Incidence of Primary Aldosteronism in Patients with Hypokalemia (IPAHK+): Study Design and Baseline Characteristics.

Hypokalemia plays a central role for case finding, course, treatment decision, and prognosis of patients with primary aldosteronism. However, to date there is a lack of high-level evidence about the incidence of primary aldosteronism in hypokalemic patients. The IPAHK+study is an epidemiological, cross-sectional, monocentric study to provide evidence on the incidence of PA in a hypokalemic population. The aim of the current analysis was to describe the baseline characteristics of the first 100 patients eligible for study inclusion. The recruitment of patients with hypokalemia (≤3 mmol/l) is carried out continuously on a referral-basis by the central laboratory of the University Hospital Zurich through an automated suitability testing and data delivery system. The careful evaluation of the first 100 reported patients was based on the available reporting system. Out of 28 140 screened patients, 222 (0.79%) were identified with a serum potassium value of≤3 mmol/l (mean 2.89±0.02 mmol/l). Mean potassium levels were slightly lower in non-hypertensive subjects compared to hypertensive subjects (mean difference 0.07 mmol/l, p=0.033), while no significant difference was found between the sexes and patients with and without the diagnosis of primary aldosteronism, atrial fibrillation, or the use of diuretics. The incidence of PA was 4% in the total population studied and 7.5% in the subgroup of hypertensive patients. In conclusion, the continuous enrollment of patients from the IPHAK+hypokalemia registry into the IPAHK+trial will provide evidence about the actual incidence of primary aldosteronism in a hypokalemic outpatient population.

Association between serum potassium levels and adverse outcomes in chronic kidney disease: the Fukushima CKD cohort study.

BACKGROUND: Serum potassium disorders, commonly observed in chronic kidney disease (CKD), are reportedly associated with higher mortality, but their impact on renal outcomes is still controversial. METHODS: The present study used the longitudinal data of the Fukushima CKD cohort study to investigate the relationships between hypokalemia and hyperkalemia and adverse outcomes such as renal outcomes and all-cause mortality in Japanese patients with non-dialysis-dependent CKD. The study involved 1330 CKD patients followed-up for 2.8 years. The primary endpoint of the present study was a kidney event, defined as a combination of doubling of baseline serum creatinine and end-stage kidney disease. RESULTS: Hyperkalemia (≥ 5.0 mmol/L) was noted in 10.6% and hypokalemia (< 4.0 mmol/L) in 16.4% of the study population. Significant U-shaped associations were observed between potassium levels and both kidney events and all-cause mortality on univariate Cox regression analyses. After adjustment for covariates, both hypokalemia and hyperkalemia were significantly associated with an increased risk of kidney events, with the lowest risk at a serum potassium of 4.0-4.4 mmol/L. Compared with a reference level of 4.0-4.4 mmol/L, the adjusted hazard ratio for kidney events was 2.49 (1.33-4.66) for serum potassium < 4.0 mmol/L, 1.72 (1.00-2.96) for 4.5-4.9 mmol/L, and 2.16 (1.15-4.06) for ≥ 5.0 mmol/L. There was no significant association between serum potassium levels and mortality after multivariate adjustment. CONCLUSION: Hypokalemia and hyperkalemia were associated with an increased risk of CKD progression, but not with mortality in Japanese patients with non-dialysis-dependent CKD.

Acute and Life-threatening Complications in Cushing Syndrome: Prevalence, Predictors, and Mortality.

CONTEXT: Cushing syndrome (CS) results in significant morbidity and mortality. OBJECTIVE: To study acute and life-threatening complications in patients with active CS. METHODS: We performed a retrospective cohort study using inpatient and outpatient records of patients with CS in a tertiary center. A total of 242 patients with CS were included, including 213 with benign CS (pituitary n = 101, adrenal n = 99, ectopic n = 13), and 29 with malignant disease. We collected acute complications necessitating hospitalization, from appearance of first symptoms of hypercortisolism until 1 year after biochemical remission. Mortality data were obtained from the national registry. Baseline factors relating to and predicting acute complications were tested using uni- and multivariate analysis. RESULTS: The prevalence of acute complications was 62% in patients with benign pituitary CS, 40% in patients with benign adrenal CS, and 100% in patients with ectopic CS. Complications observed in patients with benign CS included infections (25%), thromboembolic events (17%), hypokalemia (13%), hypertensive crises (9%), cardiac arrhythmias (5%), and acute coronary events (3%). Among these patients, 23% had already been hospitalized for acute complications before CS was suspected, and half of complications occurred after the first surgery. Glycated hemoglobin (HbA1c) and 24-hour urinary free cortisol positively correlated with the number of acute complications per patient. Patients with malignant disease had significantly higher rates of acute complications. Mortality during the observation period was 2.8% and 59% in benign and malignant CS, respectively. CONCLUSIONS: This analysis highlights the whole spectrum of acute and life-threatening complications in CS, and their high prevalence even before disease diagnosis and after successful surgery.

