothesis Multiplex proteomics could improve understanding and risk prediction of major adverse cardiovascular events (MACE) in type 2 diabetes. This study assessed 80 cardiovascular and inflammatory proteins for biomarker discovery and prediction of MACE in type 2 diabetes. Methods We combined data from six prospective epidemiological studies of 30-77-year-old individuals with type 2 diabetes in whom 80 circulating proteins were measured by proximity extension assay. Multivariable-adjusted Cox regression was used in a discovery/replication design to identify biomarkers for incident MACE. We used gradient-boosted machine learning and lasso regularised Cox regression in a random 75% training subsample to assess whether adding proteins to risk factors included in the Swedish National Diabetes Register risk model would improve the prediction of MACE in the separate 25% test subsample. Results Of 1211 adults with type 2 diabetes (32% women), 211 experienced a MACE over a mean (+/- SD) of 6.4 +/- 2.3 years. We replicated associations (< 5% false discovery rate) between risk of MACE and eight proteins: matrix metalloproteinase (MMP)-12, IL-27 subunit alpha (IL-27a), kidney injury molecule (KIM)-1, fibroblast growth factor (FGF)-23, protein S100-A12, TNF receptor (TNFR)-1, TNFR-2 and TNF-related apoptosis-inducing ligand receptor (TRAIL-R)2. Addition of the 80-protein assay to established risk factors improved discrimination in the separate test sample from 0.686 (95% CI 0.682, 0.689) to 0.748 (95% CI 0.746, 0.751). A sparse model of 20 added proteins achieved a C statistic of 0.747 (95% CI 0.653, 0.842) in the test sample. Conclusions/interpretation We identified eight protein biomarkers, four of which are novel, for risk of MACE in community residents with type 2 diabetes, and found improved risk prediction by combining multiplex proteomics with an established risk model. Multiprotein arrays could be useful in identifying individuals with type 2 diabetes who are at highest risk of a cardiovascular event.

Place, publisher, year, edition, pages
SPRINGER, 2018
Keywords
Biomarkers, Major adverse cardiovascular event, Proteomics, Risk, Type 2 diabetes
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-361262 (URN)10.1007/s00125-018-4641-z (DOI)000437432200006 ()29796748 (PubMedID)
Funder
EU, Horizon 2020, 634869Swedish Research Council, 2012-2215Swedish Research Council, 2015-03477Swedish Society of MedicineSwedish Heart Lung Foundation
Available from: 2018-10-11 Created: 2018-10-11 Last updated: 2018-10-11Bibliographically approved
Wandell, P., Carlsson, A. C., Sundquist, J. & Sundquist, K. (2018). The association between relevant comorbidities and dementia in patients with atrial fibrillation. GEROSCIENCE, 40(3), 317-324
Open this publication in new window or tab >>The association between relevant comorbidities and dementia in patients with atrial fibrillation
2018 (English)In: GEROSCIENCE, ISSN 2509-2715, Vol. 40, no 3, p. 317-324Article in journal (Refereed) Published
Abstract [en]

Risk of dementia is increased in patients with atrial fibrillation (AF). We aimed to study associations between relevant comorbidities and prevalent as well as incident dementia in AF patients. Study population included all adults (n = 12,283) >= 45 years diagnosed with AF at 75 primary care centers in Sweden 2001-2007. Logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (95% CI) for associations between comorbidities and prevalent dementia. In a subsample (n = 12,096), (excluding patients with dementia diagnosed before AF onset), Cox regression was used to estimate hazard ratios (HR) with 95% CIs for association between comorbidities, and incident dementia, after adjustment for age, socioeconomic factors and anticoagulant treatment. Totally 937 patients (7.6%), 388 men (5.8%) and 549 women (9.7%), were diagnosed with dementia. After adjustments, prevalent dementia was more common in (ORs, 95% CI) men with congestive heart failure (CHF), stroke, and depression; in women with CHF and depression, and among women > 75 years with stroke, but less common in women with hypertension. During a 5.6-year follow-up (standard deviation 2.5), 750 patients (6.2%; 322 men, 4.9%, and 428 women, 7.8%) were diagnosed with incident dementia. An increased risk of incident dementia was found among men with diabetes and depression; a decreased risk among men and women with CHF, and among women with hypertension, myocardial infarction cerebrovascular diseases. The findings regarding incident dementia need to be interpreted with great caution, as they may have been subject to survival bias.

