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Stenemo, M., Nowak, C., Byberg, L., Sundström, J., Giedraitis, V., Lind, L., . . . Ärnlöv, J. (2018). Circulating proteins as predictors of incident heart failure in the elderly.. European Journal of Heart Failure, 20(1), 55-62
Open this publication in new window or tab >>Circulating proteins as predictors of incident heart failure in the elderly.
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2018 (English)In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 20, no 1, p. 55-62Article in journal (Refereed) Published
Abstract [en]

AIMS: To identify novel risk markers for incident heart failure using proteomic profiling of 80 proteins previously associated with cardiovascular pathology.

METHODS AND RESULTS: Proteomic profiling (proximity extension assay) was performed in two community-based prospective cohorts of elderly individuals without heart failure at baseline: the Prospective Investigation of the Vasculature in Uppsala Seniors [PIVUS, n = 901, median age 70.2 (interquartile range 70.0-70.3) years, 80 events]; and the Uppsala Longitudinal Study of Adult Men [ULSAM, n = 685, median age 77.8 (interquartile range 76.9-78.1) years, 90 events]. Twenty-nine proteins were associated with incident heart failure in the discovery cohort PIVUS after adjustment for age and sex, and correction for multiple testing. Eighteen associations replicated in ULSAM. In pooled analysis of both cohorts, higher levels of nine proteins were associated with incident heart failure after adjustment for established risk factors: growth differentiation factor 15 (GDF-15), T-cell immunoglobulin and mucin domain 1 (TIM-1), tumour necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2), spondin-1 (SPON1), matrix metalloproteinase-12 (MMP-12), follistatin (FS), urokinase-type plasminogen activator surface receptor (U-PAR), osteoprotegerin (OPG), and suppression of tumorigenicity 2 (ST2). Of these, GDF-15, U-PAR, MMP-12, TRAIL-R2, SPON1 and FS were associated with worsened echocardiographic left ventricular systolic function at baseline, while only TIM-1 was positively associated with worsened diastolic function (P < 0.02 for all).

CONCLUSION: Proteomic profiling identified several novel associations between proteins involved in apoptosis, inflammation, matrix remodelling, and fibrinolysis with incident heart failure in elderly individuals. Our results encourage additional studies investigating the underlying mechanisms and the clinical utility of our findings.

Keyword
Biomarkers, Epidemiology, Heart failure, Left ventricular dysfunction, Proteomics, Risk prediction
National Category
Clinical Medicine
Research subject
Health and Welfare
Identifiers
urn:nbn:se:du-26378 (URN)10.1002/ejhf.980 (DOI)000423809700007 ()28967680 (PubMedID)
Available from: 2017-10-05 Created: 2017-10-05 Last updated: 2018-02-22Bibliographically 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.

Keyword
All-cause mortality, CRP, Community based cohort, Cytokines, Inflammation, Oxidative stress, Tumor necrosis factor
National Category
Clinical Medicine
Research subject
Health and Welfare
Identifiers
urn:nbn:se:du-27418 (URN)10.1016/j.atherosclerosis.2018.03.020 (DOI)29547707 (PubMedID)2-s2.0-85043538100 (Scopus ID)
Available from: 2018-03-19 Created: 2018-03-19 Last updated: 2018-03-26Bibliographically 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. KEY MESSAGES We found congestive heart failure and cerebrovascular diseases to be consistently associated with mortality in both women and men. We found hypertension to be associated with lower mortality risk among women ≥75 years of age, although this finding must be interpreted with caution. Depression was found to be associated with increased mortality risk among men and women aged 65-74 years of age.

Keyword
Coronary heart disease, cerebrovascular disease, congestive heart failure, depression, diabetes, gender, hypertension
National Category
Clinical Medicine
Research subject
Health and Welfare
Identifiers
urn:nbn:se:du-26633 (URN)10.1080/07853890.2017.1407036 (DOI)29172794 (PubMedID)2-s2.0-85035104390 (Scopus ID)
Available from: 2017-11-29 Created: 2017-11-29 Last updated: 2018-02-22Bibliographically approved
Hållmarker, U., Lindbäck, J., Michaëlsson, K., Ärnlöv, J., Åsberg, S., Wester, P., . . . James, S. (2018). Survival and incidence of cardiovascular diseases in participants in a long-distance ski race (Vasaloppet, Sweden) compared to the background population.. European Heart Journal - Quality of Care and Clinical Outcomes
Open this publication in new window or tab >>Survival and incidence of cardiovascular diseases in participants in a long-distance ski race (Vasaloppet, Sweden) compared to the background population.
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2018 (English)In: European Heart Journal - Quality of Care and Clinical Outcomes, ISSN 2058-5225, E-ISSN 2058-1742Article in journal (Refereed) Epub ahead of print
National Category
Clinical Medicine
Research subject
Health and Welfare
Identifiers
urn:nbn:se:du-27113 (URN)10.1093/ehjqcco/qcy005 (DOI)29390055 (PubMedID)
Available from: 2018-02-06 Created: 2018-02-06 Last updated: 2018-02-06Bibliographically approved
Cornelis, M. C., Gustafsson, S., Ärnlöv, J., Elmståhl, S., Söderberg, S., Sundström, J., . . . Ingelsson, E. (2018). Targeted proteomic analysis of habitual coffee consumption. Journal of Internal Medicine, 283(2), 200-211
Open this publication in new window or tab >>Targeted proteomic analysis of habitual coffee consumption
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2018 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 283, no 2, p. 200-211Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Coffee drinking has been implicated in mortality and a variety of diseases but potential mechanisms underlying these associations are unclear. Large-scale systems epidemiological approaches may offer novel insights to mechanisms underlying associations of coffee with health.

