Metabolically healthy obesity and the risk of all-cause and cardiovascular disease mortality in a Korean population: a prospective cohort study.
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ABSTRACT: Objectives
This study aimed to examine the association between metabolically healthy obesity and all-cause and cardiovascular disease (CVD) mortality in a Korean population.Design
A prospective study.Setting
This study used data from the Korean Genome and Epidemiology Study.Participants
A total of 140 137 participants were followed up over a median period of 9.2 years. Participants were categorised into four groups according to obesity (obese: body mass index ≥25 kg/m2 or non-obese) and metabolic health (metabolically unhealthy: two or more metabolic abnormalities or metabolically healthy).Primary and secondary outcome measures
All-cause and CVD mortality of the participants until 31 December 2018 were ascertained by the National Health Insurance Service of beneficiary status of Korea.Results
Metabolically unhealthy non-obese participants were at elevated risk of all-cause mortality (HR, 1.12; 95% CI, 1.04 to 1.21; p=0.0019) and CVD mortality (HR, 1.39; 95% CI, 1.17 to 1.65; p=0.0002), particularly mortality from ischaemic heart disease (IHD) (HR, 1.54; 95% CI, 1.10 to 2.14; p=0.0116) compared with metabolically healthy non-obese participants. Surprisingly, metabolically healthy obese participants were at reduced risk of all-cause mortality (HR, 0.89; 95% CI, 0.81 to 0.98; p=0.0197). Metabolically unhealthy obese participants were at elevated risk of CVD mortality (HR, 1.51; 95% CI, 1.26 to 1.81; p<0.0001) and IHD mortality (HR, 1.88; 95% CI, 1.35 to 2.63; p=0.0002) compared with metabolically healthy non-obese participants.Conclusions
In a Korean population, metabolically healthy obese participants had reduced risk of all-cause mortality compared with their non-obese counterparts, whereas metabolically unhealthy participants had elevated risk of CVD mortality, in particular mortality from IHD regardless of obesity.
SUBMITTER: Kim SA
PROVIDER: S-EPMC8423515 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: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.
| S-EPMC6830582 | biostudies-literature
Project description:BACKGROUND:Whether being metabolically healthy obese (MHO)-defined by the presence of obesity in the absence of metabolic syndrome-is associated with subsequent cardiovascular disease (CVD) remains unclear and may depend on the participants' age. We examined the association of being MHO with CVD risk in the elderly. METHODS AND FINDINGS:This study included 5,314 individuals (mean age 68 years) from the prospective population-based Rotterdam Study. We categorized our population in groups according to body mass index (BMI) and presence and absence of metabolic syndrome, and estimated the hazard ratio (HR) and 95% confidence interval (95%CI) for every group by using Cox proportional hazard models. Among 1048 (19.7%) obese individuals we identified 260 (24.8%) MHO subjects. Over 14 years of follow-up there were 861 incident CVD cases. In the multivariable adjusted analysis, we did not observe an increased CVD risk in MHO individuals (HR 1.07, 95%CI 0.75-1.53), compared to normal weight individuals without metabolic syndrome. CVD risk was increased by the presence of metabolic syndrome in normal weight (HR 1.35, 95%CI 1.02-1.80), overweight (HR 1.32, 95%CI 1.09-1.60) and obese (HR 1.33, 95%CI 1.07-1.66) individuals, compared to those with normal weight without metabolic syndrome. In a mediation analysis, 71.3% of the association between BMI and CVD was explained by the presence of metabolic syndrome. CONCLUSIONS:In our elderly population, we found that the presence of obesity without metabolic syndrome did not confer a higher CVD risk. However, metabolic syndrome was strongly associated with CVD risk, and was associated with an increased risk in all BMI categories. Therefore, preventive interventions targeting cardiometabolic risk factors could be considered in elderly, regardless of weight status.
