Our understanding of the pathophysiological role of lipoprotein (a) in cardiovascular disease and its clinical importance has improved, but there are still gaps in our knowledge and analytical performance that hinder the appropriate management of patients. Further information about the physiological functions of lipoprotein (a), if any, and its interactions with other risk factors is required.
NishinoMItoTYasunoMKuryuTYamadaYAbeH: Serum lipoprotein (a) as a risk factor for thoracic aortic atherosclerosis in subjects aged >40 years. Am J Cardiol1993, 72:227–229.
2.
ShintaniSKikuchiSHamaguchiHShiigaiT: High serum lipoprotein (a) levels are an independent risk factor for cerebral infarction. Stroke1993, 24:965–969.
3.
JovicicAIvanisevicVIvanovicI: Lipoprotein (a) in patients with carotid atherosclerosis and ischemic cerebrovascular disorders. Atherosclerosis1993, 98:59–65.
4.
MullerHMDiekstallFFSchmidtEMarzWCanzlerHDemelerU: Lipoprotein (a): A risk factor for retinal vascular occlusion. Ger J Opthalmol1992, 1:338–341.
5.
Pedro BotetJSentiMNoguesXRubies PratJRoquerJD'OlhaberriagueL: Lipoprotein and apolipoprotein profile in men with ischemic stroke. Role of lipoprotein (a), triglyceride-rich lipoproteins, and apolipoprotein E polymorphism. Stroke1992, 23:1556–1562.
6.
CambillauMSimonAAmarJGiralPAtgerVSegondP: Serum Lp(a) as a discriminant marker of early atherosclerotic plaque at three extracoronary sites in hypercholesterolemic men. The PCVMETRA group. Arterioscler Thromb1992, 12:1346–1352.
MolgaardJKlausenICLassvikCFaergemanOGerdesLUOlssonAG: Significant association between low-molecular-weight apolipoprotein (a) isoforms and intermittent claudication. Arterioscler Thromb1992, 12:895–901.
9.
BarbirMKushwahaSHuntBMackenAThompsonGRMitchellA: Lipoprotein (a) and accelerated coronary artery disease in cardiac transplant recipients. Lancet1992, 340:1500–1502.
10.
SchreinerPJMorrisettJDSharrettARPatschWTyrolerHAWuK: Lipoprotein (a) as a risk factor for preclinical atherosclerosis. Arterioscler Thromb1993, 13:826–833. This case-control study of intima-medial thickening in external carotid arteries compared individuals whose vessel wall thickness was above the 90th percentile with those with thicknesses below the 75th percentile. Results, which were adjusted for age and other cardiovascular risk factors, suggest that increased Lp(a) levels are associated with preclinical cardiovascular pathology. This reinforces the concept that Lp(a) is more than just an inhibitor of thrombolysis.
11.
WattsGFKearneyEMTaubNASlavinBM: Lipoprotein (a) as an independent risk factor for myocardial infarction in patients with common hypercholesterolaemia. J Clin Pathol1993, 46:267–270.
12.
SandholzerCSahaNKarkJDReesAJarossWDieplingerH: Apo(a) isoforms predict risk for coronary heart disease. A study in six populations. Arterioscler Thromb1992, 12:1214–1226. In this case-control study of patients suffering their first myocardial infarct, an increased odds ratio of 1.82 was evident for men in the top 20% of the apo(a) distribution. For women, apo(a) isoforms B, S1 or S2, but not apo(a) level were associated with an odds ratio of 2.5. This interesting sex difference suggests that the isoforms themselves may be predictive.
13.
KarkJDSandholzerCFriedlanderYUtermannG: Plasma Lp(a), apolipoprotein (a) isoforms and acute myocardial infarction in men and women: A case-control study in the Jerusalem population. Atherosclerosis1993, 98:139–151.
14.
GueveraJJanAYKnappRTulinskyAMorrisettJD: Comparison of binding sites of modeled apo(a) kringle-like sequences in human lipoprotein (a). Arterioscler Thromb1993, 13:758–770.
15.
ZysowBRLawnRM: The relationship of lipoprotein (a) to hemostasis. Curr Opin Lipidol1993, 4:484–489. This is an excellent synopsis of the interaction between apo(a) and the haemostatic system. It also draws attention to the interesting effect of apo(a) on smooth muscle cell involvement resulting from its interaction with tissue plasminogen activator on the activation of pro-transforming growth factor beta.
16.
HarpelPBorthW: Fibrin, lipoprotein (a), plasmin interactions: A model linking thrombosis and atherogenesis. Ann N Y Acad Sci1992, 667:233–238.
17.
LiuJNHarpelPCPannellRGurewichV: Lipoprotein (a): A kinetic study of its influence on fibrin-dependent plasminogen activation by prourokinase or tissue plasminogen activator. Biochemistry1993, 32:9694–9700.
