Hyperlipidaemia refers to elevated levels of one or more of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) in the blood.1
Dyslipidaemia is an umbrella term for hypercholesterolaemia, hyperlipidaemia and mixed dyslipidaemia. In mixed dyslipidaemia, LDL-C and TG levels are elevated and often accompanied by low levels of high-density lipoprotein cholesterol (HDL-C).2
Approximately 6 in 10 adults in England have serum cholesterol levels above 5 mmol/L.2
Heterozygous familial hypercholesterolaemia (FH) is one of the most common primary hyperlipidaemia, occurring in between one in 250 and one in 500 in the UK.
Homozygous FH is rare, affecting one in a million people.3
The causes of hyperlipidaemia can be divided into primary hyperlipidaemia and secondary hyperlipidaemia.
Most cases of primary hyperlipidaemia are due to genetic factors and environmental factors interacting. However, single-gene disorders may also be present.
Familial hypercholesterolaemia is usually caused by mutations in the low-density lipoprotein receptor (LDLR) gene which are inherited in an autosomal dominant pattern.
Secondary causes of hyperlipidaemia should be excluded before primary hyperlipidaemia may be diagnosed.4
The causes of secondary hyperlipidaemia can be further described by type of lipid that is elevated in the blood:4
Hyperlipidaemia is usually asymptomatic. Patients can present with features of acute pancreatitis such as sudden onset of severe central abdominal pain often radiating to the back, shock, and abdominal discolouration due to significantly increased levels of TG.
Questions that should be asked in the history include:5
Patients with hyperlipidaemia may develop signs such as tendon xanthomata, xanthelasma and premature corneal arcus.
Tendon xanthomata are hard, painless nodules usually on the knuckles of the hands, the Achilles tendons, or rarely on the extensor hallucis longus and triceps tendons. The presence of tendon xanthomata, particularly on the Achilles tendon, indicates FH.
Xanthelasma are lipid-laden nodules on the eyelids and premature corneal arcus are bluish rims surrounding the irises of the eyes.
A lipid profile is a blood test that indicates the serum levels of total cholesterol (TC), non-high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol (LDL-C), HDL-C and triglycerides (TG). The TC/HDL ratio offers the most accurate assessment of cardiovascular risk and is used in the QRISK2 score to calculate the 10-year risk of developing conditions such as myocardial infarction or stroke.
Current NICE guidelines do not suggest a fasting sample to assess a lipid profile.
When considering secondary causes of hyperlipidaemia, it is important to order specific tests as outlined in the following table:
Table 1. Investigations for Secondary Hyperlipidaemia.
NICE recommends that a diagnosis of hyperlipidaemia be made based on clinical findings, lipid profile and family history rather than the use of strict lipid cut‑off values alone. Familial hypercholesterolaemia should be diagnosed based on the Simon Broome diagnostic criteria or the Dutch Lipid Clinical Network (DLCN) criteria/score.
The management of hyperlipidaemia can be divided into conservative, medical and surgical and aims to reduce the risk of cardiovascular diseases due to long-term uncontrolled hyperlipidaemia.
All patients with hyperlipidaemia should be encouraged to adopt several lifestyle modifications, such as consuming a diet low in saturated fats and cholesterol and high in fruits, vegetables, mono- and polyunsaturated fats, exercising for at least 150 minutes per week with at least 30 minutes per day, reducing alcohol intake to <14 units per week for both men and women and avoiding binge drinking, and stopping smoking by enrolling on a smoking cessation programme.
Hyperlipidaemia due to secondary causes usually resolves following treatment of the underlying condition. Lipid-lowering drugs can play a key role in treating primary lipid disorders and for primary and secondary prevention of cardiovascular diseases. Examples of lipid-lowering drugs and their mechanism of action are shown in the table below.
Hyperlipidaemia is a condition involving increased levels of one or more of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) in the blood. Familial hyperlipidaemia (FH) is the most common primary hyperlipidaemia and can be diagnosed using the Simon Broome diagnostic criteria or the Dutch Lipid Clinical Network (DLCN) criteria/score.
The following table provides a summary of types of lipid-lowering drugs, examples of drugs in each class, their mechanism of action, and indication for use:
Lipid-lowering drugs
Examples
Mechanism of action
Indication
HMG-CoA reductase inhibitors (statins)
Atorvastatin, simvastatin
Inhibit conversion of HMG-CoA to mevalonic acid, a cholesterol precursor
First-line for hyperlipidaemia, primary and secondary prevention of cardiovascular diseases
Bile acid sequestrants
Cholestyramine
Prevents intestinal absorption of bile acids
Considered if statins and ezetimibe are contraindicated
Ezetimibe
–
Prevents intestinal absorption of cholesterol
Second-line if statins are contraindicated or as an addition to initial statin therapy for poorly-controlled hyperlipidaemia
Fibrates
Gemfibrozil, fenofibrate
Activates PPAR-𝛂 to increase triglyceride clearance and increase HDL-C synthesis
Considered if statins and ezetimibe are contraindicated
Niacin
–
Inhibits lipolysis
Considered if statins and ezetimibe are contraindicated
PCSK9 inhibitors
Alirocumab, evolocumab
Inactivation of LDL-receptor degradation, hence increases LDL clearance from the blood
For poorly controlled hyperlipidaemia despite maximal tolerated lipid-lowering therapy
For patients with FH or uncontrolled hyperlipidaemia despite maximum drug treatment and lifestyle modifications, LDL apheresis – a type of dialysis treatment that removes LDL-C from the blood – can be considered.8 Liver transplantation may be considered for patients with homozygous FH with no significant improvement following treatment with lipid-modifying therapy and LDL apheresis.8
If not diagnosed and treated early, major atherosclerotic complications can occur including: ischaemic heart disease, acute coronary syndrome, peripheral vascular disease, stroke, erectile dysfunction and mesenteric ischaemia.5
Complications may also occur due to adverse drug reaction (ADR) of lipid-lowering drugs, particularly statins and fibrates. The most severe form is rhabdomyolysis, a condition in which there is a breakdown of myocytes causing a release of myoglobin and creatinine kinase into the bloodstream. If not treated early, this can lead to renal and multiorgan failure and eventually, death. Patients with rhabdomyolysis typically present with muscle pain and dark urine. A raised serum creatinine kinase at least 5 times the upper limit of normal is diagnostic.10
Key clinical features of hyperlipidaemia include tendon xanthomata, xanthelasma and corneal arcus, particularly in familial hyperlipidaemia. A non-fasting lipid profile is the main investigation to diagnose hyperlipidaemia. Secondary and reversible causes of hyperlipidaemia must be ruled out and treated before making a diagnosis of and managing primary hyperlipidaemia.
Lipid-lowering therapy is the mainstay treatment for hyperlipidaemia. LDL apheresis and liver transplantation can be considered in patients with no significant improvement following lipid-lowering therapy. Complications of untreated hyperlipidaemia include major atherosclerotic and cardiovascular complications. Rhabdomyolysis is a severe adverse drug reaction of statins and fibrates which can lead to renal failure and death if not treated early.
