Strong Bones Equals Weak Heart
!Abstract and link to article is at the bottom of this page
by Jennifer Gibson, PharmD
Adequate calcium intake is an important nutritional factor for skeletal health. Calcium (when taken with adequate Vitamin D) prevents bone loss and decreases the risk of fractures and associated morbidity and mortality. Most adults require 1000 mg of calcium daily. (Children and postmenopausal women require slightly more.) For decades, physicians and pharmacists have been advocating calcium supplementation to ensure adequate intake for patients, particularly postmenopausal women, owing to a belief that calcium supplementation offered significant benefits without many adverse consequences. Now, a new meta-analysis in the British Medical Journal (BMJ) claims that calcium supplementation, in fact, leads to an increased risk for cardiovascular events.
The authors of the BMJ analysis evaluated 15 randomized, double-blinded, placebo-controlled studies that involved the use of calcium supplements (at least 500 mg daily) in adults over age 40. In total, the pooled analysis included approximately 20,000 patients. The mean age of study participants was _72 years, and 83% were women. The average follow-up period of the studies was 4 years. Surprisingly, the authors found a significant 30% increased risk of heart attack in patients receiving calcium. An increased risk was also seen for stroke and sudden death, but these results were not significant. In real-world terms, the authors suggest that treating 1000 people with calcium for 5 years will prevent 26 fractures, but will cause 14 heart attacks, 10 strokes, and 13 deaths.__
Of note, cardiovascular events were not the primary endpoint of any study included in the meta-analysis. And, both calcium citrate and calcium carbonate were included in the evaluation. However, calcium supplementation with vitamin D was excluded from the study. (Vitamin D is essential to adequate nutrition and bone health, and the Women’s Health Initiative found that calcium plus vitamin D had no effect on cardiovascular risk factors. Plus, a review in Annals of Internal Medicine recently reported that vitamin D may actually reduce cardiovascular risk.)
The BMJ meta-analysis is not the first to suggest that calcium may have a detrimental effect on cardiovascular health. A study by the same lead researcher in 2008 also found a significant increase in cardiovascular risk with calcium supplementation among nearly 1500 postmenopausal women. However, the previously-mentioned Annals study and a recent pharmacoepidemiological evaluation of calcium suggest that calcium plus vitamin D has no effect on cardiovascular events or death.
One take-away point from all of these studies is that no increased cardiovascular risk has ever been associated with dietary calcium intake. By consuming 3 to 4 portions of dairy and soy daily, most people will meet their recommended daily intake of calcium. Ideally, calcium supplements should be used to make up the difference between dietary intake and daily requirements. But, most people who take supplements consume the entire recommended daily allowance of calcium as a supplement, ignoring the fact that they likely consume close to that through a healthy diet. In the BMJ analysis, the risk of cardiovascular events was stronger among people who had higher dietary calcium intake in addition to taking supplements, proving that if a little is good, a lot is not always better.
Patients should focus on dietary sources of calcium, and be mindful to include fruits, vegetables, legumes, and fish that contain surprising amounts of the bone-building nutrient. A large study of postmenopausal women found that high dietary calcium intake was associated with a decrease in mortality risk associated with heart disease.
More follow-up is needed to define whether the type of calcium supplement or simultaneous vitamin D supplementation alters cardiovascular risk. For now, clinicians should encourage dietary intake of calcium, and use supplements as a way to augment — but not replace — the recommended daily intake.
