Refractory hypercholesterolaemia is a condition where cholesterol levels in the blood remain high despite treatment with standard therapies, such as statins and lifestyle changes. This guide explains the condition, its causes, symptoms, treatments, and how to manage living with it.
What is Refractory Hypercholesterolaemia?
Refractory hypercholesterolaemia refers to persistently high levels of low-density lipoprotein (LDL) cholesterol (often called “bad cholesterol”) that do not respond adequately to conventional treatments. Cholesterol is a fatty substance in your blood that is essential for building cells, but too much LDL cholesterol can increase the risk of heart disease and stroke by causing fatty deposits (plaques) to build up in your arteries.
This condition is often linked to genetic factors or other underlying health issues and requires more intensive or specialised treatments to lower cholesterol levels effectively.
Background on Refractory Hypercholesterolaemia
- History: The condition has been increasingly recognised in recent decades as researchers have developed a better understanding of why some individuals do not respond well to standard cholesterol-lowering therapies.
- Global Impact: Refractory hypercholesterolaemia contributes significantly to the burden of cardiovascular disease worldwide, particularly in individuals with familial hypercholesterolaemia (a genetic condition that causes very high cholesterol levels).
Causes, Incidence, and Prevalence
Causes
Refractory hypercholesterolaemia can result from a combination of genetic and environmental factors:
- Genetic Factors: Conditions like familial hypercholesterolaemia (FH), caused by mutations in genes such as LDLR, APOB, or PCSK9, can make it difficult for the body to clear LDL cholesterol from the blood.
- Secondary Causes: Other health conditions, such as hypothyroidism (underactive thyroid), kidney disease, or poorly controlled diabetes, can contribute to high cholesterol levels.
- Lifestyle Factors: While diet and exercise play a role in managing cholesterol, some people with refractory hypercholesterolaemia may not respond to lifestyle changes alone due to underlying biological factors.
Incidence and Prevalence
- Incidence: The exact number of new cases diagnosed annually is unclear due to underdiagnosis, but familial hypercholesterolaemia affects approximately 1 in 250 people globally.
- Prevalence: Around 10–20% of people with high cholesterol may have refractory hypercholesterolaemia that does not respond adequately to standard treatments.
Who is Affected?
- Age of Onset: Symptoms often appear in early adulthood for those with familial hypercholesterolaemia but may develop later in life for others.
- Gender: Both men and women are affected equally.
- Ethnicity: The condition occurs across all ethnic groups but may be more common in populations with higher rates of familial hypercholesterolaemia due to genetic factors.
Geographic Distribution
Refractory hypercholesterolaemia occurs worldwide but may be more prevalent in regions with higher rates of obesity, diabetes, or other cardiovascular risk factors.
How Does Refractory Hypercholesterolaemia Impact You?
Symptoms
The condition itself does not cause noticeable symptoms until complications arise. However, persistently high LDL cholesterol levels increase the risk of:
- Heart attacks (myocardial infarctions).
- Peripheral artery disease (reduced blood flow to the limbs).
In individuals with familial hypercholesterolaemia, physical signs like xanthomas (fatty deposits under the skin) or corneal arcus (a white ring around the cornea) may be present.
Living With Refractory Hypercholesterolaemia
Living with this condition often involves ongoing medical care and adherence to specialised treatments. Regular monitoring of cholesterol levels and cardiovascular health is essential.
Expected Life Expectancy
With appropriate management, many individuals with refractory hypercholesterolaemia can live long and healthy lives. However, untreated or poorly managed cases significantly increase the risk of premature cardiovascular events.
Managing and Treating Refractory Hypercholesterolaemia
Available Treatments
Treatment for refractory hypercholesterolaemia focuses on lowering LDL cholesterol levels as much as possible to reduce cardiovascular risk:
- Medications:
- PCSK9 Inhibitors: Injectable medications like alirocumab or evolocumab help lower LDL cholesterol by enhancing its removal from the bloodstream.
- Ezetimibe: Reduces cholesterol absorption from food in the intestines.
- Bempedoic Acid: A newer oral medication that lowers LDL cholesterol by targeting a specific enzyme involved in its production.
- Statins (if tolerated): High-intensity statins like atorvastatin or rosuvastatin remain a cornerstone of treatment.
- Lipoprotein(a)-Lowering Therapies:For individuals with elevated lipoprotein(a), emerging treatments are under investigation.
- Lifestyle Changes:
- Adopt a heart-healthy diet rich in fruits, vegetables, whole grains, lean proteins, and healthy fats while avoiding saturated fats and trans fats.
- Engage in regular physical activity (at least 150 minutes of moderate exercise per week).
- Maintain a healthy weight.
- Avoid smoking and limit alcohol consumption.
- Advanced Therapies:
- Lipoprotein Apheresis: A procedure similar to dialysis that removes LDL cholesterol directly from the blood; used for severe cases.
- Gene Therapy: Experimental treatments aim to correct genetic mutations responsible for familial hypercholesterolaemia.
Ongoing Clinical Research
Research into refractory hypercholesterolaemia continues to explore new therapies and improve outcomes for patients:
- RNA-Based Therapies: Drugs like inclisiran target PCSK9 production at the genetic level for long-lasting LDL reduction.
- Gene Editing Techniques: Technologies like CRISPR-Cas9 are being studied for their potential to correct genetic mutations permanently.
- Biomarker Studies: Efforts are underway to identify biomarkers that predict treatment response or cardiovascular risk more accurately.
For information on clinical trials related to refractory hypercholesterolaemia, visit clinicaltrials.gov.
Support Groups and Resources
If you have been diagnosed with refractory hypercholesterolaemia, connecting with support groups can provide valuable information and emotional support:
- Heart UK – The Cholesterol Charity (org.uk)– Offers resources specifically for individuals struggling with high cholesterol.
- Familial Hypercholesterolemia Foundation (FH Foundation) (org)– Focuses on education and advocacy for people living with inherited high cholesterol conditions.
- British Heart Foundation (BHF) (org.uk)– Provides general support for managing cardiovascular health.
- European Atherosclerosis Society (EAS) (eas-society.org)– Offers educational resources on lipid disorders like refractory hypercholesterolaemia.