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a_ARTS > 11/16- Cardiac and Vascular Aging > Flashcards

11/16- Cardiac and Vascular Aging Flashcards

1
Q

What do studies show for early aging vs. later aging studies?

A

Early studies:

  • Reduced resting cardiac output (index)
  • Increased systolic BP
  • Increased diastolic BP
  • Decreased ejection fraction

Later studies:

  • Unchanged resting cardiac output (index)
  • Increased systolic BP
  • Unchanged diastolic BP
  • Unchanged ejection fraction
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2
Q
  • __% of men after the __ decade have no evidence of CAD at autopsy
  • Women lag by ____
A
  • 25% of men after the 6th decade have no evidence of CAD at autopsy
  • Women lag by 2 decades
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3
Q

T/F: CAD is not normal aging

A

True!

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4
Q

What are age changes in arterial structure?

A

Irregularities in size and shape of endothelial cells

  • Hints of replicative senescence at areas of turbulence (high cellular turnover)

Also:

  • Fragmentation of elastin in internal elastic lamina and media
  • Calcification of media
  • Increased lumen diameter, vessel length, wall thickness
  • Collagen increases, cross- linking, especially in subendothelium
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5
Q

Describe age changes in arterial function

A
  • Reduced compliance, increased impedance (stiffness)
  • Increased systolic BP; no change or small decrease in diastolic pressure
  • Wider pulse pressure
  • Decreased blood pressure response to vasodilator drugs
  • Decreased endothelium production of vasoactive substances (especially NO)
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6
Q

How does systolic BP change with age? Describe

  • Gender
A

Systolic BP increases with age

  • For men (Framingham study), systolic BP increased 5/decade until 60 and then the slope shifted up to 10/decade
  • For women, SBP started lower but shifter to higher slope earlier
  • Diastolic BP remains unaltered (80 in men; 70-80 in women)
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7
Q

What happens to pulse wave velocity with increasing stiffness?

A

Pulse wave velocity increases with increasing stiffness (how we measure stiffness; how fast pressure waves run in the wall of the blood vessel)

  • PWV = D/delta t
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8
Q

What happens to the large artery stiffness with age? Describe

A

Large arteries stiffen with age

  • Likely due to collagen and elastin changes
  • Stiffer arteries provide less cushioning function (higher peaks result) and pressure reflections occur
  • Reflection of large artery changes not small vessel change
  • Not atherosclerosis
  • Diameter and length of aorta increase (uncoiling of the old aorta)
  • Disease changes add to age changes
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9
Q

How are age-related changes different from atherosclerosis:

  • Populations affected
  • Heterogenous/uniform
  • Lumen changes
  • Severity
  • Inflammatory component
  • Cholesterol factor
A

(STILL CONSIDER: age increases risk of atherosclerosis)

Atherosclerosis:

  • Unique to Western man
  • Heterogeneous
  • Compromises lumen
  • Severity related to turbulence and shear stresse
  • Has inflammatory component
  • Cholesterol is cofactor

Age-related changes:

  • Occur in most species
  • Uniform in large arteries
  • Lumen enlarges
  • Not localized to sites of stress
  • No white cells or others participate
  • Independent of cholesterol
  • But age increases risk of atherosclerosis
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10
Q

What are cardiac changes that occur with aging?

A
  • Increased left atrial size
  • Mild left ventricular hypertrophy
  • Reduced left ventricular cavity size
  • Moderate cellular hypertrophy in ventricles
  • Increased lipofuscin
  • Increased fibrous tissue in atria and ventricles
  • Accumulation of fat and collagen between muscle bundles
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11
Q

What happens to old cardiac mycoytes?

A

They are hypertrophied

  • After birth, cardiac myocytes cannot increase in number
  • Cardiac mass increases by hypertrophy of cells
  • Myocyte diameter and length increase in hearts from healthy older people and animals
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12
Q

What happens to the sino-atrial node with age?

A

There is decreased volume of sino-atrial node with age

  • Reduced number of pacemaker cells in the sino-atrial node (90% dead by age 70) with most volume replaced by fat
  • More modest losses at A-V node
  • Minimal changes in distal conduction system
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13
Q

What are changes in heart rate with age?

