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Cardiovascular DiseaseWHO June 2010, Geneva
Population Health Research Institute,
McMaster University, Hamilton, Canada
NUI Galway, Galway, Ireland
DISCLOSURESPI‐INTERSTROKECo‐PI: PURE‐MRIPEER‐REVIEW Canadian Institutes of Health Research (CIHR) Heart and Stroke Foundation of Canada (HSFC)Canadian Stroke Network (CSN)Pfizer Cardiovascular Award
UNRESTRICTED INDUSTRY GRANTMerck, Sharp and DohmeBoehringer‐IngelheimAstra Zeneca
OVERVIEWGlobal burden of CHD and Stroke
PHRI Studies Traditional Risk factors for Acute Vascular Syndromes
International Case‐control studiesINTERHEART and INTERSTROKE
Deficit in knowledge of risk factors for chronic vascular syndrome (e.g. Covert stroke)
‘Causes of the causes’PURE prospective cohort study, and FAMILY study
Not include clinical trials (e.g. Polycap trial)
GLOBAL BURDEN OF CHD AND STROKE
Coronary Heart DiseaseLeading cause of mortality globally7.3 million deaths in 2001
Over 75% occurring in low/middle income countries
Stroke2nd leading cause of adult disability globally3rd leading cause of death worldwide (leading in cause of death in many regions)5.7 million deaths in 2005 (7.8 million 2030)
87% in low/moderate‐income countriesStrong et al Lancet Neurol 2007;6:182‐87; Sousa et al Lancet 2009
CHANGE IN THE RANK ORDER OF DISEASE BURDEN FOR 15 LEADING CAUSES, WORLD, 1990‐2020 (DALYS)
Lower resp infDiarrh disPerinatalUnipolar major dep.IHDCerebrovascularTBMeaslesTraffic accidentsCong anomaliesMalariaCOPDFallsIron-defic anaemiaProt-energy malnut
1 IHD2 Unipolar major dep.3 Traffic accidents4 Cerebrovascular5 COPD6 Lower resp inf7 TB8 War9 Diarrhoeal dis10 HIV11 Perinatal12 Violence13 Cong anomalies14 Self-inflicted injuries15 Trach., bronch. & lung CA
123456789101112131415
16 17 19 28 33 19 24 25 37 39
1990 2020
Prevention of Cardiovascular Disease
• Critical component of ‘Successful Ageing’ of a Population
• Prevention requires identification of modifiable risk factors, quantify their importance, and develop interventions that are applicable in low, middle and high income countries
• Target both Acute and Chronic vascular disease
– Acute Coronary Syndrome (MI) and stroke
– Congestive heart failure, chronic renal impairment, PVD, Subclinical (covert) stroke
