QuestionSBA
QuestionChoice
Cranberry juice potentially increases the anticoagulant effect of warfarin.
62294
b
Cranberry juice
QuestionChoice
Grapefruit juice/pulp is proven to have interactions with more than 40 drugs. By interacting with statins (atorvastatin, simvastatin, lovastatin), it inhibits CYP3A4 activity leading to the development of unwanted side effects such as myopathy and rhabdomyolysis.
62293
a
Grapefruit juice
QuestionChoice
Apple juice and orange juice inhibit fexofenadine absorption and decrease aliskiren concentration and renin activity.
62296
d
Orange juice
QuestionChoice
Apple juice and orange juice inhibit fexofenadine absorption and decrease aliskiren concentration and renin activity.
62297
e
Apple juice
QuestionChoice
Pomegranate juice increases the INR in response to warfarin.
62295
c
Pomegranate juice
Concept
Chapter
# Summary

Hyperlipidaemia is an umbrella term used to describe high serum levels of cholesterol and/or triglycerides. It is an important cardiovascular risk factor and is commonly targeted with lipid-lowering treatment either as primary or secondary prevention. It is often asymptomatic but may present with tendon xanthomata, corneal arcus and xanthelasmata. Investigations include a lipid profile, liver function tests, HbA1c and renal function. The QRISK calculator is used to estimate a patient's 10 year risk of having a stroke or heart attack and guides who should be recommended primary prevention (typically those with a score of 10% or higher). Management is typically with statins in the first instance, alongside lifestyle advice, addressing any secondary causes of hyperlipidaemia and considering other cardiovascular risk factors.

# Definition

Hyperlipidaemia refers to raised levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides or a combination of these. Dyslipidaemia includes hyperlipidaemia but also encompasses low levels of high-density lipoprotein cholesterol (HDL-C) which is also a cardiovascular risk factor. 

Hyperlipidaemia is associated with atherosclerosis, where fibrofatty plaques form in the walls of arteries. These lead to narrowing and hardening of the vessels, reducing blood flow to target organs. If plaques rupture, this leads to thrombosis with subsequent obstruction of the artery (either partial or complete), which may manifest clinically for example as a stroke or myocardial infarction.

# Epidemiology

- Hyperlipidaemia is very common - 59% of adults had raised total cholesterol in the 2021 Health Survey for England
- This rose to 72% of adults aged 45 to 64
- Risk factors include:
- Older age
- Male sex
- Being overweight or obese
- Eating a diet high in saturated fats and trans-fatty acids
- Sedentary lifestyle
- Smoking
- Alcohol excess
- Medical conditions (e.g. diabetes, chronic kidney disease)
- A small proportion of cases are due to familial hypercholesterolaemia (FH)
- Approximately 1 in 500 of the UK population have heterozygous FH 
- Homozygous FH is more severe but rarer, affecting around 1 in every 300,000 people
- FH is significantly underdiagnosed, with only around 4% of cases identified

# Aetiology

**Causes of hypercholesterolaemia without hypertriglyceridaemia:**

- Familial hypercholesterolaemia
- Nephrotic syndrome
- Hypothyroidism
- Cholestatic liver disease e.g. primary biliary cirrhosis
- Cushing's syndrome
- Anorexia nervosa
- Medications e.g. ciclosporin

**Causes of hypertriglyceridaemia +/- hypercholesterolaemia:**

- Diabetes
- Pregnancy
- End-stage renal disease
- HIV 
- Alcohol excess
- Metabolic syndrome
- Monoclonal gammopathy
- Medications e.g. steroids, isotretinoin, antiretrovirals
- Familial combined hyperlipidaemia

# Signs and Symptoms

Patients are often asymptomatic and detected incidentally with a lipid profile - those with a family history of an inherited hyperlipidaemia or premature coronary heart disease may be screened.

All patients with established cardiovascular disease (e.g. ischaemic heart disease, stroke, peripheral vascular disease) should have their lipid levels checked and secondary prevention treatment offered.

Clinical signs may also be seen:

- Tendon xanthomata (hard painless nodules on the knuckles and Achilles tendons, typically seen in FH)
- Xanthelasma (yellow cholesterol deposits on the eyelids)
- Corneal arcus (blue/grey rim surrounding the iris) - these are normal in older people but may indicate hyperlipidaemia under the age of 40

# Investigations

**Bedside:**

- **Urine dip** to screen for proteinuria if chronic kidney disease (CKD) or nephrotic syndrome is suspected
- **Blood glucose** to screen for diabetes
- **ECG** may show ischaemic changes due to coronary artery disease
- **Pregnancy test** in women of childbearing age (statins are contraindicated in pregnancy and breastfeeding)

**Blood tests:**

- **Lipid profile** to diagnose hyperlipidaemia - a total cholesterol of > 9 mmol/L or non-HDL of > 7.5 mmol/L warrants specialist assessment for FH
- **U&Es** to screen for renal failure
- **LFTs** may be deranged in cholestatic liver disease and albumin will be low in nephrotic syndrome; patients with significantly abnormal LFTs should not be started on statins
- **HbA1c** to screen for diabetes
- **Thyroid function tests** if there are clinical signs of thyroid disease
- **Creatine kinase** in patients with a history of persistent generalised unexplained muscle symptoms (e.g. myalgia)

