Relation between alkaline phosphatase, serum phosphate, and all-cause or cardiovascular mortality

Marcello Tonelli, Gary Curhan, Marc Pfeffer, Frank Sacks, Ravi Thadhani, Michal L. Melamed, Natasha Wiebe, Paul Muntner

Research output: Contribution to journalArticle

156 Citations (Scopus)

Abstract

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 (Ptrend=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 (Ptrend 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 • 1.73 m. 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.

Original languageEnglish (US)
Pages (from-to)1784-1792
Number of pages9
JournalCirculation
Volume120
Issue number18
DOIs
StatePublished - Nov 2009

Fingerprint

Alkaline Phosphatase
Phosphates
Mortality
Serum
Nutrition Surveys
Cholesterol
Kidney Diseases
Myocardial Infarction
Glomerular Filtration Rate
Population
Renal Insufficiency
Survivors
Dialysis
Confidence Intervals
Liver
Enzymes

Keywords

  • Cardiovascular diseases
  • Cohort studies
  • Kidney failure, chronic
  • Metabolism
  • Myocardial infarction

ASJC Scopus subject areas

  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Relation between alkaline phosphatase, serum phosphate, and all-cause or cardiovascular mortality. / Tonelli, Marcello; Curhan, Gary; Pfeffer, Marc; Sacks, Frank; Thadhani, Ravi; Melamed, Michal L.; Wiebe, Natasha; Muntner, Paul.

In: Circulation, Vol. 120, No. 18, 11.2009, p. 1784-1792.

Research output: Contribution to journalArticle

Tonelli, M, Curhan, G, Pfeffer, M, Sacks, F, Thadhani, R, Melamed, ML, Wiebe, N & Muntner, P 2009, 'Relation between alkaline phosphatase, serum phosphate, and all-cause or cardiovascular mortality', Circulation, vol. 120, no. 18, pp. 1784-1792. https://doi.org/10.1161/CIRCULATIONAHA.109.851873
Tonelli, Marcello ; Curhan, Gary ; Pfeffer, Marc ; Sacks, Frank ; Thadhani, Ravi ; Melamed, Michal L. ; Wiebe, Natasha ; Muntner, Paul. / Relation between alkaline phosphatase, serum phosphate, and all-cause or cardiovascular mortality. In: Circulation. 2009 ; Vol. 120, No. 18. pp. 1784-1792.
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abstract = "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 (Ptrend=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 (Ptrend 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 • 1.73 m. 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.",
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T1 - Relation between alkaline phosphatase, serum phosphate, and all-cause or cardiovascular mortality

AU - Tonelli, Marcello

AU - Curhan, Gary

AU - Pfeffer, Marc

AU - Sacks, Frank

AU - Thadhani, Ravi

AU - Melamed, Michal L.

AU - Wiebe, Natasha

AU - Muntner, Paul

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N2 - 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 (Ptrend=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 (Ptrend 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 • 1.73 m. 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.

AB - 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 (Ptrend=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 (Ptrend 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 • 1.73 m. 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.

KW - Cardiovascular diseases

KW - Cohort studies

KW - Kidney failure, chronic

KW - Metabolism

KW - Myocardial infarction

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