Salim Yusuf President, World Heart Federation. Can we halve premature CVD globally in a generation?

Transcription

1 Salim Yusuf President, World Heart Federation Can we halve premature CVD globally in a generation?

2 Contribution of NCD and CVD to the Global Mortality and GBD in 1998 (LIC & MIC) Disease Contrib of NCD s to total global mortality (%) LIC + MIC Contrib to global NCD mortality (%) Contrib of NCD s to total burden of disease (%) LIC + MIC Contrib to NCD burden of disease Total NCD (%) CVD million deaths annually in the world One third are from CVD

3 INTERHEART: Case-control study 1. Is the impact of risk factors on MI similar or variable in different regions or ethnic groups? 2. What proportion of the risk of MI can be explained by known risk factors? Funds: Started with 25K eventually $4 mill (visible ) + invisible $$ Logistics: Shipping bloods frozen at low costs from 52 countries. Standardizing questionnaires (eg diet ) to obtain comparable data. 10 years 52 countries, 270 sites, 600 investigators, >30 papers

4 Over 1,500 centres in 83 countries in all inhabited continents * Hamilton UK * Milan * * Bangalore * Beijing * * Sao Paolo * * Rosario Cape Town Argentina, Australia, Austria, Bahrain, Bangladesh, Belgium, Benin Republic, Botswana, Brazil, Cameroon, Canada, Chile, China, Colombia, Croatia, Czech Republic, Dem. Rep. of Congo, Denmark, Egypt, Finland, France, Germany, Greece, Guatemala, Hong Kong, Hungary, India, Iran, Ireland, Israel, Italy, Japan,Kenya, Kuwait, Malaysia, Mexico, Mozambique, Nepal, Netherlands, New Zealand, Nigeria, Norway, Pakistan, Philippines, Poland, Portugal, Qatar, Russia, S. Korea, Seychelles, Singapore, Slovakia, South Africa, Spain, Sri Lanka, Sultanate of Oman, Sweden, Switzerland, Taiwan, Thailand, Turkey, UAE, Ukraine, United Kingdom, USA, Zimbabwe

5 Risk of AMI associated with Risk Factors in the Overall Population Risk factor % Cont % Cases PAR (99% CI) ApoB/ApoA-1(5 v 1) (49.6, 58.6) Curr smoking (33.9,39.0) Diabetes (11.2, 13.5) Hypertension (21.7, 25.1) Abd Obesity (3 v 1) (30.2, 37.4) Psychosocial (22.6, 35.8) Veg & fruits daily (10.0, 16.6) Exercise (20.1, 31.8) Alcohol (9.3, 20.2) Combined (88.1, 92.4)

6 OR (99% CI) INTERHEART: Apolipoprotein B/A- 1 and MI Deciles: Cont Cases Median

7 OR (95% CI) Low Levels of Smoking and MI Never Adjusted for age sex and region

8 INTERHEART: ApoB/ApoA-1 ratio (top quintile vs lowest quintile) and MI Region N Cont. % Overall W Eur CE Eur MEC Afr S Asia China/HK SE Asia ANZ S Am N Am OR (99% CI)

9 Risk of AMI associated with current or former smoking, overall and by region Region n Cont.% OR (99%CI) Overall Overall (2.11,2.44) W Eur W Eur (1.47,2.62) CE Eur CE Eur (1.60, 2.30) MEC MEC (2.19,3.19) Afr Afr (1.60, 2.96) S Asia S (2.03,2.89) Asia Ch/HK China/HK (2.00,2.65) SEAs/Jpn SE Asia (1.54,2.49) ANZ ANZ (2.03,3.86) S Am S Am (1.92,2.87) N Am N (1.14,2.88) Am

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11 HETEROGENEITY OF STROKE SUBTYPE Hemorrhagic stroke (17%) Ischemic stroke (83%) Intracerebral hemorrhage (59%) Small vessel (lacunar) disease (25%) Atherothrombotic disease (20%) SAH (41%) Albers GW et al. Chest. 1998;114:683S-698S. Rosamond WD et al. Stroke. 1999;30: Cardioembolism (20%) Cryptogenic (35%)

12 INTERSTROKE-PHASE 1 International standardized case-control study Shared methodology with INTERHEART Yusuf et al INTERHEART Lancet 2004 O Donnell et al Neuroepidemiology countries (6,000 participants) Mar 07-Apr 10 HIC: Australia, Canada, Croatia, Denmark, Germany, Iran, Poland S America: Argentina, Brazil, Chile, Colombia, Ecuador, Peru Asia: China, India, Philippines, Malaysia Africa: Mozambique, Nigeria, South Africa, Sudan, Uganda Case: First stroke admitted within 5 days of symptom onset Proxy respondents for patients unable to complete Qs Control: No history of stroke (Matched for age and

13 INTERSTROKE:10 RISK FACTORS Hypertension, smoking, WHR, physical Activity, diet, diabetes mellitus, Apo B/A1, Alcohol, Cardiac, Psychosocial (Phase I: 6000, 22 countries) All Stroke Ischemic Stroke I CH PAR 99%CI PAR 99%CI PAR 99%CI 5 RISK FACTORS 90.0 ( ) 90.6 ( ) 90.8 ( )* Adjusted for region, sex, age and other factors Martin O Donnell S. Yusuf..Lancet 2010.

