Arterial Stiffness and Central Blood Pressure: Ready for Prime Time ?

Arterial stiffness and central blood pressure: ready for prime time ?

Phil Chowienczyk King’s College London British Heart Foundation Centre

Arterial stiffness and central blood pressure: ready for prime time ?

“It’s the blood pressure stupid”

Why bother/complicate by measuring arterial stiffness and central blood pressure ?

Arterial stiffness

• What is it ? • Why does it matter ? • How should we use it ?

Stiffness and elasticity

Stress

Strain

Young’s elastic modulus E = “Pulling force”/ “Stretch” E = Stress/strain

Elastic modulus modulus Elastic

Strain Stiffness of an artery

Pressure P Pressure P + DP

wall thickness h

Diameter D Diameter D + DD

Distensibility = DD/(DP  D) (mmHg-1)

DP  D E = DD  h Elastic modulus and distending pressure

Berry & Greenwald 1976 Pulse wave velocity: PWV

PWV= L /DT

E.h PWV= ρ.D

h, wall thickness DT ρ, density D, diameter Arterial stiffness

• What is it ? • Why does it matter ? • How should we use it ?

Ventricular-vascular coupling

Ventricular contraction PPPP P Aortic stiffness MAPP

Peripheral resistance

MAP = Cardiac output x Peripheral resistance

Ventricular-vascular coupling

Ventricular contraction PPPP P Aortic stiffness MAPP

Peripheral resistance

MAP = Cardiac output x Peripheral resistance

PP ≈ PWV x Flow

Ventricular-vascular coupling

Ventricular contraction PPPP P Aortic stiffness MAPP

Peripheral resistance

MAP = Cardiac output x Peripheral resistance

PP ≈ PWV x Flow

PP ≈ PWV x Ventricular contraction (rate of)

Pulse pressure ≈ PWV x Flow

n = 18 Mean±SD Parameter (mmHg) RMSE 3.4±1.3 P1 1.9±5.3 SBP 1.4±2.0 P2 0.9±3.4

Vennin et al. Non-invasive calculation of the aortic blood pressure waveform from the flow velocity waveform: a proof of concept. Am J Physiol - Heart Circ Physiol, 2015, 309(5), H969-H976 Arterial pressure components by age

Stanley S. Franklin et al. Circulation. 1997;96:308-315

ISH (SBP ³140 mm Hg and DBP <90 mm Hg)

SDH (SBP ³140 mm Hg and DBP ³90 mm Hg)

IDH (SBP <140 mm Hg and DBP ³90 mm Hg)

17% 16% 16% 20% 20% 11% 100

0 <40 40-49 50-59 60-69 70-79 80+ Age

Franklin et al. Hypertension 2001;37: 869-874. Association of PWV with risk factors: a systematic review 29,970 Subjects

Cecelja et al Hypertension 2009 Association of PWV with risk factors: a systematic review 29,970 Subjects

Cecelja et al Hypertension 2009 Mechanical stress, inflammation and calcification

Marina Cecelja, and Philip Chowienczyk Hypertension. 2010;56:29-30

MAP (acute) PP (chronic)

 BP  PWV

Marina Cecelja, and Philip Chowienczyk Hypertension. 2010;56:29-30

Blacher et al. Circulation 1999 Vlachopoulos et al. JACC 2010 Arterial stiffness

• What is it ? • Why does is it matter ?  Determinant of pulse pressure  Integrative measure of impact of BP on the arterial wall  Predictive of outcome • How should we use it ?

Arterial stiffness

• What is it ? • Why does it matter ?  Determinant of pulse pressure  Integrative measure of impact of BP on the atrial wall  Predictive of outcome • How should we use it ?

The role of vascular biomarkers for primary and secondary prevention. A position paper from the European Society of Cardiology Working Group on peripheral circulation

Table 1Criteria for vascular biomarkers to qualify as clinical surrogate endpoints. 1 Proof of concept Do novel biomarker levels differ between subjects with and without outcome?

Does the novel biomarker predict development of future outcomes in a 2 Prospective prospective cohort or nested case-cohort study? validation

Does it add predictive information over and above established, standard risk 3 Incremental value markers?

4 Clinical utility Does it change predicted risk sufficiently to change recommended therapy?

Does the use of the novel biomarker improve clinical outcomes, especially 5 Clinical outcomes when tested in a randomized clinical trial?

Does the use of the biomarker improve clinical outcomes sufficiently to 6 Cost-effectiveness justify the additional costs?

