Dyslipidemia and Atherosclerosis PowerPoint Presentation

Slide 1 -

1 DISORDERS OF LIPID METABOLISM & DISEASES RELATED Scientific Office By : Hossam Erian

Slide 2 -

2 SECTION I DYSLIPIDAEMIA

Slide 3 -

3 What is The Meaning of Dyslipidemia? DYSLIPIDAEMIA * Dyslipidemia expresses the broadest term explaining any lipid disorder (any abnormally high levels lipoproteins in blood) . * It explains also any abnormal ratio between different types of lipoproteins ( HDL , LDL , VLDL ) .

Slide 4 -

4 * Dyslipidaemia includes also another term HYPERLIPIDAEMIA What Is Hyperlipidaemia ? Hyperlipidemia is a more specific term , it explains elevated blood cholesterol OR elevated triglycerides OR both of them

Slide 5 -

5 Terminology of Lipid Disorders : * Hypercholesterolemia → Elevated blood cholesterol level . * Hypertriglyceridemia → Elevated triglyceride levels in blood * Hypolipoproteinemia → Decreased levels of lipoproteins (HDL) * Hypoalphalipoproteinemia → Decreased level of HDL .

Slide 6 -

6 Classification of Hyperlipidaemia * Classification of hyperlipidemia … ( hypercholesterolemia & hypertriglyceridemia) is usually according to cause or etiology . * Hyperlipidaemia is classified as : Primary hyperlipidemia → Caused by genetic factors. Secondary hyperlipidemia →Caused by ( diet / disease / drug).

Slide 7 -

7 Primary Hypercholesterolemia Familial Hypercholesterolemia (F H) * (FH) is the example of primary hypercholesterolemia It is due to genetic defects in LDL receptors → ↑ blood cholesterol.

Slide 8 -

8 Primary Hypertriglyceridaemia : * It is a form of hyperlipidaemia due to elevated level of chylomicrons which is called Hyperchylomicronemia .

Slide 9 -

9 Familial Combined Hyperlipidaemia (genetic): * In that type , the family members are suffering from : * Primary hypercholesterolemia → ↑ cholesterol level . * Hypertriglyceridemia → ↑ triglycerides & chylomicrons . * Elevated LDL , VLDL .

Slide 10 -

10 Secondary Causes of Hyperlipidaemia 1 – Diet (high fat & cholesterol intake) . 2 – Diabetes mellitus. 3 – Pregnancy . 4 – Obesity . 5 – Drugs like (Beta blockers , thiazide diuretics).

Slide 11 -

11 6 – Nephrotic syndrome . 7 – Systemic lupus erythromatosus (an auto-immune disease) . 8 – Hypothyroidism (decreased activity of the thyroid gland). N.B : Saturated fats in the diet raise levels of LDL by suppressing the activity of LDL receptors and increasing liver production of cholesterol .

Slide 12 -

12 SECTION 2 ATHEROSCLEROSIS

Slide 13 -

13 ATHEROSCLEROSIS What Is Atherosclerosis ? * Atherosclerosis is a disease in which fatty substances are gradually formed in the inner layer of the coronary arteries → narrowing (stenosis) → occlusion of coronary arteries → reduction of blood flow to heart tissue →myocardial infarction

Slide 14 -

14 General View on Anatomical Structure of The Artery Wall * The artery wall consists of 3 layers : 1 – The Adventitia Layer : * The outer layer , composed of connective tissue, it supports and protects the vessel.

Slide 15 -

15 3 – The interna Layer : * The inner layer , composed of a thin endothelial cells which form a smooth lining to help the blood to flow through the artery with the minimal resistance . 2 – The Media Layer : * The middle layer , composed of smooth muscles and elastic tissue (elastic fibers).

