Taking risk prediction to the next level. advances in biomarker research for atherosclerosis

Current Pharmaceutical Design

Volumn 19, Issue 33, 2013, Pages 5929-5941

  Siemelink, Marten ^a   van der Laan, Sander ^a   Timmers, Leo ^a   Hoefer, Imo ^a   Pasterkamp, Gerard ^a  

^a UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

Author keywords

Atherosclerosis; Biomarkers; Cardiovascular; Discovery; Drug; Novel

Indexed keywords

ANTILIPEMIC AGENT; BIOLOGICAL MARKER; C REACTIVE PROTEIN; CD36 ANTIGEN; CREATININE; CYSTATIN; FATTY ACID BINDING PROTEIN 4; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; LOW DENSITY LIPOPROTEIN CHOLESTEROL; MICRORNA 1; MICRORNA 122; MICRORNA 126; MICRORNA 145; MICRORNA 146A; MICRORNA 155; MICRORNA 182; MICRORNA 222; MICRORNA 29A; MICRORNA 375; NEUTROPHIL COLLAGENASE; SUBTILISIN; TRANSFORMING GROWTH FACTOR BETA; TRIACYLGLYCEROL; TROPONIN T;

ATHEROSCLEROSIS; ATHEROSCLEROTIC PLAQUE; CARDIOVASCULAR MORTALITY; CARDIOVASCULAR RISK; CELL POPULATION; CHOLESTEROL BLOOD LEVEL; CYTOKINE RELEASE; DIASTOLIC BLOOD PRESSURE; DISEASE COURSE; DRUG RESEARCH; ENDOTHELIAL PROGENITOR CELL; FLOW CYTOMETRY; GENE CONTROL; GENETIC ASSOCIATION; GENETIC VARIABILITY; GENETICS; HUMAN; HYPERCHOLESTEROLEMIA; IN VITRO STUDY; MEMBRANE VESICLE; MONOCYTE; PERIPHERAL BLOOD MONONUCLEAR CELL; PREDICTION; PREDICTIVE VALUE; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN DEPLETION; REVIEW; RISK ASSESSMENT; SIGNAL NOISE RATIO; SINGLE NUCLEOTIDE POLYMORPHISM; SYSTOLIC BLOOD PRESSURE; T LYMPHOCYTE; THROMBOCYTE;

ANIMALS; ATHEROSCLEROSIS; BIOLOGICAL MARKERS; BIOMEDICAL RESEARCH; DRUG DISCOVERY; HUMANS; PRIMARY PREVENTION; RISK FACTORS; SECONDARY PREVENTION;

EID: 84884267072     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/13816128113199990371     Document Type: Review

References (214)

1. Ge Y, Wang TJ. Circulating, imaging, and genetic biomarkers in cardiovascular risk prediction. Trends in cardiovascular medicine 2011; 21(4): 105-12.
2. Pikula A, Beiser AS, DeCarli C, et al. Multiple biomarkers and risk of clinical and subclinical vascular brain injury: the Framingham Offspring Study. Circulation 2012; 125(17): 2100-7.
3. Wang TJ. Assessing the role of circulating, genetic, and imaging biomarkers in cardiovascular risk prediction. Circulation 2011; 123(5): 551-65.
4. Wang TJ, Gona P, Larson MG, et al. Multiple biomarkers for the prediction of first major cardiovascular events and death. The New England J medicine 2006; 355(25): 2631-9.
5. Buckley DI, Fu R, Freeman M, Rogers K, Helfand M. C-reactive protein as a risk factor for coronary heart disease: a systematic review and meta-analyses for the U.S. Preventive Services Task Force. Annals of internal medicine 2009; 151(7): 483-95.
6. Loscalzo J. Association studies in an era of too much information: clinical analysis of new biomarker and genetic data. Circulation 2007; 116(17): 1866-70.
7. Quillard T, Libby P. Molecular imaging of atherosclerosis for improving diagnostic and therapeutic development. Circulation research 2012; 111(2): 231-44.
8. Cole JE, Mitra AT, Monaco C. Treating atherosclerosis: the potential of Toll-like receptors as therapeutic targets. Expert review of cardiovascular therapy 2010; 8(11): 1619-35.
9. Schunkert H, Samani NJ. Elevated C-reactive protein in atherosclerosis-chicken or egg? The New England J medicine 2008; 359(18): 1953-5.
10. Jaumdally R, Varma C, Macfadyen RJ, Lip GYH. Coronary sinus blood sampling: an insight into local cardiac pathophysiology and treatment? Eur heart J 2007; 28(8): 929-40.
11. Avgerinos ED, Kadoglou NPE, Moulakakis KG, Giannakopoulos TG, Liapis CD. Current role of biomarkers in carotid disease: a systematic review. International J stroke: official J the International Stroke Society 2011; 6(4): 337-45.
12. Battistoni A, Rubattu S, Volpe M. Circulating biomarkers with preventive, diagnostic and prognostic implications in cardiovascular diseases. Int J Cardiol 20121; 157(2): 160-8.
13. Surinova S, Schiess R, Hüttenhain R, Cerciello F, Wollscheid B, Aebersold R. On the development of plasma protein biomarkers. J proteome research 2011; 10(1): 5-16.
14. Mebazaa A, Vanpoucke G, Thomas G, et al. Unbiased plasma proteomics for novel diagnostic biomarkers in cardiovascular disease: identification of quiescin Q6 as a candidate biomarker of acutely decompensated heart failure. Eur Heart J 2012; 33(18): 2317-24.
15. Théry C, Ostrowski M, Segura E. Membrane vesicles as conveyors of immune responses. Nature reviews. Immunology 2009; 9(8): 581-93.
16. Mause SF, Weber C. Microparticles: protagonists of a novel communication network for intercellular information exchange. Circulation Res 2010; 107(9): 1047-57.
17. Simons M, Raposo G. Exosomes--vesicular carriers for intercellular communication. Curr Opinion Cell Biol 2009; 21(4): 575-81.
