Research paper| Volume 108, ISSUE 2, P149-157, August 1994

Decreased plasma levels of lipoprotein(a) in patients with hypertriglyceridemia

      This paper is only available as a PDF. To read, Please Download here.


      Lipoprotein(a) (Lp(a)) is an atherogenic lipoprotein which is similar in structure to, but metabolically distinct from, LDL. Factors modulating plasma Lp(a) concentrations are poorly understood. To investigate the possible interaction of Lp(a) with triglycerides, we determined the apo(a) phenotype, Lp(a) concentration, and distribution of Lp(a) in a group of patients with triglycerides > 400 mg/dl (n = 60) compared with a control group (n = 128). Lp(a) concentrations were significantly lower in hypertriglyceridemic patients (mean ± S.E., 13 ± 4 mg/dl; median, 6 mg/dl; 25/75 percentile, 2–13 mg/dl) as compared with the controls (mean, 22 ± 2 mg/dl; median, 10 mg/dl; 25/75 percentile, 7–30 mg/dl.) Plasma Lp(a) concentrations in the hypertriglyceridemic patients correlated negatively with triglyceride levels (r = -0.69, P = 0.03). The difference in Lp(a) levels between patients and controls was maintained when subjects were stratified by apo(a) phenotype and type of hyperlipidemia. After subdividing the hypertriglyceridemic patients into one group with apo(a) isoforms ≤ S2 and one group with apo(a) isoforms Math EqS3, we found that the differences in plasma Lp(a) concentrations between patients and controls were more pronounced in the group with the lower molecular weight apo(a) isoforms. These data indicate that hypertriglyceridemia is associated with lower plasma Lp(a) concentrations and suggest that increased levels of triglyceride-rich lipoproteins may influence the metabolism of Lp(a).


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Utermann G.
        The mysteries of lipoprotein(a).
        Science. 1989; 246: 904
        • Scanu A.M.
        • Fless G.M.
        Lipoprotein(a). Heterogeneity and biological relevance.
        J. Clin. Invest. 1990; 85: 1709
        • Dahlin G.H.
        • Guyton J.R.
        • Attar M.
        • Farmer J.A.
        • Kautz J.A.
        • Gotto Jr., 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
        • Armstrong V.W.
        • Cremer P.
        • Eberle E.
        • et al.
        The association between serum Lp(a) concentrations and angiographically assessed coronary atherosclerosis. Dependence on serum LDL levels.
        Atherosclerosis. 1986; 62: 249
        • 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
        • Lawn R.M.
        • Wade D.P.
        • Hammer R.E.
        • Chiesa G.
        • Verstuyft J.G.
        • Rubin E.M.
        Atherogenesis in transgenic mice expressing human apolipoprotein(a).
        Nature. 1992; 360: 670
        • McLean J.W.
        • Tomlinson J.E.
        • Kuang W.J.
        • et al.
        cDNA sequence of human apolipoprotein(a) is homologous to plasminogen.
        Nature. 1987; 330: 132
        • Gaubatz J.W.
        • Ghanem K.I.
        • Guevara Jr, J.
        • Nava M.L.
        • Patsch W
        • Morrisett J.D.
        Polymorphic forms of human apolipoprotein(s): inheritance and relationship of their molecular weights to plasma levels of lipoprotein(a).
        J. Lipid Res. 1990; 31: 603
        • Utermann G.
        • Menzel H.J.
        • Kraft H.G.
        • Duba N.C.
        • Kemmler H.G.
        • Seitz C.
        Lp(a) glycoprotein phenotypes. Inheritance and relation to Lp(a)-lipoprotein concentrations in plasma.
        J. Clin. Invest. 1987; 80: 458
        • Boerwinkle E.
        • Menzel H.J.
        • Kraft H.G.
        • Utermann G.
        Genetics of the quantitative Lp(a) lipoprotein trait. III Contribution of Lp(a)glycoprotein phenotypes to normal lipid variation.
