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This guide provides a structured approach to interpreting a lipid profile and is based on NICE guidelines in the United Kingdom. NICE guidance is updated periodically, so it is essential to ensure that you are always following the most recent NICE guidelines or the guidelines in your area.
Lipids
Lipids are fats the body requires for energy, energy storage and cell membrane structure.
The main groups of lipids are cholesterol, triglycerides (comprised of glycerol and fatty acids), free fatty acids and phospholipids. They are obtained through dietary intake and manufactured in the liver. Since lipids are not water-soluble, they are transported in the lymphatic system and bloodstream in combination with proteins, creating structures which are called lipoproteins.
When lipids, especially cholesterol, are present in the plasma in high concentrations, they are a risk factor for cardiovascular disease due to their role in forming atheromatous plaques in the walls of blood vessels.
For more information, see the Geeky Medics guides to lipids and cholesterol metabolism.
Lipid profile
A lipid profile is a blood test quantifying cholesterol and triglyceride plasma concentrations.
Cholesterol
Cholesterol values are reported as follows:
- Total cholesterol
- High-density lipoprotein cholesterol (HDL-C): cholesterol which is being carried in HDL. HDL-C is often described to patients as ‘good’ cholesterol, because it mediates the transport of cholesterol to the liver, where it is excreted from the body, in a process known as reverse cholesterol transport. There is an inverse relationship between HDL cholesterol and the risk of cardiovascular disease.
- Non-high-density lipoprotein cholesterol (non-HDL-C): cholesterol carried in lipoproteins other than HDL, including low-density lipoprotein cholesterol (LDL-C). Non-HDL-C is calculated by subtracting HDL-C from total cholesterol. Non-HDL cholesterol is described as ‘bad’ cholesterol because of its central role in the pathogenesis of atherosclerosis.
- Total cholesterol to HDL ratio: a measure of HDL-C concentration relative to the total cholesterol.
Triglycerides
Elevated concentrations of triglycerides are associated with post-prandial hyperlipidaemia and reduced HDL-C, making hypertriglyceridaemia an independent risk factor for cardiovascular disease. At concentrations over 10mmol/L, triglycerides are also associated with pancreatitis.
Why perform a lipid profile?
There are three sets of circumstances in which a lipid profile is requested.
Screening
Adults between the ages of 40 and 74 years without cardiovascular disease may be offered a lipid profile as part of an NHS health check. The result can be used as part of the QRISK3 score, which estimates an individual’s risk of cardiovascular disease in the next ten years.
Additionally, a patient of any age who is noted to have features of hyperlipidaemia on physical examination, such as tendon xanthoma, xanthelasma or corneal arcus, should have a lipid profile performed.
Recent cardiovascular event
Patients who have had a recent cardiovascular event (e.g. myocardial infarction, stroke) should have a lipid profile to guide future risk reduction strategies.
Monitoring
Patients with hyperlipidaemia and those who have had a cardiovascular event should have lipid profile monitoring to assess the effectiveness of lipid-lowering treatment (e.g. statins).
Do patients need to fast?
Since 2014, NICE guidance has stated that most patients do not need to fast before a lipid profile blood test.
However, a fasting sample should be obtained in certain circumstances (e.g. initial test shows severe hyperlipidaemia, hypertriglyceridaemia).
Acute illness/injury
A lipid profile should not be performed within six weeks of any acute illness or injury, as there is a temporary reduction in cholesterol during this period.
Interpreting a lipid profile
Does the patient have severe hyperlipidaemia?
The first step is to identify patients with severe hyperlipidaemia.
Severe hyperlipidaemia is defined as:
- Total cholesterol >7.5mmol/L (hypercholesterolaemia) and/or
- Non-HDL-C >5.9 mmol/L (hypercholesterolaemia) and/or
- Triglycerides >4.5mmol/L (hypertriglyceridaemia)
Some patients will have predominant hypercholesterolaemia, some will have predominant hypertriglyceridemia, and others will have mixed hyperlipidaemia.
Identify any secondary causes
Any secondary causes of hypercholesterolaemia or hypertriglyceridemia should be identified, as these may have led to elevated results.
Secondary causes of hypercholesterolaemia include:
- Pregnancy
- Hypothyroidism
- Cholestatic liver disease
- Nephrotic syndrome
- Drugs (e.g. diuretics, ciclosporin, corticosteroids, androgens)
Secondary causes of hypertriglyceridaemia include:
- Uncontrolled diabetes mellitus
- Chronic kidney disease
- Hepatocellular liver disease
- Alcohol excess
- Metabolic syndrome (including impaired glucose tolerance, hypertension, central obesity)
- Drugs (e.g. beta-blockers, retinoids and corticosteroids)
These conditions should be identified and, where possible, treated before repeating the lipid profile.
