Week 4 lecture - CVD

Question 1

CVD

Answer 1

‘A collective term describing the diseases affecting the heart and circulatory system’

Question 2

The 3 main diseases studied in relation to CVD and PA

Answer 2

Coronary heart disease, heart attacks, strokes

Question 3

Cardiorespiratory fitness and long-term survival in “low-risk” adults (Barlow et al 2012):

Answer 3

• 11,190 healthy men and women aged 30-50 years at entry, followed for 27 years, 774 died during follow-up (214 due to CVD).
• A 1 MET increase in baseline cardiorespiratory fitness was associated with an 18% reduction in CVD deaths after adjustment for confounders.

Question 4

Association of PA and fitness with coronary heart disease by genetic risk (Tikkanen et al 2018):

Answer 4

• UK biobank
• Pts at highest risk of CVD were those with the highest genetic risk
  Those with high levels of fitness have a 50-60% lower risk of developing CVD regardless of genetic risk

Question 5

Observational studies:

Answer 5

• Are influenced by confounding factors.
• Enable lots of questions to be answered from the same cohort.
  Assume behaviour measured at baseline remains stable over time (may not necessarily be true).
• Cannot draw cause and effect conclusions

Question 6

Atherosclerosis:

Answer 6

• A progressive disease that starts early and develops over the life course
• Involves a build up of fatty material within the arterial wall. Overtime this will narrow the blood vessel and start to impede blood flow. Ultimately this can lead to cardiovascular events.
• Deposits of plaque – fatty material, cholesterol, calcium and cellular debris – caused the artery to considerably narrow.
  A myocardial infarction happens when the coronary artery becomes blocked.

Question 7

Layers of an endothelial cell:

Answer 7

Inner layer = the intima – lined by a layer of endothelial cells (these are in direct contact with the blood) and this is where lots of the early processes in atherosclerosis take place.
Middle layer = media (contains lots of smooth muscle cells for vasodilation and vasoconstriction etc)
Outer layer = contains substances like collagen which give a lot of structure and support to the blood vessel

Question 8

Development of atherosclerosis:

Answer 8

1) Endothelial permeability, lipid uptake and fatty streak formation
2) Formation of advanced lesions
3) Plaque rupture

First stage of atherosclerosis is due to injury to first layer – Once the intima is damaged or injured it increases the permeability and allows substrates like lipids to enter and accumulate within the arterial wall. This leads to an inflammatory response – immune cells like monocytes get attracted to the area. These will enter and differentiate into macrophages within the arterial wall
- Macrophages digest and ingulf the lipid that has accumulated – take on foamy appearance, which overtime forms a fatty streak (the 1st visible lesion of atherosclerosis)
Overtime lipid and over debris accumulate within this legion. Smooth muscle cells and collagen move to the legion and start to accumulate. This will increase the size of legion, which will be covered in a fibrous plaque (Hardening of blood vessel wall). Here we have a more advanced atherosclerotic legion.
Over many years plaque grows and narrows artery to impede blood flow. This can cause blood clots and CV events

Question 9

Fatty streak and fibrous plaque

Answer 9

Fatty streak and fibrous plaque develop during the first 2 decades of life. Its not until we reach a 45% impediment of blood flow that manifestations of the disease occur.
Ages: 10-20 years: fatty streak, 30 years: fibrous plaque, 40 Years: Calcification, complicated lesion: haemorrhage, ulceration, thrombosis, 50-70 years: Infarct, stroke, gangrene, aneurysm

Question 10

Mechanisms responsible for the protective effect of physical activity and cardiorespiratory fitness:

Answer 10

• Body fatness
• Physical fitness
• Physiological mechanisms: insulin sensitivity, lipid and lipoprotein metabolism, blood pressure, vascular function, inflammation

Question 11

Risk factors on the causal pathway to CVD:

Answer 11

• Lipid profile
• BP
• Hypertension

Question 12

Lipoproteins fractions:

Answer 12

Chylomicrons transport dietary triacylglycerol from the small intestine to the peripheral tissues
VLDL transports endogenous triacylglycerol that’s synthesised at the liver to other peripheral tissues
LDL is the main transporter of cholesterol to other peripheral tissues
HDL is thought to be protective – removes cholesterol from the circulation in reverse cholesterol transport
Elevated levels of triacylglycerol in chylomicrons and VLDL, and elevated cholesterol in LDL are risk factors for atherosclerosis and CVD.

