Cardio Ageing

Question 1

What conditions increase the risk of heart failure?

Answer 1

Hypertension
Heart attack
Vascular disease

Diabetes
Obesity

Structural abnormalities
Genetic cardiomyopathy

Question 2

What is the difference between HFrEF and HFpEF?

Answer 2

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

Question 3

What tissue remodelling occurs in the ageing heart?

Answer 3

Angiogenic potential and vascular function
Valvular stiffening
Impaired conduction
Diastolic dysfunction
Large artery fibrosis & atherosclerosis
ECM fibrosis & myocyte hypertrophy

Question 4

How does angiogenic potential and vascular function change in the ageing heart?

Answer 4

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.

Question 5

How do valves change in the ageing heart?

Answer 5

Valves stiffen

Increase in collagen and calcium deposition, and stenosis

Decrease in proliferation and extensibility

Question 6

How does conduction change in the ageing heart?

Answer 6

Slower conduction = AP duration increases

Voltage decreases in QRS and T wave on ECG

Question 7

How does diastole change in the ageing heart?

Answer 7

Diastolic dysfunction = a condition where the heart’s left ventricle becomes stiff or less able to relax properly during diastole

Question 8

How do large arteries change in the ageing heart?

Answer 8

Fibrosis and atherosclerosis occurs

Increase in collagen deposistion and intimal thickness

Question 9

How does ECM change in the ageing heart?

Answer 9

Fibrosis and myocyte hypertrophy

Muscle cells increase in size to compensate for the increased workload on the heart

Question 10

What is the equation for ejection fraction?

Answer 10

Stroke volume / EDV

Question 11

What is the normal value for ejection fraction?

Answer 11

50% - 65%

Approx half the blood volume in the LV should get pumped out during each heartbeat

Question 12

Do genetics play a role in cardiac ageing?

Answer 12

Yes

Question 13

What are possible agents with anti-inflammaging properties?

Answer 13

RAAS inhibitors
Statins
Acetylsalicylic acid
IL-6 inhibitors

Question 14

What is a regulator of fibroblast activation?

Answer 14

TGF-beta

Question 15

What happens when we inhibit IL-11?

Answer 15

IL11 and its receptor is highly expressed in fibroblasts when given TGF-beta

Inhibiting IL11 stops fibroblasts from becoming activated
STOPS fibrosis

Question 16

Would we be better off without IL11?

Answer 16

IL11 can be helpful for animals that can regenerate

But for us humans, IL11 may not be needed

Question 17

Name 5 pathologies that occur with ageing/stress/heart failure development

Answer 17

Collagen accumuation
ECM stiffer
Fibrosis increases
Cardiomyocyte hypertrophy
Diastolic function is impaired

Question 18

What does CHIP stand for?

Answer 18

Clonal hematopoiesis of indeterminate potential

Question 19

What is clonal hematopoiesis of indeterminate potential?

Answer 19

Common bone marrow abnormality

Induced by age-related DNA mutations, which give rise to proinflammatory immune cells

Question 20

What is the association between clonal hematopoiesis and heart failure?

Answer 20

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

Question 21

What are some potential treatment targets for clonal hematopoiesis-related inflammation?

Answer 21

JAK2 inhibitors & NLRP3 Inhibitors

Prevents the activation of inflammasomes, which then activates caspase1 and gasderminD to produce proinflammatory cytokines

Question 22

What are SGLT2 inhibitors used for?

Answer 22

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