Lipid Disorders and Cardiovascular Health

Lipid Disorders

• Hyperlipidemia is a risk factor for cardiovascular mortality.

Lipids in Plasma

• Major lipids in plasma include:
  • Fatty acids (FA)
  • Triacylglycerols (TAG)
  • Sterols
  • Phospholipids

Lipid Transport

• Lipids are transported in plasma by associating with proteins (albumin and lipoproteins).
• Lipoproteins have a hydrophobic center and a hydrophilic coat.
• Components of lipoproteins include:
  • Triglycerides (TG)
  • Cholesterol ester
  • Phospholipids
  • Apolipoproteins

Apolipoproteins

• Functions of apolipoproteins:
  • Components of lipoproteins
  • Ligands for receptors
  • Cofactors for enzymes

Lipoprotein Types

• Chylomicron (dietary lipids): mucosal cells → peripheral tissues → liver
• VLDL / LDL (lipid synthesized in liver): liver → peripheral tissues
• HDL (cholesterol): peripheral tissues to liver (in liver: metabolism and storage)

Lipid Disorders

• Primary hyperlipidemia: genetics, appears early in life
• Secondary hyperlipidemia: caused by another disorder in the body that increases lipid levels

Rare Causes of Hypolipoproteinemia

• Abetalipoproteinemia:
  • Caused by defect in apo B synthesis
  • Absence of LDL, VLDL, and CM in plasma
  • Clinical manifestations: fat malabsorption, retinitis pigmentosa, ataxic neuropathy
• Hypobetalipoproteinemia:
  • Caused by apo B deficiency
  • Characterized by low LDL, VLDL, and CM levels
  • Decreased ASCVD risk
• Alpha-Lipoprotein Deficiency or Tangier’s disease:
  • Caused by increased apo A-1 catabolism
  • Low HDL-C levels
  • Hyperplastic, orange tonsils

Primary Causes of Lipoprotein Abnormalities

• Familial Hypercholesterolemia:
  • Autosomal dominant condition
  • Defect in LDL receptor
  • High cholesterol from early childhood
  • Clinical manifestations: xanthelasma, tendon xanthomas, corneal arcus lipus
• Familial Dysbetalipoproteinemia:
  • Increased levels of IDL, CM remnants
  • Apo E-2/E-2 phenotype
  • Clinical manifestations: tubero-eruptive xanthomas
• Familial Combined Hyperlipidemia:
  • Elevated VLDL and LDL
  • Overproduction of VLDL by liver
  • Clinical manifestations: cutaneous manifestations, increased risk of coronary artery disease
• Familial Hypertriglyceridemia:
  • Markedly elevated VLDL
  • Normal LDL
  • Clinical manifestations: increased risk of coronary artery disease, pancreatitis
• Familial Chylomicronemia:
  • Elevated chylomicrons in blood
  • LPL deficiency
  • Clinical manifestations: eruptive xanthomas, recurrent abdominal pain due to pancreatitis

Laboratory Lipid Profile

• Total cholesterol, HDL-C, and triglycerides are measured directly in the lab
• LDL cholesterol can be calculated using the equation: LDL-C = Total Cholesterol – (HDL-C + TG/2.2)

Classification of Lipid Levels

• Total cholesterol:
  • < 5.2 mmol/L: desirable
  • 5.2-6.2 mmol/L: borderline high
  • ≥ 6.2 mmol/L: high
• LDL cholesterol:
  • < 2.6 mmol/L: optimal
  • 2.6-3.3 mmol/L: near optimal
  • 3.3-4.1 mmol/L: borderline high
  • ≥ 4.1 mmol/L: high
• Triglycerides:
  • < 1.69 mmol/L: optimal
  • 1.7-2.3 mmol/L: near optimal
  • 2.3-4.5 mmol/L: borderline high
  • ≥ 4.5 mmol/L: high
• HDL cholesterol:
  • < 1.03 mmol/L (males): low
  • < 1.3 mmol/L (females): low
  • ≥ 1.55 mmol/L: high