Cardiac allograft vasculopathy mediates the relationship between vitamin D deficiency and cardiovascular mortality following heart transplantation.

BACKGROUND

Patients undergoing orthotopic heart transplantation (OHT) often have vitamin D deficiency (VDD) and cardiac allograft vasculopathy (CAV). Both VDD and CAV are associated with activation of the renin-angiotensin-aldosterone system. Although VDD is associated with adverse cardiovascular outcomes in multiple cohorts, the impact of VDD in OHT patients remains unknown. We hypothesized that lower VD levels would independently predict the presence of CAV and adverse cardiovascular outcomes.

METHODS

In 327 participants with OHT recruited prospectively and followed for outcomes, baseline presence of CAV and all-cause and cardiovascular mortality at 5 years were evaluated. Multivariate logistic, cox, and Fine-Gray regression models were used to explore the associations between VDD and outcomes.

RESULTS

VDD, present in 95 (29.1%) participants at enrollment, was associated with double the risk of 5-year mortality (HR: 2.08, 95% CI: 1.20-3.60), which was driven mostly by cardiovascular death (SHR: 2.21, 95% CI: 1.13-4.31), and also associated with a 3-fold higher likelihood of having CAV (OR: 3.08, 95% CI: 1.39-6.80) after adjustment for demographic and clinical covariates. There was a significant interaction between VDD and CAV on cardiovascular death (P = .042). Mediation analysis showed that CAV grade accounts for 26.5% of the overall association between VD and cardiovascular mortality.

CONCLUSION

VDD is an independent predictor of all-cause mortality, cardiovascular mortality, and presence of CAV in patients with OHT. Higher CAV grade appears to mediate, at least in part, the impact of VD levels on cardiovascular mortality, suggesting that VDD may contribute to higher risk of death through development of CAV.