Download PDF
Open Access
CC BY-NC-ND 4.0 · TH Open 2026; 10: a28115034
DOI: 10.1055/a-2811-5034
Original Article

Combined Effect of Hemoglobin Levels and Obesity on the Risk of Incident Venous Thromboembolism: The Tromsø Study

Authors

  • Lisa Jakobsen

    1   Department of Clinical Medicine, University of Tromsø—Thrombosis Research Group (TREC), Tromsø, Norway

  • Fridtjof B. Rinde

    1   Department of Clinical Medicine, University of Tromsø—Thrombosis Research Group (TREC), Tromsø, Norway

  • John-Bjarne Hansen

    1   Department of Clinical Medicine, University of Tromsø—Thrombosis Research Group (TREC), Tromsø, Norway
    2   Thrombosis Research Center (TREC), Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway

  • Vânia M. Morelli

    1   Department of Clinical Medicine, University of Tromsø—Thrombosis Research Group (TREC), Tromsø, Norway
    2   Thrombosis Research Center (TREC), Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway

  • Sigrid K. Brækkan

    1   Department of Clinical Medicine, University of Tromsø—Thrombosis Research Group (TREC), Tromsø, Norway
    2   Thrombosis Research Center (TREC), Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
Further Information
Also available at
  Permissions and Reprints


Graphical Abstract

Abstract

Background

Red blood cells (RBCs) are key determinants of blood viscosity, which is related to thrombosis risk. Obesity is a well-recognized risk factor for venous thromboembolism (VTE). Whether the combination of these two risk factors synergistically increases VTE risk has not been studied. We aimed to investigate the joint effect of high hemoglobin and obesity on the risk of VTE in a population-based cohort.

Methods

We included 35,801 participants from the Tromsø 4–7 surveys (1994–2016). All first-lifetime VTEs were validated and recorded from enrollment throughout 2020. Hemoglobin levels were categorized as low (women: <13.2 g/dL, men: <14.7 g/dL), medium (women: 13.2–14.0 g/dL, men: 14.7–15.5 g/dL), and high (women: ≥14.1 g/dL, men: ≥15.6 g/dL). Body mass index (BMI) was categorized as normal weight (<25 kg/m2), overweight (25–29.9 kg/m2), and obese (≥30 kg/m2). Hazard ratios (HRs) for VTE with 95% confidence intervals (CIs) were estimated according to combined categories of hemoglobin and BMI in models adjusted for age, sex, cancer, arterial cardiovascular disease, and smoking.

Results

During 17.3 years of median follow-up, 1,040 cases of VTE occurred. In normal weight individuals, the HR of VTE according to high hemoglobin levels was 1.22 (95% CI: 0.90–1.66). The HR of VTE in obese individuals with low hemoglobin was 1.81 (95% CI: 1.35–2.43), while the HR of VTE in obese individuals with high hemoglobin levels was 1.71 (95% CI: 1.30–2.25), compared with those with normal weight and low hemoglobin.

Conclusion

Combination of high hemoglobin and obesity did not yield excess VTE risk, suggesting no evidence of biological interaction between these factors in the pathogenesis of VTE.

Keywords

obesity - hemoglobin - interaction - venous thromboembolism

Supplementary Material



Publication History

Received: 16 January 2026

Accepted: 10 February 2026

Accepted Manuscript online:
13 February 2026

Article published online:
24 February 2026

© 2026. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

Bibliographical Record
Lisa Jakobsen, Fridtjof B. Rinde, John-Bjarne Hansen, Vânia M. Morelli, Sigrid K. Brækkan. Combined Effect of Hemoglobin Levels and Obesity on the Risk of Incident Venous Thromboembolism: The Tromsø Study. TH Open 2026; 10: a28115034.
DOI: 10.1055/a-2811-5034
 