18.
HervioLChapmanMJThilletJLoyauSAngles-CanoE: Does apolipoprotein (a) heterogeneity influence lipoprotein (a) effects in fibrinolysis? Blood1993, 82:392–397.
19.
LesnikPVonicaAGuerinMMoreauMChapmanMJ: Anticoagulant activity of tissue factor pathway inhibitor in human plasma is preferentially associated with dense subspecies of LDL and HDL and with Lp(a). Arterioscler Thromb1993, 13:1066–1075.
20.
TerresWKrewittMHammCW: Effects of lipoprotein (a) on in-vitro lysis of whole blood thrombi from healthy volunteers. Thromb Res1993, 69:479–487.
21.
EzrattyASimonDILoscalzoJ: Lipoprotein (a) binds to human platelets and attenuates plasminogen binding and activation. Biochemistry1993, 32:4628–4633.
22.
HalvorsenSSkjonsbergOHBergRRuyterRGodalHC: Does Lp(a) lipoprotein inhibit the fibrinolytic system? Thromb Res1992, 68:223–232.
23.
LacknerCBoerwinkelELeffertCCRahmigTHobbsHH: Molecular basis of apolipoprotein (a) isoform size heterogeneity as revealed by pulsed-field gel electrophoresis. J Clin Invest1991, 87:2153–2161.
24.
ScanuAMMilesLAFlessGMPfaffingerDEisenbergJAngles-CanoE: Rhesus monkey lipoprotein (a) binds to lysine sepharose and U937 monocytoid cells less efficiently than human lipoprotein (a). Evidence for the dominant role of kringle 437. J Clin Invest1993, 91:283–291.
25.
HarpelPCGordonBRParkerTS: Plasmin catalyzes binding of lipoprotein (a) to immobilized fibrinogen and fibrin. Proc Natl Acad Sci USA1989, 86:3847–3851.
26.
HarpelPCChangVTBorthW: 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 USA1992, 89:10193–10197.
AnzarJEstellesABretoMEspanaFAlosT: Euglobulin clot lysis induced by tissue-type plasminogen activator is reduced in subjects with increased levels of lipoprotein (a). Thromb Res1992, 66:569–582.
29.
GlueckCJGlueckHITracyTSpeirsJMcCrayCStroopD: Relationships between lipoprotein (a), lipids, apolipoproteins, basal and stimulated fibrinolytic regulators, and d-dimer. Metabolism1993, 42:236–246.
30.
SmithEBCrosbieL: Does lipoprotein (a) [Lp(a)] compete with plasminogen in human atherosclerotic lesions and thrombi? Atherosclerosis1991, 89:127–136. This study, which analysed thrombi and atherosclerotic plaques, did not demonstrate the expected inverse relationship between Lp(a) and plasminogen. Although this may be a consequence of analytical factors, it raises questions about the presumed antagonism of plasminogen by Lp(a).
31.
Bas LeerinkCDuifPFGimpelJAKortlandtWBoumaBNvan RijnHJ: Lysine-binding heterogeneity of Lp(a): Consequences for fibrin binding and inhibition of plasminogen activation. Thromb Haemost1992, 68:185–188. The authors describe the isolation of a subfraction of Lp(a) that fails to bind lysine-sepharose. The subfraction did not differ detectably in terms of apo(a) isoforms, but the unbound fraction did not bind fibrin fragments or inhibit the activation of plasminogen by tissue plasminogen activator. This may resolve some of the inconsistencies that have so far been a feature of thrombolytic studies involving apo(a).
32.
ArmstrongVWHarrachBRobenekHHelmholdMWalliAKSeidelD: Heterogeneity of human lipoprotein Lp(a): Cytochemical and biochemical studies on the interaction of two Lp(a) species with the LDL receptor. J Lipid Res1990, 31:429–441.
33.
LoscalzoJWeinfeldMFlessGMScanuAM: Lipoprotein (a), fibrin binding, and plasminogen activation. Arteriosclerosis1990, 10:240–245. The authors describe one of the most likely mechanisms by which Lp(a) affects atherosclerosis.
34.
CushingGLGaubatzJWNavaMLBurdickBJBocanTMGuytonJR: Quantitation and localization of apolipoproteins (a) and B in coronary artery bypass vein grafts resected at re-operation. Arteriosclerosis1989, 9:593–603.
35.
HoffHFO'NeilJYashiroA: Partial characterization of lipoproteins containing apo(a) in human atherosclerotic lesions. J Lipid Res1993, 34:789–798.
36.
PepinJMO'NeilJAHoffHF: Quantification of apo(a) and apoB in human atherosclerotic lesions. J Lipid Res1991, 32:317–327. This paper provides some of the first evidence for a preferential accumulation of Lp(a) in the atherosclerotic plaque.
