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April 6, 1994, Vol 271, No. 13 >
ARTICLE | April 6, 1994

Lipoprotein(a) in Coronary Heart Disease: Title and subTitle BreakIs It a Risk Factor After All? FREE

Victor Gurewich, MD; Murray Mittleman, MPH
[+] Author Affiliations

Reprint requests to Vascular Research Laboratory, Burlington Bldg, Room 554H, Deaconess Hospital, 185 Pilgrim Rd, Boston, MA 02215 (Dr Gurewich).


JAMA. 1994;271(13):1025-1026. doi:10.1001/jama.1994.03510370077037
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References

The role of lipoprotein(a) [Lp(a)] in coronary heart disease (CHD), once considered to be well established, has recently been put into question. For example, in a prospective, nested case-control study of the Helsinki Heart Study participants, Jauhiainen et al1 found no significant increase in risk of CHD associated with higher levels of Lp(a) among 138 hyperlipidemic men who developed coronary events compared with 130 controls. A similar lack of association between Lp(a) and clinical CHD was reported by Simons et al2 from a cross-sectional analysis of 1202 men and 1512 women older than 60 years. The skewed and broad distribution of Lp(a) levels, ranging from 1.0 mg/dL (0.03 mmol/L) to 210.0 mg/dL (5.25 mmol/L), was strikingly similar in the two groups. Finally, in a report published recently in The JOURNAL involving the prospective Physicians' Health Study, Ridker et al3 found a "virtually identical" Lp(a) distribution among 296

REFERENCES

1 +
Jauhiainen M, Koskinen P, Ehnholm C, 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.
2 +
Simons L, Friedlander Y, Simons J, McCallum J.  Lipoprotein(a) is not associated with coronary heart disease in the elderly: cross-sectional data from the Dubbo study. Atherosclerosis . 1993;;99:87-95.
3 +
Ridker PM, Hennekens CH, Stampfer MJ.  A prospective study of lipoprotein(a) and the risk of myocardial infarction. JAMA . 1993;;270:2195-2199.
4 +
Barnathan ES.  Has lipoprotein 'little' (a) shrunk? JAMA . 1993;;270:2224-2225.
5 +
Schaefer EJ, Lamon-Fava S, Jenner JL, et al.  Lipoprotein(a) levels and risk of coronary heart disease in men: the Lipid Research Clinics Coronary Primary Prevention Trial. JAMA . 1994;;271:999-1003.
6 +
Rosengren A, Wilhelmsen L, Eriksson E, Risberg B, Wedel H.  Lipoprotein(a) and coronary heart disease: a prospective case-control study in a general population sample of middle aged men. BMJ . 1990;;301:1248-1251.
7 +
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.
8 +
Dahlen GH, Guyton JR, Altar M, Farmer JA, Kautz JA, Gotto AM.  Association of levels of lipoprotein(a), plasma lipids, and other lipoproteins with coronary artery disease documented by angiography. Circulation . 1986;;74:758-765.
9 +
Wiklund O, Angelin B, Olofsson S-O, et al.  Apolipoprotein(a) and ischaemic heart disease in familial hypercholesterolemia. Lancet . 1990;;335:1360-1363.
10 +
Genest JJ Jr, Martin-Munley SS, McNamara JR, et al.  Familial lipoprotein disorders in patients with premature coronary artery disease. Circulation . 1992;;85: 2025-2033.
11 +
Albers JJ, Marcovina SM, Lodge MS.  The unique lipoprotein(a): properties and immunochemical measurement. Clin Chem . 1990;;36:2019-2026.
12 +
