Hyperlipidaemia Flashcards
Describe briefly the exogenous and endogenous pathways for lipid metabolism [5]
Exogenous:
- Dietary lipids broken down by pancreatic lipase into FFA monoacylglycerol
- Broken down by bile into micelles and taken up by enterocytes where they form triglycerides
- In enterocytes, triglycerides and cholesterol are packaged into chylomicrons
- Apo-B-48 is core molecule of chylomicron
- Chylomicrons are absorbed through lymphatic system and delivered by systemic circulation via lymphatic duct
Apolipoprotein [] on the chylomicron that is able to bind to LDL receptors and be uptake by hepatocytes.
A
B
C
D
E
Apolipoprotein [] on the chylomicron that is able to bind to LDL receptors and be uptake by hepatocytes.
A
B
C
D
E
Describe briefly the endogenous and endogenous pathways for lipid metabolism [5]
- In the liver, cholesterol may be synthesised de novo by the conversion of acetyl coenzyme A into mevalonate and then cholesterol by the action of HMG-CoA reductase
- Cholesterol and triglycerides are formed into very-low-density lipoproteins (VLDL).
- VLDLs are broken down by lipases in circulation into intermediate density lipoproteins; these are metabolised by liver or converted to LDLs
- The majority of LDLs are cleared from the circulation by LDL receptors found on hepatocytes. The remainder is **cleared by peripheral tissue. **
very-low-density lipoproteins (VLDL) have which core structural protein? [1]
Apo B-100
State three signs that indicate hyperlipidaemia [3]
Corneal arcus: white or grey opaque ring in the corneal margin
Tendon xanthoma: hard, non-tender nodular enlargement of tendons. Common on knuckles and achilles
Xanthelasma: yellow plaques on the upper eyelids
What are the arrows pointing to? [1]
Tendon xanthoma
What is the name for this sign of hyperlipidaemia? [1]
Corneal arcus
What initial investigations would you use for hyperlipidaemia? [5]
- Non-fasting full lipid profile
- HbA1c
- Assess for secondary causes of hyperlipidaemia (e.g. alcohol, smoking, CKD)
- Assess risk for anti-lipid therapy (includes baseline renal, thyroid, and liver profiles +/- CK if unexplained muscle pain)
- Determine any contraindications/drug interactions
- If non-fasting TG > 4.5 mmol/L arrange a fasting sample
In which cases should you suspect familial hypercholesterolaemia? [2]
- Total cholesterol > 7.5 mmol/L, AND/OR
- Personal or family history (first-degree relative) of premature coronary artery disease (a cardiovascular event < 60 years)
A specialist referral to a lipid clinic should be made regardless of family history if:
Clinical diagnosis of [], OR
Total cholesterol > [] mmol/L, AND/OR
LDL cholesterol > [] mmol/L, AND/OR
Non-HDL cholesterol > [] mmol/L OR
Fasting triglycerides > [] mmol/L
Clinical diagnosis of FH, OR
Total cholesterol > 9.0 mmol/L, AND/OR
LDL cholesterol > 6.5 mmol/L, AND/OR
Non-HDL cholesterol > 7.5 mmol/L OR
Fasting triglycerides > 10 mmol/L
Statins inhibit which enzyme? [1]
What is the MoA? [2]
Statins inhibit HMG-CoA reductase
It converts HMG-CoA into mevalonic acid, which is a cholesterol precursor.
The reduction in hepatic cholesterol production leads to upregulation of hepatic LDL receptors that reduce circulating levels of LDL in the blood.
When should patients take statins? [1]
Why? [1]
at night as HMG Co-A reductase is most active at night
hether a statin is high-intensity depends on the type and dose. For example, [] 20 mg PO once daily is a high-intensity treatment, whereas [] 10 mg PO once daily is a low-intensity treatment.
hether a statin is high-intensity depends on the type and dose. For example, atorvastatin 20 mg PO once daily is a high-intensity treatment, whereas simvastatin 10 mg PO once daily is a low-intensity treatment.
Which drug class are commonly used alongside statins to reduce serum lipid levels (if statins have not work by themselves) [1]
Name an example
Fibrates are commonly used in combination with statins where there has been an inadequate fall in serum lipids.
- E.g. ezetimibe
Describe the MoA of fibrates [5]
- Reduce triglyceride synthesis in the liver
- Increase removal of LDL particles
- Induce lipoprotein lipase gene transcription
- Stimulate cellular fatty acid uptake
- Increase HDL production by inducing apo-AI and apo-AII gene transcription
What is the MoA of Bempedoic acid? [1]
What is the drug class? [1]
adenosine triphosphate citrate lyase (ACL) inhibitor. It works by inhibiting the synthesis of cholesterol in the liver, which lowers LDL-C.
What type of drug are the following? [1]
Alirocumab: monoclonal antibody
Evolocumab: monoclonal antibody
Inclisiran: small interfering mRNA
PCSK9 inhibitors
Name three PCSK9 inhibitors that can reduce lipid levels [3]
Alirocumab: monoclonal antibody
Evolocumab: monoclonal antibody
Inclisiran: small interfering mRNA
Describe the MoA of PCSK9 inhibitors
What are the indications for statins use? [4]
Ages ≤84 and QRISK ≥10% over the next ten years (if ≥85 years consider comorbidities, frailty, life expectancy)
Type 2 diabetes mellitus and QRISK ≥10% over the next ten years
Type 1 diabetes mellitus and additional risk (Age > 40, diabetes > 10 years, other CVD risk factors, established nephropathy): Can be considered in all patients with Type 1 diabetes mellitus
Patients with CKD (eGFR < 60 mL/min/1.73m2 and/or albuminuria)
Following initiation of a statin, patients should have a full lipid profile repeated at 3 months. The aim is to achieve a reduction in non-HDL cholesterol by > []% from baseline (targets are higher in familial hyperlipidaemia).
Following initiation of a statin, patients should have a full lipid profile repeated at 3 months. The aim is to achieve a reduction in non-HDL cholesterol by > 40% from baseline (targets are higher in familial hyperlipidaemia).
What is the first line treatment (and dose) for hyperlipidaemia [1]
If lifestyle factors are ineffective or inappropriate then statin therapy with atorvastatin 20 mg PO once at night should be advised (this is a high-intensity statin regimen).
State three complications of statin use [3]
Myopathy
Liver impairment
? Intracerebral haemorrhage
FH is one of the most common autosomal dominant genetic disorders. A mutation may be identified in one of which three keys genes? [3]
Low-density lipoprotein receptor (LDLR) gene: also referred to as the ApoB/E receptor - most common
Proprotein convertase subtilisin kexin 9 (PCSK9) gene
Apolipoprotein B gene
Describe the treatment regime for FH [6]
- High-intensity statin therapy
- Ezetimibe: alone in those unable to have statins or in combination
- PCSK9 inhibitors (e.g. alirocumab)
A variety of additional options are usually restricted to patients with homozygous FH and include:
- Evinacumab (new therapy for homozygous FH)
- Lomitapide (inhibits microsomal triglyceride transfer protein)
- Other therapies (e.g. aphesis, liver transplantation)
