36,269 patients with chronic cardiovascular, metabolic and renal conditions: impact on clinical outcomes, medical resource use and health-related costs of deranged serum potassium levels
Authors: Jimenez S , Cainzos-Achirica M , Monterde D , Garcia-Eroles L , Vela E , Cleries M , Enjuanes C , Yun S , Garay A , Moliner P , Alcoberro L , Calero E , Hidalgo E , Corbella X , Comin-Colet J 
Published: November 2020

Abstract

Background
Chronic Heart Failure (CHF) and its risk factors at stage A of the disease are conditions that trends to facilitate potassium (K+) derangements, for pathophysiology mechanisms and medication use than could facilitate both hyper- and hypokalamia. Studies on the associations between potassium derangements and clinical outcomes in these patient populations have yielded mixed findings, and the implications for healthcare expenditure are unknown.

Purpose
The objectives of our analysis was to asses the population-based associations between hyperkalemia, hypokalemia (compared to normokalemia) and all-cause death, urgent hospitalization, emergency department visits, daycare visits, and a yearly healthcare expenditure &gt;85th percentile, in patients with chronic heart failure, chronic kidney disease, diabetes mellitus, hypertension and ischemic heart disease.

Methods
Population-based, longitudinal study including up to 36,269 patients from the Public Healthcare Area with at least one of those conditions. We used three linked administrative, hospital and primary care healthcare databases with exhaustive information on sociodemographics, medical diagnoses, pharmacy dispensing and laboratory data. Participants were identified and followed between 2015 and 2017, had to be ≥55 years old and have at least one serum potassium measurement recorded; and were classified as hyperkalemic, hypokalemic or normokalemic. Four analytic designs were used to evaluate prevalent and incident disease cases as well as prevalent and incident use of renin-angiotensin-aldosterone system inhibitors

Results
The majority of study participants remained normokalemic during the 3 months following study entry (ranging 94%–96%) and hyperkalemia was twice as frequent as hypokalemia. In all analyses, compared to normokalemic patients those with hyperkalemia had a worse crude event-free survival for all endpoints, and the worst survival was observed for hypokalemic patients [see Figure 1: prevalent case analysis; Kaplan-Meier cumulative survivor function curves for all-cause death (upper left), hospitalization (upper right), ED visits (lower left) and daycare visits (lower right)].
In multivariable-adjusted analyses, hyperkalemia was robustly and significantly associated with an increased risk of all-cause death (hazard ratios from Cox regression models ranging 1.31–1.68) and with an increased odds of a yearly healthcare expenditure &gt;85th percentile (odds ratios 1.21–1.29). Associations were even stronger in hypokalemic patients (hazard ratios for all-cause death 1.92–2.60; odds ratios for healthcare expenditure &gt;percentile 85th 1.81–1.85).

Conclusions
Experimental studies are needed to confirm whether prevention of potassium derangements reduces mortality and healthcare expenditure in patients with these chronic conditions. Until then, our findings provide further observational evidence on the potential importance of maintaining normal potassium levels in this setting.
Figure 1

Funding Acknowledgement
Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): The present study was funded by an unrestricted research grant from Vifor Pharma.