Definition and Diagnosis of Dyslipidaemias

Essentials

• Dyslipidaemias increase the total risk of arterial disease significantly; the aim of treatment is to decrease the risk.
• On a population level, the main health-promoting lipid values are total plasma cholesterol below 5.0 mmol/l and LDL cholesterol below 3.0 mmol/l.
• Lipid levels should be measured:
  • in patients with arterial disease (coronary artery disease, cerebral artery disease, arteriosclerosis obliterans (ASO)), diabetes or renal failure
  • in asymptomatic people with an increased risk of arterial disease according to a locally relevant risk calculator
  • in young adults with a single significant risk factor or early-onset arterial disease in the family
  • otherwise in men by 40 years of age, at the latest, and in women by 50 years of age or by menopause, at the latest.
• Efforts should be made to identify familial hypercholesterolaemia in patients and their family (indication for consultation of specialized care).
• Secondary dyslipidaemia, most often due to (even subclinical) hypothyroidism, should be identified.
• Screening lipid levels in the whole population is not the primary means of preventing arterial disease. Instead, the emphasis should be on general promotion of a healthy diet and lifestyle, complemented by action in the community (e.g. in canteens, sports facilities, etc.).
  • Screening is not recommended for symptomless people over 75 years of age or for children. For hypercholesterolaemia in children, see Diagnosis and Treatment of Childhood Hypercholesterolaemia.

Diagnosis

• Definition of dyslipidaemia
  • Plasma LDL cholesterol level exceeding 3.0 mmol/l or
  • triglyceride level exceeding 1.7 mmol/l or
  • HDL cholesterol level below 1.0 in men or 1.2 mmol/l in women.
• One test is not sufficient to give a reliable idea of plasma lipid levels: test cholesterol, HDL cholesterol, LDL cholesterol and triglycerides twice.
  • Fasting is usually of minor significance for lipid tests.
    • Meals have little effect on total cholesterol levels.
    • A meal will raise triglyceride levels by about 0.3 mmol/l, if the plasma triglyceride level is < 5 mmol. If the level is higher, measure the fasting value.
  • LDL and HDL cholesterol levels are today measured by a direct method.
    • If no direct method is available, calculate using the Friedewald formula (Calculator Ldl).
  • The target level for LDL cholesterol depends on the total risk of arterial disease, see Table Treatment of Dyslipidaemias.
• Other tests (in special cases)
  • Non-HDL cholesterol (= total cholesterol minus HDL cholesterol)
    • Shows the concentration of all atherogenic lipoproteins (VLDL, IDL and LDL).
    • Can be used whenever triglyceride levels are elevated or LDL cholesterol cannot be determined.
    • The treatment goals are 0.8 mmol/l higher than the respective LDL cholesterol levels.
  • Lipoprotein (a)
    • A lipoprotein(a) level exceeding 500 mg/l is a risk factor for atherosclerosis.
    • The distribution is skewed due to very high levels detected rarely.
    • Testing once may be indicated to investigate a strong hereditary predisposition to arterial disease or if LDL levels do not fall as expected despite statin treatment.
  • The significance of testing apolipoproteins (apoB, apoA1) is limited by the lack of standardization of the test methods.

Common hypercholesterolaemia

• The most common form of dyslipidaemia
• A combined effect of diet, excessive energy intake (obesity) and hereditary predisposition

Secondary dyslipidaemias

• Consider whether elevated lipid levels could be due to some other treatable disease (Table T1) or drug (Table T2).
  • Of these, hypothyroidism is the most important cause.

• Note that pregnancy may elevate plasma cholesterol and triglyceride levels significantly.
• Acute myocardial infarction and infections lower the levels transiently.

Familial hypercholesterolaemia (FH)

• Autosomal dominant inheritance
  • Estimated prevalence: 1:500 and 1:1 000 000 for heterozygous and homozygous FH, respectively (estimates vary by source)
• Suspect FH in an adult with:
  • plasma cholesterol ≥ 8 mmol/l (LDL ≥ 5 mmol/l) or
  • early-onset coronary artery disease (men < 55 years, women < 60 years) in the patient or a first-degree relative or
  • early sudden cardiac death of a first-degree relative or
  • tendinous xanthomas in the patient or a first-degree relative.
• The clinical probability of FH can be classified based on Dutch Lipid Clinic Network scoring http://www.mdcalc.com/dutch-criteria-familial-hypercholesterolemia-fh.
• Typical clinical pictures include:
  • tendinous xanthomas in Achilles tendons, knees and finger extensor tendons
  • arcus lipoides and xanthelasmas (Picture 1).

Familial combined dyslipidaemia

• Is fairly common.
• Increases the risk of arterial disease as much as common dyslipidaemia of an equivalent level.
• Family history of arterial disease is common.
• Typically both cholesterol and triglycerides, as well as the apoB concentration, are elevated.

Other hereditary dyslipidaemias

• Other, rare dyslipidaemias also exist, such as type 3 hyperlipidaemia http://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=3264. Find out about locally relevant diseases from local sources.

Hypertriglyceridaemia

• Mild hypertriglyceridaemia (2.0-5.0 mmol/l) is often only a result of genetic and environmental factors in combination with lifestyle factors (overweight, alcohol) or with poor glycaemic control in patients with diabetes.
• About 1% of the population have autosomal dominantly inherited primary hypertriglyceridaemia.
• Greatly elevated triglyceride levels (> 5-10 mmol/l) carry a risk of pancreatitis and eruptive xanthomatosis. Some patients have joint symptoms that may be due to gout.

Metabolic syndrome

• Metabolic syndrome is a cluster of risk factors significantly increasing the risk of arterial disease and diabetes; see Metabolic Syndrome.
• Metabolic syndrome involves:
  • increased waist circumference
  • elevated triglyceride levels
  • low HDL levels
  • hypertension
  • elevated fasting glucose levels.

Risk calculators

• To assess the need for treatment, the total risk of arterial disease should be assessed, in adults either based on a history of arterial disease or other disease (diabetes, chronic kidney disease, FH) associated with an equivalent risk or, in healthy people, by using risk assessment tools.
• SCORE assesses the risk of death in arterial disease within 10 years.
  • SCORE Charts, see http://www.escardio.org/Education/Practice-Tools/CVD-prevention-toolbox/SCORE-Risk-Charts
  • HeartScore interactive tool, see http://www.escardio.org/Education/Practice-Tools/CVD-prevention-toolbox/HeartScore
• The Healthy Heart Score survey is based on lifestyle behaviours and is well suited for persons below 40 years of age http://healthyheartscore.sph.harvard.edu/.
• Find out about calculators specifically designed for local population.
• The lifetime risk can be assessed either by extrapolating the age to 60 years, using the same risk factors, or by using a relative risk chart (in SCORE).

Workup in patients with lipid levels requiring treatment