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Original Contribution |

Serum Potassium Levels and Mortality in Acute Myocardial Infarction FREE

Abhinav Goyal, MD, MHS; John A. Spertus, MD, MPH; Kensey Gosch, MS; Lakshmi Venkitachalam, PhD; Philip G. Jones, MS; Greet Van den Berghe, MD, PhD; Mikhail Kosiborod, MD
[+] Author Affiliations

Author Affiliations: Department of Medicine, Emory School of Medicine and Department of Epidemiology, Emory Rollins School of Public Health, Atlanta, Georgia (Dr Goyal); Saint Luke's Mid America Heart Institute, Kansas City, Missouri (Drs Spertus, Venkitachalam, and Kosiborod, Ms Gosch, and Mr Jones); Department of Medicine, University of Missouri, Kansas City (Drs Spertus and Kosiborod); and Department of Intensive Care Medicine, University Hospital Gasthuisberg, University of Leuven, Leuven, Belgium (Dr Van den Berghe).


JAMA. 2012;307(2):157-164. doi:10.1001/jama.2011.1967.
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Published online

Context Clinical practice guidelines recommend maintaining serum potassium levels between 4.0 and 5.0 mEq/L in patients with acute myocardial infarction (AMI). These guidelines are based on small studies that associated low potassium levels with ventricular arrhythmias in the pre−β-blocker and prereperfusion era. Current studies examining the relationship between potassium levels and mortality in AMI patients are lacking.

Objective To determine the relationship between serum potassium levels and in-hospital mortality in AMI patients in the era of β-blocker and reperfusion therapy.

Design, Setting, and Patients Retrospective cohort study using the Cerner Health Facts database, which included 38 689 patients with biomarker-confirmed AMI, admitted to 67 US hospitals between January 1, 2000, and December 31, 2008. All patients had in-hospital serum potassium measurements and were categorized by mean postadmission serum potassium level (<3.0, 3.0-<3.5, 3.5-<4.0, 4.0-<4.5, 4.5-<5.0, 5.0-<5.5, and ≥5.5 mEq/L). Hierarchical logistic regression was used to determine the association between potassium levels and outcomes after adjusting for patient- and hospital-level factors.

Main Outcome Measures All-cause in-hospital mortality and the composite of ventricular fibrillation or cardiac arrest.

Results There was a U-shaped relationship between mean postadmission serum potassium level and in-hospital mortality that persisted after multivariable adjustment. Compared with the reference group of 3.5 to less than 4.0 mEq/L (mortality rate, 4.8%; 95% CI, 4.4%-5.2%), mortality was comparable for mean postadmission potassium of 4.0 to less than 4.5 mEq/L (5.0%; 95% CI, 4.7%-5.3%), multivariable-adjusted odds ratio (OR), 1.19 (95% CI, 1.04-1.36). Mortality was twice as great for potassium of 4.5 to less than 5.0 mEq/L (10.0%; 95% CI, 9.1%-10.9%; multivariable-adjusted OR, 1.99; 95% CI, 1.68-2.36), and even greater for higher potassium strata. Similarly, mortality rates were higher for potassium levels of less than 3.5 mEq/L. In contrast, rates of ventricular fibrillation or cardiac arrest were higher only among patients with potassium levels of less than 3.0 mEq/L and at levels of 5.0 mEq/L or greater.

Conclusion Among inpatients with AMI, the lowest mortality was observed in those with postadmission serum potassium levels between 3.5 and <4.5 mEq/L compared with those who had higher or lower potassium levels.

Figures in this Article

Potassium homeostasis is critical to prevent adverse events in patients with cardiovascular disease. Several studies have demonstrated a relationship between low serum potassium levels, usually less than 3.5 mEq/L, and the risk of ventricular arrhythmias in patients with acute myocardial infarction (AMI).17 On the basis of these studies, experts and professional societies have recommended maintaining potassium levels between 4.0 and 5.0 mEq/L,8,9 or even 4.5 to 5.5 mEq/L,10 in AMI patients. However, most prior studies were conducted before the routine use of β-blockers, reperfusion therapy, and early invasive management in eligible patients with AMI. In addition, these studies were small (usually <1000 patients), which precluded a robust assessment of the relationship between potassium levels and mortality. Furthermore, most of these studies focused on the outcome of postinfarction ventricular arrhythmias, which occur much less frequently in the current AMI treatment era. Therefore, there is a lack of current, adequately powered studies that define the optimal range of serum potassium levels with respect to mortality and other important clinical outcomes in patients with AMI.

To address this critical knowledge gap, we analyzed data from Cerner Health Facts, a database of patients hospitalized with AMI in the United States between 2000-2008. Our objectives were (1) to characterize the distribution and trend of serum potassium levels during hospitalization in patients with AMI; (2) to determine the relationship between serum potassium levels and in-hospital mortality; and (3) to evaluate the relationship between potassium levels and ventricular arrhythmias or cardiac arrest in patients with AMI.

