Background : The development of cardiac allograft vasculopathy (CAV) portends an adverse clinical outcome in heart transplant recipients. Previous studies of clinical predictors of CAV have investigated small cohorts and have not evaluated the volumetric extent of disease. This study determined predictors of progression of the volumetric severity of vasculopathy in a large cohort of heart transplant recipients. Methods : Serial intravascular ultrasound examinations were performed in 119 heart transplant recipients at 1 month and 1 year following transplantation. Clinical predictors of serial changes in atheroma volume were determined. In particular, the impact of donor and recipient age stratified according to the median was investigated. Results : Patients ( donor age 33.3 ± 14.2 years, recipient age 54.5 ± 12.6 years, 71.9 % male) demonstrated an increase in atheroma volume (64.2 ± 41.7 mm 3 at 1 month vs. 78.1 ± 53.4 mm 3 at 1 year, p < 0.001) and a decrease in lumen volume (334.2 ± 197.3 mm 3 at 1 month vs. 321.6 ± 187.8 mm 3 at 1 year, p = 0.001). Greater increases in atheroma volume were observed in the setting of older donor age (r = 0.24, p = 0.008), older recipient age (r = 0.23, p = 0.01) and recipients not treated with an angiotensin-converting enzyme (ACE) inhibitor (without ACE inhibitor, 21.1 ± 33.3 mm 3 vs. with ACE inhibitor, 9.1 ± 27.6 mm 3 , p = 0.03). In multivariate analysis, donor age ( p = 0.01) and the lack of treatment with an ACE inhibitor ( p = 0.02) remained independent predictors of increases in atheroma volume. Increased disease progression with age was attenuated with the use of ACE inhibitors (table ). Conclusion : Donor age and ACE inhibitor treatment are major determinants of CAV progression. This analysis suggests that treatment with ACE inhibitors would attenuate age-related progression of CAV. Large randomized clinical trials are warranted to ascertain such a beneficial effect.