OBJECTIVE: We performed an analysis of known and novel protein markers linked to cardiovascular disease and their association with habitual coffee intake in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS, n=816) and followed-up top proteins in the Uppsala Longitudinal Study of Adult Men (ULSAM, n=635) and EpiHealth (n=2418).

METHODS: In PIVUS and ULSAM, coffee intake was measured by 7-day dietary records while a computer-based food frequency questionnaire was used in EpiHealth. Levels of up to 80 proteins were assessed in plasma by a proximity extension assay.

RESULTS: Four protein-coffee associations adjusted for age, sex, smoking and BMI, met statistical significance in PIVUS (FDR<5%, P<2.31×10(-3) ): leptin (LEP), chitinase-3-like protein 1 (CHI3L), Tumor necrosis factor (TNF) receptor 6 and TNF-related apoptosis-inducing ligand. The inverse association between coffee intake and LEP replicated in ULSAM (β, -0.042 SD per cup of coffee, P=0.028) and EpiHealth (β, -0.025 SD per time of coffee, P=0.004). The negative coffee-CHI3L association replicated in EpiHealth (β, -0.07, P=1.15×10(-7) ), but not in ULSAM (β, -0.034, P=0.16).

CONCLUSIONS: The current study supports an inverse association between coffee intake and plasma LEP and CHI3L1 levels. The coffee-CHI3L1 association is novel and warrants further investigation given links between CHI3L1 and health conditions that are also potentially influenced by coffee. 

Keyword
biomarkers, coffee, epidemiology, population, proteomics
National Category
Clinical Medicine
Research subject
Health and Welfare
Identifiers
urn:nbn:se:du-26458 (URN)10.1111/joim.12703 (DOI)000425830100008 ()29044854 (PubMedID)
Available from: 2017-10-23 Created: 2017-10-23 Last updated: 2018-03-08Bibliographically approved
Wuopio, J., Östgren, C. J., Länne, T., Lind, L., Ruge, T., Carlsson, A. C., . . . Ärnlöv, J. (2018). The association between circulating endostatin and a disturbed circadian blood pressure pattern in patients with type 2 diabetes. Blood Pressure, 1-7
Open this publication in new window or tab >>The association between circulating endostatin and a disturbed circadian blood pressure pattern in patients with type 2 diabetes
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2018 (English)In: Blood Pressure, ISSN 0803-7051, E-ISSN 1651-1999, p. 1-7Article in journal (Refereed) Epub ahead of print
Abstract [en]

BACKGROUND: Endostatin, cleaved from collagen XVIII in the extracellular matrix, is a promising circulating biomarker for cardiovascular damage. It possesses anti-angiogenic and anti-fibrotic functions and has even been suggested to be involved in blood pressure regulation. Less is known if endostatin levels relate to circadian blood pressure patterns. In the present paper we studied the association between circulating levels of endostatin and nocturnal dipping in blood pressure.

METHODS: We used the CARDIPP-study, a cohort of middle aged, type 2 diabetics (n = 593, 32% women), with data on both 24-hour and office blood pressure, serum-endostatin, cardiovascular risk factors, and incident major cardiovascular events. Nocturnal dipping was defined as a >10% difference between day- and night-time blood pressures.

RESULTS: Two-hundred four participants (34%) were classified as non-dippers. The mean endostatin levels were significantly higher in non-dippers compared to dippers (mean ± standard deviation: 62.6 ± 1.8 µg/l vs. 58.7 ± 1.6 µg/l, respectively, p = .007). Higher serum levels of endostatin were associated with a diminished decline in nocturnal blood pressure adjusted for age, sex, HbA1c, mean systolic day blood pressure, hypertension treatment, glomerular filtration rate, and prevalent cardiovascular disease (regression coefficient per SD increase of endostatin -0.01, 95% CI, -0.02-(-0.001), p = .03). Structural equation modelling analyses suggest that endostatin mediates 7% of the association between non-dipping and major cardiovascular events.