INTERHEART
1. What are the most important risk factors for myocardial infarction, in middle and low-income countries
2. Is the impact of risk factors on MI similar or variable in different regions or ethnic groups?
3. What proportion of the risk of MI can be explained by known risk factors (population-attributable risk)?
Standardized International Case-control study in 52countries worldwide (15,152 cases 14,820 controls)
Cases and controls from 52 Countries Representing Every Inhabited Continent
RussiaSeychellesSingaporeS AfricaSpainSri LankaSultanate of OmanSwedenThailandUAEUKUSAZimbabwe
KuwaitMalaysiaMexicoMozambiqueNepalNew ZealandNetherlandsNigeriaPakistanPhilippinesPolandPortugalQatar
CroatiaCzech RepEgyptGermanyGreeceGuatemalaHungaryIndiaIranIsraelItalyJapanKenya
ArgentinaAustraliaBahrainBangladeshBeninBotswanaBrazilCameroonCanadaChileChina/Hong KongColombia
INTERHEARTPopulation Attributable Risk > 90% for nine easily measured risk factors
Risk factor Controls (%) Cases (%) OR (95% CI)* PAR (%)
Apo B/A1 ratio† 20.0 33.5 3.3 (2.8‐3.8) 49.2
Current smoking 26.8 45.2 2.9 (2.6‐3.2) 35.7
Psychosocial factors ‐ ‐ 2.7 (2.2‐3.2) 32.5
Abdominal obesity 33.3 46.3 1.6 (1.5‐1.8) 20.1
Hypertension 21.9 39.0 1.9 (1.7‐2.1) 17.9
Vegetables and fruit 42.6 32.8 0.7 (0.7‐0.8) 13.7
Exercise 19.3 14.3 0.9 (0.8‐0.97) 12.2
Diabetes 7.5 18.5 2.4 (2.1‐2.7) 9.9
Alcohol intake 24.5 24.0 0.9 (0.8‐1.9) 6.7
All risk factors ‐ ‐ 129.2 (90‐185) 90.4
Yusuf et al INTERHEART Lancet 2004;364:937‐52
Risk of AMI associated with current or former smoking, overall and by region
Region n Cont.% OR (99%CI)
Overall 26527 47.9 2.27 (2.11,2.44)
W Eur 1403 55.0 1.96 (1.47,2.62)
CE Eur 3624 54.2 1.92 (1.60, 2.30)
MEC 3301 45.4 2.64 (2.19,3.19)
Afr 1339 53.8 2.18 (1.60, 2.96)
S Asia 3706 41.0 2.43 (2.03,2.89)
China/HK 6062 42.7 2.30 (2.00,2.65)
SE Asia 2131 57.1 1.96 (1.54,2.49)
ANZ 1267 54.2 2.80 (2.03,3.86)
S Am 3068 48.9 2.35 (1.92,2.87)
N Am 626 64.6 1.82 (1.14,2.88)
0.5 1 2 4 8
Low Levels of Smoking and MI
0.75
1
2
4
8
Never 1-2 3-4 5-6 7-8 9-10 11-12 13-14 15-16 17-18 19-20 21+
OR
(95%
CI)
Adjusted for age sex and region
INTERSTROKE‐PHASE 1
• International standardized case‐control study – Shared methodology with INTERHEART
• 22 countries (6,000 participants) Mar 07‐Mar 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– 1‐month follow‐up (m‐Rankin)
• Control: No history of stroke (Matched for age and gender)– Community and hospital‐based controls
Yusuf et al INTERHEART Lancet 2004O’Donnell et al Neuroepidemiology 2010
CHALLENGES TO STROKE EPIDEMIOLOGY STUDIES
• All large global epidemiological studies are challenging
• INTERHEART provided evidence of feasibility
SPECIFIC TO STROKE• Valid determination of Stroke Subtype
• (Ischemic, ICH and SAH) requires routine CT of brain
• Until recently, very limited availability in low‐income settings
• Questionnaire‐based research• Presents challenges, given many patients with stroke are unable to
communicate
• Surrogate respondents (Robust Questionnaire: INTERHEART) O’Donnell and Yusuf Lancet Neurol 2009
INTERSTROKE POPULATION (CASES)
All HIC S America China/SEA India African 3,000 422 151 1146 958 323Age (Mean SD) 61.1 (12.7) 66.0 (13.3) 65.6 (13.4) 58.5 (11.6) 58.9 (12.0) 57.7 (15.3)
Age < 45 years (%) 339 (11.3) 30 (7.1) 12 (7.9) 123 (10.7) 107 (11.2) 67 (20.7)
