Risk factors and surrogate indicators for cardiovascular disease are prevalent in Common Variable Immunodeficiency and associate with inflammatory phenotype

Aidan Jia Sheng Yu¹Fernando Moreira¹Andrew Symes¹Keegan Curlewis²Mary O'Sullivan¹Joseph Jayasundera¹Fatema-Zahra El Rhermoul¹Charley Lever¹Kostadin Stoenchev¹Ke Li Chow¹Omer Faruk Uysal³Ahmad M Alharbi³Sarita Workman¹Neil Halliday^4,5Arian Dominic John Laurence¹Nisha Verma¹Susan Tadros¹Sorena Kiani-Alikhan¹Joseph Barnett²Siobhan Oisin Burns^1,6John R Hurst³David M Lowe^1,6*

• ¹Department of Clinical Immunology, Royal Free London NHS Foundation Trust, London, United Kingdom
• ²Department of Radiology, Royal Free London NHS Foundation Trust, London, United Kingdom
• ³UCL Respiratory, University College London, London, United Kingdom
• ⁴Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust, London, United Kingdom
• ⁵University College London Institute for Liver and Digestive Health, University College London, London, United Kingdom
• ⁶University College London Institute of Immunity and Transplantation, London, United Kingdom

Background Common variable immunodeficiency (CVID) is traditionally characterised by recurrent infections and immune dysregulation, but growing evidence suggests an increased risk of endothelial dysfunction and premature atherosclerosis in this population. Objective To evaluate cardiovascular risk in patients with CVID through integration of clinical risk factors, biomarkers of endothelial dysfunction, and radiographic surrogates of subclinical atherosclerosis. Methods A total of 101 CVID patients and 56 matched household controls were recruited. Data collected included cardiovascular risk factors, blood biomarkers (D-dimer, von Willebrand factor [vWF], fibrinogen, ESR, CRP), and immunological profiles. Existing imaging was reviewed, including thoracic CT for assessment of coronary artery calcification (CAC) and FibroScan for controlled attenuation parameter (CAP) scores; aortic pulse wave velocity (aPWV) was measured in a subset of participants. Subgroup analysis compared infection-only versus inflammatory/complex phenotypes of CVID. Results CVID patients demonstrated high rates of hyperlipidaemia (38.6%), hypertension (23.8%), and diabetes/prediabetes (14.9%). CAC was present in 37%, with 82.4% having no known prior cardiovascular disease. Hepatic steatosis and elevated aPWV were observed in 30% and 6.5%, respectively. Patients with CAC were older and had higher rates of hypertension, diabetes, hyperlipidaemia, chronic kidney disease, elevated median vWF (227.5 vs 167 IU/dL, p=0.001), D-dimer (370.5 vs 271 ng/mL, p=0.011), and aPWV (8.2 vs 6.0 m/s, p=0.006). Patients with an inflammatory phenotype had higher vWF (224 vs 163 IU/dL, p<0.001) and D-dimer (314 vs 205 ng/mL, p=0.043) levels than those with infection-only CVID. Conclusion CVID is associated with a substantial burden of cardiovascular risk factors and subclinical atherosclerosis, especially in the inflammatory phenotype.