Specialists in cardiovascular disease and lipid management Professor Ahmet Fuat, Dr Jaimini Cegla, Dr Tina Khan and Dr Mayur Patel discuss key features of familial hypercholesterolaemia (FH) and other genetic lipid disorders. To complete the full module and log 2 CPD points visit Pulse365.
Learning objectives
This module will enhance your understanding of genetic lipid disorders, including:
- The key features of FH and when to test for the condition.
- Different types of FH, their prevalence and associated risks.
- The process for screening and diagnosis of FH.
- How FH should be managed and the benefits of lipid-lowering interventions.
- Features of polygenic hypercholesterolaemia, its prevalence and associated risks.
- The contribution of Lipoprotein(a) to increased inherent CVD risk, when it should be tested for and how it is managed.
1. GPs see many lipid results each day – what result, or pattern of results, should make us think of FH?
Familial Hypercholesterolaemia (FH) is a genetic disorder characterised by high cholesterol levels, specifically low-density lipoprotein cholesterol (LDL-C), which can lead to an increased risk of cardiovascular disease (CVD).
The following results from lipid testing should raise suspicion amongst GPs, in line with the Simon Broome thresholds:1
- Elevated total cholesterol (>7.5mmol/L) or LDL-c (>4.9mmol/L) in adults.
- Elevated total cholesterol (>6.7mmol/L) or LDL-c (>4.0 mmol/L) in children below the age of 16.
The serum triglyceride concentration should also be normal but could be elevated if there is a secondary cause present such as poorly controlled diabetes or obesity. Therefore, the presence of elevated serum triglycerides with elevated serum cholesterol and LDL-C should not discount the possibility of FH. It is also useful to review a patient’s historical lipid result if available, as patients with FH tend to have persistently elevated serum cholesterol and LDL-C above the Simon Broome thresholds (see Question 4).
2. What would be other pointers to this condition?
In addition to LDL-C levels, there are several other factors that serve as potential indicators of FH. These include:
- A family history of FH or atherosclerotic cardiovascular disease (ASCVD) in the form of acute coronary heart disease, stroke, transient ischemic attack or peripheral arterial disease in one or more first degree relatives below the age of 60 or one or more second-degree relatives below the age of 50. In the case of a family history of FH, ideally any diagnosis in a relative will have been confirmed by genetic testing.
- A personal history of CVD such as heart attacks or strokes, occurring before the age of 55 in men or 65 in women.
- Clinical features such as:
- tendon xanthoma (pathognomonic with total cholesterol >7.5mmol/L) which involves the thickening of the tendons caused by lipid infiltration, frequently affecting the Achilles but can also involve other tendons at the metacarpophalangeal joint or elbow extensors.
- Xanthelasma (cholesterol deposits in the eyelids)
- Corneal arcus (cholesterol deposits in the cornea). This symptom should raise a higher level of suspicion in adults under the age of 45.
It is important to note that the absence of these clinical signs does not exclude a diagnosis of FH.
3. What types of FH exist, how common are they and what level of risk do they confer upon the individual?
FH exists in two main forms that are primarily distinguished by their genetic inheritance patterns: heterozygous FH (HeFH) or homozygous FH (HoFH). Each type has different prevalence rates and associated risks, but both significantly increase an individual’s overall susceptibility to CVD.
- HeFH is inherited from one parent and is the most common monogenic disorder, affecting 1 in 250 of the population.2 People with HeFH will typically have cholesterol levels that are 2-3 times higher than normal, leading to a significantly increased risk of premature CVD. If left untreated, men with HeFH aged 50 and above have a 50% increased risk of a cardiovascular event, whilst women aged 60 and above have a 30% increased risk.3 With early identification and treatment, however, people can expect to lead a relatively normal life.
- HoFH is inherited from both parents and is much rarer, affecting 1 in 250,000 individuals.2 It is associated with very high cholesterol levels and consequently carries an extremely high risk of severe CVD. Indeed, without aggressive treatment, individuals with HoFH will likely develop coronary heart disease during childhood.
To complete the full module and log 2 CPD hours towards revalidation visit Pulse365
Professor Ahmet Fuat is a GPSI in Cardiology in Darlington and Honorary Professor of Primary Care Cardiology at Durham University; Dr Jaimini Cegla is Consultant in Chemical Pathology and Metabolic Medicine, Imperial College Healthcare NHS Trust; Dr Tina Khan is Consultant Cardiologist, Royal Brompton and Harefield Hospitals; and Dr Mayur Patel is Consultant in Chemical Pathology and Metabolic Medicine, Oxford University Hospitals NHS Foundation Trust
References
- NICE. Familial hypercholesterolemia: identification and management. [CG71] Last updated October 2019
- HEART UK. Familial Hypercholesterolaemia. August 2024
- NHS England. Cardiac Networks: Familial Hypercholesterolemia. August 2024
