Cardio Diabetes Master Class Asian chapter January 28
Cardio Diabetes Master Class Asian chapter January 28 -30 2011, Shanghai Presentation topic Slide lecture prepared and held by: John Deanfield, MD University College London, United Kingdom
Incidence of major vascular events (%) Heart Protection Study: Impact of Diabetes on CV outcome 50 Placebo Simvastatin 40 mg 40 RRR 12% RRR 22% 30 RRR 19% RRR 23% 20 RRR 31% 10 1009 0 972 Diabetes + CHD 5683 5722 No diabetes + CHD 519 551 Diabetes + other CVD 1481 1449 No diabetes + other CVD 1455 1457 Diabetes + no CVD HPS Collaborative Group. Lancet. 2003; 361: 2005
CVD Accounts for 71% of Costs of Chronic Complications of Diabetes Total US expenditure in 2002 = US$ 24. 6 billion Cardiovascular disease 71 % 11% Neurological symptoms Renal complications 8% 5% Peripheral vascular disease Endocrine/metabolic Ophthalmic complications Other American Diabetes Association. Diabetes Care 2003; 26: 917 -32
Cholesterol in China (2000 -2001) 25 8. 8 8 7. 5 6 4 Aware Treated Controlled ≥ 200 mg/dl 21. 3 Prportion % 10 ≥ 240 mg/dl 3. 5 3. 4 1. 9 2 1. 5 0 20 18. 1 14. 0 15 11. 3 11. 6 9. 5 10 5 0 Men Women 112, 500, 000 Borderline HC Men 42, 540, 000 HC Women 90, 803, 000 Low HDL Jiang H. Circulation, 2004; 110: 405 -411
Diabetes in China : 1994 -2008 Yang NEJM 2010 362 1090 -101
Potentially Modifiable Risk Factors and MI : INTERHEART Study 15152 Cases 14820 Controls in 262 Centres in 52 Countries 9 RFs acounted for 90% of MI in men and 94% in women 3 Odds 2 Ratio 1 0 ys l . t Ac ho co Al Ph eg /V Fr ty si be O BP ss re A 1 po /A o. B M St D Ap g in 40 ok Sm 60 PAR (%) 20 0 -20 Yusuf Lancet September 11 2004
Temporal Mortality Trends in MI in Patients with and without Diabetes (a comparison of 1762 patients in 1995 with 1642 patients in 2003) Cubbon RM et al. Eur Heart J 2007; 28: 540– 545
Atherosclerosis: Risk Reduction Strategy Lifetime Risk q Treat to lower levels q Target global risk q Start earlier
CARDS: Cumulative Hazard for MI and CV death 15 Relative Risk -37% (95% CI: -52, -17) Cumulative Hazard (%) Placebo P=0. 001 10 Atorvastatin 5 0 0 1 2 3 4 4. 75 Years
Cumulative incidence of major cardiovascular events Time to First Major Cardiovascular Event in Patients With Diabetes TNT Study HR = 0. 75 (95% CI 0. 58, 0. 97) P=0. 026 0. 20 Atorvastatin 10 mg 0. 15 Atorvastatin 10 mg Atorvastatin 80 mg 0. 10 0. 05 Relative risk reduction = 25% 0 0 1 2 Time (years) 3 4 5 6
Residual Disease Progression in Diabetes Despite Intensive LDL-C Lowering Δ Percent Atheroma Volume 1. 5 1. 0 0. 5 0. 0 -0. 5 No DM LDL<80 No DM LDL>80 DM LDL<80 DM LDL>80 Nicholls J Amer Coll Cardiol 2008; 52: 255 -62
Age-adjusted CVD death rate/10, 000 person-years Multiple Risk Factors and CVD Death in Diabetic and Non diabetic Men (MRFIT) 140 120 No Diabetes 100 80 60 40 20 0 None One only Two only All three Number of risk factors Stamler J et al Diabetes Care 1993; 16: 434.
