Background: Higher levels of serum alkaline phosphatase (AlkP) are associated with excess mortality in dialysis patients, but whether AlkP is associated with adverse outcomes among people without kidney failure is unknown.
Methods and results: We first analyzed the association between AlkP and cardiovascular outcomes among 4115 participants with a previous myocardial infarction (the Cholesterol And Recurrent Events [CARE] study). Results were validated by analyzing the association between AlkP and mortality in an independent sample of 14,716 adults from the general US population (the Third National Health and Nutrition Examination Survey). A graded, independent association was noted between baseline tertile of AlkP and the adjusted hazard ratio of all-cause mortality in CARE participants (P(trend)=0.02). After adjustment for serum phosphate, hepatic enzymes, and other potential confounders, participants with AlkP in the highest tertile had an adjusted hazard ratio of 1.43 (95% confidence interval 1.08 to 1.89) compared with those in the lowest tertile. Multivariable-adjusted associations between higher AlkP and all-cause and cardiovascular mortality were present in the Third National Health and Nutrition Examination Survey (P(trend) across tertiles of AlkP=0.006 and 0.038, respectively). Findings from both CARE and the Third National Health and Nutrition Examination Survey were similar among individuals with and without evidence of kidney disease, defined by estimated glomerular filtration rate <60 mL min(-1) 1.73 m(-2).
Conclusions: We found an independent relation between higher levels of AlkP and adverse outcomes among survivors of myocardial infarction and in a general population sample. The excess risk of death was present in people without evidence of kidney disease and was particularly high among people with higher levels of both AlkP and serum phosphate.