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June 24, 1992, Vol 267, No. 24 >
ARTICLE | June 24, 1992

Lipoprotein(a): Title and subTitle BreakA Genetic Risk Factor for Premature Coronary Heart Disease FREE

Angelo M. Scanu, MD
[+] Author Affiliations

This article is one of a series sponsored by the American Heart Association.

Reprint requests to University of Chicago, 5841 S Maryland, MC5041, Chicago, IL 60637 (Dr Scanu).


JAMA. 1992;267(24):3326-3329. doi:10.1001/jama.1992.03480240088040
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Article
References

Lipoprotein(a) (Lp[a]) can be defined as a lipoprotein particle having as a protein moiety apolipoprotein B-100 (the protein associated with low-density lipoprotein) disulfide-linked to apolipoprotein(a), the distinctive glycoprotein of Lp(a) that is homologous to plasminogen. Several forms of Lp(a) occur in the circulation. This polymorphism is related to the apolipoprotein(a) size heterogeneity that is controlled by the several alleles of the apolipoprotein(a) gene. High plasma levels of Lp(a) have been correlated with an increased risk for atherothrombotic cardiovascular disease by a mechanism that is as yet undefined. Pathogenicity may also derive from Lp(a) particles that have been modified by events believed to occur when Lp(a), after traversing the artery endothelium, reaches the intima. Aside from several promising leads, there are no universally accepted ways to lower high plasma Lp(a) levels. At this time, it is best to target efforts toward the modifiable risk factors by using appropriate diets and exercise programs and, whenever necessary, drug therapy.

(JAMA. 1992;267:3326-3329)