Arrange specialist review
Patients who do not have a secondary cause, or if hyperlipidaemia persists following management of the secondary cause, will need further investigation and, often, referral to a specialist lipid clinic for consideration of conditions such as familial hypercholesterolaemia, familial hypertriglyceridaemia, or familial combined hyperlipidaemia.
Patients in whom the secondary cause cannot be modified (e.g. where causative drugs are essential for the management of comorbidities) may also require referral to a specialist lipid clinic.
Familial hypercholesterolaemia
Familial hypercholesterolaemia causes elevated levels of low-density lipoprotein cholesterol (LDL-C). Patients often have a family history of cardiovascular disease and may develop clinical signs of hyperlipidaemia (e.g. tendon xanthoma).
Familial hypercholesterolaemia is usually caused by mutations in the low-density lipoprotein receptor (LDLR) gene, resulting in an autosomal dominant inheritance pattern.
Familial hypertriglyceridaemia and familial combined hyperlipidaemia are both also dominantly inherited disorders.
Why was the lipid profile performed?
Further interpretation of results will depend on why the lipid profile blood test was performed.
Screening
Where the test was done for screening, ask: what do these results tell me about this patient’s risk of future cardiovascular disease?
NICE does not define risk based on specific lipid levels in isolation. Instead, recommendations for lifestyle modification and/or lipid-lowering drug treatments are based upon the QRISK3 calculator (so-called because it is the third version of the calculator). QRISK3 combines the lipid profile results with other information, including smoking status, blood pressure, height and weight.
There are certain groups for whom QRISK3 is not suitable, as they should all be considered to be at increased risk of CVD:
- Age >85
- Type 1 diabetes
- Chronic kidney disease (eGFT <60)
- Inherited lipid metabolism disorder
The QRISK3 score estimates the likelihood of an individual patient developing cardiovascular disease over the next ten years. If the risk is 10% or greater, the patient should be given lifestyle advice regarding modifiable risk factors (e.g. smoking, diet, obesity, and physical activity). The patient should also be offered lipid-lowering therapy (atorvastatin), either at the same time as lifestyle advice or later if lifestyle modification alone is ineffective in lowering lipid concentrations. This is referred to as primary prevention.
In some groups of patients, for example, those who are severely obese (BMI >40kg/m2), those with serious mental illness and those with autoimmune disorders (e.g. systemic lupus erythematosus), the QRISK3 score may be an underestimate of their cardiovascular risk. This is also the case in patients with significant hypertriglyceridaemia. In these patients, it may be necessary to initiate lipid-lowering treatment even when the estimated risk is less than 10%.
Target cholesterol levels
Although NICE does not recommend the use of lipid profile results in isolation to guide management, the NHS advises patients on the following cholesterol treatment target levels:
- Total cholesterol: should be 5mmol/L or less
- HDL-C: should be >1 mmol/L in men and >1.2 mmol/L in women
- Total cholesterol to HDL ratio: should be <6
Primary prevention of cardiovascular disease
NICE recommend atorvastatin 20mg once daily as lipid-lowering therapy for the primary prevention of cardiovascular disease.
For more information, see the Geeky Medics guide to statin counselling.
Recent cardiovascular event
Where a lipid profile was performed following a recent cardiovascular event, ask: what do these results tell me about the patient’s risk of further cardiovascular events?
The QRISK3 tool cannot be used in these patients, as it is only validated for patients without established cardiovascular disease.
Most patients who have suffered a cardiovascular event will be offered treatment with a statin, irrespective of their baseline lipid values (secondary prevention). First-line treatment for secondary prevention is atorvastatin 80mg once daily. Baseline lipid values will be used to assess the effectiveness of that treatment (described below).
Monitoring
Where the test was done for monitoring purposes, ask: what do these results tell me about the effectiveness of the current treatment strategy?
In primary and secondary prevention, the target is to reduce non-HDL-C (‘bad cholesterol’) by >40% from baseline levels after three months of treatment with a statin.
Editor
Dr Chris Jefferies
References
- Boon, NA. Colledge, NR, Walker, BR (eds). Davidson’s Principles & Practice of Medicine 20th Ed. Churchill Livingstone Elsevier, 2006
- Lab Tests Online UK. Cholesterol Test. Available from: [LINK]
- Marshall, William J and Bangert, Stephen K. Clinical Chemistry (Sixth Edition). Elsevier Limited, 2008
- NHS England. Summary of National Guidance for Lipid Management for Primary and Secondary Prevention of CVD. Available from: [LINK]
- NHS Health Check. Results and Action Plan online patient information leaflet (last reviewed March 2020). Available from: [LINK]
- NICE CKS. Hypercholesterolaemia – familial. Available from: [LINK]
- NICE CKS. Lipid therapy – primary prevention of CVD. Available from: [LINK]
- ClinRisk Ltd. QRISK3 calculator. Available from: [LINK]
