Plasma proprotein convertase subtilisin/kexin type 9 levels and the risk of first cardiovascular events

European Heart Journal

Volumn 37, Issue 6, 2016, Pages 554-560

  Ridker, Paul M ^a   Rifai, Nader ^b   Bradwin, Gary ^b   Rose, Lynda ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b BOSTON CHILDREN S HOSPITAL   (United States)

Author keywords

Apolipoprotein B; Epidemiology; Myocardial infarction; PCSK9; Prevention

Indexed keywords

APOLIPOPROTEIN A1; APOLIPOPROTEIN B; APOLIPOPROTEIN B100; C REACTIVE PROTEIN; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; LOW DENSITY LIPOPROTEIN CHOLESTEROL; PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9; SERINE PROTEINASE; TRIACYLGLYCEROL; UNCLASSIFIED DRUG; BIOLOGICAL MARKER; PCSK9 PROTEIN, HUMAN; PROPROTEIN CONVERTASE 9;

ADULT; AGE; ARTICLE; BLOOD PRESSURE; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CASE CONTROL STUDY; COHORT ANALYSIS; CONTROLLED STUDY; DIABETES MELLITUS; FEMALE; FOLLOW UP; HUMAN; HYPERLIPIDEMIA; HYPERTENSION; MAJOR CLINICAL STUDY; MEDICAL HISTORY; OBESITY; PREDICTIVE VALUE; PRIMARY PREVENTION; PRIORITY JOURNAL; PROSPECTIVE STUDY; PROTEIN BLOOD LEVEL; SMOKING; AGED; BLOOD; CARDIOVASCULAR DISEASES; ENZYMOLOGY; IMMUNOASSAY; METABOLISM; MIDDLE AGED; RISK FACTOR;

AGED; APOLIPOPROTEINS B; BIOMARKERS; C-REACTIVE PROTEIN; CARDIOVASCULAR DISEASES; CASE-CONTROL STUDIES; CHOLESTEROL, HDL; FEMALE; HUMANS; IMMUNOASSAY; MIDDLE AGED; PROPROTEIN CONVERTASE 9; PROSPECTIVE STUDIES; RISK FACTORS;

EID: 84959462562     PISSN: 0195668X     EISSN: 15229645     Source Type: Journal    
DOI: 10.1093/eurheartj/ehv568     Document Type: Article

References (26)

