Plasma fibrinogen levels and all-cause and cause-specific mortality in an Italian adult population: results from the Moli-sani study

Submitted: 21 June 2022
Accepted: 16 December 2022
Published: 27 January 2023
Abstract Views: 1261
PDF: 296
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.


Epidemiological data on the association between fibrinogen levels and mortality are scarse and controversial. Longitudinal analyses were performed, separately by sex, on 17,689 individuals from the Moli-sani study [53% women, ≥35 years, free from cardiovascular disease (CVD) or cancer at enrolment], to evaluate the association between plasma fibrinogen and all-cause and cause-specific mortality. Over a median follow-up of 11.2 years, 1,058 deaths (34.7% CVD, 36.3% cancer) were ascertained. Both in the lowest (1.12-2.64 g/L) and highest (≥3.62 g/L) fibrinogen quintiles, women had an increased all-cause mortality hazard, when compared with third quintile (2.97-3.23 g/L). Dose-response analyses showed a U-shaped relationship in women (P overall <0.0001; P non-linear association <0.0001), but a positive linear association for all-cause mortality in men (P overall 0.0038; P non-linear association 0.76). Similar trends for a U-shaped association were observed for CVD mortality, while no association was observed with cancer deaths. A U-shaped association of fibrinogen levels with other-cause mortality was also found in both sexes. This study shows that not only higher but also lower fibrinogen levels represent hazard for mortality when compared to normal levels; U-shaped curves being prevalently observed in women.



PlumX Metrics


Download data is not yet available.



