DYSLIPIDAEMIADr.Hasan Fahmawi, MRCP(London), FRCP(Edin)

Lipid profile

• Total cholesterol• HDL• LDL• Triglycerides• Patient must be fasting for 12 hours

Metabolism

• In the fasting state, the liver is the main source of plasma lipids, as itacquires them from food (saturated and trans- unsaturated fattyacids, which reduce LDLRs). They are transported to other tissues bysecretion of VLDLs which are rich in TG. They are converted to IDLcleared by LDLR in the liver.

Investigations• Screening for primary or secondary prevention of CVD.• Investigation of patients with clinical features of lipid disorders and their relatives.• Monitoring of response to diet, weight control and medications.• Post prandial LDL = TC - HDL - (TG/2.2) mmol/l.• or• Fasting LDL = TC- HDL -(TG/5)mg/dL• Friedewald formula• The formula will become unreliable when TG levels exceed 4mml/l• or 350mg/dL.• Measurement of non –HDL or ApoB-100 ( which increase the affinity of LDLR) may

asses risk of CVD more accurately than LDL particularly when TG levels are increased.

• Elevated TG levels are common in obesity, diabetes and insulinresistance and are frequently associated with low HDL and increasedLDL. This is one situation in which measurement of non-HDL or

• Apo-B may provide more accurate risk management.• Metabolic Syndrome – usually central obesity, DM, hypertension,

high uric acid, increased LDL, TG and low HDL., none-alcoholic fattyliver and in women polycystic ovary.

Causes of secondary hyperlipidaemia

Classification-- Hypercholesteraemia

• Hypercholesteraemia is a polygenic disorder that is the most commoncause of a mild to moderate increase in LDL. Physical sings, cornealarcus and xanthelasma.

• FH is a more severe disorder, prevalence 0.4%, and caused by loss offunction mutations affecting LDLR gene,(inheritance autosomaldominant)

• LDLR degradation, xanthomas of the Achilles or extensor digitorumtendons, and onset of corneal arcus before the age of 40 is suggestive,so genetic and biochemical family screening is a cost effective methodof case detection. Homozygosity more in consanguineous marriage.CVD as a child.

Hypertriglyceridaemia

• Polygenic, excessive intake of alcohol, carbohydrates, DM.,• dietary fat and retinoids. TG level above 10 mmol (880mg/dl)• may pose risk for acute pancreatitis.• Loss of function mutations in the gene encoding lipoprotein lipase.• This is inherited as autosomal recessive, that is not readily

amenable to drug therapy, may present in childhood as episodesof acute abdominal pain and pancreatitis. Hepatomegaly, lipaemiaretinales and eruptive xanthoma may occur. May be inherited asautosomal dominant(APOA5 gene)

•

Mixed hyperlipidaemia

• Hypertriglyceridaemia as well as increase in LDL and IDL. Treatment of TGmay improve TG faster than cholesterol.

• Primary mixed hyperlipidaemia is polygenic in origin and both componentsmay contribute to the risk CVD. It is associated with insulin resistance.

• Familial combined hyperlipidaemia is a term used to identify an inheritedtendency towards the over-production of atherogenic Apo B containinglipoproteins. It results in elevation of cholesterol, TG or both in differentbody members at different times. It is associated with increased CVD, butit doesn’t produce any pathognomonic physical signs, and it is common andsubstantially modified by factors such as age and weight.

Dysbetalipoproteinaemia

• Called type 3 hyperlipidaemia or remnant hyperlipidaemia, involvesaccumulation of roughly equimolar levels of cholesterol and TG.

• Accumulation of IDL and Chylomicron remnants, which areatherogenic together with obesity and DM. Premature CVD iscommon, as is PVD. It may result in palmar xanthomas, tuberousxanthomas or tendon xanthomas

Management

• Patients who have CVD, DM, chronic renal failure, familialHypercholesteraemia, or absolute CV risk in the next 10 years over20% must receive medical treatment.

• Target levels• HDL over 1mmo/L (38mg/dL).• TG 2mmol/L (180mg/dL)• LDL 1.8 mmol (74mg/dL)• Total cholesterol less than 5 mmol/L (150mg/dL) and 4 mmol

(150mg/dL)in high risk patients and in secondary prevention of CVdisease.

Non-Pharmacological management

• Reduced intake of saturated and trans-unsaturated fat to7-10% oftotal energy.

• Reduce intake of cholesterol, high index glycaemic carbohydrates.• Exercise, loss of weight.• Vegetables, fruits, pulses• Alcohol reduction.• Plant sterols, olive oil, nuts.

Pharmacological management

• Hypercholesterolaemia• 1- Statins inhibit HMGGCoA ,reduce LDL by 60%, TG by 40%,• Increase HDL by 10%.• Ezetimibe inhibit NPCA1L1 which is responsible for absorption of

dietary and bile cholesterol.• Bile acid-sequestering resins, cholestyramine, colestipol• PCSK9 inhibitors which increase LDLR Evolocumab.• S/C inj.every 2-4 wks.• Nicotinic acid reduce peripheral fatty acid release.

• TG• Fibrates- reduce TG by 50%, increase HDL by 20%, LDL changes are

variably. DM control.• Mixed hyperlipidaemia—statin plus fenofibrate probably safer than

gemfibrozil, concerning myopathy.• Fibrate plus ezetimibe when cholesterol is not too high.• Statin and fish oil hen TG is not too high.• Asses treatment after 6 wks (12 wks for fibrates)• Dyslipidaemia in pregnancy.