Hypercholesterolemia 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 dyslipidemia, which encompasses elevated triglycerides, low levels of HDL-C, and qualitative lipid abnormalities.
Hypercholesterolemia 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 hypercholesterolemia and atherosclerosis include myocardial infarction, ischemic cardiomyopathy, sudden cardiac death, ischemic stroke, erectile dysfunction, claudication, and acute limb ischemia.
Risk factors for secondary hypercholesterolemia include a sedentary lifestyle and a diet characterized 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.
Hypercholesterolemia 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.
Hypercholesterolemia is treated with lifestyle modifications such as dietary changes, exercise, and smoking cessation, as well as pharmacologic intervention with statin therapy and selective use of other lipid-lowering drugs.
Hypercholesterolemia, an elevation of total cholesterol (TC) and/or LDL-C or non-HDL-C (defined as the subtraction of HDL-C from TC) in the blood, is also often referred to as dyslipidemia, to encompass the fact that it might be accompanied by a decrease in HDL-C, an increase in triglycerides, or qualitative lipid abnormalities. Dyslipidemia 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 dyslipidemia. For example, evidence suggests that lipoprotein(a) ≥80th percentile is abnormal and linked to elevated cardiovascular risk.
History and exam
Key diagnostic factors
- family history of early onset of coronary heart disease or dyslipidemia 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 ≥190 mg/dL without diabetes mellitus (age 20-75 years)
without clinical ASCVD: LDL-C ≥160 mg/dL without diabetes mellitus (age 20-39 years)
without clinical ASCVD: LDL-C 70-189 mg/dL without diabetes mellitus (age 40-75 years)
without clinical ASCVD: LDL-C 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, 10-year ASCVD predicted risk <7.5% and no risk factors (age 40-75 years)
without clinical ASCVD: with diabetes mellitus, 10-year ASCVD predicted risk ≥7.5% and risk enhancers (age 40-75 years)
without clinical ASCVD: with diabetes mellitus (age >75 years)
severe familial hypercholesterolemia
- Obstructive liver disease
- Nephrotic syndrome
- Chronic renal insufficiency
- Cardiovascular disease: risk assessment and reduction, including lipid modification
- 2022 ACC Expert Consensus Decision Pathway on the role of nonstatin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk: a report of the American College of Cardiology Solution Set Oversight Committee
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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