Lipids and Lipoproteins - tests and disease correlation

1 - 5 μIU/mL

Normal values of fasting insulin

4.5 - 5.2%

Normal values of HbA1c (Normal)

Low-density lipoprotein cholesterol (LDL-C)

• is the primary target of therapy

• Bad cholesterol

• Leads to plaque buildup, resulting in decreased blood flow.

Hypertriglyceridemia

An independent risk factor for coronary heart disease (CHD)

Nephrotic Syndrome

• The filtration system is already compromised, which allows leakage of macromolecules, especially albumin.

• Leaky filtration leads to protein loss, which can result in edema.

Nephritic Syndrome

• The problem is with the nephron or the microscopic filtration system.

• Urine may appear reddish due to blood leakage and may have bubbles or foam on the surface.

• Inflammation of the nephron can cause red blood cells and foam to appear in the urine.

Elevations in Lipoprotein (a)

• Causes thrombosis and the formation of atherosclerosis.

• The formation of atherosclerotic plaque can lead to atherosclerotic stenosis.

• Plaque in the aortic valve can lead to aortic valve stenosis.

Remnant Lipoproteins

• Can cause plaque buildup in the intimal layer of blood vessels, decreasing the vessel’s caliber and reducing blood perfusion.

• This leads to more problems, such as atherosclerotic stenosis, ischemia, or even stroke.

Fibrinogen

• Markers of prothrombotic states (acute phase reactants).

• Genetics accounts for about 50% of the variability in fibrinogen levels.

Elevated homocysteine levels

• Increase the risk of cardiovascular diseases.

• Linked to medications.

Homocysteine

injures the arterial wall

High-Sensitivity C-Reactive Protein (hs-CRP)

High-Sensitivity C-Reactive Protein (hs-CRP)

Impaired Fasting Plasma Glucose

After 8 to 12 hours of fasting, FBS ranges from 100 to 125 mg/dL.

Carotid Intimal-Medial Thickening

Carotid Intimal-Medial Thickening

Coronary artery calcium deposition

Calcified arteries indicate advanced atherosclerosis.

TRUE

TRUE OR FALSE: Children with high blood cholesterol levels typically maintain high blood cholesterol levels through adulthood.

Polygenic (Nonfamilial) Hypercholesterolemia

• The cause is likely multifactoral

• Patients who develop age-related increases in cholesterol that do not respond to lifestyle modification.

Familial Hypercholesterolemia

• Autosomal dominant disorder.

• Mutations in the LDL-receptor gene on chromosome 19.

• An inherited genetic disorder that causes dangerously high levels of low-density lipoprotein (LDL).

• Defective receptors cannot bind or clear low-density lipoprotein (LDL) from the circulation.

Heterozygous FH

• Occurs in 1 in 500 individuals.

• Associated with premature atherosclerotic disease.

• LDL-C levels are typically >220 mg/dL.

Homozygous FH

• Present in childhood.

• LDL levels >400 mg/dL.

• Premature symptomatic coronary heart disease (CHD).

Statins

are a type of pharmacologic agent that inhibit 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase

Familial defective apolipoprotein B (ApoB)

• Autosomal dominant disorder.

• The apolipoprotein B (ApoB) gene is on chromosome 2.

• Interferes with the recognition of apoB-100 by the LDL receptor.

• Missense mutation (Arg3500Gln) in the LDLR-binding domain of ApoB-100.

Sitosterolemia

• Extremely rare autosomal recessive disorder.

• Phytosterols (plant sterols) are absorbed and accumulate in plasma and peripheral tissues.

• Mutations in the ABCG8 or ABCG5 gene are located at chromosome 2p21

Autosomal dominant hypercholesterolemia

• Autosomal dominant.

• Disorder PCSK9 gene on chromosome 1.

PCSK9

• is involved in cholesterol homeostasis in the liver.

• It is secreted into the plasma.

• It binds to LDL receptors on the cell surface and marks them for degradation.