Data Source and Study Cohort

The data source for this investigation was the Cerner Corporation's Health Facts AMI database. This database includes 67 US hospitals with 39 759 consecutive patients with AMI hospitalized between January 1, 2000, and December 31, 2008. Documentation of AMI required a primary discharge diagnosis of AMI, using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnostic codes 410.xx, along with positive cardiac biomarkers. For this analysis, we included 38 689 patients with biomarker-confirmed AMI who also had at least 1 in-hospital serum potassium measurement (eFigure 1).

Data in the Health Facts database were obtained from patients' electronic medical records and included demographics (age, sex, and race); medical history, comorbidities, and in-hospital procedures documented by ICD-9-CM codes; comprehensive laboratory data (including all in-hospital potassium measurements); pharmacy data; in-hospital mortality; and hospital characteristics. All data were deidentified before being provided to the investigators; therefore, an exemption from review was provided by the Saint Luke's Hospital institutional review board.

The 67 hospitals that contributed data to this analysis had a median duration of participation with the Health Facts database of 2.9 years (interquartile range [IQR], 1.2-5.3 years), and a median of 219 patients with AMI (IQR, 48-1030) per center. These hospitals were comparable in their characteristics to those reported in other national registries11: they were most commonly urban (88.5%), were less frequently teaching hospitals (35.9%), represented all geographic regions of the United States (Northeast 38.5%, Midwest 25.6%, South 26.9%, and West 9%), and a broad range of sizes (bed size 1-99, 26.9%; 100-199, 20.5%; 200-299, 23.1%; 300-499, 17.9%; and ≥500 beds, 11.5%).

Inpatient Serum Potassium Measurements and Outcomes

The Health Facts database included all AMI patients' serum potassium levels and their time of measurement relative to hospital admission. The admission (baseline) serum potassium level was defined as the first potassium level obtained during hospitalization. The mean postadmission serum potassium level was defined as the average of all potassium levels measured after the admission level but before hospital discharge. Our primary focus was the relationship between mean postadmission potassium levels and outcomes, because postadmission potassium levels are potentially modifiable during AMI hospitalization and are the subject of guidelines concerning AMI management.810 Additional analyses were also conducted to assess the relationship between admission potassium levels (a nonmodifiable factor in AMI patients) and outcomes. All serum potassium values were measured and reported in mEq/L (1 mEq/L = 1 mmol/L).

The primary outcome for this analysis was in-hospital mortality, as documented in the Health Facts database. Secondary outcomes included the composite of ventricular fibrillation or flutter (documented by ICD-9-CM codes 427.4, 427.41, or 427.42) or cardiac arrest (ICD-9-CM code 427.5) during hospitalization.

Statistical Analysis

Baseline demographics and clinical characteristics were compared among patients categorized by the following mean postadmission serum potassium levels: less than 3.0, 3.0 to less than 3.5, 3.5 to less than 4.0, 4.0 to less than 4.5, 4.5 to less than 5.0, 5.0 to less than 5.5, and 5.5 or greater mEq/L. Hierarchical logistic regression was then used (with hospital site as a random effect to account for clustering across centers) to assess the independent association between mean postadmission serum potassium levels and mortality, after adjustment for potential patient- and hospital-level confounders.

For multivariable models, factors previously demonstrated to be prognostically significant or thought to be clinically important, and covariates identified in bivariate analyses as predictors of in-hospital mortality were considered.12,13 The following models were generated sequentially to determine the successive influence of potential confounders on the relationship between mean postadmission serum potassium levels (reference group, 3.5-<4.0 mEq/L) and mortality: (1) unadjusted; (2) adjusted only for age and sex; (3) adjusted for age, sex, and admission glomerular filtration rate (GFR) calculated by the Modification of Diet in Renal Disease equation14; and (4) adjusted for age, sex, GFR, and the following covariates: race; baseline comorbidities captured by ICD-9-CM codes (diabetes, heart failure, hypertension, cerebrovascular disease, peripheral vascular disease, chronic obstructive pulmonary disease, dementia, dialysis); admission potassium level; other laboratory values on admission (glucose, white blood cell count, hematocrit); peak cardiac troponin level (an estimate of infarct size); number of potassium checks per patient; cardiogenic shock and acute respiratory failure on admission (determined by ICD-9-CM codes); in-hospital procedures captured by ICD-9-CM codes (cardiac catheterization, percutaneous coronary intervention, and coronary artery bypass graft surgery); acute kidney injury as defined by the Acute Kidney Injury Network15,16 (an increase in serum creatinine by ≥0.3 mg/dL, or a relative increase in serum creatinine of ≥50%, during hospitalization); length of hospital stay; and medications during hospitalization (fibrinolytic therapy, aspirin, clopidogrel, ticlopidine, β-blockers, angiotensin-converting enzyme [ACE] inhibitors or angiotensin II receptor blockers, calcium channel blockers, nitrates, diuretics, bronchodilators, statins, insulin treatment, and oral antihyperglycemic agents).

