Association of elevated serum PO4, Ca x PO4 product, and parathyroid hormone with cardiac mortality risk in chronic hemodialysis patients

Hyperphosphatemia is highly prevalent among patients with end-stage renal d isease (ESRD) and is associated with increased mortality risk in hemodialys is (HD) patients. The mechanism through which this mortality risk is mediat ed is unclear. Data from two national random samples of HD patients (n=12,8 33) was used to test the hypothesis that elevated serum PO4 contributes mai nly to cardiac causes of death. During a 2-yr follow-up, the cause-specific relative risk (RR) of death for patients was analyzed separately for sever al categories of cause of death, including coronary artery disease (CAD), s udden death, and other cardiac causes, cerebrovascular and infection. Cox r egression models were fit for each of the eight cause of death categories, adjusting for patient demographics and non-cardiovascular comorbid conditio ns. Time at risk for each cause-specific model was censored at death that r esulted from any of the other causes. Higher mortality risk was seen for pa tients in the high PO, group (>6.5mg/dl) compared with the lower PO4 group (less than or equal to6.5mg/dl) for death resulting from CAD (RR 1.41 P<0.0 005), sudden death (RR 1.20, P<0.01), infection (RR 1.20; P<0.05), and unkn own causes (RR 1.25, P<0.05). Patients in the high PO4 group also had non-s ignificantly increased RR of death from other cardiac and cerebrovascular c auses of death. The RR of sudden death was also strongly associated with el evated Ca x PO4 product (RR 1.07 per 10 mg(2)/dl(2); P<0.005) and serum par athyroid hormone levels greater than 495 pg/ml (RR 1.25; P<0.05). This stud y identifies strong relationships between elevated serum PO4. Ca x PO4 prod uct, and parathyroid hormone and cardiac causes of death in HD patients, es pecially deaths resulting from CAD and sudden death. More vigorous measures to reduce the prevalence of these factors in HD patients may result in imp roved survival.