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Hyperlipidaemia (polygenic)
This common condition can increase the risk of cardiovascular diseases, such as heart attacks and strokes. It typically affects adults and is managed through a combination of lifestyle changes and, if needed, medication.
Overview
Polygenic hyperlipidaemia is a very common condition characterised by elevated levels of certain fats, called lipids, in the bloodstream. These lipids include cholesterol and triglycerides. Unlike conditions caused by a single gene change, polygenic hyperlipidaemia results from the combined influence of many different genetic variations, each having a small effect, along with lifestyle and environmental factors [PMID:33678099].
Having high levels of blood lipids can contribute to the hardening and narrowing of arteries, a process known as atherosclerosis. This can increase the risk of developing cardiovascular diseases, including heart attacks and strokes. Effective management is important for reducing these long-term health risks.
Symptoms & clinical features
Polygenic hyperlipidaemia typically does not cause noticeable symptoms directly. The elevated lipid levels are usually discovered through routine blood tests, often as part of a general health check-up or when investigating other health concerns. Because there are no immediate symptoms, many people may be unaware they have the condition.
However, the long-term effects of untreated hyperlipidaemia can lead to symptoms related to cardiovascular disease. These might include chest pain (angina), shortness of breath, or symptoms of a stroke, but these are consequences of the complications rather than the hyperlipidaemia itself. In very rare and severe cases of extremely high lipid levels, small fatty deposits called xanthomas might appear on the skin or tendons, but this is less common with polygenic forms.
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Affected organs
The primary impact of polygenic hyperlipidaemia is on the cardiovascular system. Elevated lipid levels can lead to the build-up of fatty plaques in the arteries, affecting blood vessels throughout the body. This process, known as atherosclerosis, can narrow the arteries and reduce blood flow.
Organs most significantly affected by this reduced blood flow include the heart, potentially leading to coronary artery disease; the brain, increasing the risk of strokes; and the peripheral arteries, which can affect blood supply to the limbs. The liver also plays a central role in lipid metabolism, and while hyperlipidaemia isn't a primary liver disease, the liver's function is crucial in processing and regulating blood lipid levels.
Risks & severity
Polygenic hyperlipidaemia is very common and its severity can vary widely among individuals. The condition typically manifests in adulthood, with lipid levels often rising progressively with age. The main risk associated with polygenic hyperlipidaemia is a significantly increased lifetime risk of cardiovascular diseases, such as coronary heart disease, heart attacks, and strokes [PMID:30133866].
The exact age of onset for complications depends on the specific combination of genetic factors, lifestyle choices, and the duration of elevated lipid levels. While individual genetic variations each have a small effect, their cumulative impact, alongside factors like diet, exercise, and smoking, can lead to substantial elevations in blood lipids and a corresponding increase in cardiovascular risk. Early detection and management are key to mitigating these long-term health risks.
Genetic causes
Polygenic hyperlipidaemia is caused by the combined effect of multiple genetic variations across several different genes, rather than a single dominant genetic change. These genetic variations each contribute a small amount to the overall risk of elevated blood lipids. Several genes have been studied for their role in lipid metabolism.
For example, variations in the *APOE* gene are known to influence how cholesterol and other lipids are transported and processed in the body. *APOE* provides instructions for making apolipoprotein E, a protein that helps carry fats in the bloodstream and is important for maintaining lipid balance [PMID:30133866]. Other genes, such as *CETP* (cholesteryl ester transfer protein) and *HMGCR* (3-hydroxy-3-methylglutaryl-CoA reductase), also play roles in lipid metabolism and can have variations that contribute to hyperlipidaemia [PMID:24076609]. The *HMGCR* gene, for instance, encodes an enzyme involved in cholesterol synthesis, and its activity is a target for cholesterol-lowering medications.
Inheritance pattern
Polygenic hyperlipidaemia follows a polygenic or complex inheritance pattern. This means that it is not inherited in a simple Mendelian fashion (like autosomal dominant or recessive conditions), but rather arises from the interplay of many different genetic changes, each with a small effect, combined with environmental and lifestyle factors.
While there is often a tendency for hyperlipidaemia to run in families, this is not due to a single 'hyperlipidaemia gene' being passed down. Instead, family members may share a similar combination of genetic predispositions and similar lifestyle factors, both contributing to their risk. Therefore, if one family member has polygenic hyperlipidaemia, other close relatives may also have an increased risk, but the inheritance is not predictable in the same way as single-gene disorders.
