Coronary Artery Disease and Atherosclerosis

Coronary Artery Disease (CAD)

• Narrowing or blockage of coronary arteries, usually due to plaque buildup.
• Coronary arteries supply oxygen-rich blood to the heart.
• Plaque limits how much blood can reach the heart.

Coronary Atherosclerosis

• Buildup of fats, cholesterol, and other substances on artery walls.
• This buildup is called plaque.
• Plaque can cause arteries to narrow, blocking blood flow.
• Plaque can lead to a blood clot.

Causes of Atherosclerosis

• Exact cause is unknown.
• May start with damage or injury to the inner layer of an artery.
• Damage may be caused by:
  • High triglycerides
  • High blood pressure
  • Smoking
  • Insulin resistance
  • High cholesterol
  • Diabetes
  • Obesity
  • Inflammation from an unknown cause or from diseases such as arthritis

Pathophysiology of Atherosclerosis

• Low-density lipoprotein molecules (LDL) become oxidized by oxygen free radicals.
• Oxidized LDL comes in contact with an artery wall, causing damage.
• The body's immune system sends specialized white blood cells (macrophages and T-lymphocytes) to absorb oxidized-LDL, forming foam cells.
• These white blood cells cannot process the oxidized-LDL and eventually rupture.
• The artery becomes inflamed.
• Cholesterol plaque causes muscle cells to enlarge and form a hard cover over the affected area.
• The hard cover narrows the artery, reduces blood flow, and increases blood pressure.

Lipid Profile

• Lipoproteins: LDL and HDL
• LDL: (normal level, less than 130 mg/dL)
  • Primary transporters of cholesterol and triglycerides into the cell.
  • Deposit these substances in the walls of arterial vessels.
• HDL: (normal range in men, 35 to 65 mg/dL; in women, 35 to 85 mg/dL)
  • Have a protective action.
  • Transport cholesterol away from the tissue and cells of the arterial wall to the liver for excretion.
• Cholesterol: (normal level, less than 200 mg/dL, High: = 240 mg/dL)
• Triglycerides: (normal range, 40 to 150 mg/dL)
  • Composed of free fatty acids and glycerol, stored in the tissue and are a source of energy.

Stages of Atherosclerosis

Normal Heart and Artery vs. Artery with Plaque Buildup

• Red blood cells
• Coronary artery
• Heart | * Artery wall
• Red blood cells
• Plaque
• Narrowed coronary artery
• Heart
• Fat |

Physiologic Factors that Increase Risk of Atherosclerosis

Modifiable

• Having diabetes
• Tobacco smoking (increases risk by 200% after several pack years)
• High blood pressure
• Elevated serum C-reactive protein concentrations

Nonmodifiable

• Advanced age
• Male sex
• Having close relatives who have had some complication of atherosclerosis (e.g., coronary heart disease or stroke)
• Genetic abnormalities (e.g. familial hypercholesterolemia)

Lesser or Uncertain

• Being obese (in particular central obesity)
• Sedentary lifestyle
• High carbohydrate intake
• Elevated serum levels of triglycerides
• Stress

Signs and Symptoms of Atherosclerosis

• Depend on the degree of narrowing of the arterial lumen, thrombus formation and obstruction of blood flow.
• Inadequate supply of blood leads to oxygen deprivation in muscle (ischemia).
• Angina pectoris, chest pain brought about by myocardial ischemia, usually caused by coronary atherosclerosis.
• If blood supply decreases significantly and for a longer period, myocardial infarction can occur.
• Damaged myocardium is replaced by scar tissue, causing various degrees of myocardial dysfunction.
• Inadequate cardiac output and heart failure can occur.

Treatment of Atherosclerosis

• Non-pharmacological means (cessation of smoking and regular exercise) are usually the first line of treatment.
• If non-pharmacological methods do not work, medicines are usually the next step.
• Statins:
  • Widely prescribed for treating atherosclerosis.
  • Examples: lovastatin, simvastatin, and fluvastatin.
  • Action: block cholesterol synthesis, lower LDL and triglyceride levels, and increase HDL.
• Nicotinic acids:
  • Another class of medications used to treat atherosclerosis.