Lutsey, P. L. | Search bioRxiv

bioRxiv2017

A Pilot Randomized Trial of Oral Magnesium Supplementation on Supraventricular Arrhythmias

BackgroundMagnesium is believed to have a physiologic role in cardiac contractility, and evidence from epidemiologic and clinical studies has suggested that low serum concentrations of magnesium may be associated with increased risk of atrial fibrillation (AF).\n\nObjectiveAs part of the planning effort for a large randomized trial to prevent AF with magnesium supplementation, we conducted a 12-week pilot study to assess adherence to oral magnesium supplementation and matching placebo, estimate the effect on circulating magnesium concentrations, and evaluate the feasibility of using an ambulatory monitoring device (ZioPatch) for assessing premature atrial contractions (PACs), a predictor of AF.\n\nDesignDouble-blind randomized pilot clinical trial comparing supplementation with 400 mg magnesium oxide daily (versus placebo) over 12 weeks of follow-up. The ZioPatch was applied for 14 days at baseline and the end of follow-up. Adherence to the assigned treatment, and changes in PACs, serum magnesium concentration, glucose and blood pressure were assessed.\n\nResultsA total of 59 participants, 73% women and average age 62 years, were randomized. 98% of participants completed follow-up. Those assigned to the magnesium supplement took 75% of tablets as compared to 83% for those in the placebo group. Change in magnesium concentrations was significantly greater for those given magnesium supplement compared to placebo (0.07; 95% confidence interval (CI): 0.03, 0.12 mEq/L; p = 0.002). ZioPatch was worn for an average of 13.0 of the requested 14 days at baseline; at the end of follow-up, the average number of days of monitoring was 13.0 days for the magnesium supplement group and 12.7 days for the placebo group. For log PAC burden (episodes per hour), the average change from baseline was -0.05 (95% CI: -0.31, 0.20) for those randomized to magnesium supplement and 0.04 (95% CI: -0.24, 0.31) for those randomized to placebo (p=0.79 for difference). Gastrointestinal problems were reported by 50% of participants in the magnesium supplement group and 7% in the placebo group. Only one person in the magnesium supplement group and none in the placebo group experienced adverse events which led to treatment discontinuation.\n\nConclusionsIn this pilot randomized clinic trial, although gastrointestinal side effects to the magnesium supplement were common, adherence, measured by pill counts, was very good and, as a consequence, magnesium concentrations were greater for those randomly assigned to the magnesium supplement compared to placebo. Participant acceptance of the planned monitoring with ZioPatch was also very good. While the difference in the change in PACs was not significant, this pilot study was small, short-term, and did not include participants at high risk of AF. Thus, we could not reliably evaluate the effect of magnesium supplementation on PACs.\n\nClinicaltrials.gov registrationNCT02837328

clinical trials↗

bioRxiv2017

Large Meta-Analysis Provides Evidence For An Association Of Serum Vitamin D With Pulmonary Function

