prof. michal vrablíklp (a) aip homocystein 19 metabolic syndrome obesity smoking lack of physical...

Cardiovascular Risk FactorsProf. Michal Vrablík

1The screen versions of these slides have full details of copyright and acknowledgements

Cardiovascular Risk Factors

11

Prof. Michal Vrablík

1st Medical Faculty, Charles University

Prague, Czech Republic

Cardiovascular risk and risk factors

What is cardiovascular risk ?

Is the risk important ?

How to assess the risk ?

2

How to assess the risk ?

What are the risk factors ?

Which risk factors are most important ?

Can we predict future ?

There are different risks…

Absolute vs. relative risk

Individual vs. population risk

Sh t l t i k

3

Short vs. long term risk



CVD – leading cause of adult mortality worldwide

CAD 7.2 mil

Cancer 6.3

Cerebrovascular disease 4.6

Acute respiratory infections 3.9

Tuberculosis 3 0

4

Tuberculosis 3.0

COPD 2.9

Dairhea (disenteria incl.) 2.5

Malaria 2.1

AIDS 1.5

Hepatits B 1.2

Institut Pasteur de Lille, France, 1996

Leading causes of death, Canada, 1998

Cardiovascular diseases 79,11737%

Cancers 58,81728%

Diabetes 5,4963%

Respiratory diseases 18,8889%

5

Others 31,35815%

Infectious diseases 3,4972%

Accidents/poisonings 13,5606%

In 1995 CVD accounted for 37% of deaths in Canada,

of which IHD accounted for 21%

CVD mortality, USA, 1980-2003

6

Males Females



Standardized mortality- Czech Rep., 1990-2006

Men Women

CVD CVDrespiratory

respiratoryGI tract

7www.uzis.czwww.uzis.cz

cancer cancer

GI tract

injuries injuries

other other

Global burden of cardiovascular disease

According to WHO estimates:

16.6 million people die of CVD worldwide each year

CVD contributed to approximately one third of global deaths

I 2001

8

In 2001:

7.2 million deaths from CHD

5.5 million deaths from stroke

Clinical care of CVD is costly and prolonged

Adapted from International Cardiovascular Disease Statistics Adapted from International Cardiovascular Disease Statistics 20032003; American Heart Association; American Heart Association

Distribution of age, gender and diagnostic category, EUROASPIRE III

Gender Age Diagnostic category

405060708090

100

9

(years)

www.escardio.org

0102030

Survey 1 24.9 59.3 47.8 25.6 25.6 25.8 23.0Survey 2 25.2 59.4 48.1 24.8 27.8 26.1 21.2Survey 3 23.1 60.9 40.6 28.3 49.8 9.9 12.0

Women (%) Mean age

Age < 60

yrs (%)

CABG (%)

PTCA(%)

AMI (%)

ISCHAEMIA (%)



Atherogenesis

Foamcells

Fattystreak

Intermediatelesion Atheroma

Fibrousplaque

Complicatedlesion/rupture

10

Endothelial dysfunction

Smooth muscleand collagen

From first decade From third decade From fourth decade

Growth mainly by lipid accumulation Thrombosis,hematoma

Adapted from Stary HC et al., Circulation 1995; 92:1355-1374

Endothelial dysfunction in atherosclerosis

11Adapted from Ross R., N Engl J Med 1999; 362:115–126

Clinical manifestations of atherosclerosis

Coronary heart disease

– Angina pectoris, myocardial infarction, sudden cardiac death

12

Cerebrovascular disease

– Transient ischaemic attacks, stroke

Peripheral vascular disease

– Intermittent claudication, gangrene

…because of risk factors !



Risk factors

Measurable variables associated with manifestation of a disease in clinical and experimental studies

Their modification influences future incidence

13

Their modification influences future incidence of the disease

Risk factors for cardiovascular disease

Modifiable vs. non-modifiable

Traditional vs. emerging/non-traditional

14

Well established vs. new

Risk factors for cardiovascular disease

Modifiable– Smoking

– Dyslipidaemia

• raised LDL-C

• low HDL-C

• raised triglycerides

Non-modifiable– Personal history of CHD

– Family history of CHD

– Age

– Gender

15

– Raised blood pressure

– Diabetes mellitus

– Obesity

– Dietary factors

– Thrombogenic factors

– Lack of exercise

– Excess alcohol consumption

Adapted from: Pyörälä K et al., Eur Heart J 1994; 15:1300–1331



Levels of risk associated with smoking, hypertension and hypercholesterolaemia

x3

Hypertension (SBP >195 mmHg)