Hypokalemia is frequent and has prognostic implications in stable patients attending the emergency department.

BACKGROUND: Potassium disturbances are associated with adverse prognosis in patients with chronic conditions. Its prognostic implications in stable patients attending the emergency department (ED) is poorly described. AIMS: This study aimed to assess the prevalence of dyskalemia, describe its predisposing factors and prognostic associations in a population presenting the ED without unstable medical illness. METHODS: Post-hoc analysis of a prospective, cross-sectional, multicenter study in the ED of 11 French academic hospitals over a period of 8 weeks. All adults presenting to the ED during this period were included, except instances of self-drug poisoning, inability to complete self-medication questionnaire, presence of an unstable medical illness and decline to participate in the study. All-cause hospitalization or deaths were assessed. RESULTS: A total of 1242 patients were included. The mean age was 57.2±22.3 years, 51% were female. The distribution according to potassium concentrations was: hypokalemia<4mmol/L(n = 620, 49.9%), normokalemia 4-5mmol/L(n = 549, 44.2%) and hyperkalemia >5mmol/L(n = 73, 0,6%). The proportion of patients with a kalemia<3.5mmol/L was 8% (n = 101). Renal insufficiency (OR [95% CI] = 3.56[1.94-6.52], p-value <0.001) and hemoglobin <12g/dl (OR [95% CI] = 2.62[1.50-4.60], p-value = 0.001) were associated with hyperkalemia. Female sex (OR [95% CI] = 1.31[1.03-1.66], p-value = 0.029), age <45years (OR [95% CI] = 1.69 [1.20-2.37], p-value = 0.002) and the use of thiazide diuretics (OR [95% CI] = 2.04 [1.28-3.32], p-value = 0.003), were associated with hypokalemia<4mmol/l. Two patients died in the ED and 629 (52.7%) were hospitalized. Hypokalemia <3.5mmol/L was independently associated with increased odds of hospitalization or death (OR [95% CI] = 1.47 [1.00-2.15], p-value = 0.048). CONCLUSIONS: Hypokalemia is frequently found in the ED and was associated with worse outcomes in a low-risk ED population.

Impact of plasma potassium normalization on short-term mortality in patients with hypertension and hypokalemia or low normal potassium.

BACKGROUND: Hypokalemia is common in patients treated with antihypertensive drugs, but the impact of correcting hypokalemia is insufficiently studied. We examined the consequences of hypokalemia and borderline hypokalemia correction in patients with hypertension. METHODS: We identified 8976 patients with hypertension and plasma potassium concentrations ≤3.7 mmol/L within 100 days from combination antihypertensive therapy initiation. The first measurement between 6 and 100 days after the episode with potassium ≤3.7 mmol/L was retained. We investigated all-cause and cardiovascular mortality within 60-days from the second potassium measurement using Cox regression. Mortality was examined for seven predefined potassium intervals derived from the second measurement: 1.5-2.9 mmol/L (n = 271), 3.0-3.4 mmol/L (n = 1341), 3.5-3.7 (n = 1982) mmol/L, 3.8-4.0 mmol/L (n = 2398, reference), 4.1-4.6 mmol/L (n = 2498), 4.7-5.0 mmol/L (n = 352) and 5.1-7.1 mmol/L (n = 134). RESULTS: Multivariable analysis showed that potassium concentrations 1.5-2.9 mmol/L, 3.0-3.4 mmol/L, 4.7-5.0 mmol/L and 5.1-7.1 mmol/L were associated with increased all-cause mortality (HR 2.39, 95% CI 1.66-3.43; HR 1.36, 95% CI 1.04-1.78; HR 2.36, 95% CI 1.68-3.30 and HR 2.62, 95% CI 1.73-3.98, respectively). Potassium levels <3.0 and > 4.6 mmol/L were associated with increased cardiovascular mortality. The adjusted standardized 60-day mortality risks in the seven strata were: 11.7% (95% CI 8.3-15.0%), 7.1% (95% CI 5.8-8.5%), 6.4% (95% CI 5.3-7.5%), 5.4% (4.5-6.3%), 6.3% (5.4-7.2%), 11.6% (95% CI 8.7-14.6%) and 12.6% (95% CI 8.2-16.9%), respectively. CONCLUSIONS: Persistent hypokalemia was frequent and associated with increased all-cause and cardiovascular mortality. Increase in potassium to levels > 4.6 mmol/L in patients with initial hypokalemia or low normal potassium was associated with increased all-cause and cardiovascular mortality.

