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Atrial fibrillation and cause of death, sex differences in mortality, and anticoagulation treatment in low-risk patients
Örebro University, School of Medical Sciences.
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Atrial fibrillation (AF) is the most common arrhythmia but information on cause of death in patients with AF is sparse, and whether individuals at low risk of cerebral infarction (CVL) should receive antico-agulant medication is controversial. Studies of sex differences with respect to mortality risk have shown conflicting results.

Methods: Data were obtained from Swedish National Registers. In Study I, there were 272 186 AF patients and matched controls and in Studies II and III, 9519 AF patients and no other diagnosis and matched controls. Study IV compared treatment with warfarin to no treatment in 48 433 patients with AF. Hazard ratio (HR) was calculated with 95% confidence intervals and outcome rates as number per 1000 person-years.

Results: Ischemic heart disease (IHD) was the most common underlying cause of death and was present in 40.2% of AF patients at a HR of 1.7 (1.4-2.1). CVL/stroke was a cause of death in 13.1%, HR 2.7 (1.8-4.0). Among underlying and contributing causes of death, the most common diagnoses were IHD in 43.5%, HR 1.7 (1.4-2.0) and heart failure in 33.1%, HR 2.9 (2.2-3.7). The HRs for mortality in females with AF in age categories ≤65, 65-74, and 75-85 were 2.15, 1.72, and 1.44, and for males 1.76, 1.36, and 1.24. The rates of mortality in females with AF in age categories 55-64, 65-74, and 75-85 were 6.2, 20.7, and 57.3, and for males 8.5, 27.3, and 64.5. In patients 65-74 years, females with a CHA2DS2-VASc score of 2, and males with a score of 1 receiving warfarin treatment showed a significantly reduced risk of cerebral infarc-tion/stroke, HR 0.46 (0.25-0.83) for females and for males, HR 0.39 (0.21-0.73).

Conclusions: Most common causes of death in AF patients were CVL/stroke, heart failure, and IHD. HR of mortality in patients with AF was higher in females than in males but absolute risk was higher in males with AF compared to females with AF. Anticoagulant therapy was benefi-cial in patients ≥65 years, regardless of the CHA2DS2-VASc score.

Place, publisher, year, edition, pages
Örebro: Örebro University , 2018. , p. 71
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 176
Keywords [en]
Atrial fibrillation, Cerebral infarction, Anticoagulation, Cause of death, Mortality risk, Sex differences, CHA2DS2-VASc score
National Category
General Practice Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:oru:diva-65530ISBN: 978-91-7529-236-6 (print)OAI: oai:DiVA.org:oru-65530DiVA, id: diva2:1187994
Public defence
2018-05-04, Örebro universitet, Campus USÖ, hörsal C2, Södra Grev Rosengatan 32, Örebro, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2018-03-06 Created: 2018-03-06 Last updated: 2018-03-26Bibliographically approved
List of papers
1. All-cause mortality in 272 186 patients hospitalized with incident atrial fibrillation 1995-2008: a Swedish nationwide long-term case-control study
Open this publication in new window or tab >>All-cause mortality in 272 186 patients hospitalized with incident atrial fibrillation 1995-2008: a Swedish nationwide long-term case-control study
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2013 (English)In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, no 14, p. 1061-1067Article in journal (Refereed) Published
Abstract [en]

Aims To evaluate long-term all-cause risk of mortality in women and men hospitalized for the first time with atrial fibrillation (AF) compared with matched controls. Methods and results A total of 272 186 patients (44% women) <= 85 years at the time of hospitalization with incidental AF 1995-2008 and 544 344 matched controls free of in-hospital diagnosis of AF were identified. Patients were followed via record linkage of the Swedish National Patient Registry and the Cause of Death Registry. Using Cox regression models, the long-term relative all-cause mortality risk, adjusted for concomitant diseases, in women vs. controls was 2.15, 1.72, and 1.44 (P < 0.001) in the age categories <= 65, 65-74, and 75-85 years, respectively. The corresponding figures for men were 1.76, 1.36, and 1.24 (P < 0.001). Among concomitant diseases, neoplasm, chronic renal failure, and chronic obstructive pulmonary disease contributed most to the increased all-cause mortality vs. controls. In patients with AF as the primary diagnosis, the relative risk of mortality was 1.63, 1.46, and 1.28 (P < 0.001) in women and 1.45, 1.17, and 1.10 (P < 0.001) in men. Conclusion Atrial fibrillation was an independent risk factor of all-cause mortality in patients with incident AF. The concomitant diseases that contributed most were found outside the thromboembolic risk scores. The highest relative risk of mortality was seen in women and in the youngest patients compared with controls, and the differences between genders in each age category were statistically significant.

