Cardiovascular System
& Aging
February 28th, 2018
Alyssa Rudolph
Sex Differences in the Biology and Pathology
of the Aging Heart
Overview:
● Age associated changes
○ Cellular Aging
○ Structural changes
○ Frailty
● Age impacting cardiac function
○ Pacemaker/cardiac conduction
○ Cardiac Remodeling
○ Systolic & diastolic functions
● Cellular mechanisms + dysfunction
○ Chronic activation of pathways
○ Mitochondrial dysfunction
Cardiovascular Disease (CVD)
● ↑ Age = ↑ Risk
● Age itself
● Aging heart = more susceptible
● Macroscopic & microscopic
● Chronological aging vs. biological aging
Age-associated Changes
Macroscopic level changes
● Epicardial adipose tissue deposition
● Calcification of regions
● Morphologic structure
● Left ventricular (LV) wall thickening
Figure 1.
Age-associated Changes
Microscopic level change
● Sinoatrial node (SAN) pacemaker cells ↓
● Ventricular myocyte ↓
○ Men vs. women
○ Age-related cell loss > mechanical burden > compensatory hypertrophy
○ Volume increases with age
● Proliferation of cardiac fibroblasts
● Gross + cellular change = myocardial function
Animals Exhibit Changes Seen in Humans
● Animal cardiac change similar to human
○ Rats & mice = 50% mortality at 24 months
○ Humans = 85-year of age
● Epicardial fat deposition, valve calcification, atrial hypertrophy
● Larger animals = fibroblast proliferation, collagen accumulation
● Ventricular myocyte hypertrophy - guinea pigs, rabbits
○ Males vs. females
● Age-dependent myocyte loss and hypertrophy occur at same rates?
● Frailty Index Score:
Frailty Counting deficits in health
Total # of potential deficits
● Aged mice
○ Myocyte hypertrophy = high frailty scores
Biological age
● Age dependent remodeling linked to frailty
○ More than chronological age
Impact of Age
● Heart structure
○ Calcification of aortic valves = impairs movement
● Pacemaker + cardiac conduction
○ Age-associated decline in responsiveness
○ Heart rate (HR) changes, lying vs. seated
○ Decline in pacemaker cell number > lower HR in older adults
● SAN dysfunction > development of bradyarrhythmias
● Age dependent changes affect conduction
Impact of Age: Atrial Remodelling
● Slow early LV filling
○ Increases diastolic pressure > atrial dilatation and hypertrophy
○ Atrial contraction enhanced
○ Promotes late diastolic filling
● Consequence = reduced cardiac output > heart failure
● Loss of SAN cells, atrial mycotes
● Age-related changes + hypertrophy = atrial fibrillation
○ Higher incidence in men
○ Men vs. women, additional studies needed
Impact of Aging: Sex + systolic function
Male Female
● Systolic function found to decline with age ● No decline in systolic function
● Ventricular myocytes declines with age ● No decline in myocytes with age
● Likely to experience heart failure with ● Less likely to experience heart failure with
reduced ejection fraction (HFrEF) reduced ejection fraction
Impact of Aging: Diastolic dysfunction
● LV fills slower as we age
● Slowing of relaxation in diastole = predispose aging heart to
failure
○ Preserved ejection fraction (HFpEF)
○ Increased wall thickness, diastolic dysfunction
● Risk factors differ for sexes
○ Myocardial ischemia, men
○ Hypertension, women
● Treatment lacks for HFpEF
○ Studying aging rodents
○ Potential relevance to humans
Impact of Aging: Cardiac function + exercise
● Maximum heart rate decline with age
● Exercise
○ Activates sympathetic stimulation
○ Release of catecholamines
○ Activation of b-adrenergic receptors
○ Rate/force of contraction
● Evidence = response to b-adrenergic stimulation ↓ with age
○ Humans + animals
● Lower MHR impair ability of aging heart
● Response to exercise is different
Calcium ● Regulation of intracellular calcium affect heart
Homeostasis contractions
● Altered calcium homeostasis >
slowed relaxation + diastolic dysfunction
● Slower calcium decay + prolonged availability =
negative effects cardiac function
Pathway activation
B-adrenergic Pathway
● High-levels of catecholamines > chronic activation of beta-adrenergic pathways
○ Humans + animals
● Activation can damage heart
○ increasing mitochondrial reactive oxygen species (ROS)
● Chronic activation desensitize elements of signalling
○ Limits HR response
● Male, female difference = additional studies
Mitochondrial Dysfunction
● Heart = mitochondrial rich
● ROS generation ↑ age
● Age associated increase in ROS damaging
● ROS generation and mitodoncdrrial damage contribute to cardiac aging
Cardiovascular System + Aging:
In Summary
➔ CVD increases with age - both sexes
➔ Men and women predisposed differently as they age
➔ Marked-age dependent changes exist
➔ Age-related structural changes exist & have clinical consequences
➔ Frailty impacts cardiac aging
➔ Further research needed for treatments of CVD in both sexes
