High serum phosphorus levels after fasting 12 or more hours are associated with an increased risk of all-cause and cardiovascular mortality, according to a new study.

Among individuals fasting for 12 or more hours, those in the highest quartile of serum phosphorus had a significant 74% increased risk of all-cause mortality and a significant 2-fold increased risk of cardiovascular mortality compared with those in the lowest quartile, investigators reported online ahead of print in the American Journal of Kidney Diseases. Serum phosphorus was not associated with all-cause or cardiovascular mortality among individuals fasting less than 12 hours.

Investigators Alex R. Chang, MD, MS, of Geisinger Health System in Danville, Pa., and Morgan E. Grams, MD, PhD, of Johns Hopkins University in Baltimore, said the much stronger association between serum phosphorus levels and mortality  among individuals with longer fasting duration suggests that risk prediction may be enhanced with the use of fasting phosphorus levels.

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Drs. Chang and Grams noted that serum phosphorus levels exhibit a diurnal variation, with a midmorning trough, an early afternoon peak followed by a plateau, and a higher peak in the early morning hours. “Diet may amplify this variation: higher phosphorus intake results in higher mean 24-hour serum phosphorus levels, with the early afternoon increase particularly exaggerated by dietary phosphorus intake and diminished by phosphorus restriction,” the researchers explained.


As dietary phosphorus intake may introduce random variability in serum phosphorus levels, the researchers said they hypothesized that the association between serum phosphorus and mortality would be stronger with longer fasting duration among participants in the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994). For their study, Drs. Chang and Grams analyzed data from 12,984 NHANES III participants aged 20 years and older.


Higher serum phosphorus levels might increase death risk by promoting vascular calcification or endothelial dysfunction, the researchers pointed out. Another possibility, they noted, is that serum phosphorus levels “could reflect subtle alternations in bone mineral metabolism because most phosphorus is stored in bone; markers of bone turnover, such as alkaline phosphatase, have been associated with vascular calcification and death.”