Place, publisher, year, edition, pages
SPRINGER, 2018
Keywords
Atrial fibrillation, Dementia, Gender, Hypertension
National Category
Nursing
Identifiers
urn:nbn:se:uu:diva-362175 (URN)10.1007/s11357-018-0029-8 (DOI)000440106900008 ()29934733 (PubMedID)
Funder
Swedish Research CouncilForte, Swedish Research Council for Health, Working Life and Welfare
Available from: 2018-10-05 Created: 2018-10-05 Last updated: 2018-10-05Bibliographically approved
Wandell, P., Carlsson, A. C., Holzmann, M., Ärnlöv, J., Johansson, S.-E., Sundquist, J. & Sundquist, K. (2017). Association between antithrombotic treatment and hemorrhagic stroke in patients with atrial fibrillation-a cohort study in primary care. European Journal of Clinical Pharmacology, 73(2), 215-221
Open this publication in new window or tab >>Association between antithrombotic treatment and hemorrhagic stroke in patients with atrial fibrillation-a cohort study in primary care
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2017 (English)In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 73, no 2, p. 215-221Article in journal (Refereed) Published
Abstract [en]

The objective of this study was to study the association between antithrombotic treatment and risk of hemorrhagic stroke (HS) in patients with atrial fibrillation (AF) treated in primary health care. Study population included all adults (n = 12,215) 45 years and older diagnosed with AF at 75 primary care centers in Sweden 2001-2007. Outcome was defined as a first hospital episode with a discharge episode of HS after the AF diagnosis. Association between HS and persistent treatment with antithrombotic agents (warfarin, acetylsalicylic acid (ASA), clopidogrel) was explored using Cox regression analysis, with hazard ratios (HRs) and 95 % CIs. Adjustment was made for age, socioeconomic status, and co-morbid cardiovascular conditions. During a mean of 5.8 years (SD 2.4) of follow-up, 162 patients (1.3 %; 67 women and 95 men) with HS were recorded. The adjusted risk associated with persistent warfarin treatment compared to no antithrombotic treatment consistently showed no increased HS risk, HR for women 0.53 (95 % CI 0.23-1.27) and for men 0.55 (95 % CI 0.29-1.04); corresponding HRs for ASA were, for women, 0.45 (95 % CI 0.14-1.44) and, for men, 0.56 (95 % CI 0.24-1.29). In this clinical setting, we found no evidence pointing to an increased risk of HS with antithrombotic treatment.

Keywords
Atrial fibrillation, Hemorrhagic stroke, Gender, Cardiovascular co-morbidity, Anticoagulants, Mortality
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-316015 (URN)10.1007/s00228-016-2152-8 (DOI)000392308200010 ()27826643 (PubMedID)
Funder
Swedish Research Council, K2012-70X-15428-08-3
Available from: 2017-02-24 Created: 2017-02-24 Last updated: 2017-11-29Bibliographically approved
Wandell, P., Carlsson, A. C., Li, X., Gasevic, D., Arnlov, J., Holzmann, M. J., . . . Sundquist, K. (2017). Atrial fibrillation in immigrant groups: a cohort study of all adults 45 years of age and older in Sweden. European Journal of Epidemiology, 32(9), 785-796
Open this publication in new window or tab >>Atrial fibrillation in immigrant groups: a cohort study of all adults 45 years of age and older in Sweden
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2017 (English)In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 32, no 9, p. 785-796Article in journal (Refereed) Published
Abstract [en]

