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CC BY 4.0 · TH Open 2017; 01(02): e146-e154
DOI: 10.1055/s-0037-1608942
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Visceral Adiposity Is an Independent Determinant of Hypercoagulability as Measured by Thrombin Generation in Morbid Obesity

P. B. Chitongo
1   Department of Haematological Medicine, King's Thrombosis Centre, King's College Hospital, London, United Kingdom
,
L. N. Roberts
1   Department of Haematological Medicine, King's Thrombosis Centre, King's College Hospital, London, United Kingdom
,
L. Yang
2   Department of Endocrinology, King's College Hospital, London, United Kingdom
,
R. K. Patel
1   Department of Haematological Medicine, King's Thrombosis Centre, King's College Hospital, London, United Kingdom
,
R. Lyall
3   Department of Respiratory Medicine, Kings College Hospital, London, United Kingdom
,
R. Luxton
4   Faculty of Health and Applied Sciences, University of the West of England, Bristol, United Kingdom
,
S. J. B. Aylwin
2   Department of Endocrinology, King's College Hospital, London, United Kingdom
,
R. Arya
1   Department of Haematological Medicine, King's Thrombosis Centre, King's College Hospital, London, United Kingdom
› Institutsangaben
Weitere Informationen

Publikationsverlauf

14. August 2017

10. Oktober 2017

Publikationsdatum:
15. Dezember 2017 (online)

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Abstract

Introduction Increased visceral adipose tissue (VAT) has been shown to be associated with the development of insulin resistance, type 2 diabetes, stroke, and ischemic heart disease. It remains unknown whether fat distribution impacts on coagulation markers and/or the risk of venous thrombosis. This study evaluates markers of hypercoagulability in class III obesity (body mass index [BMI] >40 kg/m2) compared with nonobese controls. We further investigated whether hypercoagulability was influenced by VAT, metabolic syndrome, and metabolic markers, including adiponectin.

Patients and Methods Ninety patients were recruited from the obesity clinic at King's College Hospital from November 2009 to December 2011. The inclusion criteria were class III obesity (BMI ≥40 kg/m2) and age 18 to 65 years. A control group (healthy ambulatory participants, with a BMI < 30 kg/m2) was recruited from volunteers responding to advertisement. Abdominal VAT and subcutaneous adipose tissue surface areas were determined by evaluation of a single-slice CT at spinal vertebra L4.

Results Thrombin generation revealed a significantly increased peak and endogenous thrombin potential in patients compared with controls. Lag time and time to peak (ttP) were also significantly prolonged in patients. VAT was found to have the strongest association with thrombin generation parameters: lag time (β = 0.378; p < 0.001), peak thrombin (0.378; p = 0.04), and ttP (β = 0.373; p = 0.001). BMI was found to be a predictor for lag time only (β = 0.313; p = 0.003). SAT was not associated with any of the thrombin generation parameters (data not shown). VAT was found to be an independent determinant of peak thrombin, lag time, and ttP. The study suggests not only fat mass but also fat distribution, particularly visceral adiposity, mediates hypercoagulability in obesity.

Keywords

coagulation factors - visceral adipose tissue - hemostatic marker - tissue factor pathway inhibitor - venous thrombosis
 