| S-EPMC4839559 | biostudies-other
Project description:BACKGROUNDMetabolically healthy obesity (MHO) and metabolically healthy overweight (MH-OW) have been suggested to be important and emerging phenotypes with an increased risk of cardiovascular disease (CVD). However, whether MHO and MH-OW are associated with all-cause mortality remains inconsistent.METHODSThe association of MHO and MH-OW and all-cause mortality was determined in a Chinese community-based prospective cohort study (the Kailuan study), including 93,272 adults at baseline. Data were analyzed from 2006 to 2017. Participants were categorized into 6 mutually exclusive groups, according to BMI and metabolic syndrome (MetS) status. The primary outcome was all-cause death, and accidental deaths were excluded.RESULTSDuring a median follow-up of 11.04 years (interquartile range, 10.74-11.22 years), 8977 deaths occurred. Compared with healthy participants with normal BMI (MH-NW), MH-OW participants had the lowest risk of all-cause mortality (multivariate-adjusted HR [aHR], 0.926; 95% CI, 0.861-0.997), whereas there was no increased or decreased risk for MHO (aHR, 1.009; 95% CI, 0.886-1.148). Stratified analyses and sensitivity analyses further validated that there was a nonsignificant association between MHO and all-cause mortality.CONCLUSIONSOverweight and obesity do not predict increased risk of all-cause mortality in metabolic healthy Chinese individuals.FUNDINGNational Natural Science Foundation of China (NSFC; 81673247, 81872682 and 81773527), the NSFC Joint Project, and the Australian National Health and Medical Research Council (NHMRC; NSFC 81561128020-NHMRC APP1112767).
| S-EPMC7455121 | biostudies-literature
Project description:We investigated the association among metabolically healthy obesity (MHO), cardiovascular disease (CVD)risk, and all-cause mortality in the Asian population. We searched databases from inception to 16 November, 2019 and pooled data using a random-effects model. Subgroup analysis was conducted according to the following comparison groups: MHNW (without overweight or underweight participants) and MHNO (non-obese, including overweight and underweight participants). Nineteen studies were included. The mean Newcastle-Ottawa Scale score was 7.8. Participants with MHO had a significantly higher CVD risk (odds ratio (OR) = 1.36, 95% confidence interval (CI) = 1.13-1.63) and significantly lower risk of all-cause mortality (OR = 0.88, 95% CI = 0.78-1.00) than the comparison group. Subgroup analyses revealed participants with MHO had a significantly higher CVD risk than MHNW participants (OR = 1.61; 95% CI = 1.24-2.08; I2 = 73%), but there was no significant difference compared with MHNO participants (OR, 1.04; 95% CI, 0.80-1.36; I2 = 68%). Participants with MHO had a significantly lower risk of all-cause mortality (OR = 0.83; 95% CI = 0.78-0.88; I2 = 9%) than MHNO participants, but a borderline significantly higher risk of all-cause mortality than MHNW participants (OR = 1.30; 95% CI = 0.99-1.72; I2 = 0%). The CVD risk and all-cause mortality of the MHO group changed depending on the control group. Thus, future studies should select control groups carefully.
| S-EPMC7068615 | biostudies-literature
Project description:Aims/hypothesisPeople with obesity and a normal metabolic profile are sometimes referred to as having 'metabolically healthy obesity' (MHO). However, whether this group of individuals are actually 'healthy' is uncertain. This study aims to examine the associations of MHO with a wide range of obesity-related outcomes.MethodsThis is a population-based prospective cohort study of 381,363 UK Biobank participants with a median follow-up of 11.2 years. MHO was defined as having a BMI ≥ 30 kg/m2 and at least four of the six metabolically healthy criteria. Outcomes included incident diabetes and incident and fatal atherosclerotic CVD (ASCVD), heart failure (HF) and respiratory diseases.ResultsCompared with people who were not obese at baseline, those with MHO had higher incident HF (HR 1.60; 95% CI 1.45, 1.75) and respiratory disease (HR 1.20; 95% CI 1.16, 1.25) rates, but not higher ASCVD. The associations of MHO were generally weaker for fatal outcomes and only significant for all-cause (HR 1.12; 95% CI 1.04, 1.21) and HF mortality rates (HR 1.44; 95% CI 1.09, 1.89). However, when compared with people who were metabolically healthy without obesity, participants with MHO had higher rates of incident diabetes (HR 4.32; 95% CI 3.83, 4.89), ASCVD (HR 1.18; 95% CI 1.10, 1.27), HF (HR 1.76; 95% CI 1.61, 1.92), respiratory diseases (HR 1.28; 95% CI 1.24, 1.33) and all-cause mortality (HR 1.22; 95% CI 1.14, 1.31). The results with a 5 year landmark analysis were similar.Conclusions/interpretationWeight management should be recommended to all people with obesity, irrespective of their metabolic status, to lower risk of diabetes, ASCVD, HF and respiratory diseases. The term 'MHO' should be avoided as it is misleading and different strategies for risk stratification should be explored.
