Hyperlipidaemia – 10 revision facts

Hyperlipidaemia – 10 revision facts

Key Points

• Hyperlipidaemia refers to elevated levels of lipids in the blood, primarily cholesterol and triglycerides
• It is a major risk factor for atherosclerosis, which can lead to ischaemic heart disease (IHD) and stroke
• Management involves lifestyle modifications and pharmacological treatment, primarily with HMG CoA reductase inhibitors (statins)
• Early identification and treatment are crucial to reducing the risk of cardiovascular events.

Cholesterol

What is cholesterol?

It is a fat which all humans need to keep healthy. Many different cells make cholesterol. The liver makes about a quarter of the total. Its function is to help the body make cell membranes, many hormones, and vitamin D. It is not a disease. The diagram above is what it looks like as a chemical.

1. Definition

Hyperlipidaemia is the abnormal elevation of lipids in the blood, including cholesterol, triglycerides, or both. It can be classified based on the lipid profile:

• Hypercholesterolaemia: Elevated total cholesterol or low-density lipoprotein (LDL) cholesterol
• Hypertriglyceridaemia: Elevated triglycerides
• Mixed (combined) hyperlipidaemia: Elevation of both cholesterol and triglycerides.

2. Epidemiology

• Hyperlipidaemia is very common, affecting around 60% of adults, with variations based on age, sex, and ethnicity
• Men are more likely to have high cholesterol levels compared to women until menopause, after which the risk in women increases
• Age-related increase: Lipid levels generally rise with age, increasing the risk of cardiovascular disease
• It is a significant contributor to the burden of cardiovascular diseases, which remain one of the leading causes of death in the UK.

3. Risk factors

• Non-modifiable
  • Age: Risk increases with advancing age
  • Gender: Men are at higher risk earlier in life; risk in women increases after menopause
  • Family history: Genetic predisposition plays a significant role, particularly in conditions like familial hypercholesterolaemia.
• Modifiable
  • Diet: High intake of saturated fats, trans fats, and cholesterol
  • Obesity: Particularly central obesity
  • Sedentary lifestyle
  • Excessive alcohol consumption: Contributes mainly to hypertriglyceridaemia
  • Smoking: Lowers HDL (‘good’) cholesterol and increases total cholesterol
  • Comorbidities: Diabetes, hypertension, chronic kidney disease (CKD), and hypothyroidism.

4. Causes

• Primary (genetic):
  • Familial hypercholesterolaemia (FH): An autosomal dominant disorder characterised by high LDL cholesterol
  • Polygenic hypercholesterolaemia: A common genetic condition resulting from multiple gene variations
  • Familial combined hyperlipidaemia: Elevated cholesterol and triglycerides due to genetic factors.
• Secondary (acquired):
  • Dietary factors: High intake of saturated fats and sugar
  • Medications: E.g. corticosteroids, antiretrovirals, beta-blockers, thiazides, and oral contraceptives
  • Medical conditions: Hypothyroidism, nephrotic syndrome, chronic kidney disease, liver disease, and type 2 diabetes.

5. Symptoms

• Asymptomatic: Most individuals with hyperlipidaemia are asymptomatic and are diagnosed through routine blood tests.
• Physical signs (in severe cases)
  • Xanthomas: Yellowish deposits of lipid under the skin, particularly around the eyes (xanthelasma), tendons (tendon xanthomas), or over joints
  • Corneal arcus: A grey-white ring around the cornea, often seen in younger patients with familial hypercholesterolaemia
  • Hepatosplenomegaly: Can occur in severe hypertriglyceridaemia.

Corneal arcus

Corneal arcus and xanthelesma

Tendon xanthoma

6. Diagnosis

• History and physical examination: Assess for risk factors, family history, and signs of lipid deposits
• Risk assessment: Use scoring systems like QRISK3 to determine the risk of cardiovascular disease and guide treatment decisions.

