1. Cardiovascular risk factors: are they useful screening tests?
Malcolm Law
Wolfson Institute of Preventive Medicine
Barts and The London School of Medicine

2. Mortality in Britain Ischaemic heart disease 130,000 deaths per year
Stroke 63,000 deaths per year
Together one third of all deaths

3. Average values of risk factors: present day
and prehistoric values at age 60
Present
Western
Prehistoric
Proportion of present
Western below
prehistoric average
Systolic BP (mmHg) <1%
Serum cholesterol (mmol/l) <1%
Plasma homocysteine (mmol/l) <10%
Body mass index (kg/m2) <10%
Law & Wald BMJ 2002;324:1570-6
Ubbink J Nutr 1996;126:1254S-7S

4. Blood pressure and IHD in a meta-analysis of cohort studies
Relative risk
Usual diastolic BP (mmHg)
MacMahon et al Lancet 1990

5. Blood pressure and stroke in a meta-analysis of cohort studies
Relative risk
Diastolic BP (mmHg)
MacMahon et al Lancet 1990

6. Serum cholesterol and ischaemic heart disease
Did not die
of IHD
Died of IHD
DR = 15%
FPR = 5%
Serum cholesterol (mmol/l)
BUPA cohort study

7. Blood pressure and ischaemic heart disease
Did not die
of IHD
Died of IHD
DR = 13%
FPR = 5%
Diastolic blood pressure (mmHg)
BUPA cohort study

8. Serum homocysteine and ischaemic heart disease
Did not die
of IHD
Died of IHD
DR = 13%
FPR = 5%
Serum homocysteine (mmol/L)
(log scale)
BUPA cohort study

9. Blood pressure and stroke
Did not die
of stroke
Died of stroke
DR = 24%
FPR = 5%
Diastolic blood pressure (mmHg)
BUPA cohort study

10. Systolic blood pressure 28% Ischaemic heart disease
Disease concentration in the 10% of the population with the most extreme risk factor values
Proportion of cases in the
most extreme 10%
Stroke
Systolic blood pressure 28%
Ischaemic heart disease
Systolic blood pressure 21%
Serum cholesterol 21%
Plasma homocysteine 20%
Body mass index 22%
Law & Wald BMJ 2002;324:1570-6

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

12. Why combining risk factors is less effective than one would think?
LDL cholesterol detects 17% of cases for 5% FPR
Systolic BP also detects 17% of cases for 5% FPR

13. Why combining risk factors is less effective than one would think?
LDL cholesterol detects 17% of cases for 5% FPR
Systolic BP also detects 17% of cases for 5% FPR
What proportion would be detected if we used both?

14. Why combining risk factors is less effective than one would think?
LDL cholesterol detects 17% of cases for 5% FPR
Systolic BP also detects 17% of cases for 5% FPR
What proportion would be detected if we used both?
17% + (17% of 83%) = 31%

15. Why combining risk factors is less effective than one would think?
LDL cholesterol detects 17% of cases for 5% FPR
Systolic BP also detects 17% of cases for 5% FPR
What proportion would be detected if we used both?
17% + (17% of 83%) = 31%
But the FPR would no longer be 5% - it would be nearly 10%

16. Why combining risk factors is less effective than one would think?
LDL cholesterol detects 17% of cases for 5% FPR
Systolic BP also detects 17% of cases for 5% FPR
What proportion would be detected if we used both?
17% + (17% of 83%) = 31%
But the FPR would no longer be 5% - it would be nearly 10%
This is what is often overlooked
Keeping FPR at 5%, detect 22% instead of 17% for one alone

17. If you found a group with a very high risk few people are in it
The paradox of risk
If you found a group with a very high risk
few people are in it
so one misses most of the cases

18. Example
Healthy man age 60 who: smokes cigarettes
cholesterol in top 5%
(7.6mmo/L)
blood pressure in top 5%
(175 mmHg systolic)
Absolute risk of MI or stroke = 9% per year
(12 fold increase)
But prevalence of such men is 6 per 10,000
[Five GPs between them would have one]

19. The paradox of risk
Annual risk of IHD event or stroke in men aged 60
Risk Detection Positive
cut-off rate rate
0.25% 99% 98%

20. The paradox of risk
Annual risk of IHD event or stroke in men aged 60
Risk Detection Positive
cut-off rate rate
0.25% 99% 98%
0.5% 88% 73%

21. The paradox of risk
Annual risk of IHD event or stroke in men aged 60
Risk Detection Positive
cut-off rate rate
0.25% 99% 98%
0.5% 88% 73%
1% 52% 28%

22. The paradox of risk
Annual risk of IHD event or stroke in men aged 60
Risk Detection Positive
cut-off rate rate
0.25% 99% 98%
0.5% 88% 73%
1% 52% 28%
2% 16% 5%

23. The paradox of risk
Annual risk of IHD event or stroke in men aged 60
Risk Detection Positive
cut-off rate rate
0.25% 99% 98%
0.5% 88% 73%
1% 52% 28%
2% 16% 5%
4% 1% 0%

24. Groups with an annual risk of heart attack or stroke of 5% or more
event rate
(fatal or not)
annual
death
rate
Previous myocardial infarction 5% 10%
Previous stroke 5% 10%
Angina without MI 3% 6%
Transient ischaemic attacks without stroke 2% 5%
Law at al Arch Intern Med 2002;162:

25. Asking for a history of any of these disorders
is a screening enquiry
It has a detection rate of about 50% ond a low FPR

26. Proportion with such a history
About half of deaths from heart disease and stroke occur in people with a history of a first non-fatal event
Proportion with such a history
MI stroke
Men aged 60 7% 3%
70 15% 7%
Women aged 60 4% 2%
70 5% 3%
Health Survey for England

27. In people with no history of disease
age alone is the best screening test
age cut-off 55 years - detection rate 94%
positive rate = 23%

28. Conclusions Cardiovascular risk factors are important aetiologically
Lowering them can greatly reduce risk
But they are poor screening tests - they do not usefully discriminate
between people who will and will not have an ischaemic
heart disease event or stroke
The best screening test is the presence of existing disease.
In people without existing disease it is age