Association of obesity phenotypes with electrocardiographic left ventricular hypertrophy in the general population

Objective

Increasing evidence doubts the benign nature of metabolically healthy obesity (MHO). An investigation of the association of MHO and other obesity phenotypes with electrocardiographic left ventricular hypertrophy (ECG-LVH), a risk factor for cardiovascular disease (CVD), can give insight into the pathophysiological basis for increased risk of CVD linked to these phenotypes.

Prevalence and clinical profile of metabolic obesity and phenotypic obesity in Asian Indians

Background

We estimated the prevalence of metabolically obese nonobese (MONO), metabolically obese obese (MOO), and metabolically healthy obese (MHO) individuals and correlated this with the prevalence of coronary artery disease (CAD) compared to metabolically healthy nonobese (MHNO) in urban South Indians.

Method

Study subjects (n = 2350) were recruited from the Chennai Urban Rural Epidemiology Study. Generalized obesity was defined as a body mass index (BMI) ≥25 kg/m², based on the World Health Organization Asia Pacific guidelines. Metabolic syndrome (MS) was diagnosed based on the South Asian Modified-National Cholesterol Education Programme criteria. Coronary artery disease was defined by known myocardial infarction or Q waves on resting electrocardiogram.

Results

Metabolically obese nonobese was defined as nonobese subjects (BMI < 25 kg/m²) with MS, MOO as obesity (BMI ≥ 25 kg/m²) with MS, MHO as obese subjects (BMI ≥ 25 kg/m²) with no MS, and MHNO as no obesity or MS. Metabolically obese nonobese was identified in 355 (15.1%), MOO in 348 (14.8%), MHO in 312 (13.3%), and MHNO in 1335 (56.8%) subjects. The prevalence of CAD among the MONO, MOO, MHO, and MHNO was 5.5%, 4.2%, 1.4%, and 2.6%. However, when age standardization was done, there was no statistically significant increase in the risk of CAD among MONO [odds ratio (OR) = 1.300, 95% confidence interval (CI) 0.706–2.394, p = .339], MOO (OR = 1.651, 95% CI 0.852–3.199, p = .137), and MHO (OR = 0.524, 95% CI 0.250–2.130, p = .564) groups compared to MHNO, perhaps due to small numbers.

Conclusion

Metabolic obesity may have different clinical implications than phenotypic obesity.     

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

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.

Impact of respiratory function on the progression from metabolically healthy non-overweight to metabolically abnormal phenotype

Background and aims

Recent studies identified that metabolically abnormal non-overweight phenotype is a risk factor for cardiovascular diseases. However, only little is known about risk factors for the progression from metabolically healthy non-overweight (MHNO) to metabolically abnormal phenotype. In this study, we investigated the impact of respiratory function on the progression from MHNO to metabolically abnormal phenotype.

Associations of metabolically healthy obesity with prevalence and progression of coronary artery calcification: Results from the Heinz Nixdorf Recall Cohort Study

Background and aims

There is controversy on the potentially benign nature of metabolically healthy obesity (MHO), i.e., obese persons with few or no metabolic abnormalities. So far, associations between MHO and coronary artery calcification (CAC), a measure of subclinical atherosclerosis, have mainly been studied cross-sectionally in Asian populations. We assessed cross-sectional and longitudinal MHO CAC associations in a Caucasian population.

Metabolically Healthy Obesity and Risk of Incident CKD

Background and objectives

Metabolically healthy obesity (MHO) is a unique obesity phenotype that apparently protects people from the metabolic complications of obesity. The association between MHO phenotype and incident CKD is unclear. Thus, this study investigated the association between MHO phenotype and incident CKD.

Design, setting, participants, & measurements

A total of 3136 Japanese participants were enrolled in an 8-year follow-up cohort study in 2001. Metabolically healthy status was assessed by common clinical markers: BP, triglycerides, HDL cholesterol, and fasting plasma glucose concentrations. Body mass index ≥25.0 kg/m² was defined as obesity. CKD was defined by proteinuria or eGFR of <60 ml/min per 1.73 m². To calculate the odds ratio for incident CKD, logistic regression analyses were performed.

Results

The crude incidence proportions of CKD were 2.6% (56 of 2122 participants) in participants with the metabolically healthy nonobesity phenotype, 2.6% (8 of 302) in those with the MHO phenotype, 6.7% (30 of 445) in those with the metabolically abnormal nonobesity phenotype, and 10.9% (29 of 267) in those with the metabolically abnormal obesity phenotype. Compared with metabolically healthy nonobesity phenotype, the odds ratios for incident CKD were 0.83 (95% confidence interval [95% CI], 0.36 to 1.72; P=0.64) for MHO, 1.44 (95% CI, 0.80 to 2.57; P=0.22) for metabolically abnormal nonobesity, and 2.80 (95% CI, 1.45 to 5.35; P=0.02) for metabolically abnormal obesity phenotype after adjustment for confounders, including age, sex, smoking statues, alcohol use, creatinine, uric acid, systolic BP, HDL cholesterol, and impaired fasting glucose or diabetes.