Question 13

% Triglycerides in lipoproteins:

Answer 13

• Chylomicron: 80-90%
• VLDL: 55-65%
• LDL: 10%
• HDL: 5%

Question 14

Exercise training and lipoproteins: STRRIDE (Slentz et al 2007):

Answer 14

• 24hr after the last training session:
  -Exercise resulted in an increase in HDL concentrations and a reduced in VLDL-TAG
  -Exercise training reduced small dense LDL – these are particularly atherogenic as they can easily accumulate in wall
• 15 days after the last training session benefits were decreased – the magnitude of change was attenuated – suggests we may need to regularly apply the exercise stimulus to maintain the benefit on the lipid profile
• Exercise is beneficial in terms of lipid profile: reductions in triacylglycerol and increases in HDL

Question 15

How can an increase in HDL cholesterol with exercise training contribute to reducing the risk of CV disease?

Answer 15

Removes cholesterol and transports it to the liver for excretion
- Elevated cholesterol is a major risk factor for atherosclerosis
Regular exercise elevates plasma HDL cholesterol and lowers triglyceride. Findings for total/ LDL cholesterol are less consistent.

Question 16

Blood pressure and CVD

Answer 16

Exercise can have both acute and chronic effect on BP
Single bouts of exercise can cause a transient reduction in BP
With accumulated and continuous walking there was significant reduction in systolic and diastolic BP

Question 17

Post exercise hypotension

Answer 17

A phenomenon describing a prolonged decrease in resting blood pressure in the minutes and hours following acute exercise

Question 18

Kokkinos et al. (1996) Effects of regular exercise on blood pressure and left ventricular hypertrophy in African American men with severe hypertension:

Answer 18

• Exercise caused a significant decrease in DBP evident at 16 and 32 weeks (even with ‘substantial reductions in medication’)
• Significant decrease in interventricular septum thickness and left ventricular mass at 16 weeks.
• Highlights potential for exercise as a non-pharmacological treatment for improving BP in pts with hypertension

Question 19

Anti-hypertensive effects of aerobic exercise: physiological mechanisms:

Answer 19

Mean arterial blood pressure = cardiac output  systemic vascular resistance
* Systemic vascular resistance = resistance to blood flow within the systemic circulation- determined by the balance between vasodilation and vasoconstriction of the blood vessels.
In aerobic exercise the reduction in systemic vascular resistance is greater than the increase in cardiac output – suggests vasodilation (less resistance to blood flow) is the primary driver that explains the reduction in BP with exercise

Question 20

Aerobic exercise reduces systemic vascular resistance:

Answer 20

• Vasodilation = primary driver explaining the reduction in BP with exercise
• Exercise releases histamine into skeletal muscle
• Exercise also resets the arterial baroreflex. This reduces sympathetic nerve activity and norepinephrine, which causes less vasoconstriction
• Reduction in norepinephrine promotes vasodilation – increases cross sectional area of blood vessel – aids blood flow
• Exercise training decreases thickness of the vessel wall increasing cross sectional area – less resistance to flow – reduced BP

Question 21

Endothelial function defintion

Answer 21

‘Ability of the endothelium to interact with vascular smooth muscle to influence blood flow”

Question 22

Endothelial dysfunction and atherosclerosis

Answer 22

Endothelial dysfunction occurs at every stage of the atherosclerotic process
- The intima allows adhesion of cells e.g., monocytes
- Endothelial function can increase susceptibility of the blood vessel to rupture
The endothelium also plays an important role in terms of vascular adaptations to exercise

Question 23

Exercise training and coronary endothelial function in patients with coronary artery disease (Hambrecht et al 2000):

Answer 23

• Exercise increases endothelium dilation
• Acetylcholine in a normal blood vessel causes vasodilation but in a damaged blood vessel it causes vasoconstriction
• Exercise resulted in a 54% improvement in the vasodilatory response with the infusion of acetylcholine
• This method of assessing endothelial function with the infusion of acetylcholine is very invasive – can’t be used as standard practice

Question 24

Most common method for measuring endothelial function

Answer 24

Flow mediated dilation (non-invasive technique where a cuff is placed on the upper arm- inflate cuff to occlude blood flow- when cuff is released, vasodilatory response of the brachial artery (which gives us an indication of vascular function) can be measured.

Question 25

Exercise effect on endothelial function

Answer 25

Functional adaption: NO induced vasodilation:
Exercise causes an increase in blood flow through the vessel. This results in an upregulation of the enzyme eNOS. This enzyme catalyses NO (a potent vasodilator). Once NO is released from the endothelial cells, it diffuses to the smooth muscle cell, causing it to relax. It is there that improvements in vascular function is observed.
* NO diffuses into smooth muscle cell causing it to relax – improvement in endothelial function

Question 26

Structural adaption to exercise training: arterial remodelling (Tinken et al 2008):

Answer 26

Reduction in thickness of vessel wall
Increase in cross sectional area of vessel
Improved vascular function
Regular exercise may enlarge the coronary arteries, lower blood pressure, reduce the risk of blood clots, improve endothelial function and reduce chronic inflammation