Thromb Haemost 2022; 122(01): 067-079
DOI: 10.1055/a-1492-6143
Coagulation and Fibrinolysis

Lifestyle Influences Changes in Fibrin Clot Properties Over a 10-Year Period on a Population Level

1   Centre of Excellence for Nutrition, North-West University, Potchefstroom, South Africa
,
1   Centre of Excellence for Nutrition, North-West University, Potchefstroom, South Africa
2   Medical Research Council Unit for Hypertension and Cardiovascular Disease, North-West University, Potchefstroom, South Africa
,
Marike Cockeran
3   School of Mathematical and Statistical Sciences, Faculty of Natural and Agricultural Sciences, North-West University, Potchefstroom, South Africa
,
1   Centre of Excellence for Nutrition, North-West University, Potchefstroom, South Africa
2   Medical Research Council Unit for Hypertension and Cardiovascular Disease, North-West University, Potchefstroom, South Africa
› Author Affiliations
Funding The PURE-SA-NW study was funded by the North-West University, South African National Research Foundation (SANRF), Population Health Research Institute, South African Medical Research Council (SAMRC), the North West Province Health Department, and the South Africa-Netherlands Research Program on Alternatives in Development. Grants from the Academy of Medical Sciences UK (Newton Fund Advanced Fellowship Grant - AMS-NAF1-Pieters) and Research Grants from the SAMRC to M.P. supported hemostasis and genetics work reported herein. None of the funding bodies was involved in the design of the study, collection, analysis, or interpretation of the data or in writing of this manuscript. Opinions expressed and conclusions arrived at are those of the authors and are not to be attributed to the funding sources.

Abstract

Case–control and observational studies have provided a plausible mechanistic link between clot structure and thrombosis. We aimed to identify lifestyle, demographic, biochemical, and genetic factors that influence changes in total fibrinogen concentration and clot properties over a 10-year period in 2,010 black South Africans. Clot properties were assessed with turbidimetry and included lag time, slope, maximum absorbance, and clot lysis time. Linear mixed models with restricted maximum likelihood were used to determine whether (1) outcome variables changed over the 10-year period; (2) demographic and lifestyle variables, biochemical variables, and fibrinogen single-nucleotide polymorphisms influenced the change in outcome variables over the 10-year period; and (3) there was an interaction between the exposures and time in predicting the outcomes. A procoagulant risk score was furthermore created, and multinomial logistic regression was used to determine the exposures that were associated with the different risk score categories. In this population setting, female gender, obesity, poor glycemic control, increased low-density lipoprotein cholesterol, and decreased high-density lipoprotein cholesterol contributed to the enhanced progression to prothrombotic clot properties with increasing age. Alcohol consumption on the other hand, offered a protective effect. The above evidence suggest that the appropriate lifestyle changes can improve fibrin clot properties on a population level, decreasing cardiovascular disease risk and thus alleviate the strain on the medical health care system.

Supplementary Material



Publication History

Received: 23 February 2021

Accepted: 25 April 2021

Accepted Manuscript online:
27 April 2021

Article published online:
18 June 2021

© 2021. Thieme. All rights reserved.