18. Camussi G, Deregibus MC, Bruno S, Cantaluppi V, Biancone L. Exosomes/microvesicles as a mechanism of cell-to-cell communication. Kidney international 2010; 78(9): 838-48.
19. Hron G, Kollars M, Weber H, et al. Tissue factor-positive microparticles: Cellular origin and association with coagulation activation in patients with colorectal cancer 2007; 119-23.
20. Taylor DD, Gercel-Taylor C. MicroRNA signatures of tumorderived exosomes as diagnostic biomarkers of ovarian cancer. Gynecologic oncology 2008; 110(1): 13-21.
21. Davila M, Amirkhosravi A, Coll E, et al. Tissue factor-bearing microparticles derived from tumor cells: impact on coagulation activation. J thrombosis and haemostasis: JTH 2008; 6(9): 1517-24.
22. Mack M, Kleinschmidt A, Brühl H, et al. Transfer of the chemokine receptor CCR5 between cells by membrane-derived microparticles: a mechanism for cellular human immunodeficiency virus 1 infection. Nature medicine 2000; 6(7): 769-75.
23. Rozmyslowicz T, Majka M, Kijowski J, et al. Platelet-and megakaryocyte-derived microparticles transfer CXCR4 receptor to CXCR4-null cells and make them susceptible to infection by X4-HIV. AIDS (London, England) 2003; 17(1): 33-42.
24. Fevrier B, Vilette D, Archer F, et al. Cells release prions in association with exosomes. Proc Natl Acad Sci USA 2004 Jun 29; 101(26): 9683-8.
25. Robertson C, Booth S A, Beniac DR, Coulthart MB, Booth TF, McNicol A. Cellular prion protein is released on exosomes from activated platelets. Blood 2006; 107(10): 3907-11.
26. Mallat Z, Hugel B, Ohan J, Leseche G, Freyssinet J-M, Tedgui A. Shed Membrane Microparticles With Procoagulant Potential in Human Atherosclerotic Plaques: A Role for Apoptosis in Plaque Thrombogenicity. Circulation 1999; 99(3): 348-53.
27. Leroyer AS, Isobe H, Lesèche G, et al. Cellular origins and thrombogenic activity of microparticles isolated from human atherosclerotic plaques. J Am College Cardiol 2007; 49(7): 772-7.
28. Rautou P.-E, Vion A.-C, Amabile N, et al. Microparticles, vascular function, and atherothrombosis. Circulation research 2011; 109(5): 593-606.
29. Amabile N, Guérin AP, Leroyer A, et al. Circulating endothelial microparticles are associated with vascular dysfunction in patients with end-stage renal failure. J Am Society of Nephrology: JASN 2005; 16(11): 3381-8.
30. Densmore JC, Signorino PR, Ou J, et al. Endothelium-derived microparticles induce endothelial dysfunction and acute lung injury. Shock (Augusta, Ga.) 2006; 26(5): 464-71.
31. Brodsky SV, Zhang F, Nasjletti A, Goligorsky MS. Endotheliumderived microparticles impair endothelial function in vitro. Am J Physiol Heart Circulatory Physiol 2004; 286(5): H1910-5.
32. Agouni A, Lagrue-Lak-Hal AH, Ducluzeau PH, et al. Endothelial dysfunction caused by circulating microparticles from patients with metabolic syndrome. Am J Pathol 2008; 173(4): 1210-9.
33. Barry OP, Pratico D, Lawson J A, FitzGerald G A. Transcellular activation of platelets and endothelial cells by bioactive lipids in platelet microparticles. The J clinical investigation 1997; 99(9): 2118-27.
34. Barry OP, Praticò D, Savani RC, FitzGerald G A. Modulation of monocyte-endothelial cell interactions by platelet microparticles. J Clinical Investigation 1998; 102(1): 136-44.
35. Mesri M, Altieri DC. Endothelial cell activation by leukocyte microparticles. J immunology (Baltimore, Md.: 1950) 1998; 161(8): 4382-7.
36. Scanu A, Molnarfi N, Brandt KJ, Gruaz L, Dayer J-M, Burger D. Stimulated T cells generate microparticles, which mimic cellular contact activation of human monocytes: differential regulation of pro-and anti-inflammatory cytokine production by high-density lipoproteins. J leukocyte Biol 2008; 83(4): 921-7.
37. Rautou P-E, Leroyer AS, Ramkhelawon B, et al. Microparticles from human atherosclerotic plaques promote endothelial ICAM-1-dependent monocyte adhesion and transendothelial migration. Circulation research 2011; 108(3): 335-43.
38. Brill A, Dashevsky O, Rivo J, Gozal Y, Varon D. Platelet-derived microparticles induce angiogenesis and stimulate post-ischemic revascularization. Cardiovascular research 2005; 67(1): 30-8.
39. Chou J, Mackman N, Merrill-Skoloff G, Pedersen B, Furie BC, Furie B. Hematopoietic cell-derived microparticle tissue factor contributes to fibrin formation during thrombus propagation. Blood 2004; 104(10): 3190-7.
40. Gasser O, Schifferli J A. Activated polymorphonuclear neutrophils disseminate anti-inflammatory microparticles by ectocytosis. Blood 2004; 104(8): 2543-8.
41. Yang C, Mwaikambo BR, Zhu T, et al. Lymphocytic microparticles inhibit angiogenesis by stimulating oxidative stress and negatively regulating VEGF-induced pathways. American J physiology. Regulatory, integrative and comparative physiology 2008; 294(2): R467-76.
42. Raimondo F, Morosi L, Chinello C, Magni F, Pitto M. Advances in membranous vesicle and exosome proteomics improving biological understanding and biomarker discovery. Proteomics 2011; 11(4): 709-20.
43. Simak J, Gelderman MP, Yu H, Wright V, Baird A E. Circulating endothelial microparticles in acute ischemic stroke: a link to severity, lesion volume and outcome. J thrombosis and haemostasis: JTH 2006; 4(6): 1296-302.
