The concept of risk

Risk factor - causal factor,

association RF diseases long-term,
strong, specific, time dependent (e.g. chol
x atherosclerosis)

Risk factor - predictor of the

disease,
marker of the disease development
(e.g. hs-CRP- high CV risk, homocysteine
x CHD)
 Relative risk (RR)
(RR
Risk of individual expressed in
relation to the standard risk = 1
e.g. risk of coronary event in men
with normal RF

The rate of disease among subjects

with RFs divided by the rate of
disease in subjects without RFs
 Relative Risk
assessment
diseases yes disease no
RF yes a b
RF no c d

RR = a/(a+b) : c/(c+d)

What is the difference (%) of disease prevalence

if RF is present or is not present
 Odds ratio (OR)
OR = a.d / b.c
Mantel Haenszel method statistical
evaluation of the relative risk with the
confidential limits (on the minimal 5% level
of the probability)
Adjustement of OR for age and other RFs.

e.g. 1) OR 1.75 (1.02 3.5)

RR is significantly increased about 75%
e.g. 2) OR = 0.75 (0.15 1.09)
RR is non significantly decreased about 25%
 Regular alcohol consumption and 12-
year morbidity and mortality in middle-
aged men from the Pilsen population
Cancer
Cancer in smokers OR 1,3 (1,11-1,
STR

MI

Non-fatal CHD: OR 0,76 (0,60-0,97)

Total and CV
mortality

RR
0,5 0,75 1 1,5

Rosolov H. et al.: Pilsen Longitudinal Study I. Cardiology 1994;85:61-68

 Continuous risk

Sir George Pickering blood pressure

is a continuous variable and its
relationship to rate of CHD or stroke
are smoothly continuous since the
normal BP values

RISK IS IN FACT CONTINUOUS!

Dg of hypertension is an artificial dichotomy
 Normal BP Hypertension
Number of STR (%)

25 50

20 40
SBP
risk
distribution
15 30 curve

10 20

5 10 Number
of cases

0 0
100 120 140 160 180 200

Systolic blood pressure (SBP-mmHg)

 Metabolic syndrome increases CV
mortality

CV mortality
RR (95% CI)
Cummulative risk (%)

3.55 (1.986.43)
With
metabolic
syndrome

Without
metabolic
syndrome

0 2 4 6 8 10 12 years
Kuopio Ischaemic Heart
Disease Risk Factor Study
Lakka HM et al. JAMA 2002;288:2709-2716.
J-shaped and U-shaped
risk factor relations
 Absolute risk

Risk of persons developing a disease in a

defined period
Probability (%) of disease occurance in a
time period.
Important for the clinical practice!
----------------------------------------------------------
Incidence of the disease / 100 000 persons
RISK TABLE SCORE

Absolute risk
For the subjects with low level of HDL-ch
 Attributable risk

AR = Risk difference = the

difference in disease rates
between exposed and unexposed
individuals.
 PROCAM Study
CHD risk according to LDL and TG levels
The main risk factors for AS

Cholesterol (LDL-ch)
Smoking
Arterial hypertension
Diabetes mellitus (insulin
resistance - metabolic syndrome)
Obesity
Stress
The general source of CHD

Fatty nutrition weith high level

of saturated fatty acids

The main casual risk factor

cholesterol (LDL-ch)
MRFIT Study epidemiological study
in middle-aged men
Changes of plasma lipids level
changes of CV risk

1% decrease LDL-C
1% decrease CHD 1% increase HDL-C
3% decrease of CHD

Third Report of the NCEP Expert Panel. NIH Publication No. 01-3670
2001. http://hin.nhlbi.nih.gov/ncep_slds/menu.htm
 Reduction of total (LDL) cholesterol
= reduction of CV mortality

Meta-analysis of 38 primary and secondary preventive interventional

studies, more than 98 000 patients
0.0
Total mortality, p=0.04
0.2

0.4
Mortality, (log
relelative risk)
0.6
Coronary mortality, p=0.012

0.8

1.0
0 4 8 12 16 20 24 28 32 36
Cholesterol reduction (%)

Gould AL et al. Circulation 1998;97:946952

 Prof. Rory Collins
Oxford University, UK
10 000 000 high risk subjects treated by statins
spare 50 000 lifes each year (i.e. 1 000 lifes per
week)

Heart Protection Study (2002)

