Dyskalemia, cardiac structure and function, and risk of adverse cardiovascular events in patients with chronic kidney disease

Background Dyskalemia is common in patients with chronic kidney disease (CKD) and has been associated with adverse outcomes in cardiovascular patient populations. However, the connection between plasma potassium levels, cardiac structure and function, and risk of cardiovascular events in patients with CKD remains incompletely characterized. Purpose This analysis aimed to evaluate the risk of adverse cardiovascular events and the association with cardiac structure and function across plasma potassium levels (mmol/L) in patients with CKD. Methods Outpatients with non-dialysis-dependent CKD were included from the prospective CPH-CKD ECHO cohort study. Exclusion criteria were heart failure (HF), atrial fibrillation (AF) or cerebral ischemia at baseline. A combined endpoint was defined as all-cause mortality or incident HF, AF, cerebral infarction and myocardial infarction. Follow-up was conducted through Danish national registries. Restricted cubic splines were used to visualize the association between continuous plasma potassium levels and the risk of the combined endpoint, and to identify potential cut-off values associated with an increased risk. Risk was assessed using uni- and multivariable Cox regression models, the latter of which was adjusted for age, sex, systolic blood pressure, diabetes, chronic ischemic heart disease, CKD stage, albuminuria level, and left ventricular ejection fraction (LVEF). Results A total of 867 patients were included. Higher potassium levels were associated with lower LVEF as well as increased left ventricular mass index and left atrial volume index (Table 1). During a median follow-up of 8.7 years [IQR 7.1, 9.5], the combined endpoint occurred in 267 (30.8%) patients, while the incidence of all-cause mortality was 215 (24.8%). Restricted spline analyses demonstrated an increased risk of the combined endpoint at K <3.7 and >4.1 mmol/L (Figure 1). In total, 162 patients (18.7%) had a potassium below cut-off (<3.7 mmol/L), 382 (44.1%) had a potassium above cut-off (>4.1 mmol/L), while 544 (62.7%) had a potassium level below or above cut-off (<3.7 or >4.1 mmol/L). In univariable Cox regression, potassium levels below or above cut-off were associated with an increased risk of the combined endpoint and all-cause mortality (HR=1.55 (1.20 - 1.99) and HR=1.81 (1.35-2.42), respectively; p <0.001). After multivariable adjustment, potassium levels above or below cut-off remained associated with all-cause mortality (HR = 1.47 (1.03-2.12), p = 0.037). Conclusion Higher potassium levels were associated with altered cardiac structure and function in patients with CKD. Plasma potassium levels <3.7 and >4.1 mmol/L were also associated with an increased risk of the combined cardiovascular endpoint. These findings suggest that closer monitoring of plasma potassium levels in patients with CKD may improve cardiovascular risk stratification in this population.