Increased Vascular Age in Patients with Fanconi Anemia after Hematopoietic Cell Transplantation: Results of a...

Fanconi anemia (FA) is a bone marrow failure and cancer predisposition syndrome associated with an accelerated aging phenotype. Additionally, patients with FA have a high risk of developing metabolic syndrome. However, there is a lack of data on their subsequent risk of long-term cardiovascular disease. Carotid ultrasound imaging provides structural and functional measurements of the carotid artery and has been used to assess cardiovascular risk in the general population as well as in some patients after hematopoietic cell transplantation (HCT). The primary objective of this descriptive study was to assess the long-term cardiovascular disease risk in patients with FA as measured by carotid ultrasound. Secondary objectives included identifying factors contributing to cardiac risk and vascular aging in this patient population. We performed a cross-sectional single-institution study to examine the vascular health in patients with FA, including carotid artery ultrasound imaging. Patients were 1:1 matched to healthy controls by sex, age, and body mass index (BMI). Clinical data were obtained through the University of Minnesota Bone Marrow Transplant database, which included metabolic laboratory studies and HCT data. Two-sample t tests were used to compare carotid ultrasound variables between FA and control cohorts. Four carotid ultrasound imaging variables were used for analysis: carotid intima media thickness (cIMT), lumen diameter, diameter distensibility, and incremental elastic modulus. Continuous variables, such as blood pressure, age, and BMI, were evaluated using Spearman's correlation coefficient (R), with tests of the null hypothesis that R = 0. Forty-nine patients with FA underwent carotid ultrasound imaging between 2016 and 2019. The median age of the cohort was 13 years (range, 5 to 34 years). In this cohort, biallelic mutations in FANCA (n = 35), FANCC (n = 6), and FANCD2 (n = 3) were the most common gene mutations. Forty-three patients in the cohort underwent 1 allogeneic HCT, and 2 patients underwent 2 HCTs. Of those requiring transplantation, the median time from HCT to carotid ultrasound was 6 years (range, 1 to 22 years). Five patients had a history of acute graft-versus-host disease (GVHD), and 2 patients had a history of chronic GVHD. Analysis of carotid ultrasound imaging demonstrated that patients with FA had a significantly higher median cIMT compared to controls (0.56 mm versus 0.43 mm; P < .01). Additionally, the FA cohort had lower compliance (0.11 mm^2. mm Hg^-1 vs 0.15 mm^2. mm Hg^-1; P < .01) and distensibility (median, 12.1% versus 12.8%; P = .01). Bivariate analysis demonstrated that older FA patient age was associated with a significant decrease in vessel elasticity, which was not seen in the control cohort. There was no association between increased BMI and decreased vessel elasticity in either the FA or control cohort. The results of this descriptive study demonstrate increased arterial stiffness, particularly at an early age in patients with FA. As arterial stiffness is associated with an increased risk for cardiac disease in the general population, prospective studies should evaluate this correlation specifically in patients with FA and identify disease-modifying agents such as statins.