Topic: Drug consult
Drug Consult Example
Date and time requested: September 23, 2013 at 10:00 AM
Date and time answered: September 27, 2013 at 5:00 PM
Pharmacy has been consulted re: Are calcium supplements associated with coronary heart disease in adult patients?
Background:
Calcium supplementation has long been recommended for promoting bone health and is often utilized for the prevention and treatment of osteoporosis.1 It has been reported that in the older population close to 50% of men and 70% of women are users of calcium supplements.1 In most adult patients, the recommended daily allowance (RDA) of elemental calcium is 1000 mg. In females aged 51 and greater, the RDA is slightly increased at 1200 mg.2 Calcium administration is generally well tolerated with the most commonly occurring adverse effects being gastrointestinal discomfort, constipation, flatulence and nausea.3 Recently, there has been speculation about a correlation between calcium supplementation and cardiovascular risk. While some studies have reported cardiovascular benefits such as improvements in blood pressure and lipid panels, some concerning data linking calcium supplementation to increased risk of stroke, myocardial infarction and cardiovascular death has also been published.1 It has been hypothesized that excess calcium intake via supplementation may lead to cardiac calcium phosphate deposits which are correlated with risk of atherosclerosis, coronary heart disease and death.1
Literature Search Strategy:
A search was conducted using Ovid MEDLINE (2009 to September week 2 2013). Terms searched included supplemental calcium, calcium supplement, coronary heart disease and cardiovascular disease. The Boolean operator OR was first used to combine the terms supplemental calcium and calcium supplement and then used again to combine the terms coronary heart disease and cardiovascular disease. The Boolean operator AND was subsequently utilized to combine the results from supplemental calcium, OR calcium supplement, with coronary heart disease OR cardiovascular disease. The search was limited to the English language and humans and yielded 13 results. Of the 13 articles, 9 were excluded for being review articles, 2 were excluded because they focused on dietary rather than supplemental calcium intake and 1 was excluded for being focused specifically on myocardial infarction and stroke. The article to be discussed was chosen because it is relevant to the topic as it looks specifically at cardiovascular risk related to calcium supplementation in both men and women.
Results/Literature Analysis:
A prospective study was conducted to determine if calcium intake was associated with risk of death from heart disease, cerebrovascular disease or cardiovascular disease.1 Included participants were male and female AARP members with ages ranging from 50 to 71 years. Participants were geographically located in 6 states (California, Florida, Louisiana, New
Jersey, North Carolina, and Pennsylvania) in addition to 2 cities (Atlanta and Detroit). Patients were excluded if they did not complete their own baseline questionnaire, if they had a history of heart disease, stroke, diabetes, end-stage kidney disease or cancer with the omission of skin cancer if it was not melanoma. Patients were also excluded if their total dietary energy or calcium intakes were excessive (as defined by interquartile range calculations). In total 388,229 subjects were included in trial analysis and were followed for a duration of twelve years. While the above criteria did capture older adults which is a population with prevalent use of calcium supplements, the ages of enrolled patients does limit the external validity to apply results to both younger and older patients. Exclusion criteria did help improve internal validity of the study by excluding some confounding conditions, but also by excluding those with prior heart disease, we are prevented from making an assessment as to whether or not calcium supplementation would affect cardiovascular risk in those with a preexisting cardiac condition. As heart disease is a top cause of mortality in this country, this information would be valuable and further studies in this population may be warranted. At baseline, patients were asked to self-report three items. First, dietary calcium intake was assessed by a food frequency questionnaire which considered both portion sizes as well as frequency of ingestion of each of 124 listed items during the course of the previous year. Second, participants reported the frequency range (i.e. 1 to 3 times per week) as well as dose of any calcium supplements taken. And third, regularity and variety of any multivitamins taken was also reported. Based on the information provided, investigators calculated each patient’s calcium intake by dietary calcium alone, supplemental calcium alone (calcium supplement plus multivitamin) and total calcium (dietary plus supplemental). Overall 56% of women and 23% of men stated they took individual calcium supplements, were non-Hispanic white and had a lower consumption of alcohol, red meat and total fat. Although investigators attempted to standardize