Transcript Arterial Stiffness by Dr Sarma

ARTERIAL STIFFNESS
Dr.R.V.S.N.Sarma., M.D., M.Sc., (Canada)
Consultant Physician and Chest Specialist
The Blood Vessels and the Cardiovascular System
Figure 15-1: Functional model of the cardiovascular system
Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings
Make Up of Bllod Vessels: Arteries and Arterioles
• Endothelium
• Elastic tissues
• Rebounds
• Evens flow
• Smooth muscles
• Fibrous tissue
• Tough
• Resists stretch
Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings
Figure 15-2: Blood vessels
Blood 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 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 Flow
Figure 15-10: Factors that influence mean arterial pressure
Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings
Arterioles as a group have a
greater cross sectional area than
the large vessels.
How can their resistance be
greater?
Branching to smaller radius vessels increases resistance
r=1
A= 3.14
Res=1
A
r = .707
A= 1.57
Res=4
B
C
B and C in parallel have a
combined resistance of 2 and a
cross sectional area of 3.14
Resistance ~ ( r4)
Area ~ (r 2 )
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
120/80
Systolic
hypertension >140
Compliance =  volume/ pressure
Mean and Pulse Pressure
1
Pa  Pd + ( Ps - Pd )
3
Mean Arterial Pressure
Pa  Pv

Q=
R
R
Pa - Pv = Q
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
What are arteries for?
• Conduits
– To conduct blood to the organs and periphery
• Impedance matching
– Minimise cardiac work
– Minimise pulse pressure
– Control flow according to demand
Conduit arteries: large
arteries near the heart and
their main branches
Questions
• Why are conduit arteries distensible?
• What are arteries made of?
• Why do large arteries become stiffer with age (and
disease)?
• Why are some people affected more than others?
Arteries are distensible because:
• The wheel has yet to evolve in the animal
kingdom (bacteria have propellers)
• Therefore(?) the heart is a pulsatile pump.
120
• Its output consists of a pulse wave
superimposed on a steady component.
100
80
1 sec
Aortic pulse wave
Pressure [mmHg]
Systolic pressure
120
100
80
Mean Arterial Pressure
1 second
Diastolic pressure
Pulse pressure = systolic pressure - diastolic pressure
Pressure [mmHg]
Systolic pressure
120
100
80
Mean Arterial Pressure
1 second
Diastolic pressure
Pulse pressure = systolic pressure - diastolic pressure
• MAP determined by resistance of peripheral arteries = Pd +1/3 PP
• Pulse pressure determined by elasticity of large arteries
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
2.0
Relative Radius
R
R
P
P
1.5
R
R
P
P
1.0
0
100
Pressure (mmHg)
200
Variation of Einc with stretch
Einc [Nm-2 x 105]
15
10
5
0
1.0
1.2
1.4
1.6
1.8
R/Ro
2.0
2.2
2.4
2.6
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:
– Kidney
– Cerebral
– Coronary
– Peripheral
nephroangiosclerosis
stroke
angina, M.I.
stenosis, aneurysm
• Arteries constitute the target, the battleground and the common
denominator of cardiovascular complications.
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
technique.
and
widely
used
• 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.
Blood = incompressible fluid
Artery = elastic conduit
}
Propagation along
the arterial tree
Systole
L.V.
PULSE WAVE VELOCITY
Principles
• 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.
PULSE WAVE VELOCITY
Arterial Buffering function
Systole
Diastole
Large arteries store a part of the ejection volume during systole and
restore it during diastole.
Intermittent cardiac output
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
Determining Factors
+++
•Age
•Blood pressure
From + to ++
•
•
•
•
•
•
Plasma cholesterol
Glycemia
Smoking status
Gender
Atherosclerosis
Genetic Factors
ARTERIAL STIFFNESS
Clinical Implications and Epidemiological Data
Arterial Stiffness
Cardiovascular risk
Compliance
Atherosclerosis
Distensibility
LVH
PWV
Pulse pressure
Systolic HT
Stroke
CHD
ARTERIAL DISTENSIBILITY
Arterial distensibility in coronary heart desease (CHD).
Systolic pressure
(mmHg)
Distensibility
(cm² x dynes-1)
CHD
Normal
n = 24
n = 18
117+ 4
121 + 4
1.6 + 0.1 3.4 + 0.4
NS
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
Left ventricular
mass/volume
r = 0.61
p < 0.001
1.5
1.0
= NT (normotensive)
= HTA
0.6
PWV m/sec
(Bouthier et al, Am Heart J 1985)
5
10
15
Relationship between arterial stiffness and number
of atheromatous vessels
Abdominal aorta
Common carotid artery
30
*
*
*
20
Stiffness index (b)
Stiffness index (b)
30
10
0
*
20
*
10
0
N
0-VD
1-VD
2-VD
3-VD
N
0-VD
1-VD
2-VD
3-VD
VD: vessel disease
adapted from Hirai et al.
