Professor of cardiology and internal medicine Atherosclerosis Saadeldeen majeed Professor of cardiology and internal medicine

Pathogenesis of Atherosclerosis According to injury hypothesis considers atherosclerosis to be a diffuse, slowly progressing, chronic inflammatory response of the arterial wall initiated by injury:

Pathogenesis of Atherosclerosis 1. Chronic endothelial injury. 2 .Insudation of lipoproteins [LDL]. 3. Modification of lipoproteins by oxidation. 4. Adhesion of blood monocytes. 5. Adhesion of platelets.

Pathogenesis of Atherosclerosis 6. migration of smooth muscle cells from the media into the intima. 7. proliferation of smooth muscle cells in the intima. 8. enhanced accumulation of intra and extra cellular lipids.

ATHEROSCLEROTIC PLAQUE The change of the large arterial intima is called atherosclerotic plaque or atheroma atherosclerotic plaque is the intimal thickening with lipid accumulation It consists of fibrous cap, necrotic core and fibrous basis.

Atherosclerotic plaque It has three principle components: 1- cells –smooth muscle cells, macrophages, other leukocytes. 2 - Extra cellular matrix- collagen, elastic fibers, and proteoglycans. 3 - Intra cellular and extra cellular lipids.

Normal coronary artery Lumen has been distended at a pressure of 100mmHg with 10% formal saline used with permission from M.J. Davies Atlas of Coronary Artery Disease 1998 Lippincott-Raven Publishers

Eccentric plaque with a central zone containing yellow lipid Early coronary atherosclerosis Eccentric plaque with a central zone containing yellow lipid used with permission from M.J. Davies Atlas of Coronary Artery Disease 1998 Lippincott-Raven Publishers

Stable angina. Eccentric coronary stenosis used with permission from M.J. Davies Atlas of Coronary Artery Disease 1998 Lippincott-Raven Publishers

Stable angina. Eccentric coronary stenosis thick cap used with permission from M.J. Davies Atlas of Coronary Artery Disease 1998 Lippincott-Raven Publishers

Unstable angina with plaque disruption used with permission from M.J. Davies Atlas of Coronary Artery Disease 1998 Lippincott-Raven Publishers

Unstable angina with plaque disruption The plaque cap is torn, projects into the lumen, exposing a mass of thrombus filling the lipid core used with permission from M.J. Davies Atlas of Coronary Artery Disease 1998 Lippincott-Raven Publishers

Development of Atherosclerotic Plaques 2.03 Fatty streak Normal Lipid-rich plaque Foam cells Fibrous cap Lipid core Thrombus Ross R. Nature. 1993;362:801-809.

Vulnerable Versus Stable Atherosclerotic Plaques 2.05 Vulnerable Plaque Lumen Thin fibrous cap Inflammatory cell infiltrates: proteolytic activity Lipid-rich plaque Lipid Core Fibrous Cap Stable Plaque Thick fibrous cap Smooth muscle cells: more extracellular matrix Lipid-poor plaque Lumen Lipid Core Fibrous Cap Libby P. Circulation. 1995;91:2844-2850.

Major modifiable Risk Factors Cigarette smoking (passive smoking?) Elevated total or LDL-cholesterol Hypertension (BP 140/90 mmHg or on antihypertensive medication) .. Low HDL cholesterol (<40 mg/dL)† Obesity: Body Mass Index (BMI) Weight (kg)/height (m2) Weight (lb)/height (in2) x 703 Obesity BMI >30 kg/m2 with overweight defined as 25-<30 kg/m 2 Abdominal obesity involves waist circumference >40 in. in men, >35 in. in women Physical inactivity: most experts recommend at least 30 minutes moderate activity at least 4-5 days/week † HDL cholesterol 60 mg/dL counts as a “negative” risk factor; its presence removes one risk factor from the total count.

Nonmodifiable Risk Factors Age- Age (men 45 years; women 55 years) the older you get, the greater the chance. Sex- males have a greater rate even after women pass menopause. Race- minorities have a greater chance. Family history- if family members have had CHD, there is a greater chance. Family history of premature CHD CHD in male first degree relative <55 years CHD in female first degree relative <65 years Unchangeable Risk Factors: Age, the older you get the greater the chance of heart disease. Four out of five people who die of congestive heart disease are 65 years of age or older. Sex, males have a greater rate of congestive heart disease. Race, minorities have a greater chance of heart disease. African Americans have a greater chance of high blood pressure. The risk is also higher in Mexican Americans, America Indians, native Hawaiians and Asian Americans. Also included as unchangeable risk factors is your family history and your own personal medical history.

