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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.

ABSTRACT: INTRODUCTION:Metabolically 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 ANALYSIS:The 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 I2 statistics 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 DISSEMINATION:As 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 NUMBER:CRD42019121766.

SUBMITTER: Tian S

PROVIDER: S-EPMC6830582 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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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.

Tian Simiao S Liu Yazhuo Y Feng Ao A Lou Keli K Dong Huimin H

BMJ open 20191028 10

<h4>Introduction</h4>Metabolically 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 me ...[more]

PMID: 31662402

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Project description:ImportancePeople classified by a priori definitions as having metabolically healthy obesity have frequently been found to be at increased risk of mortality, compared with individuals with metabolically healthy normal weight, suggesting these definitions may be insufficient.ObjectivesTo systematically derive a new definition of metabolic health (MH) and investigate its association with cardiovascular disease (CVD) mortality and total mortality.Design, setting, and participantsIn a cohort study using data from the third National Health and Nutrition Examination Survey (NHANES-III), a representative survey using complex multistage probability sampling, anthropometric factors, biomarkers, and blood pressure (BP) associated with total and CVD mortality among participants with obesity were identified with Cox proportional hazards regression. Area under the receiver operating characteristic was calculated to identify predictive factors for mortality to be used to define MH, cutoff levels were determined by the Youden index, and the findings were validated through comparison with the independent UK Biobank cohort, a population-based prospective study. All nonpregnant participants in the databases aged 18 to 75 years with no history of CVD, body mass index greater than or equal to 18.5, and who fasted 6 or more hours before examination in NHANES-III were included; participants in the UK Biobank cohort who did not have blood measurements were excluded. The study was conducted from 2015 to 2020.ExposuresBody mass index and MH were defined by the new definition and compared with 3 a priori definitions.Main outcomes and measuresCardiovascular disease mortality and total mortality.ResultsWithin the NHANES-III (n = 12 341) cohort, mean (SD) age was 41.6 (29.2) years, 50.7% were women, and mean follow-up was 14.5 (2.7) years. Within the UK Biobank (n = 374 079) cohort, mean (SD) age was 56.2 (8.1) years, 55.1% were women, and mean follow-up was 7.8 (1.0) years. Use of blood pressure (BP)-lowering medication (hazard ratio [HR] for CVD mortality, 2.41; 95% CI, 1.50-3.87 and total mortality, 2.05; 95% CI, 1.47-2.84), diabetes, and several continuous factors were associated with mortality. Of all significant continuous factors, the combination of systolic BP and waist-to-hip ratio showed the highest area under the receiver operating characteristic (CVD mortality: 0.775; 95% CI, 0.770-0.781; total mortality: 0.696; 95% CI, 0.694-0.699). Thus, MH was defined as systolic BP less than 130 mm Hg, no BP-lowering medication, waist-to-hip ratio less than 0.95 for women and less than 1.03 for men, and no self-reported (ie, prevalent) diabetes. In both cohorts, metabolically healthy obesity was not associated with CVD and total mortality compared with metabolically healthy normal weight. For NHANES-III, the hazard ratio was 0.68 (95% CI, 0.30-1.54) for CVD mortality and 1.03 (95% CI, 0.70-1.51) for total mortality. For UK Biobank, the hazard ratio was 1.17 (95% CI, 0.81-1.69) for CVD mortality and 0.98 (95% CI, 0.87-1.10) for total mortality. Regardless of body mass index, all metabolically unhealthy groups displayed increased risks.Conclusions and relevanceThis newly proposed definition of MH may identify a subgroup of people with obesity without increased risk of mortality and stratify risks in people who are overweight or normal weight.

Project description:IntroductionInfluenza virus infection is known to increase the risk of cardiovascular events, especially in populations with pre-existing cardiovascular disease (CVD). Considering that influenza is vaccine preventable, international guidelines recommend high-risk populations with CVD receive an influenza vaccine every year. However, there are various classifications of recommendations and levels of evidence. Previous systematic reviews concluded uncertain evidence on influenza vaccine efficacy for preventing cardiovascular events in the general population or in populations with pre-existing CVD. Limited safety data of influenza vaccines were reported for populations with pre-existing CVD. Randomised controlled trials with larger sample sizes relative to previous studies are emerging, the findings of these trials are likely to be highly influential on summary efficacy estimates.Methods and analysisWe aim to perform a living systematic review and a prospective meta-analysis to evaluate the efficacy and safety of influenza vaccines compared with no vaccines or placebo for preventing mortality or CVD events in the general population and in populations with pre-existing CVD. Any types of randomised controlled trial and observational study meeting the Population, Intervention, Comparator, Outcome and Study design criteria for the research question will be selected for inclusion. The living systematic review status will be maintained for 3 years with an update for every 6 months. Mainstream medical literature databases will be independently searched by two authors with predefined strategies. Two authors will perform the risk of bias assessment with consensus. Narrative synthesis and meta-analyses will be performed to summarise the results.Ethics and disseminationFormal ethical review is not required as this study does not involve primary data collection. We will publish results of the living systematic review and prospective meta-analysis in a peer-reviewed journal. Findings will also be presented at relevant meetings.Prospero registration numberCRD42021222519.

Project description:BackgroundThere is heterogeneity among obese individuals, as some appear to have healthier metabolic profiles and decreased health risks. These individuals are defined as metabolically healthy obese (MHO), whilst those with unhealthy metabolic profiles are defined as metabolically unhealthy obese (MUO). To date, most research on MHO has been cross-sectional or focused on disease prognosis. However, longitudinal studies are required to provide greater insight into the life course factors that contribute to the development of MHO. This study aims to systematically review longitudinal studies investigating the association between life course exposures and future MHO status.MethodsElectronic databases (MEDLINE, SCOPUS, and Web of Science) will be searched using a trialled search strategy. Studies will be included following a double-screening process according to inclusion criteria to assess eligibility. Studies eligible for inclusion will include those that have a longitudinal observational design where a life course exposure occurred or was measured at least 1 year before the outcome, investigate a human study population, are published in English after 1956, and investigate the association between ≥ 1 life course exposure and ≥ 1 outcome that reflects a measure of cardiometabolic resilience to obesity. Accepted life course exposures will include body size, body composition, pubertal development, smoking, diet, physical activity, sedentary behaviour, and psychosocial stress. The primary measure of cardiometabolic resilience to obesity will be MHO as an outcome (at follow-up). Studies investigating the development of cardiometabolic risk factors in an obese group without specifying MHO will also be accepted, such as the development of the metabolic syndrome (MetS) in an obese group. Key results of included studies will be tabulated, and a narrative synthesis will be conducted.DiscussionThis will be the first systematic review to summarise the literature on the life course correlates of MHO. Importantly, it may highlight which modifiable lifestyle factors could be targeted to delay the onset of cardiometabolic complications among the obese.Systematic review registrationPROSPERO CRD42017057992.

Dataset Information

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.

Publications

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.

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