Cardio Ageing Flashcards
What conditions increase the risk of heart failure?
Hypertension
Heart attack
Vascular disease
Diabetes
Obesity
Structural abnormalities
Genetic cardiomyopathy
What is the difference between HFrEF and HFpEF?
With reduced EF, this means the heart has become weakened/damaged so cannot pump the blood out effectively
With preserved EF, the heart can contract normally, but it cannot relax fully so less blood fills it
What tissue remodelling occurs in the ageing heart?
Angiogenic potential and vascular function
Valvular stiffening
Impaired conduction
Diastolic dysfunction
Large artery fibrosis & atherosclerosis
ECM fibrosis & myocyte hypertrophy
How does angiogenic potential and vascular function change in the ageing heart?
Decline in both angioenesis and vacular function
Decreased VEGF, PDGF and NO bioavailability
The heart’s ability to form new blood vessels becomes impaired, partly due to a decrease in endothelial cell function, lower VEGF production, and increased fibrosis in the vascular walls.
How do valves change in the ageing heart?
Valves stiffen
Increase in collagen and calcium deposition, and stenosis
Decrease in proliferation and extensibility
How does conduction change in the ageing heart?
Slower conduction = AP duration increases
Voltage decreases in QRS and T wave on ECG
How does diastole change in the ageing heart?
Diastolic dysfunction = a condition where the heart’s left ventricle becomes stiff or less able to relax properly during diastole
How do large arteries change in the ageing heart?
Fibrosis and atherosclerosis occurs
Increase in collagen deposistion and intimal thickness
How does ECM change in the ageing heart?
Fibrosis and myocyte hypertrophy
Muscle cells increase in size to compensate for the increased workload on the heart
What is the equation for ejection fraction?
Stroke volume / EDV
What is the normal value for ejection fraction?
50% - 65%
Approx half the blood volume in the LV should get pumped out during each heartbeat
Do genetics play a role in cardiac ageing?
Yes
What are possible agents with anti-inflammaging properties?
RAAS inhibitors
Statins
Acetylsalicylic acid
IL-6 inhibitors
What is a regulator of fibroblast activation?
TGF-beta
What happens when we inhibit IL-11?
IL11 and its receptor is highly expressed in fibroblasts when given TGF-beta
Inhibiting IL11 stops fibroblasts from becoming activated
STOPS fibrosis
Would we be better off without IL11?
IL11 can be helpful for animals that can regenerate
But for us humans, IL11 may not be needed
Name 5 pathologies that occur with ageing/stress/heart failure development
Collagen accumuation
ECM stiffer
Fibrosis increases
Cardiomyocyte hypertrophy
Diastolic function is impaired
What does CHIP stand for?
Clonal hematopoiesis of indeterminate potential
What is clonal hematopoiesis of indeterminate potential?
Common bone marrow abnormality
Induced by age-related DNA mutations, which give rise to proinflammatory immune cells
What is the association between clonal hematopoiesis and heart failure?
Mutations in HSCs and progenitors give rise to clones that expand over time
Factors stimulate clonal proliferation
These mutated cells enter blood stream and myocardium and cause atherosclerosis and impaired cardiac function
Inflammasome-mediated response = central to clonal hematopoiesis-induced heart failure
What are some potential treatment targets for clonal hematopoiesis-related inflammation?
JAK2 inhibitors & NLRP3 Inhibitors
Prevents the activation of inflammasomes, which then activates caspase1 and gasderminD to produce proinflammatory cytokines
What are SGLT2 inhibitors used for?
Lowers blood gucose by promoting glucose excretion via urine = decrease in blood volume
The reduction in blood volume helps lower preload (the volume of blood returning to the heart), reducing the workload on the heart and improving its pumping efficiency.
Fluid overload is a key contributor to worsening heart failure, particularly in HFrEF
