Effects of Calcium, Magnesium, and Potassium Concentrations on Ventricular Repolarization in Unselected Individuals
Raymond NoordamWilliam J. YoungReem SalmanJørgen K. KantersMarten E. van den BergHenry J. LinSandhi Maria BarretoMary L. BiggsGinevra BiinoEulalia CatamoMaria Pina ConcasJun DingDaniel S. EvansLuisa FocoNiels GrarupLeo‐Pekka LyytikäinenMassimo ManginoHao MeiPeter J. van der MostMartina Müller‐NurasyidChristopher P. NelsonYong QianL. RepettoM. Abdullah SaidNabi ShahKatharina SchrammPedro Guatimosim VidigalStefan WeißJie YaoNuno R. ZilhäoJennifer A. BrodyPeter S. BraundMarco BrumatEric CampanaParaskevi ChristofidouMark J. CaulfieldAlessandro De GrandiAnna F. DominiczakAlex S. F. DoneyGuðný EiríksdóttirChristina EllervikLuana GiattiMartin GögeleClaus GraffXiuqing GuoPim van der HarstPeter K. JoshiMika KähönenBryan KestenbaumMaria Fernanda Lima‐CostaAllan LinnebergArie C. MaanThomas MeitingerSandosh PadmanabhanCristian PattaroAnnette PetersAstrid PetersmannPeter SeverMortiz SinnerXia ShenAlice StantonKonstantin StrauchElsayed Z. SolimanKirill V. TarasovKent D. TaylorChris H. L. ThioAndré G. UitterlindenSimona VaccargiuMélanie WaldenbergerAntonietta RobinoAdolfo CorreaFrancesco CuccaSteven R. CummingsMarcus DörrGiorgia GirottoVilmundur GuðnasonTorben HansenSusan R. HeckbertChristian R. JuhlStefan KääbTerho LehtimäkiYongmei LiuPaulo A. LotufoMario PirastuPeter P. PramstallerAntônio Luiz Pinho RibeiroJerome I. RotterNilesh J. SamaniHarold SniederTim D. SpectorBruno H. StrickerNiek VerweijJames F. WilsonJ. Wouter JukemaAndrew TinkerChristopher Newton‐ChehNona SotoodehniaDennis O. Mook‐KanamoriPatricia B. Munroe
Key result
Lower serum calcium is linked to ~12-ms longer QT intervals.
- MD -11.5 ms
- 95% CI -13.7 to -9.3
- n=153,014
Why the study?
Recognition and knowledge of electrolyte associations in cardiac electrophysiology are based on in vitro models and patients with severe conditions, lacking data in the general population.
Do variations in serum electrolyte concentrations affect electrocardiographic intervals in the general population?
Study Design
Type
Meta-Analysis (n=153,014)
Multicenter
Yes
Structured PICO
Do variations in serum electrolyte concentrations affect electrocardiographic intervals in the general population?
P
Population
153,014 unselected individuals (mean age 55.1 years, 54.4% women) from 33 studies assessed for associations between serum electrolyte concentrations and cardiac electrophysiology.
E
Exposure
Serum electrolyte concentrations (calcium, potassium, sodium, and magnesium in mmol/l)
O
Outcome
Electrocardiographic intervals (RR, QT, QRS, JT, and PR intervals)surrogate
Main Result
Mean Difference: -11.5 (95% CI -13.7–-9.3)
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“The results show that 2% of the population studied have a blood calcium concentration which prolongs the heart's electrical activity by 5 milliseconds or more. This is a cut off used in drug development to prioritise new drugs for further investigation due to the risk of abnormal heart rhythms. The effects may be even more relevant in women, but this is an observation requiring further investigation.”
“We caution overinterpretation of data that implicate slight lengthening in QT intervals as 'clinically relevant.' Slight QT prolongation, by itself, may have no specific meaning or prognostic value.”
“An important limitation of epidemiological/observational research is that causality is difficult to ascertain and associations we observed do not have a clear biological interpretation or meaning.”
Implication
Lower serum calcium and higher serum magnesium concentrations are associated with clinically relevant prolongation of the QT interval in the general population.
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.
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Cite This Study
Noordam et al. (2019) conducted a meta-analysis in General population (n=153,014). Serum electrolyte concentrations (calcium, magnesium, potassium, sodium) vs. Different concentrations (continuous) was evaluated on Electrocardiographic intervals (QT, JT, RR, QRS, and PR) (MD -11.5 ms, 95% CI -13.7 to -9.3). Lower calcium was associated with longer QT intervals (-11.5 ms; 99.75% CI -13.7 to -9.3), whereas higher magnesium was associated with longer QT intervals (7.2 ms; 99.75% CI 1.3 to 13.1).