Clinical Manifestations of Atherosclerosis 2.09 Coronary heart disease Stable angina, acute myocardial infarction, sudden death, unstable angina Cerebrovascular disease Stroke, TIAs Peripheral arterial disease Intermittent claudication, increased risk of death from heart attack and stroke American Heart Association, 2000.

FORMS OF ATHEROSCLEROSIS CEREBRAL ARTERIES INJURY CARDIAC ARTERIES INJURY RENAL ARTERIES INJURY AORTA INJURY INTESTINAL ARTERIES INJURY EXTREMITY ARTERIES INJURY

What Does It Look Like? The coronary artery is narrowed reducing the flow of oxygen to the heart. It is easier for plaque to get inside a narrower artery.

CEREBRAL FORM OF ATHEROSCLEROSIS Acute form may be as Hemorrhage within The brain due to rupture Of atherosclerotic aneurism

CEREBRAL FORM OF ATHEROSCLEROSIS Chronic form may be as encephalopathy With cerebral atrophy (decreasing memory)

Extremity form of atherosclerosis Acute form may be as gangrenous necrosis.

Aortic form of atherosclerosis Various forms of aorta lesion

RENAL FORM OF ATHEROSCLEROSIS Acute form may be as infarction Chronic form is called Atherosclerotic Nephrosclerosis or Primary contracted kidney

Intestinal form of atherosclerosis Acute form may be as gangrenous necrosis of the intestine Chronic form may be as ischemic enterocolitis

The Skinny on Fat Saturated fats- basically means the fat is saturated with hydrogen, they are solid at room temperature. Examples are lard and butter. Why are they bad for you? They increase levels of LDL , decrease HDL and increase total cholesterol. Saturated fats can cause an increase in cholesterol. What is saturated fat? It is fat that is saturated with hydrogen and is a solid at room temperature. Examples are lard and butter. Saturated fats increase levels of LDL, decrease levels of HDL and increases total cholesterol. The American Heart Association recommends you limit saturated fat intake to 7-10% of your total calories.

The Skinny on Fat What are monounsaturated fats? They are liquid at room temperature but start to solidify in the refrigerator. Decrease total cholesterol and lower LDL levels. Monounsaturated fat includes canola, olive and peanut oils and avocados.

The Skinny on Fat What are trans fatty acids? They are unsaturated fats but they tend to raise total and bad cholesterol. Where do you find them? In fast-food restaurants Commercial baked goods. Examples: doughnuts, potato chips, cupcakes. Trans fatty acids have hydrogen added to them to give them a longer shelf life and they also tend to lower HDL levels.

What about Omega 3? Type of polyunsaturated fat. Consistently lowers serum triglycerides and may also have an effect on lowering blood pressure. Found in oily fish such as salmon, tuna, and herring. Is available as a supplement. The American Heart Association recommends eating fish two times per week. Mention other fish that contain Omega 3 fatting acids. Omega 3 fatty acids are available as a supplement but research is till being done to determine the supplements’ effectiveness.

Physical Inactivity Increasing physical activity has been shown to decrease blood pressure. Moderate to intense physical activity for 30-45 minutes on most days of the week is recommended. Exercise can help control blood cholesterol, diabetes and obesity, as well as help lower blood pressure.

Cigarette Smoking Causes an increase in blood pressure Usually have lower levels of HDL Within 1 year of quitting, CHD risk decreases, within 2 years it reaches the level of a nonsmoker.

Diabetes Mellitus At any given cholesterol level, diabetic persons have a 2 or 3 x higher risk of atherosclerosis! Insulin is required to maintain adequate levels of lipoprotein lipase, an enzyme needed to break down bad cholesterols. About 2/3 of the people with diabetes die of some type of heart or blood vessel disease.

Obesity People who are obese have 2 to 6 times the risk of developing hypertension. Location of the body fat is significant. Pears of apples? People who are obese have 2 to 6 times the risk of developing hypertension even if they have no other risk factors.

Approaches to Primary and Secondary Prevention Primary prevention involves prevention of onset of disease in persons without symptoms. Primordial prevention involves the prevention of risk factors causative o the disease, thereby reducing the likelihood of development of the disease. Secondary prevention refers to the prevention of death or recurrence of disease in those who are already symptomatic

Prevention Get regular medical checkups. Control your blood pressure. Check your cholesterol. Don’t smoke. Exercise regularly. Maintain a healthy weight. Eat a heart-healthy diet. Manage stress. Prevention