Subscribe to RSS
DOI: 10.1055/s-2005-918598
© Georg Thieme Verlag Stuttgart · New York
Lipoprotein(a): Koronare Herzerkrankung - klinische Bedeutung und Therapieoptionen
Lipoprotein(a) in coronary heart disease: clinical significance and therapeutic optionsPublication History
eingereicht: 17.5.2005
akzeptiert: 18.7.2005
Publication Date:
27 October 2005 (online)

Seit der Erstbeschreibung von Lipoprotein(a) (Lp(a)) beschäftigt sich die kardiovaskuläre Forschung mit der Frage, wie dieses Molekül sowohl atherogene als auch thrombogene Prozesse beeinflusst. Aufgrund der Vielzahl der Anfragen von Patienten mit Lp(a)-Erhöhung und koronarer Herzerkrankung (KHK) zur Apherese-Therapie oder zu Alternativen ist es notwendig, wissenschaftlich und medizinisch Antworten auf die Frage nach Therapiemöglichkeiten erhöhter Lp(a)-Konzentrationen zu suchen. Seit den 70er Jahren erkannte man zunehmend den pathogenen Einfluss des Lp(a)-Moleküls auf die Entstehung der Arteriosklerose und der KHK. Darüber hinaus wurde in den letzten 15 Jahren auch die negative Bedeutung von Lp(a) für das endotheliale fibrinolytische System beschrieben. Gerade der negative Einfluss auf die Fibrinolyse in Kombination mit der LDL-ähnlichen, arteriosklerotischen Wirkung ist das eigentliche Risiko für atherothrombotische (und spontane) Komplikationen im gesamten kardiovaskulären System und sollte in verstärktem Maße die Forschung beschäftigen. Dabei repräsentiert die Subpopulation der Patienten mit einer kleineren Isoform des apo(a)-Anteils des Lp(a) eine Risikogruppe, die z. B. mittels Immunadsorptionsapherese oder lebenslanger verstärkter Antikoagulation vor weiteren Komplikationen geschützt werden könnte. Die klinische Bedeutung des Lp(a) und die therapeutischen Möglichkeiten werden vor dem Hintergrund der vorliegenden Studien diskutiert.
Literatur
- 1
Agewall S, Fagerberg B.
Lipoprotein(a) was an independent predictor for major coronary events in treated hypertensive
men.
Clin Cardiol.
2002;
25
287-290
Reference Ris Wihthout Link
- 2
Akaike M, Azuma H, Kagawa A. et al .
Effect of aspirin treatment on serum concentrations of lipoprotein(a) in patients
with atherosclerotic diseases.
Clin Chem.
2002;
48
1454-1459
Reference Ris Wihthout Link
- 3
Angelin B.
Therapy of lowering lipoprotein(a) levels.
Curr Opin Lipidol.
1997;
8
337-341
Reference Ris Wihthout Link
- 4
Armstrong V W, Schleef J, Thiery J, Muche R, Schuff-Werner P, Eisenhauer T, Seidel D.
Effect of HELP-LDL-apheresis on serum concentrations of human lipoprotein(a): kinetic
analysis of the post-treatment return to baseline levels.
Eur J Clin Invest.
1989;
19
235-240
Reference Ris Wihthout Link
- 5
Bambauer R, Schiel R, Latza R.
Low-density Lipoprotein Apheresis: An Overview.
Therap Apher Dial.
2003;
7
382-390
Reference Ris Wihthout Link
- 6
Beisiegel U, Niendorf A, Wolf K, Reblin T, Rath M.
Lipoprotein(a) in the arterial wall.
Eur Heart J.
1990;
11
174-183
(Suppl E)
Reference Ris Wihthout Link
- 7
Berg K.
A new serum type system in man: the LP system.
Acta Pathol Microbio Scand.
1963;
59
369-382
Reference Ris Wihthout Link
- 8
Boerwinkle E.
Genetics of plasma lipoprotein(a) concentrations.
Curr Opin Lipidol.
1992;
3
128-136
Reference Ris Wihthout Link
- 9
Bosch T, Keller C.
Clinical effects of direct adsorption of lipoprotein apheresis: beyond cholesterol
reduction.
Therap Apher Dial.
2003;
7
341-344
Reference Ris Wihthout Link
- 10
Cantin V, Gagnon F, Moorjani S. et al .