  • References

  • 1 Health and Social Care Information Centre. The Health Survey for England - 2012 Trend Tables. London: 2013. Available at: http://www.hscic.gov.uk/catalogue/PUB13219 . Accessed May 15, 2017
    PubMedGoogle Scholar
  • 2 Stein PD, Beemath A, Olson RE. Obesity as a risk factor in venous thromboembolism. Am J Med 2005; 118 (09) 978-980
    CrossrefPubMedGoogle Scholar
  • 3 Darvall KA, Sam RC, Silverman SH, Bradbury AW, Adam DJ. Obesity and thrombosis. Eur J Vasc Endovasc Surg 2007; 33 (02) 223-233
    CrossrefPubMedGoogle Scholar
  • 4 Fisman EZ, Tenenbaum A. Adiponectin: a manifold therapeutic target for metabolic syndrome, diabetes, and coronary disease?. Cardiovasc Diabetol 2014; 13: 103
    CrossrefPubMedGoogle Scholar
  • 5 Drolet R, Bélanger C, Fortier M. , et al. Fat depot-specific impact of visceral obesity on adipocyte adiponectin release in women. Obesity (Silver Spring) 2009; 17 (03) 424-430
    CrossrefPubMedGoogle Scholar
  • 6 Karcher HS, Holzwarth R, Mueller HP. , et al. Body fat distribution as a risk factor for cerebrovascular disease: an MRI-based body fat quantification study. Cerebrovasc Dis 2013; 35 (04) 341-348
    CrossrefPubMedGoogle Scholar
  • 7 Yang L, Samarasinghe YP, Kane P, Amiel SA, Aylwin SJ. Visceral adiposity is closely correlated with neck circumference and represents a significant indicator of insulin resistance in WHO grade III obesity. Clin Endocrinol (Oxf) 2010; 73 (02) 197-200
    PubMedGoogle Scholar
  • 8 Brochu M, Starling RD, Tchernof A. , et al. VAT is additionally an independent predictor of all-cause mortality in men. Obesity (Silver Spring) 2000; 14: 336-341
    PubMedGoogle Scholar
  • 9 van der Kooy K, Seidell JC. Techniques for the measurement of visceral fat: a practical guide. Int J Obes Relat Metab Disord 1993; 17 (04) 187-196
    PubMedGoogle Scholar
  • 10 Sowers JR. Obesity as a cardiovascular risk factor. Am J Med 2003; 115 (115, Suppl 8A): 37S-41S
    CrossrefPubMedGoogle Scholar
  • 11 Lovejoy JC, de la Bretonne JA, Klemperer M, Tulley R. Abdominal fat distribution and metabolic risk factors: effects of race. Metabolism 1996; 45 (09) 1119-1124
    CrossrefPubMedGoogle Scholar
  • 12 Gallagher D, Visser M, Sepúlveda D, Pierson RN, Harris T, Heymsfield SB. How useful is body mass index for comparison of body fatness across age, sex, and ethnic groups?. Am J Epidemiol 1996; 143 (03) 228-239
    CrossrefPubMedGoogle Scholar
  • 13 Rush EC, Goedecke JH, Jennings C. , et al. BMI, fat and muscle differences in urban women of five ethnicities from two countries. Int J Obes 2007; 31 (08) 1232-1239
    CrossrefPubMedGoogle Scholar
  • 14 Ottaviani E, Malagoli D, Franceschi C. The evolution of the adipose tissue: a neglected enigma. Gen Comp Endocrinol 2011; 174 (01) 1-4
    CrossrefPubMedGoogle Scholar
  • 15 Motoshimo H, Wu X, Sinha MK. , et al. Differential regulation of adiponectin secretion from cultured human omental and subcutaneous adipocytes: effects of insulin and rosaglitazone. J Clin Endocrinol Metab 2002; 87 (12) 5662-5667
    CrossrefPubMedGoogle Scholar
  • 16 Ay L, Kopp HP, Brix JM. , et al. Thrombin generation in morbid obesity: significant reduction after weight loss. J Thromb Haemost 2010; 8 (04) 759-765
    CrossrefPubMedGoogle Scholar
  • 17 Campello E, Zabeo E, Radu CM. , et al. Hypercoagulability in overweight and obese subjects who are asymptomatic for thrombotic events. Thromb Haemost 2015; 113 (01) 85-96
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 18 Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28 (07) 412-419
    CrossrefPubMedGoogle Scholar
  • 19 International Diabetes Federation. The IDF Consensus Worldwide Definition of the Metabolic Syndrome. Available at: http://www.idf.org/webdata/docs/MetS_def_update2006.pdf . Accessed May 15, 2017
    PubMedGoogle Scholar
  • 20 Bagot CN, Marsh MS, Whitehead M. , et al. The effect of estrone on thrombin generation may explain the different thrombotic risk between oral and transdermal hormone replacement therapy. J Thromb Haemost 2010; 8 (08) 1736-1744
