Atrial fibrillation, venous thromboembolism, and risk of pulmonary hypertension: A Swedish Nationwide Register Study

Background Atrial fibrillation (AF) is a recognized risk factor for systemic arterial- and venous thromboembolism (VTE), including pulmonary embolism (PE), and may thereby contribute to the development of chronic thrombo-embolic pulmonary hypertension (PH). AF may also play a direct role in the development of post-capillary PH. We aimed to investigate the association between AF - with or without incident VTE - and the occurrence of PH.

A total of 521 988 patients diagnosed with AF between 1987–2013, without a previous diagnosis of VTE or PH, were identified from the Swedish National Patient Register (NPR) and matched for age, sex, and county with 1 017 277 population controls without AF, VTE or PH.

The mean age of the AF patients was 71.1 (SD ±10.1) years and 42.8 % were women. During a median follow-up period of 11 (IQR 5.1,17) years, 4 454 (0.9%) AF patients and 1 855 (0.2%) controls were diagnosed with PH, HR 4.7 (4.4-5.0). The AF group had a significantly higher comorbidity burden at baseline, with a mean CHA2DS2-VASc of 2.9 compared to 2.1 in controls. In the absence of intercurrent VTE, the HR of PH was 4.2 (3.9-4.5) among AF patients compared to controls. Intercurrent VTE increased the HR of PH a further 1.9-fold (1.7-2.1) and 3.5 (3.1-4.0), among AF patients and controls, respectively. The HR for PH in AF patients with incident VTE was 8.1 (7.3-9.1).

AF was associated with a markedly increased risk of developing incident PH, and this risk was further increased by incident VTE. Competing Interest Statement The authors have declared no competing interest. Clinical Trial N A Funding Statement This work was supported by grants from the following: the Swedish state under an agreement between the Swedish Government and the County Councils Concerning Economic Support of Research and Education of Doctors [grant number ALFGBG-427301, ALFGBG-966211, ALFGBG-971608, ALFGBG-979104]; the Swedish Heart and Lung Foundation [grant number 2015-0438, 2018-0589, 2021-0345]; the Swedish Research Council [2018-02527, VRREG 2019-00193]. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the Regional Ethics Review Board in Gothenburg (Dnr. 104-15). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Footnotes ↵† Deceased Data Availability Original data are available through contact with Dr. Martin Adiels, responsible for the statistical analysis of the study.