Block A - Medicine - Endocrine Teaching Clinic - Lipid disorders Flashcards
Calculated LDL- C formula
Friedewald Formula: LDL-C = TC – HDL-C – (TG/2.2)
Does not apply if TG>4.5 mmol/l
Cut-offs for LDL- C, HCL-C and TC
Causes of secondary hyperlipidemia
- Diabetes mellitus type II
- Alcohol abuse
- Hypothyroidism (LDL receptors are downregulated)
- Chronic renal failure
- Nephrotic syndrome (liver synthesizes protein to compensate)
- Cholestatic liver disease (jaundice)
Ddx secondary hyperlipidemia: Isolated increase Triglyceride
- Type II Diabetes mellitus
- Alcohol abuse
- Chronic Renal Failure
Ddx secondary hyperlipidaemia:
Isolated high cholesterol
Hypothyroidism
Cholestatic liver disease
Ddx secondary hyperlipidaemia:
Both increase TG and Cholesterol
Nephrotic syndrome
Types of Primary Hyperlipidemia
Common (polygenic) hypercholesterolaemia
Familial combined hyperlipidaemia
Familial hypercholesterolaemia
Remnant hyperlipidaemia
Chylomicronaemia syndrome
Familial hypertriglyceridaemia
HDL hypercholesterolaemia
Ddx primary hyperlipidemia associated with pancreatitis
Remnant hyperlipidaemia
Chylomicronaemia syndrome **
Familial hypertriglyceridaemia **
Ddx primary hyperlipidemia with high CVD risk
Common (polygenic) hypercholesterolaemia
Familial combined hyperlipidaemia
Familial hypercholesterolaemia **
Remnant hyperlipidaemia **
LDL level that indicates genetic forms of hypercholesterolemia
LDL-C ≧190 mg/dL (4.9 mmol/L)
Familial hypercholesterolaemia
- Inheritance
- Pathophysiology
- Clinical manifestations
Inheritance: Autosomal dominant (chromosome 19, 4
classes of mutations)
Pathophysiology: Defective function of LDL receptors, cannot clear LDL
Clinical manifestations:
- Corneal arcus
- Xanthelasma
- Tendon Xanthomata
- Cutaneous xanthomata, Tuberous/ Palmar/ Planar
- Myocardial infarction, Angina, Sudden cardiac death
Treatment of familial hypercholesterolemia
Lifestyle modification: control CVD risk factors and diet
Drugs:
HMG CoA reductase inhibitor + cholesterol absorption inhibitor (2nd)
Resins, fibrates, nicotinic acid
PCSK9 inhibitor
Last-line:
LDL apheresis, liver transplant, gene therapy (homozygous FH)
Partial ileal bypass vena-caval shunt
List CVD risk factors
How to assess 10-year CVD risk
For patients with multiple (2+) risk factors: perform 10-year risk assessment
o Framingham Risk Chart
o PROCAM Risk Chart
o European Coronary Risk Chart
o Joint British Societies Coronary Prediction Risk Chart
o New Zealand Cardiovascular Risk Prediction Chart
Systemic approach to the treatment of primary dyslipidemias
- Make an accurate diagnosis: baseline lipid levels, repeat testing
- Identify and control other CVD risk factors, 10-year CVD risk
- Initiate therapeutic lifestyle modifications changes ± lipid lowering drugs
- Monitor drug efficacy, side effects, combination
Outline diet modifications for primary dyslipidemia
All fats are high in calories, aim to reduce
Replace saturated fats (animal products) with monounsaturated or polyunsaturated fats (plant products)
Increase fruits, vegetables, whole-grain foods
Limit alcohol intake
Macro:
Total fat 25-35% of total calories
Carbohydrate 50-60% of total calories
Cholesterol <200 mg/day
LDL-C goals for patients with/ without CVD
LDL-C <2.6mmol/L - Without CVD
LDL-C <1.8mmol/L - With CVD
Outline the tiers of treatment for primary dyslipidemia
Primary: Monotherapy with high-intensity statin (Rosuvastatin or atorvastatin)
Secondary: Rosuvastatin/ Atorvastatin + Ezetimibe