Nonlinear trends for all continuous covariates were tested through the use of restricted cubic splines, given the complex relationship between potassium levels and several baseline variables. We then conducted 2 sensitivity analyses to determine the robustness of the mortality models and minimize the possibility of residual confounding. First, patients who died within 24 hours of admission were excluded to reduce possible survivor bias. In a second sensitivity analysis, we analyzed whether the association between mean postadmission potassium level and in-hospital mortality differed among patients who were treated or untreated with potassium supplementation during hospitalization.

Additional analyses were also conducted to determine the relationship between admission serum potassium levels and in-hospital mortality using the same potassium comparison groups: less than 3.0, 3.0 to less than 3.5, 3.5 to less than 4.0 (reference group), 4.0 to less than 4.5, 4.5 to less than 5.0, 5.0 to less than 5.5, and 5.5 or greater mEq/L. As before, the following successive models were generated: unadjusted; adjusted for age and sex; adjusted for age, sex, and admission GFR; and adjusted for age, sex, GFR, plus all other covariates listed previously. Separate multivariable logistic regression models were then constructed (using the same covariates) to determine rates of the composite of ventricular arrhythmias or cardiac arrest (instead of mortality) across strata of mean postadmission potassium levels and admission potassium levels, with the same reference group (3.5 to <4.0 mEq/L).

A 2-sided P value of .05 was considered to be statistically significant, and 95% CIs were presented for all odds ratios (ORs). Analyses were conducted with SAS software version 9.2.

Serum Potassium Levels and Baseline Characteristics

A total of 38 689 patients with biomarker-confirmed AMI had at least 1 serum potassium level measured during hospitalization. Potassium level at admission was measured in 38 689 patients, 37 208 (96.2%) of whom had the admission potassium level measured within the first 24 hours of hospitalization. Additional (postadmission) potassium levels were obtained in 34 026 patients. The mean (SD) number of potassium measurements per patient during hospitalization was 5.9 (SD, 5.9), and the median number of measurements per patient was 4.0 (IQR, 2.0-7.0). The distribution of admission serum potassium levels approximated that of a normal distribution (Figure 1), with a mean admission potassium level of 4.2 mEq/L (SD, 0.6 mEq/L), and a median admission potassium level of 4.1 mEq/L (IQR, 3.8-4.4 mEq/L). During hospitalization, potassium values tended to remain fairly constant (Figure 2), with a mean postadmission potassium value of 4.2 mEq/L (SD, 0.6 mEq/L), and a median value of 4.1 mEq/L (IQR 3.8-4.5 mEq/L).

Place holder to copy figure label and caption
Figure 1. Distribution of Serum Potassium Levels at Admission in the Overall Population (N = 38 689)
Graphic Jump Location

Median potassium level at admission was 4.1 mEq/L (vertical dotted line). Each x-axis interval is equal to or greater than the lower limit of the interval and less than the upper limit. The first interval includes all serum potassium levels less than 2.0 mEq/L and the last interval includes all that are 8.0 mEq/L or greater.

Place holder to copy figure label and caption
Figure 2. Trend of Serum Potassium Levels During Hospitalization
Graphic Jump Location

Each data point indicates the median and bars indicate the interquartile range of all potassium levels in the overall population that were measured during a half-day (or 12-hour) time period. On the x-axis, each tick mark corresponds to a half-day period of hospitalization. The numbers of patients for each half-day period are: 0.5 d, 34 921; 1.0 d, 17 480; 1.5 d, 14 169; 2.0 d, 14 208; 2.5 d, 11 496; 3.0 d, 11 276; 3.5 d, 8775; 4.0 d, 8614; 4.5 d, 6839; 5.0 d, 6733; 5.5 d, 5421; 6.0 d, 5425; 6.5 d, 4321; 7.0 d, 4411; 7.5 d, 3573; 8.0 d, 3457; 8.5 d, 2861; 9.0 d, 2847; 9.5 d, 2292; and 10.0 d, 2347.

Baseline characteristics of the 34 026 study patients by strata of mean postadmission serum potassium are shown in Table 1. The relationship between potassium levels and baseline variables was complex: U-shaped for some variables (age, female sex, glucose level at admission, cardiogenic shock, and acute kidney injury); and inverted U-shaped for other variables (prior myocardial infarction, dyslipidemia, smoking history, GFR at admission, in-hospital revascularization procedures, and use of several in-hospital medications including aspirin, β-blockers, statins, and ACE-inhibitors). Similar relationships between baseline characteristics and strata of admission potassium levels were observed (eTable 1).