37.
KostnerGMBihara VargaM: Is the atherogenicity of Lp(a) caused by its reactivity with proteoglycans? Eur Heart J1990, 11 (suppl E):184–189.
38.
TabasILiYBrociaRWXuSWSwensonTLWilliamsKJ: Lipoprotein lipase and sphingomyelinase synergistically enhance the association of atherogenic lipoproteins with smooth muscle cells and extracellular matrix. A possible mechanism for low density lipoprotein and lipoprotein (a) retention and macrophage foam cell formation. J Biol Chem1993, 268:20419–20432.
39.
BottalicoLAKeeslerGAFlessGMTabasI: Cholesterol loading of macrophages leads to marked enhancement of native lipoprotein (a) and apolipoprotein (a) internalization and degradation. J Biol Chem1993, 268:8569–8573. This description of a specific receptor for Lp(a) is important because it may have implications for Lp(a) catabolism and its pathophysiological role in atherosclerosis. It is particularly intriguing that the receptor is only expressed after macrophages become loaded with acetyl LDL.
40.
YashiroAO'NeilJHoffHF: Insoluble complex formation of lipoprotein (a) with low density lipoprotein in the presence of calcium ions. J Biol Chem1993, 268:4709–4715. The authors report that Lp(a) forms insoluble complexes with calcium ions at physiological concentrations. LDL, acetyl LDL, very-low-density lipoprotein and especially desialated LDL bind to these complexes. The process is inhibited by HDL3. This may represent an additional mechanism for lipid deposition in artery walls.
41.
NaruszewiczMSelingeEDavignonJ: Oxidative modification of lipoprotein (a) and the effect of beta-carotene. Metabolism1992, 41:1215–1224.
42.
HaberlandMEFlessGMScanuAMFogelmanAM: Malonyldialdehyde modification of lipoprotein (a) produces avid uptake by human monocyte-macrophages. J Biol Chem1992, 267:4143–4151.
43.
De RijkeYBJurgensGHesselsEMHermannAvan BerkelTJ: In-vivo fate and scavenger receptor recognition of oxidized lipoprotein (a) isoforms in rats. J Lipid Res1992, 33:1315–1325.
44.
GraingerDJKirschenlhorHLMetcalfJCWeissbergLWadeDPLawnRM: Proliferation of human smooth muscle cells promoted by lipoprotein (a). Science1993, 260:1555–1558.
45.
KarmanskyIGruenerN: Roles of immobilized glycosylated proteins and lipoprotein (a) in adhesivity of endothelial cells: Possible implications for atherogenesis. Cell Biol Int Rep1992, 16:503–515.
46.
RaderDJCainWZechLUsherDBrewerHB: Variation in lipoprotein (a) concentrations among individuals with the same apolipoprotein (a) isoform is determined by the rate of lipoprotein (a) production. J Clin Invest1993, 91:443–447.
47.
MatsubaraMAtsumiTNamiokaK: Plasma lipoprotein (a) levels in patients with hyperthyroidism [in Japanese]. Nippon Naibunpi Gakkai Zasshi1993, 69:556–561.
48.
de BruinTWvan BarlingenHvan Linde Sibenius TripMvan Vuurst de VriesARAkveldMJErkelensDW: Lipoprotein (a) and apolipoprotein B plasma concentrations in hypothyroid, euthyroid and hyperthyroid subjects. J Clin Endocrinol Metab1993, 76:121–126.
49.
EdenSWiklundOOscarssonJRosenTBengtssonBA: Growth hormone treatment of growth hormone-deficient adults results in a marked increased in Lp(a) and HDL cholesterol concentrations. Arterioscler Thromb1993, 13:296–301. The authors draw attention to the slightly unexpected association between Lp(a) and growth hormone.
50.
OlivecronaHEricssonSBerglundLAngelinB: Increased concentrations of serum lipoprotein (a) in response to growth hormone treatment. BMJ1993, 306:1726–1727.
51.
JennerJLOrdovasJMLamon FavaSSchaeferMMWilsonPWCastelliWP: Effects of age, sex, and menopausal status on plasma lipoprotein (a) levels. The Framingham Offspring Study. Circulation1993, 87:1135–1141.
52.
WebbATReaveleyDAO'DonnellMO'ConnorBSeedMBrownEA: Lipoprotein (a) in patients on maintenance haemodialysis and continuous ambulatory peritoneal dialysis. Nephrol Dial Transplant1993, 8:609–613.
53.
BarbagalloCMAvernaMRSparacinoVGalioneACaputoFScafidiV: Lipoprotein (a) levels in end-stage renal failure and renal transplantation. Nephron1993, 64:560–564.
54.