Is lipoprotein(a) an independent risk factor for ischemic heart disease in men? The
Quebec Cardiovascular Study.
J Am Coll Cardiol.
1998;
31
519-525
Reference Ris Wihthout Link
- 11
Carlson L A, 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
271-176
Reference Ris Wihthout Link
- 12
Cremer P, Nagel D, Mann H. et al .
Ten-year follow-up results from the Goettingen Risk, Incidence and Prevalence Study
(GRIPS). I. Risk factors for myocardial infarction in a cohort of 5790 men.
Atherosclerosis.
1997;
129
221-230
Reference Ris Wihthout Link
- 13
Crouse J R.
New developments in the use of niacin for treatment of hyperlipidemia: new considerations
in the use of an old drug.
Coron Artery Dis.
1996;
7
321-326
Reference Ris Wihthout Link
- 14
Dahlen G H, Guyton J R, Attar M, Farmer J A, Kautz J A, Gotto A M.
Association of levels of lipoprotein Lp(a), plasma lipids and other lipoproteins with
coronary artery disease documented by angiography.
Circulation.
1986;
74
758-765
Reference Ris Wihthout Link
- 15
Danesh J, Collins R, Peto R.
Lipoprotein(a) and coronary heart disease. Meta-analysis of prospective studies.
Circulation.
2000;
102
1082-1085
Reference Ris Wihthout Link
- 16
Dangas G, Mehran R, Harpel P C. et al .
Lipoprotein(a) and inflammation in human coronary atheroma: association with the severity
of clinical presentation.
J Am Coll Cardiol.
1998;
32
2035-2042
Reference Ris Wihthout Link
- 17
Dujovne C A, Harris W S, Altman R, Overhiser R W, Black D M.
Effect of atorvastatin on hemorheologic-hemostatic parameters and serum fibrinogen
levels in hyperlipidemic patients.
Am J Cardiol.
2000;
85
350-353
Reference Ris Wihthout Link
- 18
Espeland M A, Marcovina S M, Miller V. et al. for the PEPI investigators .
Effect of postmenopausal hormone therapy on lipoprotein(a) concentration.
Circulation.
1998;
97
979-986
Reference Ris Wihthout Link
- 19
Evans R W, Shpilber O, Shaten B J, Ali S, Kamboh I, Kuller L.
Prospective association of lipoprotein(a) concentrations and apo(a) size with coronary
heart disease among men in the Multiple Risk Factor Intervention Trial.
J Clin Epidemiol.
2001;
54
51-57
Reference Ris Wihthout Link
- 20
Executive summary of the third report of the national cholesterol education programm
(NECP) .
Expert panel on detection, evaluation and treatment of high blood cholesterol in adults
(adult treatment panel III).
JAMA.
2001;
285
2486-2497
Reference Ris Wihthout Link
- 21
Frank S, Gauster M, Strauss J, Hrzenjak A, Kostner G M.
Adenovirus mediated apo(a)-antisense-RNA expression efficiently inhibits apo(a) synthesis
in vitro and in vivo.
Gene Therapy.
2001;
8
425-430
Reference Ris Wihthout Link
- 22
Ginsberg H N, Kris-Etherton P, Dennis B. et al .
Effects of reducing dietary saturated fatty acids on plasma lipids and lipoproteins
in healthy subjects: the DELTA Study, protocol 1.
Arterioscler Thromb Vasc Biol.
1998;
18
441-449
Reference Ris Wihthout Link
- 23
Gonbert S, Malinsky S, Sposito A C. et al .
Atorvastatin lowers lipoprotein(a) but not apolipoprotein(a) fragment levels in hypercholesterolemic
subjects at high cardiovascular risk.
Atherosclerosis.
2002;
164
305-311
Reference Ris Wihthout Link
- 24
Grainger D J, Kirschenlohr H L, Mecalfe J C, Weissberg P L, Wade D P, Lawn R M.
Proliferation of human smooth muscle cells promoted by lipoprotein(a).
Science.
1993;
260
1655-1658
Reference Ris Wihthout Link
- 25
Harpel P C, Chang V T, Borth V.
Homocysteine and other sulfhydryl compounds enhance the binding of lipoprotein(a)
to fibrin: a potential biochemical link between thrombosis, atherogenesis, and sulfhydryl
compound metabolism.