| S-EPMC8382657 | biostudies-literature
Project description:PurposeAlthough thyroid hormones are irrefutably implicated in cardiovascular physiology, the impact of within-reference range variations of thyroid function on cardiovascular disease (CVD) remains unclear. Elucidating this is important, since it could foster preventive treatment and reduce global CVD burden. We therefore investigated the impact of within-reference range variations of thyroid function on all-cause and cardiovascular mortality.MethodsWe included community-dwelling individuals aged 28-75 years from a prospective cohort study, without known use of thyroid-affecting therapy and with thyrotropin within reference range. Associations of thyroid function with mortality were quantified using Cox models and adjusted for sociodemographic and cardiovascular risk factors.ResultsMean (SD) age of the 6,054 participants (52.0% male) was 53.3 (12.0) years. During 47,594 person-years of follow-up, we observed 380 deaths from all causes and 103 from CVDs. Although higher thyrotropin was not associated with all-cause mortality (adjusted HR 1.02, 95% CI 0.92-1.14), point estimates for cardiovascular mortality diverged toward increased risk in younger (<72 years) participants (1.31, 1.00-1.72) and decreased risk in elderly (≥72 years) (0.77, 0.56-1.06). Higher free thyroxine (FT4) was associated with all-cause mortality (1.18, 1.07-1.30) and with cardiovascular mortality only in elderly (1.61, 1.19-2.18), but not in younger participants (1.03, 0.78-1.34). Higher free triiodothyronine (FT3) was associated with all-cause mortality in females only (1.18, 1.02-1.35). FT3 was not associated with cardiovascular mortality (0.91, 0.70-1.18).ConclusionsCommunity-dwelling elderly individuals with high-normal thyroid function are at increased risk of all-cause and cardiovascular mortality, reinforcing the need of redefining the current reference ranges of thyroid function.
| S-EPMC7881952 | biostudies-literature
Project description:Identifying those parameters that could potentially predict the deterioration of metabolically healthy phenotype is a matter of debate. In this field, epigenetics, in particular DNA methylation deserves special attention. The aim of the present study was to analyze the long-term evolution of methylation patterns in a subset of metabolically healthy subjects in order to search for epigenetic markers that could predict the progression to an unhealthy state. Twenty-six CpG sites were significantly differentially methylated, both at baseline and 11-year follow-up. These sites were related to 19 genes or pseudogenes; a more in-depth analysis of the methylation sites of these genes showed that CYP2E1 had 50% of the collected CpG sites differently methylated between stable metabolically healthy obesity (MHO) and unstable MHO, followed by HLA-DRB1 (33%), ZBTB45 (16%), HOOK3 (14%), PLCZ1 (14%), SLC1A1 (12%), MUC2 (12%), ZFPM2 (12.5%) and HLA-DQB2 (8%). Pathway analysis of the selected 26 CpG sites showed enrichment in pathways linked to th1 and th2 activation, antigen presentation, allograft rejection signals and metabolic processes. Higher methylation levels in the cg20707527 (ZFPM2) could have a protective effect against the progression to unstable MHO (OR: 0.21, 95%CI (0.067-0.667), p < 0.0001), whilst higher methylation levels in cg11445109 (CYP2E1) would increase the progression to MUO; OR: 2.72, 95%CI (1.094-6.796), p < 0.0014; respectively). DNA methylation status is associated with the stability/worsening of MHO phenotype. Two potential biomarkers of the transition to an unhealthy state were identified and deserve further investigation (cg20707527 and cg11445109). Moreover, the described differences in methylation could alter immune system-related pathways, highlighting these pathways as therapeutic targets to prevent metabolic deterioration in MHO patients.
| S-EPMC8508854 | biostudies-literature
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.
