11 CARDIOVASCULAR HEALTH Flashcards
1
Q
What does CVD stand for?
What does it refer to?
A
Cardiovascular disease
CVD refers to a general term for conditions affecting the heart and blood vessels.
2
Q
Name 5 conditions included in CVD
A
- Atherosclerosis
- Hypertension
- Angina
- Myocardial infarction
- Stroke
3
Q
What are some lifestyle factors that increase CVD risk?
A
Unhealthy diet, lack of exercise, excess body fat, stress, smoking
4
Q
What is the Endothelium (ED)?
A
A monolayer of endothelial cells lining the blood interface throughout the CVS including cardiac chambers
5
Q
Define shear stress in the context of the cardiovascular system.
A
Frictional force of blood on endothelial cells
6
Q
What/where is the glycocalyx (GX) and what does it do (3)?
A
The glycocalyx (GX), a carbohydrate-rich protective layer covering the ED, regulates permeability, controls NO production and acts as a mechanosensor of blood shear stress.
7
Q
What can damage the glycocalyx (5)?
A
- Inflammation
- Hyperglycaemia
- Endotoxemia
- Oxidised low-density lipoproteins
- Abnormal blood shear stress
8
Q
What are the key functions of the ED? (6)
A
- Semi-permeable barrier: Role in fluid balance through selective movement of substances e.g., glucose and oxygen.
- Regulates vascular tone: Secretes vasodilators (e.g., NO) and vasoconstrictors (e.g., endothelin).
- ACE Enzymes: Contains angiotensin-converting enzyme (ACE) ― plays a key role in regulating blood pressure.
- Angiogenesis: ED cells are the origin of all new blood vessels.
- Haemostasis: The luminal surface of ED prevents platelet adherence and coagulation (non-thrombotic, anticoagulant).
- Immune defence: Healthy ED cells deflect leukocyte adhesion and oppose local inflammation.
9
Q
What is phenotype modulation?
A
Altering physical form/structure through the interaction of the genotype and environment
10
Q
Where are Vascular Smooth Muscle Cells (VSMCs) located and what is their role?
A
Located in the tunica media and play a key role in vessel contraction and dilation (regulate blood circulation and pressure). Help maintain the integrity and elasticity of blood vessels whilst limiting immune cell infiltration.
11
Q
What pathological conditions impact the function of VSMCs
A
Inflammation, oxidative stress, telomere damage
12
Q
What happens to VSMCs under pathological conditions?
A
VSMCs undergo phenotypic modulation, altering cell structure and function.
These changes are central to vascular disease,
especially atherosclerosis and hypertension
13
Q
What is eNOS?
A
eNOS = endothelial
nitric oxide synthase
14
Q
What are the physiological effects of NO?
A
- Regulates vascular tone
- reduces platelet aggregation and VSMC proliferation
- inhibits leukocyte adhesion and inflammatory cytokines
- opposes oxidation of LDLs.
15
Q
What is the result of reduced Nitric Oxide?
A
Reduced NO contributes to atheroma formation and CVD.
16
Q
How is NO generated?
A
It is continuously generated from L-arginine by endothelial nitric oxide synthase (eNOS).
17
Q
What regulates NO synthesis?
A
Vitamin D regulates NO synthesis by mediating eNOS.
18
Q
What are the characteristics and function of normal endothelial cells, and how does this change in the presence of oxidative stress and inflammation (activated state)?
A
- Impermeable to large molecules > increased permeability.
- Anti-inflammatory > increased inflammatory cytokines.
- Deflects leukocyte adhesion > leukocyte adhesion occurs.
- Produce the vasodilators NO & prostacyclin > reduced production of vasodilators.
- Resists thrombosis > Increased risk of thrombosis.
19
Q
What are the characteristics and function of normal VSMCs, and how does this change in the presence of oxidative stress and inflammation (activated state)?
A
- Normal contractile function > contractile dysfunction.
- Maintains extracellular matrix > Increased extracellular matrix synthesis.
- Contained within the tunica media > Migration into the tunica intima
and proliferation of VSMCs
20
Q
What are PPARs and what gene expression are they involved in?
A
Peroxisome proliferator-activated receptor (PPARs) are nuclear transcription factors that control gene expression involved in:
* adipogenesis
* lipid and glucose metabolism
* cellular proliferation and apoptosis.
21
Q
Do PPARs have a beneficial or negative effect on inflammation and ED health?
A
Beneficial
22
Q
What is the role of PPARα in cardiovascular health?
A
↑ HDL-C, ↓TGs and inflammation, anti-atherosclerotic
23
Q
List natural PPAR-α agonists (7).
A
Green tea, resveratrol, oregano, thyme, rosemary, naringenin, omega-3
24
Q
What effect does PPAR-γ have?
Name 3 natural PPAR-γ agonists.
A
Reduces blood glucose, fatty acids, insulin.
Apigenin, hesperidin, curcumin, resveratrol, EGCG
25
Name key risk factors for CVD (20)
| Broad categories of risk
* Family history / Genetics
* Ethnicity (south asian, sub-saharan)
* Gender (male)
* Dislipidaemia
* Hypertension
* Mitochondrial dysfunction
* Elevated homocysteine
* Thyroid hormone dysregulation
* Inflammation
* Obesity
* Insulin resistance
* Increased Advanced Glycation End Productions (AGEs)
* Smoking
* Sedentary lifestyle
* Chronic stress
* Periodontal disease
* Heavy metals
* Melatonin deficiency
* Dysbiosis
* Poor diet (excess protein, trans fats, fructose, nutrient deficiencies)
26
Which genetic polymorphisms are associated with CVD risk?
MnSOD, NOS3, MTHFR, ACE
27
Which ethnicities have an enhanced risk of CVD?
South Asian, sub-Saharan African
28
Why is CVD risk in women often underestimated?
Vague symptoms, mistaken for menopause or heartburn
29
What is LP(a)
Lp(a) = lipoprotein A, a form
of LDL. Also acts as a clotting
factor further ↑ CVD risk.
30
Dyslipidemia is a largely preventable risk factor for CVD.
