Atherosclerosis Part 1 Atherosclerosis The general term for hardening of the arteries The most prevalent form of atherosclerosis is characterized by the accumulation of lipid, particularly cholesteryl esters, in the arterial intima. Initial occurrence of lipid deposits inside arterial smooth muscle cells and macrophages. At this stage the lipid deposits are reversible, and no permanent damage to the vessel wall results. - This early lesion is called Fatty streak: Subsequently lipids begin to accumulate extracellularly in the arterial intima. When the lesion progresses to this stage, it is no longer completely reversible. Recent studies on diet-induced atherosclerosis in monkeys indicate that some lipid can be removed from even advanced lesions so that the atherosclerotic areas actually can be made to shrink. - This shrinking process is called regression.

Symptoms No symptoms until the damage to the arteries is severe enough to restrict blood flow atherosclerosis can cause angina pectoris intermittent claudication transient ischemic attacks stroke

Diagnosis angiography (X ray after injection of a radiopaque dye) Doppler ultrasound velocity detection plethysmography (a technique that produces a tracing of the pulse pattern) CT scan (computed tomography)

Treatment Medication is unsatisfactory since damage has already been done Cholesterol lowering drugs - lowering LDL cholesterol Anticoagulant drugs - to minimize secondary clotting Blood pressure medications -such as beta blockers, angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers Surgical treatments: balloon angioplasty Coronary artery bypass replacement of peripheral vessels with woven plastic tube grafts

Guidelines for Classification and Follow-up Based on Total Plasma Cholesterol Concentration Total Cholesterol mg/dl (mM) ClassificationRecommended Follow-up < 200 (< 5.2) Desirable blood cholesterol Repeat blood test within 5 years 200 to 239 (5.2 to 6.2) Borderline high cholesterol Without CAD* or CAD risk factors provide dietary information and recheck annually With CAD or CAD risk factors - obtain lipoprotein analysis; further action based on LDL-cholesterol value > 240 (> 6.2) High blood cholesterol Obtain lipoprotein analysis; further action based on LDL-cholesterol value

Coronary Heart Disease Deaths Serum Cholesterol Quintile (mg/dL) Normotensive Nonsmoker Hypertensive Smoker < to to to > Death per 1000 in men to 35 to 57 years of age

CHD Risk Factors other than LDL-Cholesterol Male sex Family history of premature CHD (definite myocardial infarction or sudden death before age 55 in a parent or sibling) Cigarette smoking Hypertension Low HDL-cholesterol concentration (below 35 mg/dL confirmed by repeated measurements) Diabetes mellitus History of definite cerebrovascular or occlusive peripheral vascular disease Severe obesity (> 30% overweight) Iron overload Elevated Homocysteine Acute inflammation (elevated CRP)

Folic Acid Cycle

Mechanism producing atherosclerosis and tissue infarction

Possible effect of LDL This scheme suggests that oxidatively modified LDL may enhance the accumulation of macrophages by attracting circulating monocytes while inhibiting tissue macrophage motility

Some functions shared by endothelial cells, smooth muscle cells, and macrophages from the arterial wall that may play role in atherogenesis