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This systematic review of trials and observational studies examines conflicting evidence about potential cardiovascular risks associated with high levels of calcium intake.

Gout is a common type of inflammatory arthritis in patients seen by primary care physicians.To review evidence about treatment of acute gout attacks, management of hyperuricemia to prevent attacks, and discontinuation of medications for chronic gout in adults.Multiple electronic databases from January 2010 to March 2016, reference mining, and pharmaceutical manufacturers.Studies of drugs approved by the U.S. Food and Drug Administration and commonly prescribed by primary care physicians, randomized trials for effectiveness, and trials and observational studies for adverse events.Data extraction was performed by one reviewer and checked by a second reviewer. Study quality was assessed by 2 independent reviewers. Strength-of-evidence assessment was done by group discussion.High-strength evidence from 28 trials (only 3 of which were placebo-controlled) shows that colchicine, nonsteroidal anti-inflammatory drugs (NSAIDs), and corticosteroids reduce pain in patients with acute gout. Moderate-strength evidence suggests that low-dose colchicine is as effective as high-dose colchicine and causes fewer gastrointestinal adverse events. Moderate-strength evidence suggests that urate-lowering therapy (allopurinol or febuxostat) reduces long-term risk for acute gout attacks after 1 year or more. High-strength evidence shows that prophylaxis with daily colchicine or NSAIDs reduces the risk for acute gout attacks by at least half in patients starting urate-lowering therapy, and moderate-strength evidence indicates that duration of prophylaxis should be longer than 8 weeks. Although lower urate levels reduce risk for recurrent acute attacks, treatment to a specific target level has not been tested.Few studies of acute gout treatments, no placebo-controlled trials of management of hyperuricemia lasting longer than 6 months, and few studies in primary care populations.Colchicine, NSAIDs, and corticosteroids relieve pain in adults with acute gout. Urate-lowering therapy decreases serum urate levels and reduces risk for acute gout attacks.Agency for Healthcare Research and Quality. (Protocol registration: http://effectivehealth-care.ahrq.gov/ehc/products/564/1992/Gout-managment-protocol-141103.pdf).

Background Conflicting evidence exists regarding potential cardiovascular risks associated with high levels of calcium intake. Purpose To update and reanalyze 2 systematic reviews to examine the effects of calcium intake on cardiovascular disease (CVD) among generally healthy adults. Data sources MEDLINE; Cochrane Central Register of Controlled Trials; Scopus, including EMBASE; and previous evidence reports from English-language publications from 1966 to July 2016. Study selection Randomized trials and prospective cohort and nested case-control studies with data on dietary or supplemental intake of calcium, with or without vitamin D, and cardiovascular outcomes. Data extraction Study characteristics and results extracted by 1 reviewer were confirmed by a second reviewer. Two raters independently assessed risk of bias. Data synthesis Overall risk of bias was low for the 4 randomized trials (in 10 publications) and moderate for the 27 observational studies included. The trials did not find statistically significant differences in risk for CVD events or mortality between groups receiving supplements of calcium or calcium plus vitamin D and those receiving placebo. Cohort studies showed no consistent dose-response relationships between total, dietary, or supplemental calcium intake levels and cardiovascular mortality and highly inconsistent dose-response relationships between calcium intake and risks for total stroke or stroke mortality. Limitations CVD disease outcomes were secondary end points in all trials. Dose-response metaregression analysis of cohort studies was limited by potential confounding, ecological bias, and imprecise measures of calcium exposures. Data were scarce regarding very high calcium intake-that is, beyond recommended tolerable upper intake levels. Conclusion Calcium intake within tolerable upper intake levels (2000 to 2500 mg/d) is not associated with CVD risk in generally healthy adults. Primary funding source National Osteoporosis Foundation.