Chemical Pathology 4: Lipid Profile Flashcards
Physiological importance of lipids
- Highest energy-yielding metabolic fuel
- Fat-soluble vitamins absorption
- Heat-insulation, shock-protection
- Cell membrane constituent
- Steroid biosynthesis
- Nerve conduction
5 types of lipids
- Fatty acids
- Glycerol esters: Triglycerides/TAG, Phospholipids
- Sphingolipids
- Sterols: Cholesterol, Steroid hormones, Bile acids
- Terpenes (Fat soluble vitamins)
Normal lipid and lipoprotein metabolism
TAG:
- From diet
- From catabolism of carbohydrates, proteins, other fatty acids in liver
Cholesterol:
- From diet
- From liver synthesis
Laboratory investigations
- Lipid profile (implication on coronary heart disease)
- Total Cholesterol, HDL, LDL, TAG
- Non-HDL-C - Lipoprotein pattern
- Visual
- Overnight standing
- Electrophoresis
- Ultracentrifugation - Secondary causes
- TFT
- RFT/LFT
- Fasting glucose
- HbA1c
- Urinary protein - Atherosclerosis risk assessment: Carotid artery doppler
- SE of drug treatment (e.g. Statin): LFT, Creatine phosphokinase (CPK)
- Lipid profile
Total cholesterol, HDL, LDL, TAG
- Total cholesterol measurement: non-fasting sample maybe used
- LDL decreases in acute events (e.g. AMI) - recommend to take blood
—> within 24 hours of acute onset
—> 4-6 weeks after recovery
—> Friedewald equation for calculated LDL-C (NOT valid in high TAG): TC - HDL-C - TG/5 - TAG: fasting for 8-12 hours required
—> juice / black coffee may be allowed
—> non-fasting will increase TAG
Reasons: - fasting levels for standardising prandial + activity status
- post-prandial rise in TAG
- LDL-C estimated using Friedewald equation —> if TAG too high >4.5 —> implies existence of other lipoprotein
- many major trials are based on fasting lipids
- now some suggest use of ***non-fasting lipid profiles —> more prevalent
- elevated ***non-fasting TAG level is an indication of increased CVD risk
—> food intake may be regarded as a “stress test” for lipoprotein metabolism
—> increase sensitive of TAG as a risk factor
—> variability of food intake interfere with standardisation of measurements
—> samples collected ~4 hours after food intake are particularly informative
—> direct measurement of LDL-C —> +/- repeat with a fasting and 4 hour postprandial TAG - Use of non-HDL cholesterol (Total minus HDL-C)
—> more accurate estimation of ***CVD risk than LDL-C
—> better for assessment of treatment response
—> usually 0.5-0.8 mmol/L higher than corresponding LDL-C levels
Advantages of non-fasting lipid profile
- Non-fasting status predominate (fasting is not physiological)
- Modest difference between fasting / non-fasting
- No strong evidence suggest fasting is superior in terms of CVD risk prediction
- Improve patient convenience, compliance
- Blood taking spread throughout working day (not only morning) —> relieve workload
- Safe (less frisk of hypoglycaemia)
Structure of lipoprotein
餡:
- Cholesterol ester
- TAG
外層:
- Free cholesterol
- Phospholipid
- Apoprotein
Classification of lipoprotein
- Nature
- Proportion of lipids
- Different Apolipoproteins
—> Heterogeneous with various size, densities etc.
Classification by physiological functions:
- Chylomicrons - transport of exogenous TAG
- VLDL - transport of endogenous TAG
- LDL - transport of cholesterol from liver to other tissues
- HDL - transport of cholesterol from peripheral tissues / other lipoproteins to liver
- IDL - one of remnant lipoproteins
Classification by chemical properties:
1. Ultracentrifugation (densities)
2. Electrophoresis (sizes)
3. Immunochemical
—> 5 major classes: HDL, LDL, IDL, VLDL, Chylomicron
—> each class is heterogenous e.g. HDL has > 14 members, HDL1, 2, 3 etc.
