Cardiovascular Health Flashcards
What is the general term given to conditions affecting the heart and blood vessels, such as atherosclerosis, hypertension, angina, myocardial infarction and stroke?
Cardiovascular Disease (CVD)
Name 3 conditions that may be grouped under Cardiovascular Disease (CVD)
Atherosclerosis
Hypertension
Angina
Myocardial infarction
Stroke
List 3 things that greatly increase CVD risk.
High intake of processed foods
++ Sugar
++ Salt
Unhealthy fats
Alcohol
Lack of exercise
Excess body fat
Stress
Smoking
What is the endothelium?
A monolayer of endothelial cells lining the blood interface throughout the CVS, including cardiac chambers.
Normal functioning of the endothelium is CRITICAL to vascular health. True or false?
True
What is the glycocalyx?
A carbohydrate-rich protective layer covering the endothelium.
What is the name given to the carbohydrate-rich protective layer that covers the endothelium?
Glycocalyx
What is the function of the glycocalyx?
Regulate endothelial permeability
Control nitric oxide production
Acts as a mechanosensor of blood shear stress
What is blood shear stress, and what acts as a mechanosensor of it?
Blood shear stress is the force of flowing blood on the endothelial surface of the blood vessel.
The glycocalyx is the sensor of this.
Where would you find the glycocalyx?
Covering the endothelium (throughout the cardiovascular system)
List 3 things that may damage the glycocalyx
Inflammation
Hyperglycaemia
Endotoxemia
Oxidised LDL
Abnormal blood shear stress
Damage to the ___________ commonly precedes further damage to the endothelium, promoting lipid deposition and atherosclerosis
Glycocalyx
What name is given to the frictional force of blood on endothelial cells?
Blood shear stress
List 3 key functions of the endothelium
Semi-permeable barrier: fluid balance, host defence, movement of substances
Regulates vascular tone: secretes vasodilators and vasoconstrictors
Enzymes: Contains angiotensin converting enzyme (ACE) - key role in regulating blood pressure
Angiogenesis: endothelial cells are the origin of all new blood vessels
Haemostasis: the luminal surface of endothelium prevents platelet adherence and coagulation
Immune defence: healthy endothelial cells deflect leucocyte adhesion and oppose local inflammation
Name one vasodilator and one vasoconstrictor secreted by the endothelium.
Nitric oxide (vasodilator)
Endothelin (vasoconstrictor)
Which part of the cardiovascular system contains angiotensin-converting enzyme (ACE)?
The endothelium
Which type of cells are the origin of all new blood vessels?
Endothelial cells
What is the role of nitric oxide in the cardiovascular system?
Vasodilator
What is the role of endothelin in the cardiovascular system?
Vasoconstrictor
Which type of cells, located in the tunica media of blood vessels, regulate blood circulation and pressure by playing a key role in vessel contraction and dilation?
Vascular Smooth Muscle cells (VSMCs)
In which layer of blood vessels would you find vascular smooth muscle cells?
In the tunica media
What is the role of vascular smooth muscle cells and where would you find them?
They regulate blood circulation and blood pressure.
Found in the tunica media
Which cells maintain the integrity and elasticity of blood vessels, whilst limiting immune cell infiltration?
Vascular smooth muscle cells.
What is phenotype modulation?
Altering of physical form/structure through the interaction between the genotype and environment.
List 2 things that may cause phenotypic modulation of vascular smooth muscle cells.
Inflammation
Oxidative stress
Telomere damage
Why are phenotypic changes to vascular smooth muscle cells central to vascular disease, especially atherosclerosis and hypertension?
Because vascular smooth muscle cells regulate blood circulation and pressure, and limit immune cell infiltration.
What does nitric oxide play in cardiovascular health? (List 3 things)
Regulates vascular tone
Reduces platelet aggregation
Inhibits leukocyte adhesion
Inhibits inflammatory cytokines
Opposes oxidation of LDLs
Which enzyme is required to generate nitric oxide from L-arginine?
eNOS
(endothelial nitric oxide synthase)
Nitric oxide is continuously generated from the amino acid L-___________ by the enzyme eNOS.
L-arginine
Nitric oxide diffuses easily from the endothelium into _____________ cells and the bloodstream.
