Dyslipidaemia Flashcards
What is hyperlipidaemia?
Elevation of one or more plasma lipid fractions.
What are the types of hyperlipidaemia?
Hypercholesterolaemia and hypertriglyceridemia
What is hypercholesterolaemia?
An elevation of total cholesterol, low-density lipoprotein cholesterol (LDL-C) or non-high-density lipoprotein cholesterol (HDL-C) (defined as the subtraction of HDL-C from TC) in the blood.
What is hypertriglyceridemia?
Fasting plasma triglyceride level ≥2.3 mmol/L (≥200 mg/dL)
What is the aetiology of primary hyperlipidaemia? (x5)
- Familial hypercholesterolaemia: reduced functional hepatic LDL receptors
- Familial hypertriglyceridemia: autosomal dominant
- Hypertriglyceridemia: lipoprotein lipase or apo-CII deficiency
- Familial combined hyperlipidaemia
- Remnant hyperlipidaemia: accumulation of LDL remnants
What is the aetiology of secondary hyperlipidaemia? (x4 and x6)
- CHOLESTEROL: sedentary lifestyle, excess saturated fats and trans-fatty acids consumption, obesity, hypothyroidism, nephrotic syndrome, cholestatic liver disease, drugs e.g., thiazides, oestrogens, glucocorticoids.
- TRIGLYCERIDES: sedentary lifestyle, obesity, diabetes, hepatocellular disease, hypothyroidism, nephrotic syndrome, CF, anorexia nervosa, drugs such as glucocorticoids, beta blockers and oestrogens
What is the pathophysiology of hypercholesterolaemia?
- Develops from abnormal lipoprotein metabolism, mainly arising from reduction of LDL receptor activity or expression, and consequently diminished hepatic LDL clearance from the plasma.
- LDL accumulates in intima of systemic arteries by interacting with ECM and proteoglycans. This allows oxidation and macrophage ingestion, where LDL forms foam cell and develops into atheromatous plaque
What is the role of HDL?
Shuttle in periphery for transport of cholesterol esters back to the liver – cardioprotective.
What is the pathophysiology of hypertriglyceridemia?
- Liver secretes triglyceride rich VLDL which are metabolised by lipoprotein lipases in tissues for energy
- Diet triglycerides are transported from the GI tract as chylomicrons and also cleared by lipoprotein lipases
- Diminished lipase activity results in accumulation of these triglyceride-rich lipoproteins
What are the signs and symptoms of hyperlipidaemia?
- Symptoms of CVS complications such as weak peripheral pulses, carotid bruit
- LIPID DEPOSITS: xanthelasmas (around eyes), corneal arcus, tendons xanthomas (extensor tendons of hands, Achilles, patella tendon), tuberous xanthomas on knees and elbows (see photo), lipidaemia retinalis (pale retinal vessels) in severe hypertriglyceridemia
What are the investigations for hypertriglyceridemia?
- Fasting lipid profile: ≥2.3 mmol/L (≥200 mg/dL)
- Glucose, TFTs, LFTs, U&Es to exclude secondary causes
What are the investigations for hypercholesterolaemia?
- LIPID PROFILE: total cholesterol, LDL-C, HDL-C, and triglycerides. Non-HDL-C is calculated by subtraction of HDL-C from total cholesterol
- Glucose, TFTs, LFTs, U&Es to exclude secondary causes
What is target cholesterol in medical management of hypercholesterolaemia?
Less than 4 mmol/L
What is target triglycerides in medical management of hypertriglyceridemia?
Less than 2 mmol/L
How is high cholesterol treated? (x4)
- HMG-CoA reductase inhibitors: statins. Then consider adding the following:
- Ezetimibe: inhibits cholesterol absorption in gut, can be considered if statins not tolerated
- PCSK9 inhibitor such as alirocumab
- Colestyramine: bile acid sequestrant which increases LDL receptor expression on hepatocytes