Keywords
Atrial fibrillation, Mortality, Gender, Age, Long term
National Category
Cardiac and Cardiovascular Systems
Research subject
Cardiology
Identifiers
urn:nbn:se:oru:diva-38709 (URN)10.1093/eurheartj/ehs469 (DOI)000317424300014 ()23321349 (PubMedID)2-s2.0-84876218799 (Scopus ID)
Note

Funding agencies ar:

AstraZeneca R&D, Mölndal, Sweden

Örebro Heart Foundation Research and

Committee of Örebro University Hospital

Available from: 2014-11-18 Created: 2014-11-18 Last updated: 2018-07-23Bibliographically approved
2. Gender-related differences in risk of cardiovascular morbidity and all-cause mortality in patients hospitalized with incident atrial fibrillation without concomitant diseases: A nationwide cohort study of 9519 patients
Open this publication in new window or tab >>Gender-related differences in risk of cardiovascular morbidity and all-cause mortality in patients hospitalized with incident atrial fibrillation without concomitant diseases: A nationwide cohort study of 9519 patients
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2014 (English)In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 177, no 1, p. 91-99Article in journal (Refereed) Published
Abstract [en]

Background: Previous studies of patients with "lone" and "idiopathic" atrial fibrillation (AF) have provided conflicting evidence concerning the development, management and prognosis of this condition.

Methods: In this nation-wide, retrospective, cohort study, we studied patients diagnosed with incidental AF recorded in national Swedish registries between 1995 and 2008. Controls were matched for age, sex and calendar year of the diagnosis of AF in patients. All subjects were free of any in-hospital diagnosis from 1987 and until patients were diagnosed with AF and also free of any diagnosis within one year from the time of inclusion. Follow-up continued until 2009. We identified 9519 patients (31% women) and 12,468 matched controls.

Results: Relative risks (RR) versus controls for stroke or transient ischemic attack (TIA) in women were 19.6, 4.4, 3.4 and 2.5 in the age categories <55, 55-64, 65-74 and 75-85, years respectively. Corresponding figures for men were 3.4, 2.5, 1.7 and 1.9. RR for heart failure were 6.6, 6.6, 6.3 and 3.8 in women and 7.8, 4.6, 4.9 and 2.9 in men. All RR were statistically significant with p < 0.01. RR for myocardial infarction and all-cause mortality were statistically significantly increased only in the two oldest age categories in women and 65-74 years in men.

Conclusions: Patients with AF and no co-morbidities at inclusion had at least a doubled risk of stroke or TIA and a tripled risk of heart failure, through all age categories, as compared to controls. Women were at higher RR of stroke or TIA than men. (C) 2014 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-SA license (http://creativecommons.org/licenses/by-nc-sa/3.0/).

Place, publisher, year, edition, pages
Elsevier, 2014
Keywords
Atrial fibrillation, Cardiovascular morbidity, Mortality, Cohort, Nationwide
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:oru:diva-56310 (URN)10.1016/j.ijcard.2014.09.092 (DOI)000343895000046 ()25499348 (PubMedID)
Note

Funding Agencies:

AstraZeneca RD Mölndal

Örebro Heart Foundation

Research Committee of Örebro University Hospital OLL 2012-265231

Available from: 2017-03-14 Created: 2017-03-14 Last updated: 2018-06-19Bibliographically approved
3. Patients without comorbidities at the time of diagnosis of atrial fibrillation: causes of death during long-term follow-up compared to matched controls
Open this publication in new window or tab >>Patients without comorbidities at the time of diagnosis of atrial fibrillation: causes of death during long-term follow-up compared to matched controls
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2017 (English)In: Clinical Cardiology, ISSN 0160-9289, E-ISSN 1932-8737, Vol. 40, no 11, p. 1076-1082Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Little is known about the long-term, cause-specific mortality risk in patients without comorbidities at the time of diagnosis of atrial fibrillation (AF).

METHODS: From a nation-wide registry of patients hospitalized with incident AF between 1995 and 2008 we identified 9 519 patients with a first diagnosed AF and no comorbidities at the time of AF diagnosis. They were matched with 12 468 controls. The follow-up continued until December 2008. Causes of death were classified according to the ICD-10 codes.

