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Metabolically Healthy Obesity, Transition to Metabolic Syndrome, and Cardiovascular Risk.

ABSTRACT: 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.

SUBMITTER: Mongraw-Chaffin M

PROVIDER: S-EPMC6002856 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Metabolically Healthy Obesity, Transition to Metabolic Syndrome, and Cardiovascular Risk.

Mongraw-Chaffin Morgana M Foster Meredith C MC Anderson Cheryl A M CAM Burke Gregory L GL Haq Nowreen N Kalyani Rita R RR Ouyang Pamela P Sibley Christopher T CT Tracy Russell R Woodward Mark M Vaidya Dhananjay D

Journal of the American College of Cardiology 20180501 17

<h4>Background</h4>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.<h4>Objectives</h4>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.<h4>Methods< ...[more]

PMID: 29699611

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Project description:BackgroundMetabolically healthy obesity (MHO) and its transition to unhealthy metabolic status have been associated with risk of cardiovascular disease (CVD) in Western populations. However, it is unclear to what extent metabolic health changes over time and whether such transition affects risks of subtypes of CVD in Chinese adults. We aimed to examine the association of metabolic health status and its transition with risks of subtypes of vascular disease across body mass index (BMI) categories.Methods and findingsThe China Kadoorie Biobank was conducted during 25 June 2004 to 15 July 2008 in 5 urban (Harbin, Qingdao, Suzhou, Liuzhou, and Haikou) and 5 rural (Henan, Gansu, Sichuan, Zhejiang, and Hunan) regions across China. BMI and metabolic health information were collected. We classified participants into BMI categories: normal weight (BMI 18.5-23.9 kg/m²), overweight (BMI 24.0-27.9 kg/m²), and obese (BMI ≥ 28 kg/m²). Metabolic health was defined as meeting less than 2 of the following 4 criteria (elevated waist circumference, hypertension, elevated plasma glucose level, and dyslipidemia). The changes in obesity and metabolic health status were defined from baseline to the second resurvey with combination of overweight and obesity. Among the 458,246 participants with complete information and no history of CVD and cancer, the mean age at baseline was 50.9 (SD 10.4) years, and 40.8% were men, and 29.0% were current smokers. During a median 10.0 years of follow-up, 52,251 major vascular events (MVEs), including 7,326 major coronary events (MCEs), 37,992 ischemic heart disease (IHD), and 42,951 strokes were recorded. Compared with metabolically healthy normal weight (MHN), baseline MHO was associated with higher hazard ratios (HRs) for all types of CVD; however, almost 40% of those participants transitioned to metabolically unhealthy status. Stable metabolically unhealthy overweight or obesity (MUOO) (HR 2.22, 95% confidence interval [CI] 2.00-2.47, p < 0.001) and transition from metabolically healthy to unhealthy status (HR 1.53, 1.34-1.75, p < 0.001) were associated with higher risk for MVE, compared with stable healthy normal weight. Similar patterns were observed for MCE, IHD, and stroke. Limitations of the analysis included lack of measurement of lipid components, fasting plasma glucose, and visceral fat, and there might be possible misclassification.ConclusionsAmong Chinese adults, MHO individuals have increased risks of MVE. Obesity remains a risk factor for CVD independent of major metabolic factors. Our data further suggest that metabolic health is a transient state for a large proportion of Chinese adults, with the highest vascular risk among those remained MUOO.

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.

Dataset Information

Metabolically Healthy Obesity, Transition to Metabolic Syndrome, and Cardiovascular Risk.

Publications

Metabolically Healthy Obesity, Transition to Metabolic Syndrome, and Cardiovascular Risk.

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