Where Your Calcium Comes From Matters for CVD Risk: MESA Study

Patrice Wendling

October 26, 2016

BALTIMORE, MD — Ten-year follow-up from the Multi-Ethnic Study of Atherosclerosis (MESA) shows no excess cardiovascular risk with dietary calcium intake but suggests calcium supplements may be associated with a higher risk of coronary artery calcification (CAC)[1].

Among participants with a baseline CAC of zero, the relative risk of developing incident CAC over the 10 years was 27% lower for those with the highest total daily calcium intake (>1453 mg) compared with the lowest intake (<434 mg) after full adjustment (RR 0.73; 95% CI 0.57–0.93).

After total calcium intake was accounted for, however, the risk of incident CAC was 22% higher in participants who used calcium supplements than in those who did not (RR=1.22; 95% CI 1.07–1.39), according to data reported October 11, 2016 in the Journal of the American Heart Association.

Senior study investigator Dr Erin Michos (Johns Hopkins University School of Medicine, Baltimore, MD) told heartwire from Medscape, "I think most of the cardiology community has already bought into the fact that there's no cardiovascular benefit for any of these multivitamins or supplements. So most cardiologists will not be recommending or prescribing calcium supplements. The larger question, though, is whether, if they have patients on them, they are going to tell patients to stop them."

That may be somewhat challenging in light of a spate of conflicting studies including an oft-cited meta-analysis by the Auckland Calcium Study investigators showing that use of calcium supplements increased the risk of MI by about a quarter in postmenopausal women, while another 2015 meta-analysis found no increased risk of CHD.

Add to that, a just-published joint clinical guideline from the National Osteoporosis Foundation and the American Society for Preventive Cardiology stating that dietary and supplemental calcium are safe for CV health at recommended amounts.

Michos pointed out that the new guideline was based on a meta-analysis[2] of largely observational cohort studies but excluded those without a specific calcium dose, including the EPIC-Heidelberg cohort analysis[3] showing that calcium supplement users had an 86% increased risk of MI.

"One of the things that the new meta-analysis by Chung et al did show was that there was no dose response, meaning that more was not better. So if people are able to reach the [recommended] amount of calcium through their diet, they don't need to be taking supplements," Michos said.

She added that there is no evidence of a benefit with calcium supplements and at the very least it's known they can cause kidney stones, bloating, and constipation.

"Everyone agrees that dietary calcium seems to be safe . . . but I personally think the data for supplements is inconclusive and that the body metabolizes calcium very differently when it comes from supplements vs diet."

The present analysis involved 5548 MESA participants with no history of CVD (52% female; aged 45–84 years). Unlike prior studies, including an ancillary study of the Women's Health Initiative that failed to find a higher CAC burden in women receiving calcium/vitamin D supplements using a single computed tomography (CT) scan at 7 years, in this study CAC was measured by CT at baseline and again 10 years later in 2742 participants. Baseline total calcium intake was assessed from diet using a food frequency questionnaire and calcium supplements by a medication inventory. Total daily calcium intake was categorized into quintiles.

Among 1567 participants with no baseline CAC, the highest quintile of total calcium intake, as previously noted above, was associated with a lower risk of incident CAC, while the risk of CAC was 22% higher in those using supplements.

Adjusted Risk Estimates for Incident CAC

Total daily calcium intake quintile Relative risk* 95% CI
1: <434.9 mg 1 Reference
2: 434.9–650.7 mg 0.95 0.79–1.14
3: 650.7–936.5 mg 1.02 0.85–1.23
4: 936.5–1453.5 mg 0.86 0.69–1.05
5: >1453.5 mg 0.73 0.57–0.93
Calcium supplements 1.22 1.07–1.39
*Fully adjusted for demographics, lifestyle factors, CVD risk factors, and use of calcium supplements

The results suggest that any protective effect of calcium intake and incident CAC occurs in participants with high dietary calcium intake, "which could be a proxy for overall healthier diets," the investigators concluded.

The study was supported by contracts from the National Heart, Lung, and Blood Institute and by grants from the National Center for Research Resources. Michos reported receiving an honorarium from Siemens Diagnostics for work unrelated to the study; the coauthors reported no relevant financial relationships.

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