REFERENCES

1 +
Scanu AM, Fless GM.  Lp(a): lipoprotein(a): heterogeneity and biological relevance. J Clin Invest . 1991;;85:1709-1715.
2 +
Scanu AM.  Lipoprotein(a): a genetically determined cardiovascular pathogen in search of a function. J Lab Clin Med . 1990;;116:142-146.
3 +
Fless GM, Pfaffinger DJ, Eisenbart JD, Scanu AM.  Solubility, immunochemical, and lipoprotein binding properties of apoB1OO-apo(a), the protein moiety of lipoprotein(a). J Lipid Res . 1990;;31:909-918.
4 +
Utermann G.  The mysteries of lipoprotein(a). Science . 1989;;246:904-910.
5 +
McLean JW, Tomlinson JE, Kuang W-J, et al.  cDNA sequence of human apolipoprotein(a) is homologous to plasminogen. Nature . 1987;;330:132-137.
6 +
Makino K, Scanu AM.  Lipoprotein(a): nonhuman primate models. Lipids . 1991;;26:679-683.
7 +
Tomlinson JE, McLean JW, Lawn RM.  Rhesus monkey apolipoprotein(a): sequence, evolution and site of synthesis. J Biol Chem . 1989;;264:5957-5965.
8 +
Laplaud PM, Beaubatie L, Rall SJ Jr, Luc G, Saboureau M.  Lipoprotein(a) is the major apoB-containing lipoprotein in the plasma of a hibernator, the hedgehog. J Lipid Res . 1988;;29:1157-1170.
9 +
Lackner C, Boerwinkle E, Leffert C, Rahmig T, Hobbs H.  Molecular basis of apolipoprotein(a) isoform size heterogeneity as revealed by pulsed-field gel electrophoresis. J Clin Invest . 1991;;87:2153-2161.
10 +
Azrolan N, Gavish D, Breslow JL.  Plasma lipoprotein(a) concentration is controlled by apolipoprotein(a) (apo[a]) size and the abundance of hepatic apo(a) mRNA in a cynomolgus monkey model. J Biol Chem . 1991;;266:13866-13872.
11 +
Henriksson P, Angelin B, Berglund L.  Hormonal effects on serum Lp(a) levels: marked reduction during estrogen treatment in males with prostatic cancer. Arterioscler Thromb . 1991;;11: 1423a.
12 +
Albers JJ, Taggart H, Applebaum-Bowden D, Haffner S, Chesnut CH, Hazzard WR.  Reduction of lecithin cholesterol acyl transferase, apolipoprotein B and Lp(a) lipoprotein with the anabolic steroid stanozolol. Biochim Biophys Acta . 1984;;795:293-296.
13 +
Kapelrud H, Bangstad H-J, Dahl-Jorgensen K, Berg K, Hanssen KF.  Serum Lp(a) lipoprotein concentrations in insulin dependent diabetic patients with microalbuminuria. BMJ . 1991;;303:675-678.
14 +
Mbewu AD, Durrington PN.  Lipoprotein(a): structure, properties and possible involvement in thrombogenesis and atherogenesis. Atherosclerosis . 1990;;85:1-14.
15 +
Parra HJ, Mezdour H, Cachera C, Dracon M, Tacquet A, Fruchart JC.  Lp(a) lipoprotein in patients with chronic renal failure treated by hemodialysis. Clin Chem . 1987;;33:721-725.
16 +
Jenkins AJ, Steele JS, Janus ED, Best JD.  Increased plasma apolipoprotein(a) levels in IDDM patients with microalbuminuria. Diabetes . 1991;;40: 787-790.
17 +
Edelstein C, Pfaffinger D, Scanu AM.  Long term primary human hepatocytes in culture produce an apoB-apo(a) complex that is isolated from the medium at density <1.006 g/ml. Arterioscler Thromb . 1991;;11:1424a.
18 +
Berg K.  A new serum type system in man: the Lp system. Acta Pathol Microbiol Scand . 1963;;59: 369-382.
19 +
Scanu AM, Scandiani L.  Lipoprotein(a): structure, biology and clinical relevance. Adv Intern Med . 1991;:36;249-270.
20 +
Dahlen G.  Incidence of Lp(a) among populations.  In: Scanu AM, ed. Lipoprotein(a) . Orlando, Fla: Academic Press Inc; 1990;;11:151-173.
21 +
Sorrentino MJ, Vielhauer C, Eisenbart JD, Fless GM, Scanu AM, Feldman T.  Plasma lipoprotein(a) protein concentration in coronary artery disease in black patients compared with white patients. Am J Med . In press.
22 +
Walton KW, Hitchens J, Magnani HN, Khan M.  A study of methods of identification and estimation of Lp(a) lipoprotein and of its significance in health, hyperlipidaemia and atherosclerosis. Atherosclerosis . 1974;;20:323-346.
23 +
Rath M, Niendorf A, Reblin T, Dietel M, Krebber HJ, Beisiegel U.  Detection and quantitation of lipoprotein(a) in the arterial wall of 107 coronary bypass patients. Arteriosclerosis . 1989;;9:579-592.
24 +
Cushing GL, Gaubatz JW, Nava ML, et al.  Quantitation and localization of apolipoprotein(a) and B in coronary artery bypass vein grafts resected at re-operation. Arteriosclerosis . 1989;;9:593-603.
25 +
