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![Page 1: Vascular compliance as a novel cardiovascular risk factor Dr Ian B. Wilkinson Senior Lecturer & BHF Research Fellow University of Cambridge.](https://reader036.fdocuments.in/reader036/viewer/2022062519/56649e415503460f94b3307e/html5/thumbnails/1.jpg)
Vascular compliance as a novel cardiovascular risk factor
Dr Ian B. Wilkinson
Senior Lecturer & BHF Research Fellow
University of Cambridge
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Hypertension and the Arterial Waveform
F.A. Mohamed 1874
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“ These persons appear to pass through life pretty much as others do and generally do not suffer from their high blood pressure except in their petty ailments
upon which it imprints itself… As age advances the enemy gains accession of strength … the individual has now passed forty years, perhaps fifty of age, his
lungs begin to degenerate, he has a cough in the winter time, but by his pulse you will know him … Alternatively headache, vertigo, epistaxis, and a
passing paralysis, a more severe apopleptic seizure, and then the final blow…”
F.A. Mahomed, 1879
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Riva Rocci and Korotkoff, ~1905
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“ When you can measure what your are speaking about, and can express it in
numbers, you know something about it; but when you cannot measure it, when you
cannot express it in numbers, your knowledge is of a meagre and unsatisfactory
kind.”
Lord Kelvin, 1891
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Actuary Data Relating Blood Pressure to Mortality 1935-1954
Metropolitan Life Insurance Company 1961
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Modern Techniques for Assessing Arterial Stiffness
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Arterial Stiffness: a definition
Stiffness: the resistance of an elastic body to deflection by an applied force.
The stiffness E of a body that deflects a distance δ under an applied force F is:
FE
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Elastic Bodies
unstretched springHooke’s Law:Fspring = -kx
Spring constant
kx
F
2F
2x
It takes twice as much force to stretch a spring twice as far
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Smooth muscle cells
Elastic lamellae
Endothelium
Lamellar subunit
Schematic Diagram of a Large Artery
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Why Have Elastic Arteries
Diastole Systole
Reduces peak pressureMaintains diastolic pressure
Smoothes blood flowImproves efficiency
V
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Effect of Arterial Stiffening
Systolic pressure Diastolic pressure
Arterial remodelling Arterial stiffness
NO production
Systolic hypertension
Risk Shear stress
Cyclical stress
Heart failureMyocardial ischaemia
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Effect of Aortic Stiffening on Blood Pressure
Saeki et al. Circ Res 1995;76:132-141
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Indices of Arterial Stiffness
Mackenzie and Wilkinson. QJM 1999;95:67
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Pulse Wave Velocity
Elastic Stiff
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Measuring PWV
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ApplanationTonometry of the Carotid Artery
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Does stiffness matter…..?
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Pulse Pressure and Aortic PWV
Haynes et al. Am Heart J 1936;4:385
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Isolated Systolic Hypertension is Associated with Increased Aortic Stiffness
169 untreated subjects, 114 controls
6
7
8
9
10
11
12
13
14
ISH Control
Pul
se W
ave
Vel
ocity
(m
/s)
P<0.001
Yasmin et al. ATVB 2004;25:372
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Aortic PWV Predicts the Risk of Developing Hypertension
n=499, 4.9 year follow-up
Najjar et al. JACC 2008;51:377
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Relationship Between Left Ventricular Mass and Aortic Stiffness in Dialysis Patients
Barenbrock et al. KI 1994;45:1397
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Aortic PWV and Cardiovascular Risk
Blacher. Hypertension 1999;33:1111
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PWV and Mortality in End-Stage Renal Failuren=241; mean age 51; 6 year follow up
Blacher et al. Circulation 1999;99:2434
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The Independent Predictive Value of Arterial Stiffness
Consensus Statement: Eur Heart J 2006; 27:2588
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Predictive Value of Aortic PWV for Stroke Death in Hypertensives
n=1715; 8 yr follow up; mean age 51 years
Laurent S Stroke 2003; 34:1203
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Predictive Value of Aortic PWV for Stroke Death in Hypertensives
n=1715; 8 yr follow up; mean age 51 years
Laurent S Stroke 2003; 34:1203
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Predictive Value of Aortic PWV and PP for Stroke Death After Correcting for Other Risk Factors
n=1715; 8 yr follow up; mean age 51 years
Laurent S Stroke 2003; 34:1203
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Hansen et al., Circulation 2006; 113: 664-70
Predictive Value of Aortic PWV & Blood Pressure Danish Monica Study n=1,678, 9.4yr follow-up, 154 events
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Predictive Value of Aortic PWV & Blood Pressure Danish Monica Study n=1,678, 9.4yr follow-up, 154 events
Hansen et al., Circulation 2006; 113: 664-70
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Predictive Value of Aortic PWV & Blood Pressure Danish Monica Study n=1,678, 9.4yr follow-up, 154 events
Hansen et al., Circulation 2006; 113: 664-70
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Addition of Novel Biomarkers Does not Improve Risk Prediction
Wang et al NEJM 2006;355:25
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Aortic PWV Improves Risk Prediction
