Ethnic influences on stroke risk Francesco P Cappuccio MD MSc FRCP FFPH

2 Selected leading causes of death worldwide in 1990 Number of deaths (million) Lancet 1997;349: M (~70%) in developing countries

3 Prevalence of severe disability in men Age groups (per 1,000) Lancet 1997;349:

4 Ezzati M et al. Lancet 2002;360: Mortality due to leading global risk factors

5 Stroke is preventable! Time trends –rapid change in stroke mortality is likely to have resulted from change in incidence rates, so factors determining onset of disease must have changed

6 Trends in age-adjusted mortality from stroke in the US

7 Stroke is preventable! Time trends –rapid change in stroke mortality is likely to have resulted from change in incidence rates, so factors determining onset of disease must have changed Geographic variations –large international differences in stroke mortality –they are not fixed, e.g. in Japanese migrants

8 Prevalence of hypertension in populations of African origin (ICSHIB) R Cooper et al Am J Pub Health 1997; 87: Age and sex-adjusted prevalence (%) Prevalence of hypertension in populations of European vs African origin Age and sex-adjusted prevalence (%) R Cooper et al. BMC Medicine 2005; 3: 2

9 Mortality from Stroke amongst Japanese migrants Am J Epidemiol 1990;131: Deaths per 100,000 population

10 Stroke is preventable! Time trends –rapid change in stroke mortality is likely to have resulted from change in incidence rates, so factors determining onset of disease must have changed Geographic variations –large international differences in stroke mortality –they are not fixed, e.g. in Japanese migrants Causes of stroke –many can be avoided –effect reversible in a few years, e.g. RCTs

11 Results from a meta-analysis of 10 trials of anti-hypertensive drug therapy Total of 9278 active treatment and 9264 control patients

12 Risk Factors for Stroke Inherent biological traits –age, sex, ethnic background Physiological characteristics –blood pressure, fibrinogen, BMI, homocysteine, etc. Pathological factors –atrial fibrillation, diabetes, sickle cell disease Behaviour –smoking, diet, alcohol, OC Social characteristics –social class Environmental Features –temperature, season, etc. Genetics –candidate genes (AGT, Na-channel, G-protein, adducin,...)

13 Blood Pressure, Stroke and CHD

14 Variations by ethnic groups in the UK Burden of vascular disease Detection, management and control of hypertension Application of national guidelines Assessment of risk Non-drug therapy Pharmacological treatment

15 IHD and CVD Mortality in England & Wales (1983) in people aged yrs MenWomen S.M.R.% Balarajan R. BMJ 1991;302:560-4

16 Cause of death from vascular disease in US blacks and whites (1991 NYC Medical Examiner’s Office) MEN WOMEN (n=417) (n=170) ______________________________ Age at death (years)51.7 vs vs 61.5* Atherosclerotic0.4 ( )*0.4 ( )** Hypertensive2.2 ( )*3.1 ( )** Age-adjusted OR (95% CI) *p<0.01, **p<0.001 Hypertension 1998;31:1070-6

17 Incidence of first ever stroke in London (1995-6) Stewart JA et al. Br Med J 1999;318: yrs younger!

18 Infarct Large-vessel disease Multiple Infarcts Small-vessel disease Types of stroke Haemorrhage Intracerebral

19 Incidence of first ever stroke subtype in London (1995-6) Stewart JA et al. Br Med J 1999;318: *age-adjusted

20 Prevalence of hypertension * by age and ethnic group in South London African origin South Asian White African origin South Asian White *BP >160 and/or >95 mmHg or on therapy Heart 1997;78:555-63

21 Detection, Management and Control of Hypertension in S. London (1994-6) Inadequately treated 50.6% 49.4% 47.0% 10.1% 25.3% 13.4% 17.8% 13.5% 12.7% 21.5% 11.8% 26.9% Adequately treated Untreated Undetected Cappuccio FP et al. Heart 1997;78:555-63

22 Stroke Mortality and Quality of Hypertension Control Du et al. BMJ 1997 p<0.01 Adjusted Odds Ratios Cases 267 Controls 534 Average SBP achieved with Rx in last 5 yrs

23 Prevention and management of CVD based on overall absolute risk of disease, rather than individual risk factor management Recent guidelines now adopt this paradigm shift (JBS-2, BHS IV, NSF for CHD, NICE) Risk estimates based on 10-year prospective experience of Framingham cohort (sub-urban American white middle-class men and women) The burden of cardiovascular disease is not distributed equally among society. Ethnic groups have disproportionately high risk…but… Risk Assessment and Treatment Choices

24 Relationship between CHD and CVD risks by ethnic origin CHD overestimates CVD CHD under estimates CVD Cappuccio FP et al. Br Med J 2002;325: Sensitivity (%) 1.30 ( ) 1.40 ( ) 1.48 ( )

25 British evidence None prospective CHD and CVD risk by Framingham score not consistently related in ethnic groups [Cappuccio FP e al. BMJ 2002;325:1271-4] Discrepancies between predicted risks by ethnic group and SMR by country of birth [Quirke TP et al. Heart 2003;89:785-6] Inconsistent predictions between Framingham, FINRISK and SCORE in ethnic groups [Bhopal R et al. J Pub Health 2005;27:93-100] Age-adjustment to reduce inconsistency of Framingham risk across ethnic groups [Aarabi M et al. Eur J Cardiovasc Prev Rehab 2005;12:46-51]

26 ETHRISK A modified Framingham CHD and CVD risk calculator for British black and minority ethnic groups Heart 2006;92:

27 In people of African origin high blood pressure more common low plasma renin activity sensitive to changes in sodium intake sodium retention and volume expansion A slave trader licking a slave’s face to assess his fitness for the voyage across the Atlantic

28 BHS - NICE Guidelines

29 ALLHAT: blood pressure control* blacks vs non-blacks Wright JT et al. JAMA 2005;293: * % below 140/90 mmHg Chlorthalidone Amlodipine Lisinopril

30 ALLHAT: outcomes in blacks vs non-blacks Wright JT et al. JAMA 2005;293:

31 Stroke & ethnic minority groups Compared to whites, Africans & Caribbeans: have a lower incidence of CHD have a higher risk of stroke, renal failure and LVH BP more sensitive to salt restriction & benefit more from dietary advice alone low plasma renin and angiotensin  reduced response to ACE-i & ARBs (or  -blockers) as monotherapy – however, see ALLHAT Improved efficacy to ACE-inhibitors/ ARBs in combination with diuretics or CCBs Compared to whites, South Asians: have a greater incidence of CHD have also a higher risk of stroke and renal failure some sub-groups have high blood pressure and some have very high smoking rates metabolic abnormalities more common