Effects_of_Calcium__Magnesium__and.....pdf (798.51 kB)
Download file

Effects of calcium, magnesium, and potassium concentrations on ventricular repolarization in unselected individuals.

Download (798.51 kB)
posted on 17.08.2021, 16:54 by Raymond Noordam, William J Young, Reem SalmanReem Salman, Jørgen K Kanters, Martin 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 Lyytikainen, Massimo Mangino, Hao Mei, Peter J. van der Most, Martina 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 Eiríksdottir, 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, LifeLines Cohort Study, Arie C. Maan, Thomas Meitinger, Sandosh Padmanabhan, Cristian Pattaro, Annette Peters, Astrid Petersmann, Peter Sever, Mortiz F Sinner, Xia Shen, Alice V StantonAlice V Stanton, Konstantin Strauch, Elsayed Z Soliman, Kirill 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, Neil 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, Helen R. Warren

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.


Medical Research Council (Grant code MR/R017468/1)

National Institute for Health Research Biomedical Research Centre at Barts and the London School of Medicine and Dentistry.

CNPq (Bolsa de produtividade em pesquisa, 310679/2016-8)

National Institute of Science andTechnology for Health Technology Assessment (IATS/CNPq, project: 465518/2014-1)

FAPEMIG (Programa Pesquisador,Mineiro, PPM-00428-17

CNPq (Bolsa de produtividade em pesquisa, 303137/2014-2)

British Heart Foundation grant numbers RG/07/005/23633 and SP/08/005/25115

European Union Ingenious HyperCare Consortium

Integrated Genomics, Clinical Research, and Care in Hypertension (grant number LSHM-C7-2006-037093)

U54GM115428 from the National Institute of General Medical Sciences

Dutch Science Organization (ZonMW-VENI Grant 916.14.023)

Axa Research Fund

NWO VENI grant (016.186.125)

Netherlands Organization for Health Research and Development (ZonMw) [Priority MedicinesElderly 113102005; and DoelmatigheidsOnderzoek 80-82500-98-10208]

European Union’s Horizon 2020 research and innovation programme under grant agreement No 733100

British Heart Foundation grant RG/15/15/31742



The original article is available at https://www.sciencedirect.com

Published Citation

Noordam R, et al. Effects of calcium, magnesium, and potassium concentrations on ventricular repolarization in unselected individuals. J Am Coll Cardiol. 2019;73(24):3118-3131.

Publication Date

17 June 2019

PubMed ID



  • School of Pharmacy and Biomolecular Sciences

Research Area

  • Vascular Biology




  • Submitted Version (Preprint)