16

x1.6 x4x6

x16x4.5 x9

Serum cholesterol level (>8.5 mmol/L, 330 mg/dL)

Smoking

Adapted from Poulter N et al., 1993Adapted from Poulter N et al., 1993

PROCAM: Combination of risk factors increases risk of MI

60

80

100

120

e of

MI/1

000

pts

17Prevalence (%): 54.9 22.9 2.6 2.3 9.4 8.0 Prevalence (%): 54.9 22.9 2.6 2.3 9.4 8.0

Adapted from Assman G, Schulte H., Am Heart J 1988; 116:1713–1724

0

20

40

Inci

denc

Non-modifiable risk factors

Age

– Men > 45, women > 55

Gender (males > females)

Family history of premature CVD

18

Family history of premature CVD

– 1st degree male/female relative < 55/65

Personal history of CVD (!)

Genetic risk factors

Subclinical atherosclerosis (?)



Modifiable risk factors

TraditionalDyslipidemia

Arterial hypertension

Diabetes mellitus

Metabolic syndrome

Newapoproteins

Lp (a)

AIP

homocystein

19

Metabolic syndrome

Obesity

Smoking

Lack of physical activity

Atherogenic diet

Psychosocial stress

homocystein

hsCRP

Dyslipidemia: a significant risk factor for CVD

20

Structure of lipoproteins

Free cholesterol

Phospholipid

Triglyceride

21

Cholesteryl esterApolipoprotein



Classification of dyslipidaemias:Fredrickson (WHO) classification

22

Types of lipoprotein particles

Triglyceride-rich lipoproteins

– Chylomicrons

– Very low-density lipoprotein (VLDL)

23

Very low density lipoprotein (VLDL)

Cholesterol-rich lipoproteins

– Low-density lipoprotein (LDL)

– High-density lipoprotein (HDL)

The framingham study: relationship between cholesterol and CHD risk

100

125

150

e pe

r 100

0

24Adapted from Castelli WP., Am J Med 1984; 76:4–12

0

25

50

75

<204(<5.3)

205-234(5.3–6.1)

235-264(6.1–6.8)

265-294(6.8–7.6)

>295(>7.6)

CH

D in

cide

nc

Serum total cholesterol, mg/dL (mmol/L)



35

Seven countries study: relationship of serum cholesterol to mortality

30

25

20CH

D/

CH

D/1

000

1000

men

men Northern Europe

United States

25Adapted from Verschuren WM et al., J Am Med Assoc 1995; 274(2):131–136

Serum total cholesterol, mmol/L (mg/dL)

15

10

5

0

Dea

th ra

te fr

om

Dea

th ra

te fr

om

2.60(100)

3.25(125)

3.90(150)

4.50(175)

5.15(200)

5.80(225)

6.45(250)

7.10(275)

7.75(300)

8.40(325)

9.05(350)

Southern Europe, Inland

Southern Europe, Mediterranean

Japan

Serbia

LDL cholesterol

Strongly associated with atherosclerosis and CHD events

10% increase results in an approximate 20% increase in CHD risk

26

Most of the cholesterol in plasma is found in LDL particles

Smaller denser LDL are more atherogenic than larger, less dense particles

Relationship between LDL-C and CV event rate

4S - Rx

4S - Pl

LIPID - Pl15

20

25

30

rate

(%)

- Secondary prevention- Primary prevention

Rx - Statin therapyPl - Placebo

27Adapted from Ballantyne CM et al., Am J Cardiol 1998; 82:3Q–12Q

LDL-C achieved mg/dL (mmol/L)

WOSCOPS - PlAFCAPS/TexCAPS - Pl

ASCOT - PlAFCAPS/TexCAPS - RxWOSCOPS - Rx

ASCOT - Rx

ALLHAT - Rx ALLHAT - Pl

HPS - Pl

LIPID - RxCARE - Rx

LIPID - Pl

PROSPER - PlCARE - Pl

HPS - Rx

PROSPER - Rx

0

5

10

15

70 (1.8) 90 (2.3) 110 (2.8) 130 (3.4) 150 (3.9) 170 (4.4) 190 (5.0) 210 (5.4)

