Comparison between Central and Peripheral Pulse Pressure as Determinants of Intermediate Cardiovascular PhenotypesC Delles, U Neisius, G Bilo, C Taurino, JD McClure, MP Schneider,K Kawecka-Jaszcz, K Stolarz-Skrzypek, Ł Klima, JA Staessen,T Kuznetsova, J Redon, F Martinez, E Agabiti Rosei, O Melander,F Zannad, P Rossignol, S Laurent, C Collin, L Lonati,A Zanchetti, AF Dominiczak

BHF Glasgow Cardiovascular Research CentreInstitute of Cardiovascular and Medical SciencesUniversity of Glasgow

Cardiovascular ContinuumBlood Pressure Determines Cardiovascular Risk

Prospective Studies Collaboration. Lancet 2002

Cardiovascular ContinuumPulse Pressure Refines Cardiovascular Risk

Franklin SS et al. Circulation 1999

Cardiovascular Continuum

Franklin SS et al. Circulation 2001

Pulse Pressure Refines Cardiovascular Risk

Cardiovascular ContinuumCentral BP Causes Central Artery Damage

Hypertension 2007; 50: 154-160

Cardiovascular ContinuumQuestion

Is central blood pressure a better predictor of cardiovascular riskthan peripheral blood pressure

in young to middle-aged people?

Cardiovascular ContinuumQuestion

Is central v pulse v pressure a better predictor of cardiovascular riskthan peripheral v pulse v pressure

in young to middle-aged people?

Cardiovascular ContinuumQuestion

Is central v pulse v pressure a better predictor of intermediate CV phenotypes

than peripheral v pulse v pressurein young to middle-aged people?

Cardiovascular ContinuumInGenious HyperCare

10

1112

13 1417 16 15

98

1-37 64

29

518 21

19

20

22

23

24

2526-27

30

31

10

1112

13 1417 16 15

98

1-37 64

29

518 21

19

20

22

23

24

2526-27

30

31

Index Patient

• Hypertension diagnosed < 50 years• Caucasian• Age 18-60• Index patient on treatment with ≥ 2 drugs or

SBP ≥ 160 • DBP ≥ 95 on two different occasions if

untreated • At least three 1st degree relatives of whom at

least one should be affected (< 50 years ) and at least one from a different generation

Examples of Possible Family Structures

affected

unaffected

index patient

Cardiovascular ContinuumPatients

Hypertensive n=331

Normotensive n=204

P-value

Age, years 51±15 39±16 <0.001 Sex, male/female 156/175 85/119 0.026 Height, cm 168±9 168±9 ns Weight, kg 79.6 [70.0;91.0] 70.9 [61.5;82.2] <0.001 BMI, kg/m² 27.7 [25.0;31.4] 24.9 [22.0;28.4] <0.001 Sitting pSBP, mmHg 141±16 128±14 <0.001 Sitting pDBP, mmHg 85±10 78±9 <0.001 Sitting Heart rate, /min 69±12 71±10 ns Coronary heart disease, % 4.4 2.0 0.02 Creatinine, μmol/L 78 [64;87] 72 [62; 83] 0.01 eGFR, mL/min 89±21 99±25 <0.001 Diabetes mellitus, % 10.0 3.0 <0.001 Supine pSBP, mmHg 135 [125;146] 126 [117;135] <0.001 Supine pDBP, mmHg 81±11 76±9 <0.001 Supine cSBP, mmHg 123 [114;135] 113 [102;124] <0.001 Supine cDBP, mmHg 82±11 77±10 <0.001 Supine pPP, mmHg 54 [46;63] 49 [43;57] <0.001 Supine cPP, mmHg 42 [35;50] 34 [29;43] <0.001 C-IMT, mm 0.62 [0.52;0.75] 0.55 [0.48;0.65] <0.001 LVMI, g/m².7 41.6 [35.4;49.0] 35.4 [30.5;41.5] <0.001 PWV, m/s 8.12 [7.08;9.70] 7.00 [6.10;7.88] <0.001 ACR, mg/mmol 0.74 [0.48;1.28] 0.69 [0.39;1.17] ns