Serum Potassium Levels at Hospital Discharge and One-Year Mortality among Hospitalized Patients.

Background and Objectives: The optimal range of serum potassium at hospital discharge is unclear. The aim of this study was to assess the relationship between discharge serum potassium levels and one-year mortality in hospitalized patients. Materials and Methods: All adult hospital survivors between 2011 and 2013 at a tertiary referral hospital, who had available admission and discharge serum potassium data, were enrolled. End-stage kidney disease patients were excluded. Discharge serum potassium was defined as the last serum potassium level measured within 48 hours prior to hospital discharge and categorized into ≤ 2.9, 3.0-3.4, 3.5-3.9, 4.0-4.4, 4.5-4.9, 5.0-5.4 and ≥ 5.5 mEq/L. A Cox proportional hazards analysis was performed to assess the independent association between discharge serum potassium and one-year mortality after hospital discharge, using the discharge potassium range of 4.0-4.4 mEq/L as the reference group. Results: Of 57,874 eligible patients, with a mean discharge serum potassium of 4.1 ± 0.4 mEq/L, the estimated one-year mortality rate after discharge was 13.2%. A U-shaped association was observed between discharge serum potassium and one-year mortality, with the nadir mortality in the discharge serum potassium range of 4.0-4.4 mEq/L. After adjusting for clinical characteristics, including admission serum potassium, both discharge serum potassium ≤ 3.9 mEq/L and ≥ 4.5 mEq/L were significantly associated with increased one-year mortality, compared with the discharge serum potassium of 4.0-4.4 mEq/L. Stratified analysis based on admission serum potassium showed similar results, except that there was no increased risk of one-year mortality when discharge serum potassium was ≤ 3.9 mEq/L in patients with an admission serum potassium of ≥ 5.0 mEq/L. Conclusion: The association between discharge serum potassium and one-year mortality after hospital discharge had a U-shaped distribution and was independent of admission serum potassium. Favorable survival outcomes occurred when discharge serum potassium was strictly within the range of 4.0-4.4 mEq/L.

Association between serum potassium levels and short-term mortality in patients with atrial fibrillation or flutter co-treated with diuretics and rate- or rhythm-controlling drugs.

AIMS: We investigated the association between potassium levels and 90-day all-cause mortality in atrial fibrillation or flutter (AF) patients co-treated with diuretics and rate- or rhythm-controlling drugs. METHODS AND RESULTS: During 2000-12, first-time AF patients treated with beta-blockers, amiodarone, sotalol, verapamil, or digoxin combined with any diuretic within 90 days post-AF discharge were included. Following co-treatment, a potassium measurement within 90 days after initiating diuretic treatment was required. Mortality risk associated with potassium <3.5, 3.5-3.7, 3.8-4.0, 4.5-4.7, 4.8-5.0, and >5.0 mmol/L (reference: 4.1-4.4 mmol/L) was assessed using multivariable Cox regression. In total, 14 425 AF patients were included (median age: 78 years; women: 52%). Patients most often received beta-blocker monotherapy (29%), beta-blockers and digoxin combined (25%), digoxin monotherapy (24%), amiodarone monotherapy (3%), and verapamil monotherapy (3%). Increased 90-day mortality risk was associated with <3.5 mmol/L [hazard ratio (HR) 2.05, 95% confidence interval (CI) 1.68-2.50], 3.5-3.7 mmol/L (HR 1.28, 95% CI 1.05-1.57), 4.5-4.7 mmol/L (HR 1.20, 95% CI 1.02-1.41), 4.8-5.0 mmol/L (HR 1.37, 95% CI 1.14-1.66), and >5.0 mmol/L: (HR 1.84, 95% CI 1.53-2.21). Compared with beta-blocker monotherapy, rate- or rhythm-controlling drugs did not modify the association between potassium groups and mortality risk. CONCLUSION: In addition to hypo- and hyperkalaemia, low and high normal range potassium levels were associated with increased 90-day mortality risk in AF patients co-treated with diuretics and rate- or rhythm-controlling drugs. These associations were independent of rate- or rhythm-controlling drugs.

