Association between obesity and a prothrombotic state: the Framingham Offspring Study

Guido A. Rosito; Ralph B. D’Agostino; Joseph Massaro; Izabella Lipinska; Murray A. Mittleman; Patrice Sutherland; Peter W. F. Wilson; Daniel Levy; James E. Muller; Geoffrey H. Tofler

doi:10.1160/TH03-01-0014

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2004; 91(04): 683-689
DOI: 10.1160/TH03-01-0014

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Association between obesity and a prothrombotic state: the Framingham Offspring Study

Guido A. Rosito

¹Hospital Clinicas, Porto Alegre, Brazil

,

Ralph B. D’Agostino

²Boston University Mathematical and Statistical Department, Boston, Massachusetts, USA

,

Joseph Massaro

²Boston University Mathematical and Statistical Department, Boston, Massachusetts, USA

,

Izabella Lipinska

³Institute for Prevention of Cardiovascular Disease, Beth Israel Deaconess Medical Center, Bosten, Massachusetts, USA

,

Murray A. Mittleman

³Institute for Prevention of Cardiovascular Disease, Beth Israel Deaconess Medical Center, Bosten, Massachusetts, USA

,

Patrice Sutherland

⁴Framingham Heart Study

,

Peter W. F. Wilson

⁴Framingham Heart Study

,

Daniel Levy

⁴Framingham Heart Study

,

James E. Muller

⁵Massachusetts General Hospital, Massachusetts, USA

,

Geoffrey H. Tofler

⁶Royal North Shore Hospital, Sydney, Australia

› Author Affiliations

Abstract

Summary

Although obesity is associated with increased cardiovascular risk, the mechanism has not been fully explained. Since thrombosis is a critical component of cardiovascular disease, we examined the relationship between obesity and hemostatic factors. We studied 3230 subjects (55% females, mean age 54 years) without a history of cardiovascular disease in cycle 5 of the Framingham Offspring Study. Obesity was assessed by body mass index and waist-to-hip ratio. Fasting blood samples were obtained for fibrinogen, plasminogen activator inhibitor (PAI-1) antigen, tissue plasminogen activator (tPA) antigen, factor VII antigen, von Willebrand factor (VWF), and plasma viscosity. Body mass index was directly associated with fibrinogen, factor VII, PAI-1 and tPA antigen in both men and women (p<0.001) and with VWF and viscosity in women. Similar associations were present between waist-to-hip ratio and the hemostatic factors. With minor exceptions for VWF and viscosity, all associations persisted after controlling for age, smoking, total and HDL cholesterol, triglycerides, glucose level, blood pressure, and use of antihypertensive medication. The association between increased body mass index and waist-to-hip ratio and prothrombotic factors and impaired fibrinolysis suggests that obesity is a risk factor whose effect is mediated in part by a prothrombotic state.