Table Graphic Jump LocationTable 1. Baseline Characteristics By Mean Postadmission Serum Potassium Levela
Serum Potassium Levels and In-Hospital Mortality

Of the 38 689 study patients, 2679 (6.9%; 95% CI, 6.7%-7.2%) died during hospitalization. There was a U-shaped relationship between in-hospital mortality and mean postadmission potassium level (Table 2, Figure 3). Compared with the reference group (3.5-<4.0 mEq/L; mortality rate, 4.8%; 95% CI, 4.4%-5.2%), mortality was comparable for patients with a mean postadmission potassium level of 4.0 to less than 4.5 mEq/L (5.0%; 95% CI, 4.7%-5.3%), multivariable adjusted OR, 1.19; 95% CI, 1.04-1.36. Mortality was twice as great for potassium of 4.5 to less than 5.0 mEq/L (10.0%; 95% CI, 9.1%-10.9%) (multivariable adjusted OR, 1.99; 95% CI, 1.68-2.36), and was even greater at higher potassium levels. Similarly, mortality rates were higher for potassium levels of less than 3.5 mEq/L. This U-shaped relationship was only slightly attenuated and persisted after stepwise adjustments for covariates (Table 2). The U-shaped relationship was similar in patients who did or did not receive potassium supplementation during hospitalization (adjusted P value for interaction, .18). Similar results were also obtained when restricting analyses to patients still alive at 24 hours (data not shown). The association between admission serum potassium levels and in-hospital mortality was also U shaped but not as pronounced as for mean postadmission serum potassium levels (eTable 2; eFigure 2).

Place holder to copy figure label and caption
Figure 3. Rates of In-Hospital Mortality and of the Composite of Ventricular Fibrillation or Cardiac Arrest by Mean Postadmission Serum Potassium Level
Graphic Jump Location

Each x-axis interval is equal to or greater than the lower limit of the interval and less than the upper limit. The first interval includes all serum potassium levels less than 3.0 mEq/L; the last interval includes all levels equal to or greater than 5.5 mEq/L. Numbers of events and event rates are listed in Table 2.

Table Graphic Jump LocationTable 2. In-Hospital Event Rates and Logistic Regression Models for Mortality, and Separately for Ventricular Fibrillation or Cardiac Arrest, by Mean Postadmission Potassium Level
Serum Potassium Levels and Ventricular Arrhythmias or Cardiac Arrest

Of the 38 689 patients with AMI, 1707 (4.4%; 95% CI, 4.2%-4.6%) had an episode of ventricular fibrillation, ventricular flutter, or cardiac arrest during hospitalization. For mean postadmission potassium levels (Table 2; Figure 3), rates of ventricular arrhythmias or cardiac arrest were relatively flat across a wide range of potassium levels (3.0-<5.0 mEq/L), in contrast to mortality rates for which the optimal mean postadmission potassium range was narrower (3.5-<4.5 mEq/L). After adjustment for all covariates (including potassium level at admission), rates of ventricular arrhythmias or cardiac arrest were higher (compared with the reference group, 3.5-<4.0 mEq/L) only for the lowest and highest mean postadmission potassium levels (<3.0 mEq/L and ≥5.0 mEq/L; Table 2). For potassium levels at admission, compared with the reference group of 3.5 to less than 4.0 mEq/L, rates of ventricular arrhythmias or cardiac arrest increased for lower (<3.5 mEq/L) but not for higher potassium levels (eTable 2; eFigure 2).

Power Analysis

We observed a 2-fold greater risk of mortality associated with a mean postadmission potassium level of 4.5 to less than 5.0 mEq/L (mortality rate, 10.0%; 95% CI, 9.1%-10.9%) compared with 3.5 to less than 4.0 mEq/L (mortality rate, 4.8%; 95% CI, 4.4%-5.2%), or compared with 4.0 to less than 4.5 mEq/L (mortality rate, 5.0%; 95% CI, 4.7%-5.3%). Based on the sample size and variation in outcomes observed in this study, we had greater than 99.9% power to detect a 2-fold difference in mortality rates between the lower third (3.5-<4.0 mEq/L) or middle third (4.0-<4.5 mEq/L), compared with the upper third (4.5-<5.0 mEq/L), of the “clinically normal” potassium range of 3.5 to 5.0 mEq/L.

In this retrospective cohort study of patients with AMI, we found a U-shaped relationship between serum potassium levels and in-hospital mortality. The lowest mortality was observed among patients with potassium level between 3.5 and 4.5 mEq/L, with higher mortality rates observed for potassium levels of at least 4.5 mEq/L or less than 3.5 mEq/L. In contrast, rates of ventricular arrhythmias or cardiac arrest were flat in patients with potassium levels between 3.0 and 5.0 mEq/L, and higher rates were observed only for potassium levels of less than 3.0 mEq/L or at least 5.0 mEq/L. Although these associations were observed for potassium levels at admission (a nonmodifiable risk factor) and postadmission mean potassium levels (a modifiable risk factor), the association of mean postadmission potassium levels with mortality remained robust, even after adjusting for potassium level at admission.

