High and low serum potassium associated with cardiovascular events in diuretic-treated patients

To determine the relationship of moderately high and low concentrations of serum potassium with cardiovascular disease events among treated hypertensive patients.

An observational cohort study with prospectively collected data.

A worksite treatment program for mild hypertension.

All program participants with baseline and at least one annual follow-up measure of serum potassium; 7,653 individuals with 6.7 years mean follow-up met these criteria.

Outcome events were admissions to hospital because of cardiovascular disease, and deaths. The research question regarding serum potassium categories was formulated after data collection. The serum potassium concentration (mean +/- 2SD) of the study population was used to define low (3.0-3.5 mmol/l), high (5.1-5.9 mmol/l) and middle (3.6-5.0 mmol/l) categories.

Individuals with low (n = 146) and high (n = 226) serum potassium had significantly greater risk for cardiovascular disease events than those in the middle category (n = 7,281). Multivariate adjusted hazard ratios from Cox models were 2.6 [95% confidence intervals (CI) 1.5-4.4] for the low potassium group and 1.7 (95% CI 1.0-2.7) for the high potassium group, with the middle group as reference. Among 1,679 individuals who regularly took diuretics, hazard ratios were 4.3 (95% CI 2.4-7.9) for the low potassium group and 6.7 (95% CI 2.8-15.9) for the high group. Neither low nor high potassium was significantly associated with outcome events for those not regularly using diuretics.

These data confirm an association of mild hypokalemia with increased cardiovascular events among diuretic-treated hypertensive patients. In addition, we have found a similar increased cardiovascular risk associated with modest hyperkalemia among these patients. Whether modification of these serum potassium concentrations would alter that risk remains to be determined.