Aging and Vascular System

8/16/2019 Aging and Vascular System

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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

Documents

Aging and Vascular System