Cholesterol is required for cell membrane structure, steroid hormone synthesis and production of bile acids. The main source is de novo hepatic synthesis. Dietary intake contributes to a smaller degree, predominantly through regulation of hepatic cholesterol production.

Cholesterol circulates in the blood combined with triglycerides and proteins as lipoprotein particles. The two main lipoproteins contributing to total cholesterol (TC) are high-density lipoprotein (HDL) and low-density lipoprotein (LDL). A raised LDL cholesterol (LDL-C), or a raised TC:HDL-C ratio is associated with the development of atherosclerosis and increased cardiovascular risk (CVR).

Indications for total cholesterol and HDL-C measurement include:

Assessment of CVR using ASSIGN / QRISK in individuals who are not already considered high-risk*. SIGN-149 recommends CVR assessment at least every 5 years for all:

• adults ≥40 years
• adults with a 1^st-degree relative who has premature atherosclerotic CV disease, or familial dyslipidaemia

Screening for suspected familial dyslipidaemia

Assessment of the efficacy of a lipid-lowering intervention (usually lifestyle change and/or statin therapy). SIGN-149 recommends baseline and follow-up lipid measurements for individuals starting a statin.

A non-fasting combination of total cholesterol, HDL-C and triglycerides will usually be adequate for the assessment of CVR, or when assessing the efficacy of a lipid-lowering intervention. Where triglycerides exceed 4.5 mmol/L, a repeat fasting measurement is recommended.

LDL cholesterol is usually calculated, and this requires the measurement of total cholesterol, HDL-C and triglycerides. LDL-C is best requested on a fasting sample. Measurement is indicated for suspected Familial Hypercholesterolaemia, or when assessing eligibility for PCSK9 inhibitor therapy.

*Individuals at high risk of CVD:

• established cardiovascular disease
• stage 3 or higher chronic kidney disease, or micro- or macroalbuminuria
• familial hypercholesterolaemia
• diabetes over the age of 40 years
• diabetes under the age of 40 years with: a long duration of diabetes (20 years); or – micro- or macroalbuminuria; or – proliferative retinopathy or autonomic neuropathy

• Pregnancy (cholesterol rises during pregnancy)
• Acute illness (can give a misleadingly low result)

• To monitor response to a lipid-lowering intervention
• Repeat cardiovascular risk assessment (at least every five years in low risk individuals over the age of 40 but for some patients annually is more appropriate).

1. Scottish Intercollegiate Guidelines Network (SIGN). Risk estimation and the prevention of cardiovascular disease. Edinburgh: SIGN; 2017. (SIGN publication no. 149). [cited 04 Oct 2022]. https://www.sign.ac.uk/sign-149-risk-estimation-and-the-prevention-of-cardiovascular-disease
2. Lab Tests Online-UK [Internet]. Association for Clinical Biochemistry and Laboratory Medicine. Cholesterol Test [updated 2021 Apr; cited 2022 Oct 04]. Available from: https://labtestsonline.org.uk/tests/cholesterol-test
3. Marshall WJ, Lapsley M, & Day A, Ayling R, editors. Clinical Biochemistry: Metabolic and Clinical Aspects. 3rd Edition. London: Churchill Livingstone; 2014.

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