This study is among the first that is adequately powered to evaluate the association between the full range of serum potassium levels and mortality following AMI, and suggests that maintaining serum potassium levels between 3.5 and 4.5 mEq/L may be more advisable than the 4.0 to 5.0 mEq/L range currently recommended by practice guidelines in patients with AMI.8,9

Outcomes associated with in-hospital potassium levels in patients with AMI have been described previously.16 Most of these studies included fewer than 1000 patients and concluded that low potassium levels (usually <3.5 mEq/L) were associated with higher rates of postinfarction ventricular arrhythmias.16 On the basis of those studies, current AMI guidelines recommend maintaining serum potassium between 4.0 and 5.0 mEq/L,8,9 and some experts even advise a higher range of 4.5 to 5.5 mEq/L.10

However, the studies on which these guidelines were based have significant limitations. First, they focused on postinfarction ventricular arrhythmias, and were underpowered to examine the relationship between potassium levels and mortality. To our knowledge, the largest prior study included 1074 patients with AMI and demonstrated a U-shaped relationship between potassium levels and early postinfarction ventricular fibrillation events, but lacked power to show an association between potassium level and mortality.17,18 Second, most prior studies were conducted before routine use of β-blockers, reperfusion therapy, and early invasive approaches for patients with AMI.1,2,46 β-Blockers reduce the incidence of postinfarction mortality and sudden cardiac death19,20; raise serum potassium levels (by blocking epinephrine-induced depression of potassium levels through β-receptor stimulation)2124; and suppress hypokalemia-mediated ventricular arrhythmias.2124 Third, the rate and prognostic value of ventricular arrhythmias and cardiac arrest following AMI is much lower in the current era of AMI management compared with 20 years ago.2527 Therefore, the old AMI studies on which current potassium guidelines are based may no longer apply to contemporarily managed patients with AMI.

This study should be considered in the context of several potential limitations. The relationship between potassium levels and mortality was U shaped, whereas the rate of ventricular fibrillation or cardiac arrest was relatively flat across a wide range of mean postadmission potassium levels, except for extreme values (<3.0 and ≥5.0 mEq/L). In our opinion, this discrepancy between the steeper increase in mortality rates and the less steep increase in rates of ventricular fibrillation or cardiac arrest at the extremes of potassium levels may represent a bias in the coding of ventricular arrhythmia and cardiac arrest events in hospitalized patients. Although hypokalemia has traditionally been associated with heightened ventricular excitability and an increased risk of ventricular arrhythmias, hyperkalemia has been associated with reduced ventricular excitability, with other causes of cardiac arrest occurring more frequently, including complete heart block and sinus arrest.28,29 It is possible that these nonshockable rhythms associated with hyperkalemia (while still potentially fatal) may be less likely to be coded as cardiac arrest than rhythms of ventricular origin. Indeed, the inaccuracy of cardiac arrest diagnosis codes among patients who die during hospitalization has been previously reported.30 To overcome this limitation, we designated our primary outcome in this study to be mortality, which is unbiased and of much greater clinical significance than ventricular arrhythmias in the current AMI treatment era.

Our study was observational, and despite the use of robust methods and hierarchical modeling with statistical adjustment, there is a possibility of residual confounding, or that the relationship between potassium level and clinical events may represent reverse causation. In particular, the large ORs for mortality at the extremes of potassium levels (<3.0 and ≥5.5) are based on a small number of events (Table 2), may be affected by outliers, and may represent high illness severity rather than a causal relationship. Large trials that randomize patients with AMI to different potassium targets would be necessary to definitively establish the optimal range for maintaining serum potassium levels in patients with AMI, but such trials are unlikely to be undertaken given the high cost and extensive regulatory procedures required for their conduct. Until such trials are conducted, our findings suggest that overly aggressive repletion of potassium levels (which is often automated through the implementation of hospital order sets) may not be advisable in patients with AMI (particularly in those with levels between 3.5 and 3.9 mEq/L), as potassium levels of at least 4.5 mEq/L are associated with harm.

Our study applies only to patients with AMI and may not extrapolate to patients with other cardiac conditions, including heart failure. Recent analyses from a trial of highly selected heart failure patients suggest that potassium levels of less than 4.0 mEq/L are associated with higher mortality,31,32 but β-blockers (which alter potassium levels and mortality rates in heart failure patients) were not used in that study.33 Studies such as ours should be replicated in the heart failure population.

In conclusion, our large study of patients with AMI challenges current clinical practice guidelines that endorse maintaining serum potassium levels between 4.0 and 5.0 mEq/L. These guidelines are based on small, older studies that focused only on ventricular arrhythmias (and not mortality) and were conducted before the routine use of β-blockers, reperfusion therapy, and early invasive management in AMI patients. Our data suggest that the optimal range of serum potassium levels in AMI patients may be between 3.5 and 4.5 mEq/L and that potassium levels of greater than 4.5 mEq/L are associated with increased mortality and should probably be avoided.

Corresponding Author: Abhinav Goyal, MD, MHS, Emory Schools of Public Health and Medicine, 1518 Clifton Rd NE, Room 3027, Atlanta, GA 30322 (agoyal4@emory.edu).

