ARTERIAL STIFFNESS

Dr.R.V.S.N.Sarma., M.D., M.Sc., (Canada)

Consultant Physician and Chest Specialist

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

The Blood Vessels and the Cardiovascular SystemThe Blood Vessels and the Cardiovascular System

Figure 15-1: Functional model of the cardiovascular system

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

• Endothelium

• Elastic tissues

• Rebounds

• Evens flow

• Smooth muscles

• Fibrous tissue

• Tough

• Resists stretch

Make Up of Bllod Vessels: Arteries and ArteriolesMake Up of Bllod Vessels: Arteries and Arterioles

Figure 15-2: Blood vessels

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

Blood Pressure: Generated by Ventricular ContractionBlood Pressure: Generated by Ventricular Contraction

Figure 15-4: Elastic recoil in the arteries

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

More Blood Pressures: Pulse and Mean Arterial PressuresMore Blood Pressures: Pulse and Mean Arterial Pressures

Figure 15-5: Pressure throughout the systemic circulation

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

Factors Controlling MAP : The Driving Pressure for Blood FlowFactors Controlling MAP : The Driving Pressure for Blood Flow

Figure 15-10: Factors that influence mean arterial pressure

Arterioles as a group have a greater cross sectional area than the large vessels.

How can their resistance be greater?

r = 1A= 3.14Res=1

B and C in parallel have a combined resistance of 2 and a cross sectional area of 3.14

A

r = .707A= 1.57Res=4

B

C

Resistance ~ ( r4)Area ~ (r 2 )

Branching to smaller radius vessels increases resistance

The heart pumps in short spurts. The compliant aorta stores this energy during ejection and releases it during diastole so that flow into the periphery continues throughout the cardiac cycle

The bagpipe player blows into the bag in short spurts. That energy is stored in the bag and the air escapes through the pipes in a continuous stream thanks to the bag's compliance.

If the vessels were rigid pipes then all forward flow would have to occur during the ejection period which is only about 1/3 of the cardiac cycle.

Blood pressure would have to be 3 times higher during that period to maintain the cardiac output.

Why is aortic pressure pulsatile?

With each ejection the aortic volume increases by one stroke volume

If aortic compliance were to decrease, pulse pressure will increase.

Pulse pressure = stroke volume/compliance

Aging reduces aortic compliance

Pulse pressure naturally increases with age

Compliance = volume/ pressure

120/80

Systolic hypertension >140

Mean and Pulse Pressure

P P +1

3P - P )a d s d (

Mean Arterial Pressure

Q =P P

Ra v

P - P = Q Ra v

MAP = cardiac output x total resistance

Arterial Elasticity Stores Pressure and Maintains Flow

Factors Controlling Blood Pressure

Peripheral resistance mean arterial pressure

Cardiac output mean arterial pressure

Stroke volume pulse pressure

Arterial compliance pulse pressure

Heart Rate pulse pressure

Blood Volume arterial & venous

• Conduits– To conduct blood to the organs and periphery

• Impedance matching– Minimise cardiac work– Minimise pulse pressure– Control flow according to demand

What are arteries for?

• What are arteries made of?

• Why do large arteries become stiffer with age (and disease)?

• Why are some people affected more than others?

QuestionsConduit arteries: large arteries near the heart and their main branches

• Why are conduit arteries distensible?

Arteries are distensible because:

80

100

120

1 sec

• The wheel has yet to evolve in the animal kingdom (bacteria have propellers)

• Therefore(?) the heart is a pulsatile pump.

• Its output consists of a pulse wave superimposed on a steady component.

Systolic pressure

Diastolic pressure

Mean Arterial Pressure

Pulse pressure = systolic pressure - diastolic pressure

80

100

120

1 second

Pre

ssur

e [m

mH

g]Aortic pulse wave

• MAP determined by resistance of peripheral arteries = Pd +1/3 PP

• Pulse pressure determined by elasticity of large arteries

Pulse pressure = systolic pressure - diastolic pressure

Systolic pressure

Diastolic pressure

Mean Arterial Pressure

80

100

120

1 second

Pre

ssur

e [m

mH

g]

The pulse is a wave of dilatation

With thanks to Chris Martyn

Speed of the wave is related to the stiffness of the artery it is

traveling in

The stiffer the artery;

the higher the wave speed

Wave speed is proportional to the square root of arterial stiffness

Stress, strain and elastic modulus

• Stress (, sigma)– Force per unit area = (F/A)

• Strain (, epsilon)– Change in length per unit length = (L/L0)

• Elastic (Young’s) modulus (E)– stress/strain =

F L0

A L=

2001000

Pressure (mmHg)

Rela

tive R

ad

ius

1.0

1.5

2.0

P

P

R R

P

P

R R

2.62.42.22.01.81.61.41.21.0

R/Ro

0

5

10

15

Einc [Nm-2 x 105]

Variation of Einc with stretch

WHY THE ARTERY?

