Hypercholesterolaemia is most commonly, but not exclusively, defined as elevated levels of low-density lipoprotein cholesterol (LDL-C) or non-high-density lipoprotein cholesterol (HDL-C); an alternative term is dyslipidaemia, which encompasses elevated triglycerides, low levels of HDL-C, and qualitative lipid abnormalities.
Hypercholesterolaemia is an important risk factor for atherosclerotic cardiovascular disease, including cerebrovascular disease, coronary heart disease, and peripheral arterial disease; it is usually symptomatically quiescent until significant atherosclerosis has developed.
Complications of hypercholesterolaemia and atherosclerosis include myocardial infarction, ischaemic cardiomyopathy, sudden cardiac death, ischaemic stroke, erectile dysfunction, claudication, and acute limb ischaemia.
Risk factors for secondary hypercholesterolaemia in industrialised populations include a sedentary lifestyle and a diet characterised by the excessive consumption of saturated fats, trans-fatty acids, and cholesterol. Other associations include diabetes, excess body weight mainly in the abdominal region, hypothyroidism, nephrotic syndrome, and cholestatic liver disease. Low HDL-C levels are associated with smoking and abdominal obesity.
It is diagnosed by a lipid profile, consisting of measurements of total cholesterol, LDL-C (estimated or direct), HDL-C, and triglycerides. Non-HDL-C is calculated by the subtraction of HDL-C from total cholesterol.
Hypercholesterolaemia is treated with lifestyle modifications such as dietary changes, exercise, and smoking cessation, as well as pharmacological intervention with statin therapy, and selective use of the cholesterol absorption inhibitor ezetimibe or a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor.
Hypercholesterolaemia, an elevation of total cholesterol (TC) and/or low-density lipoprotein cholesterol (LDL-C) or non-high-density lipoprotein cholesterol (HDL-C) (defined as the subtraction of HDL-C from TC) in the blood, is also often referred to as dyslipidaemia, to encompass the fact that it might be accompanied by a decrease in HDL-C, an increase in triglycerides, or qualitative lipid abnormalities. Dyslipidaemia is classified as serum TC, LDL-C, triglycerides, apolipoprotein B, or lipoprotein(a) concentrations above the 90th percentile, or HDL-C or apolipoprotein A-I concentrations below the 10th percentile for the general population. However, these classic percentile cut-off points should not be used too rigidly in defining dyslipidaemia. For example, evidence suggests that lipoprotein(a) ≥80th percentile is abnormal and linked to elevated cardiovascular risk.
History and exam
Key diagnostic factors
- presence of risk factors
- family history of early onset of coronary heart disease or dyslipidaemia in first-degree relatives
- history of cardiovascular disease
- consumption of saturated fats and trans-fatty acids
- excess body weight (especially abdominal obesity)
- tendinous xanthomas
Other diagnostic factors
- arcus cornealis with onset before the age of 45 years
- tuberous xanthomas
- insulin resistance and type 2 diabetes mellitus
- excess body weight (body mass index >25 kg/m²)
- cigarette smoking
- cholestatic liver disease
- nephrotic syndrome
- use of certain medications
1st investigations to order
- lipid profile
- serum thyroid-stimulating hormone (TSH)
Investigations to consider
- genetic testing
with clinical ASCVD: very high risk
with clinical ASCVD: not very high risk and age ≤75 years
with clinical ASCVD: not very high risk and age >75 years
without clinical ASCVD: LDL-C ≥4.9 mmol/L (≥190 mg/dL) without diabetes mellitus (age 20-75 years)
without clinical ASCVD: LDL-C ≥4.1 mmol/L (≥160 mg/dL) without diabetes mellitus (age 20-39 years)
without clinical ASCVD: LDL-C 1.8 to 4.9 mmol/L (70-189 mg/dL) without diabetes mellitus (age 40-75 years)
without clinical ASCVD: LDL-C 1.8 to 4.9 mmol/L (70-189 mg/dL) without diabetes mellitus (age >75 years)
without clinical ASCVD: with diabetes mellitus and risk enhancers (age 20-39 years)
without clinical ASCVD: with diabetes mellitus and no risk factors (age 40-75 years)
without clinical ASCVD: with diabetes mellitus and multiple risk factors (age 40-75 years)
without clinical ASCVD: with diabetes mellitus (age >75 years)
severe familial hypercholesterolaemia
- Obstructive liver disease
- Nephrotic syndrome
- Chronic renal insufficiency
- VA/DoD clinical practice guideline for the management of dyslipidemia for cardiovascular risk reduction
- Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the management of dyslipidemia and prevention of cardiovascular disease algorithm – 2020 executive summary
High cholesterol: questions to ask your doctorMore Patient leaflets
Cardiovascular Risk Assessment in Men (10-year, patient information, Framingham 2008)
Cardiovascular Risk Assessment in Women (10-year, patient information, Framingham 2008)More Calculators
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