Asymptomatic aortic stenosis (AS) is a frequent condition that may cause hyponatremia due to neurohumoral activation. We examined if hyponatremia heralds poor prognosis in patients with asymptomatic AS, and whether AS in itself is associated with increased risk of hyponatremia. The study question was investigated in 1,677 individuals that had and annual plasma sodium measurements in the SEAS (Simvastatin and Ezetimibe in AS) trial; 1,873 asymptomatic patients with mild-moderate AS (maximal transaortic velocity 2.5 to 4.0 m/s) randomized to simvastatin/ezetimibe combination versus placebo. All-cause mortality was the primary endpoint and incident hyponatremia (P-Na+ <137 mmol/L) a secondary outcome. At baseline, 4% (n = 67) had hyponatremia. After a median follow-up of 4.3 (interquartile range 4.1 to 4.6) years, 140 (9%) of those with initial normonatremia had developed hyponatremia, and 174 (10%) had died. In multiple regression Cox models, both baseline hyponatremia (hazard ratio [HR] 2.1, [95% confidence interval 1.1 to 3.8]) and incident hyponatremia (HR 1.9, [95% confidence interval 1.0 to 3.4], both p ≤ .03) was associated with higher all-cause mortality as compared with normonatremia. This association persisted after adjustment for diuretics as a time-varying covariate. Higher N-terminal pro b-type natriuretic peptide levels and lower sodium levels at baseline was associated with higher risk of incident hyponatremia. Conversely, assignment to simvastatin/ezetimibe protected against incident hyponatremia. In conclusion, both prevalent and incident hyponatremia associate with increased mortality in patients with AS. The prevalence of hyponatremia is around 4% and the incidence about 2% per year, which is comparable to that of older adults without AS.
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