44. Peterson DB, Sander T, Kaul S, et al. Comparative proteomic analysis of PAI-1 and TNF-alpha-derived endothelial microparticles. Proteomics 2008; 8(12): 2430-46.
45. Mitchell PS, Parkin RK, Kroh EM, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA 2008; 105(30): 10513-8.
46. Chen X, Ba Y, Ma L, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 2008; 18(10): 997-1006.
47. Zhang Y, Liu D, Chen X, et al. Secreted monocytic miR-150 enhances targeted endothelial cell migration. Molecular cell 2010; 39(1): 133-44.
48. Zernecke A, Bidzhekov K, Noels H, et al. Delivery of microRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection. Science signaling 2009; 2(100): ra81.
49. Gamazon ER, Ziliak D, Im HK, et al. Genetic architecture of microRNA expression: implications for the transcriptome and complex traits. American J human genetics 2012; 90(6): 1046-63.
50. Gosling J, Slaymaker S, Gu L, et al. MCP-1 deficiency reduces susceptibility to atherosclerosis in mice that overexpress human apolipoprotein B. J Clinical Investigation 1999; 103(6): 773-8.
51. Nakashima Y, Raines EW, Plump A. S, Breslow JL, Ross R. Upregulation of VCAM-1 and ICAM-1 at Atherosclerosis-Prone Sites on the Endothelium in the ApoE-Deficient Mouse. Arteriosclerosis, Thrombosis, Vascular Biol 1998; 18(5): 842-51.
52. Qiao JH, Tripathi J, Mishra NK, et al. Role of macrophage colonystimulating factor in atherosclerosis: studies of osteopetrotic mice. Am J Pathol 1997; 150(5): 1687-99.
53. Emeson EE, Shen ML, Bell CG, Qureshi A. Inhibition of atherosclerosis in CD4 T-cell-ablated and nude (nu/nu) C57BL/6 hyperlipidemic mice. Am J Pathol 1996; 149(2): 675-85.
54. Zhou X, Nicoletti A., Elhage R, Hansson GK. Transfer of CD4+ T Cells Aggravates Atherosclerosis in Immunodeficient Apolipoprotein E Knockout Mice. Circulation 2000; 102(24): 2919-22.
55. Zhou X, Stemme S, Hansson GK. Short communication. International J language & communication disorders / Royal College of Speech & Language Therapists 1996; 149: 359-66.
56. Asahara T. Isolation of Putative Progenitor Endothelial Cells for Angiogenesis. Science 1997; 275(5302): 964-6.
57. Kuroi A, Imanishi T, Suzuki H, et al. Clinical Characteristics of Patients With Kawasaki Disease and Levels of Peripheral Endothelial Progenitor Cells and Blood Monocyte Subpopulations. Circulation J 2010; 74(12): 2720-5.
58. Ludwig A, Jochmann N, Kertesz A, et al. Smoking decreases the level of circulating CD34+ progenitor cells in young healthy women--a pilot study. BMC women's health 2010; 10: 20.
59. Schmidt-Lucke C, Rössig L, Fichtlscherer S, et al. Reduced number of circulating endothelial progenitor cells predicts future cardiovascular events: proof of concept for the clinical importance of endogenous vascular repair. Circulation 2005; 111(22): 2981-7.
60. van Oostrom O, Nieuwdorp M, Westerweel PE, et al. Reconstituted HDL increases circulating endothelial progenitor cells in patients with type 2 diabetes. Arteriosclerosis, thrombosis, and vascular biology 2007; 27(8): 1864-5.
61. Werner N, Kosiol S, Schiegl T, et al. Circulating endothelial progenitor cells and cardiovascular outcomes. The New England J medicine 2005; 353(10): 999-1007.
62. Westerweel PE, Hoefer IE, Blankestijn PJ, et al. End-stage renal disease causes an imbalance between endothelial and smooth muscle progenitor cells. American J physiology. Renal physiology 2007; 292(4): F1132-40.
63. Westerweel PE, Luijten RKM a C, Hoefer IE, Koomans H A, Derksen RHWM, Verhaar MC. Haematopoietic and endothelial progenitor cells are deficient in quiescent systemic lupus erythematosus. Annals of the rheumatic diseases 2007; 66(7): 865-70.
64. Westerweel PE, Visseren FLJ, Hajer GR, et al. Endothelial progenitor cell levels in obese men with the metabolic syndrome and the effect of simvastatin monotherapy vs. simvastatin/ezetimibe combination therapy. Eur Heart J 2008; 29(22): 2808-17.
65. Heine GH, Ortiz A, Massy ZA, et al. Monocyte subpopulations and cardiovascular risk in chronic kidney disease. Nature Rev Nephrol 2012; 8(6): 362-9.
66. Rogacev KS, Cremers B, Zawada AM, Seiler S, Binder N, Ege P, et al. CD14++CD16+ Monocytes Independently Predict Cardiovascular Events: A Cohort Study of 951 Patients Referred for Elective Coronary Angiography. J Am College Cardiol 2012; xx(x).
67. Barisione C, Garibaldi S, Ghigliotti G, et al. CD14CD16 monocyte subset levels in heart failure patients. Disease markers 2010; 28(2): 115-24.
68. Ulrich C, Heine GH, Gerhart MK, Köhler H, Girndt M. Proinflammatory CD14+CD16+ monocytes are associated with subclinical atherosclerosis in renal transplant patients. American J transplantation: official J Am Society Transplantation Am Soc Transplant Surgeons 2008; 8(1): 103-10.
69. Schipper HS, Nuboer R, Prop S, et al. Systemic inflammation in childhood obesity: circulating inflammatory mediators and activated CD14(++) monocytes. Diabetologia 2012; 55(10): 2800-10.
70. Ulrich C, Heine GH, Garcia P, et al. Increased expression of monocytic angiotensin-converting enzyme in dialysis patients with cardiovascular disease. Nephrology, dialysis, transplantation: official publication Eur Dialysis Transplant Association-Eur Renal Association 2006; 21(6): 1596-602.