  • References

  • 1 Khan F, Tritschler T, Kahn SR, Rodger MA. Venous thromboembolism. Lancet 2021; 398 (10294): 64-77
    Search in Google Scholar
  • 2 Schulman S, Lindmarker P, Holmström M. et al. Post-thrombotic syndrome, recurrence, and death 10 years after the first episode of venous thromboembolism treated with warfarin for 6 weeks or 6 months. J Thromb Haemost 2006; 4 (04) 734-742
    Search in Google Scholar
  • 3 Klok FA, van der Hulle T, den Exter PL, Lankeit M, Huisman MV, Konstantinides S. The post-PE syndrome: A new concept for chronic complications of pulmonary embolism. Blood Rev 2014; 28 (06) 221-226
    Search in Google Scholar
  • 4 Cushman M, Barnes GD, Creager MA. et al; American Heart Association Council on Peripheral Vascular Disease; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; Council on Epidemiology and Prevention; and the International Society on Thrombosis and Haemostasis. Venous Thromboembolism Research Priorities: A Scientific Statement From the American Heart Association and the International Society on Thrombosis and Haemostasis. Circulation 2020; 142 (06) e85-e94
    Search in Google Scholar
  • 5 Raskob GE, Angchaisuksiri P, Blanco AN. et al; ISTH Steering Committee for World Thrombosis Day. Thrombosis: A major contributor to global disease burden. Arterioscler Thromb Vasc Biol 2014; 34 (11) 2363-2371
    Search in Google Scholar
  • 6 Braekkan SK, Siegerink B, Lijfering WM, Hansen JB, Cannegieter SC, Rosendaal FR. Role of obesity in the etiology of deep vein thrombosis and pulmonary embolism: Current epidemiological insights. Semin Thromb Hemost 2013; 39 (05) 533-540
    Search in Google Scholar
  • 7 Frischmuth T, Tøndel BG, Brækkan SK, Hansen JB, Morelli VM. The risk of incident venous thromboembolism attributed to overweight and obesity: The Tromsø Study. Thromb Haemost 2024; 124 (03) 239-249
    Search in Google Scholar
  • 8 Horvei LD, Brækkan SK, Hansen JB. Weight change and risk of venous thromboembolism: The Tromsø Study. PLoS ONE 2016; 11 (12) e0168878
    Search in Google Scholar
  • 9 French SA, Lutsey PL, Rosamond W, MacLehose RF, Cushman M, Folsom AR. Weight change over 9 years and subsequent risk of venous thromboembolism in the ARIC cohort. Int J Obes (Lond) 2020; 44 (12) 2465-2471
    Search in Google Scholar
  • 10 Klovaite J, Benn M, Nordestgaard BG. Obesity as a causal risk factor for deep venous thrombosis: A Mendelian randomization study. J Intern Med 2015; 277 (05) 573-584
    Search in Google Scholar
  • 11 Klarin D, Emdin CA, Natarajan P, Conrad MF, Kathiresan S. INVENT Consortium. Genetic analysis of venous thromboembolism in UK Biobank Identifies the ZFPM2 locus and implicates obesity as a causal risk factor. Circ Cardiovasc Genet 2017; 10 (02) e001643
    Search in Google Scholar
  • 12 Lindström S, Germain M, Crous-Bou M. et al; INVENT Consortium. Assessing the causal relationship between obesity and venous thromboembolism through a Mendelian Randomization study. Hum Genet 2017; 136 (07) 897-902
    Search in Google Scholar
  • 13 Kim MS, Kim WJ, Khera AV. et al. Association between adiposity and cardiovascular outcomes: An umbrella review and meta-analysis of observational and Mendelian randomization studies. Eur Heart J 2021; 42 (34) 3388-3403
    Search in Google Scholar
  • 14 Landin K, Stigendal L, Eriksson E. et al. Abdominal obesity is associated with an impaired fibrinolytic activity and elevated plasminogen activator inhibitor-1. Metabolism 1990; 39 (10) 1044-1048
    Search in Google Scholar
  • 15 Rosito GA, D'Agostino RB, Massaro J. et al. Association between obesity and a prothrombotic state: The Framingham Offspring Study. Thromb Haemost 2004; 91 (04) 683-689
    Search in Google Scholar