14 INTERSTROKE INVESTIGATORS American Heart Association 2010 Top 10 Most Important Advance in Stroke Research

15 When do risk factors develop? Preconception? Intrauterine? Early childhood? Late childhood? Early adulthood? NEED A LIFE-COURSE APPROACH TO UNDERSTANDING RISK FACTORS.

16 BP (mm/hg) BP (mm/hg) FAMILY Study (905 babies from 859 pregnancies) Blood Pressures at birth, 1, 2, 3 and 5 years 105 Mean Systolic BP (± 1 SE) 65 Mean Diastolic BP (± 1 SE) SBP 45 DBP N N Birth Time (years) 40 Birth Time (years)

17 Lipids (mmol/l) FAMILY Study Mean LDL- C at birth, 1, 3 and 5 years,3.0 LDL,2.5,2.0,1.5 LDL,1.0,0.5 N ,0.0 Birth Time (years)

18 What are the causes of the causes?

19 Prospective Urban Rural Epidemiologic (PURE) Study 220,000 adults(500,000 people) from 25 countries (LIC, MIC, HIC) Urban and Rural 900 communities Societal level influences (Socioeconomic, tobacco & other health policies, relative food prices and availability, built environment, indoor/outdoor pollution) Lifestyle behaviours X genes Individual risk factors CVD, DM, Obesity, Cancers,Obstructive Airways Disease,Renal dis,injuries.

20 Is there a relationship between the built environment as assessed by photos and obesity in countries of different economic level?

21 Left side view Methods: How photos were taken Photograph taken of street scene in each direction from the start point during the EPOCH community observation walk Captures the entire street from each direction including sidewalks, roads, structures, trees, etc. Back View Starting Point Across Street View Front View

22 Urban (Canada)- High Score Score= Urban (Canada)- Low Score Score= 35.33

23 Canada Low-Middle Income Countries Coefficient = P = Coefficient = P < Interaction Canada X LMIC: P< 0.001

24 Ecological correlation advertising & BMI Advertising Correlation coefficient EP2 Junk food 0.741*** ***p<0.0001

25 Tobacco policy vs quit rates Chow C PURE

26 Conceptual differences Biologic risk factors are deterministic Social factors are contextual. The interactions between the two can be variable. Understanding the causes of health requires an appreciation of both levels of risk factors and their interactions

27 Number (%) of Major or All CVD for Different Sub-Groups in PURE (n=152,609) Baseline Condition Total no. with Condition (%) Follow-up Major CVD N = 3,488 (2.23 %) CVD 7,743 (5.1) 673 (19.3) Hypert (History or 140/90) 62,034(40.7) 2,317 (66.4) Current Smoker 31,397 (20.6) 1,021 (29.4) CVD, Hypert or Smoker 84,078 (55) 2,822 (80.9) Diabetes(History or FPG >7mmol) CVD, Hypert, Smoker or Diabetes 16,071(10.5) 905 (26.0) 88,326 (57.9) 2,929 (84.0)

28 Interventions with Clear Evidence 1. Tobacco avoidance 2. Hypertension control 3. Secondary prevention Approach: Identify gaps & barriers and make these interventions impactful (legal, societal and health systems framework + affordable + efficient delivery mechanisms)

29 Secondary Prevention Drugs in PURE Yusuf et al Lancet 2011 Antiplatelet Agents Beta Blockers % ACE Inhibitors or ARBs Statins

30 Global Burden of Hypertension 1 billion adults: Half a billion undiagnosed Half a billion diagnosed Quarter of a billion untreated Quarter of a billion treated Treated: Half uncontrolled 800+ million individuals with hypertension are undiagnosed, untreated, or poorly treated

31 Global Trends in Risk Factors Anand & Yusuf, Lancet 2011 Anand, Yusuf Lancet Feb 2011

32 Prevalence of hypertension awareness, treatment and control in 18 countries (154,000 people) Aware

33 Prevalence awareness, treatment and control of hypertension in S Africa, Zimbabwe and Tanzania

34 Monthly cost of 4 CVD medications as a percentage of households capacity-to-pay(pure,in press Lancet) Urban Rural Urban Rural Urban Rural Urban Rural Urban Rural HIC UMIC LMIC LIC ex. India India Statins Beta blockers ACE-inhibitors Aspirin

