Risk factors

Calcium supplements linked to mortality, valve replacement risks in aortic stenosis patients


Long-term continuous calcium supplementation should be avoided in aortic stenosis patients where possible, to avoid increasing mortality and valve-replacement risks, cardiologists say.

A retrospective study of 2,657 elderly patients with mild-to-moderate aortic stenosis and no supplements, vitamin D supplements or calcium with or without vitamin D found those on calcium had a “significantly higher risk” of death and aortic valve replacement over a median of 69-months than their non-calcium-taking counterparts.

Despite controversy surrounding the supplements’ utility, optimal intake and relationship with cardiovascular (CV) disease risk and mortality, its use is increasing, particularly in post-menopausal women susceptible to osteoporosis and bone fractures.

The current findings warrant careful consideration about the non-mandatory use of calcium supplements and suggest long-term consumption should be avoided in elderly aortic stenosis patients, the study and an accompanying editorial warned.

Published in Heart, the study assessed all-cause and CV mortality, along with aortic valve replacement outcomes in patients 60 years and over with aortic valve areas between 1.0 and 2.0 cm2 on index echocardiogram.

It reported calcium (500–2,000 mg/day) plus/minus vitamin D (any dose available over-the-counter) users were more likely to die from any cause (absolute rate [AR]: 43/1,000 person years, hazard ratio [HR]: 1.31, 95% CI: 1.07–1.62, P = 0.009) than those without supplements.

They also had a higher risk of CV death and a greater need for aortic valve replacement (AR: 13.7/1000 person-years; HR: 2.0, 95% CI: 1.31–3.07, P = 0.001 and AR: 88.2/1000 person-years, HR: 1.48, 95% CI: 1.24–1.78, P < 0.001, respectively).

Notably, vitamin D alone had “no observed impact on survival in [this] study, consistent with prior randomised trials”, the study read, nor did it affect aortic valve replacement need.

Practical implications

While these results seem fairly clear-cut, they “should be interpreted with caution”, the study authors — cardiologists from the Cleveland Clinic Foundation, Ohio, wrote.

It faced several limitations, including those inherent in a retrospective study, lack of supplement dose effect measurement and potential ascertainment bias. Further, calcium users had more comorbidities at baseline.

Previous trials have had inconsistent results regarding calcium intake and survival, and the relationship “may be subject to a host of factors, including mode (supplementation vs diet) and dosage of intake, studied population by sex, age or community, and duration of follow-up”, the authors wrote.

Additionally, patients on calcium supplements for osteoporosis, hypoparathyroidism and other disease states may have been at greater risk of CV disease and mortality before study onset.

However, past studies have linked oral calcium to progressive coronary arterial calcification, myocardial infarction and stroke, with supplementation thought to increase serum calcium, leading to extraosseous calcification, and ultimately, higher CV mortality “through downstream alterations in endothelial function and blood coagulation”, the editorialist, a cardiologist from the Medical University of Vienna, noted.

Osteoporotic processes lend credence to this theory, where bone demineralisation “releases excessive calcium and phosphate into circulation” and has been associated with faster aortic stenosis progression, valve calcifications and higher all-cause and CV mortality, they continued.

Therefore, it has “recently been recommended that management of osteoporosis should include screening for CV and respiratory disease risk”.

Regarding calcium supplements, safety, along with patients’ CV disease and risk factors should be considered when choosing osteoporosis treatment or prevention options, the editorial read.

“Excitingly, vitamin D supplementation alone remained neutral with respect to [aortic valve replacement] and was not linked to any mortality increase in multivariable analyses, so that the assumed beneficial effects concerning osteoporosis and bone metabolism are maintained in patients with [aortic stenosis].”

“In patients with calcific [aortic stenosis] and high-risk CV, the present study strongly adds to the evidence that long-term continuous calcium supplementation should be avoided if not mandatory,” the editorial concluded.

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