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Blood pressure parameters and pulse wave velocity for cardiovascular-renal prevention
Jacques Blacher
Unité HTA, prévention et thérapeutique cardiovasculaires Centre de diagnostic et de thérapeutique, Hôtel-Dieu, Paris
May 2015
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Disclosures Jacques Blacher
∙ No financial participation in the capital of a healthcare company.
∙ No permanent interest (work contract, regular remuneration...) in a healthcare company.
∙ Occasional direct and indirect interests (clinical trials, scientific work, scientific committees, expert reports, conferences, colloquia, training courses, participation at various symposia, writing of brochures...), remunerated where appropriate, for most companies that market cardiovascular drugs or other medicinal products used in my areas of expertise (ARDIX-THERVAL, AMGEN, ASTRAZENECA, BAYER, BMS, BOUCHARA RECORDATI, DAÏCHI SANKYO, DANONE, EUTHERAPIE, GSK, IPSEN, MENARINI, MERCK SERONO, MSD, NOVARTIS, PIERRE FABRE, PILEJE,
ROCHE, SANOFI, SERVIER, TAKEDA).
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Risk assessment strategies
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Risk assessment strategies
• Systolic versus diastolic ?• Pulse pressure versus systolic ?• Young versus old ?• Central versus peripheral ?• PWV versus BP ?• Comparison of different biomarkers -
problem of intercorrelations
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Risk of CHD Death According to Systolic BP and Diastolic BP in MRFIT
Stamler et al. Arch Intern Med. 1993;153:598-615.
<112 112- 118- 121- 125- 129- 132- 137- 142- ? 151Systolic BP (mm Hg)
0
1
2
3
4
1 2 3 4 5 6 7 8 9 10
Systolic
Diastolic
(Lowest 10%) (Highest 10%)
Ad
just
ed R
elat
ive
Ris
k
Decile
<71 71- 76- 79- 81- 84- 86- 89- 92- ? 98Diastolic BP (mm Hg)
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Risk assessment strategies
• Systolic versus diastolic ?• Pulse pressure versus systolic ?• Young versus old ?• Central versus peripheral ?• PWV versus BP ?• Comparison of different biomarkers -
problem of intercorrelations
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Darné B et al. Pulsatile versus steady component of blood pressure: a cross-sectional analysis and a prospective analysis
on cardiovascular mortality. Hypertension 1989;13:392-400
• Blood pressure divided into 2 components: pulse and mean, rather than systolic and diastolic
• 18 336 men + 9351 women aged 40-69• Follow-up: 9.5 years• Strong correlation between PP and MAP• Principal component analysis = 2 independent parameters• Relation between pulsatile component and LVH• Relation between steady component index and CV death in
both sexes• Relation between pulsative component index and death from
CHD in women > 55
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Blacher et al. Arch Intern Med. 2000;160.
Pulse Pressure Predicts Risk Best In Older Hypertensives - A Meta-Analysis
2-Y
ear
Ris
k O
f E
nd
Po
int
Systolic Blood Pressure (mm Hg)
Diastolic Pressure (mm
Hg)
EWPHE (N=840)
Syst-Eur (N=4695)
Syst-China (N=2394)
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Mortality Rates (per 10000 person-years)in the 9 groups of patients
Cardiovascular Mortality
Benetos A. et al. Hypertens. 1999; 33: 44-52.
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Risk assessment strategies
• Systolic versus diastolic ?• Pulse pressure versus systolic ?• Young versus old ?• Central versus peripheral ?• PWV versus BP ?• Comparison of different biomarkers -
problem of intercorrelations
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Franklin S, et al. Hemodynamic Patterns of Age-Related Changes in Blood Pressure. The Framingham Heart Study. Circulation 1997; 96: 308-315.
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Franklin S. Does the relation of blood pressure to coronary heart disease risk change with aging ? Circulation.2001; 103: 1245-9.