* Which lifestyle and dietary factors can underlie this? (5)
* What life stage increases CVD risk? (1)
* What diseases increase CVD risk? (3)
Associated with sedentary lifestyle, excess alcohol, smoking, obesity, high intake of saturated and trans fat
Risk increases in menopause
Risk increases with T2DM, hypothyroidism and chronic kidney disease.
31
Why is mitochondrial dysfunction a CVD risk factor?
What key nutrient in the ETC might be depleted in CVD patients and why?
* ATP is required to pump Calcium ions out of myocardial cells. This allows relaxation and maintains electrochemical gradient across myocardial cell membrane.
* CoQ10 - use of statins.
32
Why is elevated homocysteine regarded as a CVD risk factor?
Associated with LDL oxidation, monocyte adhesion and ED dysfunction
33
Deficiency of which vitamins can lead to elevated homocysteine?
Folate, B12, B6
34
What genetic polymorphisms impact homocysteine levels? (3)
MTHFR, MTR, MTRR
35
Which two nutrients apart from B vitamins are needed for the methylation of homocysteine?
Choline, betaine
36
How could the thyroid be implicated in cardiovascular disease risk?
Thyroid Hormone (TH) receptors are present in the myocardium and vascular tissue and minor TH changes can alter CV homeostasis. Hypo and hyperthyroidism are linked with ED dysfunction, dyslipidaemia and BP changes.
37
Why is inflammation a CVD risk factor?
What vicious circle applies between CVD & inflammation?
Name key causes of inflammation (7).
Inflammation contributes to ED dysfunction. Inflammation is linked with ↑ endothelin-1 (ET-1), a potent vasoconstrictor peptide. Elevated ET-1 leads to fibrosis of VSMCs and ↑ ROS.
Vicious circle: ED dysfunction, cholesterol accumulation between the tunica intima and media and recruitment of monocytes and T-cells drives the inflammatory response.
Causes include: dyslipidaemia, dysbiosis and intestinal permeability, ROS, diabetes, obesity and smoking.
38
Why is obesity a CVD risk factor?
Name 2 hormones which link obesity and CVD, whether they are raised or decreased in obesity and how they play a role in CVD.
Obesity perpetuates inflammation contributing to vascular breakdown and metabolic complications:
- ↓ Adiponectin = disrupted expression of ED cells = less protection against CVD
- ↑ Leptin = ↑ Sympathetic Nervous System activity = sodium retention, vasoconstriction & ↑ blood pressure.
39
Inflammation is linked with an increase in which vasoconstrictor peptide?
Endothelin-1 (ET-1)
40
Which gene polymorphisms may increase Endothelin-1 and CVD risk?
Polymorphisms of EDN1
41
Why is insulin resistance a CVD risk factor?
IR generates chronic hyperglycaemia leading to oxidative stress, inflammation and cellular damage:
- IR contributes to the lipid triad and dyslipidaemia.
- Dysfunctional insulin signalling → ED damage + Dyslipidaemia = leads to atherosclerotic plaque formation.
- IR → glucose is not cleared from the bloodstream as quickly as needed = ↑ risk of glycosylation reactions & AGEs.
42
What is the Lipid triad?
* high plasma TGs
* low HDL
* small dense LDLs
43
What does glycation refer to?
The chemical addition of glucose molecule to lipids or proteins
44
What are advanced glycation end products (AGEs)?
Harmful compounds formed when protein or lipids become glycated after exposure to glucose.
45
Via which two main mechanisms do AGEs exert their effects?
Via receptor-mediated and non-receptor mediated mechanisms.
46
What is the receptor RAGE
The receptor for advanced glycation end products (RAGE) is a single transmembrane receptor expressed on activated endothelial and vascular smooth muscle cells & immune cells. (Also on neurons, bone forming cells, and a variety of cancer cells).
47
What is the receptor-mediated mechanism of AGEs?
AGEs bind to the cell receptor RAGE, increasing inflammatory cytokines and ROS via NADPH activation.
48
What is the non-receptor mediated mechanism of AGEs?
Increased extracellular matrix synthesis, trapping ED LDL and cross binding with collagen causing vascular stiffening.
49
What does AGE/RAGE signaling lead to?
Oxidative stress, vascular ED and immune cell dysfunction.
Induces fibroblast differentiation and downregulates intracellular detoxifying mechanisms.
50
What causes an increase in AGEs?
Advancing age, high refined carbohydrates, processed foods, meat, dairy, high heat cooking, smoking, sedentary lifestyle
51
What is the result of renal accumulation of AGEs?
Kidney dysfunction
52
What does the AGER gene encode?
RAGE
53
Which nutrient can ameliorate AGE-mediated complications?
Vitamin D
54
How does smoking impact cardiovascular health?
- ↑ oxidative stress (ROS react with NO to form harmful peroxynitrite)
- Lowers antioxidants (1 cigarette = 25 mg loss of vitamin C)
- Nicotine over-stimulates SNS and increases BP.
55
How can exercise contribute to cardiovascular health?
Positive effect on lipid profile, blood pressure, insulin sensitivity, and NO production
56
How does chronic stress impact cardiovascular health?
- May cause ED dysfunction (especially with other risks e.g., smoking).
- Activates Sympathetic Nervous System (SNS) and HPA-axis, ultimately ↑ inflammatory cytokines.
- ↑ heart rate and blood pressure through the SNS.
- Raised activity of the amygdala increases arterial inflammation.
57
How does stress increase heart rate and blood pressure?
Through SNS activation
58
What is the effect of periodontal disease on systemic inflammation?
↑ TNF, IL-1, IL-6, CRP
59
Why is periodontal disease a CVD risk factor?
Periodontal disease increase systemic inflammation (↑ TNF, IL-1, IL-6, CRP) which impairs vasodilation. It promotes endothelial dysfunction, arterial stiffness, ↑ fibrinogen
60
How does heavy metals increase CVD risk?
Heavy metals induce oxidative stress, lipid peroxidation and inflammatory cytokines.
Cadmium and lead compete with zinc. A zinc deficiency increases atherosclerosis risk.
61
How does melatonin affect cardiovascular health?
Melatonin is a potent antioxidant with anti-hypertensive properties that protects against coronary artery disease.
62
What is TMAO, where does it originate from and what is the association with CVD?
Trimethylamine-N-oxide (TMAO) is a proinflammatory metabolite.