Author Contributions: Drs Goyal and Kosiborod had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Goyal, Kosiborod.

Acquisition of the data: Spertus, Kosiborod.

Analysis and interpretation of the data: Goyal, Spertus, Gosch, Venkitachalam, Jones, Van den Berghe, Kosiborod.

Drafting of the manuscript: Goyal.

Critical revision of the manuscript for important intellectual content: Goyal, Spertus, Gosch, Venkitachalam, Jones, Van den Berghe, Kosiborod.

Statistical analysis: Gosch, Jones.

Obtained funding: Spertus, Kosiborod.

Administrative, technical, or material support: Spertus, Kosiborod.

Study supervision: Goyal, Kosiborod.

Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Funding/Support: The research for this article was funded by internal funds from Saint Luke's Mid America Heart Institute, Kansas, City, Missouri. The Cerner Corporation facilitated the collection of the deidentified Health Facts data but provided no external funding for this study.

Role of the Sponsors: The Cerner Corporation provided the data but had no role in study funding; conception, design, or conduct of the study; management, analysis, or interpretation of the data; or the preparation, review, or approval of the manuscript.

This article was corrected for wording in figure legends on January 9, 2012.

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Brown MJ, Brown DC, Murphy MB. Hypokalemia from beta2-receptor stimulation by circulating epinephrine.  N Engl J Med. 1983;309(23):1414-1419
PubMed   |  Link to Article
Nordrehaug JE, Johannessen KA, von der Lippe G, Sederholm M, Grøttum P, Kjekshus J. Effect of timolol on changes in serum potassium concentration during acute myocardial infarction.  Br Heart J. 1985;53(4):388-393
PubMed   |  Link to Article
Nordrehaug JE, Johannessen KA, von der Lippe G, Myking OL. Circulating catecholamine and potassium concentrations early in acute myocardial infarction: effect of intervention with timolol.  Am Heart J. 1985;110(5):944-948
PubMed   |  Link to Article
Johansson BW, Dziamski R. Malignant arrhythmias in acute myocardial infarction: relationship to serum potassium and effect of selective and non-selective beta-blockade.  Drugs. 1984;28:(suppl 1)  77-85
PubMed   |  Link to Article
Høfsten DE, Wachtell K, Lund B, Mølgaard H, Egstrup K. Prevalence and prognostic implications of non-sustained ventricular tachycardia in ST-segment elevation myocardial infarction after revascularization with either fibrinolysis or primary angioplasty.  Eur Heart J. 2007;28(4):407-414
PubMed   |  Link to Article
Volpi A, Cavalli A, Santoro E, Tognoni G.GISSI Investigators.  Incidence and prognosis of secondary ventricular fibrillation in acute myocardial infarction: evidence for a protective effect of thrombolytic therapy.  Circulation. 1990;82(4):1279-1288
PubMed   |  Link to Article
Huikuri HV, Tapanainen JM, Lindgren K,  et al.  Prediction of sudden cardiac death after myocardial infarction in the beta-blocking era.  J Am Coll Cardiol. 2003;42(4):652-658
PubMed   |  Link to Article
Gettes LS. Electrolyte abnormalities underlying lethal and ventricular arrhythmias.  Circulation. 1992;85(1):(suppl)  I70-I76
PubMed
Podrid PJ. Potassium and ventricular arrhythmias.  Am J Cardiol. 1990;65(10):33E-44E, discussion 52E
PubMed   |  Link to Article
Hsia DC. Accuracy of Medicare reimbursement for cardiac arrest.  JAMA. 1990;264(1):59-62
PubMed   |  Link to Article
Alper AB, Campbell RC, Anker SD,  et al.  A propensity-matched study of low serum potassium and mortality in older adults with chronic heart failure.  Int J Cardiol. 2009;137(1):1-8
PubMed   |  Link to Article
Bowling CB, Pitt B, Ahmed MI,  et al.  Hypokalemia and outcomes in patients with chronic heart failure and chronic kidney disease: findings from propensity-matched studies.  Circ Heart Fail. 2010;3(2):253-260
PubMed   |  Link to Article
The Digitalis Investigation Group.  The effect of digoxin on mortality and morbidity in patients with heart failure.  N Engl J Med. 1997;336(8):525-533
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Figure 1. Distribution of Serum Potassium Levels at Admission in the Overall Population (N = 38 689)
Graphic Jump Location

Median potassium level at admission was 4.1 mEq/L (vertical dotted line). Each x-axis interval is equal to or greater than the lower limit of the interval and less than the upper limit. The first interval includes all serum potassium levels less than 2.0 mEq/L and the last interval includes all that are 8.0 mEq/L or greater.

