11/16- Cardiac and Vascular Aging Flashcards
What do studies show for early aging vs. later aging studies?
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
- __% of men after the __ decade have no evidence of CAD at autopsy
- Women lag by ____
- 25% of men after the 6th decade have no evidence of CAD at autopsy
- Women lag by 2 decades
T/F: CAD is not normal aging
True!
What are age changes in arterial structure?
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
Describe age changes in arterial function
- 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)
How does systolic BP change with age? Describe
- Gender
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)
What happens to pulse wave velocity with increasing stiffness?
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
What happens to the large artery stiffness with age? Describe
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
How are age-related changes different from atherosclerosis:
- Populations affected
- Heterogenous/uniform
- Lumen changes
- Severity
- Inflammatory component
- Cholesterol factor
(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
What are cardiac changes that occur with aging?
- 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
What happens to old cardiac mycoytes?
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
What happens to the sino-atrial node with age?
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
What are changes in heart rate with age?
- 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
What happens to the intrinsic heart rate with age?
- What are consequences of this
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
Describe more about changes to max heart rate with exertion
- Equation
- Modifiable?
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
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?
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
How do responses to sympathetic nervous system change with age? Describe
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
Recap
Old people have unchanged resting heart rates but lower max heart rates
What is the net result of these cardiac changes with aging?
Decrease in max oxygen utilization (VO2 max)
Describe VO2 max (max oxygen utilization) changes with age
- Due to what
- 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
What are determinants of VO2 max?
- 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
Describe decreased max VO2 with age?
- Effects of exercise
- 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
T/F: There is no difference in efficiency between old and young
True (work vs. cardiac output maintains linear relationship)
T/F: LV ejection fraction decreases with age. Why?
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
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
_______ 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
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
___ 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
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
What are the 3 main determinants of diastolic function?
- Active relaxation
- Passive stiffness
- Uniformity of LV
- Heart rate and CO impact adquacy
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
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
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
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)
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
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
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
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
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
