Mortality from aortic stenosis: prospective study of serum calcium and phosphate

To investigate the associations between levels of serum calcium and phosphate and subsequent death from aortic stenosis, and the implications for prevention.

A prospective (nested case-control) analysis of serum calcium and phosphate levels was performed in stored samples from the British United Provident Association prospective study of 21 520 men aged 35-64, followed for up to 32 years. There were 49 men without baseline valvular heart disease who subsequently died of aortic stenosis. Each was matched, for age, duration of sample storage and number of freeze-thaw cycles, with four unaffected control subjects. Odds ratios for death from aortic stenosis were estimated by logistic regression.

Mean serum calcium concentration was higher in men who died of aortic stenosis than in those who did not (2.44 vs. 2.39 mmol L^-1 ; P = 0.01). The risk of death from aortic stenosis in the highest calcium tertile was 2.87-fold higher than in the lowest tertile (95% confidence interval 1.22-6.76). There was a continuous dose-response relationship; risk of death from aortic stenosis increased by 51% (11-105%) per 0.1 mmol L^-1 increase in serum calcium, equivalent to a 34% (10-52%) lower risk per 0.1 mmol L^-1 decrease. Serum phosphate was not significantly higher in men who died of aortic stenosis than in those who did not (1.0 vs. 0.99 mmol L^-1 ; P = 0.76).

The association between serum calcium and subsequent mortality from aortic stenosis is of potential preventive significance. If confirmed quantitatively in other similar cohort studies, the results suggest that a very small reduction in serum calcium (about 5%) could translate into a large (about one-third) reduction in aortic stenosis.