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ChangingCardiovascular risk environment
andthe interpretation of current guidelines
Dr P. Ismahun SpJP, FIHA
Malang, 21 Maret 2009
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Hypertension
Dyslipidemia
Diabetes
Mellitus Obesity
Risk Factors on Global CardiovascularDisease Burden
Smoking
Lp(a)
Homocystein
No exercise
Others (+ 200)
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Hypertension
Dyslipidemia
Diabetes
Mellitus Obesity
Smoking
Lp(a)
Homocystein
No exercise
Others (+ 200)
Joint effects of Risk Factors on GlobalCardiovascular Disease Burden
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Blood pressure and AtheromaLessons from veins
Veins dont develop atheroma even in peoplewith elevated Cholesterol low pressure system ;
Pulmonary Hypertension associated with
atheroma of pulmonary venous system ;
Venous grafts into coronary circulation (highpressure) develop atheroma ;
Pressure is permissive for the development of
atheroma ;
Logical to lower cholesterol and pressure toreduce the risk of developing atheroma.
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Normal Prehypertension Hypertension
JNC 7 Categories
30
25
20
15
10
5
0
-5
-10
-15
-20
P < 0.001
P = 0.01
P = 0.039
Changei
nAtheromavolume(mm3)
Effect of Blood Pressure onProgression of Coronary Atheroma
J Am Coll Cardiol 2006;48: 833-8
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Majority of US Hypertensive Patients Not at
SBP Goal of
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NHANES = National Health and Nutrition Examination Survey; SBP = systolic blood pressure;
DBP = diastolic blood pressure.
Burt VL et al. Hypertension. 1995;26:60-69.Whyte JL et al. J Clin Hypertens. 2001;3:211-216.
NHANES III: Poor Systolic BP Control
Underlies Inadequate BP Control Overall
Only 34.3%
Reach SBP Goal
73% Reach DBP Goal
250
DBP(mm Hg)
50
100
150
200
140
0 50 100 150
9023.6% 10.7%
49.6% 16.1%SBP(mm Hg)
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Coronary Disease by Usual SBP
Usual SBP (mm Hg)
HazardRatioand
95%CI
32.0
16.0
8.0
4.0
2.0
1.0
0.5
110 120 130 140 150 160
-10 mm Hg
70 years
60-69 years
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2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 10.5 11.0
Men 30-59 years, Serum cholesterol (mmol/l)
25
20
15
10
5
0
Year 72778287
92
Serum cholesteroldistribution by study year,men aged 30 to 59 years inFinland
Jousilahti, P. et al. Circulation 1998;97:1087-1094
5 Mmol/l = 193 mg/dl
6 Mmol/l = 231.6 mg/dl
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50
40
30
20
10
0
5.5
5
4.5
4
3.5
3
2.5
2
1.5
1
0.5
0
Serum Cholesterol CHD deaths Odds ratio
5.0 5.0-6.49 6.5-7.99 >8.0
Serum Cholesterol level (Mmol/l)
Distribution of serumcholesterol and
coronary heart disease(CHD) deaths of men inFinland, aged 30 to 59years (1972, 1977, and1982 cohorts combined)
and odds ratio of CHDmortality associatedwith serum cholesterol
Jousilahti, P. et al. Circulation
1998;97:1087-1094
5 Mmol/l = 193 mg/dl
6 Mmol/l = 231.6 mg/dl
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2.00
1.00
0.50
0.25
3.6 3.8 4.0 4.2 4.4 4.6 4.8
139 147 155 162 170 178 186
Mean Usual Cholesterol (mmol/L, mg/dL)
9
4
12
18
What is Normal Cholesterol ?
Relative risk of death (+) from CHD by quartiles of baseline total
cholesterol in 9021 Chinese people with 8 13 years follow-up.
