INTERHEART: Focus on 9 risk or protective factors Design Large international case-control study Participants 12,461 cases; 14,637 controls; 52 countries Objective To determine association of first MI with: Smoking Lipids Hypertension Diabetes Obesity Diet Physical Alcohol Psychosocial activity consumption factors* Follow-up 4 years, February 1999–March 2003 *eg, stress, depression Yusuf S et al. Lancet. 2004;364:937-52.

INTERHEART: ApoB-ApoA1 ratio—Graded relation to MI risk, no evidence for a threshold 8 4 Odds ratio for 1st MI (99% CI) 2 1 0.75 1 2 3 4 5 6 7 8 9 10 ApoB-ApoA1 ratio (deciles) Number of controls 1210 1206 1208 1207 1209 Number of cases 435 496 610 720 790 893 1063 1196 1366 1757 Median 0.43 0.53 0.60 0.66 0.72 0.78 0.85 0.93 1.04 1.28 Note: odds ratio plotted on a doubling scale Yusuf S et al. Lancet. 2004;364:937-52.

INTERHEART: Significant association of MI risk with hypertension Region n Overall 26,916 Western Europe 1425 Central and Eastern Europe 3636 Middle East Crescent 3404 Africa 1355 South Asia 3881 China/Hong Kong 6075 Southeast Asia 2141 Australia and New Zealand 1269 South America 3100 North America 630 0.25 0.5 1 2 4 8 16 Odds ratio (95% CI) Adjusted for age, sex, smoking Note: odds ratio plotted on a doubling scale Yusuf S et al. Lancet. 2004;364:937-52.

Odds ratio for 1st MI (99% CI) INTERHEART: Impact of multiple risk factors on CV risk 2.9 2.4 1.9 3.3 13.0 42.3 68.5 182.9 333.7 512 256 128 Odds ratio for 1st MI (99% CI) 64 32 16 8 4 2 1 Smk (1) DM (2) HTN (3) ApoB- ApoA1 (4) 1+2+3 All 4 All 4 + Obes All 4 + Ps All risk factors Smk = smoking DM = diabetes HTN = hypertension Obes = obesity Ps = psychosocial factors Note: odds ratio plotted on a doubling scale Yusuf S et al. Lancet. 2004;364:937-52.

INTERHEART: Association of risk factors with acute MI in women and men Gender Current smoking F M Diabetes F M Hypertension F M Abdominal obesity F M Psychosocial index F M Fruits/Vegetables F M Exercise F M Alcohol F M ApoB-ApoA1 ratio F M 0.25 0.5 1 2 4 8 16 Adjusted for age, sex, geographic region Note: odds ratio plotted on a doubling scale Odds ratio (99% CI) Yusuf S et al. Lancet. 2004;364:937-52.

Adherence to simultaneous antihypertensive and lipid-regulating drug therapy Retrospective analysis of data from PHARMetrics Integrated Outcomes Database 38 40 35 29 30 Patients adhering to therapy (%) 23 25 20 15 10 5 LRD first, AHD added AHD first, LRD added AHD + LRD initiated simultaneously Adapted from Chapman RH et al. AHA Scientific Sessions 2003. Abstract 3417. LRD = lipid-regulating drug; AHD = antihypertensive drug

INTERHEART: Clinical implications • 9 simple and modifiable risk factors are strongly associated with acute MI worldwide. • These 9 risk factors account for >90% of the PAR globally and in most regions. • Abnormal ApoB-ApoA1 ratio and smoking are the 2 most important risk factors and account for over two thirds of the PAR. • Implementing preventive strategies based on our current knowledge would prevent the majority of premature CHD worldwide. PAR = population attributable risk Apo = apolipoprotein Yusuf S et al. Lancet. 2004;364:937-52.