Vascular smooth muscle cells
Which vitamin regulates nitric acid synthesis by mediating eNOS?
Vitamin D
What role does vitamin D play in the cardiovascular system?
It regulates nitric oxide synthesis by mediating eNOS.
Reduced ________ _________ contributes to atheroma formation and CVD.
Nitric oxide
List 3 ways in which oxidative stress and inflammation impacts endothelial cells / the endothelium
Increases permeability
Increases inflammatory cytokines
Increases leukocyte adhesion
Reduces vasodilators
Increases risk of thrombosis
List 3 ways in which oxidative stress and inflammation impacts vascular smooth muscle cells.
Increases inflammatory cytokines
Increases extracellular matrix synthesis
Causes them to migrate into the tunica intima
Causes them to proliferate
What are PPARs?
Nuclear transcription factors that control gene expression
What do PPARs control?
Gene expression
What is the name given to the nuclear transcription factors that control gene expression?
PPARs
What do PPARs do for CV health (2 things)?
Decrease inflammation
Promote endothelial health
PPAR__ activation increases HDL-C, reduces triglycerides and inflammation and is anti-artherosclerotic.
PPARa
What does PPAR-a do in the CV system (list 2 things)?
Increases HDL-C
Reduces triglycerides
Reduces inflammation
Anti-atherosclerotic
List 3 PPARa agonists
Green tea
Resveratrol
Oregano
Thyme
Rosemary
Naringenin (citrus bioflavonoid)
Omega-3
What does PPAR-y do for the CV system (list 2 things)
Reduces blood glucose
Reduces fatty acids
Reduces insulin
List 3 natural PPAR-y agonists
Apigenin
Hesperidin
Curcumin
Resveratrol
EGCG
What does PPAR stand for?
Peroxisome proliferator-activated receptor (PPAR)
List 3 risk factors for cardiovascular disease
Family history - siblings and parents
Genetics - various polymorphisms including MTHFR and ACE
Ethnicity - particularly south asian / African
Gender - primarily male but female risk is increasing
Dislipidemia
Hypertension
Mitochondrial dysfunction
Elevated homocysteine
Low folate and B12
Thyroid dysfunction
Inflammation
Obesity
Insulin resistance
Chronic stress
Periodontal disease
Heavy metals
Melatonin deficiency
Why is risk of CVD underestimated in women?
Because women tend to experience more vague physical signs
List 2 of the vague CVD signs that may be seen in women
Lightheaded with exertion
Symptoms easily mistaken for the menopause or heartburn
Describe dyslipidemia
Increased total cholesterol, LDL, VLDL, IDL, Lp(a), triglycerides, with decreased HDL-C
________, a form of LDL, also acts as a clotting factor, further increasing CVD risk.
Lp(a) - lipoprotein A
List 3 things associated with the development of dyslipidaemia
Sedentary lifestyle
Excess alcohol
Smoking
Obesity
High sat & trans fat intake
Menopause
T2DM
Hypothyroidism
Chronic kidney disease
Dyslipidemia is largely preventable, true or false?
True
CVD pathologies tend to appear 5 years earlier in those with hypertension. True or false?
True
Why does mitochondrial dysfunction contribute to CVD?
ATP is required to pump Ca ions out of myocardial cells, allowing relaxation and maintaining the electrochemical gradient across the myocardial cell membrane.
Elevated homocysteine is associated with LDL oxidation, monocyte adhesion and endothelial dysfunction.
List 3 things that elevated homocysteine may be related/due to.
Low folate and B12 - needed for re-methylation of homocysteine to methionine.
Low B6 - a co-factor in conversion of homocysteine to cysteine in the methylation cycle
Genetic polymorphisms - MTHFR, FUT2, TCN, etc
Thyroid dysfunction - Thyroid hormone receptors are present in the myocardium and vascular tissue. Minor thyroid changes can impact CV homeostasis.
Inflammation - from various origins
Which common SNP may contribute to elevated homocysteine?
MTHFR - impacts supply of methyl groups needed to methylate B12 and in turn, re-methylate homocysteine to methionine.
Why are hypo and hyperthyroidism linked to endothelial dysfunction, dyslipidemia and BP changes?