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What we define
asnormalvalues for BloodPressure and Cholesterol are basedon usual values for our
populationsthese are not normalvalues for a human being, they arethe usual values of a human being
at risk of dying prematurely fromvascular disease
B. Williams, 2006
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The Population Burden ofCardiovascular Disease is in thosepeople with modest elevations ofmultiple risk factors, NOT thosewith single, extreme elevations ofsingle risk factors.
B. Williams, 2006
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MI=myocardial infarction; PS=psychosocial.
Reproduced with permission from Yusuf S et al. Lancet. 2004;364:937-952.Please see prescribing information at the end of this slide presentation.
Increased Number of CV Events (MI) in Patients
with Hypertension Plus Other CV Risk Factors
OddsRatio(99%C
I)
512
256
128
64
32
16
8
4
2
1
2.9(2.6-3.2)
2.4(2.1-2.7)
1.9(1.7-2.1)
3.3(2.8-3.8)
13.0(10.7-15.8)
42.3(33.2-54.0)
68.5(53.0-88.6)
182.9(132.6-252.2)
333.7(230.2-483.9)
Smoking(1)
Diabetes(2)
HTN(3)
Lipids(4)
1+2+3 All 4 + Obes + PS All RFsRisk Factors
Risk Ratio
HTN + 3 RiskFactors
HTN >20-Fold Increase
OR from 1.9 (HTN only) to
42.3
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Multiple CV Risk Factors in Addition toHypertension Result in a High CVD Risk
*Reference=nondiabetic, nonsmoker woman, aged 50 years with total cholesterol (TC)=4.0 mmol/L
and HDL-C=1.6 mmol/L.Jackson R et al. Lancet. 2005;365:434-441.
Increasing No. of Additional Risk Factors
0
5
10
15
20
25
30
35
40
45
50
5-YearCVDRis
kper100Peop
le
+ 60years
+ Diabetes+ Male+ HDL-
1 mmol/L
+ Smoker+ TC-7 mmol/L
Reference
3%6%
12%
18%
24%
33%
44%110
120
130
140
150
160
170
180
BP (mm Hg)
M H i P i H Addi i l
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90.3%with 3 risk factors
Most Hypertensive Patients Have AdditionalRisk Factors
REACH Registry
81.8%HTN*
Bhatt DL et al. JAMA. 2006;295:180-189.
*140/90 mm Hg at baseline.
Risk factors include: treated diabetes mellitus, diabetic nephropathy, asymptomatic
carotid stenosis 70%, Systolic blood pressure [SBP], 150 mm Hg, treated
hypercholesterolaemia, current smoking, men 55 y, women 70 y.
N=67,888patients aged45 years orolder from 44countries
HTN=hypertension;
REACH=Reduction of
Atherothrombosis for
Continued Health.
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Wong ND et al.Arch Intern Med2007; 167: 2431-2436.
NHANES :Prevalence ofhypertension, treated and controlled,
in patient subsets by comorbidity
Population subset HTNprevalence(%)
HTNtreated
(% of thosewith HTN)
HTNcontrolled
(% of thosewith HTN)
No CV comorbidities 23.1 66.5 64.6
HTN and dyslipidemia 51.8 68.0 49.3
HTN and diabetes 73.7 84.0 61.2a
HTN and CKD 81.8 65.9 42.2b
HTN and heart failure 71.4 83.4 48.8
a.`Rate based on treatment goal
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1. Prospective Studies Collaboration, Lancet,2002;300:1903-1913; 2. Rodgers A et al,Pros Medicine, 2004;1; 3. Cholesterol Treatment Trials Collaborators, Lancet,2005.
Preventing Cardiovascular Disease
High BP and High Cholesterol are majorrisk factors for CHD and Stroke Most people who develop CHD or Strokedo not have very high BP or Cholesterol
values but their values are not normal,either !