1. Abifadel M, Varret M, Rabes JP, Allard D, Ouguerram K, Devillers M, Cruaud C, Benjannet S, Wickham L, Erlich D, Derre A, Villeger L, Farnier M, Beucler I, Bruckert E, Chambaz J, Chanu B, Lecerf JM, Luc G, Moulin P, Weissenbach J, Prat A, Krempf M, Junien C, Seidah NG, Boileau C. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet 2003;34:154-156.
2. Cohen J, Pertsemlidis A, Kotowski IK, Graham R, Garcia CK, Hobbs HH. Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9. Nat Genet 2005;37:161-165.
3. 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: 1264-1272.
4. Horton JD, Cohen JC, Hobbs HH. Molecular biology of PCSK9: its role in LDL metabolism. Trends Biochem Sci 2007;32:71-77.
5. Seidah NG, Prat A. The biology and therapeutic targeting of the proprotein convertases. Nat Rev Drug Disc 2012;11:367-383.
6. Koren MJ, Scott R, Kim JB, Knusel B, Liu T, Lei L, Bolognese M,Wasserman SM. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 as monotherapy in patients with hypercholesterolaemia (MENDEL): A randomised, double-blind, placebo-controlled, phase 2 study. Lancet 2012;380:1995-2006.
7. Stein EA, Mellis S, Yancopoulos GD, Stahl N, Logan D, Smith WB, Lisbon E, Gutierrez M, Webb C, Wu R, Du Y, Kranz T, Gasparino E, Swergold GD. Effect of a monoclonal antibody to PCSK9 on LDL cholesterol. N Engl J Med 2012;366: 1108-1118.
8. Ridker PM. LDL cholesterol: controversies and future therapeutic directions. Lancet 2014;384:607-617.
9. Stein EA, Honarpour N, Wasserman SM, Xu F, Scott R, Raal FJ. Effect of the proprotein convertase subtilisin/kexin 9 monoclonal antibody, AMG 145, in homozygous familial hypercholesterolemia. Circulation 2013;128:2113-2120.
10. Lambert G, Chatelais M, Petrides F, Passard M, Thedrez A, Rye KA, Schwahn U, Gusarova V, Blom DJ, Sasiela W, Marais AD. Normalization of low-density lipoprotein receptor expression in receptor defective homozygous familial hypercholesterolemia by inhibition of PCSK9 with alirocumab. J Am Coll Cardiol 2014;64: 2299-2300.
11. Huijgen R, Boekholdt SM, Arsenault BJ, Bao W, Davaine JM, Tabet F, Petrides F, Rye KA, DeMicco DA, Barter PJ, Kastelein JJP, Lambert G. Plasma PCSK9 levels and clinical outcomes in the TNT (treating to new targets) trial. J Am Coll Cardiol 2012;59:1778-1784 (retracted).
12. Werner C, Hoffmann MM, Winkler K, Bohm M, Laufs U. Risk prediction with proprotein convertase subtilisin/kexin type 9 (PCSK9) in patients with stable coronary disease on statin treatment. Vascul Pharmacol 2014;62:94-102.
13. Welder G, Zineh I, Pacanowski MA, Troutt JS, Cao G, Konrad RJ. High-dose atorvastatin casuses a rapid sustained increasein human serum PCSK9 and disrupts its correlation with LDL cholesterol. J Lipid Res 2010;51:2714-2721.
14. Ridker PM, Cook NR, Lee IM, Gordon D, Gaziano JM, Manson JE, Hennekens CH, Buring JE. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med 2005;352:1293-1304.
15. Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000;342:836-843.
16. Suk Danik J, Rifai N, Buring JE, Ridker PM. Lipoprotein(a), measured with an assay independent of apolipoprotein(a) isoform size, and risk of future cardiovascular events among initially healthy women. JAMA 2006;296:1363-1370.
17. Ridker PM, Stampfer MJ, Rifai N. Novel risk factors for systemic atherosclerosis: A comparison of C-reactive protein, fibrinogen, homocysteine, lipoprotein(a), and standard cholesterol screening as predictors of peripheral arterial disease. JAMA 2001;285:2481-2485.
18. Lakoski SG, Lagace TA, Cohen JC, Horton JD, Hobbs HH. Genetic and metabolic determinants of plasma PCSK9 levels. J Clin Endocrin Metab 2009;94:2537-2543.
19. Dubuc G, Tremblay M, Pare G, Jacques H, Hamelin J, Benjannet S, Boulet L, Genest J, Bernier L, Seidah NG, Davignon J. A new method for measurement of total plasma PCSK9: clinical applications. J Lipid Res 2010;51:140-149.
20. Lambert G, Ancellin N, Charlton F, Comas D, Pilot J, Keech A, Patel S, Sullivan DR, Cohn JS, Rye KA, Barter PJ. Plasma PCSK9 concentrations correlate with LDL and total cholesterol in diabetic patients and are decreased by fenofibrate treatment. Clin Chem 2008;54:1038-1045.
21. Mayne J, Raymond A, Chaplin A, Cousins M, Kaefer N, Gyamera-Acheampong C, Seidah HG, Mbikay M, Chretien M, Ooi TC. Plasma PCSK9 levels correlate with cholesterol in men but not women. Biochem Biophys Res Commun 2007;361: 451-456.
22. Roubstova A, MunkondaMN, Awan Z, Marcinkiewicz J, CHamberalnd A, Lazure C, Cianflone K, Seidah NG, Prat A. Circulating proprotein convertase subtilisin/kexin 9 (PCSK9) regulates VLDLR protein and triglyceride accumulation in visceral adipose tissue. Arterioscler Thromb Vasc Biol 2011;31:785-791.
23. Horton JD, Goldstein JL, Brown MS. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest 2002;109: 1125-1131.
24. Zaid A, Roubstova A, Essalmani R, Marcinkiewicz J, Chamberland A, Hamelin J, Tremblay M, Jacques H, JinW, Davignon J, Seidah NG, Prat A. Proprotein convertase subtilis/kexin type 9 (PCSK9) hepatocyte-specific low-density lipoprotein receptor degradation and critical role in mouse liver regeneration. Hepatology 2008; 48 :646-654.
25. Grefhorst A, McNutt MC, Lagace TA, Horton JD. Plasma PCSK9 preferentially reduces liver LDL receptors in mice. J Lipid Res 2008;49:1303-1311.
26. Kosenko T, Golder M, Leblond G, Weng W, Lagace TA. Low density lipoprotein binds to proprotein convertase subtilisin/kexin type-9 (PCSK9) in human plasma and inhibits PCSK9-mediated low density lipoprotein receptor degradation. J Biol Chem 2013;288:8279-8288.