Post on 06-Jul-2018
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Aging and the Vascular
System
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• NIH sponsored study
• Started in 1958
• Community dwelling
healthy volunteers
• Repeated
measurements
The Baltimore Longitudinal Study of
Aging (BLSA)
BLSA
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Age-Associated Increase in Aortic
Diameter
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Age-Associated Increase in Carotid
Intima-Media Thickness
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Age-Associated Increase in Carotid
Intima-Media Thickness
Virmani Am J Pathol 1991;139:1119
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Age-Associated Increase in Aorto-
Femoral Pulse Wave Velocity
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Arterial Stiffness
Functional Significance
• Regulation of Pulse wave velocity
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Arterial System
Structural Classification
Large arterial segment – elastic arteries
- Aorta- Brachiocephalic- Carotid
Musculoelastic arteries- Brachial
- Radial- Femoral
Muscular arteries- Small arteries- Arterioles
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Arterial SystemStructural/Functional Relationships
IN HEALTH
Type of ArteryMajor Wall
Component
Functional
Characteristics
• Large arterial
segment (elastic
arteries)
Elastin Compliance
• Musculoelastic
arteries
Elastin
Smooth muscleCompliance
• Muscular
arteries
Smooth muscle Resistance
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Arterial SystemStructural/Functional Relationships
IN AGING AND DISEASE
Type of ArteryMajor Wall
Component
Functional
Characteristics
• Large arterial
segment (elastic
arteries)
Fragmentation of
Elastin
Deposition of Collagen
and Calcium
Increased stiffness
• Musculoelastic
arteries
Elastin
Smooth muscleCompliance
• Muscular arteriesSmooth muscle
RemodellingIncreased Resistance
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Changes in Blood Pressure with Age
0 20 6040 80
50
200
150
100
Age (years)
P r e s s u r e ( m
m H g )
Systolic
Diastolic
Mean
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Pressure Pulse Waves
(Incident, Reflected, Summation)
Summation
IncidentReflected
Aorta Musculoelastic& Muscular Arteries
YOUNG
Systole Diastole
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Reflected Waves
Hemodynamic Implications
IN YOUNG ADULTS
Low central (aortic) pulse wave velocityReturn of reflective wave during diastoleEnhancement of diastolic BPMaintenance of normal coronary perfusion
Adequate left ventricular - arterial coupling
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Pressure Pulse Waves
(Incident, Reflected, Summation)
Summation
IncidentReflected
Aorta Musculoelastic& Muscular Arteries
ELDERLY
Systole Diastole
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Reflected Waves Hemodynamic Implications
IN ELDERLY HYPERTENSIVE SUBJECTS
Decrease in aortic compliance
Marked increase in central (aortic) pressure Pressure wave velocity Return of reflected wavesin systole Appearance of late systolic peakDisproportionate increase in systolic over diastolic BP
Left ventricular arterial mismatch* Increase in left ventricular afterload* Decrease in coronary perfusion pressure
? Predisposition to coronary insufficiency
A f R fl d W
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Compliant Stiff
PP
AI%
PP
AI%
Assessment of Reflected Waves
(Augmentation Index)
Carotid Arterial Waveforms
(Applanation Tonometry)
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Endothelial Function vs AgeEndothelial Function and Age
Celermajer, J Am Coll Cardiol 1994;24:471 AGE (years)
A A i t d h i
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• Lumen size• Intima-media thickness• Stiffness (compliance)• Endothelial dysfunction
• Blood Pressure
• Other – Angiogenesis, VEGF, wound repair response – Deficits in sympathetic nervous system and
baroreflex response
Age-Associated changes in
Vascular Structure and Function
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The Epidemic of Hypertension:Prevalence in US Adult Population
411
21
44
54
64 65
18-29 30-39 40-49 50-59 60-69 70-79 80+
Age
0
10
20
3040
50
60
70
PercentHypertensive
Based on NHANES III survey: 1988-1991HTN defined by BP >140/90 or treated
Hypertension 1995; 25:305-315
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Classification of Hypertension
140
90
Systolic BP
Diastolic
BP
Normal
BP
Isolated
Diastolic HTN
Isolated
Systolic HTN
Mixed HTN
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Prevalence of ISH
0
10
20
30
40
50
18-24 25-34 35-44 45-54 55-64 65-74
Men
Women
Age
% I S H
Based on NHANES III Survey
Joffres, AJH 2001;14:1099
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Pathogenesis of ISH
• Increased vascular stiffness
• Increased SBP• Decreased DBP
• Widening of the Pulse Pressure
PP = SBP-DBP
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Isolated Systolic Hypertension
• Historically viewed as part of the
“natural” aging process, a benign
condition• However, epidemiologic studies
demonstrated that ISH associated with
increased CV morbidity and mortality• Clinical trials showed that treating ISH
reduces CV events (36% - 54% reduction in
CHF)
Joint Influence of Systolic BP and Pulse Pressure on CHD Risk
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Joint Influence of Systolic BP and Pulse Pressure on CHD Risk
(Framingham Cohort)
Adapted from Franklin et al. Circulation 1999;100:354. P = probability for coefficients.
n=1924
160140-159
120-139
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Blood Pressure Components
Determinants
Mean Arterial Pressure
- Cardiac output- Systemic vascular resistance
Pulse Pressure- Left ventricular ejection- Large arterial stiffness (compliance)- Early pulse wave reflection- Heart rate
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Therapeutic Interventions
Goals of antihypertensive Therapy
• Reduction in systolic blood pressure
• Reduction in pulse pressure
• Improvement in viscoelastic properties
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Therapeutic Interventions
Effects of Antihypertensive Therapy
Systolic Blood
PressurePulse Pressure
Viscoelastic
Properties
Morbidity/
Mortality
Decrease Decrease Improvement Improved
Decrease Decrease No change Increased
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Relation of Hemodynamic/BP
Components and Cardiovascular Risks
Age (years) Parameter Mechanism
40 DBP SVR
41-60
SBP
DBP
PP
Stiffness
SVR
> 60
SBP PP
DBP
PWV
Stiffness (abnormalelastic properties
Mechanisms of PP Increase in
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Mechanisms of PP Increase in
Hypertension↑ Arterial
Stiffness
↑ PWV
↑ ↑ SBP
↑ SVR
↑ DBP
Systolic (rather than
diastolic augmentation ) ↑, ↔, ↓ DBP
↑ PP
Therefore, we need therapeutic interventions which not only lower BP,
but do so in a manner which does not further ↑ PP, but decreases it.
(vasoconstriction /
structural remodeling)
-
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Aging/Senescence as aCardiovascular Risk Factor
AgingSenescence
Systolic BP Pulse Pressure
Diabetes
Mellitus
Renal Disease/
Proteinuria
LVH
Arterial
Stiffness
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Novel Cardiovascular Risk
Factors
- LVH
- Systolic hypertension
- High pulse pressure
- Arterial Stiffness
- Renal impairment/
proteinuria
- Stroke
- Myocardial infarction
- Heart failure- End stage renal
disease
Cardiovascular
Risk Factors
Cardiovascular
Events