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Purpose: Data describing treatment patterns of patients with venous thromboembolism (VTE) patients in Scandinavia are scarce. This study sought to address this scarcity by describing demographic and clinical characteristics, trends in the use of oral anticoagulants (OACs), and treatment patterns in patients treated for VTE in Norway between 2013 and 2017., Methods: Using data from Norway's nationwide registries, a cohort study included patients newly (after 2008) treated OACs who were diagnosed with VTE between January 2013 and December 2017 and were dispensed an OAC (warfarin, apixaban, rivaroxaban, dabigatran, or edoxaban) within 30 days. Patient characteristics and the percentage of patients with VTE who initiated treatment with each OAC for each calendar year were reported. Initial therapy persistence was assessed using Kaplan-Meier curves and compared between the OAC groups using the log-rank test., Findings: The comorbidity burden was similar between patients taking warfarin and those taking apixaban but lower among patients taking rivaroxaban. Direct oral anticoagulant (DOAC) use increased from 33.2% to 93.6% during the study period, whereas warfarin use decreased. Persistence was higher in the apixaban cohort compared with the warfarin cohort, with the difference mostly apparent after 6 months, whereas persistence was similar between the patients taking rivaroxaban and those taking warfarin., Implications: Between 2013 and 2017, DOAC use among patients with VTEs increased markedly in Norway, whereas the use of warfarin decreased. Patients taking apixaban had higher persistence compared with those taking warfarin, whereas patients taking warfarin and those taking rivaroxaban had similar persistence. Further studies with longer follow-up are required to examine the use of extended OAC treatment for VTE., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The relationship between serum levels of calcium, parathyroid hormone (PTH) and risk of venous thromboembolism (VTE) has not been addressed in population-based cohorts. We investigated the associations between serum levels of calcium and PTH, with future risk of VTE in a general adult population., Design: Population-based cohort., Methods: A total of 27 712 subjects (25-87 years) who participated in Tromsø 4 (1994-1995) and Tromsø 5 (2001-2002) surveys were included in the study, and total calcium and PTH were measured in 27 685 and 8547 subjects respectively. Incident VTE was recorded through December 31, 2012. Cox-regression models with calcium and PTH as time-varying exposures were used to calculate hazard ratios (HR) of VTE by quartiles of calcium and PTH. Quartiles of calcium and PTH were also combined to assess the effect of discordants of both PTH and calcium (e.g. highest and lowest quartiles of both calcium and PTH) on VTE risk using the middle two quartiles as reference., Results: There were 712 VTEs during 15.0 years of median follow-up. Serum levels of calcium and PTH were not associated with risk of VTE. However, subjects with discordant high serum levels of both calcium and PTH (calcium ≥2.45 mmol/L and PTH ≥4.0 pmol/L) had increased risk of VTE compared to those in subjects with normal calcium and PTH (multivariable HR: 1.78, 95% CI: 1.12-2.84)., Conclusions: Serum levels of calcium and PTH separately were not associated with future risk of VTE, but subjects with high levels of both calcium and PTH had increased risk of VTE compared to those in subjects with normal levels., (© 2017 European Society of Endocrinology.)

The relationship between chronic obstructive pulmonary disease (COPD) and risk of venous thromboembolism (VTE) has been scarcely studied in the general population. We aimed to investigate the association between COPD and risk of VTE and mortality in a population-based cohort.Spirometry was conducted in 8646 males and females, participating in the fifth (2001-02) and sixth (2007-08) surveys of the Tromsø Study. Incident VTE events during follow-up were registered from the date of inclusion to December 31, 2011. Cox-regression models with COPD stages and confounders as time varying covariates were used to calculate hazard ratios with 95% confidence intervals for VTE and all-cause mortality.During a median follow-up of 6.2 years, 215 subjects developed VTE. Subjects with COPD stage III/IV had a two-fold higher risk of secondary VTE compared to subjects with normal airflow (HR 2.05, 95% CI 1.02-4.10). COPD patients, particularly those with stage III/IV disease, with VTE had a higher mortality rate than COPD patients without VTE (50.2% versus 5.6% per year).Our findings suggest that patients with severe COPD may have increased risk of secondary VTE, and that COPD patients with VTE have a higher mortality rate than COPD patients without VTE., (Copyright ©ERS 2016.)

Objective: The relationship between thyroid function and the risk of venous thromboembolism (VTE) has not been addressed in population-based cohorts. We investigated the association between TSH levels and the risk of VTE in a general adult population., Design: Population-based cohort study., Methods: TSH was measured in 11 962 subjects aged 25-89 years who participated in Tromsø 4-6 starting in 1994-1995. Incident VTE events were recorded through 31st December 2010. Cox's regression models with TSH as a time-varying covariate were used to calculate hazard ratios (HRs) of VTE by TSH categories (low TSH: <0.05  mU/l; moderately reduced TSH: 0.05-0.19  mU/l; normal TSH: 0.20-4.00  mU/l; moderately elevated TSH: 4.01-5.00  mU/l; and high TSH: >5.00 mU/l) and within the normal range of TSH, modeling TSH as a continuous variable., Results: There were 289 VTEs during 8.2 years of median follow-up. Subjects with low (prevalence: 0.22%) and high (3.01%) TSH had slightly higher risk estimates for VTE than did subjects with normal TSH (multivariable HRs: 2.16, 95% CI 0.69-6.76 and 1.55, 95% CI 0.87-2.77 respectively), but the CIs were wide. Moreover, there was no association between TSH within the normal range and VTE (HR per 1 mU/l increase: 0.95, 95% CI 0.82-1.11)., Conclusion: Serum levels of TSH within the normal range were not associated with a risk of VTE, whereas low and high TSH levels were rare and associated with a moderately higher risk of VTE. The present findings suggest that only a minor proportion of the VTE risk in the population can be attributed to thyroid dysfunction., (© 2015 European Society of Endocrinology.)