Relative cardiovascular risk associated with SBP, DBP and PP
Single BP Components*
HR (95 % CI)†
Age < 50 ySBP 1.14 (1.06-1.24)++DBP 1.34 (1.18-1.51)+++PP 1.02 (0.89-1.17)
Age 50-59 ySBP 1.08 (1.02-1.15)+DBP 1.11 (0.99-1.24)PP 1.11 (1.02-1.22)+
Age 60 ySBP 1.17 (1.11-1.24)+++DBP 1.12 (0.99-1.27)PP 1.24 (1.16-1.33)+++
* SBP, DBP and PP were entered in separate models, adjusted for age, sex, body mass index, cigarette smoking, diabetes mellitus, and ratio of total to HDL cholesterol † HR was associated with 10 mm Hg increase in BP+ p<0.05, ++p<0.01, +++ p<0.001
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Risk assessment strategies
• Systolic versus diastolic ?• Pulse pressure versus systolic ?• Young versus old ?• Central versus peripheral ?• PWV versus BP ?• Comparison of different biomarkers -
problem of intercorrelations
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00
.25
0.5
00
.75
1
0 35 70 105 140
Pro
ba
bil
ity
of
su
rviv
al
Duration of follow-up (months)
Central PP 1st tertile
Central PP 2nd tertile
Central PP 3rd tertile
Probabilities of survival in the study population according to the level of central PP divided into tertiles. Comparison between
survival curves was highly significant (p<0.001)
Safar et al. Hypertension 2002
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0
0.25
0.50
0.75
1
0 35 70 105 140
AIX: 1st quartile
AIX: 2nd quartile
AIX: 3rd quartile
AIX: 4th quartile
Duration of follow-up (months)
Ca
rdio
va
scu
lar
su
rviv
al
Augmentation Index (AIX) and CV survival
London and al. Hypertension 2001
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00.
250.
500.
751
0 35 70 105 140
Pro
bab
ility
of
surv
ival
Duration of follow-up (months)
PP amplification 1st tertile
PP amplification 2nd tertile
PP amplification 3rd tertile
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Jankowski P, et al. Hypertension 2008 ; 51 : 848-55.
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Risk assessment strategies
• Systolic versus diastolic ?• Pulse pressure versus systolic ?• Young versus old ?• Central versus peripheral ?• PWV versus BP ?• Comparison of different biomarkers -
problem of intercorrelations
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Risk assessment strategies
• Systolic versus diastolic ?• Pulse pressure versus systolic ?• Young versus old ?• Central versus peripheral ?• PWV versus BP ?• Comparison of different biomarkers -
problem of intercorrelations
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Systolic Diastolic
Mean Pulse
Peripheral Central
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Area under ROC curves, crude and adjusted HRs per 1 SD increment
1.2 (0.9-1.6)1.5 (1.2-1.8)0.68±0.11172±46LV mass index
1.3 (1.0-1.7)2.1 (1.7-2.6)0.83±0.1111.7±3.1Aortic PWV
0.5 (0.3-0.8)0.2 (0.1-0.4)0.85±0.11110±16Bra./carot. PP
1.4 (1.1-1.8)2.2 (1.7-2.7)0.84±0.1168±25Carotid PP
1.2 (0.9-1.5)1.8 (1.5-2.3)0.78±0.1173±23Brachial PP
0.7 (0.9-1.2)0.8 (0.7-1.1)0.50±0.09108±17MBP
0.8 (0.6-1.0)0.5 (0.4-0.7)0.65±0.1083±15DBP
1.2 (0.8-1.4)1.6 (1.2-2.1)0.71±0.11152±29Carotid SBP
1.1 (0.8-1.3)1.3 (1.0-1.7)0.64±0.10156±28Brachial SBP
Adjusted HRCrude HRAUCMean±SDVariable
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Hypertension 2009
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Relative Integrated Discrimination Improvement (RIDI%) : major cardiovascular events
4% 20% 7% 13%-7%-13%
-15
-5
5
15
25
DBP vs
SBP
PP vs
SBP
MAP vs
SBP
PP vs
DBP
MAP vs
DBP
PP vs
MAP
RID
I (%
)
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From risk assessment to risk reduction strategies
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From risk assessment to risk reduction strategies
• Residual risk• Systolic versus diastolic ?• BP versus PWV ?• Peripheral BP versus central BP ?• Young versus old versus oldest old• Prevention of CAD versus prevention of
stroke ?• Prêt-à-porter versus haute couture
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0
1
2
3
4
120 150 180
Systolic blood pressure (mm Hg)
10-y
ear
CV
death
ris
k (
%)
Antihypertensive treatment
No antihypertensive treatment
0
5
10
15
20
120 150 180
Systolic blood pressure (mm Hg)