A
  • No change in resting heart rate
  • Marked decrease in max heart rate
  • Marked decrease in heart rate variability
  • Decreased heart rate response to sympathetic and parasympathetic agents
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14
Q

What happens to the intrinsic heart rate with age?

  • What are consequences of this
A

Decrease in intrinsic heart rate with age

  • Propranolol and atropine given to ablate all input to the heart
  • Intrinsic heart rate decreases 5-6 beats/decade
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15
Q

Describe more about changes to max heart rate with exertion

  • Equation
  • Modifiable?
A

Decreased max heart rate with exertion

  • For men: 220 - age = max heart rate for exercise testing
  • For women: lower peak in youth and more gradual fall in maximum; 0.85*(men from above equation)
  • No level of training can modify this decline in max heart rate
  • Decrease in heart rate reflected with illness and after sympathomimetic drugs
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16
Q

Clinical relevance slide:

  • You are working in the ER and 2 men present with pneumonia. The 80 yo has a heart rate of 120. The 25 yo has a heart rate of 170. You know the heart rate correlates with severity of illness. Which gentleman is sicker?

Why?

A

Same; heart rate of 120 in 80 yo is equivalent to 170 in a 25 yo

  • HR of 120 in 75 yo man is roughly 75% of max heart rate, the same as 170 in a 20 yo
  • 220-age = max HR for men
  • Men * 0.85 in women
  • Underestimate response to illness
  • Reinterpretation of sinus tachycardia and severity of illness
  • Resting HR does not change with age
17
Q

How do responses to sympathetic nervous system change with age? Describe

A

Decreased responses to sympathetic nervous system

  • Administration of Isoproterenol to healthy young and old people demonstrated that the chronotropic effects of sympathomimetic agents is markedly attenuated in the old
  • At doses that increased heart rate 25/min in young, the old had increase of 10/min or less
  • Inotropic and lusitropic (relaxation) responses also decreased with age
18
Q

Recap

A

Old people have unchanged resting heart rates but lower max heart rates

19
Q

What is the net result of these cardiac changes with aging?

A

Decrease in max oxygen utilization (VO2 max)

20
Q

Describe VO2 max (max oxygen utilization) changes with age

  • Due to what
A
  • VO2 max decreases with age
  • VO2 max decrease is due to cardiac and muscle factors
  • All activities become a larger relative percent of VO2 max and are perceived as harder
  • Detraining effect of bed rest may produced disability by lowering VO2 max further
21
Q

What are determinants of VO2 max?

A
  • VO2 max is dependent on cardiac output
  • Cardiac output = HR x SV
  • Diastolic function is a key determinant of VO2 max
  • Other determinents:
  • Age
  • Systolic function
  • Peak heart rate
  • LV mass
  • Gender
22
Q

Describe decreased max VO2 with age?

  • Effects of exercise
A
  • With age, max work or max oxygen consumption decrease
  • Even highly trained individuals will have this decrease despite no changes in training
  • Exercise training of sedentary older people will “buy them 30 yrs”
  • No change in efficiency; in both men and dogs the relationship between CO and VO2 max is unchanged by age
23
Q

T/F: There is no difference in efficiency between old and young

A

True (work vs. cardiac output maintains linear relationship)

24
Q

T/F: LV ejection fraction decreases with age. Why?

A

False; there is no change in LV ejection fraction in healthy elders

  • This is the result of successful adaptations
  • Whether or not exercise ejection fraction is modified by age is uncertain
25
Q

Describe the change in pattern of contraction and papillary muscles with aging

A
  • Left ventricular papillary muscles from old hearts develop as much tension as those from younger hearts
  • Tension development is slightly slower
  • Relaxation is markedly slower in the old muscles
  • Impaired relaxation impacts diastolic function
26
Q

_______ is more important to LV filling in old people

A

Atrial systolic function is more important to LV filling in old people

  • In the young, LA systole contributes only to 15% of LV filling; in the old it provides up to 50%
  • Atrial fibrillation may produce CHF in the elderly
27
Q

What happens to wedge pressure in exercising old people?