The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for the association of serum 25-hydroxyvitamin D [25(OH)D] and pulmonary function. We conducted the largest cross-sectional meta-analysis of the 25(OH)D- pulmonary function association to date, based on nine European ancestry (EA) cohorts (n=22,838) and five African ancestry (AA) cohorts (n=4,290) in the CHARGE Consortium. Data were analyzed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean (SD) serum 25(OH)D was 68 (29) nmol/L for EAs and 49 (21) nmol/L for AAs. For each 1 nmol/L higher 25(OH)D, forced expiratory volume in the first second (FEV1) was higher by 1.1 mL in EAs (95% CI: 0.9,1.3; P=2.5x10-21) and 1.8 mL (95% CI: 1.1,2.5; P=1.6x10-7) in Aas (Prace difference=0.06), and forced vital capacity (FVC) was higher by 1.3 mL in EAs (95% CI: 1.0,1.6; P=1.1x10-20) and 1.5 mL (95% CI: 0.8,2.3; P=1.2x10-4) in AAs (Prace difference=0.56). Among EAs, the 25(OH)D-FVC association was stronger in smokers: per 1nmol/L higher 25(OH)D, FVC was higher by 1.7 mL (95% CI: 1.1,2.3) for current smokers and 1.7 mL (95% CI: 1.2,2.1) for former smokers, compared to 0.8 mL (95% CI: 0.4,1.2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EAs, a stronger association was observed for smokers compared to never smokers, which supports the importance of vitamin D in vulnerable populations.\n\nCohort FundingThis work was supported by National Institutes of Health (NIH) grant number R21 HL125574 funded by the National Heart, Lung, and Blood Institute (NHLBI) and the NIH Office of Dietary Supplements (ODS) (co-Principal Investigators [co-PIs]: DBH and PAC). The corresponding author (PAC) had full access to the data for the meta-analysis, and had final responsibility for the decision to submit for publication. No funding source had any role in the analysis of the data, the writing of the manuscript, or the decision to submit it. This work was also supported in part by R01HL077612 (PI: RGB) and by the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Environmental Health Sciences (ZO1 ES043012, PI: SJL). SJL is supported by the Intramural Research Program of NIH, National Institute of Environmental Health Sciences. Infrastructure for the CHARGE Consortium is supported in part by the NHLBI grant R01HL105756.\n\nThe Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study has been funded by NIH contracts N01-AG-1-2100 and 271201200022C, the National Institute on Aging (NIA) Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). The study is approved by the Icelandic National Bioethics Committee, VSN: 00-063. The researchers are indebted to the participants for their willingness to participate in the study.\n\nThe Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by NHLBI contracts HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C. 25(OH)D measurements were conducted with the support of R01 HL103706 from the NHLBI and R01 HL103706-S1 from the NIH ODS. The authors thank the staff and participants of the ARIC study for their important contributions.\n\nThis Cardiovascular Health Study (CHS) research was supported by NHLBI contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086; and NHLBI grants U01HL080295, R01HL085251, R01HL087652, R01HL105756, R01HL103612, R01HL120393, and R01HL130114 with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through R01AG023629 from NIA. A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Vitamin D measurements were made possible by NHLBI (R01HL084443-01A2).\n\nThis work in Framingham Heart Study was supported by NHLBIs Framingham Heart Study contract (N01-HC-25195 and HHSN268201500001I). Vitamin D measurements in the Framingham study were made possible by NIA (R01 AG14759 to SLB.).\n\nThe Health Aging and Body Composition cohort study was supported by NIA contracts N01AG62101, N01AG2103, and N01AG62106, NIA grant R01-AG028050, NINR grant R01-NR012459, and in part by the Intramural Research Program of the NIA, NIH. This research was further supported by RC1AG035835, and the serum vitamin D assays were supported by R01AG029364.\n\nThe Multi-Ethnic Study of Atherosclerosis (MESA) study is conducted and supported by NHLBI in collaboration with MESA investigators. Support for MESA is provided by contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 from NHLBI, UL1-TR-000040, UL1-TR-001079, and UL1-TR-001881 from NCRR, and DK063491 from the NIDDK. The MESA Lung study was supported by grants R01 HL077612, RC1 HL100543 and R01 HL093081 from NHLBI. Support for the Mineral Metabolite dataset was provided by grant HL096875.\n\nThe Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, the Netherlands; the Organization for the Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); the Dutch Ministry of Education, Culture, and Science; the Dutch Ministry for Health, Welfare, and Sports; the European Commission (DG XII), and the Municipality of Rotterdam. LL was a postdoctoral fellow of the Research Foundation--Flanders (FWO) in Brussels, Belgium. Part of this work was supported by a FWO-grant G035014N. DSM Nutritional Products AG, Kaiseraugst, Switzerland, sponsored the Vitamin D serum analyses. The authors are grateful to the study participants, the staff from the Rotterdam Study, and the participating general practitioners and pharmacists.\n\nThe Coronary Artery Risk Development in Young Adults Study (CARDIA) is supported by contracts HHSN268201300025C, HHSN268201300026C, HHSN268201300027C, HHSN268201300028C, HHSN268201300029C, and HHSN268200900041C from the National Heart, Lung, and Blood Institute (NHLBI), the Intramural Research Program of the National Institute on Aging (NIA), and an intra-agency agreement between NIA and NHLBI (AG0005).\n\nAuthor DisclosureDr. Psaty serves on the DSMB of a clinical trial funded by the manufacturer (Zoll LifeCor) and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson.\n\nAll other authors have no conflicts of interest. There is no commercial support or financial interest from the tobacco industry for the research presented.\n\nThe study sponsors were not involved in study design, data collection, data analysis, data interpretation, report writing, or decisions to submit the paper for publication. PAC and DBH had final responsibility for the decision to submit for publication.\n\nOnline Supporting MaterialSupplemental table, figures, and methods are available.\n\nAbbreviation Footnote

epidemiology↗