11/16- Cardiac and Vascular Aging Flashcards
(39 cards)
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
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
3
Q
T/F: CAD is not normal aging
A
True!
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
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)
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)
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
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
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
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
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
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
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
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
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
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
Describe the change in pattern of contraction and papillary muscles with aging
- 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
\_\_\_\_\_\_\_ is more important to LV filling in old people
**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
What happens to wedge pressure in exercising old people?
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
\_\_\_ determines VO2 max
**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
What population has better diastolic function?
- Despite what
- E/A ratio
**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
What are the 3 main determinants of diastolic function?
1. Active relaxation
2. Passive stiffness
3. Uniformity of LV
- Heart rate and CO impact adquacy
31
Describe calcium fluxes in the old heart
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
There is ______ (increased/decrease) SR Ca uptake with age. Why?
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
Describe SR Ca handling with endurance exercise training
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
What are the clinical implications of CVS aging changes?
- 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
How does MI mortality change with age?
- Gender
There is increased mortality from MI with age in humans
- Women have 2x mortality if they have an MI
36
What is evidence for engagement of reserves at rest?
**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
Why is there a decreased ability to hypertrohy in elderly?
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
Describe ANP expression in the old rat ventricle
- 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
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
Yup