Racial and Ethnic Differences in Mortality Associated with Serum Potassium in Incident Peritoneal Dialysis Patients.

BACKGROUND: Abnormalities in serum potassium are risk factors for sudden cardiac death and arrhythmias among dialysis patients. Although a previous study in hemodialysis patients has shown that race/ethnicity may impact the relationship between serum potassium and mortality, the relationship remains unclear among peritoneal dialysis (PD) patients where the dynamics of serum potassium is more stable. METHODS: Among 17,664 patients who started PD between January 1, 2007 and December 31, 2011 in a large US dialysis organization, we evaluated the association of serum potassium levels with all-cause and arrhythmia-related deaths across race/ethnicity using time-dependent Cox models with adjustments for demographics. We also used restricted cubic spline functions for serum potassium levels to explore non-linear associations. RESULTS: Baseline serum potassium levels were the highest among Hispanics (4.2 ± 0.7 mEq/L) and lowest among non-Hispanic blacks (4.0 ± 0.7 mEq/L). Among 2,949 deaths during the follow-up of median 2.2 (interquartile ranges 1.3-3.2) years, 683 (23%) were arrhythmia-related deaths. Overall, both hyperkalemia and hypokalemia (i.e., serum potassium levels >5.0 and <3.5 mEq/L, respectively) were associated with higher all-cause and arrhythmia-related mortality. In a stratified analysis according to race/ethnicity, the association of hypokalemia with all-cause and arrhythmia-related mortality was consistent with an attenuation for arrhythmia-related mortality in non-Hispanic blacks. Hyperkalemia was associated with all-cause and arrhythmia-related mortality in non-Hispanic whites and non-Hispanic blacks, but no association was observed in Hispanics. CONCLUSION: Among incident PD patients, hypokalemia was consistently associated with all-cause and arrhythmia-related deaths irrespective of race/ethnicity. However, while hyperkalemia was associated with both death outcomes in non-Hispanic blacks and whites, it was not associated with either death outcome in Hispanic patients. Further studies are needed to demonstrate whether different strategies should be followed for the management of serum potassium levels according to race/ethnicity.

Admission serum sodium and potassium levels predict survival among critically ill patients with acute kidney injury: a cohort study.

BACKGROUND: Patients suffering from acute kidney injury (AKI) were associated with impaired sodium and potassium homeostasis. We aimed to investigate how admission serum sodium and potassium independently and jointly modified adverse clinical outcomes among AKI patients. METHODS: Patient data were extracted from the Multiparameter Intelligent Monitoring in Intensive Care Database III. Participants were categorized into three groups according to admission serum sodium and potassium, and the cut-off values were determined using smooth curve fitting. The primary outcome was 90-day mortality in the intensive care unit (ICU). Cox proportional hazards models were used to evaluate the prognostic effects of admission serum sodium and potassium levels. RESULTS: We included 13,621 ICU patients with AKI (mean age: 65.3 years; males: 55.4%). The middle category of admission serum sodium and potassium levels were 136.0-144.9 mmol/L and 3.7-4.7 mmol/L through fitting smooth curve. In multivariable Cox models, compared with the middle category, patients with hyponatremia or hypernatremia were associated with excess mortality and the HRs and its 95%CIs were 1.38 (1.27, 1.50) and 1.56 (1.36, 1.79), and patients with either hypokalemia or hyperkalemia were associated with excess mortality and the hazard ratios (HRs) and its 95% confidential intervals (95% CIs) were 1.12 (1.02, 1.24) and 1.25 (1.14, 1.36), respectively. Significant interactions were observed between admission serum sodium and potassium levels (P interaction = 0.001), with a higher serum potassium level associated with increased risk of 90-day mortality among patients with hyponatremia, whereas the effects of higher sodium level on prognostic effects of potassium were subtle. CONCLUSIONS: Admission serum sodium and potassium were associated with survival in a U-shaped pattern among patients with AKI, and hyperkalemia predict a worse clinical outcome among patients with hyponatremia.

Long QT and death in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease is not related to electrolyte disorders.