Even

t



Prevalence of raised LDL cholesterol -EUROASPIRE III

P<0.0001

40%50%60%70%80%90%

100%

28S2 vs. S1 : P=0.001S3 vs. S2 : P<0.0001S3 vs. S1 : P<0.0001www.escardio.org

0%10%20%30%

Survey 1 95.4% 95.8% 0.0% 96.8% 97.9% 0.0% 0.0% 97.0% 96.4%Survey 2 87.8% 66.3% 78.7% 86.2% 73.0% 80.0% 64.5% 83.7% 78.1%Survey 3 49.4% 26.4% 36.8% 54.2% 59.9% 56.4% 37.2% 44.5% 47.5%

Czech Rep.

Finland France Germany Hungary Italy Nether-lands

Slovenia ALL

LDL C ≥ 2.5 mmol/L for patients fasting for at least 6 hours (calculated according to Friedewald formula)

HDL cholesterol

HDL-C has a protective effect for risk of atherosclerosis and CHD

Epidemiological studies show the lower the HDL-C level, the higher the risk for atherosclerosis and CHD

( / / )

29

– low level (<40 mg/dL, 1 mmol/L) increases risk

HDL-C tends to be low when triglycerides are high

HDL-C is lowered by smoking, obesity and physical inactivity

ApoA-I is the major apolipoprotein in HDL and an elevated apoA-I is linked to reduced CVD risk

Triglycerides

May be associated with increased risk of CHD events

Link with increased CHD risk is complex

– May be direct effect of smaller TG-rich lipoproteins and/or

– May be related to:

30

• low HDL levels

• highly atherogenic forms of LDL-C

• hyperinsulinaemia/insulin resistance

• procoagulation state

• hypertension

• abdominal obesity



50

60

70

80

90

100

% Cumulativefrequency

Cumulative distribution of adjusted plasma TG levels: LDL phenotypes A and B

31

0

10

20

30

40

50

20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 500

Phenotype APhenotype B

frequency

TG (mg/dL)

Austin M et al., Circulation, 1990; 82:495-506

1 5

2.0

2.5

3.0 Men

Women

RR

Impact of TG levels on relative risk (RR) of CHD: Framingham heart study

32

0.0

0.5

1.0

1.5

00,,5757 11,,1414 11,,7171 22,,3030 22,,9090 33,,4040 44,,0000 44,,6060

TG (mmol/L)

Castelli WP, Can J Cardiol, 1988; 4:5A-10A

ApolipoproteinsProtein content of lipoproteins

ApoB levels used to estimate LDL particle number and increased CVD risk

ApoA-I - major apolipoprotein in HDL and is linked to reduced CVD risk

33

Functions of apolipoproteins include:

– Facilitation of lipid transport

– Activation of three enzymes in lipid metabolism

• lecithin cholesterol acyltransferase (LCAT)

• lipoprotein lipase (LPL)

• hepatic triglyceride lipase (HTGL)

– Binding to cell surface receptors



INTERHEART

Cases: First MI (~15,000)

Controls: Matched to cases by age (+/-5 yr and sex) at each site (~15,000)

Data collected from 262 sites in 52 countries:

Coordinated by the population health research institute,

McMaster University, Canada

34

Questionnaire: Demographics, lifestyle, health hx, psychosocial, medications

Physical measures: Height, weight, waist & hip circum, blood pressure, heart rate

Blood sample: 20 ml

Statistical: OR and PAR both presented with 99% confidence intervals

Methods: All analyses adjusted for age, sex and region

ApoB/ApoA1 (5 v 1)

Curr smoking

Diabetes

Risk of AMI associated with risk factors in the overall population

Risk factor % Cont % Cases OR (99% CI) adj for age, sex, smoking

OR (99% CI) adj for all

20.0 33.5 3.87 (3.39, 4.42) 3.25 (2.81, 3.76)

26.8 45.2 2.95 (2.72, 3.20) 2.87 (2.58, 3.19)

7.5 18.4 3.08 (2.77, 3.42) 2.37 (2.07, 2.71)