Keywords

Obesity - thrombosis - cardiovascular disease

Full Text

References

References
1 Williamson DF. Descriptive epidemiology of body weight and weight change in US adults. Ann Int Med 1993; 119: 646-9.
2 Krauss RM, Winston M, Fletcher BJ. et al. Obesity: Impact on Cardiovascular Health. Circulation 1998; 98: 1472-6.
3 NHLBI Guidelines: Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in Adults. NIH. 1999
4 Hubert HB, Feinleib M, MacNamara PM. et al. Obesity as an independent risk factor for cardiovascular disease. A 26-year follow-up of participants in the Framingham Heart Study. Circulation 1983; 67: 968-77.
5 Jousilahti P, Tuomilehto J, Vartiainen E. et al. Body weight, cardiovascular risk factors and coronary mortality: 15-year follow-up of middle-aged men and women in Eastern Finland. Circulation 1996; 93: 1372-9.
6 Smith Jr SC, Blair SN, Bonow RO. et al. AHA/ACC Guidelines for Preventing Heart Attack and Death in Patients with Atherosclerotic Cardiovascular Disease: 2001 Update. A statement for healthcare professionals from the American Heart Association and the American College of Cardiology. J Am Coll Cardiol 2001; 38: 1581-3.
7 Pi-Sunyer FX. Medical hazards of obesity. Ann Int Med 1993; 119: 655-60.
8 ECAT Angina Pectoris Study Group. ECAT angina pectoris study: baseline associations of hemostatic factors with extent of coronary atherosclerosis and other coronary risk factors in 3000 patients with angina pectoris undergoing coronary angiography. Eur Heart Journal 1993; 14: 8-17.
9 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: 1044-8.
10 Ditschuneit HH, Flechtner-Mors M, Adler G. Fibrinogen in obesity before and after weight reduction. Obesity Research 1995; 03: 43-4.
11 Avellone G, Di Garbo V, Cordova R. et al. Coagulation, fibrinolysis and haemorheology in premenopausal obese women with different body fat distribution. Thromb Res 1994; 75: 223-31.
12 Kannel WB, Feinleib M, McNamara JR. et al. An investigation of coronary heart disease in families: the Framingham Offspring Study. Am J Epidemiol 1979; 110: 281-90.
13 Welty FK, Mittleman MA, Wilson PWF. et al. Hypobetalipoproteinemia is associated with low levels of hemostatic risk factors in the Framingham Offspring Population. Circulation 1997; 95: 825-30.
14 Poli KA, Tofler GH, Larson MG. et al. Association between blood pressure and hemostatic factors in the Framingham Offspring Population. Circulation 2000; 101: 264-9.
15 Meigs JB, Mittleman MA, Nathan DM. et al. Hyperinsulinemia, hyperglycemia and impaired hemostasis: the Framingham Offspring Study. JAMA 2000; 283: 221-8.
16 Stec JJ, Silbershatz H, Tofler GH. et al. Association of Fibrinogen with Cardiovascular Risk Factors and Cardiovascular Disease in the Framingham Offspring Population. Circulation 2000; 102: 1634-8.
17 Rhoads GG, Blackwelder WC, Stemmerman GN. et al. Coronary risk factors and autopsy findings in Japanese-American men. Lab Invest 1978; 38: 304-11.
18 Jadhav PP. Tofler GH. Hemostatic risk factors for Cardiovascular Disease. Willich SN, Muller JE. (eds) Triggering of acute coronary syndromes: Implications for prevention. Dordrecht: Kluwer academic publishers; 1996: 135-51.
19 Tracy RP, Bovill EG. Thrombosis and Cardiovascular Risk in the Elderly. Arch Pathol Lab Med 1992; 116: 1307-12.
20 Heinrich J, Balleisen L, Assmann G. et al. Fibrinogen and factor VII in the prediction of Coronary Risk: Results from the PROCAM Study in healthy men. Arterioscler Thromb 1994; 14: 54-9.
21 Folsom AR, Conlan MG, Davis CE. et al. for the Atherosclerosis Risk in Communities (ARIC) Study Investigators: Relations between hemostatic variables and cardiovascular endpoints in middle-aged adults. Ann Epidemiol 1992; 02: 481-94.
22 Meade TW, Mellows S, Brozovic M. et al. Haemostatic function and ischaemic heart disease: principal results of the Northwick Park Heart Study. Lancet 1986; 02: 533-7.
23 Hamsten A, Wiman B, de Faire U. et al. Increased plasma levels of rapid inhibitor of tissue plasminogen activator in young survivors of myocardial infarction. N Engl J Med 1985; 313: 1557-63.
24 Held C, Hjemdahl P, Rehnqvist N. et al. Hemostatic markers, inflammatory parameters and lipids in male and female patients in the Angina Prognosis in Stockholm (APSIS): a comparison with healthy controls. J Intern Med 1997; 241: 59-69.
25 Ridker PM, Vaughan DE, Stampfer MJ. et al. Endogenous tissue-type plasminogen activator and risk of myocardial infarction. Lancet 1993; 341: 1165-8.
26 Lundgren CH, Brown SL, Nordt TK. et al. Elaboration of type-1 plasminogen activator inhibitor from adipocytes. A potential link between obesity and cardiovascular disease. Circulation 1996; 93: 106-10.
27 Loskutoff DJ, Samad F. The adipocyte and hemostatic balance in obesity: studies of PAI-1. Arterioscler Thromb Vasc Biol 1998; 18: 1-6.
28 Marckmann P, Toubro S, Atrup A. Sustained improvement in blood lipids, coagulation, and fibrinolysis after major weight loss in obese individuals. Eur J Clin Nutr 1998; 52: 329-33.
29 Samad F, Pandey M, Loskutoff DJ. Tissue factor gene expression in the adipose tissues of obese mice. Proc Natl Acad Sci USA 1998; 95: 7591-6.
30 Haffner SM. The insulin resistance syndrome revisited. Diabetes Care 1996; 19: 275-7.
31 Nordt TK, Klassen K, Schneider DJ. et al. Augmentation of synthesis of plasminogen activator inhibitor type-1 in arterial endothelial cells by glucose and its implications to local fibrinolysis. Arterioscler Thromb 1993; 13: 1822-8.
32 Juhan-Vague I, Thompson SG, Jespersen J. Involvement of the hemostatic system in the insulin resistance syndrome. A study of 1500 patients with angina pectoris. Arterioscler Thromb 1993; 13: 1865-73.
33 Eliasson M, Asplund K, Evrin P. et al. Hyperinsulinemia predicts low tissue plasminogen activator activity in a healthy population: The Northern Sweden MONICA Study. Metabolism 1994; 43: 1579-86.
34 Stiko-Rahm A, Wiman B, Hamsten A. et al. Secretion of plasminogen activator inhibitor-1 from cultured human umbilical endothelial cells is induced by very low density lipoprotein. Arteriosclerosis 1990; 10: 1067-73.
35 Folsom AR, Qamlieh HT, Wing RR. et al. Impact of weight loss on plasminogen activator inhibitor (PAI-1), factor VII, and other hemostatic factors in moderately overweight adults. Arterioscler Thromb 1993; 13: 162-9.
36 Svendsen OL, Hassager C, Christiansen C. et al. Plasminogen activator inhibitor-1, tissue-type plasminogen activator, and fibrinogen: Effect of dieting with or without exercise in overweight postmenopausal women. Arterioscler Thromb Vasc Biol 1996; 16: 381-5.