Objectives: COPD is the fourth-leading cause of mortality worldwide. Prolonged QTc has been found to be a long-term negative prognostic factor in ambulatory COPD patients. The aim of this study was to evaluate the extent of prolonged-QTc syndrome in COPD patients upon admission to an internal medicine department, its relationship to hypomagnesemia, hypokalemia, and hypocalcemia, and the effect of COPD treatment on mortality during hospital stay. Methods: This prospective cohort study evaluated COPD patients hospitalized in an internal medicine department. The study evaluated QTc, electrolyte levels, and known risk factors during hospitalization of COPD patients. Results: A total of 67 patients were recruited. The median QTc interval was 0.441 seconds and 0.434 seconds on days 0 and 3, respectively. Prolonged QTc was noted in 35.8% of patients on admission and 37.3% on day 3 of hospitalization. The median QTc in the prolonged-QTc group on admission was 0.471 seconds and in the normal-QTc group 0.430 seconds. There was no significant difference in age, sex, electrolyte levels, renal function tests, or blood gases on admission between the two groups. Mortality during the hospital stay was significantly higher in the prolonged-QTc group (3 deaths, 12%) than in the normal QTc group (no deaths) (P=0.04). A subanalysis was performed, removing known causes for prolonged QTc. We found no differences in age, electrolytes, or renal functions. There was a small but significant difference in bicarbonate levels. Conclusion: Our findings demonstrated that there was no correlation between QTc prolongation in hospitalized COPD patients and electrolyte levels, comorbidities, or relevant medications. A higher rate of mortality was noted in patients with prolonged QTc in comparison to normal QTc. As such, it is suggested that prolonged QTc could serve as a negative prognostic factor for mortality during hospitalization in COPD patients.

Serum potassium levels and mortality of patients with acute myocardial infarction: A systematic review and meta-analysis of cohort studies.

BACKGROUND: The evidence of current epidemiological studies investigating the association between serum potassium levels and mortality of acute myocardial infarction (AMI) patients is controversial and inadequate. DESIGN: Systematic review and meta-analysis. METHODS: Two researchers independently searched the PubMed, EMBASE and Web of Science databases to identify observational studies published prior to 31 October 2017. Similarly, two researchers separately extracted data and any differences were resolved by discussion. Pooled relative risks and 95% confidence intervals (CIs) were computed with an inverse variance-weighted random-effects model. Heterogeneity among studies was assessed with the I2 statistic. RESULTS: Seven cohort studies were included for analysis. Compared with the reference group (3.5 to <4.0 mEq/L), the pooled relative risks of mortality were 1.15 (95% CI = 1.00-1.32), 1.09 (95% CI = 0.97-1.24), 1.42 (95% CI = 1.19-1.70) and 1.85 (95% CI = 1.39-2.47) for AMI patients with a potassium level of<3.5, 4.0 to <4.5, 4.5 to <5.0, and ≥5.0 mEq/L, respectively. For admission and post-admission potassium, although J-shaped associations were also indicated, non-significant results were observed for AMI patients with potassium levels of <3.5 mEq/L when compared with the reference group. Notably, in subgroup analyses of study characteristics, stratified by study quality, geographic location, type of outcome, number of cases, type of AMI, and adjustment for potential confounders, the findings were broadly consistent across strata. CONCLUSIONS: These findings indicate that both lower (<3.5 mEq/L) and higher (≥4.5 mEq/L) serum potassium levels are associated with an increased risk of mortality of patients with AMI.

Serum electrolyte imbalance and prognostic factors of postoperative death in adult traumatic brain injury patients: A prospective cohort study.

Electrolyte imbalances are common in traumatic brain injury. It shares the cause of perioperative morbidity and mortality. Types of intravenous fluid resuscitation, osmotic diuretics, massive blood loss, and intracranial pathology were considered as the potential factors to worsen electrolyte abnormalities in these patients. The aims of this study were to report the incidence of electrolyte imbalance in traumatic brain injured patients and to assess the association between electrolyte imbalance and other prognostic factors to death within 24 hours of the injury.The study was carried out in the northern university, tertiary-care hospital of Thailand. The patients aged from 18 to 65 years old, presented with traumatic brain injury, and needed for emergency craniotomy were included. We excluded the patients who had minor neurosurgical procedures, pregnancy, and undergone cardiopulmonary resuscitation from the Emergency Department.Among 145 patients recruited, 101 (70%) had Glasgow Coma Scale (GCS) score ≤ 8, 25 (17%) had GCS score 9 to 12, and 19 (13%) had GCS score 13 to 15. The most common diagnosis were subdural hematoma and epidural hematoma, 51% and 36%, respectively. Hypokalemia was the most common electrolyte imbalance at 65.5%. The results of the use of a multivariable logistic regression model show that the odds of postoperative death in TBI patients were increased with high levels of blood glucose, hypernatremia, and acidosis.Hypokalemia was the most common electrolyte imbalance in TBI patients. Hypernatremia, acidosis, and hyperglycemia significantly increased the odds ratio of death in the first 24 hours post TBI.