| S-EPMC8105750 | biostudies-literature
Project description:Background:Metabolically healthy obesity (MHO) has been reported to be associated with the development of vascular damage by the carotid intima-media thickness, but the relationship between metabolic health and obesity phenotypes and arterial stiffness is still unknown. Our hypothesized that different metabolic health and obesity phenotypes might be associated with the development of arterial stiffness, and that subjects in MHO phenotype might not have increased risks of arterial stiffness compared with those in metabolically healthy nonobesity phenotype (MHNO), while metabolic unhealthy individuals might have increased risks of arterial stiffness. Methods:A prospective cohort of 2076 participants (aged 36-48?years) who were enrolled in the Hanzhong Adolescent Hypertension Cohort Study in 2017 was analyzed in a cross-sectional analysis. A subgroup of 202 participants from 2005 to 2017 was selected by an isometric sampling method and was included in the final longitudinal analysis. Results:We identified four metabolic health and obesity phenotypes for both the cross-sectional and longitudinal analyses as follows: MHNO, metabolically unhealthy nonobesity (MUNO), MHO, and metabolically unhealthy obesity (MUO). In the cross-sectional analysis, individuals with the MHO phenotype had the lowest brachial-ankle pulse wave velocity (baPWV) levels of the four phenotypes (P?<?0.001), and participants with the MHO phenotype had a similar risk of arterial stiffness after fully adjustment [odds ratio (OR)?=?0.99 (0.61-1.60)] as the MUNO subjects. Subjects with metabolically unhealthy status had a significantly higher risk of arterial stiffness than the MHNO individuals, particularly females (P?<?0.005). In the longitudinal analysis, subjects with the MUNO and MUO phenotypes had a significantly higher risk of arterial stiffness than the MHNO individuals after adjustment for age and sex [OR?=?5.21 (2.26-12.02), OR?=?3.32 (1.18-9.32), respectively]. Conclusions:The MHO phenotype did not significantly increase the progression of arterial stiffness. Metabolically unhealthy individuals (MUNO, MUO), regardless of obesity status, showed a worse effect for the development of arterial stiffness, particularly females. Trial registration:NCT02734472. Registered 12 April 2016 - Retrospectively registered, http:www.clinicaltrials.gov.
| S-EPMC7330959 | biostudies-literature
Project description:BACKGROUND:Debate over the cardiometabolic risk associated with metabolically healthy obesity (MHO) continues. Many studies have investigated this relationship by examining MHO at baseline with longitudinal follow-up, with inconsistent results. OBJECTIVES:The authors hypothesized that MHO at baseline is transient and that transition to metabolic syndrome (MetS) and duration of MetS explains heterogeneity in incident cardiovascular disease (CVD) and all-cause mortality. METHODS:Among 6,809 participants of the MESA (Multi-Ethnic Study of Atherosclerosis) the authors used Cox proportional hazards and logistic regression models to investigate the joint association of obesity (?30 kg/m2) and MetS (International Diabetes Federation consensus definition) with CVD and mortality across a median of 12.2 years. We tested for interaction and conducted sensitivity analyses for a number of conditions. RESULTS:Compared with metabolically healthy normal weight, baseline MHO was not significantly associated with incident CVD; however, almost one-half of those participants developed MetS during follow-up (unstable MHO). Those who had unstable MHO had increased odds of CVD (odds ratio [OR]: 1.60; 95% confidence interval [CI]: 1.14 to 2.25), compared with those with stable MHO or healthy normal weight. Dose response for duration of MetS was significantly and linearly associated with CVD (1 visit with MetS OR: 1.62; 95% CI: 1.27 to 2.07; 2 visits, OR: 1.92; 95% CI: 1.48 to 2.49; 3+ visits, OR: 2.33; 95% CI: 1.89 to 2.87; p value for trend <0.001) and MetS mediated approximately 62% (44% to 100%) of the relationship between obesity at any point during follow-up and CVD. CONCLUSIONS:Metabolically healthy obesity is not a stable or reliable indicator of future risk for CVD. Weight loss and lifestyle management for CVD risk factors should be recommended to all individuals with obesity.
| S-EPMC6002856 | biostudies-literature