Calcium Supplementation Could Increase Risk of Death in Older Adults with Cardiovascular Disease

An analysis of data from a Cleveland Clinic database indicates calcium supplementation in older adults with aortic stenosis was linked to an increased risk of mortality and worsening aortic stenosis.

An analysis of data from the Cleveland Clinic Echocardiography database is sounding the alarm on the potential impact of calcium supplementation in older adults with aortic stenosis.

A retrospective longitudinal study with data from more than 2500 patients followed for nearly 70 months, results of the study indicate calcium supplementation was associated with a 31% greater risk of mortality and a 48% greater risk of aortic valve replacement among older adults with aortic stenosis.

“Strengthened by its large sample size and extended follow-up period, our study suggests that calcium supplementation does not confer any cardiovascular benefit, and instead may reflect an elevated overall risk of aortic valve replacement and mortality, especially in those not undergoing aortic valve replacement,” wrote investigators.

With calcium and vitamin D among the most commonly supplemented vitamins and minerals among aging populations, particularly those at risk of osteoporosis, the current study was designed by investigators at the Cleveland Clinic Foundation to assess the impact of supplemental calcium and vitamin D on mortality and progression of aortic stenosis. With this in mind, investigators designed their study as a retrospective longitudinal study of patients aged 60 years and older with mild-moderate native aortic stenosis from the Cleveland Clinic Echocardiography database from 2008-2016.

From this search, investigators identified 2657 patients for inclusion in their analyses. These patients had a mean age of 74 years, 42% were women, and the median follow-up duration was 69 months. Patients included in the analyses were stratified into groups defined by the absence of supplementation, supplementation with vitamin D alone, and supplementation with calcium plus vitamin D. Of the 2657 patients included, 49% did not supplement, 12% supplemented with vitamin D alone, and 39% supplemented with calcium and vitamin D.

The primary outcomes of interest for the investigators’ analyses were mortality and aortic valve replacement. Of note, mortality was assessed as all-cause mortality, cardiovascular mortality, and non-cardiovascular mortality. Secondary outcomes of interest included aortic stenosis progression by aortic valve area and peak/mean gradients. investigators pointed out primary outcomes were assessed through survival analyses with Kaplan-Meier nonparametric method.

Overall, there were 540 deaths that occurred among the study cohort, with 150 being classified as cardiovascular death, 155 classified as noncardiovascular death, 235 were deaths of unknown etiology. A total of 774 cases of aortic valve replacement were identified during the follow-up period.

Results of the investigators’ analyses indicated supplementation with calcium and vitamin D was associated with a significantly higher risk of all-cause mortality (absolute rate [AR]=43.0/1000 person-years; HR=1.31, [95% CI, 1.07-1.62]; P=.009), cardiovascular mortality (AR, 13.7/1000 person-years; HR, 2.0 [95% CI, 1.31-3.07]; P=.001), and aortic valve replacement (AR, 88.2/1000 person-years; HR, 1.48 [95% CI, 1.24-1.78]; P <.001) compared to the nonsupplementation arm. investigators noted the increased risk of all-cause mortality was greater among those supplementing with calcium and vitamin D when compared against those supplementing vitamin D alone as well (P <.001).

Investigators pointed out analysis of those who supplemented with calcium alone, which was a cohort of 115 patients, indicated these individuals experienced a similar rate of all-cause mortality (HR, 1.24 [95% CI, 0.77-1.99]; P=.38) but a higher risk of aortic valve replacement (HR, 2.7 [95% CI, 1.76-4.08]; P <.001).

In a linked editorial, Jutta Bergler-Klein, a professor of the Medical University of Vienna, detailed the contemporary trends in supplement use among older patients, but added clinicians may need to rethink the potential risk posed by calcium supplements in those with osteoporosis at high risk for cardiovascular disease.

“In patients with calcific aortic stenosis and high-risk cardiovascular disease, the present study strongly adds to the evidence that long-term continuous calcium supplementation should be avoided if not mandatory,” wrote Bergler-Klein.

This study, “Supplemental calcium and vitamin D and long-term mortality in aortic stenosis,” was published in Heart.