Background: Patients with arterial cardiovascular disease have increased postprandial lipemia, and plasma levels of postprandial remnants are related to the progression of atherosclerosis. Studies have shown that patients with unprovoked venous thromboembolism have increased risk of arterial cardiovascular disease., Objective: To investigate whether patients with a history of unprovoked venous thromboembolism have increased postprandial lipemia., Methods: A population-based case-control study was performed in 20 patients with a history of unprovoked venous thromboembolism and 20 age- and gender-matched healthy controls. Participants were subjected to a standard fat tolerance test (1 g/kilo body weight) with subsequent blood sampling every second hour for 8 hours. Lipids were measured by traditional methods and lipoprotein subclasses by proton nuclear magnetic resonance., Results: Fasting lipids and lipoprotein subclasses did not differ between groups. The postprandial lipemia, assessed by the incremental area under the triglyceride curve, was not different in venous thromboembolism patients and healthy controls (5.0 ± 3.6 mmol/L∗h vs 5.3 ± 4.4 mmol/L∗h, P = .81). Similarly, the distribution and size of the lipoprotein subclasses obtained 4 hours postprandially did not differ between groups., Conclusion: Patients with a history of unprovoked venous thromboembolism had similar lipoprotein subclasses size, distribution, and postprandial lipemia as healthy controls. Our findings indicate that postprandial lipemia is not a link between unprovoked venous thromboembolism and arterial cardiovascular disease., (Copyright © 2013 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Background: Recent findings suggest that chronic kidney disease (CKD) may be associated with an increased risk of venous thromboembolism (VTE). Given the high prevalence of mild-to-moderate CKD in the general population, in depth analysis of this association is warranted., Methods and Results: We pooled individual participant data from 5 community-based cohorts from Europe (second Nord-Trøndelag Health Study [HUNT2], Prevention of Renal and Vascular End-stage Disease [PREVEND], and the Tromsø study) and the United States (Atherosclerosis Risks in Communities [ARIC] and Cardiovascular Health Study [CHS]) to assess the association of estimated glomerular filtration rate (eGFR), albuminuria, and CKD with objectively verified VTE. To estimate adjusted hazard ratios for VTE, categorical and continuous spline models were fit by using Cox regression with shared-frailty or random-effect meta-analysis. A total of 1178 VTE events occurred over 599 453 person-years follow-up. Relative to eGFR 100 mL/min per 1.73 m(2), hazard ratios for VTE were 1.29 (95% confidence interval, 1.04-1.59) for eGFR 75, 1.31 (1.00-1.71) for eGFR 60, 1.82 (1.27-2.60) for eGFR 45, and 1.95 (1.26-3.01) for eGFR 30 mL/min per 1.73 m(2). In comparison with an albumin-to-creatinine ratio (ACR) of 5.0 mg/g, the hazard ratios for VTE were 1.34 (1.04-1.72) for ACR 30 mg/g, 1.60 (1.08-2.36) for ACR 300 mg/g, and 1.92 (1.19-3.09) for ACR 1000 mg/g. There was no interaction between clinical categories of eGFR and ACR (P=0.20). The adjusted hazard ratio for CKD, defined as eGFR <60 mL/min per 1.73 m(2) or albuminuria ≥30 mg/g, (versus no CKD) was 1.54 (95% confidence interval, 1.15-2.06). Associations were consistent in subgroups according to age, sex, and comorbidities, and for unprovoked versus provoked VTE, as well., Conclusions: Both eGFR and ACR are independently associated with increased risk of VTE in the general population, even across the normal eGFR and ACR ranges.

Background: Previous studies have shown an association between impaired kidney function, assessed by cystatin C-based estimated glomerular filtration rate, and venous thromboembolism. The aim of this study was to investigate whether serum cystatin C was associated with a risk of venous thromboembolism among subjects with normal kidney function in a prospective population-based study., Design and Methods: Cystatin C was measured in serum from 3251 men and women with normal kidney function, aged 25-84 years, who participated in the Tromsø study in 1994-1995. Normal kidney function was defined as a creatinine-based estimated glomerular filtration rate greater than 90 mL/min/1.73 m(2) and absence of microalbuminuria. Incident venous thromboembolism was registered from the date of inclusion through to the end of follow-up, September 1, 2007. Cox-regression models were used to calculate hazard ratios with 95% confidence intervals for venous thromboembolism., Results: There were 83 incident venous thromboembolic events, of which 53 (63.9 %) were provoked, during a median of 12.3 years of follow-up. A one standard deviation (0.11 mg/L) increase in serum cystatin C levels was associated with a 43% (hazard ratio 1.43; 95% confidence interval 1.17-1.72) increased risk of total venous thromboembolism. Subjects with cystatin C levels in the top quartile (≥ 0.87 mg/L) had a 2.5-fold (hazard ratio 2.51; 95% confidence interval 1.27-4.96) increased risk of venous thromboembolism compared to those with levels in the bottom quartile (≤ 0.72 mg/L) in adjusted analysis. The risk estimates were even higher for provoked venous thromboembolism (hazard ratio 3.11; 95% confidence interval 1.23-7.86)., Conclusions: Serum cystatin C levels were associated with the risk of venous thromboembolism in subjects with normal kidney function. Our findings suggest that elevated serum cystatin C levels may promote venous thrombosis beyond reflecting impaired kidney function.