The Effects of 3 Years of Calcium Supplementation on Common Carotid Artery Intimal Medial Thickness and Carotid Atherosclerosis in Older Women: An Ancillary Study of the CAIFOS Randomized Controlled Trial

Calcium is an essential nutrient for skeletal health; however, it has been suggested that supplemental calcium may be associated with adverse cardiovascular effects, raising widespread concern about their use. One suggested mechanism is via increasing carotid atherosclerosis, however few randomized controlled trials (RCT) of calcium supplements have assessed these mechanisms. The calcium intake fracture outcome study (CAIFOS) was a 5-year RCT (1998 to 2003) of 1.2g of elemental calcium in the form of calcium carbonate in 1460 elderly women. An ancillary study of 1103 women assessed common carotid artery intimal medial thickness (CCA-IMT) and carotid atherosclerosis at year 3 (2001). The effects of supplementation were studied in intention-to-treat (ITT) and per-protocol (PP) analyses before and after adjustment for baseline cardiovascular risk factors. The mean age of participants at baseline was 75.2 +/- 2.7 years. In ITT analyses, women randomized to calcium supplementation had no difference in multivariable-adjusted mean CCA-IMT (calcium 0.778 +/- 0.006mm, placebo 0.783 +/- 0.006mm, p=0.491) and maximum CCA-IMT (calcium 0.921 +/- 0.007mm, placebo 0.929 +/- 0.006mm, p=0.404). Women randomized to calcium did not have increased carotid atherosclerosis (calcium 47.2%, placebo 52.7%, p=0.066). However, in women taking at least 80% of the supplements, a significant reduction in carotid atherosclerosis was observed in unadjusted but not in multivariate-adjusted models (p=0.033 and p=0.064, respectively). Participants in the highest tertile of total calcium (diet and supplements) had reduced carotid atherosclerosis in unadjusted and multivariable-adjusted analyses compared with participants in the lowest tertile (odds ratio [OR]=0.67 [95% confidence interval (CI) 0.50-0.90], p=0.008, and OR=0.70 [95% CI 0.51-0.96], p=0.028, respectively). In conclusion, these findings do not support the hypothesis that calcium supplementation increases carotid artery intimal medial thickness or carotid atherosclerosis, and high calcium intake may reduce this surrogate cardiovascular risk factor. (c) 2014 American Society for Bone and Mineral Research.