- Lipoprotein pattern
To investigate primary Hyper / Hypolipidaemia
- Secondary causes not need lipoprotein pattern (∵ already known)
- Visual inspection
- becomes hazy when TAG > 2.3
- excessive chylomicron, VLDL —> turbid
- excessive LDL —> clear - Lipoprotein electrophoresis
- based on charge-to-mass ratio
- serum samples loaded on agarose gel
—> lipoprotein move under electric field
—> separated lipoprotein stained with a fat stain
—> ***Chylomicron (唔郁), LDL, VLDL, HDL, Free fatty acids (最遠)
—> useful for new cases of lipid disorders
Fredrickson classification
- Purely descriptive
—> e.g. Type 1 —> Pure Hyperchylomicronaemia - No information about etiology
- Does not affect treatment / management
Clinical approach
- Identify pattern
- ↑ LDL-C
- ↑ TAG
- ↑ LDL-C + TAG
- ↑ non-HDL-C - Look for secondary causes, if none then
- Look for primary defect
- Family / genetic study
- Family cascade screening
Lipid disorders
Hyperlipidaemia vs Hypolipidaemia
Hyperlipidaemia vs Hypertriglyceridaemia vs Hypocholesterolaemia
Risk of Hypertriglyceridaemia:
- Chemical pancreatitis —> acute abdominal pain + milky blood (when TAG >10)
- Metabolic syndrome
- Fatty liver
- Postprandial hypertriglyceridaemia —> atherogenic —> lifestyle changes
Risk of Hypercholesterolaemia:
CVD
1. Coronary heart disease (CHD)
- MI, angina, heart failure
- Primary prevention / Secondary prevention
—> treat all patients with known CVD with lifestyle interventions and high intensity statin therapy, irrespective of baseline LDL-C
- Cerebrovascular disease
- stroke, TIA - Peripheral artery disease
- intermittent claudication, critical limb ischaemia - Aortic atherosclerosis and thoracic / abdominal aortic aneurysm
CVD risk calculators
- Framingham risk score, ATP III hard CHD risk score
- most commonly used - ACC / AHA pooled cohort hard CVD risk score
- SCORE CVD death risk score
- QRISK, QRISK2, JBS3
- MESA risk score
- China-PAR risk predictor
- match ethnicity in HK - NVDPA Australian calculator
***Risk factors for CVD
- Age (Male >=45, female >=55)
- Male
- High Total Cholesterol
- Low HDL-C
- BP>140/90 or On antihypertensive
- Smoking currently
- DM
- Similar as other atherosclerotic diseases
Multiple risk factors with 10-year risk for CHD >20%
Others:
- Obesity
- Sedentary lifestyle
- Family history (premature CHD in 1st degree relative)
- Hyperhomocysteinemia
- C-reactive protein
- Lipoprotein(a)
Primary prevention Treatment Guideline
記: >=10% —> Start Statin + Lifestyle modification
Various guidelines
- LDL-C as treatment target
- If LDL-C >2.6
—> calculate baseline CVD risk by risk calculator
—> treat patients at higher levels of risk (***>=10% of 10 year risk) with Statin
- All patients with elevated LDL-C should exercise, prudent diet, lose weight
After initiation of Statin therapy
—> remeasure LDL-C for patients who:
1. Not achieved expected 50% reduction in LDL-C
OR
2. Remain with LDL-C >70 / 1.8
—> possible noncompliance to statin therapy
ACC/AHA 2013 guideline: Moderate statin dose - adult: 40-75 without CVD - LDL-C: 70-189 mg/dL (1.81-4.9 mmol/L) - LDL-C: >=190 mg/dL —> high statin dose, many are ***heterozygous familial hypercholesterolemia - 10-year CVD risk: ***>=7.5%
NICE:
- 10-year CVD risk: ***>=10%
2016 European Society of Cardiology / European Atherosclerosis Society guidelines
- SCORE system 10-year CVD risk: ***>=5%
- LDL-C treatment goal: 100