Female (%) 1106 (36.9) 169 (40.0) 71 (47.0) 412 (36.0) 313 (32.7) 141( 43.7)
Intracerebral
Haemorrhage (%)
663 (22.1) 40 (9.5) 39 (25.8) 257 (22.4) 218 (22.8) 109 (33.8)
Ischaemic stroke (%) 2337 (77.9) 82 (90.5) 112 (74.2) 889 (77.6) 740 (77.2) 214 (66.3)
CT or MRI of brain (%) 99.9% 100% 100% 100% 99.7% 100%
Ischemic Stroke (78%) and ICH (22%)
ESC Barcelona 2010; O’Donnell et al INTERSTROKE Lancet (In Press) 2010
10 RISK FACTORS FOR ALL STROKEPrevalence All Stroke
Control (%)
IS(%)
ICH(%)
OR (99%CI)
PAR (99%CI)
PHx Hypertension 31.8 54.7 60.3 2.64 (2.26-3.08) 34.5 (30.3-39.0)
PHx Hypertension/BP >160/90 37.0 66.3 83.1 3.89 (3.33-4.54) 51.8 (47.7-55.8)Smoking (Current) 24.5 37.2 31.3 2.09 (1.75-2.51) 19.0 (15.5-23.2)
WHR (T3 vs T1) 33.4 42.9 35.3 1.65 (1.36-1.99) 26.6 (18.8-36.1)Diet Risk Score ( T3 vs T1) 33.2 39.1 38.2 1.35 (1.11-1.64) 13.4 (6.9-24.3)Physical Active 12.1 8.3 6.8 0.69 (0.53-0.90) 28.7 (14.7-48.6)PHx Diabetes Mellitus 11.7 21.2 10.3 1.36 (1.10-1.68) 5.0 (2.6-9.5)Alcohol (1-30/month)
(>30/month/Binge)17.510.9
14.516.5
18.316.4
0.90 (0.72-1.11)1.51 (1.18-1.92)
3.7 (0.9-14.5)
Psychosocial Stress 14.7 20.0 19.0 1.30 (1.06-1.60) 4.6 (2.1-9.6)
Depression 14.2 21.1 15.5 1.35 (1.10-1.66) 5.2 (2.6-9.8)Cardiac 4.7 13.7 4.2 2.38 (1.77-3.20) 6.6 (4.8-9.1)ApoB/A1 (T3 vs T1) 33.3 50.9 38.1 1.89 (1.49-2.40) 24.9 (15.7-37.1)
ALL RISK FACTORS PAR 90.3% (85.3-93.7)
SUBGROUPSHypertension/BP>160/90
Smoking WHR (T3 v T1)Variable
OR (99%CI) OR (99%CI) OR (99%CI)Region
HIC (n=422) 2.89 (1.85-4.51) 2.88 (1.71-4.84) 3.18 (1.84-5.50)S America (n=151) 3.51 (1.72-7.18) 3.59 (1.28-10.1) 4.59 (1.65-12.8)China/SEA (n=1,146) 4.67 (3.65-5.98) 2.21 (1.64-2.99) 1.22 (0.88-1.68)India (n=958) 4.31 (3.26-5.70) 2.15 (1.58-2.93) 1.31 (0.91-1.88)Africa (n=323) 4.65 (2.90-7.45) 2.66 (1.29-5.48) 1.78 (1.00-3.14)
SexMale (n=1,894) 3.88 (3.22-4.68) 2.46 (2.02-3.01) 1.25 (0.99-1.59)Female (n=1,106) 4.89 (3.79-6.32) 1.56 (1.03-2.36) 2.70 (1.95-3.74)
Age≤ 45 years (n=415) 8.53 (5.39-13.49) 2.77 (1.72-4.47) 1.38 (0.83-2.28)> 45 years (n=2585) 3.89 (3.31-4.57) 2.17 (1.79-2.62) 1.71 (1.39-2.09)
m-Rankin (Stroke Severity)
m-R (0-2) 4.14 (3.48-4.92) 2.04 (1.68-2.48) 1.54 (1.25-1.91)m-R (3-6) 4.51 (3.62-5.62) 2.63 (2.05-3.38) 1.62 (1.24-2.13)
What are the “causes of the causes”?
CVD
Tobacco use
Physical Activity
Nutrition and diet
Social behavior
Smoking
Diabetes
Blood pressure
Cholesterol
Overweight/ obesity
Individualbiological RFs
Individual Behavioral RFs
Community
Clean indoor air regulationTobacco taxes/ priceRegulating age of youth smokingTobacco cessation support programsSocial/ cultural norms
Food policy Access to healthy choices – eg fruits/ vegExposure to unhealthy choices – eg fast food/ vendor machines/ large portion size
Social networksSocial capital
OthersAir pollution
Stress/ anxiety/ depression
Interactions of Environment/ Behaviour with Genes
Walkability of built environmentSafety from crime/ trafficPlaces for walkingAccess to facilitiesLand use mix
Access to health care, Poverty
PURE STUDY
The Prospective Urban Rural Epidemiology (PURE)• Objective
– To examine the relationship of societal influences on human lifestyle behaviours, cardiovascular risk factors, and incidence of chronic non‐communicable diseases
• About 100,000 individual from household (35‐70 yrs) in >600 communities in 17 low‐, middle‐, and high‐income countries.