Proc Natl Acad Sci USA.
1992;
89
10& hairsp;193-10 197
Reference Ris Wihthout Link
- 26
Hervio L, Chapman J M, Thillet J, Loyau S, Anglés-Cano E.
Does apolipoprotein(a) heterogeneity influence lipoprotein(a) effects on fibrinolysis?.
Blood.
1993;
82
392-397
Reference Ris Wihthout Link
- 27
Jauhiainen M, Koskinen P, Ehnholm. et al .
Lipoprotein(a) and coronary heart disease risk: a nested case-control study of the
Helsinki Heart Study participants.
Atherosclerosis.
1991;
89
59-67
Reference Ris Wihthout Link
- 28
Jenkins D J, Kendall C W, Marchie A. et al .
Dose response of almonds on coronary heart disease risk factors: blood lipids, oxidized
low-density lipoproteins, lipoprotein(a), homocysteine, and pulmonary nitric oxide:
a randomized, controlled, crossover trial.
Circulation.
2002;
106
1327-1332
Reference Ris Wihthout Link
- 29
Kiortsis D N, Tzotas T, Giral P. et al .
Changes in lipoprotein(a) levels and hormonal correlation during weight reduction
program.
Nutr Metab Cardiovasc Dis.
2001;
11
153-157
Reference Ris Wihthout Link
- 30
Koschinsky M L, Marcovina S M.
Structure-function relationships in apolipoprotein(a): insights into lipoprotein(a)
assembly and pathogenicity.
Curr Opin Lipidol.
2004;
15
167-174
Reference Ris Wihthout Link
- 31
Kronenberg F, Kronenberg M F, Kiechl S. et al .
Role of lipoprotein(a) and apolipoprotein(a) phenotype in atherogenesis. Prospective
results from the Bruneck Study (editorial).
Circulation.
1999;
100
1154-1160
Reference Ris Wihthout Link
- 32
Kronenberg F, Neyer U, Lhotta K. et al .
The low molecular weight apo(a)-phenotype is an independent predictor for coronary
artery disease in hemodialysis patients: a prospective follow up.
J Am Soc Nephrol.
1999;
10
1027-1036
Reference Ris Wihthout Link
- 33
Loscalzo J, Weinhold M, Fless G M, Scanu A M.
Lipoprotein(a), fibrin binding and plasminogen activation.
Arteriosclerosis.
1990;
10
240-245
Reference Ris Wihthout Link
- 34
Luc G, Bard J M, Arveiler D. et al on behalf of the PRIME study group .
Lipoprotein (a) as a predictor of coronary heart disease: the PRIME Study.
Atherosclerosis.
2002;
163
377-384
Reference Ris Wihthout Link
- 35
Marcovina S M, Koschinsky M L.
Lipoprotein(a) concentration and apolipoprotein(a) size - a synergistic role in advanced
atherosclerosis?.
Circulation.
1999;
100
1151-1153
Reference Ris Wihthout Link
- 36
Marcovina S M, Koschinsky M L, Albers J J, Skarlatos S.
Report of the National Heart, Lung, and Blood Institute Workshop on Lipoprotein(a)
and Cardiovascular Disease: Recent Advances and Future Directions.
Clin Chem.
2003;
49
1785-1796
Reference Ris Wihthout Link
- 37
McLean J W, Tomlinson J E, Kuang W J. et al .
cDNA sequence of human apolipoprotein(a) is homologous to plasminogen.
Nature.
1987;
300
132-137
Reference Ris Wihthout Link
- 38
Miles L A, Fless G M, Levin E G, Scanu A M, Plow E F.
A potential basis for the thrombotic risks associated with lipoprotein(a).
Nature.
1989;
339
301-303
Reference Ris Wihthout Link
- 39
Miwa K, Nakagawa K, Yoshida N, Taguchi Y, Inoue H.
Lipoprotein(a) is a risk factor for occurrence of acute myocardial infarction in patients
with coronary vasospasm.
J Amer Coll Cardiol.
2000;
35
1200-1205
Reference Ris Wihthout Link
- 40
Nomura S, Yamamura T, Yamamoto A. et al .
The association between lipoprotein(a) and severity of coronary and cerebrovascular
atherosclerosis, especially in non-hypercholesterolemic subjects.