35 PURE STUDY PREVALENCE OF HEALTHY LIFESTYLE AMONG INDIVIDUALS WITH CVD

36 Smoking Cessation by Sex Teo et al JAMA 2013

37 Prevalence of Adoption of healthy lifestyle behaviours by country income status and by region Teo et al JAMA 2013

38 PURE STUDY CARDIOVASCULAR RISK AND EVENTS

39 Mean INTERHEART Risk Score (IHRS) Yusuf et al NEJM 2014

40 CVD Event Rates Major CVD = death from CV causes, stroke, MI and HF Non major CVD = all other CVD events that led to hospitalization Yusuf et al NEJM 2014

41 Annualized Case Fatality Rates after Specific CV Events Yusuf et al NEJM 2014

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44 Potential Cumulative Impact of 4 Simple Secondary Prevention Treatments RRR Event rate None 8% ASA 25% 6% -Blockers 25% 4.5% Lipid lowering 30% 3.0% ACE-inhibitors 25% 2.3% CUMULATIVE BENEFITS ARE LIKELY TO BE IN EXCESS OF 75% RRR, WHICH IS SUBSTANTIAL

45 A pill to prevent 80% of heart attacks BMJ 2003

46 Estimated reductions in CHD/Stroke of a Full dose Polycap in Those With Average Risk Factor Levels Reduction in Risk Factors % Relative Reduction CHD Stroke LDL-C (mmol/l) Est (Simv 40) % 10% DBP (mmhg) Est (3, full dose) % 40% Platelet function Est (ASA 100 mg) Similar 32%* 16% Combined Est - 70 to 80% 65 to 75% *RCTs suggest a smaller benefit

47 Cum RR of CVD with lifestyle modification + polypill in a smoker, with low fruits, vegs & exercise Intervention Lifestyle + Polypill Cum risk reductions at different adherence levels 50% 75% 90% Polypill + Combined lifestyle modification 70.6% 82.0% 88.4%

48 Major trials of combined therapy HOPE 3: 2x2 design to test rosuvastatin and/combo of candesartan+ thiazide vs plac in 12,700 people without CVD at moderate risk for 5.5 yrs (CIHR/AZ, 20 countries, Results 2016) TIPS -3 : Polycap (3 BP lowering agents+simv at full doses) vs plac, ASA vs plac in 4000 hi risk people for 5 yr (Wellcome/Cadilla).Results 2017.

49 Advantages of the Polypill. Improved compliance of both physicians and patients. Decreased costs( <.10 cents a day) Increased access: Non-physicians prescribe /OTC and physicians deal with resistant or complex situations and adverse effects. A basis for promoting prudent lifestyle. Potential large reductions in vascular events.

50 Reorganizing Health Delivery to enhance hypertension (and CVD) control (HOPE 4) (Colombia, Malaysia & Canada) 1. Understand and overcome barriers (patient, physician, systems) to improved BP control through customized solutions. a) Task shifting + door to door screening b) Access to inexpensive generic combination (e.g. the polypill) therapy that lowers BP & lipids substantially 2. Cluster RCT in 50 communities involving 2000 people x 2 years: Goals: to reduce SBP by 5 mmhg + IHRS by 10% which corresponds to a 25% further CVD RRR.

51 Reorganizing Health Delivery to enhance hypertension (and CVD) control 3. Stakeholders (National & local govts, societies and professional organizations) involved throughout. 4. Integrate CVD prevention into national policies & strategies to create a national NCD strategy through enabling laws (similar to FCTC for tobacco control) with organizing surveillance of risk factors and CVD.

52 CVD: The unfinished agenda Infectious causes: TB, infections and nutritional deficiencies Rheumatic valve disease Chagas disease

53 Start at the Very Begining a very good place to start! Life-styles, habits and risk factor patterns are established very early in life. Atherosclerosis is life-long process and if we intervene early (in families), then the benefits over a lifetime will be substantial. Healthy societies will lead to healthy children and more productive, active and healthy adults.

54 Males: Age Standardized IHD Mortality/ 100,000 persons by Region and Globally, , the GBD 2010 study Moran et al, Circulation In press

55 Approaches of the WHF to reduce premature CVD by 25% by Implement what is clear: tobacco & hypertension control, secondary prevention, Med type diet, improved physical activity. Widespread use of simple, proven and inexpensive treatments for acute CVD conditions.(impact in 5 yrs) 2. Implementation thru national Road maps 3. Health systems approaches to overcome barriers and reduce Evidence-Prevention/Treatment Gap 4. Capacity building globally for implementation (e.g. Emerging Leaders, capacity in primary care) (Impact in yrs) 5. Remember the children! ( impact in 25 to 50 yrs).

56 Can premature CVD become an endangered disease in 3 generations? Yes....but this will require the political will and the concerted action of society as a whole! Just lets do it!

57 Join us in Mexico City from 4 7 June 2016 WCC 2010, Beijing WCC 2012, Dubai WCC 2014, Melbourne