Diagnosis & testing
Diagnosis of polygenic hyperlipidaemia is primarily made through routine blood tests that measure lipid levels, including total cholesterol, LDL-cholesterol (often called 'bad' cholesterol), HDL-cholesterol ('good' cholesterol), and triglycerides. These tests are typically performed after a period of fasting.
If elevated lipid levels are detected, further investigations may be carried out to rule out other causes of hyperlipidaemia, such as secondary causes due to other medical conditions or medications, or single-gene forms of hyperlipidaemia. Genetic testing is generally not used for diagnosing polygenic hyperlipidaemia because many different genetic variations are involved, and lifestyle factors play a significant role. Diagnosis and initial management are usually undertaken by a GP, who may refer to a specialist if lipid levels are very high or difficult to manage.
Management & lifestyle
Management of polygenic hyperlipidaemia focuses on reducing lipid levels to lower the risk of cardiovascular disease. This typically involves a combination of lifestyle modifications and, in many cases, medication. Lifestyle changes are a cornerstone of management and include adopting a heart-healthy diet low in saturated and trans fats, regular physical activity, maintaining a healthy weight, and avoiding smoking.
If lifestyle changes are not sufficient to achieve target lipid levels, medications such as statins are often prescribed to help lower cholesterol. Other medications may also be used depending on the specific lipid profile. Management plans are individualised and developed in consultation with a GP or specialist. Regular monitoring of lipid levels is usually recommended to assess the effectiveness of treatment and adjust it as needed. Patients can access support and guidance through their GP and, if needed, specialist clinics within the NHS.
UK care pathway
Within the UK, care for individuals with hyperlipidaemia typically begins with their General Practitioner (GP). If initial blood tests reveal elevated lipid levels, the GP will often advise on lifestyle modifications and monitor progress. For individuals with significantly high lipid levels, or those with other cardiovascular risk factors, referral to specialist services, such as a lipid clinic or cardiology clinic, may be considered.
Genetic testing for polygenic hyperlipidaemia is not routinely performed within the NHS Genomic Medicine Service (GMS) due to the complex nature of the condition, involving many genes and lifestyle factors. Genetic counsellors can provide valuable information about complex inheritance patterns and discuss family history implications, especially if there is a strong family history of early-onset cardiovascular disease. While there isn't a specific NHS R-code for polygenic hyperlipidaemia testing, genetic services can help differentiate from single-gene forms of hyperlipidaemia where relevant.
Frequently asked questions
What is the difference between polygenic hyperlipidaemia and familial hypercholesterolaemia (FH)?
Polygenic hyperlipidaemia is caused by the combined effect of many common genetic variations and lifestyle factors. Familial hypercholesterolaemia (FH), in contrast, is typically caused by a change in a single gene and usually leads to much higher cholesterol levels from a younger age, with a clear inheritance pattern within families.
Can polygenic hyperlipidaemia be cured?
Polygenic hyperlipidaemia cannot be 'cured' in the sense of removing the underlying genetic predispositions. However, it can be effectively managed and controlled through lifestyle changes and, if necessary, medication. The goal of management is to reduce lipid levels and significantly lower the risk of associated cardiovascular complications.
Will my children inherit polygenic hyperlipidaemia?
Polygenic hyperlipidaemia has a complex inheritance pattern. Your children may inherit some of the genetic variations that increase risk, and if they also share similar lifestyle factors, they may have an increased chance of developing the condition. It is not inherited in a simple, predictable way like single-gene disorders, but family history is still an important risk factor.
What kind of diet is recommended for polygenic hyperlipidaemia?
A heart-healthy diet is generally recommended. This involves limiting saturated and trans fats (found in many processed foods, fatty meats, and full-fat dairy), reducing dietary cholesterol, increasing fibre intake from fruits, vegetables, and whole grains, and choosing lean proteins. It is best to discuss specific dietary advice with a GP or dietitian.
Are there any symptoms I should look out for?
Polygenic hyperlipidaemia typically does not have direct symptoms. Elevated lipid levels are usually detected through blood tests. Symptoms only tend to appear if the condition leads to complications like heart disease or stroke, which might include chest pain, shortness of breath, or neurological symptoms. Regular check-ups are important for early detection.
References
- Pedro-Botet J, Climent E, Gabarró N. Familial combined hyperlipidaemia/polygenic mixed hyperlipidaemia. Clinica e investigacion en arteriosclerosis : publicacion oficial de la Sociedad Espanola de Arteriosclerosis. 2021. PMID: 34006353