71. Ulrich C, Heine GH, Seibert E, Fliser D, Girndt M. Circulating monocyte subpopulations with high expression of angiotensinconverting enzyme predict mortality in patients with end-stage renal disease. Nephrology, dialysis, transplantation: official publication of the European Dialysis and Transplant Association-European Renal Association 2010; 25(7): 2265-72.
72. Betjes MGH, de Wit EE A, Weimar W, Litjens NHR. Circulating pro-inflammatory CD4posCD28null T cells are independently associated with cardiovascular disease in ESRD patients. Nephrology, dialysis, transplantation: official publication of the European Dialysis and Transplant Association-European Renal Association 2010; 25(11): 3640-6.
73. Alber HF, Duftner C, Wanitschek M, et al. Neopterin, CD4+CD28-lymphocytes and the extent and severity of coronary artery disease. Int J Cardiol 2009; 135(1): 27-35.
74. Dumitriu IE, Araguás ET, Baboonian C, Kaski JC. CD4+ CD28 null T cells in coronary artery disease: when helpers become killers. Cardiovascular research 2009; 81(1): 11-9.
75. Ammirati E, Cianflone D, Banfi M, et al. Circulating CD4+CD25hiCD127lo regulatory T-Cell levels do not reflect the extent or severity of carotid and coronary atherosclerosis. Arteriosclerosis, thrombosis, and vascular biology 2010; 30(9): 1832-41.
76. Breet NJ, van Werkum JW, Bouman HJ, et al. Comparison of Platelet Function Tests Undergoing Coronary Stent Implantation. JAMA: J Am Med Association 2010; 303(8).
77. Edfeldt K, Swedenborg J, Hansson GK, Yan Z-qun. Expression of toll-like receptors in human atherosclerotic lesions: a possible pathway for plaque activation. Circulation 2002; 105(10): 1158-61.
78. Hamann L, Gomma A, Schröder NWJ, et al. A frequent toll-like receptor (TLR)-2 polymorphism is a risk factor for coronary restenosis. J molecular medicine (Berlin, Germany) 2005; 83(6): 478-85.
79. Tobias PS, Curtiss LK. Toll-like receptors in atherosclerosis. Biochemical Society transactions 2007; 35(Pt 6): 1453-5.
80. Xu XH, Shah PK, Faure E, et al. Toll-Like Receptor-4 Is Expressed by Macrophages in Murine and Human Lipid-Rich Atherosclerotic Plaques and Upregulated by Oxidized LDL. Circulation 2001; 104(25): 3103-8.
81. Ishikawa Y, Satoh M, Itoh T, Minami Y, Takahashi Y, Akamura M. Local expression of Toll-like receptor 4 at the site of ruptured plaques in patients with acute myocardial infarction. Clinical science (London, England: 1979) 2008; 115(4): 133-40.
82. Liuzzo G, Angiolillo DJ, Buffon A, et al. Enhanced Response of Blood Monocytes to In vitro Lipopolysaccharide-Challenge in Patients With Recurrent Unstable Angina. Circulation 2001; 103(18): 2236-41.
83. Methe H, Kim J-O, Kofler S, Weis M, Nabauer M, Koglin J. Expansion of circulating Toll-like receptor 4-positive monocytes in patients with acute coronary syndrome. Circulation 2005; 111(20): 2654-61.
84. Versteeg D, Hoefer IE, Schoneveld A H, et al. Monocyte toll-like receptor 2 and 4 responses and expression following percutaneous coronary intervention: association with lesion stenosis and fractional flow reserve. Heart (British Cardiac Society) 2008; 94(6): 770-6.
85. Kuwahata S, Fujita S, Orihara K, et al. High expression level of Toll-like receptor 2 on monocytes is an important risk factor for arteriosclerotic disease. Atherosclerosis 2010; 209(1): 248-54.
86. Lorenzen JM, David S, Richter A, et al. TLR-4+ peripheral blood monocytes and cardiovascular events in patients with chronic kidney disease--a prospective follow-up study. Nephrology, dialysis, transplantation: official publication of the European Dialysis and Transplant Association-European Renal Association 2011; 26(4): 1421-4.
87. Hemker HC, Dieri RA, Smedt ED, Béguin S. Thrombin generation, a function test of the haemostatic-thrombotic system 2006; 553-61.
88. Rand ML, Leung R, Packham M A. Platelet function assays. Transfusion and apheresis science: official J the World Apheresis Association: official J the European Society for Haemapheresis 2003; 28(3): 307-17.
89. Pajunen P, Syvänne M, Castro G, Nieminen MS, Taskinen MR. Cholesterol efflux capacity in vitro predicts the severity and extent of coronary artery disease in patients with and without type 2 diabetes. Scandinavian cardiovascular journal: SCJ 2001; 35(2): 96-100.
90. Chirinos J A, Zambrano JP, Chakko S, et al. Ability of serum to decrease cellular acylCoA: cholesterol acyl transferase activity predicts cardiovascular outcomes. Circulation 2005; 112(16): 2446-53.
91. Khera AV, Cuchel M, de la Llera-Moya M, et al. Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis. The New England J medicine 2011; 364(2): 127-35.
92. Zhou H, Shiu SWM, Wong Y, Tan KCB. Impaired serum capacity to induce cholesterol efflux is associated with endothelial dysfunction in type 2 diabetes mellitus. Diabetes & vascular disease research: official J the International Society of Diabetes and Vascular Disease 2009; 6(4): 238-43.
93. Reiss AB, Wan DW, Anwar K, et al. Enhanced CD36 scavenger receptor expression in THP-1 human monocytes in the presence of lupus plasma: linking autoimmunity and atherosclerosis. Experimental biology and medicine (Maywood, N.J.) 2009; 234(3): 354-60.
94. Verrijn Stuart A A, Schipper HS, Tasdelen I, et al. Altered plasma adipokine levels and in vitro adipocyte differentiation in pediatric type 1 diabetes. The J clinical endocrinology and metabolism 2012; 97(2): 463-72.