CONCLUSION: We found an independent association between higher circulating levels of endostatin and a reduced difference between day- and night-time systolic blood pressure in patients with type 2 diabetes. Yet endostatin mediated only a small portion of the association between non-dipping and cardiovascular events arguing against a clinical utility of our findings.

Place, publisher, year, edition, pages
Taylor & Francis, 2018
Keyword
Ambulatory blood pressure; circadian blood pressure variation; endostatin; non-dipping; type 2 diabetes mellitus
National Category
Clinical Medicine
Research subject
Health and Welfare
Identifiers
urn:nbn:se:du-27362 (URN)10.1080/08037051.2018.1444941 (DOI)29488402 (PubMedID)2-s2.0-85042925368 (Scopus ID)
Available from: 2018-03-08 Created: 2018-03-08 Last updated: 2018-03-22Bibliographically approved
Wändell, P., Carlsson, A. C., Holzmann, M. J., Ärnlöv, J., Sundquist, J. & Sundquist, K. (2018). The association between relevant co-morbidities and prevalent as well as incident heart failure in patients with atrial fibrillation. Journal of Cardiology
Open this publication in new window or tab >>The association between relevant co-morbidities and prevalent as well as incident heart failure in patients with atrial fibrillation
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2018 (English)In: Journal of Cardiology, ISSN 0914-5087, E-ISSN 1876-4738Article in journal (Refereed) Epub ahead of print
Abstract [en]

BACKGROUND:

Congestive heart failure (CHF) is a serious complication in patients with atrial fibrillation (AF).

OBJECTIVE:

To study associations between relevant co-morbidities and CHF in patients with AF.

METHODS:

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 with 95% confidence intervals (CIs) for the associations between co-morbidities, and prevalent CHF. In a subsample (n=9424), (excluding patients with earlier CHF), Cox regression was used to estimate hazard ratios with 95% CIs for the association between co-morbidities, and a first hospital diagnosis of CHF, after adjustment for age and socio-economic factors.

RESULTS:

During 5.4 years' follow-up (standard deviation 2.5), 2259 patients (24.0%; 1135 men, 21.8%, and 1124 women, 26.7%) were diagnosed with CHF. Patients with hypertension were less likely to have CHF, while a diagnosis of coronary heart disease, valvular heart disease, diabetes, or chronic obstructive pulmonary disease (COPD), was consistently associated with CHF among men and women. CHF was more common among women with depression. The relative fully adjusted risk of incident CHF was increased for the following diseases in men with AF: valvular heart disease, cardiomyopathy, and diabetes; and for the following diseases in women: valvular heart disease, diabetes, obesity, and COPD. The corresponding risk was decreased among women for hypertension.

CONCLUSIONS:

In this clinical setting we found hypertension to be associated with a decreased risk of CHF among women; valvular heart disease and diabetes to be associated with an increased risk of CHF in both sexes; and cardiomyopathy to be associated with an increased risk of CHF among men.

Keyword
Atrial fibrillation; Congestive heart failure; Gender; Hypertension
National Category
Clinical Medicine
Research subject
Health and Welfare
Identifiers
urn:nbn:se:du-26989 (URN)10.1016/j.jjcc.2017.12.010 (DOI)29358024 (PubMedID)2-s2.0-85040616380 (Scopus ID)
Available from: 2018-01-29 Created: 2018-01-29 Last updated: 2018-03-22Bibliographically approved
Carrero, J. J., Grams, M. E., Sang, Y., Ärnlöv, J., Gasparini, A., Matsushita, K., . . . Coresh, J. (2017). Albuminuria changes are associated with subsequent risk of end-stage renal disease and mortality. Kidney International, 91(1), 244-251
Open this publication in new window or tab >>Albuminuria changes are associated with subsequent risk of end-stage renal disease and mortality
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2017 (English)In: Kidney International, ISSN 0085-2538, E-ISSN 1523-1755, Vol. 91, no 1, p. 244-251Article in journal (Refereed) Published
Abstract [en]

