Reduced blood circulating calcium level is an outstanding biomarker for preeclampsia among 48 types of human diseases

QJM. 2022 Jul 9;115(7):455-462. doi: 10.1093/qjmed/hcab222.

Abstract

Background: Calcium ion (Ca2+) is essential for human physiology by regulating various signal transduction pathways inside all cells and in the blood circulation.

Aim: We compared circulating Ca2+ levels in the healthy control against 48 different types of human diseases.

Design: A total of 144 201 independent test results of Ca2+ levels from 48 clinically defined diseases and 141 679 independent test results of Ca2+ from healthy individuals who came to the hospital for annual physical examination were retrieved during the past 5 years.

Methods: Ca2+ was determined by the standard 'Arsenazo III method' in the clinical laboratory of Affiliated Hospital of Qingdao University. We analyzed all data using RStudio V.1.3.1073 and python libraries 3.8.

Results: All 48 types of diseases had decreased Ca2+ levels than the healthy control based on either mean or median values. Patients suffering from preeclampsia had the lowest Ca2+ levels among all 48 diseases. The perfect area under the curve, sensitivity, and specificity values of 1.0, 0.96 and 0.96 indicated that Ca2+ was an excellent biomarker for diagnosing preeclampsia. Extremely low Ca2+ was present in patients suffering kidney-related diseases. Since the correlation between each disease on the statistical features is proportional to their vector distance, the two-component analysis revealed that preeclampsia, sepsis and chronic obstructive pulmonary disease were closely related among 48 diseases.

Conclusions: All human diseases were associated with reduced circulating Ca2+ levels, where the decreased Ca2+ was a perfect biomarker for preeclampsia. Kidney-related conditions were related to over-down-regulation of Ca2+ levels. The resemblance of preeclampsia to sepsis and chronic obstructive pulmonary disease based on two-component analysis suggested that the three unrelated diseases might share a similar mechanism of the circulating Ca2+ regulation.

MeSH terms

  • Biomarkers
  • Calcium / metabolism
  • Case-Control Studies
  • Female
  • Humans
  • Pre-Eclampsia* / diagnosis
  • Pregnancy
  • Pulmonary Disease, Chronic Obstructive*
  • Sepsis*

Substances

  • Biomarkers
  • Calcium