Place holder to copy figure label and caption
Figure 2. Trend of Serum Potassium Levels During Hospitalization
Graphic Jump Location

Each data point indicates the median and bars indicate the interquartile range of all potassium levels in the overall population that were measured during a half-day (or 12-hour) time period. On the x-axis, each tick mark corresponds to a half-day period of hospitalization. The numbers of patients for each half-day period are: 0.5 d, 34 921; 1.0 d, 17 480; 1.5 d, 14 169; 2.0 d, 14 208; 2.5 d, 11 496; 3.0 d, 11 276; 3.5 d, 8775; 4.0 d, 8614; 4.5 d, 6839; 5.0 d, 6733; 5.5 d, 5421; 6.0 d, 5425; 6.5 d, 4321; 7.0 d, 4411; 7.5 d, 3573; 8.0 d, 3457; 8.5 d, 2861; 9.0 d, 2847; 9.5 d, 2292; and 10.0 d, 2347.

Place holder to copy figure label and caption
Figure 3. Rates of In-Hospital Mortality and of the Composite of Ventricular Fibrillation or Cardiac Arrest by Mean Postadmission Serum Potassium Level
Graphic Jump Location

Each x-axis interval is equal to or greater than the lower limit of the interval and less than the upper limit. The first interval includes all serum potassium levels less than 3.0 mEq/L; the last interval includes all levels equal to or greater than 5.5 mEq/L. Numbers of events and event rates are listed in Table 2.

Tables

Table Graphic Jump LocationTable 1. Baseline Characteristics By Mean Postadmission Serum Potassium Levela
Table Graphic Jump LocationTable 2. In-Hospital Event Rates and Logistic Regression Models for Mortality, and Separately for Ventricular Fibrillation or Cardiac Arrest, by Mean Postadmission Potassium Level