RESULTS: During follow-up, 11.1% of patients with AF and 8.3% of controls died. Cardiovascular diseases were the most common causes of death and the only diagnoses which showed significantly higher relative risk in patients with AF than controls (HR 2.0, 95% CI 1.8-2.3), and the relative risk was significantly higher in women than in men. Stroke was a more common cause among patients with AF, 13.1% versus 9.7% (HR 2.7, 95% CI 1.8-4.0), while cerebral hemorrhage was more common among controls, 4.7% versus 10.2% (HR 0.9, 95% CI 0.6-1.5). The time from AF diagnosis to death was 6.0 ± 3.1 years.

CONCLUSIONS: In patients with incident AF and no known comorbidities at the time of AF diagnosis, only cardiovascular diseases were more often causes of death as compared to controls. Women carried a significantly higher relative risk than men.

Place, publisher, year, edition, pages
John Wiley & Sons, 2017
Keywords
atrial fibrillation, cause of death, idiopathic, morbidity, mortality
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:oru:diva-61704 (URN)10.1002/clc.22776 (DOI)000417744800020 ()28841233 (PubMedID)2-s2.0-85028540727 (Scopus ID)
Funder
AstraZeneca
Note

Funding Agency:

Örebro Heart Foundation 

Research Committee of Örebro University Hospital, Sweden 

Available from: 2017-11-13 Created: 2017-11-13 Last updated: 2018-09-18Bibliographically approved
4. Patients with atrial fibrillation and outcomes of cerebral infarction in those with treatment of warfarin versus no warfarin with references to CHA(2)DS(2)-VASc score, age and sex: A Swedish nationwide observational study with 48 433 patients
Open this publication in new window or tab >>Patients with atrial fibrillation and outcomes of cerebral infarction in those with treatment of warfarin versus no warfarin with references to CHA(2)DS(2)-VASc score, age and sex: A Swedish nationwide observational study with 48 433 patients
Show others...
2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 5, article id e0176846Article in journal (Refereed) Published
Abstract [en]

Aims: There is controversy in the guidelines as to whether patients with atrial fibrillation and a low risk of stroke should be treated with anticoagulation, especially those with a CHA(2)DS(2)-VASc score of 1 point.

Methods: In a retrospective, nationwide cohort study, we used the Swedish National Patient Registry, the National Prescribed Drugs Registry, the Swedish Registry of Education and the Population and Housing Census Registry. 48 433 patients were identified between 1 January 2006 and 31 December 2008 with incident atrial fibrillation who were divided in age categories, sex and a CHA(2)DS(2)-VASc score of 0, 1, 2 and >= 3 and they were included in a time-varying analysis of warfarin treatment versus no treatment. The primary end-point was cerebral infarction and stroke, and patients were followed until 31 December 2009.

Results: Patients with 1 point from the CHA(2)DS(2)-VASc score showed the following adjusted hazard ratios (HR) with a 95% confidence interval: men 65-74 years 0.46 (0.25-0.83), men < 65 years 1.11 (0.56-2.23) and women < 65 years 2.13 (0.94-4.82), where HR < 1 indicates protection with warfarin. In patients < 65 years and 2 points, HR in men was 0.35 (0.18-0.69) and in women 1.84 (0.86-3.94) while, in women with at least 3 points, HR was 0.31 (0.16-0.59). In patients 65-74 years and 2 points, HR in men was 0.37 (0.23-0.59) and in women 0.39 ( 0.21-0.73). Categories including age >= 65 years or >= 3 points showed a statistically significant protection from warfarin.

Conclusions: Our results support that treatment with anticoagulation may be considered in all patients with an incident atrial fibrillation diagnosis and an age of 65 years and older, i.e. also when the CHA(2)DS(2)-VASc score is 1.

Place, publisher, year, edition, pages
Public Library of Science, 2017
National Category
Cardiac and Cardiovascular Systems
Research subject
Cardiology
Identifiers
urn:nbn:se:oru:diva-57914 (URN)10.1371/journal.pone.0176846 (DOI)000400648500084 ()28472091 (PubMedID)2-s2.0-85019090489 (Scopus ID)
Note

Funding Agencies:

Research Committee of Örebro University  0LL 2012-265231 

AstraZeneca RD Mölndal  

Örebro Heart Foundation 

Available from: 2017-06-08 Created: 2017-06-08 Last updated: 2018-07-31Bibliographically approved

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