Serum Potassium and Cardiovascular Events in Heart Failure With Preserved Left Ventricular Ejection Fraction Patients.

BACKGROUND: Although serum potassium (sK) levels are closely associated with the prognosis of chronic heart failure patients, the clinical significance of sK levels in cardiovascular outcomes of heart failure with preserved ejection fraction (HFpEF) patients is not fully understood. METHODS: This study was a retrospective, single-center, observational study. We enrolled 506 consecutive HFpEF patients admitted to Kumamoto University Hospital and divided them into four groups according to the quartiles of the sK levels at discharge (Q1: sK < 4.1 mEq/l, Q2: 4.1 ≤ sK < 4.4 mEq/l, Q3: 4.4 ≤ sK < 4.7 mEq/l, and Q4: sK ≥ 4.7 mEq/l). RESULTS: No significant differences were observed in the use of all drugs (loop diuretics, mineralocorticoid receptor antagonists, renin-angiotensin-aldosterone system inhibitors, calcium channel blockers, ß-blockers, and statins) among the four groups. Hemoglobin, the estimated glomerular filtration rate, and pulse wave velocity levels were lower, and the serum sodium levels were higher in the Q4 group compared with those in the Q2 group. Kaplan-Meier analysis revealed significantly higher probabilities of both cardiovascular and HF-related events in the Q1, Q3, and Q4 groups than those in the Q2 group. Multivariate Cox proportional hazard analysis revealed that the Q1, Q3, and Q4 groups had significantly and independently higher probabilities of cardiovascular events compared with those in the Q2 group, indicating a J-shaped association between sK levels and cardiovascular events. CONCLUSIONS: sK levels at discharge could provide important prognostic information in regard to HFpEF. Further evaluation in a larger number of patients might be needed. Clinical Trials Registration: UMIN-CTR (http://www.umin.ac.jp/ctr/). Identifier: UMIN000029600. Public Access Information: Opt-out materials are available at the website: http://www.kumadai-junnai.com/home/wp-content/uploads/houkatsu.pdf.

Association of Abnormal Serum Potassium Levels with Arrhythmias and Cardiovascular Mortality: a Systematic Review and Meta-Analysis of Observational Studies.

PURPOSE: To provide the first systematic review and meta-analysis of observational studies on the association of abnormal serum potassium and cardiovascular outcomes. METHODS: Medline and ISI Web of Knowledge were systematically searched from inception until November 24, 2017. Data synthesis of relevant studies was performed using random effects model meta-analyses. RESULTS: Meta-analyses included 310,825 participants from 24 studies. In the older general population, low serum potassium was associated with a 1.6-fold increased risk of supraventricular arrhythmias (risk ratio [95% confidence interval] 1.62 [1.02-2.55]). Contrarily, high serum potassium was associated with increased cardiovascular mortality (CVM) (1.38 [1.14-1.66]). In patients with acute myocardial infarction, the risk of ventricular arrhythmias was increased for high serum potassium (2.33 [1.60-3.38]). A U-shaped association was observed with a composite cardiovascular outcome in hypertensive patients (2.6-fold increased risk with hypokalemia and 1.7-fold increased risk with hyperkalemia), with CVM in dialysis patients (1.1-fold increased risk with hypokalemia and 1.4-fold increased risk with hyperkalemia) and with CVM in heart failure patients (albeit not statistically significant). Further, only hyperkalemia was associated with an increased risk of a composite cardiovascular outcome in both dialysis (1.12 [1.03-1.23]) and chronic kidney disease (1.34 [1.06-1.71]) patients. CONCLUSIONS: Controlled clinical trials are needed to determine which populations may profit from more frequent potassium-monitoring and subsequent interventions, e.g., change or withdrawal of potassium-influencing drugs, in order to restore normal values and prevent cardiovascular outcomes. REGISTRATION DETAILS: Registration in PROSPERO (Centre for Reviews and Dissemination University of York, York, UK): CRD42016048897 ( https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=48897 ).

Association between hypo- and hyperkalemia and outcome in acute heart failure patients: the role of medications.