7 Ease of use Is it easy to use, allowing widespread application?

Is the biomarker measured uniformly in different laboratories? Are study 8 Methodological results directly comparable? consensus 9 Reference values Are there published reference values, or, at least, cut-off values? (or cut-off values) Vlachopoulos et al. Modified from: Hlatky et al. Circulation 2009. Criteria 7–9 constitute additional essential criteria to the original criteria 1–6 proposed by Hlatky and coworkers [7]. Atherosclerosis 2015 The role of vascular biomarkers for primary and secondary prevention. A position paper from the European Society of Cardiology Working Group on peripheral circulation

Recommendation Level of evidence Comments Carotid IIa A Moderate usefulness for risk stratification. ultrasonography Concomitant identification of plaque presence.

Ankle-brachial index IIa A Useful for risk stratification, especially women. Arterial stiffness Carotid-femoral pulse IIa A Useful for risk stratification. wave velocity Brachial-ankle pulse IIb B wave velocity Central IIb B haemodynamics/Wave reflections Endothelial function Flow mediated dilatation III B Requires skilled, trained operator. Reactive hyperaemia is stressful. Methodological problems are not resolved. Added value is not proven.

Endothelial peripheral III C Reactive hyperaemia is stressful. arterial tonometry Added value is not proven. Circulating biomarkers related to vascular wall biology High sensitivity C- IIb B reactive protein

Vlachopoulos et al. Atherosclerosis 2015 Arterial stiffness: clinical application

• Gold standard method time consuming/expensive • Bewildering array of “simplified” methods • Limited reclassification (10% at best) • ? Better methods of reclassification • No real agreement between experts

Can we change PWV ?

R>0.99, P<0.0001 = LNMMA

= DOB 2.5 2 = DOB 5

= DOB 10

PWV(m/s)

D 1 = NA

0 0 5 10 15 20 25 D MAP (mmHg) ARB vs. control antihypertensives on PWV

Chen et al. 2015 ARB vs. control antihypertensives on PWV

Chen et al. 2015 Hypertension and arterial stiffening

MAP (acute) PP (chronic)

 BP  PWV

Marina Cecelja, and Philip Chowienczyk Hypertension. 2010;56:29-30

• What is it?  PWV the most pragmatic definition/means of measurement • Why does it matter ?  Determinant of pulse pressure

 Integrative measure of impact of BP on the arterial wall

 Predictive of outcome • How should we use it ?  Risk stratification (but beware “simplified” techniques)

 Indication for BP treatment (research)

 Target for treatment (research)

Central vs. peripheral BP

ΔSBP

MBP

DBP Peripheral pulse Central pulse Central blood pressure: methods

Carotid ≈ Central BP

FFT IFFT

GENERAL T.F. Relative risk (RR) and 95% confidence interval (CI) of clinical events for a 1 standard deviation increase in pulse pressure (A) and systolic pressure (B), according to the site of measurement (central vs. brachial).

Vlachopoulos C et al. Eur Heart J 2010;31:1865-1871

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2010. For permissions please email: [email protected] Brachial (solid symbols) and derived central aortic (open symbols) pulse pressure with time (mean, 95% CI) for patients randomized to receive atenolol±thiazide- or amlodipine±perindopril-based therapy.

The CAFE Investigators et al. Circulation 2006;113:1213- 1225

25 SphygmoCor

20 ArtLab

cSBP (mmHg) cSBP

- Adult values 10

Mean pSBP pSBP Mean

0 <10 10-14.9 >15 Age (years)

Milne et al. 2015 Systolic amplification in children/young adults

Peripheral BP Central BP

18 years 150/80 130/80

50 years 140/80 130/80 From: Isolated Systolic Hypertension in Young and Middle-Aged Adults and 31-Year Risk for Cardiovascular Mortality: The Chicago Heart Association Detection Project in Industry Study

J Am Coll Cardiol. 2015;65(4):327-335. doi:10.1016/j.jacc.2014.10.060

• What is central blood pressure ?  SBP in the arm is amplified above that at the aortic root • Why does it matter ?  May be more closely linked to target organ damage

 May predict beneficial effects of treatments with differential effects on cSBP and pSBP

 More important (greater amplification) in children • How should we use it ?  Evaluating new treatments (research)

 ? Evaluating need for treatment in children/young adults with ISH Arterial stiffness and central blood pressure: ready for prime time ?

“It’s the blood pressure stupid”

Why bother/complicate by measuring arterial stiffness and central blood pressure ?

Arterial stiffness and central blood pressure: ready for prime time ?

“It’s the blood pressure stupid”

Why bother/complicate by measuring arterial stiffness and central blood pressure ?

Arterial stiffness the major determinant of systolic hypertension

Future: Measure PWV, start (PWV lowering) treatment