TSELEPIS
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. , MD, PhD
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The Framingham Study: Relationship Between Cholesterol
and CHD Risk
The Framingham Study: The Framingham Study: Relationship Between Cholesterol Relationship Between Cholesterol
andand CHDCHD RiskRisk
Castelli WP. Am J Med. 1984;76:4-12
0
25
50
75
100
125
150
7.6)
C
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Serum total cholesterol, mg/dL (mmol/L)
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Meta-analysis of 38 primary and secondary intervention trials
Benefits of Cholesterol LoweringBenefits of Cholesterol LoweringBenefits of Cholesterol Lowering
% in cholesterol reduction
Total mortality (p=0.004)
CHD mortality (p=0.012)
M
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0 4 8 12 16 20 24 28 32 36-1.0
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-0.6
-0.4
-0.2
-0.0
40
Gould AL et al. Circulation. 1998;97:946-952
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Platelet Adhesion and Aggregation
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Platelet Thrombus Formation
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Activation of the coagulation cascade
Mackman N. J Clin Invest. 2012; 122: 2331-36
Occlusion of an artery in the brain results in an ischaemic stroke, one of the most severe complications of atrial fibrillation (AF).
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Role of Endothelium in Coagulation
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The Fibrinolytic System
Marn F, et al. Thrombosis Research 109 (2003) 233
240
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FH
Elisaf M, Tselepis AD. Platelets 10: 124, 1999
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LDL
FH
Elisaf M, Tselepis AD. Platelets 10: 124, 1999
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LDL
LDL
LDL
LDL
Relou IAM, et al. CMLS, Cell Mol Life Sci. 60: 961, 2003
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Effect of CM and VLDL remnants on platelets
De Man FH, et al. Atherosclerosis. 2000;152:407-414
Platelet activation in Hypertriglyceridemic patients
Mochizuki M, et al. Thromb Res. 1996;81:583-593
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CMVLDL
LDLLp(a)
Lp(a)
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Lp(a)
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Badimon L. Ann. N.Y. Acad. Sci. 1254 (2012) 1832
HDL anti-atherothrombotic effects
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HDL
Calabresi L, et al. ATVB. 23: 1724, 2003
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Ex Vivo Platelet Function is Attenuated by RecHDL in patients with 2DM
Calkin AC, et al. Circulation. 2009;120:2095-2104
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Thrombus formation is attenuated by rHDL in patients with T2DM
Calkin AC, et al. Circulation. 2009;120:2095-2104
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Properties of
Dense LDL
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Elevation of plasma sdLDL concentration in patients with STEMI
Chan H-C, et al. Blood. 2013;122(22):3632-3641
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sdLDL-induced platelet aggregation and adhesion
Chan H-C, et al. Blood. 2013;122(22):3632-3641
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sdLDL-mediated Endothelial Cell dysfunction
Chan H-C, et al. Blood. 2013;122(22):3632-3641
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Chan H-C, et al. Blood. 2013;122(22):3632-3641
sdLDL-mediated Endothelial Cell dysfunction
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LDL
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oxLDL
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oxLDL
Relou IAM, et al. CMLS, Cell Mol Life Sci. 60: 961, 2003
oxLDLoxLDL
oxLDL
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Yang S-H, et al. Thromb Res. 132 (2013) 702711
Morphological changes in the platelets induced by ox-LDL
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Skrlin S, et al. Semin Cardiothorac Vasc Anesth. 2010; 14: 283
The mechanism of action of statins
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Violi F, et al. Circulation. 2013;127:251-257
Statins as antiplatelet drugs
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Violi F, et al. Circulation. 2013;127:251-257
Statins as anticoagulant drugs
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Silverstein RL. J Clin Invest. 2012;122:481484
Statins Reduce Atherothrombosis
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Potential beneficial effects of statins during and after PCI
Angeli F, et al. Ther Adv Cardiovasc Dis 2012; 6: 163
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Main characteristics of the randomized clinical trials comparing early statin therapy with placebo or
usual care in patients with ACS
Angeli F, et al. Ther Adv Cardiovasc Dis 2012; 6: 163
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Angeli F, et al. Ther Adv Cardiovasc Dis 2012; 6: 163
Impact of statin therapy on all-cause mortality in randomized clinical trials comparing early statin therapy
with placebo or usual care in patients with ACS
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Platelet aggregation
Modified from Mitsios, JV et al. Circulation. 2004;109:1335Modified from Mitsios, JV et al. Circulation. 2004;109:1335--13381338
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Pharmacodynamic Studies That Evaluated the possible Clopidogrel-Atorvastatin Interaction
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Clinical
studies that evaluated the possible Clopidogrel-Atorvastatin Interaction
Bates
ER. J Am
Coll
Cardiol
2011;57:125163
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9 9
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9 ASC
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. 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 LDL oxLDL 29 30 31 32 33 34 35 36 37 -Platelet aggregation 39 40