Developing prediction models for electrolyte abnormalities in patients indicated for antihypertensive therapy: evidence-based treatment and monitoring recommendations

Objectives: Evidence from clinical trials suggests that antihypertensive treatment is associated with an increased risk of common electrolyte abnormalities. We aimed to develop and validate two clinical prediction models to estimate the risk of hyperkalaemia and hyponatraemia, respectively, to facilitate targeted treatment and monitoring strategies for individuals indicated for antihypertensive therapy. Design and methods: Participants aged at least 40 years, registered to an English primary care practice within the Clinical Practice Research Datalink (CPRD), with a systolic blood pressure reading between 130 and 179 mmHg were included the study. The primary outcomes were first hyperkalaemia or hyponatraemia event recorded in primary or secondary care. Model development used a Fine-Gray approach with death from other causes as competing event. Model performance was assessed using C-statistic, D-statistic, and Observed/Expected (O/E) ratio upon external validation. Results: The development cohort included 1 773 224 patients (mean age 59 years, median follow-up 6 years). The hyperkalaemia model contained 23 predictors and the hyponatraemia model contained 29 predictors, with all antihypertensive medications associated with the outcomes. Upon external validation in a cohort of 3 805 366 patients, both models calibrated well (O/E ratio: hyperkalaemia 1.16, 95% CI 1.13-1.19; hyponatraemia 1.00, 95% CI 0.98-1.02) and showed good discrimination at 10 years (C-statistic: 0.69, 95% CI 0.69-0.69; 0.80, 95% CI 0.80-0.80, respectively). Conclusion: Current clinical guidelines recommend monitoring serum electrolytes after initiating antihypertensive treatment. These clinical prediction models predicted individuals' risk of electrolyte abnormalities associated with antihypertensive treatment and could be used to target closer monitoring for individuals at a higher risk, where resources are limited.