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Vascular Protection: The Role of RAA System

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Beneficial effects of bradykinin. Added to better RAS blockade. CV differences. Yes, no, maybe ... Summary. ACE Inhibitors. ARB's. Bradykinin. Blood pressure ... – PowerPoint PPT presentation

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Title: Vascular Protection: The Role of RAA System


1
Vascular ProtectionThe Role of RAA System
  • James A. Stone
  • B.P.H.E., B.A., M.Sc., M.D., Ph.D., FRCPC,
    FAACVPR, FACC
  • Clinical Associate Professor of Medicine
  • University of Calgary

2
Cardiac Risk Elimination
3
Vascular Protection
  • What is vascular protection?
  • What is the effect of RAAS on vascular health?
  • What is the evidence for vascular protection?
  • Is it all just blood pressure?
  • Summary

4
Vascular Protection
  • What is vascular protection?
  • What is the effect of RAAS on vascular health?
  • What is the evidence for vascular protection?
  • Is it all just blood pressure?
  • Summary

5
What is Vascular Protection?
  • Vascular protection
  • Event prevention
  • Maintenance of vascular health
  • Reduced endothelial oxidative stress
  • ? Final common pathway in genesis of
    atherosclerosis
  • Vascular protection event prevention
  • Prevention
  • Presymptomatic
  • Low to high risk
  • NNT high to low
  • Symptomatic
  • High to higher risk
  • NNT - low to lower

6
Vascular ProtectionWhy Should You Care?
  • 55 ( 10) y.o (fe)male physician
  • Normal blood pressure
  • Normal cholesterol
  • Normal blood sugar
  • Non-smoker
  • Normal exercise level
  • Why should you care
  • Your arteries are normal!

7
Vascular Protection
  • What is vascular protection?
  • What is the effect of RAAS on vascular health?
  • What is the evidence for vascular protection?
  • Is it all just blood pressure?
  • Summary

8
The Renin-Angiotensin Aldosterone System
McMurry et al. Circulation 2004 110 3281-3288
9
What are the effects of Bradykinin?
  • Vascular effects
  • Enhanced vasodilatation
  • ? NO production
  • ? prostaglandin production
  • ? EDHF
  • Increased fibrinolysis
  • Inhibits platelet aggregation
  • Inhibits smooth muscle cell proliferation
  • Renal effects
  • Increased sodium excretion

10
AT Receptor Function
11
Vascular Protection
  • Endothelial function
  • ACE inhibition
  • Favourable
  • AR blockade
  • Favourable
  • Improved endothelial function
  • Improved event-free survival

12
Vascular Protection Endothelial Dysfunction
Schachinger Circulation 2000 101 1899-1906
13
Vascular Protection
  • What is vascular protection?
  • What is the effect of RAAS on vascular health?
  • What is the evidence for vascular protection?
  • Is it all just blood pressure?
  • Summary

14
What is the evidence?ACE versus ARB
  • ACE Inhibitor Trials
  • ACE versus ARB
  • CHF trials
  • Renal trials
  • BP trials

15
What is the evidence?HOPE Trial(Primary
Outcome - Death/MI/Stroke)
RR0.78 (0.70-0.86)
P0.000002
16
What is the evidence?EUROPA Trial
Primary endpoint - CV death, MI or cardiac
arrest
Placebo
Perindopril
Placebo annual event rate 2.4
17
What is the evidence?PEACE Trial
18
Vascular ProtectionWhat is the evidence?
  • ACE Inhibitor Trials
  • HOPE
  • Protection
  • EUROPA
  • Protection
  • PEACE
  • Neutral
  • 11-11
  • NOT ZERO!

19
What is the evidence?ACE versus ARB
  • ACE Inhibitor Trials
  • ACE versus ARB
  • Trial designs
  • Head to head comparisons
  • Better tolerability of ARB
  • Better RAS blockade
  • Add-on therapy
  • Beneficial effects of bradykinin
  • Added to better RAS blockade
  • CV differences
  • Yes, no, maybe

20
Vascular Protection
  • What is vascular protection?
  • What is the effect of RAAS on vascular health?
  • What is the evidence for vascular protection?
  • Is it all just blood pressure?
  • Summary

21
Is it all just blood pressure?
Franco et al. Circulation 2004109 2953-2958
22
BP Lowering Effect and Drug Class
Law et al. BMJ 2003 1427-1435
23
Results by Treatment Group
24
Vascular Protection
  • What is vascular protection?
  • What is the effect of RAAS on vascular health?
  • What is the evidence for vascular protection?
  • Is it all just blood pressure?
  • Summary
  • ACE Inhibitors
  • ARBs
  • Bradykinin
  • Blood pressure
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