        Hum. Genet. 1989; 82: 73
        • Boerwinkle E.
        • Leffert C.C.
        • Lin J.
        • Lackner C.
        • Chiesa G.
        • Hobbs H.H.
        Apolipoprotein(a) gene accounts for greater than 90% of the variation in plasma lipoprotein(a) concentrations.
        J. Clin. Invest. 1992; 90: 52
        • Sandholzer C.
        • Boerwinkle E.
        • Saha N.
        • Tong M.C.
        • Utermann G.
        Apolipoprotein(a) phenotypes, Lp(a) concentration and plasma lipid levels in relation to coronary heart disease in a Chinese population: evidence for the role of the apo(a) gene in coronary heart disease.
        J. Clin. Invest. 1992; 89: 1040
        • Soutar A.K.
        • McCarthy S.N.
        • Seed M.
        • Knight B.L.
        Relationship between apolipoprotein(a) phenotype, lipoprotein(a) concentration in plasma, and low density li poprotein receptor function in a large kindred with familial hypercholesterolemia due to the pro664-leu mutation in the LDL receptor gene.
        J. Clin. Invest. 1991; 88: 483
        • Utermann G.
        • Hoppichler F.
        • Dieplinger H.
        • Seed M.
        • Thompson G.
        • Boerwinkle E.
        Defects in the low density lipoprotein receptor gene affect lipoprotein(a) lev els: multiplicative interaction of two gene loci associated with premature atherosclerosis.
        in: 8th Edn. Proc. Natl. Acad. Sci. USA. 86. 1989: 4171
        • Lackner C.
        • Boerwinkle E.
        • Leffert C.C.
        • Rahmig T.
        • Hobbs H.H.
        Molecular basis of apolipoprotein(a) isoform size heterogeneity as revealed by pulsed-field gel electrophoresis.
        J. Clin. Invest. 1991; 87: 2153
        • Rader D.J.
        • Cain W.
        • Zech L.A.
        • Usher D.
        • Brewer Jr, H.B.
        Variation in lipoprotein(a) concentrations among individuals with the same apolipoprotein(a) isoform is determined by the rate of lipoprotein(a) production.
        J. Clin. Invest. 1993; 91: 443
        • Bersot T.P.
        • Innerarity T.L.
        • Pitas R.E.
        • Rall Jr, S.C.
        • Weisgraber K.H.
        • Mahley R.W.
        Fat feeding in humans induces lipoproteins of density less than 1.006 that are enriched in apolipoprotein(a) and that cause lipid accumulation in macrophages.
        J. Clin. Invest. 1986; 77: 622
        • Reblin T.
        • Rader D.J.
        • Beisiegel U.
        • Greten H.
        • Brewer Jr., H.B.
        Correlation of apolipoprotein(a) isoproteins with Lp(a) density and distribution in fasting plasma.
        Atherosclerosis. 1992; 94: 223
        • Sandholzer C.
        • Feussner G.
        • Brunzell J.
        • Utermann G.
        Distribution of apolipoprotein(a) in the plasma from patients with lipoprotein lipase deficiency and with type III hyperlipoproteinemia. No evidence for a triglyceriderich precursor of lipoprotein(a).
        J. Clin. Invest. 1992; 90: 1958
        • Krempler F.
        • Kostner G.
        • Bolzano K.
        • Sandhofer F.
        Lipoprotein(a) is not a metabolic product of other lipoproteins containing polipoprotein B.
        Biochim. Biophys. Acta. 1979; 575: 63
        • Bojanovski M.
        • Gregg R.E.
        • Wilson D.M.
        • Brewer Jr., H.B.
        Semi automated enzyme-linked immunosorbent assay (ELISA) for the quantification of apolipoprotein B using monoclonal antibodies.
        Clin. Chim. Acta. 1987; 170: 271
        • Fless G.M.
        • Snyder M.L.
        • Scanu A.M.
        Enzymelinked immunoassay for Lp(a).
