Abstract 13300: The Risk of Incident Hypertension According to the Metabolic Health and Obesity: Definition of Metabolic Health Does Not Matter

Background: Obesity is considered to be an important risk factor for hypertension. The metabolically healthy obese (MHO) phenotype refers to obese individuals with a favorable metabolic profile. Its prognostic value remains controversial and may partly depend on differences in defining methods. We examined the risk of MHO phenotype with incident hypertension in a Korean population using four representative criteria to define metabolic health status. Design and methods: The study population comprised of 31,033 Koreans without hypertension. Participants were stratified by body mass index (BMI) (cut-off value, 25.0 kg/m2) and metabolic health state, according to four defining methods; Adult Treatment Panel (ATP)-III criteria, Wildman criteria, Karelis criteria, and Homeostasis Model Assessment (HOMA) criteria. Results: Over the median follow-up period of 35.0 months (range, 4.5-81.4 months), 4,589 of the 31,033 individuals (14.8%) developed incident hypertension. Compared with the metabolically healthy nonobese (MHNO) group, the MHO group showed increased risk of incident hypertension with a multivariate-adjusted hazard ratio (HR) of 1.42 (95% confidence interval [CI], 1.30-1.54), 1.43 (95% CI 1.31-1.57), 1.41 (95% CI 1.27-1.56), and 1.33 (95% CI 1.23-1.45), when defined by ATP-III criteria, Wildman criteria, Karelis criteria, and HOMA criteria, respectively. Metabolically unhealthy obese (MUO) individuals were at the highest risk of incident hypertension. Conclusions: MHO subjects showed a substantially higher risk of incident hypertension regardless of the definition for metabolic health. Thus, it is important to consider both metabolic health and obesity when evaluating risk of hypertension.

Download Full-text

All-Cause Mortality Risk of Metabolically Healthy Obese Individuals in NHANES III

Journal of Obesity ◽

10.1155/2012/460321 ◽

2012 ◽

Vol 2012 ◽

pp. 1-12 ◽

Cited By ~ 67

Author(s):

C. M. Durward ◽

T. J. Hartman ◽

S. M. Nickols-Richardson

Keyword(s):

Mortality Risk ◽

Cox Regression ◽

Metabolic Health ◽

Nhanes Iii ◽

Model Assessment ◽

Clinical Risk ◽

Metabolically Healthy Obese ◽

Increased Risk ◽

All Cause Mortality ◽

Metabolically Healthy

Mortality risk across metabolic health-by-BMI categories in NHANES-III was examined. Metabolic health was defined as: (1) homeostasis model assessment-insulin resistance (HOMA-IR) <2.5; (2) ≤2 Adult Treatment Panel (ATP) III metabolic syndrome criteria; (3) combined definition using ≤1 of the following: HOMA-IR ≥1.95 (or diabetes medications), triglycerides ≥1.7 mmol/L, HDL-C <1.04 mmol/L (males) or <1.30 mmol/L (females), LDL-C ≥2.6 mmol/L, and total cholesterol ≥5.2 mmol/L (or cholesterol-lowering medications). Hazard ratios (HR) for all-cause mortality were estimated with Cox regression models. Nonpregnant women and men were included (n=4373, mean ± SD, age37.1±10.9years, BMI27.3±5.8 kg/m2, 49.4% female). Only 40 of 1160 obese individuals were identified as MHO by all definitions. MHO groups had superior levels of clinical risk factors compared to unhealthy individuals but inferior levels compared to healthy lean groups. There was increased risk of all-cause mortality in metabolically unhealthy obese participants regardless of definition (HOMA-IR HR 2.07 (CI 1.3–3.4),P<0.01; ATP-III HR 1.98 (CI 1.4–2.9),P<0.001; combined definition HR 2.19 (CI 1.3–3.8),P<0.01). MHO participants were not significantly different from healthy lean individuals by any definition. While MHO individuals are not at significantly increased risk of all-cause mortality, their clinical risk profile is worse than that of metabolically healthy lean individuals.

Download Full-text

Abstract 13508: Obesity Phenotype and the Risk of Hypertension and Type 2 Diabetes: Does Cardiorespiratory Fitness Matter?