35

Hypertension

Abd obesity (3 v 1)Psychosocial

Veg & fruits daily

Exercise Alcohol intake

21.9 39.0 2.48 (2.30, 2.68) 1.91 (1.74, 2.10)

33.3 46.3 2.22 (2.03, 2.42) 1.62 (1.45, 1.80)- - 2.51 (2.15, 2.93) 2.67 (2.21, 3.22)

42.4 35.8 0.70 (0.64, 0.77) 0.70 (0.62, 0.79)

19.3 14.3 0.72 (0.65, 0.79) 0.86 (0.76, 0.97)24.5 24.0 0.79 (0.73, 0.86) 0.91 (0.82, 1.02)

All combined - - 129.2 (90.2, 185.0) 129.2(90.2, 185.0)

All combined (extremes) 333.7 (230.2, 483.9) 333.7 (230.2, 483.9)

Risk factors and risk of MI

Smoking

Diabetes

Hypertension

Abd. Obesity

← Women← Men

36

Psychol index

Fruits/Veg

Exercise (-)

Alcohol (-)

Apo B / Apo AI

Yusuf S et al., INTERHEART Lancet 2004; 364:937-952

Odds ratio (99% Cl)



ApoB/ApoA-I as a predictor of risk: INTERHEART study

R IM % C

I)

4

8

37ApoB/ApoA-I ratio (deciles)

OR

(95%

1 2 3 4 5 6 7 8 9 100.75

1

2

Yusuf S et al., INTERHEART Lancet 2004; 364:937-952

INTERHEART: conclusion

The nine factors studied accounted for 90%

of the population associated risk in men and 94%

in women (93% in young men and 96% in young

38

women); This association was seen in all

ethnic/national

groups studied

Lancet 2004;364:937-952

More accurate indicators of plasma atherogenic phenotype

Particle size of HDL, LDL and VLDL subpopulations

Esterification rate of cholesterol in HDL plasma

39

(FER HDL )

AIP – Atherogenic index of plasma /Log(TG/HDL-C)



CAD risk and HDL particle size

HDL2b largeprotective particles

40

HDL2a,3a particles of medium size

HDL3b,c smallatherogenic particles

RISKRISK

HDL protectiveHDL protective andand riskrisk particlesparticles

40

50

410

10

20

30%

Men DM2 Men Women

HDL2b HDL3b

CAD risk and LDL particle size

LDL particles bigger than 25,5nm – non-atherogenic pattern (A)

42

LDL particles smaller than 25,5nm – atherogenic pattern (B)

25,5nm

RISK



LDL sub-fractions

LDL ILDL IILDL III

penetrance oxidationscavenger receptor

43

LDL ILDL IILDL III

d= 1.04-1.06 kg/l d= 1.02-1.03 kg/ld= 1.03-1.04 kg/l

26.0 nm 27.0 nm26.6 nm

CAD risk and VLDL particle size

VLDL large particles 60-100nm - atherogenic

RISK

44

VLDL small particles30-40nm – non atherogenic

TG and HDL-C levels determinelipoprotein particle size

TGSmall LDL

Small HDL

Large VLDL

45

HDL-C

Large VLDL

Increased FERHDL



Smoking as a risk factor for CVD

46

8,000cancer*

7,000vascular disease

47

* Incl. 5000 (87%) deaths of overall 5726 of lung cancer

2,000respiratory

1,000other

Cummulative tobacco related death ratewordlwide (Peto, 1999)

orld

wid

e (m

illio

ns)

current trend unchanged

if only one half of the young started smoking in 2020

if only one half of the current adult

48

Toba

cco

rela

ted

deat

hs w

o if only one half of the current adult smokers smoked in 2020

Year



Smoking and MI risk (Parish, 1995)

RR of MI

6,3

4,7

30-39 yr

40-49 yr

Age

49Relative (RR) risk of MI in smokers and non-smokers

MIs in smokers

MIs in non-smokers

3,1

3,5

1,9

50-59 yr

60-69 yr

70-79 yr

CHD risk and smoking: dose dependence

of is

chae

mic

as

e ev

ent

2.0

1.5

50Law MR, Wald NJ. Environmental tobacco smoke and ischemic heart disease; Prog Cardiovasc Dis 2003; 46: 31-8

