Apolipoprotein(a), Fibrinopeptide A and Carotid Atherosclerosis in Middle-Aged Men

Summary

The association between apolipoprotein(a) [apo(a)], fibrinogen, fibrinopeptide A (FPA) and carotid intima-media thickness (IMT) was analyzed in Eastern Finnish men aged 50 to 60 years. Apo(a) correlated directly with carotid bifurcation (r = 0.26, p = 0.001), but not with common carotid IMT. Men in the lowest quartile of apo(a) had thinner (p = 0.013) IMT in bifurcation [1.59 mm (95% Cl 1.49; 1.68)] compared to the men in the highest [1.91 mm (95% Cl 1.73; 2.09)] apo(a) quartile. The difference remained (p=0.038) after adjusting for confounders. Plasma fibrinogen was not related to carotid IMT, whereas FPA correlated with common carotid (r = 0.21, p = 0.016) and carotid bifurcation (r = 0.21, p = 0.018) IMT. These associations abolished after adjusting for the confounders. The data suggest that apo(a) associate with carotid atherosclerosis independent of other risk factors for ischemic cardiovascular diseases.

• References

• 1 Wilhelmsen L, Svärdsudd K, Korsan-Bengtsen K, Larsson B, Welin L, Tibblin G. Fibrinogen as a risk factor for stroke and myocardial infarction. N Engl J Med 1984; 311: 501-505
• 2 Meade TW, Mellows S, Brozovic M, Miller GJ, Chakrabarti RR, North WRS, Haines AP, Stirling Y, Imeson JD, Thompson SG. Haemostatic function and ischaemic heart disease: principal results of the Nothwick Park Heart Study. Lancet 1986; ii: 533-537
• 3 Kannel WB, Wolf PA, Castelli WP, D’Agostino RB. Fibrinogen and risk of cardiovascular disease. The Framingham Study. JAMA 1987; 258: 1183-1186
• 4 Yarnell JWG, Baker IA, Sweetnam PM, Bainton D, O’Brien JR, Whitehead PJ, Elwood PC. Fibrinogen, viscosity and white blood cell count are major risk factors for ischaemic heart disease. The Caerphilly and Speedwell collaborative heart disease studies. Circulation 1991; 83: 836-844
• 5 Meade TW, Ruddock V, Stirling Y, Chakrabarti RR, Miller GJ. Fibrinolytic activity, clotting factors, and long-term incidence of ischaemic heart disease in the Northwick Park Heart Study. Lancet 1993; 342: 1076-1079
• 6 Nossel HL, Yudelman I, Canfield RE, Buttler Jr VP, Spanondis K, Wilner GD, Qureshi GD. Measurement of fibrinopeptide A in human blood. J Clin Invest 1974; 54: 43-53
• 7 Gallino A, Haeberli A, Baur HR, Straub PW. Fibrin formation and platelet aggregation in patients with severe coronary artery disease: relationship with the degree of myocardial ischemia. Circulation 1985; 72: 27-30
• 8 Theroux P, Latour J-G, Leger-Gauthier C, De Lara J. Fibrinopeptide A and platelet factor levels in unstable angina pectoris. Circulation 1987; 75: 156-162
• 9 Zenker G, Költringer P, Boné G, Niederkorn K, Pfeiffer K, Jürgens G. Lipoprotein(a) as a strong indicator for cerebrovascular disease. Stroke 1986; 17: 942-945
• 10 Seed M, Hoppichler F, Reaveley D, McCarthy S, Thompson GR, Boerwinkle E, Uterman G. Relation of serum lipoprotein(a) concentration and apolipopro-tein(a) phenotype to coronary heart disease in patients with familial hypercholesterolemia. N Engl J Med 1990; 322: 1494-1499
• 11 Fless GM, ZumMallen ME, Scanu AM. Physiochemical properties of apolipo-protein(a) and lipoprotein(a-) derived from the dissociation of human plasma Lp(a). J Biol Chem 1986; 261: 8712-8718
• 12 Tuomilehto J, Arstila M, Kaarsalo E, Kankaanpää J, Ketonen M, Kuulasmaa K, Lehto S, Miettinen H, Mustaniemi H, Palomäki P, Pusk P, Pyorala K, Salomaa V, Torppa J, Vuorenmaa T. Acute myocardial infarction (AMI) in Finland. Baseline data from the FINMONICA AMI register in 1983 to 1985
• 13 Bond MG, Wilmoth SK, Enevold GL, Strickland HL. Detection and monitoring of asymptomatic atherosclerosis in clinical trials. Am J Med 1989; 86 (Suppl. 04) 33-36
• 14 Carlson K. Lipoprotein fractionation. J Clin Pathol 1973; 26: 32-37
• 15 Clauss A. Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens. ActaHaemat 1957; 17: 237-246
• 16 Norusis M. SPSS/PC+ statistics 4.0 for the IBM PC/XT/AT and PC/2. SPSS Inc. Chicago 1990
• 17 Jauhiainen M, Koskinen P, Ehnholm C, Frick MH, Manttari M, Manninen V, Huttunen JK. Lipoprotein(a) and coronary heart disease risk: a nested case-control study of the Helsinki Heart Study participants. Atherosclerosis 1991; 89: 59-67
• 18 Schreiner P, Morrisett JD, Sharrett AR, Patsch W, Tyroler HA, Wu K, Heiss G. Lipoprotein(a) as a risk factor for preclinical atherosclerosis. Arterioscler Thromb 1993; 13: 826-833
• 19 Glagov S, Zarins C, Giddens DP, Ku DN. Hemodynamics and atherosclerosis. Insights and perspectives gained from studies of human arteries. Arch Pathol Lab Med 1988; 112: 1018-1031
• 20 Brown MS, Goldstein JL. Plasma lipoproteins. Teaching old dogmas new tricks. Nature 1987; 330: 113-114
• 21 Loscalzo J, Weinfeld M, Fless GM, Scanu A. Lipoprotein(a), fibrin binding, and plasminogen activation. Arteriosclerosis 1990; 10: 240-245
• 22 Loscalzo J. The relation between atherosclerosis and thrombosis. Circulation 1992; 86 (Suppl. 03) 95-99
• 23 Kamboh MI, Ferrel RE, Kottke BA. Expressed hypervariable polymorphism of apolipoprotein(a). Am J Hum Genet 1991; 49: 1063-1074
• 24 Gurakar A, Hoeg JM, Kostner G, Papadopoulos NM, Brewer HB. Levels of lipoprotein Lp(a) decline with neomycin and niacin treatment. Atherosclerosis 1985; 57: 293-301
• 25 Carlson LA, Hamsten A, Asplund A. Pronounced lowering of serum levels of lipoprotein Lp(a) in hyperlipidaemic subjects treated with nicotinic acid. J Intern Med 1989; 226: 271-276
• 26 Mensink RP, Zock PL, Katan MB, Homstra G. Effect of dietary cis and trans fatty acis on serum lipoprotein(a) levels in humans. J Lipid Res 1992; 33: 1493-1501
• 27 Rankinen T, Rauramaa R, Vaisanen S, Halonen P, Penttila IM. Blood coagulation and fibrinolytic factors are unchanged by aerobic exercise or fat modified diet. Randomized clinical trial in middle-aged men. Fibrinolysis 1994; 8: 48-53
• 28 Smith EB, Keene GA, Grant A, Stirk G. Fate of fibrinogen in human arterial intima. Arteriosclerosis 1990; 10: 263-275