Calcium supplements have recently been reported to be associated with an increased risk of cardiovascular events¹. However, the validity of these findings has been questioned. A major concern is that the mechanism underlying an increase in cardiovascular events has not been demonstrated². Calcium initiates cardiac and vascular contraction following influx of calcium into cardiac and smooth muscle from extracellular fluid. We have investigated whether the acute rise in serum calcium following calcium supplement administration is associated with adverse changes in cardiovascular function.
In an open interventional study, we recruited 25 volunteers (16 female, age 60.3±6.5 years, BMI 25.7±2.7 kg/m²) from the community who were not taking calcium supplements. Participants were studied before and 3 hours after a single oral dose of 1000 mg calcium citrate. We assessed well-validated markers of arterial stiffness (pulse wave velocity, PWV), arterial wave reflection (augmentation index, AIx) and myocardial perfusion (subendocardial viability ratio, SEVR) by pulse wave analysis and endothelial function (reactive hyperaemia index, RHI) by peripheral arterial tonometry.
Total and ionized serum calcium were acutely increased by 0.10±0.07 and 0.06±0.03 mmol/l respectively 3 hours after calcium citrate administration (p<0.0001 for both comparisons). Following administration of calcium citrate there was a fall in AIx from a median of 29.7% (23.8-34.0) to 26.4% (22.7-34.0, p=0.03) and increase in SEVR from 163% (148-174) to 170% (149-185, p=0.007). PWV and RHI were not significantly altered. The change in total calcium was negatively correlated with the change in AIx (r=-0.48, p=0.02).
In summary, the acute increase in serum calcium following calcium supplement administration is associated with reduced arterial wave reflection and increased myocardial perfusion. If maintained long-term, these changes would be expected to reduce cardiovascular risk. Acute serum calcium-mediated changes in these parameters of cardiovascular function are unlikely to underlie an association between calcium supplementation and cardiovascular events.

Acknowledgement: This study was supported by a grant from Foundation Daw Park.