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  • References

  • 1 Roth GA, Abate D, Abate KH. et al; GBD 2017 Causes of Death Collaborators. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018; 392 (10159): 1736-1788
  • 2 Moran A, Forouzanfar M, Sampson U, Chugh S, Feigin V, Mensah G. The epidemiology of cardiovascular diseases in sub-Saharan Africa: the Global Burden of Diseases, Injuries and Risk Factors 2010 Study. Prog Cardiovasc Dis 2013; 56 (03) 234-239
  • 3 Keates AK, Mocumbi AO, Ntsekhe M, Sliwa K, Stewart S. Cardiovascular disease in Africa: epidemiological profile and challenges. Nat Rev Cardiol 2017; 14 (05) 273-293
  • 4 Undas A, Ariëns RA. Fibrin clot structure and function: a role in the pathophysiology of arterial and venous thromboembolic diseases. Arterioscler Thromb Vasc Biol 2011; 31 (12) e88-e99
  • 5 Mills JD, Ariëns RA, Mansfield MW, Grant PJ. Altered fibrin clot structure in the healthy relatives of patients with premature coronary artery disease. Circulation 2002; 106 (15) 1938-1942
  • 6 Bridge KI, Philippou H, Ariëns R. Clot properties and cardiovascular disease. Thromb Haemost 2014; 112 (05) 901-908
  • 7 Undas A. How to assess fibrinogen levels and fibrin clot properties in clinical practice?. Semin Thromb Hemost 2016; 42 (04) 381-388
  • 8 Borissoff JI, Spronk HM, ten Cate H. The hemostatic system as a modulator of atherosclerosis. N Engl J Med 2011; 364 (18) 1746-1760
  • 9 Domingues MM, Macrae FL, Duval C. et al. Thrombin and fibrinogen γ′ impact clot structure by marked effects on intrafibrillar structure and protofibril packing. Blood 2016; 127 (04) 487-495
  • 10 Macrae FL, Domingues MM, Casini A, Ariëns RA. The (patho)physiology of fibrinogen γ′. Semin Thromb Hemost 2016; 42 (04) 344-355
  • 11 Scott EM, Ariëns RA, Grant PJ. Genetic and environmental determinants of fibrin structure and function: relevance to clinical disease. Arterioscler Thromb Vasc Biol 2004; 24 (09) 1558-1566
  • 12 Sumaya W, Wallentin L, James SK. et al. Fibrin clot properties independently predict adverse clinical outcome following acute coronary syndrome: a PLATO substudy. Eur Heart J 2018; 39 (13) 1078-1085
  • 13 Cieslik J, Mrozinska S, Broniatowska E, Undas A. Altered plasma clot properties increase the risk of recurrent deep vein thrombosis: a cohort study. Blood 2018; 131 (07) 797-807
  • 14 Celinska-Löwenhoff M, Zabczyk M, Iwaniec T, Plens K, Musial J, Undas A. Reduced plasma fibrin clot permeability is associated with recurrent thromboembolic events in patients with antiphospholipid syndrome. Rheumatology (Oxford) 2018; 57 (08) 1340-1349
  • 15 Mrozinska S, Cieslik J, Broniatowska E, Malinowski KP, Undas A. Prothrombotic fibrin clot properties associated with increased endogenous thrombin potential and soluble P-selectin predict occult cancer after unprovoked venous thromboembolism. J Thromb Haemost 2019; 17 (11) 1912-1922
  • 16 Teo K, Chow CK, Vaz M, Rangarajan S, Yusuf S. PURE Investigators-Writing Group. The Prospective Urban Rural Epidemiology (PURE) study: examining the impact of societal influences on chronic noncommunicable diseases in low-, middle-, and high-income countries. Am Heart J 2009; 158 (01) 1-7
  • 17 de Lange Z, Pieters M, Jerling JC, Kruger A, Rijken DC. Plasma clot lysis time and its association with cardiovascular risk factors in black Africans. PLoS One 2012; 7 (11) e48881
  • 18 Uitte de Willige S, de Visser MC, Houwing-Duistermaat JJ, Rosendaal FR, Vos HL, Bertina RM. Genetic variation in the fibrinogen gamma gene increases the risk for deep venous thrombosis by reducing plasma fibrinogen gamma' levels. Blood 2005; 106 (13) 4176-4183
  • 19 Lisman T, de Groot PG, Meijers JC, Rosendaal FR. Reduced plasma fibrinolytic potential is a risk factor for venous thrombosis. Blood 2005; 105 (03) 1102-1105
  • 20 Johnson R, McNutt P, MacMahon S, Robson R. Use of the Friedewald formula to estimate LDL-cholesterol in patients with chronic renal failure on dialysis. Clin Chem 1997; 43 (11) 2183-2184
  • 21 Kotzé RC, Nienaber-Rousseau C, De Lange Z, De Maat MP, Hoekstra T, Pieters M. Genetic polymorphisms influencing total and γ′ fibrinogen levels and fibrin clot properties in Africans. Br J Haematol 2015; 168 (01) 102-112
  • 22 Cronjé HT, Nienaber-Rousseau C, Zandberg L. et al. Candidate gene analysis of the fibrinogen phenotype reveals the importance of polygenic co-regulation. Matrix Biol 2017; 60-61: 16-26
  • 23 Steyn HS, Ellis SM. Practical significance (effect sizes) versus or in combination with statistical significance (p-values): research note. Management Dynamics. J Southern African Inst Manage Sci 2003; 12: 51-53