Current guidelines for chronic kidney disease (CKD) recommend using albuminuria as well as estimated glomerular filtration rate (eGFR) to stage CKD. However, CKD progression is solely defined by change in eGFR with little regard to the risk implications of change in albuminuria. This is an observational study from the Stockholm CREAtinine Measurements (SCREAM) project, a health care utilization cohort from Stockholm, Sweden, with laboratory measures from 2006-2011 and follow-up through December 2012. Included were 31,732 individuals with two or more ambulatory urine albumin to creatinine ratio (ACR) tests. We assessed the association between change in ACR during a baseline period of 1, 2, or 3 years and end-stage renal disease (ESRD) or death. Using a 2-year baseline period, there were 378 ESRD events and 1712 deaths during a median of 3 years of follow-up. Compared to stable ACR, a 4-fold increase in ACR was associated with a 3.08-times (95% confidence interval 2.59 to 3.67) higher risk of ESRD while a 4-fold decrease in ACR was associated with a 0.34-times (0.26 to 0.45) lower risk of ESRD. Similar associations were found in people with and without diabetes mellitus, with and without hypertension, and also when adjusted for the change in eGFR during the same period. The association between change in ACR and mortality was weaker: ACR increase was associated with mortality, but the relationship was largely flat for ACR decline. Results were consistent for 1-, 2-, and 3-year ACR changes. Thus, changes in albuminuria are strongly and consistently associated with the risk of ESRD and death.

Keyword
albuminuria; changes in albuminuria; death; end-stage renal disease; estimated glomerular filtration rate
National Category
Clinical Medicine
Research subject
Health and Welfare
Identifiers
urn:nbn:se:du-23557 (URN)10.1016/j.kint.2016.09.037 (DOI)000391162700028 ()27927597 (PubMedID)
Available from: 2016-12-12 Created: 2016-12-12 Last updated: 2017-11-29Bibliographically approved
Roos, V., Elmståhl, S., Ingelsson, E., Sundström, J., Ärnlöv, J. & Lind, L. (2017). Alterations in multiple lifestyle factors in subjects with the metabolic syndrome independently of obesity. Metabolic Syndrome and Related Disorders, 15(3), 118-123
Open this publication in new window or tab >>Alterations in multiple lifestyle factors in subjects with the metabolic syndrome independently of obesity
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2017 (English)In: Metabolic Syndrome and Related Disorders, ISSN 1540-4196, E-ISSN 1557-8518, Vol. 15, no 3, p. 118-123Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Many lifestyle factors have been associated with the metabolic syndrome (MetS). However, most of these studies have not considered the potential impact of obesity and have often only investigated one lifestyle factor at the time. We aimed to investigate the interplay between body mass index (BMI) and MetS with respect to multiple lifestyle factors.

METHODS: BMI and MetS [National Cholesterol Education Program (NCEP)/Adult Treatment Panel III criteria] were assessed in a sample of 18,880 subjects aged 45-75 years from the population-based EpiHealth study. Participants were categorized into six groups according to BMI category (normal weight/BMI <25 kg/m(2), overweight/BMI 25-30 kg/m(2), and obesity/BMI >30 kg/m(2)) and MetS status (+/-, NCEP criteria). A wide range of lifestyle factors related to physical activity, smoking, alcohol, sleep quality, working conditions, quality of life and stress, and eating patterns were assessed using a questionnaire.

RESULTS: Prevalent MetS (23% in the sample) was associated with less physical activity (P < 0.0001), more TV watching (P < 0.0001), more years of smoking (P < 0.0001), lower education level (P = 0.007), and experiencing a poor general quality of life (P < 0.0001). These lifestyle factors were all associated with MetS, independently of each other and independently of BMI. Similar results were generated when number of MetS components and presence/absence of individual MetS components were used as outcomes.

CONCLUSIONS: This cross-sectional study identified alterations in a number of lifestyle factors associated with MetS independently of each other and independently of BMI. Future longitudinal studies are needed to assess causal and temporal relationships between lifestyle factors and MetS development.

Keyword
MHO, lifestyle factors, metabolic syndrome, obesity
National Category
Clinical Medicine
Research subject
Health and Welfare
Identifiers
urn:nbn:se:du-24670 (URN)10.1089/met.2016.0120 (DOI)000397585500003 ()28339343 (PubMedID)
Available from: 2017-03-31 Created: 2017-03-31 Last updated: 2017-04-28Bibliographically approved
Wändell, 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]

OBJECTIVE: 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.

METHODS: 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.

RESULTS: 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).

CONCLUSIONS: In this clinical setting, we found no evidence pointing to an increased risk of HS with antithrombotic treatment.

Keyword
Anticoagulants; Atrial fibrillation; Cardiovascular co-morbidity; Gender; Hemorrhagic stroke; Mortality
National Category
Clinical Medicine
Research subject
Health and Welfare
Identifiers
urn:nbn:se:du-23336 (URN)10.1007/s00228-016-2152-8 (DOI)000392308200010 ()27826643 (PubMedID)
Available from: 2016-11-11 Created: 2016-11-11 Last updated: 2017-11-29Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-6933-4637

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