Circulation ◽

10.1161/circ.130.suppl_2.13508 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Sae Young Jae ◽

Mercedes Carnethon ◽

Won Hah Park ◽

Bo Fernhall

Keyword(s):

Type 2 Diabetes ◽

Body Mass Index ◽

Cardiorespiratory Fitness ◽

Normal Weight ◽

Incident Hypertension ◽

Metabolically Healthy Obese ◽

Increased Risk ◽

Healthy Obese ◽

Metabolically Healthy

There is conflicting evidence regarding the association between metabolically healthy obese (MHO) and metabolically unhealthy normal weight (MUNW) with incident hypertension and type 2 diabetes. The role of cardiorespiratory fitness on these associations has not been fully explored. We tested the hypothesis that obesity phenotypes predict incident hypertension and type 2 diabetes, but cardiorespiratory fitness modifies these associations in a prospective study of apparently healthy men. 3800 men (mean age 48±6 yrs, range 20-76 yrs) participated in two health examinations during 1998-2009. All subjects were free of hypertension and type 2 diabetes at baseline examination. MHO was defined as obesity (body mass index ≥ 25 kg/m2) with no more than one metabolic abnormality, and MUNW was defined as body mass index < 23 kg/m2) with two or more abnormalities. Cardiorespiratory fitness was directly measured by peak oxygen uptake during a treadmill test. Incident hypertension and type 2 diabetes were defined as blood pressure ≥140/90mmHg and as ≥6.5% of HbA1c or ≥126mg/dl of fasting glucose at second examination, respectively. During an average follow-up of 5 years (1-12 yrs), there were 371 (9.8%) men incident hypertension and 170 (4.5%) men incident type 2 diabetes. MHO and MUNW were present in 844 (22%) and 249 (6.6%) men. Compared with metabolically healthy normal weight men, MHO and MUNW men were at increased risk for hypertension (relative risk (RR) =1.82, 95% Confidence Interval (CI): 1.29-2.56 and 1.75, 1.11-2.74) and type 2 diabetes (RR=3.68, 1.92-7.07 and 5.35, 2.61-10.94), respectively. These risks in MHO and MUNW men were still persisted with adjustment for confounder variables and cardiorespiratory fitness (hypertension=1.57, 1.05-2.34 and 1.59, 1.01-2.51; type 2 diabetes=3.35, 1.63-6.89 and 4.76, 2.32-9.77). Metabolically healthy obese or metabolically unhealthy normal weight men were at increased risk of hypertension and type 2 diabetes compared with metabolically healthy normal weight men. However, these associations were not attenuated by cardiorespiratory fitness or other confounder factors.

Download Full-text

Differential Effect of Metabolic Health and Obesity on Incident Heart Failure: A Nationwide Population-Based Cohort Study

Frontiers in Endocrinology ◽

10.3389/fendo.2021.625083 ◽

2021 ◽

Vol 12 ◽

Author(s):

Hwi Seung Kim ◽

Jiwoo Lee ◽

Yun Kyung Cho ◽

Joong-Yeol Park ◽

Woo Je Lee ◽

...

Keyword(s):

Heart Failure ◽

National Health ◽

Population Based ◽

Metabolic Health ◽

Metabolically Healthy Obese ◽

Obesity Status ◽

Increased Risk ◽

Metabolically Healthy ◽

Incident Heart Failure

BackgroundMetabolically healthy obese (MHO) individuals and their association with cardiometabolic diseases have remained controversial. We aimed to explore the risk of incident heart failure (HF) based on the baseline metabolic health and obesity status as well as their transition over 2 years.MethodsThe Korean National Health Insurance Service-National Health Screening Cohort data of 514,886 participants were analyzed. Obesity was defined as BMI ≥25 kg/m2 according to the Korean Centers for Disease Control and Prevention. The metabolic health and obesity status were evaluated at baseline and after two years. Study participants were followed to either the date of newly diagnosed HF or the last follow-up visit, whichever occurred first.ResultsThe MHO group comprised 9.1% of the entire population and presented a better baseline metabolic profile than the metabolically unhealthy non-obese (MUNO) and metabolicavlly unhealthy obese (MUO) groups. During the median 71.3 months of follow-up, HF developed in 5,406 (1.5%) participants. The adjusted hazard ratios [HRs (95% CI)] of HF at baseline compared with the metabolically healthy non-obese (MHNO) group were 1.29 [1.20–1.39], 1.37 [1.22–1.53], and 1.63 [1.50–1.76] for MUNO, MHO, and MUO groups, respectively. With the stable MHNO group as reference, transition into metabolically unhealthy status (MUNO and MUO) increased the risk of HF, regardless of the baseline status. Subjects who were obese at both baseline and follow-up showed an increased risk of HF, regardless of their metabolic health status.ConclusionsMetabolic health and obesity status and their transition can predict the risk of incident HF. Losing metabolic health in baseline non-obese and obese individuals and remaining obese in baseline obese individuals showed a significantly increased risk of incident HF. Maintaining good metabolic health and a lean body may prevent the development of HF.