No of cigarettes smoked a day

Rel

ativ

e ris

k o

hear

t dis

ea

1.3

1.00 5 10 15 20 25 30

Passive smoking represents almost the same risk (80-90 %) as active smoking

(Barnoya J, Glantz SA: Cardiovascular effects of secondhand smoke: nearly as large as smoking; Circulation, 2005 May 24; 111(20):2684-98)

In EU every day one restaurant employee dies

51

due to passive smoking exposure at work

Incidence of MI in Italy decreased by 11 % after non-smoking restaurants law passed



Smoking and atherogenesis

Hemodynamics↑ BP↑ HR

Worsening of RFHypertensionType 2 DM

ObesityEnvironment Hemocoagulation

↑ Fibrinogen↑ PAI I

52

↑ HR↑ Shear stress

↑ CO

Neurohumoral regulation

Sympatic ns (KA)ACH, serotonin, NO, vasopresin

MetabolismDyslipidemia

Glucose intoleranceInsulin resistence

↑ PAI I↑ Plt aggregability

Smoking

↑ Fibrinogen

↑ Platelets

Activated platelets

↑ Erytrocytes (CO)

53

↑ Leucocytes (chronic inflammation)

Damaged endothelium (radicals)

Polycytemia, ↑ fluidity, ↑ coagulability

↑ Dyslipidemia

↑ Insulin resistance...

Endothelium damage after tobacco smoke exposure (1h)

Before

54Bernhardt et al., 2003

After



Prevalence of smokingEUROASPIRE III

P=0.6420%30%40%50%60%70%80%90%

100%

55S2 vs. S1 : P=0.83S3 vs. S2 : P=0.37S3 vs. S1 : P=0.48

* Self-reported smoking or CO in breath > 10 ppm

www.escardio.org

0%10%20%

Survey 1 22.0% 12.8% 25.0% 16.8% 23.3% 18.6% 31.8% 13.3% 20.3%Survey 2 19.3% 21.6% 24.2% 16.8% 30.1% 15.1% 28.3% 14.6% 21.2%

Survey 3 22.2% 16.8% 24.8% 18.4% 18.3% 14.0% 15.1% 12.0% 18.2%

Czech Rep.


Slovenia ALL

Diabetes: a risk factor for CVD

56

Diabetes mellitusOne of the most common non-communicable diseases

Fourth or fifth leading cause of death in most developed countries

More than 177 million people with diabetes worldwide

57

Incidence of diabetes is increasing — estimated to rise to 300 million by 2025

– Expected to triple in Africa, the Eastern Mediterranean and Middle East, and South-East Asia

– To double in the Americas

– To almost double in Europe

Adapted from International Diabetes Federation website



Mill

ions

Mill

ions

Estimates and projections for numbers of incident of type 2 diabetes (worldwide 1997-2025)

200

250

300

350

215

270*

58

MM

Adapted from Zimmet P.Z. Diabetologia 1999; 42: 499-518King H. Diabetes Care 1998; 21: 1414-1431

* * ≥≥ 20 20 years of ageyears of age

0

50

100

150

120150

Types of diabetes mellitus

Type 1 diabetes (insulin-dependent diabetes)

– Mainly in childhood/early adult life

– 10–20% of cases

Type 2 diabetes (non-insulin-dependent diabetes)

59

– Usually develops in the middle-aged/elderly

– Incidence increasing at a younger age

– 80–90% of cases

At least 50% of all people with diabetes are unaware of their condition

Adapted from International Diabetes Federation website

The chronic complications of diabetes mellitus (US)

Macrovascular complications:

Cardiovascular disease

– Leading cause of diabetes related deaths (increases mortality and stroke by 2 to 4 times)

60

Microvascular complications:

Retinopathy

– Leading cause of adult blindness

Nephropathy

– Accounts for 43% of new cases of ESRD

Neuropathy

– 60–70% of patients with diabetes have nervous system Adapted from National Diabetes Statistics US 2000



UKPDS: typical lipid profile in patients with diabetes compared with no diabetes

Women

Men

Women(232)

(224)

5.6

5.8

6 P<0.001

Men(147)

(154)

3.6

3.8

4

61Adapted from UKPDS; Diabetes Care 1997; 20:1683-1687

DMno DM

no DM DM

(193)

(216)

(208)

(201)

5

5.2

5.4

Total cholesterol mmol/L (mg/dL)