Epidemiological studies have shown that:

• Cardiovascular disease is the first cause of morbidity and mortality in western countries.

• Cardiovascular morbidity and mortality are principally related to arterial pathology.

• Arterial wall alterations are usually associated with: age, smoking, diabetes, dyslipidemia and hypertension.

WHY THE ARTERY?

• Arterial alterations can be observed at early stages in both small and large arteries.

• Alterations of the arterial wall properties favor development of arterial lesions:

• Arteries constitute the target, the battleground and the common denominator of cardiovascular complications.

– Kidney nephroangiosclerosis

– Cerebral stroke

– Coronary angina, M.I.

– Peripheral stenosis, aneurysm

WHY THE ARTERY?

• Cardiovascular morbidity and mortality are principally due to arterial lesions.

• Treatments differ by their effect on the arterial wall.

• The evaluation of cardiovascular prevention and its impact on the arterial wall is important as an intermediate marker

• Large therapeutic trials including arterial evaluation are required.

WHY PULSE WAVE VELOCITY?

• Arterial pathology is a major contributor to cardiovascular disease, morbidity and mortality.

• Most non-invasive methods to assess large arteries are ultrasound based:

– Doppler velocity measurement– Echography– High resolution Echo-tracking

Sophisticated, costly and reserved for a few clinical research labs.

WHY PULSE WAVE VELOCITY?

• Clinical assessment of large arteries requires a simple, practical method.

Pulse wave velocity = Index of arterial stiffness

• Arterial stiffness will– Play a potential etiologic role in cardiovascular disease.

– Help to recognize arterial changes.

– Constitute an "early risk marker" .

– Be useful in assessing the arterial effects of drugs.

PULSE WAVE VELOCITY

• A simple method to assess arterial stiffness and distensibility.

• A long-established and widely used technique.

• Non-invasive, accurate and reproducible.

PULSE WAVE VELOCITY

Principles

L.V.E. generates a pulse wave which will propagate along the arterial walls at a certain speed.

Propagation alongthe arterial tree

Systole

L.V.

Blood = incompressible fluid

Artery = elastic conduit }

PULSE WAVE VELOCITY

• The propagation velocity is determined by:

– the elastic and geometric properties of the arterial wall – the characteristics of the arterial wall structure.

Higher velocity = higher stiffness

= lower distensibility.

Principles

PULSE WAVE VELOCITY

Intermittent cardiac output

Systole Diastole

Large arteries store a part of the ejection volume during systole and restore it during diastole.

Arterial Buffering function

Continuous peripheral flow

•

PULSE WAVE VELOCITY

The Complior® device

COMPLIOR

Automatic Measurement (The Complior®)

• Transducer = large frequency band (0.1 - 100 Hz)

• Signal gain adjustment (manual or automatic)

• Acquisition frequency = 4 kHz

• Waveforms = entire exam stored in memory (signal data & parameters)

• Pedal for trigger acquisition

• Automatic detection and calculation of propagation delay between the 2 pulse waves

PULSE WAVE VELOCITY

• Plasma cholesterol

• Glycemia

• Smoking status

• Gender

• Atherosclerosis

• Genetic Factors

Determining Factors

•Age

•Blood pressure

+++ From + to ++

ARTERIAL STIFFNESS

Clinical Implications and Epidemiological Data

Arterial Stiffness Cardiovascular risk

Compliance

Distensibility

PWV

Pulse pressure

Atherosclerosis

LVH

Systolic HT

Stroke

CHD

ARTERIAL DISTENSIBILITY

Arterial distensibility in coronary heart desease (CHD).

CHDn = 24

Normaln = 18

Systolic pressure(mmHg)

Distensibility(cm² x dynes-1)

117+ 4 121 + 4 NS

1.6 + 0.1 3.4 + 0.4 P < 0.001

Stefanadis C et al. Am J Cardiol. 1987

PULSE WAVE VELOCITY

Aortic P.W.V. is an independent determinant of L.V.H.

1.9

1.5

1.0

0.6

5 10 15

r = 0.61p < 0.001

PWV m/sec

Left ventricularmass/volume

= NT (normotensive)

= HTA

(Bouthier et al, Am Heart J 1985)

Relationship between arterial stiffness and number of atheromatous vessels

Common carotid artery

0

10

20

30

N 0-VD 1-VD 2-VD 3-VD

Sti

ffne

ss in

dex

*

*

adapted from Hirai et al.