Niendorf A, Rath M, Wolf K, et al.  Morphological detection and quantification of lipoprotein(a) deposition in atheromatous lesions. Virchows Arch A Pathol Anat Histopathol . 1990;;417:105-111.
26 +
Smith EB, Cochran S.  Factors influencing the accumulation in fibrous plaques of lipid derived from low density lipoprotein, II: preferential immobilization of lipoprotein (a) Lp(a). Atherosclerosis . 1990;;84:173-181.
27 +
Pepin JM, O'Neil JA, Hoff HF.  Quantification of apo(a) and apoB in human atherosclerotic lesions. J Lipid Res . 1991;;32:317-327.
28 +
Loscalzo J.  A unique risk factor for atherothrombotic disease. Arteriosclerosis . 1990;;10:672-679.
29 +
Miles LA, Plow EF.  Lp(a): an interloper into the fibrinolytic system? Thromb Haemost . 1990;; 63:331-335.
30 +
Scanu AM.  Lipoprotein(a) as a cardiovascular risk factor. Trends Cardiovasc Med . 1991;;1:294-299.
31 +
Miles LA, Fless GM, Levin EG, Scanu AM, Plow EF.  A potential basis for the thrombotic risks associated with lipoprotein(a). Nature . 1989;;339:301-303.
32 +
Hajjar KA, Gavish D, Breslow JL, Nachman RL.  Lipoprotein(a) modulation of endothelial cell surface fibrinolysis and its potential role in atherosclerosis. Nature . 1989;;339:303-305.
33 +
Haberland ME, Fless GM, Scanu AM, Fogelman AM.  Malondialdehyde modification of Lp(a) produces avid uptake by human monocyte-macrophages. J Biol Chem . 1992;;267:4143-4151.
34 +
Naruszewicz M, Selinger E, Davignon J.  Oxidation of Lp(a) particles increase their uptake by macrophages. Arteriosclerosis . 1990;;10:808a.
35 +
Borth W, Chang V, Bishop P, Harpel PC.  Lipoprotein(a) is a substrate for factor XIIIa and tissue transglutaminase. J Biol Chem. 1991;;266: 18149-18153.
36 +
Scanu AM, Pfaffinger D, Fless GM, Makino K, Eisenbart J, Hinman J.  Attenuation of immunological reactivity of lipoprotein(a) by thiols and cysteine-containing compounds: structural implications. Arterioscler Thromb . 1992;;12:424-429.
37 +
Mudd SH, Levy HL, Skovby F.  Disorders of transsulfuration.  In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic Basis of Inherited Disease . New York, NY: McGraw-Hill International Book Co; 1989;:693-734.
38 +
Seed D, Hoppichler F, McCarthy S, Thompson GR, Boerwinkle E, Utermann G.  Relation of serum lipoprotein(a) concentration and apolipoprotein(a) phenotype to coronary heart disease in FH. N Engl J Med . 1990;;322:1494-1499.
39 +
Wiklund O, Angelin B, Olofsson SO, et al.  Apolipoprotein(a) and ischemic heart disease in familial hypercholesterolemia. Lancet . 1990;;335:1360-1363.
40 +
Mbewu AD, Bahatnagar PN, Durrington L, et al.  Serum lipoprotein(a) in patients heterozygous for familial hypercholesterolemia, their relatives, and unrelated control populations. Arterioscler Thromb . 1991;;11:940-946.
41 +
Gavish D, Breslow JL.  Lipoprotein(a) reduction by N-acetyl cysteine. Lancet . 1991;;337:203-204.
42 +
Schmidt EB, Klausen IC, Kristensen SD, Lervang HH, Faergeman O, Dyeberg J.  The effect of n-3 polyunsaturated fatty acid on Lp(a). Clin Chim Acta . 1991;;198:271-278.
43 +
Beil FU, Terres W, Orgass M, Greten H.  Dietary fish oil lowers lipoprotein(a) in primary hypertriglyceridemia. Atherosclerosis . 1991;;90:95-97.
44 +
Gurakar A, Hoeg JM, Kostner G, Papadopoulos M, Brewer HB Jr.  Levels of lipoprotein(a) decline with neomycin and niacin treatment. Atherosclerosis . 1985;;57:293-301.
45 +
Carlsson LA, Hamsten A, Asplund A.  Pronounced lowering of serum levels of lipoprotein Lp(a) in hyperlipidemia subjects treated with nicotinic acid. J Intern Med . 1989;;226:271-276.
46 +
Jones PH, Gotto AM, Pownall HJ, et al.  Effect of gemfibrozil on plasma lipoprotein(a) levels in type IIa hyperlipoproteinemic subjects. Arterioscler Thromb . 1991;;11:1423a.
47 +
Levitsky LL, Scanu AM, Gould SH.  Lipoprotein (a) levels in black and white children and adolescents with insulin dependent diabetes mellitus. Diabetes Care . 1991;;14:283-287.
48 +
Haffner SM, Tuttle KR, Rainwater DL.  Decrease of Lp(a) with improved glycemic control in subjects with insulin-dependent diabetes mellitus. Diabetes Care . 1991;;14:302-307.
49 +
Armstrong VW, Schleef J, Thiery J, et al.  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.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Scanu AM, Fless GM.  Lp(a): lipoprotein(a): heterogeneity and biological relevance. J Clin Invest . 1991;;85:1709-1715.