Download Full-text

Risk of Arterial Stiffness According to Metabolically Healthy Obese Phenotype: A Combined Cross-Sectional and Longitudinal Study in Kailuan Cohort

10.21203/rs.3.rs-97966/v1 ◽

2020 ◽

Author(s):

Anxin Wang ◽

Yu Wang ◽

Yingting Zuo ◽

Xue Tian ◽

Shuohua Chen ◽

...

Keyword(s):

Longitudinal Study ◽

Health Status ◽

Arterial Stiffness ◽

Metabolic Health ◽

Cross Sectional ◽

Metabolically Healthy Obese ◽

Increased Risk ◽

Healthy Obese ◽

Metabolically Healthy ◽

Healthy Participants

Abstract BackgroundTo investigate the risk of incident arterial stiffness according to metabolically healthy obese (MHO) phenotype in Chinese population.Materials and methodsThe Kailuan study is an ongoing prospective cohort study, 37,180 participants with at least one-time measurement of branchial-ankle pulse wave velocity (baPWV) were included in the cross-sectional analysis, and 16,236 participants with repeated measurement of baPWV during the follow-ups were included in the longitudinal study from March 1, 2010, to January 31, 2020. Cross-classification of body mass index (BMI) categories and metabolic health status created six groups. Linear and logistic regression analyses were used to assess the association between BMI-metabolic status phenotypes and baPWV in mono-factor and multi-factor models. ResultsThe results of cross-sectional and longitudinal investigation were basically the same, as the abnormality of baPWV increased with BMI categories in metabolically healthy participants, while the increasing tendency disappeared in metabolically unhealthy participants. A 1.6-fold, 2.8-fold increased risk for the new occurrence of arterial stiffness were documented in MHO and metabolically unhealthy obese participants compared to metabolically healthy normal weight controls in the fully adjusted model. Further stratified analysis shown that metabolic health status was an interaction factor between BMI and arterial stiffness in either study population (P<0.0001 for cross-sectional study and P=0.0003 for longitudinal study).ConclusionsMetabolic health status and BMI categories contribute to the progression of arterial stiffness, while BMI is positively associated with arterial stiffness only in metabolically healthy participants. Moreover, MHO is an intermediate stage between metabolically healthy and unhealthy status.Trial registration: ChiCTR-TNRC-11001489. Registered 24 August 2011 - Retrospectively registered, http://www.chictr.org.cn/showprojen.aspx?proj=8050

Download Full-text

Risk of incident ischemic stroke according to the metabolic health and obesity states in the Vascular-Metabolic CUN cohort

International Journal of Stroke ◽

10.1177/1747493016672083 ◽

2016 ◽

Vol 12 (2) ◽

pp. 187-191 ◽

Cited By ~ 17

Author(s):

Laura Sánchez-Iñigo ◽

David Navarro-González ◽

Alejandro Fernández-Montero ◽

Juan Pastrana-Delgado ◽

JA Martínez

Keyword(s):

