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

Raymond Noordam; 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 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 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; Helen R Warren

doi:10.1016/j.jacc.2019.03.519

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

Raymond Noordam, 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, Helen R Warren

Research output: Contribution to journal › Journal article › Research › peer-review

27 Citations (Scopus)

Abstract

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 language	English
Journal	Journal of the American College of Cardiology
Volume	73
Issue number	24
Pages (from-to)	3118-3131
Number of pages	14
ISSN	0735-1097
DOIs	https://doi.org/10.1016/j.jacc.2019.03.519
Publication status	Published - 25 Jun 2019

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Cardiac Repolarization
Graff, C.
01/08/2005 → …
Project: Research

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Noordam, R., Young, W. J., Salman, R., Kanters, J. K., van den Berg, M. E., van Heemst, D., Lin, H. J., Barreto, S. M., Biggs, M. L., Biino, G., Catamo, E., Concas, M. P., Ding, J., Evans, D. S., Foco, L., Grarup, N., Lyytikäinen, L-P., Mangino, M., Mei, H., ... Warren, H. R. (2019). Effects of Calcium, Magnesium, and Potassium Concentrations on Ventricular Repolarization in Unselected Individuals. Journal of the American College of Cardiology, 73(24), 3118-3131. https://doi.org/10.1016/j.jacc.2019.03.519

@article{36fed0fe8e3b4813955f58b75623358f,

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

abstract = "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.",

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

year = "2019",

month = jun,

day = "25",

doi = "10.1016/j.jacc.2019.03.519",

language = "English",

volume = "73",

pages = "3118--3131",

journal = "Journal of the American College of Cardiology",

issn = "0735-1097",

publisher = "Elsevier",

number = "24",

}

Noordam, R, Young, WJ, Salman, R, Kanters, JK, van den Berg, ME, van Heemst, D, Lin, HJ, Barreto, SM, Biggs, ML, Biino, G, Catamo, E, Concas, MP, Ding, J, Evans, DS, Foco, L, Grarup, N, Lyytikäinen, L-P, Mangino, M, Mei, H, van der Most, PJ, Müller-Nurasyid, M, Nelson, CP, Qian, Y, Repetto, L, Said, MA, Shah, N, Schramm, K, Vidigal, PG, Weiss, S, Yao, J, Zilhao, NR, Brody, JA, Braund, PS, Brumat, M, Campana, E, Christofidou, P, Caulfield, MJ, De Grandi, A, Dominiczak, AF, Doney, ASF, Eiriksdottir, G, Ellervik, C, Giatti, L, Gögele, M, Graff, C, Guo, X, van der Harst, P, Joshi, PK, Kähönen, M, Kestenbaum, B, Lima-Costa, MF, Linneberg, A, Maan, AC, Meitinger, T, Padmanabhan, S, Pattaro, C, Peters, A, Petersmann, A, Sever, P, Sinner, MF, Shen, X, Stanton, A, Strauch, K, Soliman, EZ, Tarasov, KV, Taylor, KD, Thio, CHL, Uitterlinden, AG, Vaccargiu, S, Waldenberger, M, Robino, A, Correa, A, Cucca, F, Cummings, SR, Dörr, M, Girotto, G, Gudnason, V, Hansen, T, Heckbert, SR, Juhl, CR, Kääb, S, Lehtimäki, T, Liu, Y, Lotufo, PA, Palmer, CNA, Pirastu, M, Pramstaller, PP, Ribeiro, ALP, Rotter, JI, Samani, NJ, Snieder, H, Spector, TD, Stricker, BH, Verweij, N, Wilson, JF, Wilson, JG, Jukema, JW, Tinker, A, Newton-Cheh, CH, Sotoodehnia, N, Mook-Kanamori, DO, Munroe, PB & Warren, HR 2019, 'Effects of Calcium, Magnesium, and Potassium Concentrations on Ventricular Repolarization in Unselected Individuals', Journal of the American College of Cardiology, vol. 73, no. 24, pp. 3118-3131. https://doi.org/10.1016/j.jacc.2019.03.519