Conclusion

MHO phenotype was not associated with higher risk of incident CKD.     

Preclinical signs of liver and cardiac damage in youth with metabolically healthy obese phenotype

Background and aims

We aimed to evaluate whether the metabolically healthy obese (MHO) phenotype was associated with hepatic steatosis (HS) or left ventricular hypertrophy (LVH) in young people with overweight (OW), obesity (OB) and morbid obesity (MOB) and whether the prevalence of these comorbidities was affected by OB severity.

Metabolically healthy obese and unhealthy normal weight in Iranian adult population: Prevalence and the associated factors

Aims

The objective of this study was to determine the prevalence and the associated factors of metabolically unhealthy in normal-weight and metabolically healthy in obese.

Association of cumulative excess weight and waist circumference exposure with transition from metabolically healthy obesity to metabolically unhealthy

Background and aimsThe association between obesity severity and duration with the transition from metabolically healthy obese/overweight (MHO) phenotype to metabolically unhealthy obese (MUO) phenotype is not well understood.Methods and resultsThis study includes the Tehran Lipid and Glucose Study participants who were initially classed as MHO. Cumulative excess weight (CEW) and cumulative excess waist circumference (CEWC) scores, which represent the accumulation of body mass index and waist circumference deviations from expected values over time (kg/m² 1 y and cm 1 y, respectively), were calculated until the transition from MHO to MUO or the end of follow-up. The sex-stratified association of CEW and CWEC with the transition from MHO to MUO was investigated by time-dependent Cox models, adjusting for confounders. Out of 2525 participants, 1732 (68.5%) were women. During 15 years of follow-up, 1886 (74.6%) participants transitioned from MHO to MUO. A significant association was found between CEW and CEWC quartiles with the development of MUO among women participants (fully adjusted hazard ratios in the fourth quartile of CEW and CEWC [95% (CI)]:1.65 [1.37–1.98] and [95% CI]: 1.83 [1.53–2.19]). There was no significant association between CEW and CEWC with the MHO transition to MUO among men participants.ConclusionOver 15 years of follow-up in TLGS, general and central obesity accumulation was associated with the increased transition from MHO to MUO among women participants. More research with a larger sample size is needed to confirm and explain why the results are different for men and women.     

The association between metabolically healthy obesity and risk of cancer: A systematic review and meta‐analysis of prospective cohort studies

The risk of cancer among adults with metabolically healthy obesity (MHO) has not yet been established. We systematically searched from inception to 15 March 2020. We included prospective cohort studies that compared participants with MHO and participants with metabolically healthy non‐obesity (MHNO) for incidence of any type of cancer. Benign tumors, cancer mortality or cancer prognosis were not in the scope of our analysis. The Newcastle–Ottawa Scale was used for quality assessment. Ultimately, eight studies with a total of 12 542 390 participants were included. The pooled meta‐analysis using random effect model showed participants with MHO demonstrated a significantly increased risk of developing cancer (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.05 to 1.23; and I² = 39%) than those with MHNO. The subgroup analysis revealed a higher pooled estimate (OR, 1.17; 95% CI, 1.01–1.35; and I² = 56%) in comparison with metabolically healthy normal weight. No evidence of effect modification by age, sex, ethnicity, smoking, sample size or length of follow‐up was found. In conclusion, the present study reports a positive association between MHO and cancer incidence. All individuals with obesity, even in the absence of metabolic dysfunction, should be encouraged to lose weight.     

Association of metabolically abnormal but normal weight (MANW) and metabolically healthy but obese (MHO) individuals with arterial stiffness and carotid atherosclerosis

Objective

Despite recent interest in differential impact of body size phenotypes on cardiovascular outcomes and mortality, studies evaluating the association between body size phenotypes and indicators of atherosclerosis are limited. This study investigated the relationship of metabolically abnormal but normal weight (MANW) and metabolically healthy but obese (MHO) individuals with arterial stiffness and carotid atherosclerosis in Korean adults without cardiovascular disease.

Methods

A total of 1012 participants (575 men and 437 women, mean age 50.8 years), who underwent a health examination between April 2012 and May 2013 were prospectively enrolled based on inclusion and exclusion criteria. Study subjects were classified according to body mass index (BMI) and the presence/absence of metabolic syndrome.

