High levels of homocysteine, lipoprotein (a) and plasminogen activator inhibitor-1 are present in patients with abdominal aortic aneurysm

Summary

Over the last few years, there has been increasing interest in the investigation of the pathogenesis of AAA, and a role for some novel risk factors, in particular thrombophilic risk factors, has been suggested. The aim of this study was to evaluate a number of thrombophilic parameters in a large group of patients with AAA. In 438 patients with AAA, and in 438 healthy subjects, selected to be comparable for age and gender with patients and without instrumental evidence of AAA, a pattern of thrombophilic parameters [homocysteine (Hcy), lipoprotein (a) [Lp(a)], plasminogen activator inhibitor-1 (PAI-1), anticardiolipin antibodies (ACA), MTHFR C677T polymorphism, prothrombin gene G20210A variant and Factor V Leiden mutation] has been evaluated. A significant difference for Hcy, PAI-1 and Lp(a) plas-After adjustment for the traditional cardiovascular risk factors, a significant increased risk of having AAA has been observed for high levels of Hcy (OR: 7.8; p<0.0001), Lp(a) (OR: 2.4; p<0.0001) and PAI-1 (OR:3.2;p<0.0001). The association has been confirmed after exclusion of patients with other localization of atherosclerosis. Moreover, a significant association between larger abdominal aortic diameters and the number of thrombophilic parameters has been reported (r = 0.13; p = 0.005). In conclusion, a significant association between abnormal levels of some metabolic parameters related to thrombosis such as Hcy, Lp(a) and PAI-1 and AAA has been observed.

Keywords

Abdominal aortic aneurysm - emerging risk factor - homocysteine - lipoprotein (a) - plasminogen activator inhibitor-1

• References

• 1 Tilson MD. Aortic aneurysm and atherosclerosis. Circulation 1992; 85: 378-9.
• 2 Sakalihasan N, Limet R, Defawe OD. Abdominal aortic aneurysm. Lancet 2005; 365: 1577-89.
• 3 Boushey CJ, Beresford SAA, Omenn GS. et al. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. JAMA 1995; 274: 1049-57.
• 4 Bescond A, Augier T, Chareyre C. et al. Homocysteine- induced elastolysis in arterial media: activation of MMP-2. Neth J Med 1998; 58: S56-S57.
• 5 Pezzini A, Del Zotto E, Archetti S. et al. Plasma homocysteine concentration, C677T MTHFR genotype, and 844ins68bp CBS genotype in young adults with spontaneous cervical artery dissection and atherothrombotic stroke. Stroke 2002; 33: 664-9.
• 6 Brunelli T, Prisco D, Fedi S. et al. High prevalence of mild hyperhomocysteinemia in patients with abdominal aortic aneurysm. J Vasc Surg 2000; 32: 531-6.
• 7 Warsi AA, Davies B, Morris-Stiff G. et al. Abdominal aortic aneurysm and its correlation to plasma homocysteine, and vitamins. Eur J Vasc Endovasc Surg 2004; 27: 75-9.
• 8 Spark JI, Laws P, Fitridge R. The incidence of hyperhomocysteinemia in vascular patients. Eur J Vasc Endovasc Surg 2003; 26: 558-61.
• 9 Strauss E, Waliszewski K, Gabriel M. et al. Increased risk of the abdominal aortic aneurysm in carriers of the MTHFR 677T allele. J Appl Genet 2003; 44: 85-93.
• 10 Stein JH, Rosenson RS. Lp(a) excess and coronary heart disease. Arch Intern Med 1997; 157: 1170-6.
• 11 Schillinger M, Domanovits H, Ignatescu M. et al. Lipoprotein(a) in patients with aortic aneurysmal disease. J Vasc Surg 2002; 36: 25-30.
• 12 Petersen E, Wagberg F, Angquist KA. Does lipoprotein (a) inhibit elastolysis in abdominal aortic aneurysms?. Eur J Vasc Endovasc Surg 2003; 26: 423-8.
• 13 Watt HC, Law MR, Wald NJ. et al. Serum triglyceride: a possible risk factor for ruptured abdominal aortic aneurysm. Int J Epidemiol 1998; 27: 949-52.
• 14 Jean-Claude J, Newman KM, Li H. et al. Possible key role for plasmin in the pathogenesis of abdominal aortic aneurysms. Surgery 1994; 116: 472-8.
• 15 Falkenberg M, Holmdahl L, Tjarnstrom J. et al. Abnormal levels of urokinase plasminogen activator protein and tissue plasminogen activator activity in human aortic aneurysms. Eur J Surg 2001; 167: 10-4.
• 16 Galli M, Luciani D, Bertolini G. et al. Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature. Blood 2003; 101: 1827-32.
• 17 Kim RJ, Becker RC. Association between factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations and events of the arterial circulatory system: A meta-analysis of published studies. Am Heart J 2003; 146: 948-57.
• 18 Sampram ESK, Lindblad B. The impact of factor V mutation on the risk for occlusion in patients undergoing peripheral vascular reconstructions. Eur J Vasc Endovasc Surg 2001; 22: 134-8.
• 19 Johnston KW, Rutherford RB, Tilson MD. et al. Suggested standards for reporting on arterial aneurysms. Subcommittee on reporting standards for arterial aneurysms, ad hoc committee on reporting standards, Society for Vascular Surgery and North American Chapter, International Society for Cardiovascular Surgery. J Vasc Surg 1991; 13: 452-8.
• 20 Cifkova R, Erdine S, Fagard R. et al. ESH/ESC Hypertension guidelines committee. Practice guidelines for primary care physicians: 2003 ESH/ESC hypertension guidelines. J Hyper 2003; 21: 1779-86.
• 21 Third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation and treatment of high blood cholesterol in adult (Adult Treatment Panel III). Final Report. Circulation 2002; 106: 3143-421.
• 22 Eagle KA, Berger PB, Calkins H. et al. ACC/AHA guideline update for perioperative cardiovascular evaluation for noncardiac surgery: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1996 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery). J Am Coll Cardiol 2002; 39: 542-53.
• 23 Barnett HJ, Meldrum HE, Eliasziw M. North American Symptomatic Carotid Evaluation Trial (NASCET) Collaborators. The appropriate use of carotid endarterectomy. CMAJ 2002; 166: 1169-79.
• 24 Bertina RM, Koeleman BP, Koster T. et al. Mutation in blood coagulation factor V associated with resistance to activate protein C. Nature 1994; 369: 64-7.
• 25 Poort SW, Rosendaal FR, Reitsma PH. et al. A common genetic variation in the 3’- untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 1996; 88: 3698-703.
• 26 Giusti B, Frusconi S, Rossi L. et al. Improvement of low-density microelectronic array technology to characterize 14 mutations/single-nucleotide polymorphisms from several human genes on a large scale. Clin Chem 2004; 50: 775-7.
• 27 Papagrigorakis E, Iliopoulos D, Asimacopoulos PJ. et al. Lipoprotein (a) in plasma, arterial wall, and thrombus from patients with aortic aneurysm. Clin Genet 1997; 52: 262-71.
• 28 Carmeliet P, Moons L, Lijnen R. et al. Urokinasegenerated plasmin activates matrix metalloproteinases during aneurysm formation. Nat Genet 1997; 17: 439-44.
• 29 Adam DJ, Ludlam CA, Ruckley CV. et al. Coagulation and fibrinolysis in patients undergoing operation for ruptured and nonruptured infrarenal aortic aneurysms. J Vasc Surg 1999; 30: 641-50.