Findings raise concern about cardiac safety of low serum phosphate

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  • Low, high-normal, and high serum phosphate were positively associated with long-term primary cardiac disease risk.

Why this matters

  • Low serum phosphate has previously been considered to be cardioprotective.
  • The present study contradicts this finding and questions the cardiac safety of hypophosphataemia.
  • This is the first study to highlight the primary cardiovascular risk significance of low serum phosphate in a large, national database cohort study.

Key results

  • At the 5-y review of eligible patients, there were 1595 (2.74%) primary cardiac events (myocardial infarction, acute coronary syndrome, revascularisation procedures).
  • At the 9-y review, there were 2268 events (11.48%).
  • Lowest outcome frequency was associated with mid-range normophosphataemia (1.01-1.25 mmol/L).
  • High (>1.5 mmol/L) or low (≤0.75 mmol/L) serum phosphate was associated with significantly higher frequencies of cardiac events (P<.001).
  • Low (OR, 1.75; P<.001), high-normal (1.26-1.50 mmol/l; OR 1.50; P<.001), and high (OR, 1.74; P=.02) mean values were associated with higher odds of primary cardiac events at 5 y.
  • A similar pattern was observed at 9 y.

Study design

  • Retrospective cohort study using patient data extracted from the Royal College of General Practitioners-Research and Surveillance Centre (RCGP-RSC) database.
  • Patients aged between 18 and 90 y without pre-existing cardiovascular diagnoses were included.
  • Funding: None disclosed.


  • Selection process may create bias towards inclusion of patients with co-morbidities for which serum phosphate requires routine measurement.