Abstract
BackgroundHypokalemia is common in patients treated with antihypertensive drugs, but the impact of correcting hypokalemia is insufficiently studied. We examined the consequences of hypokalemia and borderline hypokalemia correction in patients with hypertension.MethodsWe identified 8976 patients with hypertension and plasma potassium concentrations ≤3.7 mmol/L within 100 days from combination antihypertensive therapy initiation. The first measurement between 6 and 100 days after the episode with potassium ≤3.7 mmol/L was retained. We investigated all-cause and cardiovascular mortality within 60-days from the second potassium measurement using Cox regression. Mortality was examined for seven predefined potassium intervals derived from the second measurement: 1.5–2.9 mmol/L (n = 271), 3.0–3.4 mmol/L (n = 1341), 3.5–3.7 (n = 1982) mmol/L, 3.8–4.0 mmol/L (n = 2398, reference), 4.1–4.6 mmol/L (n = 2498), 4.7–5.0 mmol/L (n = 352) and 5.1–7.1 mmol/L (n = 134).ResultsMultivariable analysis showed that potassium concentrations 1.5–2.9 mmol/L, 3.0–3.4 mmol/L, 4.7–5.0 mmol/L and 5.1–7.1 mmol/L were associated with increased all-cause mortality (HR 2.39, 95% CI 1.66–3.43; HR 1.36, 95% CI 1.04–1.78; HR 2.36, 95% CI 1.68–3.30 and HR 2.62, 95% CI 1.73–3.98, respectively). Potassium levels <3.0 and > 4.6 mmol/L were associated with increased cardiovascular mortality. The adjusted standardized 60-day mortality risks in the seven strata were: 11.7% (95% CI 8.3–15.0%), 7.1% (95% CI 5.8–8.5%), 6.4% (95% CI 5.3–7.5%), 5.4% (4.5–6.3%), 6.3% (5.4–7.2%), 11.6% (95% CI 8.7–14.6%) and 12.6% (95% CI 8.2–16.9%), respectively.ConclusionsPersistent hypokalemia was frequent and associated with increased all-cause and cardiovascular mortality. Increase in potassium to levels > 4.6 mmol/L in patients with initial hypokalemia or low normal potassium was associated with increased all-cause and cardiovascular mortality.
Highlights
Hypokalemia is common in patients treated with antihypertensive drugs, but the impact of correcting hypokalemia is insufficiently studied
Multivariable analysis showed that potassium concentrations 1.5–2.9 mmol/L, 3.0–3.4 mmol/L, 4.7–5.0 mmol/L and 5.1–7.1 mmol/L were associated with increased all-cause mortality (HR 2.39, 95% 95% confidence interval (CI) 1.66–3.43; Hazard ratios (HR) 1.36, 95% confidence intervals (95% CI) 1.04–1.78; HR 2.36, 95% CI 1.68–3.30 and HR 2.62, 95% CI 1.73–3.98, respectively)
Increase in potassium to levels > 4.6 mmol/L in patients with initial hypokalemia or low normal potassium was associated with increased all-cause and cardiovascular mortality
Summary
Hypokalemia is common in patients treated with antihypertensive drugs, but the impact of correcting hypokalemia is insufficiently studied. We examined the consequences of hypokalemia and borderline hypokalemia correction in patients with hypertension. Several common clinical conditions and drugs are known to cause or precipitate hypokalemia [1]. Thiazides are the antihypertensive drugs most frequently associated with hypokalemia [2,3,4]. We recently demonstrated a U-shaped relationship between potassium levels and mortality among patients with hypertension. We observed an increased mortality risk even in patients with low and high normal serum potassium concentrations, suggesting a narrower than previously thought normal interval for potassium of 4.1– 4.7 mmol/L. [5] at present there is no evidence regarding the consequences of potassium normalization in patients with hypertension and hypokalemia. It is essential to examine how correction and even
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