Ischemic Stroke ◽

Hazard Analysis ◽

Normal Weight ◽

Metabolic Health ◽

Stroke Incidence ◽

Metabolically Healthy Obese ◽

Increased Risk ◽

Healthy Obese ◽

Metabolically Healthy

Background Whether obesity is a major risk factor for cardiovascular disease in the absence of metabolic comorbidities remains under debate. Indeed, some obese individuals may be at low risk of metabolic-related complications, while normal-weight individuals may not be “healthy.” Aims To assess the incidence of ischemic stroke according to the metabolic health and obesity states of 5171 participants from the Vascular-Metabolic CUN cohort. Methods A Cox proportional-hazard analysis was conducted to estimate the hazard ratio and their 95% confidence interval of stroke according to the metabolic health and obesity states based on TyG index and Adult Treatment Panel-III criteria, during 9.1 years of follow-up. Results After 50,056.2 person-years of follow-up, 162 subjects developed an ischemic stroke (incidence rate 3.23 per 1000 person-years). Metabolically healthy obese subjects did not show greater risk of stroke, while metabolically unhealthy participants, obese and non-obese, had an increased risk of stroke, compared with healthy non-obese. The hazard ratios for the multivariable adjusted model were 1.55 (95% CI: 1.36–1.77) and 1.86 (95% CI: 1.57–2.21), respectively. Conclusions Metabolically unhealthy individuals exhibited a greater risk of ischemic stroke than metabolically healthy obese individuals.

Download Full-text

Metabolic Health—The Role of Adipo-Myokines

International Journal of Molecular Sciences ◽

10.3390/ijms20246159 ◽

2019 ◽

Vol 20 (24) ◽

pp. 6159 ◽

Cited By ~ 7

Author(s):

Christine Graf ◽

Nina Ferrari

Keyword(s):

Early Life ◽

Normal Weight ◽

Cardiovascular Fitness ◽

Metabolic Health ◽

Metabolically Healthy Obese ◽

Endocrine Organs ◽

Metabolically Healthy ◽

Underlying Mechanisms ◽

Definition Of

Obesity is now a worldwide epidemic. In recent years, different phenotypes of obesity, ranging from metabolically healthy normal weight to metabolically unhealthy obese, were described. Although there is no standardized definition for these phenotypes or for metabolic health, the influence of lifestyle and early-life factors is undisputed. In this context, the ratio of muscle-to-fat tissue seems to play a crucial role. Both adipose tissue and skeletal muscle are highly heterogeneous endocrine organs secreting several hormones, with myokines and adipokines being involved in local autocrine/paracrine interactions and crosstalk with other tissues. Some of these endocrine factors are secreted by both tissues and are, therefore, termed adipo-myokines. High (cardiorespiratory) fitness as a surrogate parameter for an active lifestyle is epidemiologically linked to “better” metabolic health, even in the obese; this may be partly due to the role of adipo-myokines and the crosstalk between adipose and muscle tissue. Therefore, it is essential to consider (cardiovascular) fitness in the definition of metabolically healthy obese/metabolic health and to perform longitudinal studies in this regard. A better understanding of both the (early-life) lifestyle factors and the underlying mechanisms that mediate different phenotypes is necessary for the tailored prevention and personalized treatment of obesity.

Download Full-text

Metabolic Obesity Phenotypes and Risk of Cellulitis: A Cohort Study

Journal of Clinical Medicine ◽

10.3390/jcm8070953 ◽

2019 ◽

Vol 8 (7) ◽

pp. 953

Author(s):

Cheong ◽

Chang ◽

Cho ◽

Ryu

Keyword(s):

Cohort Study ◽

Health Status ◽

Metabolic Health ◽

Metabolic Phenotype ◽

Model Assessment ◽

Metabolic Syndrome Component ◽

Hazard Ratios ◽

Increased Risk ◽

Metabolically Healthy

No cohort studies have evaluated the effect of obesity on the risk of cellulitis according to metabolic health status. We investigated an association of BMI and metabolic health status with the development of cellulitis. We conducted a cohort study of 171,322 Korean adults who underwent a health checkup examination and were followed from 2011 to 2016 for cellulitis and hospital admission related to cellulitis, which were ascertained through the linkage to the Health Insurance and Review Agency database. Being metabolically healthy was defined as not having any metabolic syndrome component and having a homeostasis model assessment of insulin resistance <2.5. During 638,240.4 person-years of follow-up, 14,672 cases of incident cellulitis were identified with 225 cases of cellulitis-related admission. After adjustment for possible confounders, the multivariable-adjusted hazard ratios (95% CI) for incident cellulitis comparing BMIs 23–24.9, 25–29.9, and ≥30 with a BMI of 18.5–22.9 kg/m2 as the reference were 1.07 (1.02–1.11), 1.09 (1.04-1.13), and 1.19 (1.08-1.31), respectively, whereas the corresponding multivariable-adjusted hazard ratios (95% CI) for cellulitis-related admission were 1.55 (1.05–2.3), 2.47 (1.73–3.53), and 4.8 (2.86–8.05), respectively. These associations were consistently observed in both metabolically healthy and unhealthy individuals with no significant interaction. In a large cohort of apparently healthy adults, increased BMI was associated with an increased risk of cellulitis and hospitalization for cellulitis in both metabolically healthy and unhealthy individuals. Obesity appears to be an independent risk factor for cellulitis regardless of metabolic phenotype.

