Clinical Framework
Management is dictated by the primary risk:
- TG 1.7 – 10 mmol/L: Primary risk is ASCVD. Treat LDL and ApoB.
- TG > 10 mmol/L: Primary risk is Pancreatitis. Treat TG levels directly.
classification (ccs 2021)
- Screening: Non-fasting lipid profile is standard.
- Reflex: If non-fasting TG >4.5 mmol/L, repeat fasting.
| Category | Range (mmol/L) | Dominant Lipoprotein | Clinical Priority |
|---|---|---|---|
| Moderate | 1.7 – 5.6 | VLDL | ASCVD |
| Severe | 5.6 – 10.0 | VLDL + Chylomicrons | ASCVD + Monitoring |
| Critical | > 10.0 - 11.3 | Chylomicrons | Pancreatitis |
pathophysiology: saturation kinetics
- LPL Saturation: Lipoprotein Lipase (LPL) clears TG from circulation. The enzyme has a maximum capacity ().
- Zero-Order Kinetics:
- At levels >10 mmol/L, LPL is fully saturated.
- Clearance becomes constant/slow regardless of concentration.
- Clinical Consequence: A small substrate load (e.g., one fatty meal) causes disproportionate, rapid spikes in TG (e.g., from 12 25 mmol/L) because elimination pathways are blocked.
etiology & physical signs
Secondary Causes:
- Endocrine: Diabetes Mellitus (insulin required for LPL synthesis), Hypothyroidism.
- Meds: Oestrogens (OCP/HRT), Propofol, Retinoids, Thiazides, Antipsychotics.
- Lifestyle: Alcohol (inhibits lipolysis), simple sugars.
Physical Findings (Severe HTG):
- Eruptive Xanthomas: 1-5mm yellow papules on extensors/buttocks.
- Lipemia Retinalis: Creamy/pink retinal vessels (TG > 28 mmol/L).
exam trap: lab interference
- Pseudohyponatremia: Lipids displace plasma water; measured Na+ per volume is low, but physiologic Na+ is normal.
- Amylase: Falsely normal in 50% of HTG-pancreatitis due to lipemic interference. Check Lipase.
management: pancreatitis prevention
Indication: TG > 10 mmol/L (or history of pancreatitis). Goal: Reduce TG < 5.6 mmol/L to remove chylomicron burden.
- Strict Fat Restriction: < 20g fat/day (or <15% total calories).
- Mechanism: Reduces chylomicron substrate.
- Pearl: Use MCT Oil (Medium Chain Triglycerides). Absorbed via portal vein, bypassing chylomicron formation.
- Fibrates: First-line pharmacotherapy.
- Agent: Fenofibrate (Lipidil) > Gemfibrozil (safer with statins).
- Alcohol Abstinence: Mandatory.
management: ascvd risk reduction
Indication: TG 1.7 – 10 mmol/L. Goal: Reduce atherogenic particle number (ApoB).
- Statin Therapy: First-line. Lowers TG by 10-30% via VLDL clearance.
- Icosapent Ethyl (Vascepa):
- Indication (CCS 2021): Established CVD or Diabetes + Risk Factors, on statin, with TG 1.7 – 5.6 mmol/L.
- Evidence: REDUCE-IT trial (25% RRR in MACE).
- Mechanism: Membrane stabilization/pleiotropy (independent of TG lowering).
- Note: Unlike EPA+DHA (Lovaza), EPA-only (Icosapent) does not raise LDL-C.
contraindication
Do NOT use Fibrates for ASCVD risk reduction. Trials (ACCORD-Lipid, PROMINENT) show no cardiovascular benefit in statin-treated patients. Fibrates are indicated only for severe HTG to prevent pancreatitis.
acute management (active pancreatitis)
Mechanism: Mechanical obstruction of pancreatic capillaries by chylomicrons ischaemia autodigestion.
- NPO: Stops chylomicron production. Drops TG ~50% in 24h.
- Insulin Dextrose Infusion:
- Dose: 0.1 units/kg/hr.
- Mechanism: Upregulates LPL activity.
- Efficacy: Comparable to plasmapheresis; 95% success rate.
- Plasmapheresis: Reserve for severe acidosis/organ failure.
red flag: avoid heparin
Heparin releases stored LPL into circulation (transient drop) but leads to hepatic degradation and depletion of the total enzyme pool. Causes rebound hypertriglyceridemia.