Serum potassium as a predictor of adverse clinical outcomes in patients with increasing comorbidity burden

Abstract

Aims: The aim of this study was to establish whether patients with multiple comorbidities may be at elevated risk of hyperkalaemia (HK), a potentially life-threatening electrolyte imbalance, and the associated adverse clinical outcomes.

Methods and results: This was a retrospective, observational cohort study using UK primary and secondary care data. Adult patients with at least one of: resistant hypertension, chronic kidney disease stage 3+, dialysis, heart failure (HF), and diabetes, were eligible for inclusion. According to their diagnoses, patients were grouped into overlapping cohorts that were updated as multimorbidity progressed. Outcomes of interest were incident HK, all-cause mortality (ACM), and major adverse cardiovascular events (MACE). A total of 673 686 patients met the eligibility criteria, 36.3% of whom developed multimorbidity during the study period. A consistent U-shaped association was observed between serum K+ level and adjusted incidence of ACM and MACE. Hyperkalaemia was progressively more common with increasing Charlson Comorbidity Index (CCI). Relative to a CCI <3, scores of ≥3 to <6, and ≥6 were associated with 2.9- and 6.2-fold increases, respectively, in crude HK (serum K+ ≥5.0 mmol/L) incidence rate. In all condition-based cohorts except for HF, there was a clear correlation between increasing CCI and the risk of ACM and MACE associated with hypokalaemia and HK.

Conclusion: Patients with a higher CCI are at an increased risk of developing HK and appear more prone to adverse clinical outcomes associated with abnormal serum K+ levels, warranting additional routine clinical monitoring.

Keywords: Comorbidity; Hyperkalaemia; Major adverse cardiovascular events; Mortality.

Figure 1

Illustrative example of assigning follow-up time to cohorts. CKD, chronic kidney disease; HF, heart failure; ${\mathrm{K}}_n^{+}$ denotes patient’s nth potassium measurement over the study period.

Figure 2

IRRs of ACM and MACE for different serum K⁺ levels, stratified by condition-based cohort. ACM, all-cause mortality; CKD, chronic kidney disease; HF, heart failure; IRRs, incidence rate ratios; MACE, major adverse cardiovascular events; RHTN, resistant hypertension. Serum K⁺ level between 4.5 and <5.0 mmol/L was defined as the reference category.

Figure 3

IRRs of ACM for different serum K⁺ levels, stratified by condition-based cohort and CCI. ACM, all-cause mortality; CCI, Charlson’s Comorbidity Index; CKD, chronic kidney disease; HF, heart failure; IRRs, incidence rate ratios; RHTN, resistant hypertension. Serum K⁺ level between 4.5 and <5.0 mmol/L defined as the reference category.

Figure 4

IRRs of MACE for different serum K⁺ levels, stratified by condition-based cohort and CCI. CCI, Charlson’s Comorbidity Index; CKD, chronic kidney disease; HF, heart failure; IRRs, incidence rate ratios; MACE, major adverse cardiovascular events; RHTN, resistant hypertension. Serum K⁺ level between 4.5 and <5.0 mmol/L defined as the reference category.