Investigation

• Lipid profile: A fasting (and non-fasting) lipid profile measures total cholesterol, LDL cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides
• Liver function tests (LFTs): Done before starting statin therapy to check baseline liver function
• U+Es: To assess renal function, especially if secondary causes like CKD/nephrotic syndrome are suspected
• Thyroid function tests: To rule out hypothyroidism as a cause of secondary hyperlipidaemia
• HbA1c and fasting glucose: To screen for diabetes, which can contribute to dyslipidaemia
• Genetic testing: Consider in cases of suspected familial hypercholesterolaemia, particularly in young patients with high cholesterol and a strong family history of early IHD or stroke.

Differential diagnosis

• Secondary hyperlipidaemia due to hypothyroidism, nephrotic syndrome, or diabetes.
• Primary genetic disorders like familial hypercholesterolaemia, familial combined hyperlipidaemia, or dysbetalipoproteinaemia.
• Drug-induced hyperlipidaemia: Caused by medications such as corticosteroids, antiretrovirals, or diuretics.

Desirable lipid levels

• Total cholesterol (TChol): 5.0 mmol/L or less. However, about 2 in 3 adults in the UK have a TChol level of 5.0 mmol/L or above
• LDL-cholesterol (‘bad cholesterol’): 3.0 mmol/L or less
• HDL-cholesterol (‘good cholesterol’): 1.2 mmol/L or more
• TChol/HDL ratio: 4.5 or less. That is, TChol divided by HDL-cholesterol. This reflects the fact that for any given TChol level, the more HDL, the better.
• Triglyceride (TG): 1.7 mmol/L or less (borderline high = 1.8 to 2.2 mmol/L).

As a rule, the higher the LDL-cholesterol level, the greater the risk to health. A blood test only measuring total cholesterol may be misleading. A high total cholesterol may be caused by a high HDL-cholesterol level and is therefore healthy. Thus it is important to know the separate LDL and HDL-cholesterol levels.

7. Treatment

1. Lifestyle modifications:
   • Diet: Encourage a balanced diet low in saturated fats and rich in fruits, vegetables, whole grains, and omega-3 fatty acids
   • Weight management: Aim for a healthy BMI through diet and regular exercise
   • Physical activity: At least 150 minutes of moderate aerobic activity per week
   • Reduce alcohol intake: Particularly in patients with hypertriglyceridaemia
   • Smoking cessation: To improve overall cardiovascular health.
2. Pharmacological therapy:
   • Statins: First-line treatment for lowering LDL cholesterol. E.g. atorvastatin, simvastatin, rosuvastatin
   • Ezetimibe: Can be added to statins if LDL targets are not achieved or if statins are not tolerated
   • PCSK9 inhibitors: E.g. alirocumab, evolocumab, for patients with familial hypercholesterolaemia or those who cannot reach LDL goals with other treatments
   • Fibrates: Primarily used for hypertriglyceridaemia
   • Omega-3 fatty acids: Useful for lowering triglycerides.
3. Monitoring: Regular follow-up with lipid panels to assess treatment efficacy and compliance. Monitor for side effects of medications, particularly muscle symptoms with statins.

8. Complications

• Cardiovascular disease: Including IHD and stroke
• Pancreatitis: Associated with severe hypertriglyceridaemia (>10 mmol/L)
• Peripheral vascular disease (PVD): Can lead to claudication and other complications.

9. Prognosis

• The prognosis depends on the effective control of lipid levels and the management of cardiovascular risk factors
• With appropriate treatment, the risk of cardiovascular events can be significantly reduced
• Patients with familial hypercholesterolaemia have a higher risk of premature cardiovascular disease, but early identification and aggressive management can improve outcomes.

10. Prevention

• Healthy lifestyle: Maintaining a balanced diet, regular physical activity, and a healthy weight are key to preventing hyperlipidaemia
• Regular screening: Particularly in individuals with a family history of hyperlipidaemia or cardiovascular disease. QRISK assessments can guide when to start treatment
• Patient education: Encourage adherence to a heart-healthy lifestyle and compliance with prescribed medications.