Atherosclerosis: Understanding Arterial Disease, Risk Factors, and Prevention, Lecture notes of Cardiology

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ATHEROSCLEROSIS

NOTES.

Inflammation-based

arterial changes as a

mechanism of

primary importance

in atherogenesis

RUDOLF VIRCHOW RUDOLF VIRCHOW

mid 19th century

AtherosclerosisAtherosclerosis

Start from very young Start from very young

To Old age? To Old age?

Atherosclerosis

 Arteriosclerosis – loss of elasticity of the arteries;

thickening and hardening of artery walls

 Atherosclerosis – process where fatty material is

deposited along walls of arteries. This material thickens,

hardens, and can eventually block the artery.

Atherosclerosis is just one type of Arteriosclerosis

 The term atherosclerosis is derived from Greek words

athero (meaning “porridge” or “paste”) and sclerosis

(meaning “hardening”), 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

Atherosclerosis by the Numbers

 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

Transient

ischemic attack

Ischemic stroke Angina:

• (^) Stable
• (^) Unstable Myocardial infarction Peripheral arterial disease:
• (^) Intermittent claudication
• (^) Rest Pain
• (^) Gangrene
• (^) Necrosis MAJOR CLINICAL MAJOR CLINICAL MANIFESTATIONS MANIFESTATIONS OF ATHEROTHROMBOSIS OF ATHEROTHROMBOSIS

 Endothelium: The inner lining of our blood

vessels is the Endothelium. It forms a barrier

between circulating blood and the rest of the

vessel wall

 3 layers in arterial wall:

 (^) Tunica Intima - connective tissue; where lesions form  (^) Tunica Media - smooth muscle  (^) advanced atherosclerosis characterized by proliferation of smooth muscle cells here  (^) Tunica Adventitia - connective tissue; highly vascularized to provide nutrients Vascular Anatomy

Vascular endothelium Functions The vascular endothelium serves multiple functions: 1)it regulates fluid and molecule traffic between blood and tissues 2)it is an anti-coagulant surface 3)it contributes to vascular homeostasis and repair 4)it plays a vital role in vascular tone and blood flow regulation

---

Assessing this function is the most practical way of measuring endothelial function.

 Dyslipidemia

  Endothelial dysfunction

  Free radicals

  Immunologic

  Dyslipidemia

  Endothelial dysfunction

  Free radicals

  Immunologic

Atheroscler Atheroscler osis/CAD osis/CAD Atheroscler Atheroscler osis/CAD osis/CAD

Inflammat

ion

Concept Theory^ Disease (Sargowo, 1996)

LDL Serum  LDL Serum  LDL infiltration

LDL

infiltration LDL Oxidation

LDL

Oxidation Foam Cell Foam Cell Lipid Lipid Cell Proliferation Cell Proliferation Calsificasion Calsificasion Endotheli al dysfuncti on Endotheli al dysfuncti on Growth Factor Growth Factor Platelet Agregatio n Platelet Agregatio n Free Radical Free Radical

ATHEROGENE ATHEROGENE

SIS SIS

(Sargowo, 1996)

Atherosclerosis - Response to Injury  (^) Arterial Injury  (^) Can result from smoke, hypertension, cholesterol, glycated substances, vasoconstriction, homocysteine or infectious agents  (^) Normal endothelial function is not repaired by inherent mechanisms  (^) Endothelial Dysfunction and Inflammatory Response  (^) Arterial homoeostasis is altered by injury, results in inflammatory response (chemicals like histamine, leukotirenes, prostaglandins and chemotactic factors released  (^) Endothelial dysfunction is regarded as the first abnormality leading to atherosclerosis

Response to Injury