Dyslipidaemia (hypercholesterolaemia & hypertriglyceridaemia) Flashcards
Define hypertriglyceridaemia.
fasting plasma triglyceride level ≥2.3 mmol/L
When does triglyceridaemia cause chylomicronaemia? What condition may arise as a result of trigycerides >20mmol/L?
When triglyceride level is >11.3mmol/L
Pancreatitis occurs at levels >20mmol/L
How common is triglyceridaemia?
- Related to insulin resistance and linked to being obese/overweight so prevalence is rising
What are the causes of hypertriglyceridaemia?
Primary/genetic causes:
- monogenic chylomicronaemia
- polygenic HTG
- dysbetalipoproteinaemia
- combined hyperlipoproteinaemia
Secondary causes:
- obesity, DM
- lipodystrophies e.g. metabolic syndrome (high triglycerides, low HDL), hypothyroidism,
- renal disease, nephrotic syndrome, dialysis
- liver disease, NASH, viral hepatitis
- cystic fibrosis, HIV infection
- genetics - apo A-V, apo CIII and angiopoietic-like proteins 3 and 4
- anorexia nervosa
- excess alcohol (acute and chronic)
- Cushing’s
- organ transplant, sarcoidosis, SLE, myeloma
Medications
- glucocorticoids
- oestrogens, tamoxifen
- Accutane, retiinoid (bexarotene)
- antihypertensive meds like hydrochlorothiazide and non-selective beta blockers
- antiretroviral therapy
- interferons
- propofol
What is the pathophysiology of hypertriglyceridaemia (triglyceride metabolis
- TG arise from exogenous and endogenous sources
- Exogenous = dietary fats + TG-rich chylomicron particles from blood that are cleared by liver → absorbed in GI tract
- Liver secretes VLDLs into blood → peripheral tissues → metabolised by lipoprotein lipases for energy for muscle or storage by adipose tissue.
- Chylomicrons and VLDLs are cleared by tissue lipase pathways.
- When lipoprotein lipase activity is decreased the clearance VLDL/chylomicrons is impaired → accumulation of triglycerides in blood
What are the risk factors for hypertriglyceridaemia?
- FH
- overweight/obese
- high saturated fat, carb/glycaemic index diet, excess alcohol intake
- insulin resistance
- liver disease, renal disease
- hypothyroidism
- Cushing’s
- anorexia nervosa
- HIV
- CF
- medications
- acute spinal cord injury
- inflammatory/immune disorders
- organ transplant
What might you see on examination in a patient with hypertriglyceridaemia?
Lipaemia retinalis = retina is pale and retinal vessels are white
Eruptive xanthoma = small yellow papules surrounded by erythematous base (appear on buttocks, elbows, pressure sensitive spots) - below
Both uncommon. Patients typically asymptomatic
What investigation would you do for suspected hypertriglyceridaemia?
- TG level - after 12-14hr fasting
Other:
- TFTs - for hypothyroidism
- Fasting plasma glucose
- Urea, Cr, albumin - raised with low albumin in nephrOtic syndrome
- LFTs
- Serum protein electrophoresis - if suspicious of multiple myeloma/SLE
- CT - if signs of acute pancreatitis
- Apolipoprotein B
- CRP
How is hypertriglyceridaemia managed?
Conservative -
Lifestyle modification - e.g. smoking, HDLs. Recommended for 3-6month before medication is started.
Treat underlying conditions
Medical:
Statins - 40-80mg OD. Dose based on ASCVD score.
+/- non-statin LDL-lowering medications - ezetimibe, PCSK9i (e.g. evolocumab, alirocumab) or bempedoic acid
+/- isosapent ethyl or omega3acid ethyl esters - if persistent TG >1.7mmol/L
+/- fibrate e.g. gemfibrozil- do NOT give with a statin
How is acute chylomicronaemia managed?
Chylomicronaemia/acute pancreatitis - hospital admission and supportive care
- IV hydration and NBM for 48-72hrs - until TGs <5mmol/L
- Start statins once TGs <5mmol/L
- +/- IV insulin - may help lower TGs in poorly controlled DM.
What are the complications of hypertriglyceridaemia? What is the prognosis?
- Coronary events
- Acute pancreatitis
What is the prognosis with HTG?
Improves significantly with lowering of TG levels.
Once plasma lipid levels are stable they can be monitored with LFTs every 6-12 months.
Define hypercholesterolaemia.
Elevation of total cholesterol and/or LDL or non-HDL cholesterol in the blood = dyslipidaemia
Briefly describe what is meant by dyslipidaemia.
Dyslipidaemia = serum TC, LDL-C, TGs , apolipoprotein B, or lipoprotein(a) concentrations above the 90th percentile, or HDL-C or apolipoprotein A-I concentrations below the 10th percentile for the general population.
However, these classic percentile cut-off points should not be used too rigidly - evidence suggests that lipoprotein(a) ≥80th percentile is abnormal and linked to elevated CVD risk.
How common is hypercholesterolaemia?
- Depends on definition
- Approx 12% of US pop has TCs over 6.2mmol/L
- In those with CHD, dyslipidaemia presence is 80-88%
What is the pathophysiology of hypercholesterolaemia?
- Usually from abnormal lipoprotein metabolism e.g. less LDL-R expression or activity → less hepatic LDL clearance → atherosclerosis
What signs might be present on physical examination in hypercholesterolaemia?
- Obesity
- Xanthelasmas
- Tendinous xanthomas
- Tuberous xanthomas - firm, painless, red-yellow nodules
- Yellow palmar striae (should be red) - found in type III familial dys-beta-lipoproteinaemia
- Corneal arcus with onset before age 45yrs
What is the management of hypercholesterolaemia?
- Lifestyle modification - cholesterol intake should be <300mg/day, aerobic exercise, complex carbohydrates and unsaturated fat.
- High intensity statin - atorvastatin 40-80mg OD; check HDL-C and non-HDL-C at 3 months
- +/- Ezetimibe - impairs dietary and biliary cholesterol absorption; ezetimibe may be added to maximally tolerated statin
- +/- PCSK9 inhibitor - alirocumab - inhibits PCSK9 binding to LDL-R which causes degradation
- +/- Bile acid sequestrants - prevent bile reabsorption; e.g. colestyramine and colesevelam for severe hypercholesterolaemia
