Prof. Michal VrablíkLp (a) AIP homocystein 19 Metabolic syndrome Obesity Smoking Lack of physical...
Transcript of Prof. Michal VrablíkLp (a) AIP homocystein 19 Metabolic syndrome Obesity Smoking Lack of physical...
Cardiovascular Risk FactorsProf. Michal Vrablík
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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
Cardiovascular Risk FactorsProf. Michal Vrablík
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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
Cardiovascular Risk FactorsProf. Michal Vrablík
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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 (%)
Cardiovascular Risk FactorsProf. Michal Vrablík
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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 !
Cardiovascular Risk FactorsProf. Michal Vrablík
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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
Cardiovascular Risk FactorsProf. Michal Vrablík
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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 (?)
Cardiovascular Risk FactorsProf. Michal Vrablík
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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
Cardiovascular Risk FactorsProf. Michal Vrablík
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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)
Cardiovascular Risk FactorsProf. Michal Vrablík
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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
Cardiovascular Risk FactorsProf. Michal Vrablík
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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
Cardiovascular Risk FactorsProf. Michal Vrablík
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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
Cardiovascular Risk FactorsProf. Michal Vrablík
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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)
Cardiovascular Risk FactorsProf. Michal Vrablík
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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)
Cardiovascular Risk FactorsProf. Michal Vrablík
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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
Cardiovascular Risk FactorsProf. Michal Vrablík
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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
Cardiovascular Risk FactorsProf. Michal Vrablík
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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
Cardiovascular Risk FactorsProf. Michal Vrablík
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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
Cardiovascular Risk FactorsProf. Michal Vrablík
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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
Cardiovascular Risk FactorsProf. Michal Vrablík
19The screen versions of these slides have full details of copyright and acknowledgements
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.
Finland France Germany Hungary Italy Nether-lands
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
Cardiovascular Risk FactorsProf. Michal Vrablík
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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
Cardiovascular Risk FactorsProf. Michal Vrablík
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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
Cardiovascular Risk FactorsProf. Michal Vrablík
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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%
65S2 vs. S1 : P=0.21S3 vs. S2 : P=0.02S3 vs. S1 : P=0.001
* 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.
Finland France Germany Hungary Italy Nether-lands
Slovenia ALL
The metabolic syndrome
66
Cardiovascular Risk FactorsProf. Michal Vrablík
23The screen versions of these slides have full details of copyright and acknowledgements
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
Cardiovascular Risk FactorsProf. Michal Vrablík
24The screen versions of these slides have full details of copyright and acknowledgements
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
Cardiovascular Risk FactorsProf. Michal Vrablík
25The screen versions of these slides have full details of copyright and acknowledgements
Prevalence of obesity
EUROASPIRE III
P=0.0006
30%40%50%60%70%80%90%
100%
73S2 vs. S1 : P=0.009S3 vs. S2 : P=0.051S3 vs. S1 : P=0.0002
* 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.
Finland France Germany Hungary Italy Nether-lands
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
Cardiovascular Risk FactorsProf. Michal Vrablík
26The screen versions of these slides have full details of copyright and acknowledgements
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
Cardiovascular Risk FactorsProf. Michal Vrablík
27The screen versions of these slides have full details of copyright and acknowledgements
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
Cardiovascular Risk FactorsProf. Michal Vrablík
28The screen versions of these slides have full details of copyright and acknowledgements
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
Cardiovascular Risk FactorsProf. Michal Vrablík
29The screen versions of these slides have full details of copyright and acknowledgements
IMT of carotid arteries
85
86
87
Cardiovascular Risk FactorsProf. Michal Vrablík
30The screen versions of these slides have full details of copyright and acknowledgements
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
Cardiovascular Risk FactorsProf. Michal Vrablík
31The screen versions of these slides have full details of copyright and acknowledgements
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