  • 24 Field AP. Discovering Statistics Using SPSS. 2nd ed.. London: Sage Publications; 2005
  • 25 Alzahrani SH, Hess K, Price JF. et al. Gender-specific alterations in fibrin structure function in type 2 diabetes: associations with cardiometabolic and vascular markers. J Clin Endocrinol Metab 2012; 97 (12) E2282-E2287
  • 26 Bryk AH, Siudut J, Broniatowska E. et al. Sex-specific alteration to α2-antiplasmin incorporation in patients with type 2 diabetes. Thromb Res 2020; 185: 55-62
  • 27 Reddy Kilim S, Chandala SR. A comparative study of lipid profile and oestradiol in pre- and post-menopausal women. J Clin Diagn Res 2013; 7 (08) 1596-1598
  • 28 Kain K, Carter AM, Bamford JM, Grant PJ, Catto AJ. Gender differences in coagulation and fibrinolysis in white subjects with acute ischemic stroke. J Thromb Haemost 2003; 1 (02) 390-392
  • 29 Lentz SR. Thrombosis in the setting of obesity or inflammatory bowel disease. Blood 2016; 128 (20) 2388-2394
  • 30 Kotzé RCM, Ariëns RAS, de Lange Z, Pieters M. CVD risk factors are related to plasma fibrin clot properties independent of total and or γ′ fibrinogen concentration. Thromb Res 2014; 134 (05) 963-969
  • 31 Stolberg CR, Mundbjerg LH, Funch-Jensen P, Gram B, Juhl CB, Bladbjerg EM. Effects of gastric bypass followed by a randomized study of physical training on markers of coagulation activation, fibrin clot properties, and fibrinolysis. Surg Obes Relat Dis 2018; 14 (07) 918-926
  • 32 Eksteen P, Pieters M, de Lange Z, Kruger HS. The association of clot lysis time with total obesity is partly independent from the association of PAI-1 with central obesity in African adults. Thromb Res 2015; 136 (02) 415-421
  • 33 Michalska M, Iwan-Ziętek I, Gniłka W. et al. PAI-1 and α2-AP in patients with morbid obesity. Adv Clin Exp Med 2013; 22 (06) 801-807
  • 34 Prüller F, Raggam RB, Posch V. et al. Trunk weighted obesity, cholesterol levels and low grade inflammation are main determinants for enhanced thrombin generation. Atherosclerosis 2012; 220 (01) 215-218
  • 35 Mukamal KJ, Jadhav PP, D'Agostino RB. et al. Alcohol consumption and hemostatic factors: analysis of the Framingham Offspring cohort. Circulation 2001; 104 (12) 1367-1373
  • 36 Luyendyk JP, Schoenecker JG, Flick MJ. The multifaceted role of fibrinogen in tissue injury and inflammation. Blood 2019; 133 (06) 511-520
  • 37 Li R, Ren M, Luo M. et al. Monomeric C-reactive protein alters fibrin clot properties on endothelial cells. Thromb Res 2012; 129 (05) e251-e256
  • 38 Salonen EM, Vartio T, Hedman K, Vaheri A. Binding of fibronectin by the acute phase reactant C-reactive protein. J Biol Chem 1984; 259 (03) 1496-1501
  • 39 Alzahrani SH, Ajjan RA. Coagulation and fibrinolysis in diabetes. Diab Vasc Dis Res 2010; 7 (04) 260-273
  • 40 Bryk AH, Zettl K, Wiśniewski JR, Undas A. Glycation and acetylation sites on fibrinogen in plasma fibrin clot of patients with type 2 diabetes: effects of low-dose acetylsalicylic acid. Thromb Res 2021; 198: 93-98
  • 41 de Vries JJ, Hoppenbrouwers T, Martinez-Torres C. et al. Effects of diabetes mellitus on fibrin clot structure and mechanics in a model of acute neutrophil extracellular traps (NETs) formation. Int J Mol Sci 2020; 21 (19) E7107
  • 42 Pieters M, Guthold M, Nunes CM, de Lange Z. Interpretation and validation of maximum absorbance data obtained from turbidimetry analysis of plasma clots. Thromb Haemost 2020; 120 (01) 44-54
  • 43 Puccetti L, Pasqui AL, Pastorelli M. et al. Different mechanisms of fibrinolysis impairment among dyslipidemic subjects. Int J Clin Pharmacol Res 2001; 21 (3-4): 147-155
  • 44 Ząbczyk M, Hońdo Ł, Krzek M, Undas A. High-density cholesterol and apolipoprotein AI as modifiers of plasma fibrin clot properties in apparently healthy individuals. Blood Coagul Fibrinolysis 2013; 24 (01) 50-54
  • 45 Talens S, Leebeek FW, Demmers JA, Rijken DC. Identification of fibrin clot-bound plasma proteins. PLoS One 2012; 7 (08) e41966
  • 46 Folsom AR, Tang W, George KM. et al. Prospective study of γ′ fibrinogen and incident venous thromboembolism: the Longitudinal Investigation of Thromboembolism Etiology (LITE). Thromb Res 2016; 139: 44-49
  • 47 Standeven KF, Grant PJ, Carter AM, Scheiner T, Weisel JW, Ariëns RA. Functional analysis of the fibrinogen Aalpha Thr312Ala polymorphism: effects on fibrin structure and function. Circulation 2003; 107 (18) 2326-2330
  • 48 Cronjé HT, Nienaber-Rousseau C, Zandberg L, de Lange Z, Green FR, Pieters M. Fibrinogen and clot-related phenotypes determined by fibrinogen polymorphisms: independent and IL-6-interactive associations. PLoS One 2017; 12 (11) e0187712