**Special tests:**

- **Genetic testing** if a primary hyperlipidaemia is suspected

# Management

**Conservative:**

- Advise all patients on lifestyle changes to reduce their cardiovascular risk:
- Smoking cessation
- Weight loss advice if overweight or obese
- For obese patients, also assess for sleep apnoea and treat if appropriate
- Eat a diet high in fruit, vegetables, fibre and increase mono-unsaturated fat intake (e.g. olive oil)
- Reduce intake of sugar, saturated fat and salt
- Drink in moderation (less than 14 units per week spread over 3-5 days)
- Take at least 150 minutes of moderate intensity or 75 minutes of vigorous intensity exercise per week
- Do muscle-strengthening exercises on at least 2 days per week
- Offer referral to support services to help patients achieve the above changes as necessary, for example:
	- Smoking cessation services
	- Weight management services
	- Alcohol support services in patients dependent on alcohol
	- Exercise referral schemes
	- Perform a cardiovascular risk assessment
- QRISK3 is the recommended tool that calculates a patient's risk of having a heart attack or stroke over the next 10 years
	- It takes into account a range of risk factors including age, sex, comorbidities (e.g. diabetes, CKD, severe mental illness), smoking status, cholesterol/HDL ratio, blood pressure and body mass index
	- A QRISK3 score of 10% or more is an indication for primary prevention
	- In some cases, lifestyle change alone may be an appropriate first-line management step 
	- Cardiovascular risk should be reassessed after the person has tried to change their lifestyle

Treatment targets are as follows:

- Primary prevention - at least 40% reduction in non-HDL cholesterol
- Secondary prevention - LDL cholesterol ≤ 2 mmol/L or non-HDL cholesterol ≤ 2.6 mmol/L
- Consider referring patients with suspected FH or another inherited dyslipidaemia to specialist lipid management services
- Dietician input should be considered for patients with FH

**Medical:**

- Statin treatment should be offered to people with:
	- A QRISK3 of 10% or higher
	- Familial hypercholesterolemia 
	- CKD
	- Type 1 diabetes in people aged 40 years+/have had diabetes for 10 years+/with nephropathy/other cardiovascular risk factors
	- Statin treatment should be considered in:
	- People aged 85 and older, especially if they smoke or have hypertension
	- Anyone aged 18–40 with type 1 diabetes
- First line for **primary prevention** is 20 mg of atorvastatin - this can be uptitrated to a maximum of 80 mg per day if required
- For **secondary prevention,** 80 mg of atorvastatin should be started in the first instance (lower doses may be considered in patients with CKD or those at higher risk of adverse effects)
- If statins are not tolerated or contraindicated (e.g. active liver disease or unexplained persistent transaminitis), ezetimibe is the usual second-line option
- Patients should be counselled before starting statins (see patient decision aid in references section) and safety netted for side effects of muscle symptoms including rhabdomyolysis
- Patients started on statins should be monitored with a full lipid profile and liver function tests 2-3 months into treatment; liver function should be repeated again at 1 year
- Other lipid-lowering drugs may be considered if statins and/or ezetimibe are not effective or tolerated - these include:
	- Icosapent ethyl - an omega−3 fish-oil based medication with multiple mechanisms of action
	- Bempedoic acid - an inhibitor of adenosine triphosphate citrate lyase which reduces hepatic cholesterol synthesis
	- Inclisiran - an inhibitor of PCSK9 production 
	- Alirocumab and evolocumab - these are both monoclonal antibodies that inhibit PCSK9
	- Fenofibrate - reduces triglycerides with variable effects on cholesterol
	- Colestyramine - bile acid sequestrant

# Complications

- Ischaemic heart disease 
- Acute coronary syndrome
- Stroke and transient ischaemic attack
- Peripheral vascular disease
- Erectile dysfunction
- Aortic disease

# NICE Guidelines

[NICE CKS - Lipid modification - CVD prevention](https://cks.nice.org.uk/topics/lipid-modification-cvd-prevention/)

[NICE CKS - Familial hypercholesterolaemia](https://cks.nice.org.uk/topics/hypercholesterolaemia-familial/)

[NICE CKS - CVD risk assessment and management](https://cks.nice.org.uk/topics/cvd-risk-assessment-management/)

[NICE Decision Aid - Should I take a statin?](https://www.nice.org.uk/guidance/ng238/resources/patient-decision-aid-on-should-i-take-a-statin-pdf-243780159)

# References

[https://patient.info/doctor/hyperlipidaemia-pro](https://patient.info/doctor/hyperlipidaemia-pro)

[BNF Treatment Summaries - Dysplipidaemias](https://bnf.nice.org.uk/treatment-summaries/dyslipidaemias/)

[NHS Digital - Health Survey for England 2021](https://digital.nhs.uk/data-and-information/publications/statistical/health-survey-for-england/2021-part-2/adult-health-cholesterol)

[QRISK3 calculator](https://qrisk.org/)
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Hyperlipidaemia
Topic
36
Clinical Chemistry
12520
A 50-year-old woman visits the GP for a routine health checkup. She was diagnosed with type 2 diabetes a few months ago (well-controlled on oral hypoglycemics). Examination is unremarkable, with normal vital signs. Blood tests reveal very high serum cholesterol and low-density lipoprotein levels. She is advised to take Simvastatin 20mg once daily.

Which of the following are patients told to avoid whilst taking statins?
a