Results

The prevalence of metabolically healthy normal weight (MHNW), MANW, MHO, and metabolically abnormal obese (MAO) were 54.84%, 6.42%, 22.83%, and 15.91%, respectively. Individuals with MANW had significantly higher brachial-ankle pulse wave velocity and maximal carotid intima-media thickness values than those with MHO, after adjusting for age and gender (P = 0.026 and P = 0.018, respectively). The odds ratio (OR) of arterial stiffness and carotid atherosclerosis in the MANW group were significantly higher than in the MHNW group in unadjusted models. Furthermore, multivariable models showed that increased OR of carotid atherosclerosis in the MANW group persisted even after adjusting for confounding factors (OR = 2.98, 95% CI = [1.54, 5.73], P = 0.011).

Conclusions

Compared to MHNW or MHO subjects, Korean men and women with the MANW phenotype exhibited increased arterial stiffness and carotid atherosclerosis.

Clinical trials no

NCT01594710.     

Obesity is more closely related with hepatic steatosis and fibrosis measured by transient elastography than metabolic health status

ObjectiveThe pathogenesis of non-alcoholic fatty liver disease (NAFLD) involves multiple concomitant events induced by obesity and metabolic health condition. This study aimed to assess the risk of NAFLD according to metabolic health and obesity status using transient elastography (TE).Materials and MethodsA total of 2198 asymptomatic adults without chronic liver disease and who underwent a medical health check-up were recruited. Subjects were categorized into four groups according to metabolic health and obesity statuses: metabolically healthy non-obese (MHNO); metabolically unhealthy non-obese (MUNO); metabolically healthy obese (MHO); and metabolically unhealthy obese (MUO). Hepatic steatosis was defined as controlled attenuation parameter (CAP) ≥ 238 dB/m, and significant liver fibrosis was defined as liver stiffness measurement (LSM) > 7.0 kPa, as defined by TE.ResultsCompared with MHNO group, the odds ratios (ORs) [95% confidence interval (CI)] for hepatic steatosis were 2.94 [2.32–3.71], 4.62 [3.52–6.07], and 12.02 [9.08–15.92] in the MUNO, MHO, and MUO groups, respectively (P < 0.001) in crude model. Regarding liver fibrosis, there was no significant difference in the ORs in MUNO group (ORs: 0.95 [95% CI, 0.33–2.78], P value = 0.929), whereas there was a significant increase in the ORs in MHO group compared with MHNO group (ORs: 4.32 [95% CI, 1.73–10.76], P = 0.002) in the fully adjusted model.ConclusionOur results show that MHO was associated with both liver steatosis and fibrosis assessed by transient elastography. Our results suggest that a healthy metabolic profile does not protect obese adults from hepatic steatosis or fibrosis, indicating that obesity itself might contribute to liver fibrosis.     

Association of metabolic health phenotypes,obesity, and hepatocellular carcinoma risk

BackgroundThe obesity and hepatocellular carcinoma (HCC) risk association may differ by individuals’ metabolic health status.AimTo investigate the association between obesity categories and HCC risk among individuals with different metabolic health phenotypes.MethodsA case-control study among 518 HCC cases and 1,036 frequency-matched controls was conducted. Body mass index (BMI) was assessed before diagnosis. Pre-diagnosis data on dyslipidemia, hypertension, and diabetes were used to categorize participants as metabolically healthy or metabolically unhealthy. Participants were further categorized into metabolically healthy normal weight (MHNW), metabolically healthy overweight (MHOW), metabolically healthy obese (MHO), metabolically unhealthy normal weight (MUNW), metabolically unhealthy overweight (MUOW), and metabolically unhealthy obese (MHO). We used logistic regression to calculate multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs).ResultsBeing overweight (OR=1.68, 95%CI=1.21–2.34) or obese (OR=1.49, 95%CI=1.11–1.89) was associated with higher HCC risk. Among metabolically healthy participants, no association was found between being overweight or obese and HCC risk. However, among the metabolically unhealthy participants, being overweight (OR=1.89, 95%CI=1.31–2.72) or obese (OR=1.50, 95%CI=1.07–2.09) was associated with higher HCC risk. Compared to the MHNW phenotype, no association was found between the MHOW and MHO phenotypes and HCC risk, but the MUNW (OR=1.94, 95%CI=1.09–3.43), MUOW (OR=3.78, 95%CI=2.15–6.65), and MUO (OR=2.93, 95%CI=1.70–5.05) phenotypes were associated with higher HCC risk.ConclusionThe association between BMI and HCC appears to be restricted to individuals with underlying metabolic abnormalities.     

