1. Risk factor thresholds: their existence under scrutiny
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Risk factor thresholds: their existence under scrutiny
Nicholas Wald Wolfson Institute of Preventive Medicine, London
Pfizer update symposium
in vascular medicine
Amsterdam
3rd October 2003
V1.2a assumes that is finished (1.2) and discards the spares. They are still in 1.2
V1.2 is start of work on putting them side by side
V1.0 has whole collection of graphs in old order. V1.1 has spare stuff moved out to end
Nicholas Wald 2003

2. Ischaemic Heart Disease (IHD) and stroke are responsible for about one third of all deaths in Western countries.
Nicholas Wald 2003

3. Risk of IHD and stroke can be reduced by decreasing:
LDL cholesterol proven
Blood pressure proven
Platelet aggregation proven
Serum homocysteine probable
Body mass index probable
Nicholas Wald 2003

4. Examination of the dose-response relationship
Nicholas Wald 2003

5. IHD and blood pressure meta-analysis
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IHD and blood pressure meta-analysis
(age 60)
(age 60) M
Nicholas Wald 2003
McMahon et al, Lancet 1990

6. Stroke & blood pressure meta-analysis
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Stroke & blood pressure meta-analysis
MacMahon et al Lancet 1990 – check spelling
Nicholas Wald 2003
McMahon et al, Lancet 1990

7. IHD & cholesterol in a large cohort study
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IHD & cholesterol in a large cohort study
Neaton et al Arch Intern Med 1992
Nicholas Wald 2003
Neaton et al Arch Intern Med 1992

8. IHD & BMI in a large cohort study
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IHD & BMI in a large cohort study
Willett et al JAMA 1995
Nicholas Wald 2003
Willett et al JAMA 1995

9. WaldRiskFactThr_v1.3c-sk
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Diabetes & BMI
Knowler et al Am J Epidemiol 1981 [ref 9]
Nicholas Wald 2003
Knowler et al Am J Epidemiol 1981

10. No threshold in risk reduction
Implications
No threshold in risk reduction
The dose-response relationship shows that a given change in a risk factor reduces the risk of disease by a constant proportion of the existing risk irrespective of the starting level of the risk factor or of the existing risk.
Nicholas Wald 2003

11. Percentage reduction in risk for a 10 mmHg reduction in systolic blood pressure in men aged 55-64
Nicholas Wald 2003
Taken from: Prospective Studies Collaboration, Lancet 2002;360:1903

12. Percentage reduction in risk of IHD events for a 1 mmol/l reduction in serum cholesterol in men aged 55-64
Nicholas Wald 2003
Taken from: Prospective Studies Collaboration, Lancet 2002;360:1903

13. Practical implications of the straight line proportional dose-response relationships
There is benefit in modifying risk factors in people at high risk, whatever the reason for the high risk and regardless of the level of the risk factor
Nicholas Wald 2003

14. Risk reduction from risk factor modification
Nicholas Wald 2003

15. Risk reduction from risk factor modification
Nicholas Wald 2003

16. Risk reduction from risk factor modification
Reduction in risk
Reduction in risk factor
Relative
Absolute
1 unit (7 to 6)
50%
8 per 1000 per year
1 unit (5 to 4)
2 per 1000 per year
Nicholas Wald 2003

17. Defining people at high risk
Nicholas Wald 2003

18. Is it sensible to screen using risk factors such as LDL cholesterol and blood pressure?
Nicholas Wald 2003

19. Detection Rate False Positive Rate Nicholas Wald 2003

20. Nicholas Wald 2003
Nicholas Wald 2003

21. Nicholas Wald 2003
Nicholas Wald 2003

22. Nicholas Wald 2003
Nicholas Wald 2003

23. Combining risk factors to screen for ischaemic heart disease events
Proportion of events detected (DR) for a 5% FPR
apoB (or LDL cholesterol) 17%
+ systolic blood pressure 22%
+ apoA1, apo(a) 24%
+ smoking 27%
3 measures of all the above
+ smoking 28%
+ smoking, family history 29%
Wald et al Lancet 1994;343:75-9
Nicholas Wald 2003