10-y
ear
fata
l o
r n
on
fata
l C
V r
isk
(%)
Antihypertensive treatment
No antihypertensive treatment
0
1
2
3
4
120 150 180
Systolic blood pressure (mm Hg)
10-y
ear
str
oke r
isk (
%)
Antihypertensive treatment
No antihypertensive treatment
0
5
10
15
20
120 150 180
Systolic blood pressure (mm Hg)
10-y
ear
CH
D r
isk (
%)
Antihypertensive treatment
No antihypertensive treatment
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From risk assessment to risk reduction strategies
• Residual risk• Systolic versus diastolic ?• BP versus PWV ?• Peripheral BP versus central BP ?• Young versus old versus oldest old• Prevention of CAD versus prevention of
stroke ?• Prêt-à-porter versus haute couture
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From risk assessment to risk reduction strategies
• Residual risk• Systolic versus diastolic ?• BP versus PWV ?• Peripheral BP versus central BP ?• Young versus old versus oldest old• Prevention of CAD versus prevention of
stroke ?• Prêt-à-porter versus haute couture
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IMPACT OF AORTIC STIFFNESS ATTENUATION ON SURVIVAL OF PATIENTS
IN END-STAGE RENAL FAILURE • 1st step: dry weight• 2nd step: ACE inhibitor or calcium antagonist• 3rd step: calcium antagonist or ACE inhibitor (if
not well tolerated)• 4th step: ACE inhibitor or calcium antagonist +
beta-blocker• 5th step: ACE inhibitor + calcium antagonist +
beta-blockerGuérin et al. Circulation 2001;103:987-992
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Survivors
Inclusion At target BP
End of follow up
1413
9
12
10
11
Inclusion At targetBP
End of follow up
14
13
9
12
10
11
120
100
110
Non Survivors
120
100
110
PWV (m/s)
PWV (m/s)
Guerin and al. Impact of aortic stiffness attenuation on survival of patient in end stage renal failure. Circulation. 2001; 103:987-992
Changes of Mean Blood Pressure and aortic PWV
MBP (mmHg) MBP (mmHg)
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From risk assessment to risk reduction strategies
• Residual risk• Systolic versus diastolic ?• BP versus PWV ?• Peripheral BP versus central BP ?• Young versus old versus oldest old• Prevention of CAD versus prevention of
stroke ?• Prêt-à-porter versus haute couture
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From risk assessment to risk reduction strategies
• Residual risk• Systolic versus diastolic ?• BP versus PWV ?• Peripheral BP versus central BP ?• Young versus old versus oldest old• Prevention of CAD versus prevention of
stroke ?• Prêt-à-porter versus haute couture
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ARTERIAL HYPERTENSION
LVH
Atrial fibrillation
Heart failure
Ischemicstroke
Dementia
Hypertensive encephalopathy
BlindnessAortic
aneurismPeripheral arterial
disease
Chronic renal insufficiencyCerebral
haemorrhageCoronary arterydisease
Pre-eclampsia/eclampsia
Myocardial infarction
Hypertension : complications
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From risk assessment to risk reduction strategies
• Residual risk• Systolic versus diastolic ?• BP versus PWV ?• Peripheral BP versus central BP ?• Young versus old versus oldest old• Prevention of CAD versus prevention of
stroke ?• Prêt-à-porter versus haute couture
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From risk assessment to risk reduction strategies
• Residual risk• Systolic versus diastolic ?• BP versus PWV ?• Peripheral BP versus central BP ?• Young versus old versus oldest old• Prevention of CAD versus prevention of
stroke ?• Prêt-à-porter versus haute couture
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From risk assessment to risk reduction strategiesCONCLUSION
• Reliable BP measurements• Better understanding of the patho-physiology• Meta-analysis of observational studies and
therapeutic trials (structural models):• Association of different BP parameters to CV risk• Association of different BP parameters to CV risk reduction
• Dedicated therapeutic trials• Focussing on one parameter versus another• Difficult to interpret because of collinearity
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Systolic Diastolic
Mean Pulse
Peripheral Central