Vascular Health and Function in Cystic Fibrosis

The goal of this observational study is to learn whether blood vessel health and function differ between adults aged 40 years or older with cystic fibrosis (CF) who are taking CFTR modulator therapy and healthy adults of the same age and sex. As people with CF now live longer, they may face a higher risk of heart and blood vessel disease and stroke. The main question it aims to answer is: Is the function of the arteries in the arm (measured by radial artery flow-mediated dilation and low-flow mediated constriction) reduced in people with CF compared with healthy controls? Researchers will also compare the function of the neck (carotid) arteries, blood flow control in the brain, the reflexes that control blood pressure, and blood markers of inflammation and oxidative stress between the two groups. They will also look at whether these measures relate to memory and thinking, mood, and quality of life. Participants will attend a single study visit of about 2.5 to 3 hours at Liverpool Heart and Chest Hospital (or Manchester Metropolitan University for some healthy controls). During the visit they will: * Have height, weight, waist and hip size and body fat measured * Give a blood sample * Have ultrasound scans of the arm and neck arteries, including a short period with a blood pressure cuff inflated on the wrist and a few minutes with one hand in cold water * Have brain blood flow, heart rhythm, blood pressure and breathing monitored while resting, lying, standing, doing repeated squats and opening and closing their eyes * Complete short tests of memory and thinking, and questionnaires about mood and quality of life

Inclusion Criteria: Participants with CF: * Able to provide written informed consent * Aged 40 years or older * Confirmed diagnosis of cystic fibrosis based on sweat chloride testing and/or CFTR genotyping * Currently receiving CFTR modulator treatment at a recognised therapeutic dose * Clinically stable (no pulmonary exacerbation or hospitalisation in the previous 4 weeks) Healthy controls: * Able to provide written informed consent * Aged 40 years or older * Healthy, in sinus rhythm, with normal blood pressure (systolic below 140 mmHg and diastolic below 90 mmHg) * No pulmonary exacerbation or hospitalisation in the previous 4 weeks * Not taking any prescription medications (other than contraceptives and/or hormone replacement therapy) Exclusion Criteria (all participants): * History of stroke * Current use of oral nitrates * Valvular heart disease * Acute coronary syndrome within the previous 3 months * Previous organ transplantation * Uncontrolled thyroid disorder * Cancer * Current infection or pyrexia * Long-term steroids or any vasoactive medication * End-stage organ disease * Inflammatory disease (e.g. rheumatoid arthritis, systemic lupus erythematosus) * Pregnancy or breastfeeding * Current smoker or vaper, or smoked or vaped within the last 10 years * Unable to undergo vascular assessments (e.g. upper limb vascular anomaly or limb injury) * Unable to comply with fasting and pre-test instructions * Clinic blood pressure of 140/90 mmHg or higher at screening * Unable to understand written and spoken English