Atherosclerosis: Understanding Causes, Risks, and Prevention, Lecture notes of Cardiology

Download Atherosclerosis: Understanding Causes, Risks, and Prevention and more Lecture notes Cardiology in PDF only on Docsity!



In 2008 17.3 million people died from

cardiovascular diseases, and the prognosis shows

that by 2030, 23.6 million people will die from

these diseases every year

 For the past two decades, CVD mortality have

been declining in high–income countries; however,

in low and middle–income countries, the rates are

inclining alarmingly



World-wide, ischemic heart disease is also the

main cause of death and healthy years of life-lost

Atherosclerosis by the Numbers

Coronary Heart Disease  The major underlying cause is atherosclerosis. 

The term atherosclerosis , which comes from the Greek

words atheros (meaning “gruel” or “paste”) and sclerosis

(meaning “hardness”), denotes the formation of fibrofatty

lesions in the intimal lining of the large and medium-size

arteries such as the aorta and its branches, the coronary

arteries, and the large vessels that supply the brain.



Simplified Definition

The thickening and hardening of arterial walls as a

consequence of atheroma

Pathogenesis Response to injury hypothesis , Atherosclerosis is considered to be a chronic inflammatory response of the arterial wall initiated by the injury to the endothelium.

Endothelial Injury  (^) One hypothesis of plaque formation suggests that injury to the endothelial vessel layer is the initiating factor in the development of atherosclerosis.  (^) Possible injurious agents are:  Products associated with smoking;  Immune mechanisms;  Mechanical stress, such as that associated with hypertension.  (^) Hyperlipidemia, particularly LDL with its high cholesterol content, is also believed to play an active role in the pathogenesis of the atherosclerotic lesion

 Deregulation of cholesterol levels results in the existence of more LDL in the blood than can be taken up by LDL receptors. Excess LDL is oxidized becoming oxidized (ldl-ox) by oxygen free radicals  (^) Oxygen free radicals are a type of harmful body metabolism by-products. Normally free radicals are removed by anti-oxidants  In the vascular endothelial, the deficiency of Nitric Oxide (NO) antioxidant aids oxidized LDL to cause Endothelial disruption leading to platelet adhesion and fibrin deposition Role of Lipids in Plaque Development cont’d

 (^) An injury to the endothelial lining allows LDL particles, monocytes, and platelets to enter the smooth muscle tissue  (^) Inflammation at the injury site triggers the conversion of monocytes to microphages, which scavenge the LDL particles and cholesterol to form enlarged foam cells. Under the microscope, the lesion appears as a fatty streak. Foam cells eventually die, and further propagate the inflammatory process.  (^) There is also smooth muscle proliferation and migration from tunica media to intima responding to cytokines secreted by damaged endothelial cells. This would cause the formation of a fibrous capsule covering the fatty streak.  (^) Smooth muscle cells, foam cells, platelets, and LDL particles form fibrous plaque Lipids and Inflammation in Plaque Development

Fatty Streaks  Injury or infection can disrupt normal endothelial function and initiate formation of atherosclerotic lesions known as fatty streaks.  Fatty streaks are thin, flat yellow intimal discolorations that progressively enlarge by becoming thicker and slightly elevated as they grow in length  Fatty streaks typically consist of macrophages and smooth muscle cells that have become distended with lipid to form foam cells.

Pathogenesis Summary

1. Circulating LDL infiltrate endothelial cell layer
2. LDL is modified (i.e. oxidation; ox-LDL)
3. Accumulation of ox-LDL elicits an immune response (recruitment of macrophages)
4. Activated macrophages release pro-inflammatory signaling molecules (cytokines)
5. Macrophages uptake ox-LDL but are unable to ingest the modified LDL leading to Agglutination
6. Lipid laden macrophages are characterized as foam cells
7. Foam cells accumulate forming the atherosclerotic plaque

Age  A dominant influence  Atherosclerosis begins in the young, but does not precipitate organ injury until later in life  Gender  Men more prone than women, but by age 60- 70 about equal frequency  Family History  Familial cluster of risk factors  Genetic differences Non Modifiable Risk Factors in Atherosclerosis

Modifiable Risk Factors (potentially controllable)  Elevated Homocysteine: Homocysteine inhibits elements of the anticoagulant cascade and is associated with endothelial damage.  Infections: Herpes virus; Chlamydia pneumoniae: The organisms may play a role in atherosclerotic development by initiating and enhancing the inflammatory response  (^) Obesity, sedentary lifestyle, stress: lack of activity can worsen other risk factors for atherosclerosis.

• Elevated serum C-reactive protein: It may increase the likelihood of thrombus formation; inflammation marker

Modifiable risk factors