Treating only those people with significant
elevations of single risk factors will notprevent most CHD or strokes and will leave
most people at risk
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34
21
17
13
12
23
12
810
6
18
11
9
6
6
17
8
8
6
4
14
56
3
3
142+
125-131
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Class
WG-ASH Definition andClassification of Hypertension ( 2005 )
C.V.Class
B.P
ElevationC.V.D. Risk
Factor
Early Disease
Markers
Target Organ
Disease
Normal
Hypertension
Stage
1
Stage
2
Stage
3
Normal
or rareNone None
or fewNone None
Occasional /
Intermittent
> 120/80
Sustained
> 140/90
Marked &
Sustained
>140/90 &
>160/90
Early
Progre
ssive
Advan
ced
Several
Many
Many
Usually
present
Overtly
present
Overtly
present with
progression
None
Early signs
present
Overtly
present
with or without
CVD events
Writing Group of the American Society of Hypertension (WG-ASH) ; 2005
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JNC 7 2003
WritingGroup of the
American
Society ofHypertension
(WG-ASH)2005
EuropeanSociety of
Hypertension2003
EuropeanSociety of
Hypertension /
EuropeanSociety ofCardiology(ESH/ESC)
2007
BritishHypertensionSociety (BHS)
NICE 2004
Update 2006( National
Institute for
health andClinical
Excellence)
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Algorithm for Treatment of Hypertension(JNC 7 2003 )
Not at Goal Blood Pressure (100 mmHg)
2-drug combination for most(usually thiazide-type diuretic and
ACEI, or ARB, or BB, or CCB)
Stage 1 Hypertension(SBP 140159 or DBP 9099
mmHg)Thiazide-type diuretics for most.
May consider ACEI, ARB, BB, CCB,or combination.
Without CompellingIndications
Not at GoalBlood Pressure
Optimize dosages or add additionaldrugs
until goal blood pressure is achieved.
Consider consultation with hypertensionspecialist.
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A : ACE inhibitor or
Angiotensin Receptor Blocker
B : Betablocker
C : Calcium Channel Blocker
D : Diuretic
Younger ( < 55 years )
and non Black
Older ( > 55 years )
or Black
A C or D
A ( or B ) + C or D
A ( or B ) + C + D
Add either Alpha blockeror Spironolactoneor other Diuretic
Step 1
Step 2
Step 3
Step 4Resistant Hypertension
NICE / BHS 2007
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2004 PPS
Expert Panel on Detection, Evaluation, and Treatment ofHigh Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497.
High240
Borderline high200239Desirable
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2004 PPS
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Assessing CVD risk: the effect of high blood pressure
2007 guidelines on hypertension of the European Society of Hypertension (ESH) and the EuropeanSociety of Cardiology (ESC) OD: subclinical organ damage, MS: metabolic syndrome.
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Nondiabetic Men
180
160
SBP 140
120
100
180
160
SBP 140
120
100
180
160
SBP 140
120
100
180
160
SBP 140
120
100
180
160
SBP 140
120
100
180
160
SBP 140
120
100
3 4 5 6 7 8 9 10TC : HDL
3 4 5 6 7 8 9 10TC : HDL
3 4 5 6 7 8 9 10
TC : HDL
3 4 5 6 7 8 9 10
TC : HDL
Non smoker Smoker
Age under 50 years
Age 50 59 years
3 4 5 6 7 8 9 10
TC : HDL
3 4 5 6 7 8 9 10
TC : HDL
Age 60 years and over
CVD risk 20% over next 10 year
Copyright University
of Manchester
CVD risk over
next 10 years
30%
10% 20%
SBP = Systolic blood Pressure
TC : HDL = Total Cholesterol to
HDL Cholesterol ratio
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Non smoker Smoker
Age under 50 years180
160
SBP 140
120100
180
160SBP 140
120
100
180
160
SBP 140
120
100
180
160
SBP 140
120100
180
160SBP 140
120
100
180
160
SBP 140
120
100
3 4 5 6 7 8 9 10
TC : HDL
3 4 5 6 7 8 9 10
TC : HDL
3 4 5 6 7 8 9 10
TC : HDL
3 4 5 6 7 8 9 10
TC : HDL
3 4 5 6 7 8 9 10TC : HDL
