Serum lipoprotein(a) in relation to ischemic heart disease and associated risk factors
1993 (English)Doctoral thesis, comprehensive summary (Other academic)
Lipoprotein(a) (Lp(a)) consists of an LDL-like particle and the specific protein apo(a), which is very similar to plasminogen. Apo(a) contains repeated kringle structures and a serine protease domain, which cannot be activated by t-PA. Lp(a) is considered to be a predictor for atherosclerotic disease. It has been found incorporated in atherosclerotic plaques and inhibits in vitro fibrinolysis.
Lp(a) was determined in 1527 randomly selected individuals participating in the Northern Sweden WHO-MONICA project. A weak but significant relation between Lp(a) and increasing age was found. Menopausal status was the strongest independent predictor of Lp(a) level in women. Fibrinogen was independently related to Lp(a) in both sexes. Only a minor fraction of Lp(a) variance could be explained for in a multiple regression model, which is in agreement with the contention that Lp(a) is highly genetically determined.
Lp(a) was determined in 1571 patients investigated with coronary angiography because of suspected severe coronary artery disease (CAD). Patients with proven CAD at elective angiography had significantly higher Lp(a) than patients without significant CAD or healthy controls. Lp(a) was found to be an independent discriminator of CAD in both sexes.
HLA-DR genotype 13 or 17 was found more frequently in 30 male patients with angiographic CAD at young age (< 50 years) than in 30 age matched controls. These genotypes were common in patients with high Lp(a) levels, which indicates that Lp(a) may be related to immunological processes.
The reaction of Lp(a) was investigated in 32 patients with acute myocardial infarction (AMI). Lp(a) increased during the first week, but the response was comparatively weak. Individual Lp(a) responses were heterogeneous and no correlations to infarct size or changes in the acute phase proteins were found.
In a randomized cross-over study on 36 hypercholesterolaemic patients treated with simvastatin/placebo during 12+12 weeks Lp(a) did not change significantly, but patients with high Lp(a) levels at baseline tended to develop further increased Lp(a).
To conclude, Lp(a) was found to be an independent predictor of angiographic CAD in both men and women. Lp(a) levels are primarily genetically determined and only a small fraction of Lp(a) variance could be explained by other factors in this study. Lp(a) may be related to HLA DR types and immunological processes involved in atherosclerotic disease. Lp(a) increased slightly during the first week of AMI, but was not related to changes in the acute-phase proteins. The effective LDL-lowering agent simvastatin did not influence Lp(a) significantly.
Place, publisher, year, edition, pages
Umeå: Umeå universitet , 1993. , 59 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 386
Lipoprotein(a), lipids, epidemiology, coronary artery disease, coronary angiography, HLA DR, acute-phase protein, myocardial infarction, HMG CoA reductase inhibitor, simvastatin
IdentifiersURN: urn:nbn:se:umu:diva-101298ISBN: 91-7174-828-8OAI: oai:DiVA.org:umu-101298DiVA: diva2:799719
1993-10-22, Sal B, 9 tr, Regionsjukhuset, Umeå universitet, Umeå, 09:00
Diss. (sammanfattning) Umeå : Umeå universitet, 1993, härtill 5 uppsatser.2015-04-222015-03-262015-04-22Bibliographically approved