Cardiovasc Risk Fact.
1993;
3
336-343
Reference Ris Wihthout Link
- 41
Nowak-Göttl U, Junker F, Hartmeier M. et al .
Increased lipoprotein(a) is an important risk factor for venous thromboembolism in
childhood.
Circulation.
1999;
100
743-748
Reference Ris Wihthout Link
- 42 Phillips B, Ball C, Sackett D. et al .Levels of evidence and grades of recommendation. Oxford: Oxford-Centre for Evidence Based Medicine 2001
Reference Ris Wihthout Link
- 43
Plenge J K, Hernandez T L, Weil K M. et al .
Simvastatin lowers C-reactive protein within 14 days: an effect independent of low-density
lipoprotein cholesterol reduction.
Circulation.
2002;
106
1447-1452
Reference Ris Wihthout Link
- 44
Pokrovsky S N, Sussekov A, Afanasieva O I, Adamova I Y, Lyakishev A A, Kukharchuk V V.
Extracorporal immunadsorption for the specific removal of lipoprotein(a) (Lp(a) apheresis):
preliminary clinical data.
Chem Phys Lipids.
1994;
67/68
323-330
Reference Ris Wihthout Link
- 45
Scanu A M.
Lipoprotein(a) and the atherothrombotic process: Mechanistics insights and clinical
implications.
Curr Atheroscler Rep.
2003;
5
106-113
Reference Ris Wihthout Link
- 46
Schuff-Werner P, Gohlke H, Bartmann U. et al. and the HELP study group .
The HELP-LDL-apheresis multicenter study, an angiographically assessed trial on the
role of LDL-apheresis in the secondary prevention of coronary heart disease. II. Final
evaluation of the effect of regular treatment on LDL-cholesterol plasma concentration
and the course of coronary heart disease.
Eur J Clin Invest.
1994;
24
724-732
Reference Ris Wihthout Link
- 47
Seed M, Hoppichler F, Reaveley D. et al .
Relation of serum lipoprotein(a) concentration and apolipoprotein(a) phenotype to
coronary heart disease in patients with familial hypercholesterolemia.
N Engl J Med.
1990;
322
1494-1499
Reference Ris Wihthout Link
- 48
Shewmon D A, Stock J L, Rosen C J. et al .
Tamoxifen and estrogen lower circulating lipoprotein(a) concentrations in healthy
postmenopausal women.
Arterioscler Thromb.
1994;
14
1586-1593
Reference Ris Wihthout Link
- 49
Sirtori C R, Calabresi L, Ferrara S. et al .
L-Carnitine reduces plasma lipoprotein(a) levels in patients with hyper Lp(a).
Nutr Metab Cardiovasc Dis.
2000;
10
247-251
Reference Ris Wihthout Link
- 50
Terres W, Tatsis E, Pfalzer B, Beil F U, Beilsiegel U, Hamm C W.
Rapid angiographic progression of coronary artery disease in patients with elevated
lipoprotein(a).
Circulation.
1995;
91
948-950
Reference Ris Wihthout Link
- 51
Thompson G R, Maher V M, Matthews S, Kitano Y, Neuwirth C, Shortt M B.
Familial hypercholesterolaemia regression study: a randomised trial of low-density-lipoprotein
apheresis.
Lancet.
1995;
345
811-816
Reference Ris Wihthout Link
- 52
Ullrich H, Lackner K J, Schmitz G.
Lipoprotein(a) apheresis in severe coronary heart disease: an immunadsorption method.
Artif Org.
1998;
22
135-139
Reference Ris Wihthout Link
- 53
Von Depka M, Nowak-Göttl U, Eisert R. et al .
Increased lipoprotein(a) levels as an independent risk factor for venous thromboembolism.
Blood.
2000;
96
3364-3368
Reference Ris Wihthout Link
- 54
Von Eckardstein A, Schulte H, Cullen P, Assmann G.
Lipoprotein(a) further increases the risk of coronary events in men with high global
cardiovascular risk.
J Am Coll Cardiol.
2001;
37
434-439
Reference Ris Wihthout Link
Dr. med. Roman Leischik
Mittelstraße 13
58095 Hagen
Phone: 02331/182500
Fax: 02331/182570
Email: literatur@dr-leischik.de
