Brittany Ray AND Evidence Analysis Worksheet Citation Study Design Class Research Purpose Inclusion Criteria Larsson

S, Orsini N, Wolk A. Dietary calcium intake and risk of stroke: a dose-response meta-analysis. Am J Clin Nutr. 2013; 97:951-957. Dose-response meta-analysis M Is there an association between dietary calcium intake and stroke risk? They included observational prospective studies that reported RRs with 95% CIs for the association between dietary calcium intake and stroke incidence They did not include randomized trials. They excluded duplicate and irrelevant articles. They used PubMed and EMBASE to find literature with the following strategy: (calcium intake OR calcium supplements OR calcium supplementation) AND (stroke OR cerebral infarction OR cerebrovascular disease OR hemorrhage). Data extraction from two researchers included authors last name, year of publication, sex age, sample size, duration of follow-up, methods used to assess intake of calcium and determine stroke cases. Study quality was evaluated. They used 11 articles from a possible 1195 that used prospective studies for meta-analysis. They were published between 1996 and 2012. Combined they had 9095 stroke cases. They were conducted in Europe, Asia, and America. Data Collection Summary Independent variables are calcium intake and calcium supplementation. There was comparison between high and low intake, as well as dairy and non-dairy sources of dietary calcium. They estimated an RR with 95% CI for a 300-mg/day increase in calcium intake for every study. The analysis was stratified by median calcium intake in the populations. The dependent variable is stroke risk. Common confounding variables are age, smoking, BMI, physical activity, DM, hypertension, alcohol consumption, and intake of other nutrients. They found the average intake for each category and assigned it to the

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corresponding RR. They also looked for a potential nonlinear relation between calcium intake and stroke risk using a 2-stage random-effects dose response meta-analysis. They looked for heterogeneity among the studies using Q and I2 statistics. They investigated the source of calcium intake and stroke risk. Summary of Results The association between total dietary calcium intake and risk of stroke was nonlinear. When there was higher relative risk with low calcium intake, there was lower risk with higher intake and vice versa. The median intake (700mg/day) was used as a reference to estimate all RRs. There was statistically significant heterogeneity among the studies (P<0.001, I2=70.3%). They found publication bias among studies with low average calcium intake, but not among those with high average calcium intake. These associations differed among populations. A statistically significant inverse relation between calcium and stroke risk occurred in Asian populations (RR=0.78 and 95% CI=0.71-1.10), while no association was seen in American populations (RR=0.95 and 95% CI=0.81-1.10) and a weak one was seen in European populations (RR=1.03 and 95% CI=1.001.06). Publication bias may have affected these results. For studies with low average calcium intake the RR for a 300-mg/day increase in calcium intake were 0.84 for ischemic stroke, 0.80 for intracerebral hemorrhage, and 0.83 for subarachnoid hemorrhage. An overall 18% decrease in risk was found. However, due to publication bias, these results may not be reliable. The RR of stroke for a 300 mg/day increase in calcium intake for dairy calcium was 0.78 and for nondairy calcium was 0.98. There was no statistically significant association between calcium supplementation and stroke risk. Author Conclusion The results show that calcium intake may be inversely associated with stroke risk in populations with low to moderate calcium intakes. This is also true for Asian populations, but not American or European. There was an 18% reduction of stroke risk in the low to moderate intake populations. The Asian populations saw a decrease of 22%. There was not much difference between stroke types. There were inconsistent findings across populations. It may be due to the differences in calcium intake, which is much lower in Asian populations. The main source of calcium also differed. European and American populations had dairy foods as the major source, while nondairy is the main source for Asian populations. Other nutrients in dairy products may account for the conflicting results among populations. Dairy calcium intake

was inversely associated with decreased stroke risk, while nondairy calcium intake was not. Results may not be very accurate due to the found publication bias. Reviewer Comments The main strength was the type of study. Its use of prospective studies minimized selection and recall bias. There was also no conflict of interest. There are limitations. Residual confounding may skew results. Other nutrients may also interfere with results. Assessing calcium intake in the studies is most likely inaccurate. Publication bias from previous studies is likely a problem.