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Consequences of Recurrent Hyperkalemia on Cardiovascular Outcomes and Mortality
George Bakris1, Abiy Agiro2, Fan Mu3
1AHA Comprehensive Hypertension Center, University of Chicago, Chicago, Illinois, USA.
Insights
Recurrent hyperkalemia (HK) significantly increases risks for mortality and major adverse cardiovascular events (MACE+) in chronic kidney disease (CKD) patients, including those with heart failure (HF). This highlights the importance of managing HK in CKD and HF populations.
Area of Science:
- Nephrology
- Cardiology
- Epidemiology
Background:
- Hyperkalemia (HK) is linked to severe cardiovascular (CV) outcomes, but the specific impact of recurrent HK is not well understood.
- Chronic kidney disease (CKD) patients are at increased risk for both HK and adverse CV events.
Purpose of the Study:
- To evaluate mortality and CV outcomes associated with recurrent HK compared to normokalemia in patients with CKD.
- To assess these outcomes in a subset of CKD patients with co-occurring heart failure (HF).
Main Methods:
- Retrospective cohort study (REVOLUTIONIZE III) using deidentified claims data (January 2016 - August 2022).
- Inclusion of adults (≥18 years) with stage 3/4 CKD, with or without HF.
- Propensity score-matched analysis comparing patients with recurrent HK (≥2 events) to those with normokalemia.
Main Results:
- The study included 6,337 matched pairs (2,129 with HF), with well-balanced characteristics.
- Recurrent HK was associated with significantly higher risks of all-cause mortality (HR: 1.29 overall, 1.30 in HF substudy).
- Increased risks were also observed for major adverse CV events plus (MACE+) (HR: 1.53 overall, 1.45 in HF substudy) and hospitalized arrhythmia (HR: 1.94 overall, 1.85 in HF substudy).
Conclusions:
- Recurrent hyperkalemia significantly elevates the risk of all-cause mortality, MACE+, and hospitalized arrhythmia in CKD patients.
- These increased risks persist even in CKD patients with co-occurring heart failure.
- Findings underscore the critical need for vigilant monitoring and management of HK in CKD and HF populations.
Background:
Hyperkalemia (HK) has been linked to serious cardiovascular (CV) outcomes, but the impact of recurrent HK on these outcomes is ill-defined.
Objectives:
This study evaluated mortality and CV outcomes associated with recurrent HK vs normokalemia in patients with chronic kidney disease (CKD) and in a subset of patients with co-occurring heart failure (HF).
Methods:
REVOLUTIONIZE III was a retrospective cohort study of adults (aged ≥18 years) diagnosed with stage 3/4 CKD, with or without HF in Optum's deidentified Market Clarity database (January 2016 to August 2022). Patients with recurrent HK (≥2 events) were exactly and propensity score-matched to patients with normokalemia (no serum [K+] <3.5 or >5.0 mmol/L or HK diagnosis ever). The primary endpoint was all-cause mortality; secondary endpoints were CV outcomes including major adverse CV events plus (major adverse cardiovascular event or hospitalization with heart failure [MACE+]; defined as all-cause mortality or hospitalized myocardial infarction, stroke, or HF and hospitalized arrhythmia). Cause-specific Cox proportional hazard models were used to compare outcomes between cohorts.
Results:
The study included 6,337 matched pairs overall, including 2,129 with HF. Characteristics of the samples were well-balanced. Recurrent HK was associated with higher risks of all-cause mortality (HR overall: 1.29 [95% CI: 1.20-1.38]; HF substudy: 1.30 [95% CI: 1.18-1.44]), MACE+ (overall: 1.53 [95% CI: 1.43-1.65]; HF substudy: 1.45 [95% CI: 1.29-1.64]), and hospitalized arrhythmia (overall: 1.94 [95% CI: 1.74-2.16]; HF substudy: 1.85 [95% CI: 1.55-2.21]) compared with normokalemia.
Conclusions:
In patients with CKD, recurrent HK increased the risks of all-cause mortality, MACE+, and hospitalized arrhythmia compared with normokalemia, including in a subset of patients with HF.
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