• Endocytosis and intracellular degradation of the LDLR.

Autosomal recessive hypercholesterolemia

• Autosomal recessive disorder.

• Involves the ARH gene found on chromosome 1.

• LDLR expression is normal, but LDL clearance rates are low.

• Often manifests with bulk xanthomas.

• Respond to lipid-lowering medications.

• Maintained on LDL apheresis.

Diabetic Dyslipidemia

• Atherogenic dyslipidemia in persons with type 2 diabetes:  High triglycerides, Low HDL and small dense LDL

• Treatment is often directed at LDL-C.

Isolated hypertriglyceridemia

• Type 4 hyperlipidemia.

• Autosomal dominant disorder.

• Affecting approximately 1:300 to 1:50 people.

• Fasting triglyceride levels in the 200-500 mg/dL range. 

• Formation of fluffy, triglyceride-rich VLDL particles.

• Coexisting exacerbating factors: Obesity and insulin resistance.

Lipoprotein lipase deficiency (Hyperlipoproteinemia Type Hyperchylomicronemia)

• An autosomal recessive disorder. 1 or

• Presented in childhood with abdominal pain and pancreatitis

• Inability to clear chylomicrons from the blood.

• Deficiency of the enzyme lipoprotein lipase leads to uncontrolled elevation of triglycerides in the plasma.

Apolipoprotein C-II

• is an activating cofactor for lipoprotein lipase (LPL).

• Autosomal recessive form of familial hyperchylomicronemia.

• Present in children and young adults.

• Recurrent bouts of abdominal pain and pancreatitis

Lipoprotein lipase

is an enzyme that needs a cofactor or a coenzyme for it to function properly.

Apolipoprotein C-III (ApoC-III) excess

• Interferes with the activity of lipoprotein lipase.

• Binds to the carboxy-terminal portion of apolipoprotein B.

• Prevents the binding of lipoproteins to the LDL receptor.

• leads to increased accumulation of atherogenic lipoproteins in the arterial wall and heightened endothelial inflammation, predisposing the individual to thrombotic events.

Apolipoprotein A-V (ApoA-V)

• A highly hydrophobic protein that has a preference for binding to lipids and HDL particles. 

• Involved in VLDL assembly and activation of LPL-mediated triglyceride hydrolysis.

• Low levels may promote hypertriglyceridemia

Familial Combined hyperlipidemia (Type 2B)

• It could be simple hypercholesterolemia, simple hypertriglyceridemia, or mixed defect. 

• Lacks a definitive biochemical marker.

• Autosomal codominant inheritance.

Apolipoprotein C-II

is an activating cofactor for lipoprotein lipase (LPL).

Acquired combined hyperlipidemia (Secondary hyperlipidemia)

• Common in patients who have metabolic syndrome.

• High levels of free fatty acids in plasma.

• The liver increases the production of VLDL.

Apolipoprotein E

• Present on chylomicrons, VLDL, IDL, and chylomicron remnants.

• Binds to the LDL receptor.

• Clear lipoproteins from circulation.

• 3 electrophoretic isoforms.

E-2

• It has lower affinity for the LDL receptor.

• Lipoprotein particles accumulate in the blood of patients.

Hepatic lipase deficiency

Mutations of the hepatic lipase gene.

Cholesterol 7-Alpha-hydroxylase deficiency

• A recessive disorder of the CYP7A1 gene.

• Encodes cholesterol 7-alpha-hydroxylase protein.

• Enzyme involved in the first step of the classical pathway for bile acid biosynthesis. 

• Reduced hepatic LDLR activity.

• High cholesterol and high triglycerides in plasma.

• Resistant to statin therapy.

Abetalipoproteinemia

• Also known as Bassen-Kornzweig syndrome.

• An autosomal recessive disorder.

• Mutations in the MTTP gene, located on chromosome 4.

Hypobetalipoprotenemia

• An autosomal dominant disorder.

• Nonsense or missense mutations in the apolipoprotein B (apoB) gene.