BACKGROUND: The interaction between chronic medications on admission and the association between serum potassium level and outcome in patients with acute heart failure (AHF) are unknown. METHODS: Observational intercontinental study of patients admitted with AHF. 15954 patients were included from 12 cohorts in 4 continents. Main outcome was 90-day mortality. Clinical presentation (medication use, hemodynamics, comorbidities), demographic, echocardiographic, and biochemical data on admission were recorded prospectively in each cohort, with prospective adjudication of outcomes. RESULTS: Positive and negative linear relationships between 90-day mortality and sK+ above 4.5 mmol/L (hyperkalemia) and below 3.5 mmol/L (hypo-kalemia) were observed. Hazard ratio for death was 1.46 [1.34-1.58] for hyperkalemia and 1.22 [1.06-1.40] for hypokalemia. In a fully adjusted model, only hyperkalemia remained associated with mortality (HR 1.03 [1.02-1.04] for each 0.1 mmol/l change of sK+ above 4.5 mmol/L). Interaction tests revealed that the association between hyperkalemia and outcome was significantly affected by chronic medications. The association between hyperkalemia and mortality was absent for patients treated with beta blockers and in those with preserved renal function. CONCLUSIONS: In patients with AHF, sK+ > 4.5 mmol/L appears to be associated with 90-day mortality. B-blockers have potentially a protective effect in the setting of hyperkalemia.

Prognostic Impact of Mild Hypokalemia in Terms of Death and Stroke in the General Population-A Prospective Population Study.

BACKGROUND: Potassium supplementation reduces the risk of cardiovascular mortality and stroke in population studies; however, the prognostic impact of mild hypokalemia in the general population has not been thoroughly investigated. We aimed to investigate associations between mild hypokalemia and endpoints in the general population. METHODS: Participants (aged 48-76 years) from the general population study "Copenhagen City Heart Study" (n = 5916) were studied. Participants were divided into groups according to baseline values of plasma potassium (potassium): hypokalemia (<3.7 mmol/L, n = 758), normokalemia (3.7-4.5 mmol/L, n = 4973), and high potassium (>4.5 mmol/L, n = 185). Hypokalemia was further divided as potassium <3.4 mmol/L and 3.4-3.6 mmol/L. The primary endpoints were all-cause mortality and nonfatal validated ischemic stroke. The secondary endpoint was acute myocardial infarction (AMI). We adjusted for conventional risk factors, diuretics, and atrial fibrillation at baseline. RESULTS: Mean potassium in the hypokalemic group was 3.5 mmol/L (range, 2.6-3.6 mmol/L) and was associated (P < 0.05) with increased systolic blood pressure, higher CHA2DS2-VASc score, and increased use of diuretics as compared with normokalemia. Baseline atrial fibrillation was equally frequent across groups. Median follow-up-time was 11.9 years (Q1-Q3: 11.4-12.5 years). Hypokalemia was borderline associated with increased stroke risk in a multivariable Cox model (including adjustment for competing risk) as compared with normokalemia (hazard ratio [HR] 1.40; 95% confidence interval [CI], 1.00-1.98). The subgroup with potassium <3.4 mmol/L had higher stroke risk (HR 2.10; 95% CI, 1.19-3.73) and mortality risk (HR 1.32; 95% CI, 1.01-1.74) as compared with normokalemia. Hypokalemia was not associated with AMI, and no increased risk of mortality was seen with concomitant AMI and hypokalemia. No associations were seen with high potassium. CONCLUSION: In a general population mild hypokalemia is associated with increased stroke risk and, to a lesser degree, increased mortality risk.

Associations of serum potassium levels with mortality in chronic heart failure patients.

AIMS: Medication prescribed to patients suffering from chronic heart failure carries an increased risk of impaired potassium homeostasis. We examined the relation between different levels of serum potassium and mortality among patients with chronic heart failure. METHODS AND RESULTS: From Danish National registries, we identified 19 549 patients with a chronic heart failure diagnosis who had a measurement of potassium within minimum 90 days after initiated medical treatment with loop diuretics and angiotensin converting enzyme inhibitors or angiotensin-II receptor blockers. All-cause mortality was examined according to eight predefined potassium levels: 2.8-3.4 mmol/L, 3.5-3.8 mmol/L, 3.9-4.1 mmol/L, 4.2-4.4 mmol/L, 4.5-4.7 mmol/L, 4.8-5.0 mmol/L, 5.1-5.5 mmol/L, and 5.6-7.4 mmol/L. Follow-up was 90 days from potassium measurement. We estimated the risk of all-cause mortality using multivariable adjusted Cox proportional hazard model, with normal serum potassium level at 4.2-4.4 mmol/L as reference. After 90 days, the mortality in the eight strata was 14.4, 8.0, 6.3, 5.0, 5.8, 7.9, 10.3, and 21.1% respectively. In multivariable adjusted analysis, patients with potassium levels of 2.8-3.4 mmol/L [hazard ratio (HR): 3.16; confidence interval (CI): 2.43-4.11], 3.5-3.8 mmol/L (HR: 1.62; CI: 1.31-1.99), 3.9-4.1 mmol/L (HR: 1.29; CI: 1.08-1.55), 4.8-5.0 mmol/L (HR: 1.34; CI: 1.10-1.63), 5.1-5.5 mmol/L (HR: 1.60; CI: 1.29-1.97), and 5.6-7.4 mmol/L (HR: 3.31; CI: 2.61-4.20) had an increased risk of all-cause mortality. CONCLUSION: Levels within the lower and upper levels of the normal serum potassium range (3.5-4.1 mmol/L and 4.8-5.0 mmol/L, respectively) were associated with a significant increased short-term risk of death in chronic heart failure patients. Likewise, potassium below 3.5 mmol/L and above 5.0 mmol/L was also associated with increased mortality.