95. Pasterkamp G, Schoneveld AH, van der Wal AC, et al. Inflammation of the atherosclerotic cap and shoulder of the plaque is a common and locally observed feature in unruptured plaques of femoral and coronary arteries. Arteriosclerosis, thrombosis, and vascular biology 1999; 19(1): 54-8.
96. Stone GW, Maehara A, Lansky AJ, et al. A prospective naturalhistory study of coronary atherosclerosis. The New England J medicine 2011; 364(3): 226-35.
97. Hellings WE, Moll FL, De Vries J-PPM, et al. Atherosclerotic plaque composition and occurrence of restenosis after carotid endarterectomy. JAMA: the J Am Medical Association 2008; 299(5): 547-54.
98. de Kleijn DPV, Moll FL, Hellings WE, et al. Local atherosclerotic plaques are a source of prognostic biomarkers for adverse cardiovascular events. Arteriosclerosis, thrombosis, and vascular biology 2010; 30(3): 612-9.
99. Peeters W, de Kleijn DPV, Vink A, et al. Adipocyte fatty acid binding protein in atherosclerotic plaques is associated with local vulnerability and is predictive for the occurrence of adverse cardiovascular events. Eur Heart J 2011; 32(14): 1758-68.
100. Peeters W, Moll FL, Vink A, et al. Collagenase matrix metalloproteinase-8 expressed in atherosclerotic carotid plaques is associated with systemic cardiovascular outcome. Eur Heart J 2011; 32(18): 2314-25.
101. Hellings WE, Peeters W, Moll FL, et al. Composition of carotid atherosclerotic plaque is associated with cardiovascular outcome: a prognostic study. Circulation 2010; 121(17): 1941-50.
102. Sun J, Underhill HR, Hippe DS, Xue Y, Yuan C, Hatsukami TS. Sustained acceleration in carotid atherosclerotic plaque progression with intraplaque hemorrhage: a long-term time course study. JACC. Cardiovascular imaging 2012; 5(8): 798-804.
103. Stein LD. Human Genome: End of the beginning. Nature 2004; 431(October): 915-6.
104. International Human Genome Sequencing Consortium. Initial sequencing and analysis of the human genome. Nature 2001; 409(6822): 860-921.
105. International Human Genome Sequencing Consortium. Finishing the euchromatic sequence of the human genome. Nature 2004; 431(7011): 931-45.
106. Venter JC, Adams MD, Myers EW, et al. The sequence of the human genome. Science 2001; 291(5507): 1304-51.
107. Wheeler D A, Srinivasan M, Egholm M, et al. The complete genome of an individual by massively parallel DNA sequencing. Nature 2008; 452(7189): 872-6.
108. The 1000 Genomes Project Consortium. A map of human genome variation from population-scale sequencing. Nature 2010; 467(7319): 1061-73.
109. The International HapMap 3 Consortium. Integrating common and rare genetic variation in diverse human populations. Nature 2010; 467(7311): 52-8.
110. Frazer K A, Ballinger DG, Cox DR, et al. A second generation human haplotype map of over 3.1 million SNPs. Nature 2007; 449(7164): 851-61.
111. The International SNP Map Working Group. A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature 2001; 409(6822): 928-33.
112. The International Human Genome Mapping Consortium. A physical map of the human genome. Nature 2001; 409(6822): 934-41.
113. The International HapMap Consortium. A haplotype map of the human genome. Nature 2005; 437(7063): 1299-320.
114. Mills RE, Walter K, Stewart C, et al. Mapping copy number variation by population-scale genome sequencing. Nature 2011; 470(7332): 59-65.
115. Levy S, Sutton G, Ng PC, et al. The Diploid Genome Sequence of an Individual Human. PLoS biology 2007; 5(10): e254.
116. Mullen S A, Crompton DE, Carney PW, Helbig I, Berkovic SF. A neurologist's guide to genome-wide association studies. Neurology 2009; 72(6): 558-65.
117. Pearson T a, Manolio T.A. How to interpret a genome-wide association study. JAMA: the J Am Medical Association 2008; 299(11): 1335-44.
118. Manolio TA. Genomewide association studies and assessment of risk of disease. New Eng J Med 2010; 363(21): 2076-7; author reply 2077.
119. McCarthy MI, Abecasis GR, Cardon LR, et al. Genome-wide association studies for complex traits: consensus, uncertainty and challenges. Nature reviews. Genetics 2008; 9(5): 356-69.
120. Teslovich TM, Musunuru K, Smith AV, et al. Biological, clinical and population relevance of 95 loci for blood lipids. Nature 2010; 466(7307): 707-13.
121. Asselbergs FW, Guo Y, van Iperen EPA, et al. Large-Scale Gene-Centric Meta-analysis across 32 Studies Identifies Multiple Lipid Loci. Am J Human Genetics 2012;: 1-16.
122. Speliotes EK, Willer CJ, Berndt SI, et al. Association analyses of 249, 796 individuals reveal 18 new loci associated with body mass index. Nature genetics 2010; 42(11): 937-48.
123. Kathiresan S, Willer CJ, Peloso GM, et al. Common variants at 30 loci contribute to polygenic dyslipidemia. Nature genetics 2009; 41(1): 56-65.
124. Köttgen A, Glazer NL, Dehghan A, et al. Multiple loci associated with indices of renal function and chronic kidney disease. Nature genetics 2009; 41(6): 712-7.
125. Köttgen A, Pattaro C, Böger C. A, et al. New loci associated with kidney function and chronic kidney disease. Nature genetics 2010; 42(5): 376-84.
126. Chambers JC, Zhang W, Lord GM, et al. Genetic loci influencing kidney function and chronic kidney disease. Nature genetics 2010; 42(5): 373-5.
127. Voight BF, Scott LJ, Steinthorsdottir V, et al. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nature genetics 2010; 42(7): 579-89.