A

Wedge pressure increases in exercising old people

  • In young people, when demand is increased and cardiac blood flow is increased, there is NO increase in LV filling P
  • In old people, Starling’s law is used to increase CO, likely because the other responses are inadequate
28
Q

___ determines VO2 max

A

Diastole determines VO2 max

  • In a cross-sectional study, found that diastolic function (ratio of early filling: atrial component or E;A ratio) determined over 60% of VO2 max
  • Other parameters of diastolic function were almost as important
29
Q

What population has better diastolic function?

  • Despite what
  • E/A ratio
A

Athletes have better diastolic function

  • Despite cardiac hypertrophy, E/A ratio in athletes is higher (better) than sedentary controls
  • Exercised trained individuals have augmented diastolic function
  • Calorically restricted people also have augmented diastolic function
30
Q

What are the 3 main determinants of diastolic function?

A
  1. Active relaxation
  2. Passive stiffness
  3. Uniformity of LV
    - Heart rate and CO impact adquacy
31
Q

Describe calcium fluxes in the old heart

A

Calcium fluxes are impaired in the old heart

  • Move outside cell: through slow Ca channel, Na-Ca exchanged, and sarcolemma Ca pump
  • Move from SR: through SR calcium release channel and uptake by SR Ca pump
  • 90% of Ca cycles in/out of SR
  • Increased leak of Ca from old SR
32
Q

There is ______ (increased/decrease) SR Ca uptake with age. Why?

A

There is decreased SR Ca uptake with age

  • Net Ca reuptake into the SR is decreased by almost 50% in old hearts because of less pump protein (SERCA2a)
  • This slows cardiac relaxation and results in smaller stores in the SR for release in the next contraction
  • To a small extent, compensation occurs in other Ca fluxes
33
Q

Describe SR Ca handling with endurance exercise training

A

Increased SR Calcium uptake and improved relaxation with endurance exercise training

  • Old rats trained on treadmill for 1-2 mo improved SR Ca uptake to that seen in young sedentary rats
  • With improved Ca uptake, papillary muscle relaxation improved to equal that seen in young sedentary rats
  • In humans after 6 mo of endurance training, improvement in relaxation is seen
34
Q

What are the clinical implications of CVS aging changes?

A
  • S4 is a normal finding in those over 75 yo
  • This is indicative of atrial gallop and reflects the increased function of the left atrium
  • Decreased responsiveness to some CV drugs
  • Congestive heart failure becomes increasingly common with age
  • Especially that with preserved systolic function (also call normal LVEF)
35
Q

How does MI mortality change with age?

  • Gender
A

There is increased mortality from MI with age in humans

  • Women have 2x mortality if they have an MI
36
Q

What is evidence for engagement of reserves at rest?

A

Decreased response to pressure overload

  • Old and adult rats had afterload increased by constriction of the aorta
  • Hearts were harvested to evaluate the response to this hemodynamic stress
  • Immediate early response gene signals were attenuated in the old rats; prompt cardiac hypertrophy
  • Old are unable to respond further
37
Q

Why is there a decreased ability to hypertrohy in elderly?

A

Decreased skeletal actin expression after pressure overload

  • Skeletal actin expression precedes cardiac actin expression in most models of hypertrophy
  • Expression of skeletal actin increased in the adult rat heart, not the old heart
38
Q

Describe ANP expression in the old rat ventricle

A
  • ANP stimulates excretion of water and Na by the kidney
  • ANP is only expressed by the atria in normal young hearts
  • ANP is a marker of stress and compensation when seen in the ventricles
  • In the old rat, ANP is elevated in the ventricles at baseline and could not be further stimulated after additional stress
39
Q

SUMMARY

  • Age-related changes in vessel and heart do not by themselves produce disease
  • Compensation for these changes makes the old CVS more prone to decompensation in response to other insults
  • Heart failure due to diastolic dysfunction may be so common in the elderly because of underlying age-related changes
A

Yup

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