blood pressure parameters and pulse wave velocity for cardiovascular-renal prevention jacques...

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

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).

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

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)

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

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)

Mortality Rates (per 10000 person-years)in the 9 groups of patients

Cardiovascular Mortality

Benetos A. et al. Hypertens. 1999; 33: 44-52.

Franklin S, et al. Hemodynamic Patterns of Age-Related Changes in Blood Pressure. The Framingham Heart Study. Circulation 1997; 96: 308-315.

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

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

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


Ca

rdio

va

scu

lar

su

rviv

al

Augmentation Index (AIX) and CV survival

London and al. Hypertension 2001

00.

250.

500.

751

0 35 70 105 140

Pro

bab

ility

of

surv

ival


PP amplification 1st tertile

PP amplification 2nd tertile

PP amplification 3rd tertile

Jankowski P, et al. Hypertension 2008 ; 51 : 848-55.

Systolic Diastolic

Mean Pulse

Peripheral Central

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

Hypertension 2009

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 (%

)

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

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


10-y

ear

fata

l o

r n

on

fata

l C

V r

isk

(%)



0

1

2

3

4

120 150 180


10-y

ear

str

oke r

isk (

%)



0

5

10

15

20

120 150 180


10-y

ear

CH

D r

isk (

%)



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

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)

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

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

Systolic Diastolic

Mean Pulse

Peripheral Central

blood pressure parameters and pulse wave velocity for cardiovascular-renal prevention jacques...

Documents

intercorrelations slide

pulse pressure

systolic bp

hg diastolic pressure

diastolic bp

blood pressure parameters

relation of blood pressure

risk best