the self-reporting through a calibration method involving 24-hour dietary recalls, a limitation to the study is that calcium intake was not directly measured. In addition, it is possible that patients were ingesting calcium in mediums not captured in the questionnaires, such as in food items not contained on the list. Study design may also have been improved upon if investigators had collected information regarding duration of supplement use to determine if any increased risks were associated with length of use and also if there was a familial history of CVD. Although authors of this study did not explicitly specify a primary endpoint, the methods and objective were well defined. Investigators were able to access the Social Security Administration Death Master File and National Death Index Plus to determine if a subject died, and if so, what the cause of death was. Based on this information, as well as adjustments made for patient demographics, lifestyle and dietary variance, relative risks were estimated. Investigators estimated a 95% accuracy rate when pulling data from these databases. Relative risk is an appropriate method to determine level of association in a prospective cohort study, but due to the method of data collection, some error is inherent in study design. Study results showed that men who took more than 1000 mg per day of supplemental calcium in the form of both individual supplements and multivitamins as compared to men with no calcium supplementation had a 20% increased risk of cardiovascular death (RR 1.20; 95% CI, 1.05-1.36). When individual calcium supplements were considered without multivitamins, men who took more than 1000 mg per day of calcium had a 37% increased risk of death from heart disease (RR 1.37; 95% CI, 1.06-1.77). In women, no associations were seen between calcium supplementation and risk of cardiovascular mortality. Additionally, no association was found between dietary calcium intake and cardiovascular death. Given the large amount of patients in the study, the long study duration and the prevalence of calcium supplementation these increases in relative risk are highly clinically relevant.
Recommendations/Summary:
Due to the elevated risk of cardiovascular death in men who took more than 1000 mg per day of calcium supplementation, doses in this range should be avoided. While these results were not replicated in women, the authors of the study suggest that we cannot rule out the possibility that that a true association exists. Based on the above evidence I would recommend the following in both male and female patients:
• Encourage patients to meet calcium requirements through dietary intake. While dairy products are widely known to contain high calcium content, alternatives to dairy include collard greens, kale, soybeans, sardines and salmon. Calcium fortified foods are also available such as orange juice, tofu and cereals.4
• In patients unable to achieve adequate dietary intake, consider calcium supplementation at a dose less than 1000 mg per day.
• Supplements should be administered in 2 to 4 divided doses of no more than 600 mg per dose to ensure adequate absorption.5
• Example regimens:
o Ultra Strength TUMS® (1000 mg calcium carbonate; 400 mg elemental calcium). Directions: Chew one tablet by mouth twice daily.
▪ Least expensive alternative.5
▪ Absorption is best if taken with food, but may be reduced if patient is taking drugs that decrease stomach acid.5
▪ Associated with more gastrointestinal upset than alternative calcium formulations.5
o Citracal Regular® (500 mg of elemental calcium as citrate). Directions: Take one tablet by mouth twice daily.
▪ May be taken without regards for food.5
▪ Preferred in users of proton pump inhibitors or H2 receptor antagonists, as absorption is less dependent on pH and those with histories of either GI upset from calcium carbonate or kidney stones.5
• Patients requiring calcium supplementation, especially at a dose greater than 1000 mg per day, should be monitored closely for signs and symptoms of heart disease such as chest pain or shortness of breath. Stress tests may be used to assess patients for coronary heart disease at first sign of symptoms.
• Ensure adequate Vitamin D needed for calcium absorption (RDA 600 units per day).2
Closing:
Thank you for the opportunity for this consult and please let me know of any follow-up questions. I may be contacted via email at xxxx .mcphs.edu.
Respectfully,
Your Name, PharmD candidate
References:
1. Xiao Q, Murphy RA, Houston DK, Harris TB, Chow WH, Park Y. Dietary and Supplemental Calcium Intake and Cardiovascular Disease Mortality. JAMA Intern Med. 2013:173(8):639-646.
2. Lexicomp Web site. http://online.lexi.com.ezproxy.mcphs.edu/lco/action/home. Accessed September 23, 2013.
3. Natural Standard Web site. http://www.naturalstandard.com.ezproxy.mcphs.edu. Accessed September 23, 2013
4. National Osteoporosis Foundation Web site. http://www.nof.org/articles/886. Accessed September 24, 2013.
5. Dynamed Web site. http://web.ebscohost.com.ezproxy.mcphs.edu/dynamed/search/basic Accessed September 25, 2014.
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