Steno-2 Study in T 2 DM: CV Outcome* 60 Conventional therapy Primary endpoint (%) 50 P=0. 007 40 30 20 Intensive therapy 10 0 0 12 24 36 48 60 72 84 96 Months of follow-up *Death from CVD, MI, CABG, PCI, stroke, amputation, or surgery for PAD 2003; 348: 383 -393. Gæde P et al N Engl J Med
Atherosclerosis: ‘Investing in your Arteries’ Early Intervention for Lifetime Risk management
Coronary Heart Disease Mortality in Beijing 1984 -1999 2500 1822 Extra deaths Attributable to Risk Factor Changes 2000 Cholesterol 1000 Diabetes 500 0 19% BMI 4% Smoking 1% 642 fewer deaths by treatments AMI treatments -500 Hypertension treatment Secondary prevetion -1000 1984 77% Heart failure 1999 Aspirin for Angina: CABG & PTCA 41% 24% 11% 10% 2% Critchley J. Circulation, 2004; 110: 1236 -1244
Prevalence of Atherosclerosis by Donor Age 100 EEM Area 13. 2 mm 2 5. 07 mm 2 Atheroma Area 8. 13 mm 2 Prevalence of Atherosclerosis (%) 85% 80 71% 60 37% 40 20 17% 0 <20 20 -2930 -3940 -49≥ 50 32 Year Old Female Donor Age (years) Tuzcu Circ 2001 103: 2075 -10
CV Risk Factors in Childhood and Carotid IMT in Adults Risk factors measured at ages 12 -18 yrs No. of risk factors 1 2 Mean maximum carotid IMT (mm) 0 0. 88 P<0. 001 3 or 4 P<0. 001 0. 80 0. 72 0. 64 0. 56 0. 48 Men Women Raitakari et al JAMA 2003; 290; 2277 -2283
Adjusted Cumulative Incidence Framingham Heart Study Lifetime Risk Men 0. 7 69% 0. 6 Women 0. 7 ≥ 2 Major RFs 1 Major RF ≥ Elevated RF ≥ Not Elevated RF All Optimal RFs 0. 6 50% 46% 0. 5 0. 4 36% 0. 5 0. 3 0. 2 0. 1 5% 0 39% 0. 4 0. 3 50% 27% 8% 0 50 60 70 80 90 Attained Age 50 60 70 80 90 Lloyd-Jones Circ. 2006; 113: 791 -798
Age and CV Risk in Diabetes 30 25 Men with diabetes Men without diabetes 30 25 15 15 10 10 5 5 0 0 Age (years) Women with diabetes Women without diabetes 20 -3 0 31 -4 0 41 -4 46 5 -5 51 0 -6 56 0 -6 61 0 -6 66 5 -7 71 0 -7 5 76 -8 0 81 -8 5 20 Women Age (years) Booth Lancet 2006; 368: 29 -36
LDL Cholesterol and Coronary Heart Disease among Black Subjects by PCSK 9142 X or PCSK 9679 X Allele 12 50 th Percentile 20 10 0 30 0 50 100 150 200 250 300 PCSK 9142 X or PCSK 9679 X (N=85) 28% Coronary Heart Disease (%) Frequency (%) No Nonsense Mutation (n=3278) 30 P=0. 008 8 88% 4 20 0 10 0 No Yes PCSK 9142 X or PCSK 9679 X 0 50 100 150 200 250 300 LDL Cholesterol in Black Subjects (mg/dl) Cohen NEJM 2006; 354: 1264 -72
Primary Prevention: Influence of Age on Relationship Between Cholesterol and CHD Age 70 Age 50 Age 40 0% -20% -40% -60% Reduction in risk in men with 10% reduction in total cholesterol (10 cohort studies) Law MR et al. BMJ 1994; 308: 367 -372.
High-Normal BP and CVD Risk: Framingham Study High normal 130 -139/85 -89 mm Hg Normal 120 -129/80 -84 mm Hg Optimal <120/80 mm Hg Men Cumulative Incidence (%) 14 8 P<. 001 10 Women 10 12 8 6 6 4 Prehypertension P<. 001 4 2 2 0 0 0 2 4 6 8 10 12 Time (years) 14 0 2 4 6 8 10 12 Time (years) Vasan et al. N Engl J Med. 2001; 345: 1291 -1297. 14
Beyond BP? : Outcome in treated BP (n=686) vs. “Normotensive” (n=6810) Men after > 20 yrs “Normotensive” Screening BP (mm. Hg) Final BP (mm. Hg) CHD (%) Stroke (%) Cancer (%) All-cause death (%) 145 / 93 -10. 3 1. 8 10. 8 29. 2 Treated BP 185 / 114 145 / 89 20. 1* 4. 5* 8. 9 37. 4* *p <0. 02 Anderson, BMJ 1998; 317: 167
BP Treatment in Type 2 DM 4733 age 62. 2 years intensive vs standard BP treatment over 4. 7 years ACCORD Study Group NEJM 2010; 362: 1575 -1585
Cumulative Incidence (%) TROPHY Study: ARB in ‘Prehypertension’ 100 80 Placebo 60 40 Candesartan 20 0 0 1 2 Study Year 3 4 Julius NEJM 2006; 354 : 1685 -97
Lifetime Management of Atherosclerosis Risk Benefits of early intervention from q Less Exposure / burden? q Disease modification?
Cardiovascular Continuum: Vascular Biology Targets Tissue injury Atherothrombosis and progressive CV disease (MI, stroke, renal insufficiency, peripheral arterial Pathological insufficiency) remodelling Target organ damage Early tissue dysfunction - endothelium Oxidative and mechanical stress Inflammation Risk factors End-organ failure (CHF, ESRD) Death Dzau V Circ 2006 114; 2850 -2870
RAS Blockade, Adipocytes and Diabetes Lenz O Kidney International 2008 74: 851 -853
Intravascular Ultrasound of Coronary Arteries Determining the Atheroma Area Precise planimetry of EEM and lumen borders allows calculation of atheroma cross-sectional area EEM Area Lumen Area On multivariate analysis the only parameter independently associated with slowing of disease progression in the Pioglitazone group was Triglyceride/HDL-C ratio — Lumen P=0. 03 (EEM Area) Images courtesy of Cleveland Clinic Intravascular Ultrasound Core Laboratory Nicholls et al JACC 57 No 2 2011
Benefit of Treating the Metabolic Syndrome After 4 years risk of diabetes reduced by 58% 23% 11% Intervention Control % with Diabetes Tuomilehto J et al. N Engl J Med 2001; 344: 1343 -1350.
…. It is essential that the new guidelines incorporate the logical concept that a long term disease requires a long term solution Forrester JACC 2010; 56: 630 -636
A reasonable next step for ATP IV? …. Consider statins for younger persons, perhaps starting at 30 in those with risk factors that convey high lifetime risk (as opposed to 10 yr risk) for CHD Pletcher JACC 2010; 56: 637 -640
CV Risk Management-Long way to go? q Lifetime risk reduction is the target q More active management of high risk subjects such as diabetics q In addition to ‘Lower and Broader’ RF treatment, Early Management key to further reduction in CV events
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