Effects of Calcium, Magnesium, and Potassium Concentrations on Ventricular Repolarization in Unselected Individuals

Raymond Noordam (Lead / Corresponding author), William J. Young, Reem Salman, Jørgen K. Kanters, Marten E. van den Berg, Diana van Heemst, Henry J. Lin, Sandhi Maria Barreto, Mary L. Biggs, Ginevra Biino, Eulalia Catamo, Maria Pina Concas, Jun Ding, Daniel S. Evans, Luisa Foco, Niels Grarup, Leo Pekka Lyytikäinen, Massimo Mangino, Hao Mei, Peter J. van der MostMartina Müller-Nurasyid, Christopher P. Nelson, Yong Qian, Linda Repetto, M. Abdullah Said, Nabi Shah, Katharina Schramm, Pedro G. Vidigal, Stefan Weiss, Jie Yao, Nuno R. Zilhao, Jennifer A. Brody, Peter S. Braund, Marco Brumat, Eric Campana, Paraskevi Christofidou, Mark J. Caulfield, Alessandro De Grandi, Anna F. Dominiczak, Alex S. F. Doney, Gudny Eiriksdottir, Christina Ellervik, Luana Giatti, Martin Gögele, Claus Graff, Xiuqing Guo, Pim van der Harst, Peter K. Joshi, Mika Kähönen, Bryan Kestenbaum, Maria F. Lima-Costa, Allan Linneberg, Arie C. Maan, Thomas Meitinger, Sandosh Padmanabhan, Cristian Pattaro, Annette Peters, Astrid Petersmann, Peter Sever, Mortiz F. Sinner, Xia Shen, Alice Stanton, Konstantin Strauch, Elsayed Z. Soliman, Kirill V. Tarasov, Kent D. Taylor, Chris H. L. Thio, André G. Uitterlinden, Simona Vaccargiu, Melanie Waldenberger, Antonietta Robino, Adolfo Correa, Francesco Cucca, Steven R. Cummings, Marcus Dörr, Giorgia Girotto, Vilmundur Gudnason, Torben Hansen, Susan R. Heckbert, Christian R. Juhl, Stefan Kääb, Terho Lehtimäki, Yongmei Liu, Paulo A. Lotufo, Colin N. A. Palmer, Mario Pirastu, Peter P. Pramstaller, Antonio Luiz P. Ribeiro, Jerome I. Rotter, Nilesh J. Samani, Harold Snieder, Tim D. Spector, Bruno H. Stricker, Niek Verweij, James F. Wilson, James G. Wilson, J. Wouter Jukema, Andrew Tinker, Christopher H. Newton-Cheh, Nona Sotoodehnia, Dennis O. Mook-Kanamori, Patricia B. Munroe (Lead / Corresponding author), Helen R. Warren

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)


Background: Subclinical changes on the electrocardiogram are risk factors for cardiovascular mortality. Recognition and knowledge of electrolyte associations in cardiac electrophysiology are based on only in vitro models and observations in patients with severe medical conditions.

Objectives: This study sought to investigate associations between serum electrolyte concentrations and changes in cardiac electrophysiology in the general population.

Methods: Summary results collected from 153,014 individuals (54.4% women; mean age 55.1 ± 12.1 years) from 33 studies (of 5 ancestries) were meta-analyzed. Linear regression analyses examining associations between electrolyte concentrations (mmol/l of calcium, potassium, sodium, and magnesium), and electrocardiographic intervals (RR, QT, QRS, JT, and PR intervals) were performed. The study adjusted for potential confounders and also stratified by ancestry, sex, and use of antihypertensive drugs.

Results: Lower calcium was associated with longer QT intervals (−11.5 ms; 99.75% confidence interval [CI]: −13.7 to −9.3) and JT duration, with sex-specific effects. In contrast, higher magnesium was associated with longer QT intervals (7.2 ms; 99.75% CI: 1.3 to 13.1) and JT. Lower potassium was associated with longer QT intervals (−2.8 ms; 99.75% CI: −3.5 to −2.0), JT, QRS, and PR durations, but all potassium associations were driven by use of antihypertensive drugs. No physiologically relevant associations were observed for sodium or RR intervals.

Conclusions: The study identified physiologically relevant associations between electrolytes and electrocardiographic intervals in a large-scale analysis combining cohorts from different settings. The results provide insights for further cardiac electrophysiology research and could potentially influence clinical practice, especially the association between calcium and QT duration, by which calcium levels at the bottom 2% of the population distribution led to clinically relevant QT prolongation by >5 ms.

Original languageEnglish
Pages (from-to)3118-3131
Number of pages14
JournalJournal of the American College of Cardiology
Issue number24
Early online date17 Jun 2019
Publication statusPublished - 25 Jun 2019


  • cohort studies
  • electrocardiographic intervals
  • electrolytes
  • epidemiology
  • meta-analysis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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