AORTIC PWV AND DISTENSIBILITY IN STROKE
PATIENTS AND CONTROL SUBJECTS
Carotid Femoral PWV
Carotid Radial PWV
***
0
Aortic PWV (m/s)
4.9
5
**
15
8.2
(Arbitrary unit)
Aortic distensibility
10
10
13.8
9.4
5
0
controls
adapted from Lehmann
stroke
controls
stroke
ARTERIAL DISTENSIBILITY IN PATIENTS WITH
ABDOMINAL AORTIC ANEURYSM (AAA)
*
*
25
Arterial distensibility (Kpa-1.10-3 )
*
20
15
10
5
Normotensives
Hypertensives
AAA
Normotensives
Hypertensives
Supra-aneurysm
AAA
CAROTID
adapted from Boutouyrie et al.
AORTA
Aneurysm
CAROTID-RADIAL PWV IN DIABETIC SUBJECTS
16
Carotid-radial PWV (m/sec)
14
12
Healthy
10
Diabetics
8
6
4
1 to 10
11 to 20
21 to 30
31 to 40
Age (years)
adapted from Woolam et al
41 to 50
51 to 60
PULSE WAVE VELOCITY
P.W.V. in normotensives and borderline hypertensives.
10
Carotid-Femoral PWV (m/s)
9
HT = Borderline hypertensives
8
NT = Normotensives
7
6
5
70
90
110
(Girerd et al, J of Hyper, 1989)
Mean Blood Pressure (mmHg)
130
PWV AND ATHEROSCLEROSIS INDICATORS
Values are adjusted for age, sex, mean BP and pulse rate
15
p < 0.001
p = 0.001
Carotid-femoral PWV (m/s)
Carotid-femoral PWV (m/s)
15
14
13
14
13
1
2
3
4
5
Quintiles of carotid artery wall thickness
No
Unilateral
Plaques in carotid artery
Bilateral
PWV AND ATHEROSCLEROSIS INDICATORS
Values are adjusted for age, sex, mean BP and pulse rate
16
p = 0.02
14
13.5
13
Carotid-femoral PWV (m/s)
Carotid-femoral PWV (m/s)
14.5
p < 0.001
15
14
13
1
2
3
4
5
Quintiles of ankle-brachial pressure index
no
mild
moderate
Calcified plaques in the aorta
severe
CONCLUSION
• Arterial stiffness must be taken
consideration in clinical practice.
into
• 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
Wave Reflection
Increased Central
Pulse Pressure
Increased LV Load
PP
Decreased Coronary Artery
Perfusion Pressure in
Diastole
• This earlier return to the heart of
the reflected pressure wave (due
to stiffening of the arteries)
changes the aortic root pressure
waveform, … with 3 key clinical
implications
• Central pulse pressure increases
... increasing risk of stroke and renal
failure
• LV Load increases…. increasing
LV mass, and accelerating
progress towards LV hypertrophy
and heart failure
• Coronary artery perfusion
pressure in diastole reduces….
increasing risk of myocardial
ischemia
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)
PulseMetric
The morphology of the waveform should be considered when interpreting the numbers below.
CARDIAC PARAMETERS
LV Ejection Time (sec)
LV dP/dt Max (mmHg/s)
LV Contractility (1/s)
Cardiac Output (L/min)
Cardiac Index (L/min/m2)
Stroke Volume (mL)
Stroke Vol Index (mL/m2)
0.373
1,200
15.95
4.41
2.47
74.2
41.6
[Normal
Range(Male)*]
[0.207 - 0.388]
[847 - 1506]
[12.39 - 19.08]
[3.59 - 7.9]
[1.95 - 3.74]
[57.7 - 100.7]
[31.8 - 48]
SYSTEMIC VASCULAR PARAMETERS
SV Compliance
1.43
[1.02 - 2]
(mL/mmHg)
SV Resistance
1598
[871 - 1902]
(dynes/sec/cm5)
BRACHIAL ARTERY PARAMETERS
BA Compliance
0.069
[0.056 - 0.132]
(mL/mmHg)
BA Distensibility
5.44
[4.38 - 9.28]
(%/mmHg)
Brachial Artery Distensibility, SVR, CO, LV dP/dt
Uses Oscillometric BP cuff
Sphygmocor
Pulse Wave Velocity
& Augmentation Index
Uses Arterial tonometer (radial)