Calcium Intake From Diet and Supplements and the Risk of Coronary Artery Calcification and its Progression Among Older Adults: 10-Year Follow-up of the Multi-Ethnic Study of Atherosclerosis (MESA)

Anderson, John JB, et al. Journal of the American Heart Association 5.10 (2016): e003815.

http://jaha.ahajournals.org/content/5/10/e003815.full.pdf+html

Background

Although adequate calcium is necessary to maintain bone health, conflicting evidence exists regarding the potential risks associated with high levels of supplemental calcium intake and cardiovascular disease outcomes. Though the evidence is inconsistent, a number of cohort studies and randomised controlled trials have reported increased risk. One proposed mechanism is an increase in coronary artery calcification (CAC), a well-established surrogate marker of atherosclerosis and predictor of cardiovascular risk. Meta-analyses likewise have had conflicting results with both findings of an increased risk and no effect, dependent on the methodology and inclusion criteria for the included studies. Further good quality studies specifically designed to look at cardiovascular end points are important.

Study objective

John Hopkins University School of Medicine, Baltimore (USA) examined the relationship between calcium intakes from different sources (i.e. foods and supplements) and later risk of CAC in a large cohort.

Study design

This prospective cohort study consisted of 6814 men and women (mean age 62 years) of four different ethnicities, who were all free of CVD at baseline. Those with impaired renal function were excluded as this can affect calcium metabolism. Dietary assessment was carried out at baseline via the use of a validated 120-item quantitative FFQ. Those with implausibly high or low energy intakes or implausibly high reported calcium intakes were excluded from analysis. Participants were asked to bring in all medications used in the past two weeks to assess calcium supplement intake. CAC was measured in duplicate by electron-beam computed tomography (CT) or multidetector computer tomography. Baseline data from 5448 subjects was included in cross sectional analysis and longitudinal analysis was carried out using data from 2742 subjects (out of a possible 3305 that were eligible) who also had a second CT scan approximately 10 years later.

Main findings:

  • Baseline daily calcium intakes (total from food sources and supplements) were as follows:

Q1 Q2 Q3 Q4 Q5
<434.9 mg 434.9-650.7 mg 650.7-936.5 mg 936.5-1453.5 mg >1453.5 mg

  • 45.8% of the longitudinal cohort took calcium supplements.

  • 57.1% of the cohort were free of CAC at baseline.

  • Women had lower calcium intakes from the diet but higher calcium intakes from supplements than men, equating to higher mean total calcium intakes.

  • In cross sectional analysis, use of calcium supplements was not significantly associated with prevalent CAC and, in those with CAC>0 at baseline, there was no association between calcium intake and CAC burden.

  • When comparing baseline calcium intakes to CAC ~ 10 years later:

    • After adjusting for confounders, relative risk of developing CAC was lowest in the highest quintile of calcium intake (RR=0.73, 0.57-0.93), among those without CAC at baseline.

    • After adjusting for confounders and stratifying by supplement use, among those without CAC at baseline, the inverse association of high calcium intake with CAC risk was attenuated in supplement users.

    • After adjusting for confounders, among those without CAC at baseline, calcium supplement use was associated with a 22% increase in risk of developing CAC.

    • Among those with prevalent CAC at baseline, calcium intake was not associated with increased CAC progression.

Limitations of the study

Seventeen percent of the group intended for longitudinal analysis could not be included due to incomplete data which may have biased the sample. Assessments of diet and supplement intake were only carried out once during the study (at baseline) and then linked to an outcome occurring approximately 10 years later. This represents a significant limitation of the study, as diets and supplement use often change over time. Furthermore, food frequency questionnaires are less accurate than weighed diet diaries for recording dietary composition. Calcium supplement dosages used as part of the analysis were self-reported by the subjects and some were found to be implausible, introducing further potential bias. CAC is prognostic for CVD risk but is a surrogate marker rather than a hard end point measure such as CVD death and in addition, the vitamin D status of the subjects was not taken into account. It is of note that high dietary calcium intake may be a marker for a healthier diet overall, which could explain the reduced risk of CAC in those with the highest intakes rather than being due to calcium from the diet and supplements. Finally, this population were unusually healthy for their age and as the study was conducted in the US where dietary habits and supplement doses may differ, the results may not be relevant to a UK population. Most importantly, as this study was only observational in design, cause an effect cannot be established.

Author conclusions

Results showed a protective relationship between total calcium intake and incident coronary atherosclerosis, particularly among non-supplement users. However, calcium supplement use was independently associated with incident CAC; therefore calcium loading with supplements may not be entirely free of undesirable side effects. Findings should reassure individuals who are following healthy eating guidelines by eating high-calcium foods such as dairy products that consuming calcium from diet alone is not associated with incident CAC. Observational studies have suggested an association between intake of dairy products and a reduction in cardiovascular risk factors, such as blood pressure, and CVD events and death.

Wider research context

Results presented at the World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases in 2016 from the UK Biobank reported that data from 502,664 participants aged 40-69 years followed for up to 7 years revealed no association between calcium supplementation and hospitalisation or death from cardiovascular events. These results do not support the findings of the current study as they suggest no link between taking calcium supplements and CVD risk.

A newly published systematic review looked at 4 randomised trials (in 10 publications) and 27 observational trials concluded that trials did not show significant differences in CVD events or mortality between those taking calcium supplements, or those taking a placebo (Chung et al. 2016). Furthermore, cohort studies showed no consistent dose-response relationship between supplemental calcium and CVD mortality. However, other meta-analyses have reported different findings (Reid et al. 2015). There is some agreement between researchers in that dietary calcium from food in a healthy balanced diet does not have an adverse effect on cardiovascular health, and that taking very large doses of calcium above recommendations are not advised.

Relevance

The UK Reference Nutrient Intake (the amount of a nutrient that is enough to ensure that the needs of nearly all the group (97.5%) are being met) for non-lactating adults is 700 mg/day calcium. It is possible to achieve this by the consumption of a healthy, balanced diet, as described in the Eatwell Guide, which includes dairy foods or calcium-fortified dairy alternatives, as well as other dietary sources of calcium. Commercially available calcium supplements normally do not contain more than 800 mg, with multivitamin and mineral supplements often containing lower amounts. The Department of Health advise that taking up to 1500 mg per day is unlikely to cause harm. Calcium supplements at high doses do have side effects so people taking supplements should take these in moderation and only if their diets are deficient in calcium or if they have received a prescription from a health professional.

People that have been prescribed calcium and vitamin D supplements as part of their treatment or management for osteoporosis should not on the basis of the above study stop taking their supplements, but should discuss any concerns with their GP.

References

Chung M, Tang AM, Fu Z, Wang DD, Newberry SJ. Calcium Intake and Cardiovascular Disease Risk: An Updated Systematic Review and Meta-analysis. Ann Intern Med. [Epub ahead of print 25 October 2016]:. doi: 10.7326/M16-1165

Reid, I. R., Bristow, S. M. and Bolland, M. J. (2015), Cardiovascular Complications of Calcium Supplements. J. Cell. Biochem., 116: 494–501. doi:10.1002/jcb.25028