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      Calcium Intake and Serum Calcium Level in Relation to the Risk of Ischemic Stroke: Findings from the REGARDS Study

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          Abstract

          Background and Purpose

          Data on the association between calcium (Ca) and ischemic stroke are sparse and inconsistent. This study aimed to examine Ca intake and serum Ca levels in relation to risk of ischemic stroke.

          Methods

          The primary analysis included 19,553 participants from the Reasons for Geographic And Racial Differences in Stroke (REGARDS) study. A subcohort was randomly selected to create a case-cohort study (n=3,016), in which serum Ca levels were measured. Ischemic stroke cases were centrally adjudicated by physicians based on medical records. Cox proportional hazards regression for the cohort and weighted Cox proportional hazard regression with robust sandwich estimation method for the case-cohort analysis with adjustment for potential confounders were performed.

          Results

          During a mean 8.3-year follow-up, 808 incident cases of ischemic stroke were documented. Comparing the highest quintile to the lowest, a statistically significant inverse association was observed between total Ca intake and risk of ischemic stroke (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.55 to 0.95; P linear-trend=0.183); a restricted cubic spline analysis indicated a threshold effect like non-linear association of total Ca intake with ischemic stroke ( P non-linear=0.006). In the case-cohort, serum Ca was inversely associated with the risk of ischemic stroke. Compared to the lowest, the highest quintile of serum Ca had a 27% lower risk of ischemic stroke (HR, 0.73; 95% CI, 0.53 to 0.99; P linear-trend=0.013). Observed associations were mainly mediated by type 2 diabetes, hypertension, and cholesterol.

          Conclusions

          These findings suggest that serum Ca has inverse and Ca intake has threshold effect like association with risk of ischemic stroke.

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          The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis.

          Anastassios G Pittas, Joseph Lau, Frank Hu … (2007)
          Altered vitamin D and calcium homeostasis may play a role in the development of type 2 diabetes mellitus (type 2 DM). EVIDENCE ACQUISITION AND ANALYSES: MEDLINE review was conducted through January 2007 for observational studies and clinical trials in adults with outcomes related to glucose homeostasis. When data were available to combine, meta-analyses were performed, and summary odds ratios (OR) are presented. Observational studies show a relatively consistent association between low vitamin D status, calcium or dairy intake, and prevalent type 2 DM or metabolic syndrome [OR (95% confidence interval): type 2 DM prevalence, 0.36 (0.16-0.80) among nonblacks for highest vs. lowest 25-hydroxyvitamin D; metabolic syndrome prevalence, 0.71 (0.57-0.89) for highest vs. lowest dairy intake]. There are also inverse associations with incident type 2 DM or metabolic syndrome [OR (95% confidence interval): type 2 DM incidence, 0.82 (0.72-0.93) for highest vs. lowest combined vitamin D and calcium intake; 0.86 (0.79-0.93) for highest vs. lowest dairy intake]. Evidence from trials with vitamin D and/or calcium supplementation suggests that combined vitamin D and calcium supplementation may have a role in the prevention of type 2 DM only in populations at high risk (i.e. glucose intolerance). The available evidence is limited because most observational studies are cross-sectional and did not adjust for important confounders, whereas intervention studies were short in duration, included few subjects, used a variety of formulations of vitamin D and calcium, or did post hoc analyses. Vitamin D and calcium insufficiency may negatively influence glycemia, whereas combined supplementation with both nutrients may be beneficial in optimizing glucose metabolism.
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            Mediation Analysis: A Practitioner's Guide

            Tyler J. VanderWeele (2016)
            This article provides an overview of recent developments in mediation analysis, that is, analyses used to assess the relative magnitude of different pathways and mechanisms by which an exposure may affect an outcome. Traditional approaches to mediation in the biomedical and social sciences are described. Attention is given to the confounding assumptions required for a causal interpretation of direct and indirect effect estimates. Methods from the causal inference literature to conduct mediation in the presence of exposure-mediator interactions, binary outcomes, binary mediators, and case-control study designs are presented. Sensitivity analysis techniques for unmeasured confounding and measurement error are introduced. Discussion is given to extensions to time-to-event outcomes and multiple mediators. Further flexible modeling strategies arising from the precise counterfactual definitions of direct and indirect effects are also described. The focus throughout is on methodology that is easily implementable in practice across a broad range of potential applications.
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              The Reasons for Geographic and Racial Differences in Stroke Study: Objectives and Design

              Virginia Howard, Mary Cushman, LeaVonne Pulley … (2005)
              The REasons for Geographic And Racial Differences in Stroke (REGARDS) Study is a national, population-based, longitudinal study of 30,000 African-American and white adults aged ≧45 years. The objective is to determine the causes for the excess stroke mortality in the Southeastern US and among African-Americans. Participants are randomly sampled with recruitment by mail then telephone, where data on stroke risk factors, sociodemographic, lifestyle, and psychosocial characteristics are collected. Written informed consent, physical and physiological measures, and fasting samples are collected during a subsequent in-home visit. Participants are followed via telephone at 6-month intervals for identification of stroke events. The novel aspects of the REGARDS study allow for the creation of a national cohort to address geographic and ethnic differences in stroke.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Stroke
                Journal ID (iso-abbrev): J Stroke
                Journal ID (publisher-id): JOS
                Title: Journal of Stroke
                Publisher: Korean Stroke Society
                ISSN (Print): 2287-6391
                ISSN (Electronic): 2287-6405
                Publication date (Print): September 2019
                Publication date (Electronic): 30 September 2019
                Volume: 21
                Issue: 3
                Pages: 312-323
                Affiliations
                [a ]Department of Epidemiology and Biostatistics, School of Public Health, Indiana University Bloomington, Bloomington, IN, USA
                [b ]Department of Vice Chancellor for Research/Tennessee Clinical and Translational Science Institute, University of Tennessee Health Science Center, Memphis, TN, USA
                [c ]Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA
                [d ]Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, Philadelphia, PA, USA
                [e ]Department of Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, USA
                [f ]Department of Psychiatry, School of Medicine, Indiana University, Indianapolis, IN, USA
                [g ]Department of Obstetrics and Gynecology, Columbia University Irving Medical Center, New York, NY, USA
                Author notes
                Correspondence: Ka He Department of Obstetrics and Gynecology, Columbia University Irving Medical Center, 622 W. 168th, Room 16-62, New York, NY 10032, USA Tel: +1-212-305-6973 Fax:+1-212-305-2171 E-mail: kk3399@ 123456cumc.columbia.edu
                Article
                Publisher ID: jos-2019-00542
                DOI: 10.5853/jos.2019.00542
                PMC ID: 6780017
                PubMed ID: 31590475
                SO-VID: 8562bcf4-a08f-4d53-8e13-9b4054b0e8ab
                Copyright © Copyright © 2019 Korean Stroke Society
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 8 March 2019
                Date revision received : 28 June 2019
                Date accepted : 27 August 2019
                Categories
                Subject: Original Article

                Keywords: stroke,calcium,hypertension,diabetes mellitus,cholesterol
                Data availability:
                Keywords: stroke, calcium, hypertension, diabetes mellitus, cholesterol

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