[en] The inhibition of cholesterol synthesis by a statin enhances intestinal absorption of both cholesterol and various phytosterols. The atherogenic role of phytosterols, well proven in hypersitosterolemia, is now suspected in patients with premature coronary artery disease. The cholestanol/cholesterol ratio can be used as a marker of intestinal cholesterol absorption. Individuals with elevated ratio ("high absorbers") have less favourable cholesterol-lowering response and cardiovascular protection with statin therapy as compared to individuals with low ratio ("high synthesizers"). They may benefit of an adjunct therapy with phytostanols or ezetimibe, both being capable to reduce plasma concentrations of cholesterol and of phytosterols.
Radermecker, Régis ; Centre Hospitalier Universitaire de Liège - CHU > Diabétologie,nutrition, maladies métaboliques
Scheen, André ; Université de Liège - ULiège > Département des sciences cliniques > Diabétologie, nutrition et maladie métaboliques - Médecine interne générale
Language :
French
Title :
Distinction entre patients bons synthetiseurs et bons absorbeurs pour optimiser le traitement hypo- cholesterolemiant.
Alternative titles :
[en] Distinction between good synthesizer and good absorber patients to optimize cholesterol-lowering therapy
Knopp R. Drug treatment of lipid disorders. N Engl J Med 1999;341:498-511.
Baigent C, Keech A, Kearney PM, et al. Efficacy and safety of cholesterol-lowering treatment: Prospective meta-analysis of data from 90 056 participants in 14 randomised trials of statins. Lancet 2005;366:1267-78.
Jacobson TA. «The lower the better» in hypercholesterolemia therapy: A reliable clinical guideline? Ann Intern Med 2000;133:549-54.
Miettinen TA, Gylling H. Effect of statins on non-cholesterol sterol levels: Implications for use of plant stanols and sterols. Am J Cardiol 2005;96(Suppl):40-6D.
Patel MD, Thompson PD. Phytosterols and vascular disease. Atherosclerosis 2006;186:12-9.
Lammert F, Wang D QH. New insights into the genetic regulation of intestinal cholesterol absorption. Gastroenterology 2005;129:718-34.
Sudhop T, Lütjohann D, von Bergmann K. Sterol transporters: Targets of natural sterols and new lipid lowering drugs. Pharmacol Ther 2005;105:333-41.
Gylling H, Miettinen TA. The effect of plant stanol and sterol-enriched foods on lipid metabolism, serum lipids and coronary heart disease. Ann Clin Biochem 2005;42:254-63.
Bays H. Ezetimibe. Expert Opin Invest Drugs 2002;11:1587-604.
von Bergmann K, Sudhop T, Lütjohann D. Cholesterol and plant sterol absorption: Recent insights. Am J Cardiol 2005;96(Suppl. 1A):10D-4.
Altmann SW, Davis HR, Zhu L, et al. Niemann-Pick Cl like protein is critical for intestinal cholesterol absorption. Science 2004;303:1201-4.
Davis HR, Zhu LJ, Hoos LM, et al. Niemann-Pick Cl Like 1 (NPCILI) is the intestinal phytosterol and cholesterol transporter and a key modulator of whole body cholesterol homeostasis. J Biol Chem 2004;279:33586-92.
Salen G, von Bergmann K, Lütjohann D, et al. Ezetimibe effectively reduces plasma plant sterols in patients with sitosterolemia. Circulation 2004;109:966-71.
Thompson GR, Grundy SM. History and development of plant sterol and stanol esters for cholesterol-lowering purposes. Am J Cardiol 2005;96(Suppl. 1A):3D-9.
Grundy SM. Stanol esters as a component of maximal dietary therapy in the National Cholesterol Education Program Adult Treatment Panel III Report. Am J Cardiol 2005;96(Suppl. 1A):47D-50.
Moruisi KG, Oosthuizen W, Opperman AM. Phytosterols/stanols lower cholesterol concentrations in familial hypercholesterolemic subjects:A systematic review with meta-analysis. J Am Coll Nutr 2006;25:41-8.
Rédaction La Revue Prescrire. Aliments enrichis en phytostérols et phytostanols. Prescrire 2005;25:763-8.
Katan MB, Grundy SM, Jones P, et al. Efficacy and safety of plant stanols and sterols in the management of blood cholesterol levels. Mayo Clin Proc 2003;78:965-78.
Glueck CJ, Speirs T, Tracy T, et al. Relationships of serum plant sterols (phytosterols) and cholesterol in 595 hypercholesterolemic subjects, and familial aggregation of phytosterols, cholesterol, and premature coronary heart disease in hyperphytosterolemic probands and their first-degree relatives. Metabolism 1991;40:842-8.