2 +
Scanu AM.  Lipoprotein(a): a genetically determined cardiovascular pathogen in search of a function. J Lab Clin Med . 1990;;116:142-146.
3 +
Fless GM, Pfaffinger DJ, Eisenbart JD, Scanu AM.  Solubility, immunochemical, and lipoprotein binding properties of apoB1OO-apo(a), the protein moiety of lipoprotein(a). J Lipid Res . 1990;;31:909-918.
4 +
Utermann G.  The mysteries of lipoprotein(a). Science . 1989;;246:904-910.
5 +
McLean JW, Tomlinson JE, Kuang W-J, et al.  cDNA sequence of human apolipoprotein(a) is homologous to plasminogen. Nature . 1987;;330:132-137.
6 +
Makino K, Scanu AM.  Lipoprotein(a): nonhuman primate models. Lipids . 1991;;26:679-683.
7 +
Tomlinson JE, McLean JW, Lawn RM.  Rhesus monkey apolipoprotein(a): sequence, evolution and site of synthesis. J Biol Chem . 1989;;264:5957-5965.
8 +
Laplaud PM, Beaubatie L, Rall SJ Jr, Luc G, Saboureau M.  Lipoprotein(a) is the major apoB-containing lipoprotein in the plasma of a hibernator, the hedgehog. J Lipid Res . 1988;;29:1157-1170.
9 +
Lackner C, Boerwinkle E, Leffert C, Rahmig T, Hobbs H.  Molecular basis of apolipoprotein(a) isoform size heterogeneity as revealed by pulsed-field gel electrophoresis. J Clin Invest . 1991;;87:2153-2161.
10 +
Azrolan N, Gavish D, Breslow JL.  Plasma lipoprotein(a) concentration is controlled by apolipoprotein(a) (apo[a]) size and the abundance of hepatic apo(a) mRNA in a cynomolgus monkey model. J Biol Chem . 1991;;266:13866-13872.
11 +
Henriksson P, Angelin B, Berglund L.  Hormonal effects on serum Lp(a) levels: marked reduction during estrogen treatment in males with prostatic cancer. Arterioscler Thromb . 1991;;11: 1423a.
12 +
Albers JJ, Taggart H, Applebaum-Bowden D, Haffner S, Chesnut CH, Hazzard WR.  Reduction of lecithin cholesterol acyl transferase, apolipoprotein B and Lp(a) lipoprotein with the anabolic steroid stanozolol. Biochim Biophys Acta . 1984;;795:293-296.
13 +
Kapelrud H, Bangstad H-J, Dahl-Jorgensen K, Berg K, Hanssen KF.  Serum Lp(a) lipoprotein concentrations in insulin dependent diabetic patients with microalbuminuria. BMJ . 1991;;303:675-678.
14 +
Mbewu AD, Durrington PN.  Lipoprotein(a): structure, properties and possible involvement in thrombogenesis and atherogenesis. Atherosclerosis . 1990;;85:1-14.
15 +
Parra HJ, Mezdour H, Cachera C, Dracon M, Tacquet A, Fruchart JC.  Lp(a) lipoprotein in patients with chronic renal failure treated by hemodialysis. Clin Chem . 1987;;33:721-725.
16 +
Jenkins AJ, Steele JS, Janus ED, Best JD.  Increased plasma apolipoprotein(a) levels in IDDM patients with microalbuminuria. Diabetes . 1991;;40: 787-790.
17 +
Edelstein C, Pfaffinger D, Scanu AM.  Long term primary human hepatocytes in culture produce an apoB-apo(a) complex that is isolated from the medium at density <1.006 g/ml. Arterioscler Thromb . 1991;;11:1424a.
18 +
Berg K.  A new serum type system in man: the Lp system. Acta Pathol Microbiol Scand . 1963;;59: 369-382.
19 +
Scanu AM, Scandiani L.  Lipoprotein(a): structure, biology and clinical relevance. Adv Intern Med . 1991;:36;249-270.
20 +
Dahlen G.  Incidence of Lp(a) among populations.  In: Scanu AM, ed. Lipoprotein(a) . Orlando, Fla: Academic Press Inc; 1990;;11:151-173.
21 +
Sorrentino MJ, Vielhauer C, Eisenbart JD, Fless GM, Scanu AM, Feldman T.  Plasma lipoprotein(a) protein concentration in coronary artery disease in black patients compared with white patients. Am J Med . In press.
22 +
Walton KW, Hitchens J, Magnani HN, Khan M.  A study of methods of identification and estimation of Lp(a) lipoprotein and of its significance in health, hyperlipidaemia and atherosclerosis. Atherosclerosis . 1974;;20:323-346.
23 +
Rath M, Niendorf A, Reblin T, Dietel M, Krebber HJ, Beisiegel U.  Detection and quantitation of lipoprotein(a) in the arterial wall of 107 coronary bypass patients. Arteriosclerosis . 1989;;9:579-592.
24 +
Cushing GL, Gaubatz JW, Nava ML, et al.  Quantitation and localization of apolipoprotein(a) and B in coronary artery bypass vein grafts resected at re-operation. Arteriosclerosis . 1989;;9:593-603.
25 +
