Advertisement

Proportion of oxidized LDL relative to plasma apolipoprotein B does not change during statin therapy in patients with heterozygous familial hypercholesterolemia

      Abstract

      Objective

      Circulating oxidized low-density lipoprotein (LDL) has been shown to be a useful marker for identifying patients with coronary heart disease (CHD) and persons at high cardiovascular risk. The effect of cholesterol-lowering therapy on plasma level of oxidized LDL is not clear.

      Methods and results

      We investigated effects of cholesterol lowering by therapeutic intervention (2 years) with atorvastatin (80 mg daily) and simvastatin (40 mg daily) on circulating oxidized LDL (absolute level and in proportion to plasma apolipoprotein B) in relation to atherosclerosis progression (carotid intima-media thickness, carotid IMT) and to inflammation (high-sensitivity C-reactive protein, hsCRP) in 115 stable patients with heterozygous familial hypercholesterolemia (FH). Atorvastatin and simvastatin reduced plasma-oxidized LDL (−43 and −35%, respectively) in proportion to the decrease in plasma apolipoprotein B. Neither absolute nor relative level of oxidized LDL correlated with carotid IMT or hsCRP at baseline. Also changes in levels of circulating oxidized LDL were not related to changes in carotid IMT and hsCRP.

      Conclusions

      In familial hypercholesterolemia-oxidized LDL carried in plasma is strongly associated with apolipoprotein B but not with inflammation nor with carotid IMT, and statin treatment does not reduce oxidized LDL relative to apolipoprotein B.

      Keywords

      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:

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

      References

        • Ehara S.
        • Ueda M.
        • Naruko T.
        • et al.
        Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes.
        Circulation. 2001; 103: 1955-1960
        • Holvoet P.
        • Mertens A.
        • Verhamme P.
        • et al.
        Circulating oxidized LDL is a useful marker for identifying patients with coronary artery disease.
        Arterioscler Thromb Vasc Biol. 2001; 21: 844-848
        • Holvoet P.
        • Harris T.B.
        • Tracy R.P.
        • et al.
        Association of high coronary heart disease risk status with circulating oxidized LDL in the well-functioning elderly: findings from the health, aging, and body composition study.
        Arterioscler Thromb Vasc Biol. 2003; 23: 1444-1448
        • Hulthe J.
        • Fagerberg B.
        Circulating oxidized LDL is associated with subclinical atherosclerosis development and inflammatory cytokines (AIR study).
        Arterioscler Thromb Vasc Biol. 2002; 22: 1162-1167
        • Toshima S.
        • Hasegawa A.
        • Kurabayashi M.
        • et al.
        Circulating oxidized low-density lipoprotein levels. A biochemical risk marker for coronary heart disease.
        Arterioscler Thromb Vasc Biol. 2000; 20: 2243-2247
        • Steinberg D.
        • Lewis A.
        Conner memorial lecture. Oxidative modification of LDL and atherogenesis.
        Circulation. 1997; 95: 1062-1071
        • Van Tits L.
        • de Graaf J.
        • Hak-Lemmers H.
        • et al.
        Increased levels of low-density lipoprotein oxidation in patients with familial hypercholesterolemia and in end-stage renal disease patients on hemodialysis.
        Lab Invest. 2003; 83: 13-21
        • Vasankari T.
        • Ahotupa M.
        • Toikka J.
        • et al.
        Oxidized LDL and thickness of carotid intima-media are associated with coronary atherosclerosis in middle-aged men: lower levels of oxidized LDL with statin therapy.
        Atherosclerosis. 2001; 155: 403-412
        • Tamura A.
        • Watanabe T.
        • Nasu M.
        Effects of atorvastatin and pravastatin on malondialdehyde-modified LDL in hypercholesterolemic patients.
        Circ J. 2003; 67: 816-820
        • Smilde T.J.
        • Van Wissen S.
        • Wollersheim H.
        • et al.
        Effect of aggressive versus conventional lipid lowering on atherosclerosis progression in familial hypercholesterolaemia (ASAP): a prospective, randomised, double-blind trial.
        Lancet. 2001; 357: 577-581
        • Smilde T.J.
        • Trip M.D.
        • Wollersheim H.
        • et al.
        Rationale, design, and baseline characteristics of a clinical trial comparing the effects of robust vs. conventional cholesterol lowering and intima-media thickness in patients with familial hypercholesterolemia. The atorvastatin vs. simvastatin on atherosclerosis progression (ASAP) study.
        Clin Drug Invest. 2000; 20: 67-79
        • Van Wissen S.
        • Trip M.D.
        • Smilde T.J.
        • et al.
        Differential hs-CRP reduction in patients with familial hypercholesterolemia treated with aggressive or conventional statin therapy.
        Atherosclerosis. 2002; 165: 361-366
        • Demacker P.N.
        • Hessels M.
        • Toenhake-Dijkstra H.
        • Baadenhuijsen H.
        Precipitation methods for high-density lipoprotein cholesterol measurement compared, and final evaluation under routine operating conditions of a method with a low sample-to-reagent ratio.
        Clin Chem. 1997; 43: 663-668
        • Lopes-Virella M.F.
        • Virella G.
        • Evans G.
        • et al.
        Immunonephelometric assay of human apolipoprotein Al.
        Clin Chem. 1980; 26: 1205-1208
        • Smilde T.J.
        • Wollersheim H.
        • van Langen H.
        • Stalenhoef A.F.
        Reproducibility of ultrasonographic measurements of different carotid and femoral artery segments in healthy subjects and in patients with increased intima-media thickness.
        Clin Sci (Lond). 1997; 93: 317-324
        • Grundy S.M.
        • Cleeman J.I.
        • Merz C.N.
        • et al.
        Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines.
        Circulation. 2004; 110: 227-239
        • Collins-Nakai R.L.
        • Dagenais G.R.
        The role of the cardiovascular specialist in the prevention of cardiovascular diseases—executive summary.
        Can J Cardiol. 1999; 15: 7G-16G
        • Van den Berkmortel F.W.P.J.
        • Wollersheim H.
        • Van Langen H.
        • et al.
        Two years of smoking cessation does not reduce arterial wall thickness and stiffness.
        Neth J Med. 2004; 62: 235-241
        • Rifai N.
        • Ridker P.M.
        High-sensitivity C-reactive protein: a novel and promising marker of coronary heart disease.
        Clin Chem. 2001; 47: 403-411
        • Van Tits L.J.H.
        • Smilde T.J.
        • Van Wissen S.
        • et al.
        Effects of atorvastatin and simvastatin on low-density lipoprotein subfraction profile, low-density lipoprotein oxidizability, and antibodies to oxidized low-density lipoprotein in relation to carotid intima media thickness in familial hypercholesterolemia.
        J Invest Med. 2004; 52: 177-184
        • Holvoet P.
        • Collen D.
        • Van de Werf F.
        Malondialdehyde-modified LDL as a marker of acute coronary syndromes.
        JAMA. 1999; 281: 1718-1721
        • Tsimikas S.
        • Bergmark C.
        • Beyer R.W.
        • et al.
        Temporal increases in plasma markers of oxidized low-density lipoprotein strongly reflect the presence of acute coronary syndromes.
        J Am Coll Cardiol. 2003; 41: 360-370
        • Liu M.L.
        • Ylitalo K.
        • Salonen R.
        • et al.
        Circulating oxidized low-density lipoprotein and its association with carotid intima-media thickness in asymptomatic members of familial combined hyperlipidemia families.
        Arterioscler Thromb Vasc Biol. 2004; 24: 1492-1497
        • Steinberg D.
        Low density lipoprotein oxidation and its pathobiological significance.
        J Biol Chem. 1997; 272: 20963-20966
        • Bugiardini R.
        • Manfrini O.
        • Pizzi C.
        • et al.
        Endothelial function predicts future development of coronary artery disease: a study of women with chest pain and normal coronary angiograms.
        Circulation. 2004; 109: 2518-2523
        • Halcox J.P.
        • Schenke W.H.
        • Zalos G.
        • et al.
        Prognostic value of coronary vascular endothelial dysfunction.
        Circulation. 2002; 106: 653-658
        • Chen M.
        • Masaki T.
        • Sawamura T.
        LOX-1, the receptor for oxidized low-density lipoprotein identified from endothelial cells: implications in endothelial dysfunction and atherosclerosis.
        Pharmacol Ther. 2002; 95: 89-100
        • Berliner J.A.
        • Heinecke J.W.
        The role of oxidized lipoproteins in atherogenesis.
        Free Radic Biol Med. 1996; 20: 707-727
        • Ridker P.M.
        • Rifai N.
        • Rose L.
        • et al.
        Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events.
        N Engl J Med. 2002; 347: 1557-1565