Atherosclerosis

Kathryn Rennie
BMS 1
QEH Gateshead
Atherosclerosis;
 Progressive chronic inflammatory disease

◦ Affects large and medium sized arteries

◦ Characterisation includes;
 Endothelial dysfunction
 Vascular inflammation
 Build-up of lipids, cholesterol, calcium and
cellular debris within the intima of the
vessel wall which results in plaque
formation
Incidence;
 Predominantly asymptomatic; frequency
difficult to estimate
 Process begins in childhood; fatty streaks

have been found in 8-18 year olds, with

more advanced lesions developing at 25
years of age
 Higher incidence in males up to the age of

50 years
 Incidence levels usually equate between

males and females after 50 years of age

Risk Factors;
 Hyperlipidaemia
 Hypertension
 Diabetes Mellitus
 Increased fibrinogen levels
 Obesity
 Smoking
 Air pollution
 Lack of exercise
 Heredity?
Disease Progression;
Theories;
 19th century proposals;

◦ INSUDATION (Virchow)
 Associated with high blood cholesterol
 At sites of intimal damage insudation of lipid occurred
which resulted in fat accumulation and fibrosis

◦ THROMBOTIC (Rokitansky)
 Thrombotic encrustation at the site of intimal damage
 Damage initiated the plaque formation and lipid
accumulation was derived from platelets
Theories;
 20th century proposals;
◦ ‘response to injury’ theory

◦ Associated with high serum levels of LDL-cholesterol

 Movement of LDL through the vascular endothelium
 Interaction with proteoglycans and proteins that
stimulate their ‘modification’
 Modified LDL which initiate inflammatory processes
 Increase the expression and secretion of chemotactic
compounds (monocyte and T-cell recruitment)
 Proliferation and migration of SMC
 Uptake by macrophages and SMC by scavenger receptors to
form FOAM CELLS
Initiation and progression;
Clinical diagnosis and imaging;
 Coronary angiography
◦ contrast agent and x-ray
 Intravascular ultrasound
◦ images of thickness and acoustic density of vessel
wall
 Computed tomography
◦ excellent visualisation but high radiation dose
 Magnetic resonance imaging
 Ultrasonography

◦ research stage, measures vessel wall function and

anatomy
Medications;
 HMG-CoA reductase inhibitors
◦ inhibit cholesterol synthesis
◦ affect liver function

 Fibric acid derivatives

◦ increase HDL levels
◦ increase cholesterol excretion into bile
◦ hepatic and renal dysfunction

 Bile acid sequestrants

◦ block circulation of bile acids, increase faecal loss of
cholesterol
◦ inhibits entero-hepatic re-uptake of intestinal bile salts
Medications cont;
 Antioxidants
◦ Vitamin E
◦ iron deficiency anaemia

 Nicotinic acid derivatives

◦ inhibits hepatic secretion of VLDL
◦ acute liver disease

 Nutritional agents
◦ Omega-3 polyunsaturated fatty acid
◦ hyperglycaemia and bleeding due to decreased
platelet aggregation
Preventative treatments;
 Promoting healthier lifestyles?
 Diet

◦ heavy alcohol intake

◦ high levels of red or processed meat
◦ plant-based diets lowered cholesterol levels
 No smoking
◦ risk reduced after 5 years of stopping smoking
 Exercise
◦ increases HDL cholesterol levels and nitric oxide
releases
◦ 150 minutes of moderate physical activity per week
Screening?
 Essential to reduce the increasing burden of
cardiovascular diseases on the NHS
 Difficult to establish as disease is predominantly

asymptomatic (40 year health check?)

 Studies to identify ‘modifiable’ risks

(Framingham risk assessment)

 CT detection of coronary calcium and

ultrasound imaging of carotid arteries

 Research? into identifying specific biomarkers in

the blood for atherosclerosis?

References;
 Boudi B, Hayden CT, and Chowdhury HA. Atherosclerosis. [Online]. [Visited 2011
Feb 06] Available from: URL:http://emedicine.medscape.com/article/150916-print
 Anon. Sequences in progression of atherosclerosis. [Online]. [Visited 2011 Feb 06]
Available from: URL:http://emedicine.medscape.com
 Macfarlane PS, Reid R and Callander R. Pathology Illustrated. 5th Edition. Churchill
Livingstone, London, UK. 2000.
 Badimon L, Vilahur G and Padro T. Lipoproteins, Platelets, and Atherothrombosis.

Rev Esp Cardiol. 2009;62(10):1161-78.

 Anon. Atherosclerosis: An Inflammatory Disease. [Online]. [Visited 2011 Feb 06]

Available from: URL:http://emedicine.medscape.com

 Rader DJ and Daugherty A. Translating molecular discoveries into new therapies for
atherosclerosis. Nature 2008;451:904-13.
 Ladich LR, Virmani R and Kolodgie F. Atherosclerosis. [Online]. [Visited 2011 Feb

06] Available from: URL:http://emedicine.medscape.com/article/1612610-print

 Shah PK. Screening Asymptomatic Subjects for Subclinical Atherosclerosis: Can we,
does it Matter, and should we? J Am Coll Cardiol. 2010;56(2):98-105.