SERUM POTASSIUM AT BASELINE AND ON-TREATMENT AND ALL-CAUSE MORTALITY IN HYPERTENSION

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Abstract Title *

SERUM POTASSIUM AT BASELINE AND ON-TREATMENT AND ALL-CAUSE MORTALITY IN HYPERTENSION

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Co-author 1

Jia Wei Teh j.teh1@universityofgalway.ie College of Medicine Nursing and Health Science, University of Galway School of Medicine Galway Ireland *

Co-author 2

Michael Conall Dennedy dennedym@universityofgalway.ie School of Medicine, University of Galway, Galway Discipline of Advanced Therapies Galway Ireland -

Co-author 3

Conor Judge conor.judge@universityofgalway.ie College of Medicine Nursing and Health Science, University of Galway School of Medicine Galway Ireland -

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Introduction

The prevalence of hypokalaemia have been described in up to 16% in patients with hypertension while the prevalence of hyperkalaemia is 4.7% in those with hypertension. The aim of this study is to determine the association between baseline and mean on-treatment hypokalaemia and hyperkalaemia with all-cause mortality in persons with hypertension.

Methods

In this study, five randomised controlled-trial –ACCORD-BP, SPRINT, TOPCAT, ALLHAT and HDFP were included. Serum potassium was categorised as hypokalaemia (<3.5 mmol/L), normokalaemia (3.5–5.0 mmol/L), and hyperkalaemia (>5.0 mmol/L). The primary outcome was all-cause mortality. The secondary outcomes include cardiovascular death, hospitalisation for heart failure, myocardial infarction, and stroke. Baseline and mean on-treatment serum potassium levels were examined as independent variables. Associations with outcomes were assessed using Cox proportional hazards models and restricted cubic splines, both adjusted for baseline demographics, comorbidities and antihypertensive exposure. Mediation analyses incorporated average on-treatment blood pressure.

Results

Figure 1: Forest plot of primary and secondary outcomes by potassium status at baseline and on-treatment. IIn total, 70,599 participants were included in this study. The pooled cohort had a mean (SD) age of 64 (10) years, with 32,114 (45.5%) female participants. The baseline mean (SD) systolic and diastolic blood pressures were 146 (18) mmHg and 85 (13) mmHg, respectively. At baseline, 2065 (3.1%) participants had hypokalaemia and 4345 (6.5%) had hyperkalaemia while, on mean on-treatment, 2496 (3.8%) had hypokalaemia and 2262 (3.5%) had hyperkalaemia. During a mean (SD) follow-up duration of 4.47 (1.52) years, all-cause mortality occurred in 7,748 participants (11.0%) across five trials.

Baseline hypokalemia, compared with normokalemia, was not associated with all-cause mortality. Baseline hyperkalemia was associated with increased all-cause mortality (hazard ratio (HR) 1.13 [95% CI, 1.02-1.25]; P = 0.01). Conversely, both mean on-treatment hypokalemia (HR 1.50 [95% CI, 1.30-1.74]; P < 0.01) and hyperkalemia (HR 1.50 [95% CI, 1.33-1.70]; P < 0.01), were significantly associated with increased risk for all-cause mortality, compared to normokalemia. Using adjusted restricted cubic spline, baseline potassium exhibited a linear and mean on-treatment potassium exhibited a U-shaped relationship with all-cause mortality. Additionally, baseline hypokalemia was not significantly associated with any cardiovascular outcome compared with normokalemia. In contrast, mean on-treatment hypokalemia was significantly associated with increased risk of stroke (HR, 1.37 [95% CI, 1.06-1.77]; P = 0.02). Baseline hyperkalemia was significantly associated with increased cardiovascular death (HR, 1.19 [95% CI, 1.02-1.38]; P = 0.03) and myocardial infarction (HR, 1.22 [95% CI, 1.07-1.38]; P < 0.01). Mean on-treatment hyperkalemia was significantly associated with all secondary outcomes, including cardiovascular death (HR, 1.62 [95% CI, 1.36-1.94]; P < 0.01), hospitalization for heart failure (HR, 1.40 [95% CI, 1.16-1.69]; P < 0.01), myocardial infarction (HR, 1.42 [95% CI, 1.22-1.66]; P < 0.01) and stroke (HR, 1.39 [95% CI, 1.11-1.73]; P < 0.01)(Figure 1).

Conclusion

In patients with hypertension, hyperkalemia at baseline, and dyskalemia during treatment were associated with increased all-cause mortality. Serum potassium should be routinely monitored and maintained within a narrow physiological range as part of hypertension management.

Kewords