128. Saxena R, Elbers CC, Guo Y, et al. Large-Scale Gene-Centric Meta-Analysis across 39 studies Identifies Type 2 Diabetes Loci. American J human genetics 2012;: 410-25.
129. Newton-Cheh C, Johnson T, Gateva V, et al. Genome-wide association study identifies eight loci associated with blood pressure. Nature genetics 2009; 41(6): 666-76.
130. Levy D, Ehret GB, Rice K, et al. Genome-wide association study of blood pressure and hypertension. Nature genetics 2009; 41(6): 677-87.
131. Ehret GB, Munroe PB, Rice KM, et al. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature 2011; 478(7367): 103-9.
132. Hindorff L. A, Sethupathy P, Junkins H. A, et al. Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc Natl Acad Sci USA 2009; 106(23): 9362-7.
133. McPherson R, Pertsemlidis A, Kavaslar N, et al. A common allele on chromosome 9 associated with coronary heart disease. Science (New York, N.Y.) 2007; 316(5830): 1488-91.
134. Helgadottir A, Thorleifsson G, Manolescu A, et al. A common variant on chromosome 9p21 affects the risk of myocardial infarction. Science (New York, N.Y.) 2007; 316(5830): 1491-3.
135. The Wellcome Trust Case Control Consortium. Genome-wide association study of 14, 000 cases of seven common diseases and 3, 000 shared controls. Nature 2007; 447(7145): 661-78.
136. Helgadottir A, Thorleifsson G, Magnusson KP, et al. The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm. Nature genetics 2008; 40(2): 217-24.
137. Samani NJ, Raitakari OT, Sipilä K, et al. Coronary artery diseaseassociated locus on chromosome 9p21 and early markers of atherosclerosis. Arteriosclerosis, thrombosis, and vascular biology 2008; 28(9): 1679-83.
138. Schunkert H, König IR, Kathiresan S, et al. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nature genetics 2011; 43(4): 333-8.
139. Hiura Y, Fukushima Y, Yuno M, et al. Validation of the association of genetic variants on chromosome 9p21 and 1q41 with myocardial infarction in a Japanese population. Circulation journal: official J Japanese Circulation Soc 2008; 72(8): 1213-7.
140. Shen GQ, Li L, Rao S, et al. Four SNPs on chromosome 9p21 in a South Korean population implicate a genetic locus that confers high cross-race risk for development of coronary artery disease. Arteriosclerosis, thrombosis, and vascular biology 2008; 28(2): 360-5.
141. Assimes TL, Knowles JW, Basu A, et al. Susceptibility locus for clinical and subclinical coronary artery disease at chromosome 9p21 in the multi-ethnic ADVANCE study. Human molecular genetics 2008; 17(15): 2320-8.
142. The Coronary Artery Disease (C4D) Genetics Consortium. A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease. Nature genetics 2011; 43(4): 339-44.
143. Ikram M, Seshadri S, Bis J, et al. Genomewide association studies of stroke. NEJM 2009; (360): 1718-28.
144. International Stroke Genetics Consortium, Wellcome Trust Case-Control Consortium 2. Failure to Validate Association between 12p13 Variants and Ischemic Stroke. NEJM 2010; 362(16): 1547-50.
145. Bellenguez C, Bevan S, Gschwendtner A, et al. Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke. Nature genetics 2012; 44(3): 328-33.
146. Traylor M, Farrall M, Holliday EG, et al. Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE Collaboration): a meta-analysis of genome-wide association studies. Lancet neurology 2012;: 951-62.
147. Preuss M, König IR, Thompson JR, et al. Design of the Coronary ARtery DIsease Genome-Wide Replication And Meta-Analysis (CARDIoGRAM) Study: A Genome-wide association metaanalysis involving more than 22 000 cases and 60 000 controls. Circulation. Cardiovascular genetics 2010; 3(5): 475-83.
148. Bis JC, Kavousi M, Franceschini N, et al. Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque. Nature genetics 2011; 43(10): 940-7.
149. Manolio TA, Collins FS, Cox NJ, et al. Finding the missing heritability of complex diseases. Nature 2009; 461(7265): 747-53.
150. van der Net JB, Janssens ACJW, Sijbrands EJG, Steyerberg EW. Value of genetic profiling for the prediction of coronary heart disease. Am Heart J2009; 158(1): 105-10.
151. Janssens ACJW, Aulchenko YS, Elefante S, Borsboom GJJM, Steyerberg EW, van Duijn CM. Predictive testing for complex diseases using multiple genes: fact or fiction? Genetics in medicine: official J Am College Med Genetics 2006; 8(7): 395-400.
152. Stahl E a, Wegmann D, Trynka G, et al. Bayesian inference analyses of the polygenic architecture of rheumatoid arthritis. Nature genetics 2012; 44(5): 483-9.
153. Panagiotou O A, Ioannidis JP A. What should the genome-wide significance threshold be? Empirical replication of borderline genetic associations. Int J Epidemiol 2012; 41(1): 273-86.
154. Wakefield J. Commentary: Genome-wide significance thresholds via Bayes factors. International J epidemiology 2012; 41(1): 286-91.
155. Stein EA, Mellis S, Yancopoulos GD, et al. Effect of a monoclonal antibody to PCSK9 on LDL cholesterol. New England J Medicine 2012; 212(7): 408-9.
156. Stein E A, Gipe D, Bergeron J, et al. Effect of a monoclonal antibody to PCSK9, REGN727/SAR236553, to reduce low-density lipoprotein cholesterol in patients with heterozygous familial hypercholesterolaemia on stable statin dose with or without ezetimibe therapy: a phase 2 randomised controlle. Lancet 2012; 380(9836): 29-36.
157. Chan JCY, Piper DE, Cao Q, et al. A proprotein convertase subtilisin/ kexin type 9 neutralizing antibody reduces serum cholesterol in mice and nonhuman primates. Proc Natl Acad Sci USA 2009; 106(24): 9820-5.
