High Serum Phosphate is Associated with Increased Cardiac Allograft Vasculopathy and Adverse Cardiac Events Following Heart Transplantation

Background: Hyperphosphatemia is a major risk factor for death, cardiovascular (CV) events and vascular calcification in patients with and without chronic kidney disease. Even subtly higher serum phosphate (s-PHOS) levels within the “normal laboratory range” are associated with a higher risk for CV events and mortality. We therefore investigated the association between s‑PHOS levels and heart transplantation (HT) outcomes.

Methods: Between 2000 and 2017, we assessed 168 HT patients for s-PHOS levels. In accordance with the median value of all s-PHOS levels recorded during the first year post-HT, patients were divided into high (≥3.71 mg/dL, n=84) and low (Outcomes included cardiac allograft vasculopathy (CAV), cardiovascular and all-cause mortality, and non-fatal major adverse cardiac events (NF-MACE).

Results: Patients in the high s-PHOS group were younger (50 vs 55 years, p=0.015), with fewer receiving tacrolimus therapy (33 vs 62%, p=0.001). Mean s-PHOS level was 4.3±0.5 mg/dL vs 3.3±0.3 mg/dL for the high and low groups, respectively (p<0.001). Rate of CAV was significantly higher (31% vs 0, p<0.001) for the high vs low s-PHOS group. Patients with high s-PHOS had lower 10-year freedom from CV mortality, NF-MACE and combined end-point of CAV/CV mortality/NF-MACE (p<0.005, for all). Multivariate analysis adjusted for age, immunosuppression therapy, creatinine, and any treated rejection, demonstrated that high s-PHOS group was independently associated with a higher risk for adverse cardiac events (Table).

Conclusion: High post-HT s-PHOS is independently associated with increased CAV and adverse cardiac events in HT patients. Future studies are needed to examine the effect of interventions to decrease s-PHOS levels.