Total cholesterol: how cholesterol travels in lipoproteins, reference values, causes of high and low levels, familial hypercholesterolaemia.
Total cholesterol (TC) is the sum of cholesterol carried in all blood lipoproteins: LDL, HDL, VLDL and their remnants. Cholesterol itself is essential. It is a building block of every cell membrane and the raw material for steroid hormones, bile acids and vitamin D. Most of it (about 70–80 %) is made by the liver, and the rest comes from food. An excess of cholesterol carried in atherogenic particles, mainly LDL, is deposited in artery walls and drives atherosclerosis, the main cause of heart attack and stroke.
Lipid profileLipoproteinsCardiovascular risk
Desirable< 5.0 mmol/L (< 190 mg/dL)
Clearly raised≥ 6.2 mmol/L (≥ 240 mg/dL)
Very high≥ 8.0 mmol/L — suspect familial hypercholesterolaemia
Conversionmmol/L × 38.67 = mg/dL
How cholesterol travels in the blood
Fats do not dissolve in water, so they travel in lipoproteins: particles with a core of triglycerides and cholesterol esters and a shell of phospholipids, free cholesterol and proteins (apolipoproteins). Lipoproteins are classified by density. The larger and lighter the particle, the more triglyceride it carries.
Figure 1. Lipoprotein classes. Each atherogenic particle (VLDL, IDL, LDL, Lp(a)) carries one apolipoprotein B molecule; HDL carries apolipoprotein A-I and removes cholesterol from tissues.
Reference values
Total cholesterol
Interpretation (adults)
< 5.0 mmol/L (< 190 mg/dL)
desirable
5.0–6.2 mmol/L (190–239 mg/dL)
borderline to raised
≥ 6.2 mmol/L (≥ 240 mg/dL)
high
Total cholesterol alone does not define treatment; decisions are based on LDL cholesterol (or non-HDL cholesterol, apoB) and the person's overall cardiovascular risk.
High cholesterol
Lifestyle: diet rich in saturated and trans fats, excess weight, physical inactivity
Familial hypercholesterolaemia — an inherited disorder affecting about 1 in 250–300 people. LDL is very high from childhood, and heart attacks can occur before age 50–60. Signs include tendon xanthomas and an early family history.
Low values result from lipid-lowering treatment (the intended effect), hyperthyroidism, malnutrition or malabsorption, severe liver disease, chronic infection or cancer, and rare inherited disorders. Very low LDL due to effective therapy is considered safe. Unexplained low cholesterol together with weight loss deserves investigation of the underlying disease.
Cholesterol and cardiovascular risk
Large genetic, epidemiological and treatment studies show that atherogenic lipoproteins cause atherosclerosis, and that the risk depends on both their concentration and the duration of exposure. Lowering LDL cholesterol by 1 mmol/L reduces major cardiovascular events by about one fifth. The treatment goal is set according to the overall risk, which includes age, blood pressure, smoking, diabetes, kidney disease and existing atherosclerosis.
What to do
Discuss your full lipid profile (LDL, HDL, triglycerides, non-HDL cholesterol) and overall risk with a doctor. Total cholesterol of 8 mmol/L or more, or LDL of 5 mmol/L or more, warrants assessment for familial hypercholesterolaemia and screening of first-degree relatives.
References
Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111–188. doi:10.1093/eurheartj/ehz455
Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol. Circulation. 2019;139(25):e1082–e1143. doi:10.1161/CIR.0000000000000625
Ference BA, Ginsberg HN, Graham I, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J. 2017;38(32):2459–2472. doi:10.1093/eurheartj/ehx144
Cholesterol Treatment Trialists' (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670–1681. doi:10.1016/S0140-6736(10)61350-5
This article is for general information and does not replace a consultation with a doctor. Laboratory results must be interpreted by a physician together with symptoms and other tests.