Liver enzymes and vitamin D levels in metabolically healthy but obese individuals: Korean National Health and Nutrition Examination Survey

Objective

Increased liver enzymes and decreased vitamin D levels are associated with insulin resistance and type 2 diabetes. We examined liver enzymes and vitamin D levels in metabolically healthy but obese (MHO) individuals and compared the values with those of other body size phenotypes in the Korean population.

Materials/Methods

A total of 16,190 people over the age of 18 years were analyzed using data from the Fourth Korean National Health and Nutrition Examination Survey, which is a nationally representative survey. Body size phenotypes were classified into four groups by body mass index (BMI) and number of metabolic syndrome components.

Results

The prevalence of MHO was 14.9% in the entire population and 47.7% in the obese population. In a correlation analysis adjusted for age, sex, and BMI, AST and ALT levels were positively correlated with insulin resistance and cardiometabolic risk factors of the metabolic syndrome, whereas vitamin D level was negatively correlated with these variables. MHO individuals had significantly lower concentrations of AST and ALT compared to metabolically abnormal obese (MAO) subjects, although vitamin D levels were not significantly different. Furthermore, a multiple logistic regression analysis revealed that MHO individuals had lower risk of liver enzyme abnormality compared to MAO after adjusting for potential confounding factors. However, the risk of vitamin D deficiency was not significantly different among groups with different body size phenotypes.

Conclusions

Although both liver enzymes and vitamin D levels are related to insulin resistance and metabolic syndrome, only liver enzymes were independently associated with MHO phenotype.     

Metabolically obese phenotype and its dynamic change are associated with increased carotid intima-media thickness: Results from a cohort study

Background and aimsTo examine associations between metabolically obese phenotypes or their changes and increased carotid intima-media thickness (CIMT).Methods and resultsThis prospective cohort included 13,681 Chinese adults aged 20–80 years who completed follow-up health examination with carotid ultrasound and were divided according to metabolic and weight status: metabolically healthy and normal weight (MHNW); metabolically obese but normal weight (MONW); metabolically healthy but obese (MHO); metabolically abnormal and obese (MAO). Cox and logistic regression were used to evaluate the associations of the phenotypes or their changes with increased CIMT.During a mean follow-up of 33 months, 1927 participants developed increased CIMT. After adjusting for age, sex and potential biochemical confounders, MAO was significantly associated with increased CIMT (HR 1.22, 95% CI [1.07, 1.4]); the association remained significant in those 40 years or older. Compared with stable MHNW, increased CIMT risk was higher for stable MAO (OR 1.35 [1.16, 1.57]), transitional MAO from MONW (OR 1.44 [1.04, 1.97]), and transitional MHO from MHNW (OR 1.59 [1.10, 2.26]) in demographic adjusted models; only stable MAO remained significant in the multivariate adjusted model (OR 1.23 [1.05, 1.45]).ConclusionMAO significantly elevated the risk of increased CIMT. Stable MAO and obese transitions also promoted CIMT progression.     

代谢健康型肥胖与动脉粥样硬化的相关性研究

目的探讨在40岁以上的中国社区人群中,代谢健康型肥胖与动脉粥样硬化患病风险的相关性。方法来自上海嘉定社区共9525名不伴有心血管疾病的居民(男性3621名、女性5904名)参与了本项研究。每位参与者均完成了调查问卷、体格检查[包括肱踝脉搏波传导速度(brachial-ankle pulse wave velocity,baPWV)和血压(blood pressure,BP)的测量],以及实验室检查。根据体重指数(body mass index,BMI)和代谢水平,将参与者分为4组,分别是代谢健康型非肥胖(metabolically healthy non-obese,MHNO)、代谢不健康型非肥胖(metabolically unhealthy non-obese,MUNO)、代谢健康型肥胖(metabolically healthy obese,MHO)和代谢不健康型肥胖(metabolically unhealthy obese,MUO)。baPWV>1400 mm/s被定义为高baPWV水平,脉压差(pulse pressure,PP)高于人群上四分位数被定义为高PP水平。利用多元logistic回归分析模型探究MHO与高baPWV水平以及高PP水平之间的相关性。结果多元logistic回归分析显示,在校正性别、年龄、当前吸烟、当前饮酒及受教育程度之后,与MHNO组比较,MHO组人群与高baPWV水平(OR=1.18,95%CI 1.02~1.37)和高PP水平(OR=1.72,95%CI 1.43~2.08)有显著相关性。另外,MUNO和MUO组人群的高baPWV水平(MUNO为OR=3.02,95%CI 2.60~3.50;MUO为OR=3.26,95%CI 2.87~3.70)和高PP水平(MUNO为OR=2.56,95%CI 2.17~3.02;MUO为OR=3.49,95%CI 3.01~4.06)患病风险显著升高。结论中国社区中老年人群中,MHO与动脉粥样硬化患病风险升高有显著相关性。     

