Association Between Calcium Supplementation and the Risk of Cardiovascular Disease and Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: Some observational studies and randomised controlled trials (RCTs) have reported an association between calcium supplementation and increased risk of cardiovascular disease. Previous meta-analyses on the topic, based on data from RCTs and observational studies, have contradictory findings. This meta-analysis was conducted to determine the difference in associated risks of calcium supplementation with cardiovascular disease and stroke in RCTs. METHODS: Relevant studies published from database inception to 6 August 2021 were sourced from PubMed, Embase, Scopus, and the Cochrane Central Register of Controlled Trials. Any RCTs focusing on the relationship between calcium supplementation and incidence of cardiovascular disease or stroke were included. Articles were screened independently by two authors, according to the PICO criteria, with disagreements resolved by a third author. RESULTS: Twelve RCTs were included in the meta-analysis. Calcium supplementation was not associated with myocardial infarction, total stroke, heart failure admission, and all-cause/cardiovascular mortality. Subgroup analysis focusing on calcium monotherapy/calcium co-therapy with vitamin D, female sex, follow-up duration, and geographical region did not affect the findings. CONCLUSION: Calcium supplementation was not associated with myocardial infarction, total stroke, heart failure admission, and cardiovascular/all-cause mortality. Further studies are required to examine and understand these associations.

Pharmacogenetic versus clinical dosing of warfarin in individuals of Chinese and African-American ancestry: assessment using data simulation.

BACKGROUND: Clinical trials of genotype-guided dosing of warfarin have yielded mixed results, which may in part reflect ethnic differences among study participants. However, no previous study has compared genotype-guided versus clinically guided or standard-of-care dosing in a Chinese population, whereas those involving African-Americans were underpowered to detect significant differences. We present a preclinical strategy that integrates pharmacogenetics (PG) and pharmacometrics to predict the outcome or guide the design of dosing strategies for drugs that show large interindividual variability. We use the example of warfarin and focus on two underrepresented groups in warfarin research. MATERIALS AND METHODS: We identified the parameters required to simulate a patient population and the outcome of dosing strategies. PG and pharmacogenetic plus loading (PG+L) algorithms that take into account a patient's VKORC1 and CYP2C9 genotype status were considered and compared against a clinical (CA) algorithm for a simulated Chinese population using a predictive Monte Carlo and pharmacokinetic-pharmacodynamic framework. We also examined a simulated population of African-American ancestry to assess the robustness of the model in relation to real-world clinical trial data. RESULTS AND CONCLUSION: The simulations replicated similar trends observed with clinical data in African-Americans. They further predict that the PG+L regimen is superior to both the CA and the PG regimen in maximizing percentage time in therapeutic range in a Chinese cohort, whereas the CA regimen poses the highest risk of overanticoagulation during warfarin initiation. The findings supplement the literature with an unbiased comparison of warfarin dosing algorithms and highlights interethnic differences in anticoagulation control.