Rajaratnam RA, Gylling H, Miettinen TA. Independent association of serum squalene and noncholesterol sterols with coronary artery disease in postmenopausal women. J Am Coll Cardiol 2000;35:1185-91.
Sudhop T, Gottwald BM, von Bergmann K. Serum plant sterols as a potential risk factor for coronary heart disease. Metabolism 2002;51:1519-21.
Assmann G, Cullen P, Erbey JR, et al. Elevation in plasma sitosterol concentration is associated with an increased risk for coronary events in the PROCAM study (abstract). Circulation 2003;108:IV-730.
Miettinen TA, Railo M, Lepäntalo M, Gylling H. Plant sterols in serum and in atherosclerotic plaques of patients undergoing carotid endarterectomy. J Am Coll Cardiol 2005;45:1794-801.
Radermecker RP, Scheen AJ. Serum plant sterols and atherosclerosis: Is there a place for statin-ezetimibe combination? J Am Coll Cardiol 2006;47:1496-7.
Gylling H, Miettinen TA. Inheritance of cholesterol metabolism of probands with high or low cholesterol absorption. J Lipid Res 2002;43:1472-6.
Miettinen TA, Tilvis RS, Kesaniemi YA. Serum plant sterols and cholesterol precursors reflect cholesterol absorption and synthesis in volunteers of a randomly selected male population. Am J Epidemiol 1990;131:20-31.
Miettinen TA, Strandberg TE, Gylling H, for the Finnish Investigators of the Scandinavian Simvastatin Survival Study Group. Noncholesterol sterols and cholesterol lowering by long-term simvastatin treatment in coronary patients. Relation to basal serum cholestanol. Arterioscler Thromb Vasc Biol 2000;20:1340-6.
Miettinen TA, Gylling H, Strandberg T, Sarna S, for the Finnish 45 Investigators. Baseline serum cholestanol as predictor of recurrent coronary events in subgroup of Scandinavian simvastatin survival study. BMJ 1998;316:1127-30.
Hoenig MR, Rolfe BE, Campbell JH. Cholestanol: A serum marker to guide LDL cholesterol-lowering therapy. Atherosclerosis 2006;184:247-54.
Gylling H, Miettinen TA. Cholesterol absorption: Influence of body weight and the role of plant sterols. Curr Atherosclerosis Rep 2005;7:466-71.
Grundy SM, Ahrens EH Jr, Davignon J. The interaction of cholesterol absorption and cholesterol synthesis in man. J Lipid Res 1969;10:304-15.
Miettinen TA, Gylling H, Lindholm N, et al. Serum noncholesterol sterols during inhibition of cholesterol synthesis by statins. J Lab Clin Med 2003;141:131-7.
Miettinen TA, Gylling H. Synthesis and absorption markers of cholesterol in serum and lipoproteins during a large dose statin treatment. Eur J Clin Med 2003;33:976-82.
Hedman M, Miettinen TA, Gylling H, Ketomäki A, Antikainen M. Serum noncholesterol sterols in children with heterozygous familial hypercholesterolemia undergoing pravastatin therapy. J Pediatr 2006;148:241-6.
Thompson GR. Additive effects of plant sterol and stanol esters to statin therapy. Am J Cardiol 2005;96 (Suppl):37D-9.
Sudhop T, Lütjohann D, Kodal A, et al. Inhibition of intestinal cholesterol absorption by ezetimibe in humans. Circulation 2002;106:1943-8.
Miettinen TA, Gylling H. Ineffective decrease of serum cholesterol by simvastatin in a subgroup of hypercholesterolemic corornary patients. Atherosclerosis 2002;164:147-52.
Goldberg AC, Ostlund RE, Bateman JH, et al. Effect of plant stanol tablets on low-density lipoprotein cholesterol lowering in patients on statin drugs. Am J Cardiol 2006;97:376-9.
Jakulj L, Trip MD, Sudhop T, et al. Inhibition of cholesterol absorption by the combination of dietary plant sterols and ezetimibe: Effects on plasma lipid levels. J Lipid Res 2005;46:2692-8.
Cohen JC, Boerwinkle E, Mosley TH Jr, Hobbs HH. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med 2006;354:1264-72.
Tall AR. Protease variants, LDL, and coronary heart disease. N Engl J Med 2006;354:1310-2.
Hegele RA, Guy J, Ban MR, Wang J. NPCILI haplotype is associated with inter-individual variation in plasma low-density lipoprotein response to ezetimibe. Lipids Health Dis 2005;12:4.