It originates from the bacterial metabolism of choline-rich foods.
TMAO is associated with endothelial dysfunction and increased risk of CVD.
63
Which metabolites produced by gut microbiota reduces the risk of metabolic endotoxaemia and thus CVD and IR?
SCFAs.
They reduce serum lipids by inhibiting cholesterol synthesis or redirecting lipids to the liver.
64
Which foods have a high potential renal acid load (PRAL) and what is the impact of high PRAL foods on health?
Foods rich in protein such as meat and cheese. They may induce low-grade metabolic acidosis = risk for IR and CVD
65
How do trans fats affect health?
Promote dyslipidaemia, inflammation, ED dysfunction, visceral adiposity and IR risk
66
What is the consequence of high fructose intake on lipid metabolism?
Promotes de novo lipogenesis and ↑ fatty acids, especially palmitic acid which ↑ uptake of oxidised LDL (major driver of atherosclerosis and CAD).
67
Which nutrient deficiencies can be linked to cardiovascular health risks?
Vitamin C, D, E, CoQ10, Mg
68
What factors are used to calculate a QRISK score?
What does a QRISK of 10% mean?
CV risks such as age, BMI, smoking.
10% = 1 in 10 chance of developing CVD in next ten years
69
What is cardiac troponin?
Cardiac troponin proteins are released into the blood when heart muscle is damaged (such as in Myocardial Infarction)
70
What is a normal TC level?
< 5 mmol / L
71
What is a normal HDL level for men / women?
> 1 mmol / L
> 1.2 mmol / L
72
What TG and TC:HDL ratio indicates higher risk for CVD?
TG > 2.3 mmol / L
TC:HDL > 6
73
What is Lp-PLA2 and what is it upregulated in?
Enzyme produced by monocytes, macrophages and T-cells that is upregulated in atherosclerotic plaques and vascular inflammation.
74
What are the low and high risk levels for hsCRP?
< 1.0 mg/L (low risk), > 3.0 mg/L (high risk)
75
What dietary and lifestyle factors elevate both Lp-PLA2 and hsCRP?
* Smoking
* westernised diet
* sedentary lifestyle
* periodontal disease
76
What is MPO and what does it measure?
Myeloperoxidase. It is released by macrophages and measures the body's response to damaged arterial walls.
High MPO is associated with inflammation / oxidative stress and a poor prognosis.
77
What is LDL-P and why does it reveal more about CV health than LDL-C?
The number of LDL particles (LDL-P) plays a much stronger role in the development of CVD than the mass of cholesterol within these particles (LDL-C). LDL-P correlates with carotid atherosclerosis and is more closely associated with obesity, diabetes, and insulin resistance than LDL-C.
78
Which types of diets are associated with significantly reduced CVD risk?
Plant-based and mediterranean-style diets
79
List four benefits of plant-based and Mediterranean-style diets
* ↓ inflammatory mediators, ROS and RNS
* reduced adiposity and risk of thrombosis
* ↑ SCFA production
* improved insulin sensitivity
* ↑ adiponectin
* improved ED function
80
How does vitamin C promote cardiovascular health?
What dose?
* Downregulates NADPH oxidase, a key source of ROS in the vascular wall.
* Upregulates endothelial NO synthase (catalyses synthesis of NO from arginine).
* Lowers tendency for platelet aggregation.
500–1000 mg, 3 x per day
81
How does vitamin E promote cardiovascular health?
What dose?
* Protecting the endothelium from ROS and supporting NO synthesis.
* ↓ oxidation of LDL-C and deposition in arterial walls.
* Inhibits platelet aggregation and ↓ clotting factors to support healthy blood viscosity.
400–800 iu / day
82
How does Vitamin D promote CV health?
What dose?
* Modulates NO synthesis (influences cells involved in atherogenesis e.g., ED, VSMCs, monocytes and cardiac myocytes).
* Modulates RAAS and lowers BP
600–1000 iu / day
83
How do Omega-3 fatty acids support cardiovascular health
What dose?
* Improve lipid and lipoprotein profiles.
* Involved in the synthesis of key regulators of inflammation, vasodilation and platelet aggregation.
* EPA stabilises cellular membranes allowing neutralisation of extracellular ROS.
* DHA supports membrane fluidity.
3–6 g / day
84
How is Co-enzyme Q10 beneficial for cardiovascular health?
What dose?
* CoQ10 protects against endothelial dysfunction and reduces LDL oxidation (↓ atherosclerosis risk).
* Increases superoxide dismutase activity, which preserves the activity of NO (↓ risk of high BP).
* Supports mitochondrial health and production of ATP.
60–300 mg / day
85
How is Magnesium beneficial for cardiovascular health?
Which type of magnesium?
What dose?
* Regulates ion transporters (e.g. K, Ca channels), therefore modulates neuronal excitation, intracardiac conduction and myocardial contraction.
* Helps regulate vascular tone and stabilise heart rhythm.
* Magnesium glycinate / taurate at 500–800 mg / day
86
How does hawthorn promote CV health?
• Cardiac tonic, strengthens and improves vascular elasticity, ACE-inhibiting actions (↓ BP)
• Hawthorn reduces ET-1 and increases NO levels, hence having vasodilatory effects.
• Antioxidant (e.g., ↑ SOD), anti-inflammatory (inhibits NF-κB).
87
How is garlic beneficial for cardiovascular health?
What dose?
* Antihypertensive (stimulates NO production)
* Lowers homocysteine & ↓ CVD risk.
* Decreases arterial calcification (stiffness).
* Reduces LDL cholesterol and LDL oxidation.
* Enhances glutathione and SOD.
* Protects against abnormal platelet aggregation.
2-5g fresh garlic daily
88
Which stress management activities could you recommend to promote parasympathetic activity?
Diaphragmatic breathing, humming, singing
89
Recommend four herbal teas for stress relief.
Chamomile, passionflower, lemon balm, lime flower
90
What enzyme and resulting nutrient do statins block?
HMG CoA-reductase = ↓ coenzyme Q10 synthesis.
91
What is cholestyramine and how does it affect fat-soluble vitamins?
A bile acid sequestrant that ↓ absorption of fat-soluble vitamins and beta-carotene.