    CrossrefPubMedGoogle Scholar
  • 21 Hemker HC, Giesen P, AlDieri R. , et al. The calibrated automated thrombogram (CAT): a universal routine test for hyper- and hypocoagulability. Pathophysiol Haemost Thromb 2002; 32 (5-6): 249-253
    CrossrefPubMedGoogle Scholar
  • 22 Kuk JL, Church TS, Blair SN, Ross R. Does measurement site for visceral and abdominal subcutaneous adipose tissue alter associations with the metabolic syndrome?. Diabetes Care 2006; 29 (03) 679-684
    CrossrefPubMedGoogle Scholar
  • 23 Kaye SM, Pietiläinen KH, Kotronen A. , et al. Obesity-related derangements of coagulation and fibrinolysis: a study of obesity-discordant monozygotic twin pairs. Obesity (Silver Spring) 2012; 20 (01) 88-94
    CrossrefPubMedGoogle Scholar
  • 24 Cugno M, Castelli R, Mari D. , et al. Inflammatory and prothrombotic parameters in normotensive non-diabetic obese women: effect of weight loss obtained by gastric banding. Intern Emerg Med 2012; 7 (03) 237-242
    CrossrefPubMedGoogle Scholar
  • 25 Dielis AW, Castoldi E, Spronk HM. , et al. Coagulation factors and the protein C system as determinants of thrombin generation in a normal population. J Thromb Haemost 2008; 6 (01) 125-131
    PubMedGoogle Scholar
  • 26 Brodin E, Appelbom H, Osterud B, Hilden I, Petersen LC, Hansen JB. Regulation of thrombin generation by TFPI in plasma without and with heparin. Transl Res 2009; 153 (03) 124-131
    CrossrefPubMedGoogle Scholar
  • 27 Hackeng TM, Seré KM, Tans G, Rosing J. Protein S stimulates inhibition of the tissue factor pathway by tissue factor pathway inhibitor. Proc Natl Acad Sci U S A 2006; 103 (09) 3106-3111
    CrossrefPubMedGoogle Scholar
  • 28 Smid M, Dielis AW, Winkens M. , et al. Thrombin generation in patients with a first acute myocardial infarction. J Thromb Haemost 2011; 9 (03) 450-456
    CrossrefPubMedGoogle Scholar
  • 29 van Veen JJ, Gatt A, Makris M. Thrombin generation testing in routine clinical practice: are we there yet?. Br J Haematol 2008; 142 (06) 889-903
    CrossrefPubMedGoogle Scholar
  • 30 van Hylckama Vlieg A, Christiansen SC, Luddington R, Cannegieter SC, Rosendaal FR, Baglin TP. Elevated endogenous thrombin potential is associated with an increased risk of a first deep venous thrombosis but not with the risk of recurrence. Br J Haematol 2007; 138 (06) 769-774
    CrossrefPubMedGoogle Scholar
  • 31 Hron G, Kollars M, Binder BR, Eichinger S, Kyrle PA. Identification of patients at low risk for recurrent venous thromboembolism by measuring thrombin generation. JAMA 2006; 296 (04) 397-402
    CrossrefPubMedGoogle Scholar
  • 32 Tripodi A, Legnani C, Chantarangkul V, Cosmi B, Palareti G, Mannucci PM. High thrombin generation measured in the presence of thrombomodulin is associated with an increased risk of recurrent venous thromboembolism. J Thromb Haemost 2008; 6 (08) 1327-1333
    CrossrefPubMedGoogle Scholar
  • 33 Tripodi A, Legnani C, Palareti G, Chantarangkul V, Mannucci PM. More on: high thrombin generation and the risk of recurrent venous thromboembolism. J Thromb Haemost 2009; 7 (05) 906-907
    CrossrefPubMedGoogle Scholar
  • 34 Dargaud Y, Trzeciak MC, Bordet JC, Ninet J, Negrier C. Use of calibrated automated thrombinography +/− thrombomodulin to recognise the prothrombotic phenotype. Thromb Haemost 2006; 96 (05) 562-567
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 35 Calabro P, Yeh ET. Obesity, inflammation, and vascular disease: the role of the adipose tissue as an endocrine organ. Subcell Biochem 2007; 42: 63-91
    PubMedGoogle Scholar
  • 36 Pischon T, Girman CJ, Hotamisligil GS, Rifai N, Hu FB, Rimm EB. Plasma adiponectin levels and risk of myocardial infarction in men. JAMA 2004; 291 (14) 1730-1737
    CrossrefPubMedGoogle Scholar
  • 37 Lemkes BA, Hermanides J, Devries JH, Holleman F, Meijers JC, Hoekstra JB. Hyperglycemia: a prothrombotic factor?. J Thromb Haemost 2010; 8 (08) 1663-1669
    CrossrefPubMedGoogle Scholar