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01-09-2013 | Original Article

In young post-myocardial infarction male patients elevated plasminogen activator inhibitor-1 correlates with insulin resistance and endothelial dysfunction

Authors: Barbara Eržen, Mišo Šabovič

Published in: Heart and Vessels | Issue 5/2013

Abstract

Classical and nonclassical risk factors contribute to the development of myocardial infarction (MI) in young patients. The aim of the present study was to find out whether insulin resistance and impaired fibrinolysis, with increased plasminogen activator inhibitor (PAI-1), are present in young male post-MI patients, and their relation to additional markers of cardiovascular risk such as endothelial dysfunction (ED) and intima-media thickness (IMT). Forty-one male patients (on average 44 years old) in the stable phase after MI were recruited, with 25 healthy males who did not differ from patients regarding age as controls. Body mass index (BMI) and waist-to-hip ratio were measured and insulin resistance was calculated. Several coagulation/fibrinolytic parameters and inflammation markers were measured. ED was estimated by ultrasound measurement of the flow-mediated dilatation (FMD) of the brachial artery, and IMT was measured on the common carotid artery. BMI was increased in post-MI patients in comparison with healthy controls. Compared with the control group, in post-MI patients PAI-1 antigen (13.8 ± 10.6 vs 9.1 ± 7.6 ng/ml, P = 0.042), PAI-1 activity (14.8 ± 10.8 vs 9.0 ± 8.0 IU/ml, P = 0.015), and fibrinogen were significantly elevated. In patients increased PAI-1, antigen and activity were both significantly positively related to insulin resistance. We found an important negative relation between PAI-1 antigen and FMD (r = −0.32, P = 0.04) and between PAI-1 activity and FMD (r = −0.39, P = 0.01). Our results suggest that PAI-1 can be a link between obesity, insulin resistance, and MI in young patients. It is thus concluded that impaired fibrinolysis with increased PAI-1 may be an important nonclassical risk factor for MI, particularly in young males with increased BMI and insulin resistance.

Stamler J, Stamler R, Neaton JD, Wentworth D, Daviglus ML, Garside D, Dyer AR, Liu K, Greenland P (1999) Low risk-factor profile and long-term cardiovascular and non-cardiovascular mortality and life expectancy: findings for 5 large cohorts of young adult and middle-aged men and women. JAMA 282:2012–2018PubMedCrossRef

Kullo IJ, Gau GT, Tajik J (2000) Novel risk factors for atherosclerosis. Mayo Clin Proc 75:369–380PubMedCrossRef

Ridker PM, Stampfer MJ, Rifai N (2001) Novel risk factors for systemic atherosclerosis. JAMA 285:2481–2485PubMedCrossRef

Juhan-Vague I, Pyke S, Christine Alessi M, Jespersen J, Haverkate F (1996) Fibrinolytic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. Circulation 94:2057–2063PubMedCrossRef

Mavri A, Alessi MC, Bastelica D, Geel-Georgelin O, Fina F, Šentočnik JT, Stegnar M, Juhan-Vague I (2001) Subcutaneous abdominal, but not femoral fat expression of plasminogen activator inhibitor-1 (PAI-1) is related to plasma PAI-1 levels and insulin resistance and decreases after weight loss. Diabetologia 44(11):2025–2031PubMedCrossRef

Landin K, Stigendal L, Eriksson E, Krotkiewski M, Risberg B, Tengborn L, Smith U (1990) Abdominal obesity is associated with an impaired fibrinolytic activity and elevated plasminogen activator inhibitor-1. Metabolism 39:1044–1048PubMedCrossRef

Vague P, Juhan-Vague I, Aillaud MF, Badier C, Viard R, Alessi MC, Collen D (1986) Correlation between blood fibrinolytic activity, plasminogen activator inhibitor level, plasma insulin level, and relative body weight in normal and obese subjects. Metabolism 35:250–253PubMedCrossRef

Kohler HP (2002) Insulin resistance syndrome: interaction with coagulation and fibrinolysis. Swiss Med Wkly 132(19–20):241–252PubMed

Morricone L, Ferrari M, Enrini R, Inglese L, Giardini D, Garancini P, Caviezel F (1999) The role of central fat distribution in coronary artery disease in obesity: comparison of nondiabetic obese, diabetic obese, and normal weight subjects. Int J Obes Relat Metab Disord 23(11):1129–1135PubMedCrossRef

10.