3 4 5 6 7 8 9 10TC : HDL
Age 50 59 years
Age 60 years and over
Copyright University
of Manchester
CVD risk over
next 10 years
30%
10% 20%
SBP = Systolic blood Pressure
TC : HDL = Total Cholesterol to
HDL Cholesterol ratio
Nondiabetic Women
CVD risk 20% over next 10 year
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180
160
SBP 140
120
100
180
160
SBP 140
120
100
180
160
SBP 140
120
100
180
160
SBP 140
120
100
180
160
SBP 140
120
100
180
160
SBP 140
120
100
3 4 5 6 7 8 9 10TC : HDL
3 4 5 6 7 8 9 10TC : HDL
3 4 5 6 7 8 9 10
TC : HDL
3 4 5 6 7 8 9 10
TC : HDL
Non smoker Smoker
Age under 50 years
Age 50 59 years
3 4 5 6 7 8 9 10
TC : HDL
3 4 5 6 7 8 9 10
TC : HDL
Age 60 years and over
Nondiabetic Men
Chart for men and women
No chart for diabetesTreat diabetes as > 20% CVD risk
i.e. as coronary equivalents
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Primary Prevention:> 20% CVD risk over 10 years:
Secondary Prevention:
Any Vascular disease or Target organ damage or Diabetes
Treat stage 1 hypertension (> 140/90 mmHg)Prescribe statin ( irrespective of baseline total Cholesterol )Target total Cholesterol
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Most Hypertensive Patientsare at sufficient CVD risk to
benefit from a statin,irrespective of their baseline
cholesterol level
M lti l Ri k F t M t R lt
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Multiple Risk Factor Management Resultsin Greater CVD Risk Reduction
Williams B. J Am Coll Cardiol. 2005;45:813-827. Reproduced with permission from Professor Bryan Williams.
Likelihood of a Major Cardiovascular Event in theNext 10 Years in 100 People Like You
Cardiovascular Events Expected
Without Drug Therapy
M lti l Ri k F t M t R lt
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Cardiovascular Events Prevented
by Antihypertensive Therapy
Multiple Risk Factor Management Resultsin Greater CVD Risk Reduction
Likelihood of a Major Cardiovascular Event in theNext 10 Years in 100 People Like You
Williams B. J Am Coll Cardiol. 2005;45:813-827. Reproduced with permission from Professor Bryan Williams.
M lti l Ri k F t M t R lt
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Optimising Hypertension Management by Addition ofStatin Therapy May Reduce CV Events by Half
Events Prevented by
Antihypertensive TherapyEvents Prevented by
Adding Statin Therapy
Multiple Risk Factor Management Resultsin Greater CVD Risk Reduction
Likelihood of a Major Cardiovascular Event in theNext 10 Years in 100 People Like You
Williams B. J Am Coll Cardiol. 2005;45:813-827. Reproduced with permission from Professor Bryan Williams.
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2000 2001 2002 2003 2004 2005
Co-Prescribing of a Statin in Hypertension( England; n = 5,5 million )
%H
ypertens
ivePatientsC
o-prescribing
statin
35%
30%
25%
20%
15%
10%
5%
0%
B. Williams, 2006
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2000 2001 2002 2003 2004 2005%H
ypertens
ivePatientsC
o-prescribingstatin
Co-Prescribing of a Statin in Hypertension
with Diabetes.( England; n = 5,5 million )
80%
70%
60%
50%
40%
30%
20%
10%
0%
B. Williams, 2006
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Benefits of systems reform
UK changing trends
35% reduction in cardiovascular
mortality in 5 years ( 2000 2005 )
B. Williams, 2006
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ConclusionCVD is preventable;
Available treatments ( especially BP
lowering and statins ) are very effective
at reducing CVD risk and mortality;
You do not need high BP and high
cholesterol to benefit from treatment
you only need high CVD risk;
CVD risk assessment should be simple;
The benefits of treatment are very large
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