158. McKenney JM, Koren MJ, Kereiakes DJ, Hanotin C, Ferrand AC, Stein E A. Safety and efficacy of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease, SAR236553/REGN727, in patients with primary hypercholesterolemia receiving ongoing stable atorvastatin therapy. J Am College of Cardiology 2012; 59(25): 2344-53.
159. Stein EA, Mellis S, Yancopoulos GD, et al. Effect of a monoclonal antibody to PCSK9 on LDL cholesterol. NEJM 2012; 212(7): 408-9.
160. Didelez V, Sheehan N. Mendelian randomization as an instrumental variable approach to causal inference. Statistical methods in medical research 2007; 16(4): 309-30.
161. Thomas DC, Conti D. Commentary: the concept of "Mendelian Randomization". Int J Epidemiol 2004; 33(1): 21-5.
162. Davey Smith G, Ebrahim S. "Mendelian randomization": can genetic epidemiology contribute to understanding environmental determinants of disease? International J Epidemiology 2003; 32(1): 1-22.
163. Zacho J, Tybjaerg-Hansen A, Jensen JS, Grande P, Sillesen H, Nordestgaard BG. Genetically elevated C-reactive protein and ischemic vascular disease. The New England J medicine 2008; 359(18): 1897-908.
164. Elliott P, Chambers JC, Zhang W, et al. Genetic Loci associated with C-reactive protein levels and risk of coronary heart disease. JAMA: J Am Medical Association 2009; 302(1): 37-48.
165. Voight BF, Peloso GM, Orho-Melander M, et al. Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study. Lancet 2012; 6736(12): 1-9.
166. Nozaki T, Sugiyama S, Koga H, et al. Significance of a multiple biomarkers strategy including endothelial dysfunction to improve risk stratification for cardiovascular events in patients at high risk for coronary heart disease. J Am College Cardiol 2009; 54(7): 601-8.
167. Sinning J-M, Losch J, Walenta K, Böhm M, Nickenig G, Werner N. Circulating CD31+/Annexin V+ microparticles correlate with cardiovascular outcomes. Eur Heart J 2011; 32(16): 2034-41.
168. Bernal-Mizrachi L, Jy W, Jimenez JJ, et al. High levels of circulating endothelial microparticles in patients with acute coronary syndromes. American heart journal 2003; 145(6): 962-70.
169. Mallat Z, Benamer H, Hugel B, et al. Elevated Levels of Shed Membrane Microparticles With Procoagulant Potential in the Peripheral Circulating Blood of Patients With Acute Coronary Syndromes. Circulation 2000; 101(8): 841-3.
170. Nozaki T, Sugiyama S, Sugamura K, et al. Prognostic value of endothelial microparticles in patients with heart failure. Eur J Heart Failure 2010; 12(11): 1223-8.
171. Amabile N, Guérin AP, Tedgui A, Boulanger CM, London GM. Predictive value of circulating endothelial microparticles for cardiovascular mortality in end-stage renal failure: a pilot study. Nephrology, dialysis, transplantation: official publication of the European Dialysis and Transplant Association-European Renal Association 2012; 27(5): 1873-80.
172. Koga H, Sugiyama S, Kugiyama K, et al. Elevated levels of VEcadherin-positive endothelial microparticles in patients with type 2 diabetes mellitus and coronary artery disease. J Am College Cardiol 2005; 45(10): 1622-30.
173. Fichtlscherer S, De Rosa S, Fox H, et al. Circulating microRNAs in patients with coronary artery disease. Circulation research 2010; 107(5): 677-84.
174. Sondermeijer BM, Bakker A, Halliani A, et al. Platelets in patients with premature coronary artery disease exhibit upregulation of miRNA340* and miRNA624*. PloS one 2011; 6(10): e25946.
175. Takahashi Y, Satoh M, Minami Y, Tabuchi T, Itoh T, Nakamura M. Expression of miR-146a/b is associated with the Toll-like receptor 4 signal in coronary artery disease: effect of reninangiotensin system blockade and statins on miRNA-146a/b and Toll-like receptor 4 levels. Clinical science (London, England: 1979) 2010; 119(9): 395-405.
176. Hoekstra M, van der Lans C a C, Halvorsen B, et al. The peripheral blood mononuclear cell microRNA signature of coronary artery disease. Biochemical and biophysical research communications 2010; 394(3): 792-7.
177. Weber M, Baker MB, Patel RS, Quyyumi A A, Bao G, Searles CD. MicroRNA Expression Profile in CAD Patients and the Impact of ACEI/ARB. Cardiology research and practice 2011; 2011: 532915.
178. Taurino C, Miller WH, McBride MW, et al. Gene expression profiling in whole blood of patients with coronary artery disease. Clinical science (London, England: 1979) 2010; 119(8): 335-43.
179. Ai J, Zhang R, Li Y, et al. Circulating microRNA-1 as a potential novel biomarker for acute myocardial infarction. Biochemical and biophysical research communications 2010; 391(1): 73-7.
180. Widera C, Gupta SK, Lorenzen JM, et al. Diagnostic and prognostic impact of six circulating microRNAs in acute coronary syndrome. J molecular and cellular cardiology 2011; 51(5): 872-5.
181. Wang GK, Zhu JQ, Zhang JT, et al. Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans. Eur Heart J 2010; 31(6): 659-66.
182. Oerlemans MIFJ, Mosterd A, Dekker MS, et al. Early assessment of acute coronary syndromes in the emergency department: the potential diagnostic value of circulating microRNAs. EMBO molecular medicine 2012; 4(11): 1176-85.
183. D'Alessandra Y, Devanna P, Limana F, et al. Circulating microRNAs are new and sensitive biomarkers of myocardial infarction. Eur Heart J 2010; 31(22): 2765-73.
184. Gidlöf O, Andersson P, van der Pals J, Götberg M, Erlinge D. Cardiospecific microRNA plasma levels correlate with troponin and cardiac function in patients with ST elevation myocardial infarction, are selectively dependent on renal elimination, and can be detected in urine samples. Cardiology 2011; 118(4): 217-26.