92
What minerals do loop and thiazide diuretics increase excretion of?
Potassium, calcium, B1 (Thiamine)
93
Which mineral does ACE inhibitors bind with?
Zinc
94
What is the effect of beta-blockers on melatonin production?
Beta-blockers decrease melatonin production by inhibiting adrenergic beta1 receptors; block the biological pathway of CoQ10-dependent enzymes.
95
How is blood pressure (BP) reported and what does each one measure?
Ratio of systolic BP (the pressure blood exerts on arterial walls when the heart
contracts) and diastolic BP (pressure when the heart relaxes).
96
What are the signs and symptoms of hypertension?
Often asymptomatic.
Fatigue, headache, dizziness, visual disturbance
97
What drives essential hypertension?
- Vascular resistance
- Obesity
- Stress and anxiety
- Smoking
- High salt intake
| No specific underlying medical cause
98
What is secondary hypertension due to?
Disease of the kidneys, adrenals, thyroid, diabetes
99
What is malignant hypertension?
Pressure above 180/120, which risks damaging organs e.g kidneys (medical emergency)
100
Hypertension causes and risk factors
All standard CVD risk factors +
*Excess alcohol
*Excess table salt
*Excess uric acid
## Footnote
CVD risk factors:
* Family history / Genetics
* Ethnicity (south asian, sub-saharan)
* Gender (male)
* Dislipidaemia
* Hypertension
* Mitochondrial dysfunction
* Elevated homocysteine
* Thyroid hormone dysregulation
* Inflammation
* Obesity
* Insulin resistance
* Increased Advanced Glycation End Productions (AGEs)
* Smoking
* Sedentary lifestyle
* Chronic stress
* Periodontal disease
* Heavy metals
* Melatonin deficiency
* Dysbiosis
* Poor diet (excess protein, trans fats, fructose, nutrient deficiencies)
101
Which 2 mineral deficiencies contribute to hypertension, and why?
Magnesium (vasodilates)
Potassium (↑ urinary excretion of sodium, ↓ blood volume).
102
Why is **raised uric acid** a cause/risk factor of hypertension?
* Increases oxidative stress
* Increases inflammation
* Increases RAAS activity
* Increases RAGE activity
* Exacerbates endothelial insulin resistance
*Lowers NO (disrupts eNOS)
## Footnote
Hyperinsulinaemia also ↓urinary excretion of uric acid.
103
What is the food based natural Approach to hypertension
| (not about supplements)
- Adapt the Natural Approach to CVD.
- Increase potassium / sodium ratio >3:1
- Include fresh fruit and vegetables for potassium: encourages vasodilation, reduces sensitivity to angiotensin II and lowers SNS activity. Lowers NADPH oxidase, decreasing ROS in the vascular wall.
* Restrict sodium intake to 1.5g / day.
104
Why is the DASH diet good for hypertension?
What does the DASH diet consist of?
What does DASH stand for?
- Studies reveal significant systolic
and diastolic BP reduction in hypertensive individuals following the DASH diet.
- DASH consists of fresh vegetables
and fruits, legumes, nuts, seeds, whole grains, fish, lean meat and low-fat dairy. - Limits saturated fats and salt. PUFA / MUFA are preferred. Sodium is restricted.
**DASH = dietary approaches to stop hypertension**
105
How do ACE inhibitory peptides found in foods work to reduce hypertension?
Name 6 food sources?
ACE inhibitory peptides act like a decoy, encouraging ACE to react with peptides, reducing vasoconstriction via angiotensin II.
Sources include spirulina, mushrooms, spinach, hemp seeds, walnuts and bitter melon seeds.
106
Why is melatonin associated with anti-hypertensive effects?
Through GABA stimulation, angiotensin-II inhibition and it increases NO.
107
What supplements are useful for hypertension?
Vitamin B6
Vitamin C
Vitamin D
CoQ10
L-Arginine
Magnesium (Glycinate/Taurate)
108
Nutrients for hypertension: Vitamin D function
• Deficiency of vitamin D leads to overexpression of renin, activating RAS— ↑ vasoconstriction and retention of sodium and water.
• ↓ proinflammatory cytokines, ↑ NO, ED function and arterial elasticity and ↓ hs-CRP.
• The lower the levels of vitamin D the greater the risk of hypertension.
109
Nutrients for hypertension: Magnesium function & dose
Deficiency is associated with hypertension (HTN). Alterations in intracellular and extracellular magnesium affects cardiac and vascular tone and reactivity.
Glycinate/taurate
500-800mg per day
110
Nutrients for hypertension: L-arginine function & dose
Arginine is the principle substrate for vascular NO synthesis.
* Modulates the RAS, inhibiting ACE activity, thereby decreasing angiotensin II and its downstream effects.
* Hypertensive patients display high hs-CRP, low apelin (stimulates NO in ED) and increased arginase (breaks down arginine).
1000-2000mg 3x daily
111
Nutrients for hypertension: B6 function & dose
* B6 deficiency is associated with hypertension. It is an important co-factor (e.g. NA, adrenaline, serotonin). Increases cysteine synthesis, glutathione, blocks Ca
channels and reduces SNS tone. Reduced with diuretics!
112
Tissue salts for hypertension
6 x one pillule 4 times per day.
* Mag. phos. and / or Kali. phos. (may reduce systolic
and diastolic pressure) and Nat. sulph. (improves
urine output and thus helps reduce blood volume).
* Calc. fluor. ― to strengthen arterial walls, improve
elasticity and reduce arteriosclerosis.
113
What herbal mix is traditionally used for hypertension?
* The traditional ‘C.A.T.’ formula: Equal parts dried herbs infused, 1 cup 2–3 x daily.
– Crataegus spp. [hawthorn] (cardiotonic, hypotensive).
– Achillea millefolium [yarrow] (diuretic, hypotensive).
– Tilia europea [lime flower] (nervine relaxant, diuretic, anti-hyperlipidaemic).
114
Why does stress management help with hypertension?
Give 2 specific stress relief techniques and why they lower BP
Essential because of the physiological
effects of the stress response on CV health.
– Diaphragmatic breathing: Shown to decrease systolic and diastolic BP, heart rate and anxiety, and promote a sense of relaxation in pre-hypertensive and hypertensive individuals.