TY - JOUR

T1 - Effects of Calcium, Magnesium, and Potassium Concentrations on Ventricular Repolarization in Unselected Individuals

AU - Noordam, Raymond

AU - Young, William J

AU - Salman, Reem

AU - Kanters, Jørgen K

AU - van den Berg, Marten E

AU - van Heemst, Diana

AU - Lin, Henry J

AU - Barreto, Sandhi Maria

AU - Biggs, Mary L

AU - Biino, Ginevra

AU - Catamo, Eulalia

AU - Concas, Maria Pina

AU - Ding, Jun

AU - Evans, Daniel S

AU - Foco, Luisa

AU - Grarup, Niels

AU - Lyytikäinen, Leo-Pekka

AU - Mangino, Massimo

AU - Mei, Hao

AU - van der Most, Peter J

AU - Müller-Nurasyid, Martina

AU - Nelson, Christopher P

AU - Qian, Yong

AU - Repetto, Linda

AU - Said, M Abdullah

AU - Shah, Nabi

AU - Schramm, Katharina

AU - Vidigal, Pedro G

AU - Weiss, Stefan

AU - Yao, Jie

AU - Zilhao, Nuno R

AU - Brody, Jennifer A

AU - Braund, Peter S

AU - Brumat, Marco

AU - Campana, Eric

AU - Christofidou, Paraskevi

AU - Caulfield, Mark J

AU - De Grandi, Alessandro

AU - Dominiczak, Anna F

AU - Doney, Alex S F

AU - Eiriksdottir, Gudny

AU - Ellervik, Christina

AU - Giatti, Luana

AU - Gögele, Martin

AU - Graff, Claus

AU - Guo, Xiuqing

AU - van der Harst, Pim

AU - Joshi, Peter K

AU - Kähönen, Mika

AU - Kestenbaum, Bryan

AU - Lima-Costa, Maria F

AU - Linneberg, Allan

AU - Maan, Arie C

AU - Meitinger, Thomas

AU - Padmanabhan, Sandosh

AU - Pattaro, Cristian

AU - Peters, Annette

AU - Petersmann, Astrid

AU - Sever, Peter

AU - Sinner, Mortiz F

AU - Shen, Xia

AU - Stanton, Alice

AU - Strauch, Konstantin

AU - Soliman, Elsayed Z

AU - Tarasov, Kirill V

AU - Taylor, Kent D

AU - Thio, Chris H L

AU - Uitterlinden, André G

AU - Vaccargiu, Simona

AU - Waldenberger, Melanie

AU - Robino, Antonietta

AU - Correa, Adolfo

AU - Cucca, Francesco

AU - Cummings, Steven R

AU - Dörr, Marcus

AU - Girotto, Giorgia

AU - Gudnason, Vilmundur

AU - Hansen, Torben

AU - Heckbert, Susan R

AU - Juhl, Christian R

AU - Kääb, Stefan

AU - Lehtimäki, Terho

AU - Liu, Yongmei

AU - Lotufo, Paulo A

AU - Palmer, Colin N A

AU - Pirastu, Mario

AU - Pramstaller, Peter P

AU - Ribeiro, Antonio Luiz P

AU - Rotter, Jerome I

AU - Samani, Nilesh J

AU - Snieder, Harold

AU - Spector, Tim D

AU - Stricker, Bruno H

AU - Verweij, Niek

AU - Wilson, James F

AU - Wilson, James G

AU - Jukema, J Wouter

AU - Tinker, Andrew

AU - Newton-Cheh, Christopher H

AU - Sotoodehnia, Nona

AU - Mook-Kanamori, Dennis O

AU - Munroe, Patricia B

AU - Warren, Helen R

PY - 2019/6/25

Y1 - 2019/6/25

N2 - 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.

AB - 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.

U2 - 10.1016/j.jacc.2019.03.519

DO - 10.1016/j.jacc.2019.03.519

M3 - Journal article

C2 - 31221261

SN - 0735-1097

VL - 73

SP - 3118

EP - 3131

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

IS - 24

ER -

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

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