        J. Lipid Res. 1989; 30: 651
        • Knight B.L.
        • Perombelon Y.F.N.
        • Soutar A.K.
        • Wade D.P.
        • Seed M.
        Catabolism of lipoprotein(a) in familial hypercholesterolemic subjects.
        Atherosclerosis. 1991; 87: 227
        • Parra H.J.
        • Mezdour H.
        • Cachera C.
        • Dracon M.
        • Tacquet A.
        • Fruchart J.C.
        Lp(a) lipoprotein in patients with chronic renal failure treated by hemodialysis.
        Clin. Chem. 1987; 33: 721
        • Dieplinger H.
        • Lackner C.
        • Kronenberg F.
        • et al.
        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. Invest. 1993; 91: 263
        • Wanner C.
        • Rader D.J.
        • Bartens W.
        • et al.
        Elevated plasma lipoprotein(a) in patients with the nephrotic syndrome.
        Ann. Intern. Med. 1993; 119: 263
        • Rittner C.
        • Goenechea S.
        On the localisation of Ag and Lp by means of density gradient ultracentrifugation.
        Z. Immunitatsforsch. 1969; 137: 390
        • Ye S.Q.
        • Trieu V.N.
        • Stiers D.L.
        • McConathy W.J.
        Interactions of low density lipoprotein2 and other apolipoprotein B-containing lipoproteins with lipoprotein(a).
        J. Biol. Chem. 1988; 263: 6337
        • Trieu V.N.
        • McConathy W.J.
        Lipoprotein(a) binding to other apolipoprotein B containing lipoproteins.
        Biochemistry. 1990; 29: 5919
        • Trieu V.N.
        • Zioncheck T.F.
        • Lawn R.M.
        • McConathy W.J.
        Interaction of apolipoprotein(a) with apolipoprotein B-containing lipoproteins.
        J. Biol. Chem. 1991; 266: 5480
        • Armstrong M.L.
        • Heistad D.D.
        Animal models of atherosclerosis.
        Atherosclerosis. 1990; 85: 15
        • Fless G.M.
        • ZumMallen M.E.
        • Scanu A.M.
        Physicochemical properties of apolipoprotein(a) and lipoprotein(a-) derived from the dissociation of human plasma lipoprotein(a).
        J. Biol. Chem. 1986; 261: 8712
        • Pfaffinger D.
        • Schülke J.
        • Kim C.
        • Fless G.M.
        • Scanu A.M.
        Relation between apo(a) isoforms and Lp(a) density in subjects with different apo(a) phenotype: a study before and after a fatty meal.
        J. Lipid Res. 1991; 32: 679
        • Werba J.P.
        • Safa O.
        • Gianfranceschi G.
        • Michelagnoli S.
        • Sirtori C.R.
        • Franceschini G.
        Plasma triglycerides and lipoprotein(a): inverse relationship in a hyper lipidemic Italian population.
        Atherosclerosis. 1993; 101: 203
        • Kraft H.G.
        • Menzel H.J.
        • Hoppichler F.
        • Vogel W.
        • Utermann G.
        Changes of genetic apolipoprotein phenotypes caused by liver transplantation. Implications for apolipoprotein synthesis.
        J. Clin. Invest. 1989; 83: 137
        • Rainwater D.L.
        • Lanford R.E.
        Production of lipoprotein(a) by primary baboon hepatocytes.
        Biochim. Biophys. Acta. 1989; 1003: 30
        • Haffner S.M.
        • Tuttle K.R.
        • Rainwater D.L.
        Lack of change of lipoprotein(a) concentration with improved glycemic control in subjects with type II diabetes.
        Metabolism. 1992; 41: 116
        • Schnack C.
        • Pietschmann P.
        • Knöbl P.
        • Schuller E.
        • Prager R.
        • Schernthaner G.
        Apolipoprotein(a) levels and atherogenic lipid fractions in relation to the degree of urinary albumin excretion in type II diabetes mellitus.
        Nephron. 1994; 66: 273