In recent years, the potential contribution of dietary and supplemental calcium to elevating cardiovascular risk has been widely debated.1–2 Adequate intakes of calcium, along with vitamin D, have been encouraged due to the important physiological and structural roles of these nutrients, particularly in reducing bone fracture risk. Moreover, supplemental calcium has been advocated3 because the amount of calcium obtained from foods consistently falls short of current dietary recommendations.4 Although traditionally regarded as safe, recent findings have led to concerns regarding a putative association between calcium supplementation and myocardial infarction and cardiovascular‐related mortality,5–8 prompted by a randomized controlled trial that demonstrated elevated cardiovascular event risk with calcium supplementation versus placebo among postmenopausal women.9 Evidence from observational studies and exploratory analysis of a randomized controlled trial, however, has failed to demonstrate associations between calcium intake and coronary artery calcium scores in adults.10–12 Furthermore, a recent meta‐analysis did not demonstrate an increased risk for heart disease or all‐cause mortality risk in elderly women taking calcium supplementation with or without vitamin D versus those assigned to placebo.13 Currently, the available literature is sparse and inconclusive. Because both cardiovascular disease and osteoporosis contribute significantly to mortality and morbidity,14–15 further assessment of the casual relationship between calcium intake and cardiovascular risk is of importance.
A suggested mechanism by which supplemental calcium may elevate cardiovascular risk is through the acceleration of vascular calcification induced by acute elevations in circulating calcium.16 Vascular calcification is a clinical indicator of atherosclerosis and may predict cardiovascular‐related mortality.17 The investigation of a causal role of dietary or supplemental calcium in cardiovascular‐related outcomes has been hampered by a lack of sensitive experimental methodology for assessing early vascular calcification and by the extensive intervention period necessary to monitor coronary artery disease (CAD) progression in human populations.
In the present study, we used a relevant animal model for the study of CAD and both innovative and traditional methods for detecting soft tissue calcium, cardiovascular function, and CAD burden. The Ossabaw miniature swine model has translational relevance to humans because it demonstrates the full spectrum of human disease progression from metabolic syndrome to CAD with calcified atherosclerotic plaques when fed an atherogenic diet.18–19 Furthermore, their size makes the Ossabaw pig an ideal model for using imaging techniques and kinetic studies that necessitate ample blood and tissue sampling. Our group has demonstrated previously that the Ossabaw pig is an adequate model for assessing coronary artery calcification (CAC) through the use of novel calcium tracer kinetic modeling.20 The isotope 41Ca is a long‐lived (t1/2 >105 years) calcium tracer that can be measured in low concentrations (10−18 mol/L) by accelerator mass spectrometry. Previously, our group has used 41Ca tracer kinetics to monitor bone turnover and bone calcium retention.21 We recently verified that compartmental kinetic modeling of 41Ca can be used to assess early CAD‐associated calcium deposition in the coronary arteries.20
The primary aim of this study was to investigate the impact of high calcium intake from a supplemental source (calcium carbonate [CaCO3]) or dairy on coronary artery calcium deposition in the Ossabaw miniature swine fed an atherogenic diet, using novel 41Ca tracer kinetics to characterize early CAC. Secondary objectives included the investigation of the effect of high calcium intake on cardiovascular function and CAD progression, using more t