Cardiovascular ContinuumMethods

• Blood pressure (Omron)• Pulse wave analysis (mostly SphygmoCor)• Pulse wave velocity (mostly SphygmoCor)• Carotid intima-media thickness• Echocardiography• Urinary albumin:creatinine ratio

Cardiovascular ContinuumPulse Pressure and Age

Decade

cP

P/p

PP

ns

ns

ns

ns ns ns

HypertensivesNormotensives

Cardiovascular ContinuumUnivariate Analysis

Central Pulse Pressure Peripheral Pulse Pressure lo

g(p

uls

ew

ave

vel

oci

ty)

r = 0.471

P < 0.001

r = 0.372

P < 0.001

A B

log

(in

tim

a-m

ed

ia t

hic

kne

ss)

r = 0.426P < 0.001

r = 0.235P < 0.001

C D

log(central pulse pressure) log(peripheral pulse pressure)

log

(LV

MI)

r = 0.385P < 0.001

r = 0.189P < 0.001

FE

log

(AC

R)

G H

r = 0.236P < 0.001

r = 0.226P < 0.001

Cardiovascular ContinuumUnivariate Analysis

Central Pulse Pressure Peripheral Pulse Pressure lo

g(p

uls

ew

ave

vel

oci

ty)

r = 0.471

P < 0.001

r = 0.372

P < 0.001

A B

log

(in

tim

a-m

ed

ia t

hic

kne

ss)

r = 0.426P < 0.001

r = 0.235P < 0.001

C D

log(central pulse pressure) log(peripheral pulse pressure)

log

(LV

MI)

r = 0.385P < 0.001

r = 0.189P < 0.001

FE

log

(AC

R)

G H

r = 0.236P < 0.001

r = 0.226P < 0.001

Cardiovascular ContinuumAge and Intermediate Cardiovascular Phenotypes

Age, years Age, years

Cardiovascular ContinuumMultivariate Analysis

Central Peripheral

β P-value β P-value

log(PWV)

R2adj 0.399 0.413

Hypertension, (yes/no) 0.112 0.003 0.086 0.020

Heart Rate, bpm 0.128 0.001 0.098 0.009

Age, yrs 0.460 <0.001 0.515 <0.001

MAP, mmHg 0.089 0.044 0.111 0.006

log(PP) 0.226 <0.001 0.220 <0.001

Cardiovascular ContinuumMultivariate Analysis

Central Peripheral

β P-value β P-value

log(C-IMT)

R2adj 0.429 0.428

Age, yrs 0.598 <0.001 0.633 <0.001

log(PP) 0.097 0.020 0.076 0.037

log(LVMI)

R2adj 0.181 0.170

Age, yrs 0.318 <0.001 0.386 <0.001

log(PP) 0.160 0.002 0.085 0.051

Summary

• Central pulse pressure is more strongly correlated with intermediate cardiovascular phenotypes than peripheral pulse pressure.

• In a young to middle-aged cohort of normotensive and well-controlled hypertensive subjects, age is the major determinant of intermediate cardiovascular phenotypes.

• When adjusted for relevant cofactors including age, models containing either cPP or pPP predict intermediate cardiovascular phenotypes equally well.

• Limitations: cross-sectional design, case-control design and family structure.

Perspective and Clinical Relevance

• Assessment of central haemodynamic parameters provides an integrated view on blood pressure and other determinants of cardiovascular phenotypes.

• Our data do not support the notion that central blood pressure is a superior determinant of risk than peripheral blood pressure if age is taken into account.

• Large and prospective studies on the use of central haemodynamic parameters in clinical practice are still required – and under way.

Cardiovascular ContinuumResults by Study Centre

Cardiovascular ContinuumResults by Gender

gender

FemaleMale

200

150

100

50

0

age (years)cPP (mmHg)pPP (mmHg)PWV (dm/s)C-IMT (10-2 mm)LVMI (g/m2.7)4

Cardiovascular ContinuumBlood Pressure and Cardiovascular Risk

Prospective Studies Collaboration. Lancet 2002

Central BP and Antihypertensive Treatment

Williams B et al. Circulation 2006

Atenolol basedAmlodipine based

Local Pulse Pressure and Large Arteries

Circulation 1999: 100:1387-1393