Mavri A, Poredoš P, Suran D, Gaborit B, Juhan-Vague I, Poredoš P (2011) Effect of diet-induced weight loss on endothelial dysfunction: early improvement after the first week of dieting. Heart Vessels 26(1):31–38PubMedCrossRef

11.

Ikeda N, Nakajima R, Utsunomiya M, Hori M, Itaya H, Makino K, Ono T, Yamamoto M, Nemoto N, Iijima R, Hara H, Takagi T, Hara H, Nakamura M, Sugi K (2011) Higher body mass index at the time of acute myocardial infarction is associated with a favorable long-term prognosis (8-year follow-up). Heart Vessels 26(5):495–501PubMedCrossRef

12.

McGill JB, Schneider DJ, Arfken CL, Lucore CL, Sobel BE (1994) Factors responsible for impaired fibrinolysis in obese subjects and NIDDM patients. Diabetes 43:104–109PubMedCrossRef

13.

Vague P, Juhan-Vague I, Chabert V, Alessi MC, Atlan C (1989) Fat distribution and plasminogen activator inhibitor activity in nondiabetic obese women. Metabolism 38:913–915PubMedCrossRef

14.

Urano T, Kojima Y, Takahashi M, Serizawa K, Sakakibara K, Takada Y, Takada A (1993) Impaired fibrinolysis in hypertension and obesity due to high plasminogen activator inhibitor-1 level in plasma. Jpn J Physiol 43:221–228PubMedCrossRef

15.

De Pergola G, De Mitrio V, Perricci A, Cignarelli M, Garruti G, Lomuscio S, Ferri G, Schiraldi O, Giorgino R (1992) Influence of free testosterone on antigen levels of plasminogen activator inhibitor-1 in premenopausal women with central obesity. Metabolism 41:131–134PubMedCrossRef

16.

Juhan-Vague I, Vague P, Alessi MC, Badier C, Valadier J, Aillaud MF, Atlan C (1987) Relationships between plasma insulin, triglyceride, body mass index, and plasminogen activator inhibitor 1. Diabetes Metab 13:331–336

17.

Juhan-Vague I, Thompson SG, Jespersen J (1993) Involvement of the hemostatic system in the insulin resistance syndrome. A study of 1500 patients with angina pectoris. The ECAT Angina Pectoris Study Group. Arterioscler Thromb 13:1865–1873PubMedCrossRef

18.

Hamsten A, Walldius G, Szamozi A, Blombäck M, de Faire U, Dahlen G, Landou C, Wiman B (1987) Plasminogen activator inhibitor in plasma: risk factor for recurrent myocardial infarction. Lancet 2:3–9PubMedCrossRef

19.

Juhan-Vague I, Pyke SDM, Alessi MC, Jespersen J, Haverkate F, Thompson SG (1996) Fibrinolytic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. Circulation 96:2057–2063CrossRef

20.

Eržen B, Šabovič M, Šebeštjen M, Poredoš P (2007) Endothelial dysfunction, intima-media thickness, ankle-brachial pressure index, and pulse pressure in young post-myocardial infarction patients with various expressions of classical risk factors. Heart Vessels 22(4):215–222PubMedCrossRef

21.

Juhan-Vague I, Alessi MC, Joly P, Thirion X, Vague P, Declerck PJ, Serradimigni A, Collen D (1989) Plasma plasminogen activator inhibitor 1 in angina pectoris: influence of plasma insulin and acute-phase response. Arteriosclerosis 9:362–367PubMedCrossRef

22.

Haverkate F, Thompson SG, Duckert F (1995) Haemostasis factors in angina pectoris: relation to gender, age and acute-phase reaction. Thromb Haemost 73:561–567PubMed

23.

