Ectopic Cardio Vascular Disease 1 - intro. Don't ask why this is here. Flashcards
What is CVD?
Cardiovascular disease refers not just to ‘heart disease’, but also to all diseases of the heart and circulation, including coronary heart disease (angina and heart attacks) and strokes.
These are linked by their potential cause being atherosclerosis, the production of a fatty plaque (atheroma) inside the blood vessels.
Describe the global epidemiology of CVD.
In a population of over 7.3bn, 57m deaths occur per annum. Of these, AIDS is responsible for 2.9m, TB for 1.7m and malaria for 1.2m. CVD on the other hand causes 17.3m deaths per year, around 30% of all deaths.
There is an inverse correlation between wealth and CVD incidence due to improvements in lifestyle and diet.
CVD kills men 2-3x more often than women, but the effect is age dependent. CVD is far more common in young men than women. But as age increases this trend decreases to the point of inversion, at the approximate age of menopause, whose hormonal changes are linked to CVD.
At what age does CVD develop?
Early forms of atherosclerosis are very frequently present in 20-30 year olds, and 17% of US teenagers were found to have small atherosclerotic plaques in their arteries (Tuzcu et al, 2001). Even children younger than 13 showed significant fatty streaks.
Astoundingly, studies on premature babies even showed that such fatty streaks can develop in utero, a phenomenon that correlates with the cholesterol levels in the mother.
However, these early forms of atherosclerosis are reversible through lifestyle change.
What are the non-modifiable risk factors of CVD?
• Gender
• Age
o > 50 years
o Post-menopause
• History of disease
o Personal
o Family
What are the modifiable risk factors of CVD?
• Smoking • High blood pressure • Diabetes mellitus • Central Obesity • Sedentary lifestyle • High sodium intake • High alcohol intake • Psychological stress • High levels of Homocysteine • High cholesterol levels o Elevated LDL o Decrease HDL
What are the layers of an artery?
The intima, media and adventitia, or alternately the tunica intima, tunica media and tunica externa.
Describe the intima.
The innermost layer, called the intima, is a monolayer of endothelial cells with a base of collagen and proteoglycans through which a sheet of elastic fibres – the internal elastic lamina – runs.
Describe the media.
The media is a layer of smooth muscle cells (SMCs) that enable some control of vascular diameter through vasodilation and constriction.
This is bordered on the inner side by the internal elastic lamina and on the outer side by the external elastic lamina.
Describe the adventitia.
The outer layer, the adventitia, is a thick layer of connective tissue interspersed with SMCs, fibroblasts, nerves and small blood vessels (vasa recta) that supply the artery itself. This layer provides strength and elasticity to the blood vessel.
What are the roles of the endothelium?
- Regulation of vasomotor tone (the tension in the smooth muscle of the media)
- Prevents spontaneous thrombosis
- Modulates immune function through expression of adhesion molecules
- Lipid transport
- Cell transport (both active and passive)
- Vascular remodelling through cellular growth
What is viable endothelium?
Viable endothelium is the name given to the intended quiescent, protective phenotype. However, damage to the endothelium can lead to endothelial dysfunction.
What are the primary causes of damage to the endothelium?
• Turbulent blood flow
• Free Radicals/Toxins
• Oxidised LDLs
o Product of Hypercholesterolemia
• Glycated proteins
o A consequence of diabetes
• Bacterial or viral infection
o Causes Systemic inflammation
The endothelium can be damaged just by the normal continuous exposure to the high pressure of the artery lumen, and damage has also been linked to dietary imbalance, smoking and even poor dental hygiene.
What effect does shear stress have on the endothelium?
This is linked to increased endothelial stability as it activates the mechanical receptors in the cells, causing them to increase production of NO and leads to inhibition of the angiotensin 2 receptor which reduces blood pressure.
This is particularly true of unidirectional laminar flow and pulsatile shear stress.
What effect does disturbed blood flow have on the endothelium?
Regions of disturbed flow, such as artery bifurcations, branch points and regions of high curvature in the artery reduce the shear stress and have high risk of atherogenesis.
This acts through upregulation of inflammatory pathways and atherogenic factors, including ROS, NF-κB, VCAM-1 and MCP-1.
What is the first form of atherosclerosis?
Atheromata develop first as fatty streaks in the intima, a stage which, due to its reversibility, is increasingly an area of study in order to design therapies that stabilise or reduce the size of the streaks.
The size/presence of fatty streaks is a metric which can now be externally monitored by ultrasound or, in a very recent development, PET-CT scans.
What often occurs in tandem with fatty streak formation?
This often occurs in tandem with adaptive thickening of the smooth muscle, though neither is the cause of the other – their coincidence is due to a shared tendency to form in response to varying hemodynamic forces.
Adaptive thickening occurs in defined places, a process that begins at birth.