VD: vessel disease

Abdominal aorta

0

10

20

30

N 0-VD 1-VD 2-VD 3-VD

Sti

ffne

ss in

dex

(

*

**

AORTIC PWV AND DISTENSIBILITY IN STROKE PATIENTS AND CONTROL SUBJECTS

adapted from Lehmann

0

5

10

15

controls stroke

Aor

tic P

WV

(m/s

)0

5

10

controls stroke

Aor

tic d

iste

nsib

ility

(Arb

itra

ry u

nit)

*** **

8.2

4.9

9.4

13.8

Carotid Radial PWV Carotid Femoral PWV

ARTERIAL DISTENSIBILITY IN PATIENTS WITH ABDOMINAL AORTIC ANEURYSM (AAA)

5

10

15

20

25

Normotensives Hypertensives AAA Normotensives Hypertensives Supra-aneurysm Aneurysm

Art

eria

l dis

tens

ibil

ity

(Kpa

-1.1

0-3 )

AAA

*

*

CAROTID AORTA

*

adapted from Boutouyrie et al.

CAROTID-RADIAL PWV IN DIABETIC SUBJECTS

4

6

8

10

12

14

16

1 to 10 11 to 20 21 to 30 31 to 40 41 to 50 51 to 60

Age (years)

Car

otid

-rad

ial P

WV

(m

/sec

)

Healthy

Diabetics

adapted from Woolam et al

PULSE WAVE VELOCITY

P.W.V. in normotensives and borderline hypertensives.

HT = Borderline hypertensives

NT = Normotensives

10

9

8

7

6

5

70 90 110 130

Mean Blood Pressure (mmHg)

Ca

rotid

-Fe

mo

ral P

WV

(m

/s)

(Girerd et al, J of Hyper, 1989)

13

14

15

No Unilateral Bilateral

13

14

15

1 2 3 4 5

PWV AND ATHEROSCLEROSIS INDICATORSValues are adjusted for age, sex, mean BP and pulse rate

Quintiles of carotid artery wall thickness Plaques in carotid artery

Car

otid

-fem

oral

PW

V (

m/s

)

Car

otid

-fem

oral

PW

V (m

/s)

p < 0.001 p = 0.001

PWV AND ATHEROSCLEROSIS INDICATORSValues are adjusted for age, sex, mean BP and pulse rate

13

13.5

14

14.5

1 2 3 4 5

Quintiles of ankle-brachial pressure index

Car

otid

-fem

oral

PW

V (

m/s

)

p = 0.02

13

14

15

16

no mild moderate severe

Calcified plaques in the aorta

Car

otid

-fem

oral

PW

V (

m/s

)

p < 0.001

CONCLUSION

• Arterial stiffness must be taken into consideration in clinical practice.

• The Complior system is an accurate device to assess the arterial stiffness using pulse wave velocity measurements.

• The examination procedure is simple, and the method is accurate and reproducible.

Which is important ? SBP or DBP

The Impact of the Early The Impact of the Early Wave ReflectionWave Reflection

• This earlier return to the heart of This earlier return to the heart of the reflected pressure wave (due the reflected pressure wave (due to stiffening of the arteries) to stiffening of the arteries) changes the aortic root pressure changes the aortic root pressure waveform, waveform, … with 3 key clinical … with 3 key clinical implicationsimplications

• Central pulse pressure Central pulse pressure increases ... increases ... increasing risk of increasing risk of stroke and renal failurestroke and renal failure

• LV Load increases…. LV Load increases…. increasing increasing LV massLV mass, and accelerating , and accelerating progress towards LV hypertrophy progress towards LV hypertrophy and heart failureand heart failure

• Coronary artery perfusion Coronary artery perfusion pressure in diastole reduces…. pressure in diastole reduces…. increasing risk of myocardial increasing risk of myocardial ischemiaischemia

PP

Increased CentralPulse Pressure

Increased LV Load

Decreased Coronary ArteryPerfusion Pressure in Diastole

Treatment of Arterial Stiffness

• Currently approved drugs for arterial stiffness

• ACEi, ARBs

• Nitrates

• Diuretics

• Statins

• Aspirin

• Certain beta blockers

• Certain Ca channel blockers

Treatment of Arterial Stiffness

• Promising Drugs

• Endopeptidase inhibitors (Omiprilait)

• PDE inhibitors (Sildenafil group)

• Methyl Xanthines (with better safety window)

• NO donors (novel drugs avoiding tolerance)

• Drugs breaking AGE cross links (ALT 711)

PulseMetricPulseMetric

Brachial Artery Distensibility, SVR, CO, LV dP/dtUses Oscillometric BP cuff

SphygmocorSphygmocor

Pulse Wave Velocity & Augmentation Index

Uses Arterial tonometer (radial)