Niendorf A, Rath M, Wolf K, et al.  Morphological detection and quantification of lipoprotein(a) deposition in atheromatous lesions. Virchows Arch A Pathol Anat Histopathol . 1990;;417:105-111.
26 +
Smith EB, Cochran S.  Factors influencing the accumulation in fibrous plaques of lipid derived from low density lipoprotein, II: preferential immobilization of lipoprotein (a) Lp(a). Atherosclerosis . 1990;;84:173-181.
27 +
Pepin JM, O'Neil JA, Hoff HF.  Quantification of apo(a) and apoB in human atherosclerotic lesions. J Lipid Res . 1991;;32:317-327.
28 +
Loscalzo J.  A unique risk factor for atherothrombotic disease. Arteriosclerosis . 1990;;10:672-679.
29 +
Miles LA, Plow EF.  Lp(a): an interloper into the fibrinolytic system? Thromb Haemost . 1990;; 63:331-335.
30 +
Scanu AM.  Lipoprotein(a) as a cardiovascular risk factor. Trends Cardiovasc Med . 1991;;1:294-299.
31 +
Miles LA, Fless GM, Levin EG, Scanu AM, Plow EF.  A potential basis for the thrombotic risks associated with lipoprotein(a). Nature . 1989;;339:301-303.
32 +
Hajjar KA, Gavish D, Breslow JL, Nachman RL.  Lipoprotein(a) modulation of endothelial cell surface fibrinolysis and its potential role in atherosclerosis. Nature . 1989;;339:303-305.
33 +
Haberland ME, Fless GM, Scanu AM, Fogelman AM.  Malondialdehyde modification of Lp(a) produces avid uptake by human monocyte-macrophages. J Biol Chem . 1992;;267:4143-4151.
34 +
Naruszewicz M, Selinger E, Davignon J.  Oxidation of Lp(a) particles increase their uptake by macrophages. Arteriosclerosis . 1990;;10:808a.
35 +
Borth W, Chang V, Bishop P, Harpel PC.  Lipoprotein(a) is a substrate for factor XIIIa and tissue transglutaminase. J Biol Chem. 1991;;266: 18149-18153.
36 +
Scanu AM, Pfaffinger D, Fless GM, Makino K, Eisenbart J, Hinman J.  Attenuation of immunological reactivity of lipoprotein(a) by thiols and cysteine-containing compounds: structural implications. Arterioscler Thromb . 1992;;12:424-429.
37 +
Mudd SH, Levy HL, Skovby F.  Disorders of transsulfuration.  In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic Basis of Inherited Disease . New York, NY: McGraw-Hill International Book Co; 1989;:693-734.
38 +
Seed D, Hoppichler F, McCarthy S, Thompson GR, Boerwinkle E, Utermann G.  Relation of serum lipoprotein(a) concentration and apolipoprotein(a) phenotype to coronary heart disease in FH. N Engl J Med . 1990;;322:1494-1499.
39 +
Wiklund O, Angelin B, Olofsson SO, et al.  Apolipoprotein(a) and ischemic heart disease in familial hypercholesterolemia. Lancet . 1990;;335:1360-1363.
40 +
Mbewu AD, Bahatnagar PN, Durrington L, et al.  Serum lipoprotein(a) in patients heterozygous for familial hypercholesterolemia, their relatives, and unrelated control populations. Arterioscler Thromb . 1991;;11:940-946.
41 +
Gavish D, Breslow JL.  Lipoprotein(a) reduction by N-acetyl cysteine. Lancet . 1991;;337:203-204.
42 +
Schmidt EB, Klausen IC, Kristensen SD, Lervang HH, Faergeman O, Dyeberg J.  The effect of n-3 polyunsaturated fatty acid on Lp(a). Clin Chim Acta . 1991;;198:271-278.
43 +
Beil FU, Terres W, Orgass M, Greten H.  Dietary fish oil lowers lipoprotein(a) in primary hypertriglyceridemia. Atherosclerosis . 1991;;90:95-97.
44 +
Gurakar A, Hoeg JM, Kostner G, Papadopoulos M, Brewer HB Jr.  Levels of lipoprotein(a) decline with neomycin and niacin treatment. Atherosclerosis . 1985;;57:293-301.
45 +
Carlsson LA, Hamsten A, Asplund A.  Pronounced lowering of serum levels of lipoprotein Lp(a) in hyperlipidemia subjects treated with nicotinic acid. J Intern Med . 1989;;226:271-276.
46 +
Jones PH, Gotto AM, Pownall HJ, et al.  Effect of gemfibrozil on plasma lipoprotein(a) levels in type IIa hyperlipoproteinemic subjects. Arterioscler Thromb . 1991;;11:1423a.
47 +
Levitsky LL, Scanu AM, Gould SH.  Lipoprotein (a) levels in black and white children and adolescents with insulin dependent diabetes mellitus. Diabetes Care . 1991;;14:283-287.
48 +
Haffner SM, Tuttle KR, Rainwater DL.  Decrease of Lp(a) with improved glycemic control in subjects with insulin-dependent diabetes mellitus. Diabetes Care . 1991;;14:302-307.
49 +
Armstrong VW, Schleef J, Thiery J, et al.  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.

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