Ranby M.  Studies on the kinetics of plasminogen activation by tissue plasminogen activator. Biochem Biophys Acta . 1982;;704:461-469.
13 +
Harpel PC, Gordon BR, Parker TS.  Plasmin catalyses binding of lipoprotein(a) to immobilized fibrinogen and fibrin. Proc Natl Acad Sci U S A . 1989;;86:3847-3851.
14 +
Loscalzo J, Weinfeld M, Fless GM, Scanu AM.  Lipoprotein(a), fibrin-binding, and plasminogen activation. Arteriosclerosis . 1990;;10:240-245.
15 +
Edelberg JM, Gonzalez-Gronow M, Pizzo SV.  Lipoprotein(a) inhibition of plasminogen activation by tissue-type plasminogen activator. Thromb Res . 1990;;57:155-162.
16 +
Leerink CB, Gimpel JA, Kortlandt W, Bouma BN, van Rijn HJM.  Kinetic analysis of lipoprotein inhibition of plasminogen activation by tissue plasminogen activator in vitro. Fibrinolysis . 1991;;3:233-238.
17 +
Rouy D, Grailhe P, Nigon F, Chapman J, Anglés-Cano E.  Lipoprotein(a) impairs generation of plasmin by fibrin-bound tissue-type plasminogen activator: in vitro studies in a plasma milieu. Arterioscler Thromb . 1991;;11:629-638.
18 +
Halvorsen S, Skjønsberg OH, Berg K, Ruyter R, Godal HC.  Does Lp(a) lipoprotein inhibit the fibrinolytic system? Thromb Res . 1992;;68:223-232.
19 +
Mao SJT Tucci M, Tucci MA.  Lipoprotein(a) enhances plasma clot lysis in vitro. FEBS Lett . 1990;;267:131-134.
20 +
Oshima S, Uchida K, Yasu T, Uno K, Nonogi H, Haze K.  Transient increase of plasma lipoprotein(a) in patients with unstable angina pectoris: does lipoprotein(a) alter fibrinolysis? Arterioscler Thromb . 1991;;11:1772-1777.
21 +
Donders SHJ, Lustermans FATH, van Wersch JWJ.  On lipoprotein(a) and the coagulation/fibrinolysis balance in the acute phase of deep venous thrombosis. Fibrinolysis . 1993;;7:83-86.
22 +
Liu J, Harpel PC, Pannell R, Gurewich V.  Lipoprotein(a): a kinetic study of its influence on fibrin-dependent plasminogen activation by prourokinase or tissue plasminogen activator. Biochemistry . 1993;;32:9694-9700.
23 +
Liu J, Harpel PC, Gurewich V.  Fibrin-bound Lp(a) promotes plasminogen-binding but inhibits fibrin degradation by plasmin. Biochemistry . 1994;;33;2554-2560.
24 +
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.
25 +
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.
26 +
Liu J, Gurewich V.  Demonstration of covalent binding of lipoprotein(a) [Lp(a)] to fibrin and human umbilical vein endothelial cells (HUVEC). Fibrinolysis . Abstract. In press.
27 +
Cushing GL, Gaubatz JW, Nava ML, et al.  Quantitation and localization of apolipoproteins(a) and B in coronary artery bypass vein grafts resected at re-operation. Arteriosclerosis . 1989;;9:593-603.
28 +
Rath M, Niendof A, Reblin T, Dietel M, Krebber HJ, Beisiegel U.  Detection and quantification of lipoprotein(a) in the arterial wall of 107 coronary bypass patients. Arteriosclerosis . 1989;;9:579-592.
29 +
Smith E, Crosbie L.  Does lipoprotein(a) [Lp(a)] compete with plasminogen in human atherosclerotic lesions and thrombi? Atherosclerosis . 1991;;89:127-136.
30 +
Scanu AM.  Lipoprotein(a): a genetic risk factor for premature coronary heart disease. JAMA . 1992;;267:3326-3329.
31 +
Rath M, Pauling L.  Hypothesis: lipoprotein(a) is a surrogate for ascorbate. Proc Natl Acad Sci U S A . 1990;;87:6204-6207.