References

Madias JE, Shah B, Chintalapally G, Chalavarya G, Madias NE. Admission serum potassium in patients with acute myocardial infarction: its correlates and value as a determinant of in-hospital outcome.  Chest. 2000;118(4):904-913
PubMed   |  Link to Article
Nordrehaug JE, Johannessen KA, von der Lippe  G. Serum potassium concentration as a risk factor of ventricular arrhythmias early in acute myocardial infarction.  Circulation. 1985;71(4):645-649
PubMed   |  Link to Article
Friedensohn A, Faibel HE, Bairey O, Goldbourt U, Schlesinger Z. Malignant arrhythmias in relation to values of serum potassium in patients with acute myocardial infarction.  Int J Cardiol. 1991;32(3):331-338
PubMed   |  Link to Article
Kafka H, Langevin L, Armstrong PW. Serum magnesium and potassium in acute myocardial infarction: influence on ventricular arrhythmias.  Arch Intern Med. 1987;147(3):465-469
PubMed   |  Link to Article
Hulting J. In-hospital ventricular fibrillation and its relation to serum potassium.  Acta Med Scand Suppl. 1981;647:109-116
PubMed
Solomon RJ, Cole AG. Importance of potassium in patients with acute myocardial infarction.  Acta Med Scand Suppl. 1981;647:87-93
PubMed
Duke M. Thiazide-induced hypokalemia association with acute myocardial infarction and ventricular fibrillation.  JAMA. 1978;239(1):43-45
PubMed   |  Link to Article
Antman EM, Anbe DT, Armstrong PW,  et al.  ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction). 2004. http://assets.cardiosource.com/STEMI_2004.pdf. Accessed December 15, 2011
Cohn JN, Kowey PR, Whelton PK, Prisant LM. New guidelines for potassium replacement in clinical practice: a contemporary review by the National Council on Potassium in Clinical Practice.  Arch Intern Med. 2000;160(16):2429-2436
PubMed   |  Link to Article
Macdonald JE, Struthers AD. What is the optimal serum potassium level in cardiovascular patients?  J Am Coll Cardiol. 2004;43(2):155-161
PubMed   |  Link to Article
Rogers WJ, Frederick PD, Stoehr E,  et al.  Trends in presenting characteristics and hospital mortality among patients with ST elevation and non-ST elevation myocardial infarction in the National Registry of Myocardial Infarction from 1990 to 2006.  Am Heart J. 2008;156(6):1026-1034
PubMed   |  Link to Article
Kosiborod M, Inzucchi SE, Krumholz HM,  et al.  Glucometrics in patients hospitalized with acute myocardial infarction: defining the optimal outcomes-based measure of risk.  Circulation. 2008;117(8):1018-1027
PubMed   |  Link to Article
Kosiborod M, Inzucchi SE, Goyal A,  et al.  Relationship between spontaneous and iatrogenic hypoglycemia and mortality in patients hospitalized with acute myocardial infarction.  JAMA. 2009;301(15):1556-1564
PubMed   |  Link to Article
Levey AS, Coresh J, Greene T,  et al; Chronic Kidney Disease Epidemiology Collaboration.  Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate.  Ann Intern Med. 2006;145(4):247-254
PubMed   |  Link to Article
Mehta RL, Kellum JA, Shah SV,  et al; Acute Kidney Injury Network.  Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury.  Crit Care. 2007;11(2):R31
PubMed   |  Link to Article
Amin AP, Salisbury AC, McCullough PA,  et al.  Trends in the incidence of acute kidney injury in patients hospitalized with acute myocardial infarction.  Arch Intern Meddoi:10.1001/archinternmed.2011.1202
Nordrehaug JE. Malignant arrhythmia in relation to serum potassium in acute myocardial infarction.  Am J Cardiol. 1985;56(6):20D-23D
PubMed   |  Link to Article
Nordrehaug JE. Hypokalemia, arrhythmias and early prognosis in acute myocardial infarction.  Acta Med Scand. 1985;217(3):299-306
PubMed   |  Link to Article
The Norwegian Multicenter Study Group.  Timolol-induced reduction in mortality and reinfarction in patients surviving acute myocardial infarction.  N Engl J Med. 1981;304(14):801-807
PubMed   |  Link to Article
Beta-Blocker Heart Attack Trial Research Group.  A randomized trial of propranolol in patients with acute myocardial infarction: I, mortality results.  JAMA. 1982;247(12):1707-1714
PubMed   |  Link to Article
Brown MJ, Brown DC, Murphy MB. Hypokalemia from beta2-receptor stimulation by circulating epinephrine.  N Engl J Med. 1983;309(23):1414-1419
PubMed   |  Link to Article
Nordrehaug JE, Johannessen KA, von der Lippe G, Sederholm M, Grøttum P, Kjekshus J. Effect of timolol on changes in serum potassium concentration during acute myocardial infarction.  Br Heart J. 1985;53(4):388-393
PubMed   |  Link to Article
Nordrehaug JE, Johannessen KA, von der Lippe G, Myking OL. Circulating catecholamine and potassium concentrations early in acute myocardial infarction: effect of intervention with timolol.  Am Heart J. 1985;110(5):944-948
PubMed   |  Link to Article
Johansson BW, Dziamski R. Malignant arrhythmias in acute myocardial infarction: relationship to serum potassium and effect of selective and non-selective beta-blockade.  Drugs. 1984;28:(suppl 1)  77-85
PubMed   |  Link to Article
Høfsten DE, Wachtell K, Lund B, Mølgaard H, Egstrup K. Prevalence and prognostic implications of non-sustained ventricular tachycardia in ST-segment elevation myocardial infarction after revascularization with either fibrinolysis or primary angioplasty.  Eur Heart J. 2007;28(4):407-414
PubMed   |  Link to Article
Volpi A, Cavalli A, Santoro E, Tognoni G.GISSI Investigators.  Incidence and prognosis of secondary ventricular fibrillation in acute myocardial infarction: evidence for a protective effect of thrombolytic therapy.  Circulation. 1990;82(4):1279-1288
PubMed   |  Link to Article
Huikuri HV, Tapanainen JM, Lindgren K,  et al.  Prediction of sudden cardiac death after myocardial infarction in the beta-blocking era.  J Am Coll Cardiol. 2003;42(4):652-658
PubMed   |  Link to Article
Gettes LS. Electrolyte abnormalities underlying lethal and ventricular arrhythmias.  Circulation. 1992;85(1):(suppl)  I70-I76
PubMed
Podrid PJ. Potassium and ventricular arrhythmias.  Am J Cardiol. 1990;65(10):33E-44E, discussion 52E
PubMed   |  Link to Article
Hsia DC. Accuracy of Medicare reimbursement for cardiac arrest.  JAMA. 1990;264(1):59-62
PubMed   |  Link to Article
Alper AB, Campbell RC, Anker SD,  et al.  A propensity-matched study of low serum potassium and mortality in older adults with chronic heart failure.  Int J Cardiol. 2009;137(1):1-8
PubMed   |  Link to Article
Bowling CB, Pitt B, Ahmed MI,  et al.  Hypokalemia and outcomes in patients with chronic heart failure and chronic kidney disease: findings from propensity-matched studies.  Circ Heart Fail. 2010;3(2):253-260
PubMed   |  Link to Article
The Digitalis Investigation Group.  The effect of digoxin on mortality and morbidity in patients with heart failure.  N Engl J Med. 1997;336(8):525-533
PubMed   |  Link to Article

Letters

April 18, 2012
Andreas Perren, MD; Marco Previsdomini, MD; Karim Bendjelid, MD, PhD
JAMA. 2012;307(15):1578-1580. doi:10.1001/jama.2012.485.
April 18, 2012
R. Brooks Robey, MD
JAMA. 2012;307(15):1578-1580. doi:10.1001/jama.2012.486.
April 18, 2012
Abhinav Goyal, MD, MHS; John A. Spertus, MD, MPH; Mikhail Kosiborod, MD
JAMA. 2012;307(15):1578-1580. doi:10.1001/jama.2012.487.
April 18, 2012
Benjamin M. Scirica, MD, MPH; David A. Morrow, MD, MPH
JAMA. 2012;307(15):1578-1580. doi:10.1001/jama.2012.488.
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