- raised or abnormal levels of any or all lipids and/or lipoproteins in the blood.
- o familial (also called primary) caused by specific genetic abnormalities
- o acquired (also called secondary) when resulting from another underlying disorder that leads to alterations in plasma lipid and lipoprotein metabolism.
- - Normal values:
- - Total cholesterol: normal <4mmol/L, >5mmol/L (raised) >6.5mmol/L (very high)
- - Low density Lipoprotein (LDLs): normal <2mmol/L, >3mmol/L (raised) and >4.5mmol/L (very high)
- - High Density Lipoproteins (LDLs): normal >1mmol/L, <1mmol/L in men and <1.3mmol/L in women (low)
- - Triglycerides: normal <2mmol/L), >2.3mmol/L
There are several groups, but these two seem most relevant:
|Type IIa||Polygenic hypercholesterolaemia or Familial hypercholesterolemia (FH)||LDL receptor deficiency||LDL||Bile acid sequestrants, statins, niacin|
|Type IIb||Familial combined hyperlipidemia||Decreased LDL receptor and increased ApoB||LDL and VLDL||Statins, niacin, fibrate|
This may be sporadic (due to dietary factors), polygenic, or truly familial as a result of a mutation either in the LDL receptor gene on chromosome 19 (0.2% of the population) or the ApoB gene (0.2%). The familial form is characterized by tendon xanthoma, xanthelasma and premature cardiovascular disease. The incidence of this disease is about 1 in 500 for heterozygotes, and 1 in 1,000,000 for homozygotes.
Diagnosis of FH: >7.5mmol/L total chol and FH.
The high VLDL levels are due to overproduction of substrates, including triglycerides, acetyl CoA, and an increase in B-100 synthesis. They may also be caused by the decreased clearance of LDL. Prevalence in the population is 10%.
- Familial combined hyperlipoproteinemia (FCH)
- Secondary combined hyperlipoproteinemia (usually in the context of metabolic syndrome, for which it is a diagnostic criterion)
Acquired hyperlipidemias mimic primary forms and can have similar consequences. They may result in increased risk of premature atherosclerosis or, when associated with marked hypertriglyceridemia, may lead to pancreatitis (TG>10mmol/L) and other complications of the chylomicronemia syndrome.
Secondary causes of hypercholesterolaemia: hypothyroid, nephrotic syndrome, jaundice.
Secondary causes of hypertriglyceridaemia: alcohol excess, obesity, DM.
The most common causes of acquired hyperlipidemia are:
- diabetes mellitus
- Use of drugs such as diuretics, beta blockers, and oestrogens
Other conditions leading to acquired hyperlipidemia include:
- renal failure
- nephrotic syndrome
- alcohol usage
- Some rare endocrine disorders and metabolic disorders
Hereditary? Infective? How does it spread?
Treatment and management (conservative/medical/surgical)
Treatment of the underlying condition, when possible, or discontinuation of the offending drugs usually leads to an improvement in the hyperlipidemia.
Measure levels regularly: can directly measure chol, HDL and TG. Need to calculate LDL.
- Specific lipid-lowering therapy may be required in certain circumstances
- Dietary modifications (reduce chol)
- Statins (HMG-CoA reductase inhibitors – reduced chol production in liver)
- Niacin (increase HDL, lower TGs).
- Ezetimibe: selective cholesterol absorption inhibitor – effective but expensive.
T-II DM and hyperlipidaemia:
- Microalbuminuria: loss of s.2-3.5mg/mmol on 2 consecutive occasions.
- Proteinuria: 0.5g protein lost in 24hours AND 300mg albumin lost in 24hours.
- 10 year survival of T-II DM = 50% (60% of deaths due to macrovascular disease). If have microalb