Aging and the Vascular

System

The Baltimore Longitudinal Study of

Aging (BLSA)
NIH sponsored study

Started in 1958
Community dwelling
healthy volunteers
Repeated
measurements

BLSA

Age-Associated Increase in Aortic

Diameter

Age-Associated Increase in Carotid

Intima-Media Thickness

Age-Associated Increase in Carotid

Intima-Media Thickness

Virmani Am J Pathol 1991;139:1119

Age-Associated Increase in AortoFemoral Pulse Wave Velocity

Arterial Stiffness
Functional Significance
Regulation of Pulse wave velocity

Arterial System

Structural Classification

Large arterial segment elastic arteries

- Aorta
- Brachiocephalic
- Carotid

Musculoelastic arteries
- Brachial
- Radial
- Femoral

Muscular arteries
- Small arteries
- Arterioles

Arterial System
Structural/Functional Relationships
IN HEALTH
Type of Artery

Major Wall
Component

Functional
Characteristics

Large arterial
segment (elastic
arteries)

Elastin

Compliance

Musculoelastic
arteries

Elastin
Smooth muscle

Compliance

Muscular
arteries

Smooth muscle

Resistance

Arterial System
Structural/Functional Relationships
IN AGING AND DISEASE
Major Wall
Component

Functional
Characteristics

Large arterial
segment (elastic
arteries)

Fragmentation of
Elastin
Deposition of Collagen
and Calcium

Increased stiffness

Musculoelastic
arteries

Elastin
Smooth muscle

Compliance

Muscular arteries

Smooth muscle
Remodelling

Increased Resistance

Type of Artery

Arterial Stiffness

PWV (cm/sec)
Arterial Stiffness

Effect of Age and Disease

AORTA

20

40
Age (years)

60

80

Changes in Blood Pressure with Age

Pressure (mmHg)

200

150

Systolic
Mean

100

Diastolic
50

20

40
Age (years)

60

80

Pressure Pulse Waves

(Incident, Reflected, Summation)
YOUNG
Reflected

Incident

Aorta

Summation
Systole

Diastole

Musculoelastic
& Muscular
Arteries

Reflected Waves

Hemodynamic Implications
IN YOUNG ADULTS

Low central (aortic) pulse wave velocity

Return of reflective wave during diastole
Enhancement of diastolic BP
Maintenance of normal coronary perfusion

Adequate left ventricular - arterial coupling

Pressure Pulse Waves

(Incident, Reflected, Summation)
ELDERLY
Reflected

Incident

Aorta

Summation
Systole

Musculoelastic
& Muscular
Arteries

Diastole

Reflected Waves Hemodynamic Implications

IN ELDERLY HYPERTENSIVE SUBJECTS

Decrease in aortic compliance

Marked increase in central (aortic) pressure

Left ventricular arterial mismatch

Pressure wave velocity

Return of reflected waves
in systole
Appearance of late systolic peak
Disproportionate increase in systolic over diastolic BP

* Increase in left ventricular afterload

* Decrease in coronary perfusion pressure
? Predisposition to coronary insufficiency

Assessment of Reflected Waves

(Augmentation Index)
AI%

AI%
PP

PP

Compliant

Stiff

Carotid Arterial Waveforms

(Applanation Tonometry)

Endothelial Function vs Age

Endothelial Function and Age

AGE (years)

Celermajer, J Am Coll Cardiol 1994;24:471

Age-Associated changes in
Vascular Structure and Function

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

The Epidemic of Hypertension:

Percent Hypertensive

Prevalence in US Adult Population

70
60

64

65

70-79

80+

54

50

44

40
30

21

20
10

11
4

0
18-29

30-39

40-49

50-59

60-69

Age
Based on NHANES III survey: 1988-1991
HTN defined by BP >140/90 or treated
Hypertension 1995; 25:305-315

Classification of Hypertension

90
Diastolic
BP

Isolated
Diastolic HTN

Mixed HTN

Normal
BP

Isolated
Systolic HTN

140
Systolic BP

Prevalence of ISH
50

% ISH

40
30

Men
Women

20
10
0

18-24 25-34 35-44 45-54 55-64 65-74

Age

Based on NHANES III Survey

Joffres, AJH 2001;14:1099

Pathogenesis of ISH

Increased vascular stiffness

Increased SBP
Decreased DBP
Widening of the Pulse Pressure
PP = SBP-DBP

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

(Framingham Cohort)
160
140-159
120-139
<120

n=1924

Adapted from Franklin et al. Circulation 1999;100:354.

P = probability for coefficients.

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

Therapeutic Interventions
Goals of antihypertensive Therapy
Reduction in systolic blood pressure

Reduction in pulse pressure

Improvement in viscoelastic properties

Therapeutic Interventions
Effects of Antihypertensive Therapy

Pulse Pressure

Viscoelastic
Properties

Morbidity/
Mortality

Decrease

Decrease

Improvement

Improved

Decrease

Decrease

No change

Increased

Systolic Blood
Pressure

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 (abnormal
elastic properties

Mechanisms of PP Increase in
Hypertension
Arterial
Stiffness

SVR

(vasoconstriction /
structural remodeling)

DBP

PWV

Systolic (rather than

diastolic augmentation )

, ,

DBP

SBP

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.

Aging/Senescence as a
Cardiovascular Risk Factor
Systolic BP

LVH

Pulse Pressure

Aging
Senescence

Renal Disease/
Proteinuria

Arterial
Stiffness

Diabetes
Mellitus

Novel Cardiovascular Risk

Factors
Cardiovascular
Risk Factors
- LVH
- Systolic hypertension
- High pulse pressure
- Arterial Stiffness
- Renal impairment/
proteinuria

Cardiovascular
Events
- Stroke
- Myocardial infarction
- Heart failure
- End stage renal
disease