Jansson JH, Olofsson BO, Nilsson TK (1993) Predictive value of tissue plasminogen activator mass concentration on long-term mortality in patients with coronary artery disease: a 7-year follow-up. Circulation 88:2030–2034PubMedCrossRef

24.

Celermajer DS, Sorensen KE, Spiegelhalter DJ, Georgakopoulos D, Robinson J, Deanfield JE (1994) Aging is associated with endothelial dysfunction in healthy men years before the age-related decline in women. J Am Coll Cardiol 24:471–476PubMedCrossRef

25.

Hashimoto M, Akishita M, Eto M, Ishikawa M, Kozaki K, Toba K, Sagara Y, Taketani Y, Orimo H, Ouchi Y (1995) Modulation of endothelium-dependent flow-mediated dilatation of the brachial artery by sex and menstrual cycle. Circulation 92:3431–3435PubMedCrossRef

26.

Scarpellini E, Tack J (2012) Obesity and metabolic syndrome: an inflammatory condition. Dig Des 30(2):148–153CrossRef

27.

Skalicky J, Muzakova V, Kandar R, Meloun M, Rousar T, Palicka V (2008) Evaluation of oxidative stress and inflammation in obese adults with metabolic syndrome. Clin Chem Lab Med 46(4):499–505PubMedCrossRef

28.

Fernández-Real JM, Ricart W (2003) Insulin resistance and chronic cardiovascular inflammatory syndrome. Endocr Rev 24(3):278–301PubMedCrossRef

29.

Reaven GM (2005) The insulin resistance syndrome: definition and dietary approaches to treatment. Annu Rev Nutr 25:391–406PubMedCrossRef

30.

Choi KM, Lee KW, Kim SG, Kim NH, Park CG, Seo HS, Oh DJ, Choi DS, Baik SH (2005) Inflammation, insulin resistance, and glucose intolerance in acute myocardial infarction patients without a previous diagnosis of diabetes mellitus. J Clin Endocrinol Metab 90(1):175–180PubMedCrossRef

31.

Ariza CR, Frati AC, Gómez G, Almazán A (1997) Hyperinsulinemia in patients with coronary heart disease in absence of overt risk factors. Arch Med Res 28(1):115–119PubMed

32.

Ikeda N, Nakajima R, Tsunoda T, Nakamura M, Sugi K (2007) Insulin resistance and acute coronary syndrome in the young Japanese population have a strong association. Heart Vessels 22(3):165–169PubMedCrossRef

33.

DeFronzo RA, Tobin JD, Andres R (1979) Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 237:E214–E223PubMed

34.

Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419PubMedCrossRef

35.

Ascaso JF, Romero P, Real JT, Priego A, Valdecabres C, Carmena R (2001) Insulin resistance quantification by fasting insulin plasma values and HOMA index in non-diabetic population. Med Clin (Barc) 117:530–533CrossRef

36.

Furumoto T, Fujii S, Saito N, Mikami T, Kitabatake A (2002) Relationships between brachial artery flow mediated dilation and carotid artery intima-media thickness in patients with suspected coronary artery disease. Jpn Heart J 43(2):117–125PubMedCrossRef

37.

Eržen B, Šabovič M, Šebeštjen M, Keber I, Poredoš P (2007) Interleukin-6 correlates with endothelial dysfunction in young post-myocardial infarction patients. Cardiology 107(2):111–116PubMedCrossRef

Title: In young post-myocardial infarction male patients elevated plasminogen activator inhibitor-1 correlates with insulin resistance and endothelial dysfunction
Authors: Barbara Eržen
Mišo Šabovič
Publication date: 01-09-2013
Publisher: Springer Japan
Published in: Heart and Vessels / Issue 5/2013
Print ISSN: 0910-8327
Electronic ISSN: 1615-2573
DOI: https://doi.org/10.1007/s00380-012-0287-9

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In young post-myocardial infarction male patients elevated plasminogen activator inhibitor-1 correlates with insulin resistance and endothelial dysfunction

Abstract

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Abstract

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