1. The Renin-Angiotensin- Aldosterone System: Linking New Data and Mechanisms for Cardiovascular Risk Reduction VBWG

2. I.Scope of the problem II.Physiology of RAAS: Focus on angiotensin III.Role of RAAS modulation: Recent clinical trials CAD Diabetes ACEIs and ARBs IV.Management strategies for post-intervention in patients with CAD V.Appendix: Clinical guidelines Contents VBWG

3. Scope of the Problem VBWG

4. Coronary artery disease: Leading cause of hospitalization in the US Primary diagnosis Coronary atherosclerosis1$38.4 Acute MI2$27.8 Congestive HF (nonhypertensive) 4$21.8 Cardiac dysrhythmias8$14.3 Acute cerebrovascular disease9$13.9 AHA. Heart Disease and Stroke Statistics–2005 Update. $66.2 National bill (billions) Rank VBWG

5. Lifetime risk for CAD Lloyd-Jones D et al. Lancet. 1999;353:89-92. 0.5 0.4 0.3 0.2 0.1 40506070809094 0.5 0.4 0.3 0.2 0.1 40506070809094 Women Men Age (years) Cumulative risk of CAD 0 Framingham Heart Study Lifetime risk at age 40 1 in 3 1 in 2 0 VBWG

6. Yusuf S et al. Lancet. 2004;364:937-52. Odds ratio for 1st MI (99% CI) 64 512 16 1 2 256 128 32 8 4 Smk (1) DM (2) HTN (3) ApoB/A1 (4) 1+2+31–4All 4+ obesity All 4+ Psycho- social All 2.9 2.4 1.9 3.3 13.0 42.3 68.5 182.9 333.7 Multiple risk factors raise the risk for MI INTERHEART Smk = smoking; DM = diabetes mellitus; HTN = hypertension; Apo = apolopoprotein VBWG

7. Lifetime risk of diabetes for individuals born in 2000 27 40 45 37 33 31 49 53 43 39 0 10 20 30 40 50 60 WhiteBlackHispanicOther races/ ethnicities Total* Narayan KMV et al. JAMA. 2003;290:1884-90. Estimates based on National Health Interview Survey (1984–2000) Lifetime risk (%) Men Women *Weighted race/ethnic-specific values by proportion of nondiabetic US population in 2000 VBWG

8. Whiteley L et al. Diabetes Care. 2005;28:1588-93. Diabetes as a CHD risk equivalent: Impact on mortality in women and men Years Women Men 0.0 0.2 0.4 0.6 0.8 Diabetes/CHD 1.0 05111622270511162227 0.0 0.2 0.4 0.6 0.8 1.0 Diabetes CHD No Diabetes/CHD Survival rate N = 7052 men, 8354 women; age 45–64 yrs, follow-up 25 years VBWG

9. Worldwide prevalence of diabetes expected to increase Diabetes prevalence >171 million in 2000 ~366 million in 2030 World Health Organization, 2000 vs 2030 www.who.int/diabetes/. July 2005. 33 15 33 47 36 18 67 42 48 120 71 7 0 20 40 60 80 100 120 140 AfricaAmericasE MeditEuropeSE Asia W Pacific Diabetes prevalence (in millions) 2000 2030 +102% +160% +181% +44% +155% +99% VBWG

10. 0 100 200 300 400 29–4445–64≥65 New and recurrent MIs (in thousands) Age (years) Men Women 500 34 10 250 88 410 372 AHA. Heart Disease and Stroke Statistics–2005 Update. Over 1 million Americans will have an MI this year VBWG