DieplingerHLacknerCKronenbergFSandholzerCLhottaKHoppichlerF: Elevated plasma concentrations of lipoprotein (a) in patients with end-stage renal disease are not related to the size polymorphism of apolipoprotein (a). J Clin Invest1993, 91:397–401. This paper points out the lack of effect of apo(a) phenotype on Lp(a) level in end-stage renal disease.
55.
OidaKTakaiHMaedaHTakahashiSShimadaASuzukiH: Apolipoprotein (a) is present in urine and its excretion is decreased in patients with renal failure. Clin Chem1992, 38:2244–2248.
56.
DubreySWReaveleyDALeslieDGO'DonnellMO'ConnorBMSeedM: Effect of insulin-dependent diabetes mellitus on lipids and lipoproteins: A study of identical twins. Clin Sci Colch1993, 84:537–542.
57.
TaupinJMDurlachVHassaimMGilleryPJollyDBoirieY: Lipoprotein (a) and diabetes: Relationship based on 224 cases [in French]. Diabete Metab1993, 19:250–256.
58.
RitterMMLoscarMRichterWOSchwandtP: Lipoprotein (a) in diabetes mellitus. Clin Chim Acta1993, 214:45–54.
59.
CsaszarADieplingerHSandholzerCKaradiIJuhaszEDrexelH: Plasma lipoprotein (a) concentration and phenotypes in diabetes mellitus. Diabetologia1993, 36:47–51. The authors report a careful study in which apo(a) phenotype was included in case-control analysis of the effect of diabetes on Lp(a) level.
60.
VelhoGErlichDTurpinENeelDCohenPFroguelP: Lipoprotein (a) in diabetic patients and normoglycemic relatives in familial NIDDM. Diabetes Care1993, 16:742–747.
61.
HafnerSMMoralesPASternMPGruberMK: Lp(a) concentrations in NIDDM. Diabetes1992, 41:1267–1272.
62.
HearnJADonohueBCBa'allbakiHDouglasJSKingSBLemboNJ: Usefulness of serum lipoprotein (a) as a predictor of restenosis after percutaneous transluminal coronary angioplasty. Am J Cardiol1992, 69:736–739. This paper demonstrates that the pathophysiological effects of Lp(a) may have important effects on the outcome of percutaneous transluminal coronary angioplasty.
63.
TendaKSaikawaTMaedaTSatoYNiwaHInoueT: The relationship between serum lipoprotein (a) and restenosis after initial elective percutaneous transluminal coronary angioplasty. Jpn Circ J1993, 57:789–795.
64.
KostnerGM: Interrelation of Lp(a) with plasma triglycerides. InAtherosclerosis Reviews. Edited by GottoAMJrPaolettiR.New York: Raven Press; 1991, 22:131–135.
65.
WerbaJPSafaOGianfranceschiGMichelagnoliSSirtoriCRFranceschiniG: Plasma triglycerides and lipoprotein(a): Inverse relationship in a hyperlipidaemic Italian population. Atherosclerosis1993, 101:203–211.
66.
Castro CabezasMde BruinTWvan Linde Sibenius TripMKockLAJansenHErkelensDW: Lipoprotein (a) plasma concentrations associated with lipolytic activities in eight kindreds with familial combined hyperlipidemia and normolipidemic subjects. Metabolism1993, 42:756–761.
67.
SelingerEDallongevilleJDavignonJ: Apolipoprotein (a) is present in the triglyceride-rich fraction in type IV hypertriglyceridemia. Clin Biochem1993, 26:59–64.
68.
SullivanDRLamCWKJessupWDeanRTHensleyWJ: Postprandial changes in apolipoprotein (a) concentration of triglyceride-rich lipoproteins can be reproduced by in-vitro incubation: Implications for underlying mechanism. Atherosclerosis1993, 103:139–147.
69.
UtermannG: The mysteries of lipoprotein (a). Science1989, 246:904–910.
70.
HegeleRAConnellyPWCullen DeanGRoseV: Elevated plasma lipoprotein (a) associated with abnormal stress thallium scans in children with familial hypercholesterolemia. Am J Cardiol1993, 72:402–406.
71.
GenestJJMartin-MunleySMcNamaraJOrdovasJMJennerJMeyersR: Prevalence of familial lipoprotein disorders in patients with premature coronary artery disease. Circulation1992, 85:2025–2033. The authors established a significant role for Lp(a) as one of several lipoprotein and other risk factors that may underlie familial premature coronary heart disease.
WaldNJLawMWattHCWuTBaileyAJohnsonAM: Apolipoproteins and ischaemic heart disease: Implications for screening. Lancet1994, 343:75–79.
74.
ScanuAMFlessGM: Lipoprotein (a). J Clin Invest1990, 85:1709–1715. The authors' hypothesis, which proposes that Lp(a) represents a pool of cholesterol that is protected from LDL receptor uptake to meet the needs of the acute inflammatory response, has yet to be confirmed or refuted.
