title: Relation between serum phosphate level and cardiovascular event rate in people with coronary disease.
abstract: BACKGROUND
  Higher levels of serum phosphate are associated with adverse cardiovascular outcomes, especially in the setting of overt hyperphosphatemia. Given the biological importance of phosphorus, it is plausible that higher levels of serum phosphate within the normal range may also be associated with adverse outcomes.
  
  
  RESULTS
  We performed a post hoc analysis of data from the Cholesterol And Recurrent Events (CARE) study. Baseline serum phosphate levels were measured in 4127 fasting participants who were randomized to receive pravastatin 40 mg daily or placebo and followed up for a median of 59.7 months. We used Cox proportional-hazards models to examine the association between serum phosphate and adverse clinical outcomes after adjustment for potential confounders. During nearly 60 months of follow-up, 375 participants died. A significant association was noted between baseline serum phosphate level and the age-, race-, and sex-adjusted risk of all-cause death (hazard ratio per 1 mg/dL, 1.27; 95% confidence interval, 1.02 to 1.58). After categorization based on baseline phosphate level (<2.5, 2.5 to 3.4, 3.5 to 3.9, and > or =4 mg/dL) and further adjustment, a graded independent relation between phosphate and death was observed (P for trend=0.03). For instance, participants with serum phosphate > or =3.5 mg/dL had an adjusted hazard ratio for death of 1.27 (95% confidence interval, 1.02 to 1.59) compared with those with serum phosphate of <3.5 mg/dL. Higher levels of serum phosphate were also associated with increased risk of new heart failure, myocardial infarction, and the composite of coronary death or nonfatal myocardial infarction, but not the risk of stroke.
  
  
  CONCLUSIONS
  We found a graded independent relation between higher levels of serum phosphate and the risk of death and cardiovascular events in people with prior myocardial infarction, most of whom had serum phosphate levels within the normal range. Given the ready availability and low cost of serum phosphate assays, this finding may prove clinically useful.
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, Alberta, Canada. mtonelli@ualberta.ca
authors.forename: Marcello
authors.initials: M
authors.lastname: Tonelli
authors.forename: Frank
authors.initials: F
authors.lastname: Sacks
authors.forename: Marc
authors.initials: M
authors.lastname: Pfeffer
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Gao
authors.forename: Gary
authors.initials: G
authors.lastname: Curhan
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000453:epidemiology* / Q000401:mortality; D002423:Cause of Death; D002784:Cholesterol / Q000097:blood; D003327:Coronary Disease / Q000097:blood* / Q000453:epidemiology* / Q000401:mortality; D005260:Female; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D010710:Phosphates / Q000097:blood*; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D015415:Biomarkers; D010710:Phosphates; D002784:Cholesterol