Although renal dysfunction and high blood electrolyte levels are linked to poor clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF), the link between visit-to-visit variability in these laboratory parameters and long-term results is unknown. For a study, the researchers sought to determine if visit-to-visit variability in kidney function (creatinine and blood urea nitrogen [BUN] levels) and serum electrolyte (sodium, chloride, and potassium) levels are linked to the risk of negative clinical outcomes in patients with chronic, stable HFpEF. Researchers used the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) in the cohort analysis. Participants were included if they had 3 or more serial laboratory measurements and were free of events within the first 4 months of participation. From March 1, 2019, through January 31, 2020, data was evaluated. Cox proportional hazards regression models were used to assessing adjusted associations between indexes of variability in serum laboratory measurements during the first 4 months of follow-up and risk of the primary composite outcome (a composite of aborted cardiac arrest, hospitalization for heart failure, or cardiovascular death) and all-cause mortality. Depending on the availability of serial data, 2,479 (BUN) to 3,195 (potassium) of the 3,445 patients recruited in the TOPCAT experiment (mean [SD] age, 68-69 [10] years; 49.7% -51.5% female) were researched. Participants with more laboratory variability in kidney function measurements were older, had more comorbidities, and suffered from more severe HFpEF symptoms. Higher visit-to-visit variability in BUN (hazard ratio [HR] per 1-SD higher average successive variability [ASV], 1.21; 95% Confidence interval, 1.10-1.33) and creatinine (HR per 1-SD higher ASV, 1.13; 95% Confidence interval, 1.04-1.22) were independently linked to a higher risk of the primary composite outcome as well as mortality, even after controlling for other baseline confounders, changes in kidney function, medication dosages, and variability in other cardiometabolic parameters (systolic blood pressure and body mass index). The increased risk associated with greater variability in kidney function was consistent across subgroups of patients stratified by the presence of chronic kidney disease (CKD) at baseline (HR per 1-SD higher ASV, 1.39; 95% CI, 1.16-1.67; and no CKD: HR per 1-SD higher ASV, 1.13; 95% CI, 1.01-1.27), in both the placebo and spironolactone treatment arms separately (spironolactone arm: 1.30; 95% CI, 1.03-1.65 and placebo arm: HR per 1-SD higher ASV, 1.27; 95% CI, 1.04-1.56). Variability in sodium and potassium measurements in serum electrolytes were also linked to an increased risk of primary composite events (sodium: HR per 1-SD higher ASV, 1.14; 95% CI, 1.01-1.30 and potassium: HR per 1-SD higher ASV, 1.21; 95% CI, 1.02-1.44). Variability in laboratory indices of kidney function and serum electrolytes from a visit to visit is prevalent in HFpEF and is related to worse long-term clinical outcomes.