Tertiary: Rosuvastatin/ Atorvastatin + Ezetimibe + PCSK9 inhibitor/ Fibrates/ Resins/ Niacin
List first-line, second-line and combination therapy for hypercholesterolemia
1st = Statin
2nd = Resin/ Fibrate
Combo = Statin + Resin/ Fibrate
List first-line, second-line and combination therapy for combined hyperlipidemia
1st = Fibrate/ Statin
2nd = Resins
Combo = Fibrate + Statin/ Fibrate + Resin
List first-line, second-line and combination therapy for hypertriglyceridemia
1st = Fibrate
2nd = Statin, Omega-3 oil, Nicotinic acid
Combo = Fibrate + fish oil/ nicotinic acid
Interpret following lipid profile:
M/17 178cm 55kg (ideal: 78-100kg) BMI 17.4
- Total cholesterol 14.7
- TG 1.09
- LDL 13.4
- HDL 0.9
One major GI condition a/w dyslipidemia
Pancreatitis
One endocrine disorder a/w dyslipidemia
hyperlipidemia secondary to hypothyroidism
Causes Isolated hypercholesterolemia, predominantly LDL
Statins
- Examples
- Effect on lipid profile, efficacy
- Indication
- MoA
- S/E and C/I
Statins = HMG- CoA reductase inhibitors
Examples: Lovastatin, Simvastatin, Atorvastatin…
Effect: Lower LDL-C, lower TG, Increase HDL
Indications: Hypercholesterolemia; lower CHD mortality, CVD intervention, stroke rate…
MoA: Upregulate LDLr on hepatocytes, lower cholesterol synthesis, increase LDL catabolism
S/E: GI disturbance, Rash, Myopathy, Fatigue, Headache
C/I: Liver diseases
Fibrates
- Examples
- Effect on lipid profile, efficacy
- Indication
- MoA
- S/E and C/I
Fibrates = Fibric acid derivatives
Examples: Fenofibrate, Gemfibrozil, Ciprofibrate…
Effect: Lowers TG and IDL-C, Increase HDL-C
Indication: Familial hypertriglyceridemia, Familial Combined Hyperlipidemia
MoA: Increase lipoprotein lipase, Increase fecal sterol excretion, Lower liver VLDL synthesis, Lower hormone-sensitive lipase
S/E: Dyspepsia, Gallstone, Myopathy, Low libido, Hair loss
C/I: Renal or liver failure
Cholesterol absorption agent
- Examples
- Effect on lipid profile, efficacy
- Indication
- MoA
- S/E and C/I
Cholesterol absorption agent
Example: Ezetimibe (only one)
Effect: Lower LDL-C, Increase HDL-C
MoA: Block NPC1L1 >> inhibit dietary and biliary cholesterol absorption at intestines + Decrease hepatic cholesterol storage, increase cholesterol clearance from blood
S/E: headache, abdominal pain, diarrhea
C/I: Liver failure
Resins
- Examples
- Effect on lipid profile, efficacy
- Indication
- MoA
- S/E and C/I
Resins = Bile acid sequestrants
Examples: Cholestyramine, Colestipol
Effect: Lower LDL-C, Increase HDL-C
Indications: FH, FCH
MoA: Stops enterohepatic bile acid recycling + increase LDLr expression
S/E: Constipation, GI disturbance
C/I: Dys-Beta-Liproproteinemia, high TG
Niacin
- Examples
- Effect on lipid profile, efficacy
- Indication
- MoA
- S/E and C/I
Niacin = nicotinic acid
Examples: immediate/ sustained/ extended release formulas
Effect: Lower TG, VLDL-C, IDL-C, LDL-C; Increase HDL-C
Indication: All hyperlipoproteinemia (except type I)
MoA: Antilipolytic, decrease liver cholesterol synthesis, Increase catabolism of chylomicrons, VLDL, LDL
S/E: Flushing, Dry itchy skin, Duodenal ulcer, Gout, Hyperglycemia, Hepatotoxic
C/I: Peptic ulcer, gout, liver disease
PCSK9 inhibitor
- Examples
- Effect on lipid profile, efficacy
- Indication
- MoA
- S/E and C/I
Examples: Alirocumab, Evolocumab
Effect: Lower LDL-C, apoB100
MoA: PCSK9 inhibited >> cannot bind to LDLr >> LDLr not internalized in liver >> Increase overall LDLr expression >> Lower LDL
S/E: Nasopharyngitis, Injection site reaction, Arthralgia and back pain