Associations between persistent organic pollutants and metabolic syndrome in morbidly obese individuals

Background and aims

Persons with “metabolically healthy” obesity may develop cardiometabolic complications at a lower rate than equally obese persons with evident metabolic syndrome. Even morbidly obese individuals vary in risk profile. Persistent organic pollutants (POPs) are widespread environmental chemicals that impair metabolic homeostasis. We explored whether prevalence of metabolic syndrome in morbidly obese individuals is associated with serum concentrations of POPs.

Metabolically healthy obese subjects are at risk of fatty liver but not of pre-clinical atherosclerosis

Backgrounds and aimsWhether obesity increases risk of cardiovascular disease (CVD) and fatty liver because of the co-existence of other risk factors is uncertain. We investigated odds ratios (ORs) for: a) a measure of pre-clinical atherosclerosis and b) fatty liver, in metabolically healthy obese (MHO) subjects, metabolically abnormal obese (MAO) subjects and metabolically abnormal non obese subjects (MANO), using a metabolically healthy non obese (MHNO) group as the reference.Methods and results14,384 South Koreans from an occupational cohort underwent cardiac computed tomography (CT) estimation of CAC score, liver ultrasound determination of fatty liver, and measurement of cardiovascular risk factors. Pre-clinical atherosclerosis was defined by a CAC score >0. We used logistic regression to determine ORs for CAC >0, and fatty liver in MHO, MAO and MANO subjects (reference group MHNO). There was no increase in OR for CAC score >0 (OR = 0.93, [95% CIs 0.67,1.31], p = 0.68), in the MHO group, whereas there was an increase in the ORs for CAC score >0 in the MAO, and MANO groups (OR = 1.64 [95% CI 1.36,1.98], p < 0.001) and (OR = 1.38 [95% CI 1.17,1.64], p < 0.001), respectively. In contrast, for fatty liver, there was an increase in OR in each group (OR = 3.63 [95% CI 3.06, 4.31] p < 0.001); (OR = 5.89 [5.18,6.70] p < 0.001); and (OR = 1.83 [95% CI 1.69,2.08]) in the MHO, MAO group and MANO groups respectively.ConclusionMHO subjects are at risk of fatty liver but attenuated risk of pre-clinical atherosclerosis. Both MAO and MANO subjects are at risk of fatty liver and pre-clinical atherosclerosis.     

Metabolically healthy obese phenotype and risk of cardiovascular disease: Results from the China Health and Retirement Longitudinal Study

BackgroundEpidemiologic evidence on metabolically healthy obese (MHO) phenotype and cardiovascular diseases (CVD) risk remains controversial.AimsWe aim to examine the relationship between MHO and risk of CVD among the Chinese population.MethodsThe China Health and Retirement Longitudinal Study is a prospective cohort study of 7849 participants aged ≥45 years without CVD at baseline. Metabolic health status was assessed based on blood pressure, triglycerides, high-density lipoprotein cholesterol, glycated hemoglobin, fasting glucose, and C-reactive protein. A cutoff point of body mass index of 24.0 kg/m² was used to define over-weight/obesity (≥24.0 kg/m²) or normal weight (<24.0 kg/m²). CVD was based on self-reported doctor’s diagnosis of heart problems and stroke. Incidence rate ratio (IRR) with 95% confidence interval (CI) was deduced from modified Poisson regression.ResultsDuring a mean 3.6 years of follow-up, 880 incident CVD events were recorded. 789 (10.05%) were identified MHO among 3321 (42.3%) obese individuals. Compared with metabolically healthy normal weight individuals, the multivariable adjusted IRR of CVD was 1.33 (95%CI: 1.19–1.49) for MHO, 1.29 (95%CI: 1.22–1.38) for metabolically unhealthy normal weight, and 1.61 (95%CI: 1.51–1.75) for metabolically unhealthy obese in the full adjusted model.ConclusionsMHO individuals are associated with the increased risk of cardiovascular diseases among the Chinese population.     

Resource Use and Burden of Hospitalization,Outpatient, Physician,and Drug Costs in Short- and Long-term Care After Acute Myocardial Infarction

Background

Little is known about the resource use and cost burden of acute myocardial infarction (AMI) beyond the index event. We examined resource use and care costs during the first and each subsequent year, among patients with incident AMI.