185. Olivieri F, Antonicelli R, Lorenzi M, et al. Diagnostic potential of circulating miR-499-5p in elderly patients with acute non STelevation myocardial infarction. Int J Cardiol 2012;: 1-6.
186. De Rosa S, Fichtlscherer S, Lehmann R, Assmus B, Dimmeler S, Zeiher AM. Transcoronary concentration gradients of circulating microRNAs. Circulation 2011; 124(18): 1936-44.
187. Corsten MF, Dennert R, Jochems S, et al. Circulating MicroRNA-208b and MicroRNA-499 reflect myocardial damage in cardiovascular disease. Circulation. Cardiovascular genetics 2010; 3(6): 499-506.
188. Devaux Y, Vausort M, Goretti E, et al. Use of circulating microRNAs to diagnose acute myocardial infarction. Clinical chemistry 2012; 58(3): 559-67.
189. Adachi T, Nakanishi M, Nishimura K, et al. Plasma MicroRNA 499 as a Biomarker of Acute Myocardial Infarction. Clinical Chem 2010; 56(7): 1183-5.
190. Cheng Y, Tan N, Yang J, et al. A translational study of circulating cell-free microRNA-1 in acute myocardial infarction. Clinical science (London, England: 1979) 2010; 119(2): 87-95.
191. Kuwabara Y, Ono K, Horie T, et al. Increased microRNA-1 and microRNA-133a levels in serum of patients with cardiovascular disease indicate myocardial damage. Circulation. Cardiovascular genetics 2011; 4(4): 446-54.
192. Wang R, Li N, Zhang Y, Ran Y, Pu J. Circulating MicroRNAs are Promising Novel Biomarkers of Acute Myocardial Infarction. Internal Medicine 2011; 50(17): 1789-95.
193. Meder B, Keller A, Vogel B, et al. MicroRNA signatures in total peripheral blood as novel biomarkers for acute myocardial infarction. Basic research in cardiology 2011; 106(1): 13-23.
194. Gan CS, Wang CW, Tan KS. Circulatory microRNA-145 expression is increased in cerebral ischemia. Genetics and molecular research: GMR 2012; 11(1): 147-52.
195. Zeng L, Liu J, Wang Y, et al. MicroRNA-210 as a novel blood biomarker in acute cerebral ischemia. Frontiers in bioscience (Elite edition) 2011; 3: 1265-72.
196. Tan KS, Armugam A, Sepramaniam S, et al. Expression profile of MicroRNAs in young stroke patients. PloS one 2009; 4(11): e7689.
197. Li T, Cao H, Zhuang J, et al. Identification of miR-130a, miR-27b and miR-210 as serum biomarkers for atherosclerosis obliterans. Clinica chimica acta; international J clinical chemistry 2011; 412(1-2): 66-70.
198. Aoki A, Ozaki K, Sato H, et al. SNPs on chromosome 5p15.3 associated with myocardial infarction in Japanese population. J human genetics 2011; 56(1): 47-51.
199. Takeuchi F, Yokota M, Yamamoto K, et al. Genome-wide association study of coronary artery disease in the Japanese. European J Human Genetics 2012; 20(3): 333-40.
200. Wang F, Xu C-Q, He Q, et al. Genome-wide association identifies a susceptibility locus for coronary artery disease in the Chinese Han population. Nature genetics 2011; 43(4): 345-9.
201. The IBC 50K CAD Consortium. Large-scale gene-centric analysis identifies novel variants for coronary artery disease. PLoS Genetics 2011; 7(9): e1002260.
202. IL6R Genetics Consortium and Emerging Risk Factors Collaboration. Interleukin-6 receptor pathways in coronary heart disease: a collaborative meta-analysis of 82 studies. Lancet 2012;
203. The Interleukin-6 Receptor Mendelian Randomisation Analysis (IL6R MR) Consortium. The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis. Lancet 2012; 6736(12): 6-16.
204. Davies RW, Wells G A, Stewart AFR, et al. A genome-wide association study for coronary artery disease identifies a novel susceptibility locus in the major histocompatibility complex 2012.
205. Erdmann J, Grosshennig A, Braund PS, et al. New susceptibility locus for coronary artery disease on chromosome 3q22.3. Nature genetics 2009; 41(3): 280-2.
206. The International Stroke Genetics Consortium (ISGC) & the Wellcome Trust Case Control Consortium 2 (WTCCC2). Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke. Nature Genetics 2012; 44(3): 328-33.
207. Holliday EG, Maguire JM, Evans TJ, et al. Common variants at 6p21.1 are associated with large artery atherosclerotic stroke. Nature genetics 2012; 44(10): 1147-51.
208. Wain LV, Verwoert GC, O'Reilly PF, et al. Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure. Nature genetics 2011; 43(10): 1005-11.
209. The International Consortium for Blood Pressure Genome-Wide Association Studies. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature 2011; 478(7367): 103-9.
210. Dehghan A, Dupuis J, Barbalic M, et al. Meta-analysis of genomewide association studies in >80 000 subjects identifies multiple loci for C-reactive protein levels. Circulation 2011; 123(7): 731-8.
211. The Tobacco and Genetics Consortium. Genome-wide metaanalyses identify multiple loci associated with smoking behavior. Nature genetics 2010; 42(5): 441-7.
212. O'Donnell CJ, Kavousi M, Smith A, et al. Genome-wide association study for coronary artery calcification with follow-up in myocardial infarction. Circulation 2011; 124(25): 2855-64.
213. Gertow K, Sennblad B, Strawbridge RJ, et al. Identification of the BCAR1-CFDP1-TMEM170A Locus as a Determinant of Carotid Intima-Media Thickness and Coronary Artery Disease Risk 2012.
214. Murabito JM, White CC, Kavousi M, et al. Association between chromosome 9p21 variants and the ankle-brachial index identified by a meta-analysis of 21 genome-wide association studies. Circulation. Cardiovascular Genetics 2012; 5(1): 100-12.