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1 +
Jauhiainen M, Koskinen P, Ehnholm C, 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.
2 +
Simons L, Friedlander Y, Simons J, McCallum J.  Lipoprotein(a) is not associated with coronary heart disease in the elderly: cross-sectional data from the Dubbo study. Atherosclerosis . 1993;;99:87-95.
3 +
Ridker PM, Hennekens CH, Stampfer MJ.  A prospective study of lipoprotein(a) and the risk of myocardial infarction. JAMA . 1993;;270:2195-2199.
4 +
Barnathan ES.  Has lipoprotein 'little' (a) shrunk? JAMA . 1993;;270:2224-2225.
5 +
Schaefer EJ, Lamon-Fava S, Jenner JL, et al.  Lipoprotein(a) levels and risk of coronary heart disease in men: the Lipid Research Clinics Coronary Primary Prevention Trial. JAMA . 1994;;271:999-1003.
6 +
Rosengren A, Wilhelmsen L, Eriksson E, Risberg B, Wedel H.  Lipoprotein(a) and coronary heart disease: a prospective case-control study in a general population sample of middle aged men. BMJ . 1990;;301:1248-1251.
7 +
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.
8 +
Dahlen GH, Guyton JR, Altar M, Farmer JA, Kautz JA, Gotto AM.  Association of levels of lipoprotein(a), plasma lipids, and other lipoproteins with coronary artery disease documented by angiography. Circulation . 1986;;74:758-765.
9 +
Wiklund O, Angelin B, Olofsson S-O, et al.  Apolipoprotein(a) and ischaemic heart disease in familial hypercholesterolemia. Lancet . 1990;;335:1360-1363.
10 +
Genest JJ Jr, Martin-Munley SS, McNamara JR, et al.  Familial lipoprotein disorders in patients with premature coronary artery disease. Circulation . 1992;;85: 2025-2033.
11 +
Albers JJ, Marcovina SM, Lodge MS.  The unique lipoprotein(a): properties and immunochemical measurement. Clin Chem . 1990;;36:2019-2026.
12 +
Ranby M.  Studies on the kinetics of plasminogen activation by tissue plasminogen activator. Biochem Biophys Acta . 1982;;704:461-469.
13 +
Harpel PC, Gordon BR, Parker TS.  Plasmin catalyses binding of lipoprotein(a) to immobilized fibrinogen and fibrin. Proc Natl Acad Sci U S A . 1989;;86:3847-3851.
14 +
Loscalzo J, Weinfeld M, Fless GM, Scanu AM.  Lipoprotein(a), fibrin-binding, and plasminogen activation. Arteriosclerosis . 1990;;10:240-245.
15 +
Edelberg JM, Gonzalez-Gronow M, Pizzo SV.  Lipoprotein(a) inhibition of plasminogen activation by tissue-type plasminogen activator. Thromb Res . 1990;;57:155-162.
16 +
Leerink CB, Gimpel JA, Kortlandt W, Bouma BN, van Rijn HJM.  Kinetic analysis of lipoprotein inhibition of plasminogen activation by tissue plasminogen activator in vitro. Fibrinolysis . 1991;;3:233-238.
17 +
Rouy D, Grailhe P, Nigon F, Chapman J, Anglés-Cano E.  Lipoprotein(a) impairs generation of plasmin by fibrin-bound tissue-type plasminogen activator: in vitro studies in a plasma milieu. Arterioscler Thromb . 1991;;11:629-638.
18 +
Halvorsen S, Skjønsberg OH, Berg K, Ruyter R, Godal HC.  Does Lp(a) lipoprotein inhibit the fibrinolytic system? Thromb Res . 1992;;68:223-232.
19 +
Mao SJT Tucci M, Tucci MA.  Lipoprotein(a) enhances plasma clot lysis in vitro. FEBS Lett . 1990;;267:131-134.
20 +
Oshima S, Uchida K, Yasu T, Uno K, Nonogi H, Haze K.  Transient increase of plasma lipoprotein(a) in patients with unstable angina pectoris: does lipoprotein(a) alter fibrinolysis? Arterioscler Thromb . 1991;;11:1772-1777.
21 +
Donders SHJ, Lustermans FATH, van Wersch JWJ.  On lipoprotein(a) and the coagulation/fibrinolysis balance in the acute phase of deep venous thrombosis. Fibrinolysis . 1993;;7:83-86.
22 +
Liu J, Harpel PC, Pannell R, Gurewich V.  Lipoprotein(a): a kinetic study of its influence on fibrin-dependent plasminogen activation by prourokinase or tissue plasminogen activator. Biochemistry . 1993;;32:9694-9700.
23 +
Liu J, Harpel PC, Gurewich V.  Fibrin-bound Lp(a) promotes plasminogen-binding but inhibits fibrin degradation by plasmin. Biochemistry . 1994;;33;2554-2560.
24 +
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.
25 +
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.
26 +
Liu J, Gurewich V.  Demonstration of covalent binding of lipoprotein(a) [Lp(a)] to fibrin and human umbilical vein endothelial cells (HUVEC). Fibrinolysis . Abstract. In press.
27 +
Cushing GL, Gaubatz JW, Nava ML, et al.  Quantitation and localization of apolipoproteins(a) and B in coronary artery bypass vein grafts resected at re-operation. Arteriosclerosis . 1989;;9:593-603.
28 +
Rath M, Niendof A, Reblin T, Dietel M, Krebber HJ, Beisiegel U.  Detection and quantification of lipoprotein(a) in the arterial wall of 107 coronary bypass patients. Arteriosclerosis . 1989;;9:579-592.
29 +
Smith E, Crosbie L.  Does lipoprotein(a) [Lp(a)] compete with plasminogen in human atherosclerotic lesions and thrombi? Atherosclerosis . 1991;;89:127-136.
30 +
Scanu AM.  Lipoprotein(a): a genetic risk factor for premature coronary heart disease. JAMA . 1992;;267:3326-3329.
31 +
Rath M, Pauling L.  Hypothesis: lipoprotein(a) is a surrogate for ascorbate. Proc Natl Acad Sci U S A . 1990;;87:6204-6207.

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