Cystic fibrosis (CF) is a disease that affects over 11,000 people in the UK. It is a genetic condition that affects many organs including the lungs, pancreas, kidneys and liver. New drugs called "modulators" have meant people with CF are now living much longer. Until recently, heart disease was rare in CF, but with the new modulators there are increasing concerns that heart disease may become a big problem in the future. This is partly to do with the drugs causing weight gain and higher blood pressure, which are risk factors for heart disease.
My PhD project aims to find out whether the blood vessels and hearts of people with CF are healthy or diseased. I will then find out how the blood vessels are changing over time and work out what things are driving those changes.
I will measure the health of the blood vessels and heart using an ultrasound machine to understand what the pattern of disease is like and who might be at the highest risk for heart disease in the future. I will then repeat these measurements a year later. I will compare people of different ages and with different types of disease to understand what things may help us identify heart disease as soon as possible.
In the general population, doctors often use medical prediction tools to find out who is at the highest risk for heart disease. We do not know if these work for people with CF, so I will also find out whether those prediction tools are useful in CF.
It is vital to understand who may be at risk for heart disease, as one of the most effective ways of treating heart disease is to prevent it from happening. This work may pave the way for future studies to test early treatment for heart disease in those people we identify might be at high risk. Early prevention treatment could reduce the risk of heart disease and ultimately improve the length and quality of life of people living with CF. This is particularly important given people with CF already have a much shorter life expectancy than the general population.
In summary, this PhD project will help improve our understanding of heart disease in CF and help identify the best way forward to prevent heart disease causing health problems related to heart disease for these individuals in the future.
Confirmed diagnosis of cystic fibrosis, based on sweat chloride testing and/or CFTR genotyping
Aged 18 years or older
Currently receiving CFTR gene modulators, defined as elexacaftor/ tezacaftor/ ivacaftor (ETI), or any next generation gene modulators after ETI, introduced for at least 3 months
On licensed doses that is listed on Summary of Product Characteristics of each CFTR gene modulator.
On long term steroids, or any vasoactive medications
Diagnosed with end stage organ diseases
Diagnosed with rheumatoid arthritis, and/or systemic lupus erythematosus
Pregnancy or breastfeeding
Participants with CF will be recruited from the CF outpatient clinic at Liverpool Heart and Chest Hospital (face-to-face and telemedicine clinic). The study will be advertised in local GP practices and NHS trust notice boards, and contact information will be provided on the advertisements for prospective healthy controls to approach a member of the clinical-research team.
Cohort
Other
Not listed
Change in Endothelial Function Assessed by Brachial Artery Flow-Mediated Dilation (FMD)
Endothelial function will be measured by the peak percentage (%) change in brachial artery diameter from baseline following a 5-minute period of induced ischemia. The outcome is reported as a percentage. A higher percentage indicates a stronger vasodilatory response, which represents better endothelial function and a better cardiovascular outcome.
Incidence of cardiovascular events (MI, angina, stroke, TIA or cardiac death)
This outcome assesses the number of participants who experience at least one major cardiovascular event during the follow-up period. The specified events include myocardial infarction (MI), angina, stroke, transient ischemic attack (TIA), or cardiac death. The outcome is reported as a total count of participants experiencing one or more of these events. A higher number indicates a greater frequency of adverse cardiovascular outcomes within the cohort.
Change in Arterial Stiffness Assessed by Pulse Wave Velocity (PWV)
Arterial stiffness evaluated using Pulse Wave Velocity (PWV). PWV is measured in meters per second (m/s) with a theoretical minimum of 0 m/s and no defined upper maximum limit. Higher values indicate greater arterial stiffness, representing a worse cardiovascular outcome.
Change in Arterial Stiffness Assessed by Augmentation Index (AIx)
Arterial stiffness evaluated using the Augmentation Index (AIx). AIx is calculated as the difference between the second and first systolic peaks and is expressed as a percentage (%) of pulse pressure, normalized to a heart rate of 75 bpm (AIx@75). The measure has a theoretical minimum of 0% with no defined upper maximum limit. Higher values indicate greater arterial stiffness, representing a worse cardiovascular outcome.
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Liverpool Heart and Chest Hospital NHS Foundation Trust
Lead sponsor
Asthma and Lung UK
Collaborator
Liverpool John Moores University
Collaborator
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