Association of Serum Potassium with All-Cause Mortality in Patients with and without Heart Failure, Chronic Kidney Disease, and/or Diabetes.

BACKGROUND: The relationship between serum potassium, mortality, and conditions commonly associated with dyskalemias, such as heart failure (HF), chronic kidney disease (CKD), and/or diabetes mellitus (DM) is largely unknown. METHODS: We reviewed electronic medical record data from a geographically diverse population (n = 911,698) receiving medical care, determined the distribution of serum potassium, and the relationship between an index potassium value and mortality over an 18-month period in those with and without HF, CKD, and/or DM. We examined the association between all-cause mortality and potassium using a cubic spline regression analysis in the total population, a control group, and in HF, CKD, DM, and a combined cohort. RESULTS: 27.6% had a potassium <4.0 mEq/L, and 5.7% had a value ≥5.0 mEq/L. A U-shaped association was noted between serum potassium and mortality in all groups, with lowest all-cause mortality in controls with potassium values between 4.0 and <5.0 mEq/L. All-cause mortality rates per index potassium between 2.5 and 8.0 mEq/L were consistently greater with HF 22%, CKD 16.6%, and DM 6.6% vs. controls 1.2%, and highest in the combined cohort 29.7%. Higher mortality rates were noted in those aged ≥65 vs. 50-64 years. In an adjusted model, all-cause mortality was significantly elevated for every 0.1 mEq/L change in potassium <4.0 mEq/L and ≥5.0 mEq/L. Diuretics and renin-angiotensin-aldosterone system inhibitors were related to hypokalemia and hyperkalemia respectively. CONCLUSION: Mortality risk progressively increased with dyskalemia and was differentially greater in those with HF, CKD, or DM.

Admission serum potassium concentration and long-term mortality in patients with acute myocardial infarction: results from the MONICA/KORA myocardial infarction registry.

BACKGROUND: Conflicting with clinical practice guidelines, recent studies demonstrated that serum potassium concentrations (SPC) of ≥4.5 mEq/l were associated with increased mortality in patients with acute myocardial infarction (AMI). This study examined the association between SPC and long-term mortality following AMI in patients recruited from a population-based registry. METHODS: Included in the study were 3347 patients with AMI aged 28-74 years consecutively hospitalized between 1 January 2000 and 31 December 2008 and followed up until 31 December 2011. Patients were categorized into five SPC groups (<3.5, 3.5 to <4.0, 4.0 to <4.5, 4.5 to <5.0, and ≥5.0 mEq/l). The outcome of the study was all-cause mortality. Cox regression models adjusted for risk factors, co-morbidities and in-hospital treatment were constructed. RESULTS: In our study population, 249 patients (7.4%) had a low SPC (<3.5 mEq/l) and 134 (4.0%) patients had a high SPC (≥5.0 mEq/l). Patients with SPC of ≥5.0 mEq/l had the highest long-term mortality (29.9%) and in the adjusted model, their risk of dying was significantly increased (HR 1.46, 95% CI 1.03 to 2.07) compared to patients with SPC between 4.0 and <4.5 mEq/l. Analyses of increasing observation periods showed a trend towards a higher risk of dying in patients with SPC between 4.5 and <5.0 mEq/l. CONCLUSION: An admission SPC of ≥5.0 mEq/l might be associated with an increased mortality risk in patients with AMI. Patients with an admission SPC between 4.5 and <5.0 mEq/l might have an increased mortality risk in the first few years following AMI.