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Original research
Supplemental calcium and vitamin D and long-term mortality in aortic stenosis
  1. Nicholas Kassis1,
  2. Essa H Hariri1,
  3. Antonette K Karrthik2,
  4. Keerat R Ahuja2,
  5. Habib Layoun2,
  6. Anas M Saad2,
  7. Mohamed M Gad1,
  8. Manpreet Kaur2,
  9. Najdat Bazarbashi2,
  10. Brian P Griffin2,
  11. Zoran B Popovic2,
  12. Serge C Harb2,
  13. Milind Y Desai2,
  14. Samir R Kapadia2
  1. 1Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA
  2. 2Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA
  1. Correspondence to Dr Samir R Kapadia, Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, OH 44195, USA; kapadis{at}


Objective Calcium metabolism has long been implicated in aortic stenosis (AS). Studies assessing the long-term safety of oral calcium and/or vitamin D in AS are scarce yet imperative given the rising use among an elderly population prone to deficiency. We sought to identify the associations between supplemental calcium and vitamin D with mortality and progression of AS.

Methods In this retrospective longitudinal study, patients aged ≥60 years with mild-moderate native AS were selected from the Cleveland Clinic Echocardiography Database from 2008 to 2016 and followed until 2018. Groups were stratified into no supplementation, supplementation with vitamin D alone and supplementation with calcium±vitamin D. The primary outcomes were mortality (all-cause, cardiovascular (CV) and non-CV) and aortic valve replacement (AVR), and the secondary outcome was AS progression by aortic valve area and peak/mean gradients.

Results Of 2657 patients (mean age 74 years, 42% women) followed over a median duration of 69 months, 1292 (49%) did not supplement, 332 (12%) took vitamin D alone and 1033 (39%) supplemented with calcium±vitamin D. Calcium±vitamin D supplementation 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 to 1.62); p=0.009), CV mortality (AR=13.7/1000 person-years; HR=2.0, 95% CI (1.31 to 3.07); p=0.001) and AVR (AR=88.2/1000 person-years; HR=1.48, 95% CI (1.24 to 1.78); p<0.001). Any supplementation was not associated with longitudinal change in AS parameters in a linear mixed-effects model.

Conclusions Supplemental calcium with or without vitamin D is associated with lower survival and greater AVR in elderly patients with mild-moderate AS.

  • aortic valve stenosis
  • echocardiography

Data availability statement

Data are available upon reasonable request.

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Data availability statement

Data are available upon reasonable request.

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  • Twitter @kassisMD, @EssaHariri, @DesaiMilindY, @tavrkapadia

  • NK and EHH contributed equally.

  • Contributors NK, EH, AKK and SK conceived and designed the study. NK, EH, AKK, KA, HL, AS, MG, MK and NB collected, analysed and interpreted the data. NK, EH, HL, BG, ZBP, SCH, MYD and SK drafted and critically revised the manuscript. BG, ZBP, SCH, MYD and SK supervised the study. NK, EH and SK are responsible for the overall content and serve as guarantors. All authors read and approved the final manuscript.

  • Funding This work was supported by unrestricted philanthropic support to the Cleveland Clinic Heart, Vascular, and Thoracic Institute.

  • Disclaimer The funding source had no role in the design or conduct of the study; the collection, management, analyses, or interpretation of the data; the preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; internally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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