Heart and Blood Vessels Health in People With Cystic Fibrosis

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.

Inclusion Criteria: * 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. * Clinically stable at the time of assessment (no pulmonary exacerbation or hospitalisation in the past 4 weeks) Inclusion Criteria for healthy control: • Clinically stable at the time of assessment (no pulmonary exacerbation or hospitalisation in the past 4 weeks) Exclusion Criteria: * 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 * are a smoker, or have been smoking in the last 10 years * Inability to undergo vascular assessments (e.g. upper limb vascular anomalies, limb injury) * Inability to comply with fasting instructions (for blood draws) * Had an organ transplantation