24. Why combining risk factors is less effective than one would think
DR for a 5% FPR
LDL cholesterol %
Systolic BP %
What would the DR be if we used both?
17% + (17% of 83%) = %
But the FPR would increase to about 10%.
If FPR kept at 5%, DR = %
Instead of 17% for one alone.
Nicholas Wald 2003

25. Is it sensible to screen using risk factors such as LDL cholesterol and blood pressure?
- NO
Nicholas Wald 2003

26. Is it sensible to screen by asking people if they have a history of cardiovascular disease?
- YES
Nicholas Wald 2003

27. History of cardiovascular disease
About 50% of IHD deaths and about 65% of stroke deaths occur in individuals who have had a previous stroke or heart attack.
They have a much higher risk than others.
Their risk of dying is about 5% per year.
Nicholas Wald 2003

28. Is it sensible to screen using age alone?
- YES
Nicholas Wald 2003

29. IHD and stroke deaths (England and Wales 1997)
Screening using age
Age 55 and over
Age under 55
IHD and stroke deaths (England and Wales 1997)
Nicholas Wald 2003

30. WaldRiskFactThr_v1.3c-sk
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Prospective Studies Collaboration: blood pressure and ischaemic heart disease C
Lancet 2002;360:1903
Nicholas Wald 2003

31. Prospective Studies Collaboration: blood pressure and stroke
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Prospective Studies Collaboration: blood pressure and stroke D
Lancet 2002;360:1903
Nicholas Wald 2003

32. Using risk factors
There is little point in estimating a person’s risk using blood pressure, serum cholesterol and smoking habits because those who are thereby “positive”, but “negative” on the basis of their age alone, would anyway become “positive” when they are a few years older.
It is not worth the considerable cost and effort simply to delay treatment by about five years.
Nicholas Wald 2003

33. Second Joint Task force on prevention of CHD
Existing atherosclerotic disease
Adults with CHD risk  20% over ten years
Try “lifestyle” change to achieve:
BP < 140/90, cholesterol < 5 mmol/l
If the lifestyle changes do not achieve this, use drugs.
BUT about 50% of people over 55 have BP > 140/90
and about 90% of people over 55 have cholesterol > 5 mmol/l
Nicholas Wald 2003
Wood et al, Atherosclerosis, 140 (1998):

34. If 10% of people can lower their blood pressure by lifestyle changes and 10% of people can lower their serum cholesterol in this way then 40% and 80% respectively would require drugs.
What proportion of people would require drugs on account of either blood pressure or serum cholesterol?
88%
The proposed screening would identify about 90% of people aged 55 and over as needing drugs – so why not give them to all?
Nicholas Wald 2003

35. Guidance on Guidelines
Guidelines like this are not effective
We need simpler, more effective guidelines.
Nicholas Wald 2003

36. Wolfson Guidelines on Cardiovascular Disease Prevention
Lifestyle changes for all
Drugs for all with cardiovascular disease
Drugs for all above a given age (55)
Avoid testing and monitoring
Nicholas Wald 2003

37. What drugs?
Nicholas Wald 2003

38. Effect of medical intervention (pills)
Approximate risk factor reduction
Reduction in risk
IHD
Stroke
LDL cholesterol
Statin
1.8 mmol/L
61%
17%
Blood pressure
Half standard dose of 3 from:
– Thiazide – β-blocker – ACE-inhibitor or ARB
– Calcium channel blocker
10.7 mm Hg diastolic
46%
63%
Serum homocysteine
Folic acid
3 µmol/L
16%
24%
Platelet aggregation
Aspirin –
32%
Combined effect
88%
80%
Nicholas Wald 2003
150/90

39. WaldRiskFactThr_v1.3c-sk
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Put all six drugs into one daily pill.
Deleted for short version
Nicholas Wald 2003

40. anyone under 55 with a history of cardiovascular disease
Prevention strategy
A single Polypill per day composed of six active ingredients, to be taken by:
all aged 55 or more
anyone under 55 with a history of cardiovascular disease
without medical examination.
Nicholas Wald 2003

41. Conclusion
The Polypill represents a radical departure from current practice in the prevention of cardiovascular disease.
Probably no other preventive method or treatment would have as great an impact on public health in the Western world.
Nicholas Wald 2003