– Earthing/grounding: (Walking barefoot on grass or sand) improves heart rate variability, lowers night-time cortisol and promotes a parasympathetic state.
115
What exercise regime would you recommend for hypertension?
Start gently and gradually ↑ CV fitness.
Aerobic exercise e.g., walking, swimming, cycling and jogging is recommended. Avoid exercise that is very intense in short bursts e.g., sprinting, weightlifting.
116
What is mLDL
Modified LDL
| LDL modifications change their physicochemical and biological properties
117
Define atherosclerosis
Narrowing and hardening of large
and medium arteries, which reduces blood flow
118
What are the key steps in the aetiology of atherosclerosis?
In the first step, what are the key drivers which get the atherosclerosis process started?
1 - Diturbance to the glycocalyx layer and damage to endothelial cells.
* Caused by: inflammation, oxidative stress, oxidised LDLs, hyperglycaemia, endotoxaemia, abnormal shear stress dyslipidemia.
2 - Increased endotheliam permeability allows LDL to enter the intima where it is oxidised to mLDL.
3 - Pro-inflammatory cytokines and leukocytes are attracted to the area.
4 - Macrophages try to clear up the debris and imbibe LDL, which forms foam cells
5 - Dying foam cells release inflammatory cytokines. Fatty streaks are formed.
6 - Foam cell and fatty streaks accumulate cellular debris which drives further inflammation.
7 - This all activates VSMCs which start to migrate to the tunica intima where they turn into fibroblast and osteoblast like cells.
8 - These cells create an extracellular matrix and calcify the plaque.
7 - A cap is formed over the plaque to wall it off from the blood
119
What is the significance of the thickness of the atherosclerotic plaque? I.e. what are 2 possible outcomes?
What can change the thickness of the plaque once it's been formed?
1 - A thin plaque can easily rupture and cause thrombosis
2 - A thick plaque causes narrowing of the blood vessels
Inflammation thins the cap, making it more likely to rupture.
120
# Fill the gaps:
* ---- plays a central role in the formation of ----, a primary event in atherosclerosis.
* Increased permeability facilitates entry of ___ into the ___. ___
becomes ‘trapped’ within the vessel wall and is oxidised to ____
* ___ recruit ___ expressing high levels of pro-inflammatory ___. Also trigger cytokine release from ED and ___ cells.
* Macrophages imbibe lipoproteins to form ____. Cellular debris is incorporated and inflammation drives plaque formation.
* A cap is formed over the plaque to wall off the plaque from blood.
Endothelial dysfunction
fatty streaks
LDL
intima
LDL
mLDL
mLDL
leukocytes
cytokines
VSMC
foam cells
121
Aetiology of dyslipidaemia (lipids are a fundamental component of atherosclerotic plaques).
Thus, dyslipidaemia is a significant risk factor and is marked by:
– ↑ total cholesterol — ↑ LDL, VLDL, IDL, Lp(a), ↓ HDL; ↑ TGs.
* TGs are hydrophobic and must combine with lipoproteins to travel in
plasma. In a similar manner to oxidised LDLs, TG-rich lipoproteins
(e.g., VLDLs and VLDL remnants) are
prone to endothelial accumulation and uptake by foam cells and are strongly linked with endothelial dysfunction.
* High TGs are also linked with low HDLs.
122
What are key therapeutic aims to reduce atherosclerosis?
1 - Promote a healthy lipid profile
2 - Support endothelial health and vasodilation
3 - Promote liver detoxification
123
How can we promote a healthy lipid profile in Atherosclerosis/
* Avoid high saturated fat to reduce risk of CV events.
* Increase omega-3 FAs and MUFAs: E.g., avocado, unrefined olive oil. Regular EVOO consumption reduces LDL-C and oxidised LDLs, and improves post-prandial glycaemic profiles.
* EVOO polyphenols oleocanthal and oleacein have antioxidant and anti-inflammatory effects (↓ markers including CRP and IL-6).
* Increase dietary fibre (30–35 g / day). Soluble fibre (vegetables, fruits, psyllium husk, pectin, gums) are associated with a decrease in TC and LDL-C.
* Include dietary sources of beta-glucans (soluble + insoluble fibre)
e.g., oats, mushrooms, seaweed, barley.
* Red yeast rice (2400–4800 mg / day) ― contains monacolin K, an inhibitor of cholesterol synthesis via HMG CoA reductase.
124
How can we support endothelial health and vasodilation in Atherosclerosis
* * **Hawthorn berries, bilberry, blueberries and blackcurrants** are
antioxidant and support blood vessel integrity and tone.
* **Lower ET-1 levels**: Enhance citrus **flavonoids**, quercetin, epicatechins, garlic, olive oil, ginkgo, folate, and blackcurrant.
* **Beetroot** contains inorganic nitrates that convert to NO in the body. Also ↓ homocysteine ― contains betaine
which is utilised by the enzyme BHMT that re-methylates homocysteine to methionine.
* **L-theanine** ↑ NO production in ED cells through eNOS phosphorylation (**green tea** is a key source).
* **Reduce homocysteine**: **B6, folate and B12** (supplement methylfolate and methylcobalamin supplementation), **TMG** (3 g twice daily).
* **Lower fibrinogen levels**: High fibrinogen promotes atherosclerosis by increasing blood viscosity, stimulating fibrin formation and increasing platelet aggregation.
* **Mediterranean-style diets** promote healthy fibrinogen levels. Garlic reduces fibrinogen, ↑ fibrinolytic activity (also ↓ atherogenicity of LDLs).
* Mild to moderate **exercise** reduces fibrinogen levels.
125
How can we promote and support liver detoxification in Atherosclerosis?
* Ensure availability of all substrates required for **detoxification pathways.**
* **Poor liver function** can increase circulation of **inflammatory mediators**, **impede cholesterol**
metabolism and comprise essential fatty acid status.
* **Schisandra fruit** supports liver function and is a powerful activator of phase I detoxification without increasing harmful bioactivation (antioxidant and hepatoprotective effects). Enhances phase II detoxification. Dose: 2–3 dried fruit
infused twice daily. Dried berries can be eaten as a ‘superfood’.