Slide 16 -

16

Slide 17 -

17 Mechanism of Atherosclerosis In Coronary Artery 2 3 1

Slide 18 -

18 Factors Affecting Atherosclerosis : Mechanism of Atherosclerosis In Coronary Artery 1 - Age 2 – Hypertension 3– Diabetes 4 – Smoking 5 – Stress 6– Obesity 7 – High Cholesterol levels . 8 - Atherosclerosis of the coronary artery develops within 3 stages

Slide 19 -

19 Stage 1 : * An injury occurs in endothelial cells of the intema layer , due to long term stress (as high blood pressure) N.B : The coronary arteries are susceptible to such injuries because they are small sized and highly narrow branched . * This injury (lesion) in the intema either heal without damage OR → stage 2

Slide 20 -

20 Stage 2 (The Atheroma Stage) : An atherosclerotic plaque develops through the following steps 1 – Fatty streaks (thin yellowish lines of fats) are precipitated on the endothelial surface of the artery , & accumulated at the area of the injury .

Slide 21 -

21 2 – Macrophages come to the injury as a defense mechanism 3 – Macrophages engulf any debris at the injury . 4 – Due to ↑ cholesterol in blood , macrophages engulf also LDL particles containing that cholesterol .

Slide 22 -

22 5 – After macrophages ingest cholesterol , they are transformed to what is called Foam Cells which are filled with cholesterol . (they are also called cholesterol engorged foam cells) 6 – After that the foam cells are embedded under the endothelial cells forming a bulge in the artery wall , this bulge is called Atherosclerotic Plaque

Slide 23 -

23 7 – The fatty streaks reaccumulate on the atherosclerotic plaque in the artery wall and become thicker and fibrous , & become larger in size and occlude the artery lumen This is called … ATHEROMA Atheroma = Fatty streaks + Atherosclerotic plaque

Slide 24 -

24 Summary of stage 2 : Injury to intema → fatty streaks precipitation macrophages come to injury → macrophages engulf LDL cholesterol → transformed to foam cells → embedded under endothelial cells → atherosclerotic plaque which is combined with fatty streaks and fibrosis → atheroma → Occlusion of coronary

Slide 25 -

25 Stage 3 : * Atheroma occludes blood flow → the heart tissue is deprived of oxygen and nutrients → the prolonged ischemia → ischemia (lack of blood flow to the heart tissue) → cell death and tissue damage which is called Myocardial Infarction (MI)

Slide 26 -

26 Myocardial Infarction → symptoms of acute Angina Pectoris → may lead to sudden death Heart tissue becomes weak → Ventricular arrhythmia , Shock &Congestive heart failure

Slide 27 -

27 SECTION 3 RELATION BETWEEN CHOLESTEROL & CORONARY ARTERY DISEASE ( CAD )

Slide 28 -

28 Relationship between Cholesterol & Coronary Artery Disease (CAD) There are many evidences which prove that the elevated blood cholesterol increases the risk of coronary artery diseases (CAD)

Slide 29 -

29 These evidences are : 1 – Genetic Evidence 2 – Epidemiologic Evidence 3 – Intervention Study Evidence

Slide 30 -

30 1 – Genetic Evidence : * Genetic familial hypercholesterolemia (FH) is the link between cholesterol and CAD. * Individuals with this condition Lack LDL receptors that are responsible for the removal of LDL from blood .

Slide 31 -

31 * The lack of LDL receptors → elevated LDL cholesterol in blood → LDL deposit excess cholesterol in the walls of blood vessels → Atherosclerosis and CAD .

Slide 32 -

32 The lack of LDL receptors → may be : Partial Lack of LDL receptors (Heterozygous FH): * Individuals who inherit a gene for this disease from one parent → decreased or deficient number of LDL receptors (This is called Heterozygous FH).

Slide 33 -

33 * Total cholesterol levels exceed 300 mg / dl (twice the normal). * CAD usually developed by age 45 years . * Incidence of heterozygous FH is about 1 in 500 people.