To study the association between country of birth and incident atrial fibrillation (AF) in several immigrant groups in Sweden. The study population included all adults (n = 3,226,752) aged 45 years and older in Sweden. AF was defined as having at least one registered diagnosis of AF in the National Patient Register. The incidence of AF in different immigrant groups, using Swedish-born as referents, was assessed by Cox regression, expressed in hazard ratios (HRs) and 95% confidence intervals (CI). All models were stratified by sex and adjusted for age, geographical residence in Sweden, educational level, marital status, and neighbourhood socioeconomic status. Compared to their Swedish-born counterparts, higher incidence of AF [HR (95% CI)] was observed among men from Bosnia 1.74 (1.56-1.94) and Latvia 1.29 (1.09-1.54), and among women from Iraq 1.96 (1.67-2.31), Bosnia 1.88 (1.61-1.94), Finland 1.14 (1.11-1.17), Estonia 1.14 (1.05-1.24) and Germany 1.08 (1.03-1.14). Lower incidence of AF was noted among men (HRs > 0.60) from Iceland, Southern Europe (especially Greece, Italy and Spain), Latin America (especially Chile), Africa, Asia (including Iraq, Turkey, Lebanon and Iran), and among women from Nordic countries (except Finland), Southern Europe, Western Europe (except Germany), Africa, North America, Latin America, Iran, Lebanon and other Asian countries (except Turkey and Iraq). In conclusion, we observed substantial differences in incidence of AF between immigrant groups and the Swedish-born population. A greater awareness of the increased risk of AF development in some immigrant groups may enable for a timely diagnosis, treatment and prevention of its debilitating complications, such as stroke.

Keywords
Atrial fibrillation, Gender, First generatio immigrants, Neighbourhood, Second generation immigrants, Socioeconomic status
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-340966 (URN)10.1007/s10654-017-0283-6 (DOI)000414156900006 ()28702880 (PubMedID)
Available from: 2018-02-12 Created: 2018-02-12 Last updated: 2018-02-12Bibliographically approved
Steubl, D., Kumar, S. V., Tato, M., Mulay, S. R., Larsson, A., Lind, L., . . . Anders, H.-J. (2017). Circulating cathepsin-S levels correlate with GFR decline and sTNFR1 and sTNFR2 levels in mice and humans. Scientific Reports, 7, Article ID 43538.
Open this publication in new window or tab >>Circulating cathepsin-S levels correlate with GFR decline and sTNFR1 and sTNFR2 levels in mice and humans
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2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 43538Article in journal (Refereed) Published
Abstract [en]

Cardiovascular complications determine morbidity/mortality in chronic kidney disease (CKD). We hypothesized that progressive CKD drives the release of cathepsin-S (Cat-S), a cysteine protease that promotes endothelial dysfunction and cardiovascular complications. Therefore, Cat-S, soluble tumor-necrosis-factor receptor (sTNFR) 1/2 and glomerular filtration rate (GFR) were measured in a CKD mouse model, a German CKD-cohort (MCKD, n = 421) and two Swedish community-based cohorts (ULSAM, n = 764 and PIVUS, n = 804). Association between Cat-S and sTNFR1/2/GFR was assessed using multivariable linear regression. In the mouse model, Cat-S and sTNFR1/2 concentrations were increased following the progressive decline of GFR, showing a strong correlation between Cat-S and GFR (r = -0.746, p < 0.001) and Cat-S and sTNFR1/sTNFR2 (r = 0.837/0.916, p < 0.001, respectively). In the human cohorts, an increase of one standard deviation of estimated GFR was associated with a decrease of 1.008 ng/ml (95%-confidence interval (95%-CI) -1.576-(-0.439), p < 0.001) in Cat-S levels in MCKD; in ULSAM and PIVUS, results were similar. In all three cohorts, Cat-S and sTNFR1/sTNFR2 levels were associated in multivariable linear regression (p < 0.001). In conclusion, as GFR declines Cat-S and markers of inflammation-related endothelial dysfunction increase. The present data indicating that Cat-S activity increases with CKD progression suggest that Cat-S might be a therapeutic target to prevent cardiovascular complications in CKD.

National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-316474 (URN)10.1038/srep43538 (DOI)000394936800001 ()28240259 (PubMedID)
Funder
EU, Horizon 2020, 668036, 634869Swedish Research CouncilSwedish Heart Lung FoundationMarianne and Marcus Wallenberg Foundation
Available from: 2017-03-01 Created: 2017-03-01 Last updated: 2017-11-29Bibliographically approved
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