126
What supplements are especially useful in atherosclerosis?
Vitamin B3
Vitamin B5
L-Citruline
Omega-3
127
Why L-citrulline is preferrable to oral L-arginine supplementation to enhance both arginine and NO bioavailability? Name the dosage.
* It skips first pass metabolism so it's more bioavailable.
* Renal arginine regulates BP, blocks the formation of endothelin, ↓ renal sodium reabsorption, and is a potent antioxidant.
500–3000 mg / day
128
Pantothenic acid / pantetheine (B5) function Atherosclerosis
* Reduces TC, LDL, Apo-B, TG and increases HDL
* Reduces lipid deposition, oxidation and fatty streak formation. (esp in diabetic patients)
300 mg x 3 daily
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Niacin (B3) function Atherosclerosis
* Reduces TC, LDL, Apo-B, TG and increases HDL
* Decreases fibrinogen
500–3000 mg daily
## Footnote
Can cause niacin flush, and GI disturbance.
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Omega-3 function Atherosclerosis
* Improve lipid and lipoprotein profiles.
* Regulates inflammation, vasodilation and platelet aggregation.
* Reduces CVD progression and stabilises plaques.
3000–5000 mg / day.
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What foods / food extracts are particularly useful in atherosclerosis?
Beetroot
Dietary fibre
EVOO
Garlic
Pomegranate
Pine bark extract
Red yeast rice
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Pomegranate function Atherosclerosis
* Improves HDL function
* Potent antioxidant
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Pycogenol (pine bark extract) function Atherosclerosis
* Flavonoid, antioxidant, anti-inflammatory, anti-thrombotic.
* Enhances NO and ED function, reduces BP and Hs-CRP.
* Reduce foam cell formation in atherosclerosis.
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For any other nutrient, what can we say if in doubt?
## Footnote
Other nutrients inclue:
Globe artichoke
Lycopene
Bergamot
* Antioxidant
* Anti inflammatory
* Reduces serum LDL, TC and TGs.
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Other therapies for Atherosclerosis
* Sauna: ↑ circulation and arterial vasodilation. Avoid in unstable angina / recent MI and hypertension.
* Dry skin brushing: Supports circulation and lymphatic function, increases toxin elimination.
* Contrast hydrotherapy (alternating warm / cold water): improves circulation and supports removal
of toxins. If circulation is compromised end on warm.
* Tai Chi Chuan, yoga and acupuncture have shown to reduce ET-1 (endothelin) levels.
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Define Ischaemic Heart Disease (IHD)
What is it commonly caused by?
What 2 conditions fall within IHD?
An imbalance between myocardial oxygen supply and demand, is associated with inadequate arterial supply via the coronary arteries.
IHD is commonly caused by atherosclerosis.
IHD syndromes include angina (stable and unstable) and myocardial infarction.
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Define ischaemia
Ischaemia is a restriction in blood supply, causing a shortage of oxygen that is needed for cellular metabolism
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What is angina?
chest pain caused by an insufficient supply of oxygenated blood supply to the myocardium by the coronary arteries.
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Define stable angina & the signs and symptoms
Predictable transient chest pain
during exertion or emotional stress. Ischaemia with symptoms resolves once oxygen balance is restored.
Constricting chest pain (can radiate to the neck, L shoulder / arm and jaw), worsened by exertion, relieved by rest. SOB, sweating, nausea.
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Define unstable angina
Unpredictable / occurs at rest.
Plaque disruption initiates platelet aggregation, thrombus formation, and vasoconstriction. May be a precursor to acute MI.
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Causes / risk factors of Angina
Can list all CVD causes and risk factors and specifically:
* Cigarette smoking ― linked to endothelial dysfunction, CAS, vessel wall injury, oxidative stress, elevates fibrinogen, platelet activation, and inflammation. Smoking cessation
in angina can prevent recurrent angina events.
* Vitamin D deficiency ― significant correlation between vitamin D deficiency and chronic angina. Improves endothelial function by signalling for the transcription of eNOS; modulates the RAAS to lower BP.
* Family history of premature IHD is a strong risk factor for angina.
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Orthodox diagnosis and allopathic approach to Angina
* Orthodox diagnosis: ECG, cardiac
stress testing, angiography (see image).
* Allopathic approach: Nitrates
(e.g., GTN), calcium channel blockers
(e.g., amlodipine), beta-blockers
(e.g., atenolol), revascularisation
(angioplasty, stents and coronary
artery bypass graft surgery).
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Define Myocardial Infarction (MI)
What can happen in prolonged states of ischaemia?
What 2 categories is MI divided into?
An acute blockage of a coronary artery usually due to a thrombus, resulting in the death of myocardial tissue.
* Prolonged ischaemia leads to myocardial necrosis. Ischaemic myocardial cells release adenosine and lactate onto nerve endings causing pain.
* Infarcted areas produce scar tissue. The remaining tissue hypertrophies and can result in cardiac dysfunction and heart failure.
* Divided into:
– ST-Segment Elevation MI (STEMI) = full occlusion (severe).
– Non-ST-Elevation MI (NSTEMI) = partial occlusion.
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Myocardial Infarction (MI) causes and risk factors
Can list any CVD cause and specifically:
* Sex: Males ~ 3 times more likely to experience MI. High androgen levels contribute to the development of atherosclerosis.
* Psychosocial factors: Stress (e.g., financial). Loss of locus of control, sudden life events (e.g., job loss, marital separation) increase MI risk.
* Others: Drug-induced (cocaine), significant myocardial O2 demand (e.g., severe hypertension) or reduced O2 supply (e.g., severe anaemia), vasculitis syndromes (e.g., temporal arteritis).
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Myocardial Infarction (MI) signs and symptoms
Severe prolonged crushing retrosternal chest pain. Pain radiates to the left shoulder, jaw / neck or arms. Sweating, cool / clammy skin. Feeling of ‘impending doom’. Dyspnoea and syncope. Nausea, vomiting, weakness.
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Myocardial Infarction (MI):
Complications
Diagnosis
Allopathic approach
**Complications**: Arrhythmias, heart failure, cardiogenic shock, death.
* **Diagnosis**: ECG findings.
* **Allopathic approach**: Fibrinolysis, O2 therapy, morphine, nitrates, beta blockers, aspirin for acute management.