References
- Bolland MJ, Avenell A, Baron JA, Grey A, MacLennan GS, Gamble GD, & Reid IR (2010). Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ (Clinical research ed.), 341 PMID: 20671013 {July 2010 - see below}
- Bolland MJ, Barber PA, Doughty RN, Mason B, Horne A, Ames R, Gamble GD, Grey A, & Reid IR (2008). Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial. BMJ (Clinical research ed.), 336 (7638), 262-6 PMID: 18198394
- Bostick RM, Kushi LH, Wu Y, Meyer KA, Sellers TA, & Folsom AR (1999). Relation of calcium, vitamin D, and dairy food intake to ischemic heart disease mortality among postmenopausal women. American journal of epidemiology, 149 (2), 151-61 PMID: 9921960
- Hsia J, Heiss G, Ren H, Allison M, Dolan NC, Greenland P, Heckbert SR, Johnson KC, Manson JE, Sidney S, Trevisan M, & Women’s Health Initiative Investigators (2007). Calcium/vitamin D supplementation and cardiovascular events. Circulation, 115 (7), 846-54 PMID: 17309935
- Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, Gallagher JC, Gallo RL, Jones G, Kovacs CS, Mayne ST, Rosen CJ, & Shapses SA (2010). The 2011 Report on Dietary Reference Intakes for Calcium and Vitamin D from the Institute of Medicine: What Clinicians Need to Know. The Journal of clinical endocrinology and metabolism PMID: 21118827
- Shah SM, Carey IM, Harris T, DeWilde S, & Cook DG (2010). Calcium supplementation, cardiovascular disease and mortality in older women. Pharmacoepidemiology and drug safety, 19 (1), 59-64 PMID: 19757413
- Wang L, Manson JE, Song Y, & Sesso HD (2010). Systematic review: Vitamin D and calcium supplementation in prevention of cardiovascular events. Annals of internal medicine, 152 (5), 315-23 PMID: 20194238
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Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis.
BMJ. 2010 Jul 29;341:c3691. doi: 10.1136/bmj.c3691.
Bolland MJ, Avenell A, Baron JA, Grey A, MacLennan GS, Gamble GD, Reid IR.
Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92 019, Auckland 1142, New Zealand.
Comment in:
* BMJ. 2010;341:c3856.
* BMJ. 2010;341:c4995.
* BMJ. 2010;341:c4993.
* BMJ. 2010;341:c5003.
* BMJ. 2010;341:c4997.
* Ann Intern Med. 2010 Nov 16;153(10):JC5-7.
* Evid Based Med. 2010 Dec;15(6):181.
OBJECTIVE: To investigate whether calcium supplements increase the risk of cardiovascular events.
DESIGN: Patient level and trial level meta-analyses.
DATA SOURCES: Medline, Embase, and Cochrane Central Register of Controlled Trials (1966-March 2010), reference lists of meta-analyses of calcium supplements, and two clinical trial registries. Initial searches were carried out in November 2007, with electronic database searches repeated in March 2010.
STUDY SELECTION: Eligible studies were randomised, placebo controlled trials of calcium supplements (>or=500 mg/day), with 100 or more participants of mean age more than 40 years and study duration more than one year. The lead authors of eligible trials supplied data. Cardiovascular outcomes were obtained from self reports, hospital admissions, and death certificates.
RESULTS: 15 trials were eligible for inclusion, five with patient level data (8151 participants, median follow-up 3.6 years, interquartile range 2.7-4.3 years) and 11 with trial level data (11 921 participants, mean duration 4.0 years). In the five studies contributing patient level data, 143 people allocated to calcium had a myocardial infarction compared with 111 allocated to placebo (hazard ratio 1.31, 95% confidence interval 1.02 to 1.67, P=0.035). Non-significant increases occurred in the incidence of stroke (1.20, 0.96 to 1.50, P=0.11), the composite end point of myocardial infarction, stroke, or sudden death (1.18, 1.00 to 1.39, P=0.057), and death (1.09, 0.96 to 1.23, P=0.18). The meta-analysis of trial level data showed similar results: 296 people had a myocardial infarction (166 allocated to calcium, 130 to placebo), with an increased incidence of myocardial infarction in those allocated to calcium (pooled relative risk 1.27, 95% confidence interval 1.01 to 1.59, P=0.038).
CONCLUSIONS: Calcium supplements (without coadministered vitamin D) are associated with an increased risk of myocardial infarction. As calcium supplements are widely used these modest increases in risk of cardiovascular disease might translate into a large burden of disease in the population. A reassessment of the role of calcium supplements in the management of osteoporosis is warranted.