Gut Microbiota Metabolites and Risk of Major Adverse Cardiovascular Disease Events and Death: A Systematic Review and Meta‐Analysis of Prospective Studies

Background: Clinical hypomagnesemia and experimental dietary magnesium (Mg) restriction diets are associated with cardiac arrhythmias. Relationships between circulating or dietary Mg at usual concentrations or intakes and risk of cardiovascular disease (CVD), including fatal coronary heart disease (CHD), are not well established. Objective: We performed a systematic review and meta-analysis to summarize all available evidence from prospective studies on the associations between circulating and dietary Mg intake with incidence of total CVD, total CHD, and fatal CHD. Methods: Multiple literature databases and grey literature were systematically searched without language restriction from the earliest online index date to May 2012 for all prospective cohort or nested case-control studies examining the association of circulating or dietary Mg intake with incident total CVD, total CHD and fatal CHD. Two investigators evaluated full text articles for inclusion/exclusion and extracted data, independently and in duplicate. Linear dose-response relationships were assessed using generalized least-squares trend estimation, with pooled RR’s determined using fixed-effects or random-effects in the presence of heterogeneity (I2>30%). Potential non-linear associations were assessed using restricted cubic splines. Prespecified sources of heterogeneity were explored using meta-regression. Publication bias was assessed using formal statistical testing and visual inspection of funnel plots. Results: Of 2,303 abstracts reviewed, 16 studies met eligibility criteria, comprising 761,742 individuals and 11,995 total CVD, 7,534 total CHD, and 2,686 fatal CHD events. In pooled analyses, circulating Mg (per 0.2mmol/L increment) was associated with a 30% lower risk of total CVD (RR=0.70, 95% CI=0.56-0.88; I2=50%) and trends towards lower risk of total CHD (RR=0.83, 95% CI=0.75-1.05; I2=47%) and fatal CHD (RR=0.61, 95% CI=0.37-1.00; I2=80%). Dietary Mg (per 200mg/day increment) was not significantly associated with total CVD (RR=0.89, 95% CI=0.75-1.05; I2=67%), but was associated with a 22% lower risk of total CHD (RR=0.78, 95% CI=0.67-0.92; I2=44%). The association between dietary Mg and fatal CHD was non-linear (p<0.0001), with an inverse association observed up to a threshold of ~250 mg/day (compared to lower intakes, RR=0.73, 95% CI=0.62-0.86). Funnel plot asymmetry was evident for the association between circulating Mg and total CVD, explained by heterogeneity due to stronger associations (p=0.02) in studies including participants with prevalent CVD at baseline and evaluating fatal CHD. Conclusions: Circulating Mg and dietary Mg intake are associated with lower risk of CVD, in particular fatal CHD. These findings support the need for randomized clinical trials and experimental studies to evaluate the possible role of Mg in the prevention of CVD and CHD death.

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Metabolically healthy obesity and risk of cardiovascular disease, cancer, and all-cause and cause-specific mortality: a protocol for a systematic review and meta-analysis of prospective studies

BMJ Open ◽

10.1136/bmjopen-2019-032742 ◽

2019 ◽

Vol 9 (10) ◽

pp. e032742 ◽

Cited By ~ 2

Author(s):

Simiao Tian ◽

Yazhuo Liu ◽

Ao Feng ◽

Keli Lou ◽

Huimin Dong

Keyword(s):

Systematic Review ◽

Cardiovascular Disease ◽

Prospective Studies ◽

Data Extraction ◽

Meta Analysis ◽

Adjusted Relative Risk ◽

Benign Condition ◽

Specific Mortality ◽

Total Cancer ◽

Metabolically Healthy

IntroductionMetabolically healthy obese phenotype (MHO) refers to obese individuals with an adequate metabolic profile and absence of metabolic syndrome. Many prospective studies have reported the benign condition relating the MHO phenotype and its potential role in reducing risk of cardiovascular disease, total cancer, and all-cause and cause-specific mortality. However, inconsistent results were found and the question remains controversial. We aim to conduct a systematic review and meta-analysis to clarify the associations these associations from relevant prospective studies.Methods and analysisThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols 2015 statement was used to prepare this protocol. MEDLINE, Web of Science databases, EMBASE and Cochrane Database will be used for literature search from their inception up to December 2019 with restriction of published studies in English. Published prospective studies reporting adjusted relative risk (RR) estimates for the association between MHO phenotype and cardiovascular disease, total cancer, all-cause or cause-specific mortality will be included. The process of study screening, selection and data extraction will be performed independently by two reviewers, and the risk of bias for the studies included will be assessed using the Newcastle-Ottawa Quality Assessment Scale. HRs or RRs for disease events and mortality with 95% CIs will be considered as primary outcomes, and summary HRs/RRs will be pooled using random-effects models. The Cochrane’s Q and the I2statistics will be used to assess and quantify heterogeneity, respectively. Subgroup analysis will also be carried out according to study characteristics to investigate potential sources of heterogeneity.Ethics and disseminationAs this meta-analysis is performed based on the published studies, no ethical approval and patient safety considerations are required. The findings of the study will be reported and submitted to a peer-reviewed journals for publication.PROSPERO registration numberCRD42019121766.

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