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Natural approach to Ischaemic Heart Disease
- Apply the natural approach to CVD, with a focus on supporting myocardial blood flow.
- Optimise vitamin D status - supports endothelial health and promotes vasodilation (increased nitric oxide).
- Warming herbs/spices to support blood flow (ginger, cayenne).
- Increasing movement - care is needed to avoid triggering angina attacks. Gentle exercise (Tai Chi, walking).
- Address stress - breathing, nervine herbs (passionflower).
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What key nutrients can we use for ischaemic heart disease?
Vitamin D
L-Carnitine
Magnesium
Hawthorn
CoQ10
L-Arginine
Ginko Biloba
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L-carnitine function for IHD
Improves Fatty Acid utilisation and myocardial ATP production, which may also prevent the production of toxic metabolites.
1000 mg 2x daily
150
Magnesium function for IHD
*Magnesium deficiency can produce
coronary artery spasms.
*Magnesium controls the movement of calcium into smooth muscle cells, leading
to smooth muscle contraction.
*Deficiency also ↑ ROS.
200-400 mg 3x daily
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Hawthorn function for IHD
Its flavonoids have been shown to inhibit the enzyme 3',5'-cyclic-AMP, which is thought to be responsible for dilating the coronary arteries.
1000-1500 mg
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CoQ10 function for IHD
* Increases eNOS and NO, improves ED function and vascular elasticity.
* Anti-inflammatory – lowers TNF-α and IL-6.
* Antioidant - inhibits NF-κB.
100-300 (if on statins) mg daily
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L-arginine function for IHD
* Promotes vasodilation by increasing NO.
* Increases SOD levels, reduces lipid peroxidation and xanthine oxidase activity (reducing uric
acid formation); uric acid stimulates RAGE.
1000-2000 mg 3x daily
154
Ginkgo biloba function for IHD
* Enhances microcirculation and tissue perfusion (antagonises ‘platelet activating
factor’ by blocking receptors). Scavenges ROS.
60-120mg daily
155
Define Heart Failure
A syndrome in which the heart is impaired as a pump ― failing to supply sufficient blood flow.
156
Signs & symptoms of heart failure
- Breathlessness (on exertion, at rest, orthopnoea),
- Nocturnal dyspnoea
- Fluid retention (e.g., ankle
oedema, abdominal swelling).
- Fatigue
- Exercise intolerance
- Lightheadedness
- Loss of consciousness (brief)
- Tachycardia.
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Heart failure complications & allopathic approach
* Complications: Atrial fibrillation, ventricular arrhythmias, CKD, sudden cardiac death.
* Allopathic approach: Digoxin (a synthetic form of digitoxin, from
Digitalis purpurea (foxglove) that increases the force of myocardial contraction), diuretics, calcium channel blockers, ACE-inhibitors.
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Heart failure causes/risk factors
* Results from various CV conditions ― e.g., IHD (most common cause), hypertension, AF, cardiomyopathy, LVF, pulmonary hypertension, heart valve abnormalities.
– See earlier risk factors, e.g., smoking (leads to LV hypertrophy and systolic dysfunction); raised homocysteine; sedentary etc.
* Co-morbidities ― e.g., CKD,
anaemia, T2DM, thyrotoxicosis, hypothyroidism, COPD
all impair functional status and prognosis of HF.
– CKD causes a chronic proinflammatory state that can
result in atherosclerotic lesions and myocardial fibrosis.
* IR ― IR ↓ myocardial glucose utilisation and ↑ FFA oxidation,
↑ myocardial oxygen consumption and the generation of ROS. This impairs cardiac contractibility by changing sarcoplasmic reticular calcium stores and ↑ mitochondrial dysfunction.
* Obesity ― alters cardiac structure, promotes endothelial
dysfunction, contributes to IR and ↑ inflammatory cytokines.
* Nutrient deficiencies ― CoQ10 (normally ↓ ROS and ↑ NO), vitamin D (normally ↓ inflammatory cytokines and ↑ calcium absorption etc.),
B1 (common in HF due to chronic alcohol ingestion; normally acts as a coenzyme for glucose metabolism). Also vitamin B2, folate, B12,
Ca, Cu, Mg, Mn, K, Se, Fe — needed for normal cardiac metabolism.
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Natural Approach to Heart Failure
Apply the Natural Approach to CVD, with a focus on supporting myocardial energy production. Key considerations:
* Lower CVD risk factors — follow previous naturopathic approaches e.g., hypertension.
* Consider approaches for obesity, IR and T2DM.
* Correct nutrient deficiencies
* Correct identified anaemias.
* Consider a high-quality multivitamin / mineral formula.
* Correct K:Na ratio.
* Work to achieve ideal body weight.
* Encourage smoking cessation where applicable.
160
What key supplements are useful for heart failure
CoQ10
D-Ribose
Magnesium (citrate)
B1 - Thiamine
L-Carnitine
Hawthorn
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CoQ10 function for heart failure
Cardiac myocytes contain >3500 mitochondria / cell and require the highest levels of ATP activity. CoQ10 is essential in the ETC and is a powerful antioxidant.
CoQ10 depletion is associated with worse HF outcomes.
300-400mg daily
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D-ribose function for heart failure
Has been shown to regenerate low myocardial ATP with an accompanying improvement in ventricular function following ischaemia. Symptom improvements (e.g., fatigue) in chronic HF have been observed.
5-15g daily
163
Magnesium function for heart failure
Critical for ATP. When deficient increases RAAS (increasing
BP), predisposes to low K and may worsen cardiac contractility, increase vasoconstriction and deplete cardiac energy stores.
400-800mg daily (citrate)
164
Thiamine for heart failure
Thiamine is a required coenzyme in energy-producing
reactions — fuelling myocardial contraction. Note: CVD drugs e.g., diuretics cause a B1 deficiency.
100-200mg daily
165
L-carnitine for heart failure
Facilitates the transfer of fatty acids across mitochondrial membranes to initiate beta-oxidation. The heart uses free fatty acids as its main energy source!
2000-3000mg daily
166
Hawthorn for heart failure
Benefits have been observed in cases of chronic heart failure. This is attributed to hawthorn’s vasodilatory effects on the coronary arteries and potent
antioxidant properties. Increases NO.