Mosesson MW. Fibrinogen and fibrin structure and functions. J Thromb Haemost 2005;3:1894-904. DOI:
Vilar R, Fish RJ, Casini A, Neerman-Arbez M. Fibrin(ogen) in human disease: both friend and foe. Haematologica 2020;105:284-96. DOI:
Weisel JW, Litvinov RI. Fibrin Formation, Structure and Properties. Subcell Biochem 2017;82:405-56. DOI:
Peng Y, Wang H, Li YM, et al. Relation between admission plasma fibrinogen levels and mortality in Chinese patients with coronary artery disease. Sci Rep 2016;6:30506. DOI:
Liu J, Zhang Y, Lavie CJ, et al. Associations of C-reactive protein and fibrinogen with mortality from all-causes, cardiovascular disease and cancer among U.S. adults. Prev Med. 2020;139:106044. DOI:
Ariëns RA. Fibrin(ogen) and thrombotic disease. J Thromb Haemost 2013;11:294-305. DOI:
Luyendyk JP, Schoenecker JG, Flick MJ. The multifaceted role of fibrinogen in tissue injury and inflammation. Blood 2019;133:511-20. DOI:
Fibrinogen Studies Collaboration, Danesh J, Lewington S, et al. Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis [published correction appears in JAMA. 2005 Dec 14;294(22):2848]. JAMA. 2005;294:1799-809 DOI:
Woodward M, Lowe GD, Rumley A, Tunstall-Pedoe H. Fibrinogen as a risk factor for coronary heart disease and mortality in middle-aged men and women. The Scottish Heart Health Study. Eur Heart J 1998;19:55-62. DOI:
Lind P, Hedblad B, Stavenow L, et al. Influence of plasma fibrinogen levels on the incidence of myocardial infarction and death is modified by other inflammation-sensitive proteins: a long-term cohort study. Arterioscler Thromb Vasc Biol 2001;21:452-8. DOI:
Maresca G, Di Blasio A, Marchioli R, Di Minno G. Measuring plasma fibrinogen to predict stroke and myocardial infarction: an update. Arterioscler Thromb Vasc Biol 1999;19:1368-77. DOI:
Herrick S, Blanc-Brude O, Gray A, Laurent G. Fibrinogen. Int J Biochem Cell Biol. 1999;31:741-6. DOI:
Allin KH, Bojesen SE, Nordestgaard BG. Inflammatory biomarkers and risk of cancer in 84,000 individuals from the general population. Int J Cancer 2016;139:1493-500. DOI:
Lin Y, Liu Z, Qiu Y, et al. Clinical significance of plasma D-dimer and fibrinogen in digestive cancer: A systematic review and meta-analysis. Eur J Surg Oncol 2018;44:1494-503. DOI:
WHO. Global Health Estimates: Life expectancy and leading causes of death and disability. Available from:
Averna M, Noto D. Clinical utility of novel biomarkers for cardiovascular disease risk stratification. Intern Emerg Med 2012;7:S263-70. DOI:
Pieters M, Ferreira M, de Maat MPM, Ricci C. Biomarker association with cardiovascular disease and mortality - The role of fibrinogen. A report from the NHANES study. Thromb Res. 2021;198:182-9. DOI:
Ahmadi-Abhari S, Luben RN, Wareham NJ, Khaw KT. Seventeen year risk of all-cause and cause-specific mortality associated with C-reactive protein, fibrinogen and leukocyte count in men and women: the EPIC-Norfolk study. Eur J Epidemiol 2013;28:541-50. DOI:
Yano K, Grove JS, Chen R, et al. Plasma fibrinogen as a predictor of total and cause-specific mortality in elderly Japanese-American men. Arterioscler Thromb Vasc Biol 2001;21:1065-70. DOI:
Di Castelnuovo A, Costanzo S, Persichillo M, et al. Distribution of short and lifetime risks for cardiovascular disease in Italians. Eur J Prev Cardiol 2012;19:723-30. DOI:
Donati MB, Vermylen J, Verstraete M. Fibrinogen degradation products and a fibrinogen assay based on clotting kinetics. Scand J Haematol Suppl 1971;13:255-6. DOI:
Cupaiolo R, Govaerts D, Blauwaert M, Cauchie P. Performance evaluation of a new Stago® automated haemostasis analyser: The STA R Max® 2. Int J Lab Hematol 2019;41:731-7. DOI:
SAS Institute Inc, Base SAS® 9.4 Procedures Guide: Statistical Procedures, second ed., SAS Institute, Inc, Cary, NC, 2013.
Di Castelnuovo A, De Curtis A, Costanzo S, et al. Association of D-dimer levels with all-cause mortality in a healthy adult population: findings from the MOLI-SANI study. Haematologica 2013;98:1476-80. DOI:
Folsom AR, Golden SH, Boland LL, Szklo M. Association of endogenous hormones with C-reactive protein, fibrinogen, and white blood count in post-menopausal women. Eur J Epidemiol 2005;20:1015-22. DOI:
Farré AL, Modrego J, Zamorano-León JJ. Effects of hormones on platelet aggregation. Horm Mol Biol Clin Investig 2014;18:27-36. DOI:
Williams MS, Cushman M, Ouyang P, et al. Association of Serum Sex Hormones with Hemostatic Factors in Women On and Off Hormone Therapy: The Multiethnic Study of Atherosclerosis. J Womens Health (Larchmt) 2016;25:166-72. DOI:
Zegura B, Guzic-Salobir B, Sebestjen M, Keber I. The effect of various menopausal hormone therapies on markers of inflammation, coagulation, fibrinolysis, lipids, and lipoproteins in healthy postmenopausal women. Menopause 2006;13:643-50. DOI:
Bonnar J. Coagulation effects of oral contraception. Am J Obstet Gynecol 1987;157:1042-8. DOI:
Son HJ, Park JW, Chang HJ, et al. Preoperative plasma hyperfibrinogenemia is predictive of poor prognosis in patients with nonmetastatic colon cancer. Ann Surg Oncol 2013;20:2908-13. DOI:
Giaccherini C, Marchetti M, Verzeroli C, et al. Biomarkers of hypercoagulability and prediction for early disease progression and mortality in patients with metastatica gastrointestinal patients with metastatic gastrointestinal cancer. Abstract Book of the 27th SISET National Congress. Bleeding, Thrombosis, and Vascular Biology 2022;1(s1).
Parisi R, Panzera T, Russo L, et al. Fibrinogen levels in relation to colorectal cancer onset: A nested case-cohort study from the Moli-sani cohort. Front Cardiovasc Med 2022;9:1009926. DOI:
Pearson TA, Mensah GA, Alexander RW, et al. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 2003;107:499-11. DOI:
Alesci S, Borggrefe M, Dempfle CE. Effect of freezing method and storage at -20 degrees C and -70 degrees C on prothrombin time, aPTT and plasma fibrinogen levels. Thromb Res 2009;124:121-6. DOI:
de Laat-Kremers R, Di Castelnuovo A, van der Vorm L, et al. In­creased BMI and Blood Lipids Are Associated With a Hyper­coagulable State in the Moli-sani Cohort. Front Cardiovasc Med 2022;9:897733. DOI:

How to Cite

Parisi, R., Costanzo, S., de Laat-Kremers, R., Di Castelnuovo, A., De Curtis, A., Panzera, T., … Moli-sani Study Investigators, for the. (2023). Plasma fibrinogen levels and all-cause and cause-specific mortality in an Italian adult population: results from the Moli-sani study. Bleeding, Thrombosis and Vascular Biology, 2(1).