• Data collection: – Individual (e.g. medical history, lifestyle behaviors, blood and urine
collection (genetic analysis)– 4 environmental domains of interest‐the built environment, nutrition
and associated food policy, psychosocial/socioeconomic factors, and tobacco environment.
• A minimum follow‐up of 10 years is currently plannedTeo and Yusuf et al Am Heart J 2009
PURE: OVERALL BY REGIONS
OBESITY BY ECONOMIC STATUS OF COUNTRY
Obesity = BMI >=30
Advertisement for Sugary Drinks and Mean BMI
Corr Coeff =0.71
Unpublished
Adjusted for: age, sex, level of education, tobacco use, physical activity (MET score), location (urban/rural), and country (Canada, Colombia, Brazil, India, and China)
USE OF EBM THERAPIES IN THOSE WITH CVD
HIC UMIC LMIC LIC Global
1470 3504 4995 1703 11,672ASA/ Other Antiplatelets
43.13 19.92 8.82 4.93 20.2
Beta blockers 29.80 24.09 2.07 6.58 17.1
ACE – I or ARB
37.82 27.85 10.03 3.64 17.9
Statin 45.03 15.44 4.22 2.23 12.4
CVD = heart attack, angina, other heart disease, Q wave and stroke
Unpublished
CREATE Registry: Mortality by SES
5.5
7.2
5.9
6.96.5 6.4
8.2
6.6
0
2
4
6
8
10
Crude Adjusted for treatments
RichUpp Middle ClassLow Middle ClassPoor
P = < 0.001
CREATE (N=20,000)
P = 0.97
Xavier D et al. Lancet 2008
30 D
ay M
orta
l ity
Prospective registry study in 89 centres from 10 regions and 50 cities in India of 20,937 patients. Most patients were from lower middle 10737 (52.5%) and poor (19.6%) social classes.
Subclinical (Covert) Stroke‐PURE‐MRI
Cognitive loss, Depression, Parkinsonism, Gait, Frailty, Sleep Loss of ADL
PURE-Mind: (MRI of brain, cognitive and function) (1,100 in Canada)• Challenges: Measuring ADL across continuum, different settings, prospective
LADIS Study Arch Intern Med 2007Vermeer et al Lancet Neurol 2007
FAMILY Study (905 babies from 859 pregnancies)Blood Pressures at birth, 1, 2, 3 and 5 years
N 761 480 404 267 54 N 761 480 404 267 54
Unpublished
CONCLUSIONSCVD is a major global cause of mortality and dependence in high, middle and low‐income countries
Acute vascular Syndromes and (Chronic and Covert disease)
Considerable increase in knowledge about risk factors, and their modification, to prevent CVD
ACS and Acute Stroke have shared risk factors
Now need to understand the risk factors of risk factors, to guide population‐based interventions
Successful Vascular Ageing across the life‐span
ACKNOWLEDGMENTS
Prof Salim Yusuf, Director, PHRI, McMaster University
• Sonia Anand
• Jackie Bosch
• Sumathy Rangarajan
• Hertzel Gerstein
• Stephanie Ounpuu
• Janice Pogue
• Purnima Rao‐Melacini
• Jane De Jesus
• Shofiqul Islam
• Michelle Zhang
• Guillaume Pare• Romania Iqbal• Koon Teo• Matthew McQueen• Mahshid Dehghan • Manisha Madhavan • Andrew Mente• Siu Lim Chin• Fahad Razak• MyLinh Duong• Zena Samaan• Andrew Mente• Daniel Corsi
• Changchung Xie
• Rizwan Afzal
• Katherine Morrison
• Stephanie Atkinson
• Kim Hall
• Sarah McDonald
and many others!
INTERSTROKE Investigators
THANK YOU