  • 16 Darvall KA, Sam RC, Silverman SH, Bradbury AW, Adam DJ. Obesity and thrombosis. Eur J Vasc Endovasc Surg 2007; 33 (02) 223-233
    Search in Google Scholar
  • 17 Arfvidsson B, Eklof B, Balfour J. Iliofemoral venous pressure correlates with intraabdominal pressure in morbidly obese patients. Vasc Endovascular Surg 2005; 39 (06) 505-509
    Search in Google Scholar
  • 18 Willenberg T, Schumacher A, Amann-Vesti B. et al. Impact of obesity on venous hemodynamics of the lower limbs. J Vasc Surg 2010; 52 (03) 664-668
    Search in Google Scholar
  • 19 Borch KH, Nyegaard C, Hansen JB. et al. Joint effects of obesity and body height on the risk of venous thromboembolism: The Tromsø Study. Arterioscler Thromb Vasc Biol 2011; 31 (06) 1439-1444
    Search in Google Scholar
  • 20 Pomp ER, le Cessie S, Rosendaal FR, Doggen CJ. Risk of venous thrombosis: Obesity and its joint effect with oral contraceptive use and prothrombotic mutations. Br J Haematol 2007; 139 (02) 289-296
    Search in Google Scholar
  • 21 Ribeiro DD, Lijfering WM, Rosendaal FR, Cannegieter SC. Risk of venous thrombosis in persons with increased body mass index and interactions with other genetic and acquired risk factors. J Thromb Haemost 2016; 14 (08) 1572-1578
    Search in Google Scholar
  • 22 Kwaan HC, Wang J. Hyperviscosity in polycythemia vera and other red cell abnormalities. Semin Thromb Hemost 2003; 29 (05) 451-458
    Search in Google Scholar
  • 23 Guyton AC, Richardson TQ. Effect of hematocrit on venous return. Circ Res 1961; 9: 157-164
    Search in Google Scholar
  • 24 Hellem AJ, Borchgrevink CF, Ames SB. The role of red cells in haemostasis: the relation between haematocrit, bleeding time and platelet adhesiveness. Br J Haematol 1961; 7: 42-50
    Search in Google Scholar
  • 25 Gruppo Italiano Studio Policitemia. Polycythemia vera: The natural history of 1213 patients followed for 20 years. Ann Intern Med 1995; 123 (09) 656-664
    Search in Google Scholar
  • 26 Boneu B. Laboratory investigations and prediction of thrombotic risk in polycythemia vera. Nouv Rev Fr Hematol (1978) 1994; 36 (02) 183-185
    Search in Google Scholar
  • 27 Lee G, Choi S, Kim K. et al. Association between changes in hemoglobin concentration and cardiovascular risks and all-cause mortality among young women. J Am Heart Assoc 2018; 7 (16) e008147
    Search in Google Scholar
  • 28 Marchioli R, Finazzi G, Specchia G. et al; CYTO-PV Collaborative Group. Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med 2013; 368 (01) 22-33
    Search in Google Scholar
  • 29 Braekkan SK, Mathiesen EB, Njølstad I, Wilsgaard T, Hansen JB. Hematocrit and risk of venous thromboembolism in a general population. The Tromso study. Haematologica 2010; 95 (02) 270-275
    Search in Google Scholar
  • 30 Folsom AR, Wang W, Parikh R, Lutsey PL, Beckman JD, Cushman M. Atherosclerosis Risk in Communities (ARIC) Study Investigators. Hematocrit and incidence of venous thromboembolism. Res Pract Thromb Haemost 2020; 4 (03) 422-428
    Search in Google Scholar
  • 31 Rezende SM, Lijfering WM, Rosendaal FR, Cannegieter SC. Hematologic variables and venous thrombosis: Red cell distribution width and blood monocyte count are associated with an increased risk. Haematologica 2014; 99 (01) 194-200
    Search in Google Scholar
  • 32 Luo S, Au Yeung SL, Zuber V, Burgess S, Schooling CM. Impact of genetically predicted red blood cell traits on venous thromboembolism: Multivariable Mendelian Randomization Study Using UK Biobank. J Am Heart Assoc 2020; 9 (14) e016771
    Search in Google Scholar
  • 33 Li H, Duo M, Zhang Z. et al; China pUlmonary Thromboembolism REgistry Study (CURES) Investigators. Blood cell traits and venous thromboembolism in East Asians: Observational and genetic evidence. iScience 2024; 27 (09) 110671