Slide 34 -

34 Complete lack (Homozygous FH) : * Individuals who inherit genes from both parents * Total cholesterol levels range from 600 – 1000 mg / dl (4 times that of normal) Incidence is extremely rare 1 in 1000,000 people → complete lack of LDL receptors (this is called Homozygous FH).

Slide 35 -

35 2 – Epidemiologic Evidence : * Epidemiologic (population) studies examined the relationship between disease , patient and environment . Aim of these studies : To explain the link between cholesterol and CAD.

Slide 36 -

36 * The aim of Framingham heart study is to determine the most serious risk factors associated with cardiovascular disease . The Framingham Heart Study ( FHS ) * The study has followed 5000 men and women of the residents of Framingham city of Massachusetts state in USA .

Slide 37 -

37 * The study started in 1948 , the 5000 case were medically tested to record : Blood pressure , weight , age , life style and ECG (electro-cardiogram) * The medical examination is repeated every 2 years looking for signs of CAD with complete analysis of all factors associated with the incidence of CAD as…

Slide 38 -

38 Smoking , Obesity , Male sex , Age , High total blood cholesterol , Hypertension , Stress , ECG abnormalities and family history .

Slide 39 -

39 The following Diagram explains the Framingham Heart Study …. * The study has provided an important evidence linking heart disease with : 1 – Smoking . 2 – Hypertension . 3 – High blood cholesterol. * The risk of CAD increases significantly when cholesterol rises above 200 mg / dL

Slide 40 -

40 DYSLIPIDEMIA & CHD FRAMINGHAM HEART STUDY The risk of CHD increases dramatically at cholesterol levels above 230 mg/dl

Slide 41 -

41 Is Low Total Blood Cholesterol Sufficient to Confirm Low Risk of CAD ? * All studies suggest that reducing total blood cholesterol below 200 mg / dL Does not reduce the risk of CAD too much … Even if the total cholesterol is low, there may be an increased risk of CAD

Slide 42 -

42 * The Framingham heart study also confirmed that : WHY ? The normal total cholesterol does not mean that the patient is at low risk of CAD , The more important factor is the HDL cholesterol ( HDL-C ) level .

Slide 43 -

43 If total cholesterol is normal and HDL is low → high risk of CAD . If total cholesterol is normal and HDL is high → low risk of CAD . As the HDL are considered as protection against CAD So …. their low level → increases the risk of high cholesterol → high risk of CAD.

Slide 44 -

44 3 – Intervention Study Evidence : * The intervention study evidence have proved the risk between blood cholesterol and the risk of CAD through different ways: Decreasing blood cholesterol → decreases the risk of CAD .

Slide 45 -

45 Coronary Intervention Study : - This study gave a physical proof through Angiography … It is a technique through which an image of the atherosclerotic plaque on coronary artery walls is obtained through injecting a radio-opaque substance into the vessels and take X- ray photos

Slide 46 -

46 - The patients were taking special diet regimen and a lipid – lowering drug . Results : 17 % decrease in the rate of progression of atherosclerotic plaque as followed by photos.

Slide 47 -

47 1 % reduction in cholesterol → about 2 % reduction in CAD ↑ LDL → ↑ risk of CAD And ↑ HDL → ↓ risk of CAD The Helsinki Study : This study was published in 1987 to clarify the link between cholesterol & CAD . General Conclusion about Intervention Study

Slide 48 -

48 Study : Large 5 years study on about 4000 patients (men) with high cholesterol levels but no symptoms of heart disease were divided to 2 groups : 1st group : Were given a drug that decreases triglycerides and increases HDL levels (Gemfibrozil - or Lopid).

Slide 49 -

49 2nd group : Were given placebo Results : In patients who received drug therapy : HDL was increased . - LDL was moderately reduced . 34 % decrease in the risk of CAD .

Slide 50 -

50 Management & Control of Dyslipidemia 1 – Diet Therapy 2 – Exercise 3 – Excessive Weight Reduction 4 – Drug Therapy … That will be Discussed Later …. Good Luck