Review Article| Volume 34, ISSUE 1, P157-166, March 2014

Biomarkers for Cholesterol Absorption and Synthesis in Hyperlipidemic Patients

Role for Therapeutic Selection


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        • Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)
        Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Final Report.
        Circulation. 2002; 106: 3143-3421
        • Liscum L.
        Cholesterol biosynthesis.
        in: Vance D.E. Vance J.E. Biochemistry of lipids, lipoproteins and membranes. 4th edition. Elsevier, Amsterdam2002: 409-431
        • Bjorkhem I.
        • Miettinen T.
        • Reihner E.
        • et al.
        Correlation between serum levels of some cholesterol precursors and activity of HMG-CoA reducatase in human liver.
        J Lipid Res. 1987; 27: 1137-1143
        • Wang D.Q.
        New concepts of mechanisms of intestinal cholesterol absorption.
        Ann Hepatol. 2003; 2: 113-121
        • Hubacek J.A.
        • Berge K.E.
        • Cohen J.C.
        • et al.
        Mutations in ATP-cassette binding protein G5 (ABCG5) and G8 (ABCG8) causing sitosterolemia.
        Hum Mutat. 2001; 18: 359-360
        • Baumgartner S.
        • Mensink R.P.
        • Plat J.
        Plant sterols and stanols in the treatment of dysplipidemia: new insights into targets and mechanisms related to cardiovascular risk.
        Curr Pharm Des. 2011; 17: 922-932
        • Catapano A.L.
        Ezetimibe: a selective inhibitor of cholesterol absorption.
        Eur Heart J. 2001; 3: E6-E10
        • Singh P.
        • Saxena R.
        • Srinivas G.
        • et al.
        Cholesterol biosynthesis and homeostatsis in regulation of the cell cycle.
        PLoS One. 2013; 8: e58833
        • Telford D.E.
        • Sutherland B.G.
        • Edwards J.Y.
        • et al.
        The molecular mechanisms underlying the reduction of LDL apoB-100 by ezetimibe plus simvastatin.
        J Lipid Res. 2007; 48: 699-708
        • Matthan N.R.
        • Raeini-Sarjaz M.
        • Lichtenstein H.A.
        • et al.
        Deuterium uptake and plasma cholesterol precursor levels correspond as methods for measurement of endogenous cholesterol synthesis in hypercholesterolemic women.
        Lipids. 2000; 35: 1037-1044
      1. Wu AH, Ruan W, Todd J, et al. Biological variation of β-sitosterol, campesterol, and lathosterol as cholesterol absorption and synthesis biomarkers. Clin Chim Acta, in press.

        • Matthan N.R.
        • Lei Z.
        • Pencina M.
        • et al.
        Sex-specific differences in the predictive value of cholesterol homeostatic markers and 10-year cardiovascular disease event rate in Framingham Offspring Study participants.
        J Am Heart Assoc. 2013; 2: e005066 112.005066
        • Matthan N.R.
        • Pencina M.
        • laRocque J.M.
        • et al.
        Alterations in cholesterol absorption/synthesis markers characterize Framingham Offspring Study participants with CHD.
        J Lipid Res. 2009; 50: 1927-1935
        • Matthan N.R.
        • Resteghinini N.
        • Robertson M.
        • et al.
        Cholesterol absorption and synthesis markers in individuals with and without a CHD event during pravastatin therapy: insights from the PROSPER Trial.
        J Lipid Res. 2010; 51: 202-209
        • Van Himbergen T.M.
        • Otokozawa S.
        • Matthan N.R.
        • et al.
        Familial combined hyperlipidemia is associated with alterations in the cholesterol synthesis pathway.
        Arterioscler Thromb Vasc Biol. 2010; 30: 113-120
        • Salen G.
        • Shefer S.
        • Nguyen L.
        • et al.
        J Lipid Res. 1992; 33: 945-955
        • Rajaratnam R.A.
        • Gylling H.
        • Miettinen T.A.
        Independent association of serum squalene and noncholesterol sterols with coronary artery disease in postmenopausal women.
        J Am Coll Cardiol. 2000; 35: 1185-1191
        • Sudhop T.
        • Lutjohann D.
        • Kodal A.
        • et al.
        Inhibition of intestinal cholesterol absorption by ezetimibe humans.
        Circulation. 2002; 106: 1943-1948
        • Pinedo S.
        • Vissers M.N.
        • von Bergmann K.
        • et al.
        Plasma levels of plant steros and the risk of coronary artery disease: the prospective EPIC-Norfolk Population Study.
        J Lipid Res. 2007; 48: 139-144
        • Wilund K.R.
        • Yu L.
        • Xu F.
        • et al.
        Plant sterol levels are not associated with atherosclerosis in mice and men.
        Arterioscler Thromb Vasc Biol. 2004; 24: 1-7
        • Josan K.
        • Majumdar S.R.
        • McAlister F.A.
        The efficacy and safety of intensive statin therapy: a meta-analysis of randomized trials.
        CMAJ. 2008; 178: 576-584
        • Reihner E.
        • Rudling M.
        • Stahlberg D.
        • et al.
        Influence of pravastatin, a specific inhibitor of HMG-CoA reductase, on hepatic metabolism of cholesterol.
        N Engl J Med. 1990; 323: 224-228
        • Lupattelli G.
        • Siepi D.
        • De Vuono S.
        • et al.
        Cholesterol metabolism differs after statin therapy according to the type of hyperlipidemia.
        Life Sci. 2012; 90: 846-850
        • van Himbergen T.M.
        • Matthan N.R.
        • Resteghini N.A.
        • et al.
        Comparison of the effects of maximal dose atorvastatin and rosuvastatin therapy on cholesterol synthesis and absorption markers.
        J Lipid Res. 2009; 50: 730-739
        • Tremblay A.J.
        • Lamarche B.
        • Lemelin V.
        • et al.
        Atorvastatin increases intestinal expression of NPC1L1 in hyperlipidemic men.
        J Lipid Res. 2011; 52: 558-565
        • Lutjohann D.
        • von Bergmann K.
        • Sirah W.
        • et al.
        Long-term efficacy and safety of ezetimibe 10 mg in patients with homozygous sitosterolemia: a 2-year, open lapel extension study.
        Int J Clin Pract. 2008; 62: 1499-1510
        • Salen G.
        • von Bergmann K.
        • Lutjohann D.
        • et al.
        Ezetimibe effectively reduces plasma plant sterols in patients with sitosterolemia.
        Circulation. 2004; 108: 966-971
        • Thongtang N.
        • Lin J.
        • Schaefer E.J.
        • et al.
        Effects of ezetimibe added to statin therapy on markers of cholesterol absorption and synthesis and LDL-C lowering in hyperlipidemic patients.
        Atherosclerosis. 2012; 225: 388-396
        • Kishimoto M.
        • Sugiyama T.
        • Osame K.
        • et al.
        Efficacy of ezetimibe as monotherapy or combination therapy in hyperchoelsterolemic patients with and without diabetes.
        J Med Invest. 2011; 58: 86-94