Boutouyrie et al Hypertension 2002;39:10
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Arterial Stiffness and Response to TreatmentPWV and Mortality in End-Stage Renal Failure
Guerin et al. Circulation 2001
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“Only in the case of young children do we find that the elasticity of the arteries is so perfectly adapted to the requirements of the organism as it is in the case of the lower animals”
Roy: 1880
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Age and Aortic Pulse Wave Velocity: UK
Bramwell & Hill. Lancet 1922
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Age and Pulse Wave Velocity
McEniery et al JACC 2005;46:1753
Aortic
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Arterial Stiffening
Elastin Fatigue
Number of cycles Cyclical stressx
Heart rate Pulse pressurex= =
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Relationship Between Rate Pressure Product and aPWV in the Caerphilly Study
McEniery et al Caerphilly Data
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Comparison of Aortic PWV in urban and Rural Chinese Communities
Avolio et al. Hypertension 1985; 71:202
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Blood Pressure in !Kung Bushmen in Northern Botswana
Truswell et al. Am Heart J 1972;84:5
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Factors Influencing Arterial Stiffness
Zieman et al ATVB 2005;25:932
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Arterial Calcification
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Relationship Between Age and Thoracic Aortic Calcium Content in Man
Elliot et al. Calcif Tissue Int 1994;54:268
Media
Adventitia
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Multi Slice CT Quantification of Aortic Calcification
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aPWV and Abdo Calcification
Me
an
Ao
rtic
Ab
do
min
al C
alc
ium
Sco
re (
cm3
)2.0
1.5
1.0
0.5
0.0
Quartiles of aPWV4321
McEniery et al Caerphilly Data
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Calcification By Blood Pressure
McEniery et al Caerphilly Data
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Inflammation
Cardiovascular Disease
Arterial Stiffness
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Inflammation and Aortic PWV
4
5
6
7
8
9
10
<1 1 - 3 >3
CRP Category
Ao
rtic
PW
V (
m/s
)
0
P<0.001
Yasmin et al. ATVB 2004;24:969
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Rheumatoid Arthritis
• RA is chronic systemic inflammatory disease
• A worldwide distribution• Prevalence increases
with age, approaching 5% in women over age 55
• Rarely involves the large arteries directly
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Rheumatoid Arthritis is Associated with Increased Aortic PWV
Maki-Petaja et al; Circulation 2006;114:1184
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Anti-TNF- Therapy
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Effective Anti TNF- Therapy Normalizes Aortic PWV in Rheumatoid Arthritis
P= 0.004
Maki-Petaja et al; Circulation 2006;114:1184n=9
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Simvastatin Prevents Acute Inflammation-Induced Aortic Stiffening
Overall ANOVA P<0.001
P = 0.002
P = NS
5
5.5
6
6.5
7
Placebo Simvastatin
m/s
Day 14
Day 15P = 0.016
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Inflammation
Cardiovascular Disease
Arterial Stiffness
Why?
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Heritability of Pulse Wave Velocity
Ge et al. Am J HT 2007;20:1065
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Matrix Metalloproteinase-9
• Relative selectivity for elastin• Present in the circulation and aortic tissue• Inducible
– Cytokines, pro-inflammatory mediators
• Increased levels in coronary artery disease and inflammatory conditions eg kawasaki disease
Signal/Prodomain Hinge Region
Catalytic Domain Hemopexin
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MMP-9 Levels and aPWV
Yasmin et al ATVB 2005; 25: 372-378
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MMP-9 Genotype and Aortic PWV
Yasmin et al ATVB 2006; 26: 1799
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“In extreme old age, the arteries themselves, the grand instrument of the circulation, by the
continual apposition of earth, become hard, and as if it were bony, till, having lost the power of
contracting themselves they can no longer propel the blood, even through the largest channels, in consequence of which death
naturally ensues.”
John Wesley, 1703-1791
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Disparity Between Aortic and Brachial Pressure
Rowell et al. Circulation 1968; 37:954
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Peripheral Versus Aortic Pressure
Pauca AL et al. Chest 1992;102:1193
SBP
SBP
MAPDBP
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Wave reflection
Elastic Stiff
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Central Pulse Pressure Predicts Mortality in ESRF n=180; mean age 25; 4 year follow up
Safar et al, Hypertension 2002;39:735
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The Independent Predictive Value of Central Pulse Pressure
Consensus Statement: Hypertension 2007; in press
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The TIMES Friday 5th November 2004
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ASCOT Studyn=19,257, mean age 63
Dahlof et al. Lancet 2005;366:895
Stroke All cause mortality
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Pulse Wave AnalysisNon-invasive Assessment of Arterial Stiffness
Wilkinson et al. Lancet 2006; 367:627
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Differential Effect of -blockers/diuretics and ACEi inhibitors/calcium blockers on Blood Pressure in ASCOT
CAFÉ Investigators. Circulation 2006; 113:
Atenolol
Amlodipine
Atenolol
Amlodipine
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Variability in Central BP Resulting From Classification Based on Peripheral BP
McEniery et al. Hypertension 2008; in press