Research to Investigate the Link Between Immunodeficiency and Heart Disease: A Focus Group Discussion
Dr Robert L Yellon and Dr David Lowe
What is common variable immunodeficiency (CVID)?
Common variable immunodeficiency (CVID) is a condition where the immune system makes too few antibodies, proteins which fight infection. Patients with CVID are at an increased risk of infection, especially bacterial infections of the lungs and sinuses. A subset of patients with CVID also have an increased risk of inflammatory disease where the immune system mistakenly attacks the body itself. This subset of patients often has signs in the blood of inflammation, even if there is no active infection. CVID is typically treated with regular antibiotics to prevent and treat infection, and antibody replacement therapy with replacement antibodies sourced from blood donors.
What is atherosclerotic cardiovascular disease (ASCVD)?
Atherosclerotic cardiovascular disease (ASCVD) is a condition where fatty deposits build up in the walls of blood vessels. This affects blood vessels which supply the heart itself but can also affect vessels throughout the body including those that supply the brain. If these blood vessels become too narrow, the flow of blood can become reduced, starving these organs of oxygen. This can lead to symptoms such as chest pain (known as angina), heart failure, and even dementia. In addition, these fatty deposits can suddenly rupture, causing blood clots to form triggering heart attacks and strokes. It is known that ASCVD is partly triggered by chronic inflammation such as that caused by obesity, diabetes, cigarette smoking, and excessive alcohol consumption.
It has been estimated that if all individuals in England with pre-disposing conditions were diagnosed and managed according to official guidelines, 3.4 million cases of ASCVD could be prevented over the next 25 years.
Is there a relationship between immunodeficiency, inflammation, and heart disease?
Certain autoimmune diseases such as rheumatoid arthritis and lupus cause chronic inflammation which increases the risk of ASCVD. HIV, a disease which severely weakens the immune system, is also associated with chronic inflammation and ASCVD. As such, when doctors calculate a patient’s risk of ASCVD, they need to take into account whether or not the patient has one of these diagnoses. If a patient’s risk is high enough, they can be given medication to prevent further damage to the blood vessels and to prevent complications such as heart attack and stroke. Such medications include drugs to reduce blood pressure (e.g. ACE inhibitors), cholesterol (e.g. statins), and weight/blood sugar (e.g. Mounjaro).
Considering the above, it could be assumed that CVID and the accompanying inflammation increases the risk of ASCVD. Historically however the evidence for this has been limited. This may be because CVID patients once had shorter life expectancies and did not reach an age where ASCVD could develop. Nowadays however, CVID patients have a much longer lifespan, likely due to an increased access to antibody replacement therapy.
Importantly, a recent study from the Royal Free Hospital has provided evidence that CVID patients may be at a higher risk of ASCVD. This study of 101 CVID patients and 56 healthy patients showed that CVID patients had high levels of blood markers associated with blood vessel damage, and showed possible hardening of the blood vessel walls, a common finding in ASCVD. CVID patients with harder vessels showed an increased risk of other diseases associated with ASCVD, including high blood pressure, high cholesterol, diabetes, kidney disease, and previously diagnosed cardiovascular disease.
Whilst we know that CVID causes chronic inflammation, the precise mechanisms are not completely understood. It is recognised that in ASCVD, a cellular structure known as the inflammasome is over-activated, which releases excess inflammatory substances called cytokines. These cytokines contribute to blood vessel damage and the build up of fatty deposits in the vessel walls. Whether the inflammasome is also over-activated in CVID remains unclear, and could represent a mechanism by which CVID causes chronic inflammation.
A proposal to research this topic:
Our team would like to perform further research as part of a PhD project into cardiovascular risk in CVID. This would be divided into three parts:
- Repeat the Royal Free Hospital study across multiple centres, using better tests for blood vessel disease and collecting data in a standardised way. This will increase the amount of data available to improve the quality of evidence for researchers.
- Study data from a large UK health database to look for evidence of a link between CVID and ASCVD.
- Perform laboratory-based research to identify whether the inflammasome is over-activated in CVID and whether it could be contributing to ASCVD.
Why this research matters:
- If CVID increases the risk of heart disease, doctors could start checking blood pressure, cholesterol, and blood sugar levels earlier in these patients. This would improve the well-being of these patients by catching or preventing heart disease at an earlier stage.
- It may be that clinical immunologists need to play a greater role in preventing heart disease in their patients than previously thought, and as such clinical guidelines for the management of CVID may need to be updated.
- Treatments to target the inflammasome could be used to help prevent inflammation and associated heart disease in CVID patients. Such drugs are currently being investigated in clinical trials for other/related conditions, e.g. obesity with cardiovascular risk. Our research may provide evidence to support future clinical trials for patients with CVID.
Conclusion:
We would like to explore patients’ views on this proposal and get their input to design the best possible study to (a) answer the questions they think are important and (b) encourage participation by making the study attractive to patients. We are therefore seeking approximately ten patients with CVID to take part in focus group discussion. This will take place online via a Microsoft Teams meeting and should last approximately one hour.
How to express interest
If you have CVID and would like to take part in this focus group, please email the research team at cvidstudy@gmail.com with:
- Your full name
- Your date of birth
- Your best contact number
- The name of the hospital under which your CVID care is managed
Your participation is voluntary and confidential. All contributions will be used solely for research purposes.
Posted April 2026.