DMno DM

no DM DM

(116)

(124)

(131)

(139)

3

3.2

3.4

LDL-C mmol/L (mg/dL)

The major abnormality is not increase in cholesterol

OASIS: patients with diabetes at similar risk to no diabetes with CVD

-

62Adapted from Malmberg K et al., Circulation 2000;102:1014–1019

BARI: diabetes results in less favourable outcome after angioplasty than no diabetes

2525

3030

3535

lity

(%)

CABG PTCA

63

00

55

1010

1515

2020

No diabetes Diabetes

5-ye

ar m

orta

l CABG PTCA

Adapted from BARI Investigators; N Engl J Med 1996: 335:217–225



NHANES: smaller changes in CAD mortality rates in patients with diabetes than no diabetes over time

*P<0.001 vs. baseline

talit

y du

e to

IHD

0

10

20

64

*Diabetes No diabetes

Adapted from Gu K et al., JAMA 1999; 281:1291–1297

Per

cent

cha

nge

in m

ort

-50

-40

-30

-20

-10MenWomen

Prevalence of diabetesEUROASPIRE III

P=0.004

10%20%30%40%50%60%70%80%90%

100%


* Self-reported history of diagnosed diabetes

www.escardio.org

0%10%

Survey 1 21.8% 15.4% 16.7% 13.5% 26.6% 17.2% 10.3% 17.4% 17.4%Survey 2 21.5% 18.7% 27.5% 13.5% 21.1% 21.8% 13.2% 23.8% 20.1%

Survey 3 30.8% 19.1% 34.2% 22.6% 44.8% 21.7% 20.6% 18.8% 28.0%

Czech Rep.


Slovenia ALL

The metabolic syndrome

66



Hypertension

Abdominal obesity

Hyperinsulinaemia

The metabolic syndrome and associated CVD risk factors

AtherosclerosisAtherosclerosis

67

Dyslipidaemia• high TGs

• small dense LDL• low HDL-C

Diabetes

Hypercoagulability

Insulin resistance

Endothelial dysfunction

Adapted from Deedwania PC; Am J Med 1998; 105(1A):1S–3S

Criteria for diagnosis of the metabolic syndrome

IDF (2005)WC criteria is required, + any 2 of:

WC ≥ 94 cm for men ≥ 80 cmfor women

TG 1 7 l/L ifi

AHA/NHLBI (2005)Any 3 of 5 features

• WC ≥ 102 cm in men, ≥88 cm in women

• TG ≥ 1.7 mmol/L or drug treatment

68

TG ≥ 1.7 mmol/L or specific treatment

HDL< 1.0 mmol/L in males and < 1.3 mmol/L in females

BP ≥ 130 mm/Hg systolic or ≥ 85 mm/Hg diastolic ≥5.6 mmol/L

Blood glucose ≥ 5.6 mmol/L or treatment

• HDL < 0.9 mmol/L in men, < 1.1 mmol/L in women, or drug treatment

• BP ≥130 mm/Hg systolic or≥ 85 mm/Hg diastolic or drug treatment

• Blood glucose ≥ 5.5 mmol/L or drug treatment

Prevalence of MetS in the USA - NHANES

253035404550

nce

Met

S (%

)

menwomen

69

05

101520

20-70… 20-29 30-39 40-49 50-59 60-69 >70

age (years)

Pre

vale

n women



MetS and CVDNHANES III

1.5

2

2.5

/stro

ke

70

0

0.5

1

MetS TG HT HDL-c insulinresistance

obesity

Risk factors

OR

MI

Subjects with MetS have significantly higher rates of subclinical atherosclerosis and CHD

P = 0.021

P= 0.002

34%

51 %

35%

cide

nce

Subjects with MetS

Subjects without MetS

71Bonora F et al., Diabetes Care 2003; 26:1251-1257

P = 0.012

8%3%

19%

New carotid plaques Carotid stenosis >40% CHD

5 Ye

ar in

c

Overweight and obesity as a risk factorNow reached epidemic proportions in Western society

– 220,000 deaths per year in US and Canada

– 320,000 deaths per year in Western Europe (20 countries)

Associated with significant mortality and morbidity

An independent risk factor for CVD

72

p

Abdominal obesity associated with the metabolic syndrome which also includes:

– dyslipidaemia

– hypertension

– insulin resistance

Adapted from The World Health Report 2002 and International Cardiovascular Disease Statistics 2003; AHA



Prevalence of obesity

EUROASPIRE III

P=0.0006

30%40%50%60%70%80%90%

100%


* Body mass index ≥ 30 kg/m²

www.escardio.org

Survey 2 40.1% 33.6% 37.5% 30.6% 36.8% 23.6% 28.2% 28.0% 32.6%

Survey 3 37.9% 26.4% 36.8% 43.1% 49.3% 29.4% 26.5% 39.1% 38.0%

0%10%20%30%

Survey 1 31.4% 29.6% 33.4% 23.0% 23.3% 22.4% 18.9% 19.2% 25.0%

Czech Rep.


Slovenia ALL

Survival of the fittest(New Eng J Med 2002; 346:793-801 & 852-853)

2,534 men without and 3,679 men with CAD referred for exercise test

1,256 died within 6 years (2.6% annually)

Risk of death for those with peak exercise capacity

74

p p yof <5 MET was double the risk of those achieving >8 MET (regardless of the presence of other risk factors)

In women low fitness is a more important predictor of CVD than BMI or fat distribution

(JAMA 2004; 292:1179-87)

How to assess the risk?

75

RISK



Risk assessment (1)

Scoring systems

Charts

76

Algorithms

Computer assisted risk assessment tools

Risk assessment (2)

Aim:

– Identification of those at high risk and

treatment focusing

77

– Accurately and early

SCORE chart – ESC 2003(absolute risk of CVD death in 10 years)

Woman MenNon-smoker Smoker

ress

ure

ageNon-smoker Smoker

15% and over

5%-9%10%-14%

3%-4%

78Ten year risk of fatal CVD in high risk regions of Europe by gender, age, systolic blood pressure, total cholesterol and smoking status

Syst

olic

blo

od p

r

Cholesterol mmol

3%-4%2%1%<1%

10-year risk of fatal CVD in populations at high CVD risk



Framingham point score(absolute CAD risk in 10 years)

79

Atherosclerosis imaging (1)

Detection of subclinical atherosclerosis

More accurate risk assessment

Measuring the extent of atherosclerotic burden

80

Evaluation of efficacy of a therapeutic intervention

Research tool

Atherosclerosis imaging (2)

IMT determination

MR angiography

CT angiography

81

Calcium score of the coronaries

IVUS

Classical angiography



Intima media thickness (IMT)

Marker for early atherosclerosis, predictor of events

Lipid lowering is associated with reduced progression

82

Cumulative event-free rates for the combined endpoint of MI or stroke

100

95

90

1st Quintile

2nd Quintile

t-fre

e R

ate

(%)

3rd Quintile

83O’Leary et al., NEJM 1999; 340: 14–22

0 1 2 3 4 5 6 7

85

80

75

70

4th Quintile

5th Quintile

Years

Cum

ulat

ive

even

t

internal carotidinternal carotid common carotidcommon carotidcarotid bulbcarotid bulb

Carotid IMT measurement

84

carotid dilatationcarotid dilatation

external carotidexternal carotid carotid flowcarotid flowdividerdivider

1010mmmm



IMT of carotid arteries

85

86

87



Carotid IMT is a validated surrogate measure of atherosclerosis

Simple, safe, noninvasive and relatively inexpensive

Represents a composite of the life-long effect of various risk factors on the arterial wall

88

of various risk factors on the arterial wall

Independent predictor of coronary heart disease events and stroke

Requires further standardization

Example of regression of atherosclerosis with rosuvastatin in ASTEROID, measured by IVUS

89

Images courtesy of Cleveland Clinic Intravascular Ultrasound Core Laboratory

CT angiography

90



Conclusion

Major traditional risk factors contribute most to the overall CVD risk

Metabolic syndrome and type 2 diabetes are driving forces of the new CVD epidemic

M ltif t d t t t ti lti l i k f t

91

Multifaceted strategy targeting multiple risk factors is the only way to further reduce CVD risk

Effective use of all currently available preventive measures can lower the number of events by at least 50%

Thank you for your attention !

92

prof. michal vrablíklp (a) aip homocystein 19 metabolic syndrome obesity smoking lack of physical...

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