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