Because thyroid hormone receptors are present in the myocardium and vascular tissue. Minor thyroid hormone changes can alter CV homeostasis.
Inflammation is a CVD risk factor. But where might it come from?
Dyslipidaemia
Gut dysbiosis
Intestinal permeability
Oxidative stress
Diabetes
Excess adipose tissue
Smoking
Endothelial dysfunction
Obesity / excess adipose tissue
____________, a peptide that influences expression of endothelial cells, protecting against CVD is decreased in obesity.
Adiponectin
Name the cardioprotective peptide that influences expression of endothelial cells, protects against CVD and increases insulin sensitivity.
Adiponectin
List 2 ways in which obesity contributes to CVD risk
Excess adipose tissue perpetuates inflammation
Lowers levels of adiponectin (CVD protective peptide)
Contributes to insulin resistance
High leptin levels drive vasoconstriction and increased blood pressure.
Obesity is associated with high levels of __________, which causes sodium retention, vasoconstriction and increased blood pressure.
Leptin
Why is insulin resistance a risk factor for CVD?
Generates chronic hyperglycaemia, leading to oxidative stress, inflammation and cellular damage.
Contributes to the lipid triad (high TGs, low HDL, small dense LDLs) and dyslipidaemia.
Slows blood glucose clearance, increasing the risk of glycosylation reactions and production of AGEs (advanced glycation end products)
__________ + endothelial damage leads to atherosclerotic plaque formation.
Dyslipidaemia
What is glycation?
The addition of a glucose molecule to a lipid or protein
____________ = the addition of a glucose molecule to a lipid or protein.
Glycation
What are Advanced Glycation End Products (AGEs)?
Harmful compounds formed when protein or lipids become glycated after exposure to glucose.
How do advanced glycation end products (AGES) exert their effects?
- Bind to RAGE cell receptors, increasing inflammatory cytokines and ROS.
- Increase extracellular matrix synthesis, trapping endothelial LDL and cross-binding it with collagen (creating vascular stiffening)
On which cells would you find RAGE receptors?
Endothelial cells
Vascular smooth muscle cells
Immune cells
Advanced glycation end products (AGEs) increase with advancing age. True or false?
True
List 3 dietary/lifestyle factors that can contribute to the overall AGEs pool.
High refined carbohydrates
Processed foods
Processed meats
Dairy
High heat cooking - grilling, roasting, searing, frying
Smoking
Sedentary lifestyle
Which vitamin seems to ameliorate AGE-mediated complications?
Vitamin D
How does chronic stress contribute to endothelial dysfunction and CVD risk?
Activates SNS and HPA-axis, ultimately increasing inflammatory cytokines, heart rate and blood pressure, increasing arterial inflammation.
How does periodontal disease contribute to CVD?
Increases systemic inflammation, which impairs vasodilation. Promotes endothelial dysfunction.
Deficiency of which mineral increases atherosclerosis risk?
Zinc
__________’s produced by the gut microbiota, decrease the risk of metabolic endotoxemia (a key risk factor for CVD and insulin resistance) by maintaining intestinal barrier integrity.
SCFA’s
How do SCFAs reduce serum lipids?
By inhibiting cholesterol synthesis
By redirecting lipids to the liver
The gut microbiota play a role in cholesterol regulation by altering bile acids that influence systemic cholesterol levels. True or false?
True
Foods rich in ________ may induce low-grade metabolic acidosis, a risk factor for IR and CVD.
Protein
List 3 CVD risk marker tests
- Cardiac risk tools, i.e, QRISK
- Cardiac troponin (released into the blood when heart muscle is damaged)
- Lipid profile (TC:HDL >6 = higher CVD risk)
- Lp-PLA2
- hsCRP
- MPO
A TC:HDL ratio of > ___ is a higher risk for CVD
6
What is the normal level of total cholesterol?
<5 mmol/L
What is a normal level of non-HDL cholesterol?
<4 mmol/L
What is a normal level of LDL cholesterol?
<3 mmol/L
What is a normal level of HDL cholesterol?
> 1 mmol/L (men)
1.2 mmol/L (women)
LDL and HDL particle size (LDL-P and HDL-P) correlate with carotid atherosclerosis and are more closely associated with obesity, diabetes and IR than LDL-C and HDL-C. True or false?
True