 CHD, STROKE
Heart Protection Study

100%
RR=0,76
95% (0,72-0,81)
life
without 90% P< 0,0001
events
85%
STATIN

80%

75%
PLACEBO

0 1 2 3 4 5 6

years follow-up

Heart Protection Study:LANCET 2002,360:7-22

 Effects of statins
Non-lipid
Lipid mechanisms
mechanisms
Plasma
levels

Stabilisation of AS
measurable
LDL-C Inflammation

Trombogenesis
Imunomodulation
 European Guidelines on
Cardiovascular Disease
Prevention in Clinical Practice

Total cholesterol 5 mmol/l ( 4,5)

LDL chol 3 mmol/l ( 2,5)
HDL-chol 1 mmol/l in men
1,3 mmol/l in women
TG 2 mmol/l (1,7)
The main risk factors for AS

Cholesterol (LDL-ch)
Smoking
Arterial hypertension
Diabetes mellitus (insulin
resistance - metabolic syndrome)
Obesity
Stress
SMOKING
 What is the habit of
SMOKING?

1492 - Columbus found the smoking Indians

Jean Nicot tabacco local application
60th 19. century cigarette production
20. century social habit
21. century - addiction to nicotine
Disease (since Feb 2004)
Dg: F17
Why do people smoke?

Psychosocial motivation in children

Lack of self-confidence
Influence of parents, siblings, friends
stress depression
 NICOTINE as a drug

Smoke absorption is very fast in the

lung tissue

nicotine goes from arterial blood to

the brain during 10-16 sec
 NICOTINE as a drug
Nicotine activates nicotinic acetylcholin receptors in
the brain and induces secretion of dopamine
catecholamines
} increased activity of the sympathetic nervous
system!!!!

psychomotor stimulans
tolerance to nicotine is developping very quickly

(amfetamines, cocaine)
 NICOTINE as a drug

Increases morbidity and

mortality
Decreases insulin sensitivity
IR Type 2 Diabetes mellitus
 Coronary, cardiovascular and
total mortality heart rate
Coronary
2-yer mortality / 1000 inhab.

60
CArdiovascular
50
Total
40

30
Age-adjusted

20

10
0
<65 65-74 75-84 85+

Gillman MW: The Framingham Study, Am Heart J 1993;135:1148-54

 Summary

Smoking stimulates SNS (increases IR)

Main mechanism
For the CV risk elevation
In subjects with or without diabetes
Smoking in Europe

30% men 24% women

60-70% smokers would likr to stop smoking

Only 2 % of smokers are successful!
Impact of smoking

The cause of each 5th death is

SMOKING
The majority of these deaths
Is CHD
 BENEFIT of giving up
smoking
before 35 y. of age life longevity is the
same as in non-smokers !

Lung CA in 10 years risk decreases about 30 - 50%

CHD in 1 year risk decreases about 50% !!!

- in 15 years risk is the same as in non.-
smokers !!!
BENEFIT of giving up
smoking
in primary prevention

It is only one life style

cost-effective change !
 BENEFIT of giving up
smoking
in secondary prevention

Metaanalysis of the prognosis after MI

Stop smoking decreased risk of death more than

treatment of ACS: ORs = 0,54

Standard treatment: ORs = 0,75-0,88

Wilson et al., 2000
(trombolysis, aspirin, beta-blockers, statins)
 Stop smoking in CZ

Office for the patients- smokers

Phone for Czech Republic

844 600 500
12.00 do 20.00
 Intensive intervention
in stop smoking
Psychosocial and behavioral
intervention
Pharmacological therapy - 8-12 weeks
a) Nicotine substitution (chewing gum,
microtabblets, inhalator.)
b) antidepressive drugs - bupropion
1-2 weeks before of starting stop
smoking (2x150 mg)
 Intensive intervention in
stop smoking

20 % smokers stop to smoke

(i.e. 10times more than without this intervention)

 Take home messages 1

1. The concept of risk: relative risk (OR)

attributable risk
absolute risk

2. How to use Risk Table SCORE absolute risk

in primary prevention of AVD
 Take home messages 2

3. Cholesterol is the main casual risk

factor for atherosclerosis and AVD

4. Low fat diet and statins are important for

decreasing cholesterol level and CV risk
 Take home messages 3

5. Cigarette smoking is the 2nd standard risk

factor for for atherosclerosis and AVD = a
disease (addiction to nicotine)

6. Intensive intervention in giving up smoking

is more effective is only one cost-
effective change in life style for AVD
primary and secondary prevention