    Search in Google Scholar
  • 34 He J, Jiang Q, Yao Y. et al. Blood cells and venous thromboembolism risk: A two-sample Mendelian Randomization Study. Front Cardiovasc Med 2022; 9: 919640
    Search in Google Scholar
  • 35 Zwaal RF, Schroit AJ. Pathophysiologic implications of membrane phospholipid asymmetry in blood cells. Blood 1997; 89 (04) 1121-1132
    Search in Google Scholar
  • 36 Wells Jr RE, Merrill EW. Influence of flow properties of blood upon viscosity-hematocrit relationships. J Clin Invest 1962; 41 (08) 1591-1598
    Search in Google Scholar
  • 37 Jacobsen BK, Eggen AE, Mathiesen EB, Wilsgaard T, Njølstad I. Cohort profile: The Tromso Study. Int J Epidemiol 2012; 41 (04) 961-967
    Search in Google Scholar
  • 38 Hopstock LA, Grimsgaard S, Johansen H, Kanstad K, Wilsgaard T, Eggen AE. The seventh survey of the Tromsø Study (Tromsø7) 2015-2016: Study design, data collection, attendance, and prevalence of risk factors and disease in a multipurpose population-based health survey. Scand J Public Health 2022; 50 (07) 919-929
    Search in Google Scholar
  • 39 Braekkan SK, Borch KH, Mathiesen EB, Njølstad I, Wilsgaard T, Hansen JB. Body height and risk of venous thromboembolism: The Tromsø Study. Am J Epidemiol 2010; 171 (10) 1109-1115
    Search in Google Scholar
  • 40 WHO. Fact sheet: Obesity and Overweight. 2024 . Accessed September 18, 2024 at https://www.who.int/en/news-room/fact-sheets/detail/obesity-and-overweight
    Search in Google Scholar
  • 41 Gagnon DR, Zhang TJ, Brand FN, Kannel WB. Hematocrit and the risk of cardiovascular disease–the Framingham study: a 34-year follow-up. Am Heart J 1994; 127 (03) 674-682
    Search in Google Scholar
  • 42 Rothman K. Measuring interactions. In: Epidemiology: An Introduction. New York Oxford University Press; 2002
    Search in Google Scholar
  • 43 Andersson T, Alfredsson L, Källberg H, Zdravkovic S, Ahlbom A. Calculating measures of biological interaction. Eur J Epidemiol 2005; 20 (07) 575-579
    Search in Google Scholar
  • 44 Hultcrantz M, Modlitba A, Vasan SK. et al. Hemoglobin concentration and risk of arterial and venous thrombosis in 1.5 million Swedish and Danish blood donors. Thromb Res 2020; 186: 86-92
    Search in Google Scholar
  • 45 Spann AP, Campbell JE, Fitzgibbon SR. et al. The effect of hematocrit on platelet adhesion: Experiments and simulations. Biophys J 2016; 111 (03) 577-588
    Search in Google Scholar
  • 46 Dintenfass L. A study in flow, viscosity and clotting of human blood. Med J Aust 1963; 50 (01) 575-578
    Search in Google Scholar
  • 47 Quintó L, Aponte JJ, Menéndez C. et al. Relationship between haemoglobin and haematocrit in the definition of anaemia. Trop Med Int Health 2006; 11 (08) 1295-1302
    Search in Google Scholar
  • 48 Chen Z, Cao B, Liu L, Tang X, Xu H. Association between obesity and anemia in an nationally representative sample of United States adults: A cross-sectional study. Front Nutr 2024; 11: 1304127
    Search in Google Scholar
  • 49 Tarancon-Diez L, Iriarte-Gahete M, Sanchez-Mingo P. et al. Impact of obesity on iron metabolism and the effect of intravenous iron supplementation in obese patients with absolute iron deficiency. Sci Rep 2025; 15 (01) 1343
    Search in Google Scholar
  • 50 Hemade A, Salameh P. Revisiting the obesity-anaemia paradox: Inflammation and iron homeostasis in the BMI-haemoglobin relationship. Endocrinol Diabetes Metab 2025; 8 (05) e70110
    Search in Google Scholar
  • 51 Rosenblum SL. Inflammation, dysregulated iron metabolism, and cardiovascular disease. Front Aging 2023; 4: 1124178
    Search in Google Scholar