1000-1500mg daily
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Define varicose veins
Signs & symptoms
Complications
Dilated / distorted superficial veins in the lower limbs where the pressure is higher due to gravity.
* Signs and symptoms: Visible vein dilation; aching, burning, throbbing, heaviness. Worse
for prolonged standing and at the end of the day.
* Complications: ↑ venous pressure = fluid leakage into surrounding tissues (‘varicose
eczema’). Slow healing varicose ulcers.
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Define haemorrhoids
Signs & symptoms
Dilated veins in the anal canal. Internal or external.
* Signs and symptoms: Bright red blood with bowel movements, protruding haemorrhoids, anal itching.
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Varicose Veins / Haemorrhoids causes/risk factors
* Increased abdominal pressure ― constipation, obesity, pregnancy, childbirth and post-labour, ascites.
* Inherited valve defects ― an absence of some valves or faulty valves.
* Cigarette smoking (= hypoxia, which results in endothelial damage, vessel wall inflammation and a loss of elasticity).
* Being sedentary (increasing venous pressure).
* Lack of dietary connective tissue support, e.g., low vitamin C (increases type I collagen synthesis), low bioflavonoids (support connective tissue integrity).
* Portal hypertension ― increased portal vein pressure e.g., due to liver cirrhosis and heart failure.
* Increased blood viscosity and stagnation ― dehydration, liver congestion, sedentary lifestyle. Additional signs / symptoms: haemorrhoids, post-food fatigue, purple tongue, thick white / yellow tongue coating.
* Abdominal bloating (not obesity) ― distended and uncomfortable. E.g., associated with SIBO.
* Structural ― e.g., poor diaphragm motion (consider causes such as stress, asthma etc.), weak pelvic floor (consider pregnancy).
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Varicose Veins / Haemorrhoids natural approach
CNM Naturopathic Diet. Reduce inflammation, increase blood flow and speed up repair of damaged veins / valves. Correct root causes!
* Vitamin C-rich foods (to support collagen synthesis).
* Bioflavonoids such as rutin, proanthocyanidins and anthocyanins which improve the integrity of ground substance and the vascular system, whilst also acting as antioxidants. Food source examples: buckwheat (highest source of rutin) grapes, apples, cranberry, blueberry, figs, blackcurrants, capers, asparagus, green tea.
* Enhance fibrinolytic activity — garlic, onions, ginger, cayenne.
* Include bromelain sources to increase plasminogen activator status.
* Optimise liver function — alleviate downward pressure. Fibre-rich plant foods: Reduce venous pressure with defecation. Ground
flaxseed, or psyllium husk (15–30 g / day).
* Raise feet above heart (20 mins / day) — reduces blood pooling and improves venous return.
* Lymphatic drainage / massage — for mild cases only — aids circulation and avoids blood pooling. Consider dry brushing.
* Reduce weight: Address cause and exercise!
* Tissue salts — calc. fluor. (tissue strengthening). If bleeding add ferrum. phos. 4 pills x 3 daily.
* Topical application of astringent herbs: Horse chestnut, witch hazel, yarrow.
* For haemorrhoids: Sitz Bath (a shallow hip bath) with a small amount of Mg salts or a strong cup of cooled chamomile tea. Soak for 10‒15 minutes
* Regular exercise
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What nutrients and food extracts can be used to support varicose veins & haemorrhoids?
* Vitamin C with bioflavonoids
* Horse chestnut
* Gotu Kola
* Butcher's broom
* Pycnogenol
172
Vitamin C with bioflavonoids for VV/Haemorrhoids
Support connective tissue integrity ― increases collagen synthesis and ground substance integrity.
1.5-2g through the day
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Horse chestnut for VV/Haemorrhoids
* An astringent herb that ↑ venous tone by ↑ the production of prostaglandin F2, which regulates the contractile action of veins, and inhibits the
catabolism of venous tissue mucopolysaccharides. Also likely through its effects on 5-HT2A receptors.
* Inhibits enzymes that destroy
venous structures, e.g., collagenase, hyaluronidase, and elastase.
400 mg (seed) daily or 15 drops of tincture 3 x daily between meals, for 3 months. Topically as a balm. Avoid raw seed, bark, flower or leaf.
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Gotu kola for VV/Haemorrhoids
* Contains triterpenic acids that are thought to be responsible for its supportive effects on connective tissue.
* Stimulates glycosaminoglycan and collagen synthesis, which supports vein structure and improves blood flow.
500mg 2x daily. Avoid in liver disease.
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Butcher's broom for VV/Haemorrhoids
Vasoconstrictive and astringent (its ruscogenin content has anti-elastase activity, which ↓ the diameter of veins).
300-500mg 2x daily
176
Pycnogenol for VV/Haemorrhoids
Contains proanthocyanidins and has collagen stabilising properties. Decreases passive dilation and stretching and gives vein walls a greater tonic recovery and elasticity.
150-300mg daily
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Homeopathy for Varicose Veins & Haemorrhoids
* Hamemelis 3 x ― varicose veins are large, sore and easily irritated and stinging. Bleed very easily.
* Aesculus 3 x ― haemorrhoids are congested and purple. Pain in the rectum feels “as if the rectum were full of sticks”. Pain radiates to the small of the back and hips. Sharp, shooting pain upwards from the rectum.
* Nux. vomica 6C ― haemorrhoids that are better for warmth and better for passing stool. History of overindulgence in alcohol, coffee, other stimulants, etc.
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TCM approach for Varicose Veins & Haemorrhoids
- What do they define as the cause?
- What support should you give?
In TCM, it is associated with Blood stagnation (consistent with the Western understanding of poor blood circulation), but also a weak digestive system (Spleen Qi deficiency). The Spleen is said to produce Blood, govern smooth muscle and hold Blood in the vessels.
* Support Spleen Qi (Nutrition year 1).
* A tea with equal parts cinnamon, ginger, and tangerine peel stimulates Qi and blood circulation.
* Resolve Blood stasis by reducing stress and exercising frequently.
* Include foods that disperse stagnant blood, e.g., chives, leeks.
* Include blood-nourishing dark leafy greens, beetroot.
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