Hyperlipidemia Overview Quiz

Hyperlipidemia Overview

• Hyperlipidemia is an abnormal amount of lipids in the blood.
• Two types exist:
  • Hyperlipidemia: abnormally high levels of lipids and/or lipoproteins.
  • Hypolipidemia: abnormally low levels of lipids and/or lipoproteins.
• Three major lipids found in the blood are cholesterol, triglycerides, and phospholipids.
• Key lipids involved in hyperlipidemia are low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol.
  • LDL cholesterol is often called "bad" cholesterol and contributes to plaque buildup in arteries.
  • HDL cholesterol is often called "good" cholesterol and helps remove excess cholesterol from the bloodstream.

Learning Outcomes

• Students should be able to describe different types of dyslipidemia.
• Students should be able to determine the types and causes of hyperlipidemia.
• Students should be able to describe the pathophysiology of hyperlipidemia.
• Students should be able to outline strategies for controlling hyperlipidemia.

Case Study

• A 55-year-old woman presented with chest pain and shortness of breath.
• A coronary artery was occluded due to an atherosclerotic plaque, and myocardial infarction was diagnosed.
• Two questions were posed and relate to the biochemical basis of the disease, and different medications for hyperlipidemia.

Dyslipidemia Classification

• Hyperlipidemia is classified into two categories:
  • Primary (Familial): caused by genetic defects in lipid or lipoprotein metabolism. Classified using the Fredrickson classification.
  • Secondary: caused by another underlying condition, such as disease, hormonal changes, or medications.
• Different types of Primary Hyperlipidemia according to the Fredrickson classification include:
  • Type I: Familial Hyperchylomicronemia. Elevated chylomicrons, often due to a deficiency of Lipoprotein Lipase (LPL) or apoC-II. Low risk for atherosclerosis, but high risk for pancreatitis. Very rare.
  • Type IIa: Familial Hypercholesterolemia. Elevated LDL. Caused by LDL receptor deficiency or dysfunction. High risk for atherosclerosis and cardiovascular disease. Xanthomas may be present.
  • Type IIb: Familial Combined Hyperlipidemia. Elevated LDL and VLDL. Combination of genetic and lifestyle factors. High risk for atherosclerosis and cardiovascular disease.
  • Type III: Familial Dysbetalipoproteinemia (Remnant Hyperlipidemia). Elevated IDL (intermediate-density lipoproteins). High risk for atherosclerosis, specifically peripheral artery disease and premature coronary artery disease.
  • Type IV: Familial Hypertriglyceridemia. Elevated VLDL. Often associated with obesity, type 2 diabetes, or high-carbohydrate diets. Moderate risk for atherosclerosis.
  • Type V: Mixed Hyperlipidemia (Combined Hyperlipoproteinemia). Elevated VLDL and chylomicrons. Risk: Moderate for atherosclerosis; high risk for pancreatitis.

Secondary hyperlipidemia

• It is related to certain diseases, hormonal changes, and medications, such as: Obesity, diabetes mellitus, hypothyroidism, drugs (steroids, estrogens in contraceptives).

Hyperlipidemia and Atherosclerosis

• Excess LDL cholesterol accumulates in the artery walls, especially when HDL levels are low.
• Oxidized LDL particles trigger inflammation.
• White blood cells (macrophages) try to digest the cholesterol, forming "foam cells."
• Foam cells accumulate, leading to plaque formation.
• Over time, plaques harden, narrowing arteries, and reducing blood flow.
• Hyperlipidemia significantly increases the risk of cardiovascular disease (coronary artery disease, cerebrovascular disease, peripheral artery disease).

Management of Hyperlipidemia

• Aims to reduce blood lipid levels to prevent complications such as atherosclerosis, heart attacks, and strokes.
• Typically combines lifestyle changes (diet modification, exercise, quitting smoking) and if needed, medications.

Non-pharmacological therapy (Lifestyle modifications)

• Diet low in cholesterol
• Exercise
• Quit smoking
• Stress management
• Avoid risky behaviours
• Social support
• Sleep

Medications

• HMG-CoA reductase inhibitors (statins): decrease cholesterol synthesis, increase LDL receptors.
• Cholesterol absorption inhibitors: inhibit cholesterol absorption in the small intestine.
• Bile acid sequestrants (e.g., cholestyramine): prevent bile acid reabsorption to increase elimination of bile acids and cholesterol.
• Fibrates: increase lipoprotein lipase (LPL) activity, reduce VLDL levels, and decrease triglycerides.

Hypolipidemia

• Abnormally low levels of lipids and/or lipoproteins in the blood.
• Primary causes: Genetic (Tangier disease, Familial LCAT deficiency)
• Secondary causes: Hyperthyroidism, malnutrition, starvation, malabsorption, Drug-induced (statins, fibrates, niacin).

1-Tangier Disease

• Mutation in the ABCA1 gene, impacting cholesterol transport.
• Reduced cholesterol mobilization from peripheral tissues.
• Accumulation of cholesterol in various tissues (spleen, nerves, skin, lymphoid tissues).
• Very low serum HDL levels.
• Yellowish-orange discoloration of the tonsils, tonsillar enlargement, hepatosplenomegaly, peripheral neuropathy.

2-Familial LCAT Deficiency

• Mutation in the LCAT gene, impacting lecithin-cholesterol acyltransferase activity.
• Reduced esterification of cholesterol into cholesterol esters.
• Impaired HDL function.
• Extensive corneal opacification, often referred to as "fish-eye disease."