Download Full-text

Circulating Adipokines in Healthy versus Unhealthy Overweight and Obese Subjects

International Journal of Endocrinology ◽

10.1155/2014/170434 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 18

Author(s):

Assim A. Alfadda

Keyword(s):

Hdl Cholesterol ◽

Metabolic Health ◽

Bioactive Substances ◽

Metabolically Healthy Obese ◽

Cholesterol Levels ◽

Increased Risk ◽

Obese Subjects ◽

Healthy Obese ◽

Metabolically Healthy

It is now well established that not all obese subjects are at increased risk of cardiometabolic complications; such patients are termed the metabolically healthy obese. Despite their higher-than-normal body fat mass, they are still insulin sensitive, with a favorable inflammatory and lipid profile and no signs of hypertension. It remains unclear which factors determine an individual's metabolic health. Adipose tissue is known to secrete multiple bioactive substances, called adipokines, that can contribute to the development of obesity-associated complications. The goal of this study was to determine whether the circulating adipokine profiles differs between metabolically healthy and metabolically unhealthy overweight and obese subjects, thereby obtaining data that could help to explain the link between obesity and its related cardiometabolic complications. We defined metabolic health in terms of several metabolic and inflammatory risk factors. The serum adiponectin levels were higher in the healthy group and showed a positive correlation with HDL cholesterol levels in the unhealthy group. There were no differences between the two groups in the levels of serum leptin, chemerin and orosomucoid. Accordingly, adiponectin might play a role in protecting against obesity-associated cardiometabolic derangements. More studies are needed to clarify the role of different chemerin isoforms in this system.

Download Full-text

Adiponectin Levels Differentiate Metabolically Healthy vs Unhealthy Among Obese and Nonobese White Individuals

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2015-2765 ◽

2015 ◽

Vol 100 (11) ◽

pp. 4172-4180 ◽

Cited By ~ 41

Author(s):

Scott Ahl ◽

Mitchell Guenther ◽

Shi Zhao ◽

Roland James ◽

Jacqueline Marks ◽

...

Keyword(s):

Body Mass Index ◽

Body Mass ◽

Metabolic Health ◽

Model Assessment ◽

Central Adiposity ◽

Healthy Individuals ◽

Homeostasis Model Assessment ◽

Metabolically Healthy Obese ◽

Healthy Obese ◽

Metabolically Healthy

Context: Adiponectin levels (ADPN) are lower in individuals with central obesity and cardiometabolic diseases. Conversely, studies have shown paradoxical hyperadiponectinemia (HA) in metabolically healthy obese (MHO) individuals of non-European descent. Moreover, individuals with higher sc to visceral adipose tissue (ie, higher peripheral adiposity) distribution have higher ADPNs. However, it is not known whether metabolically healthy individuals have predominantly peripheral adiposity along with higher ADPNs. Objective: This study aimed to evaluate the association of ADPN and adiposity distribution with metabolic health in white individuals. Design and Setting: This was a cross-sectional study of members of “Take Off Pounds Sensibly” weight loss club and their relatives. Participants: We recruited 2486 (72% women, 61% obese) individuals. They were defined as metabolically healthy by absence of hypertension, diabetes, and dyslipidemia; and they were further classified into metabolically healthy nonobese (MHNO), metabolically unhealthy nonobese (MUNO), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO). Waist-to-hip ratios (WHRs) were used as markers of adiposity distribution. Insulin resistance was measured using homeostasis model assessment. Results: Among the four groups, MHNO had the lowest WHRs (higher peripheral adiposity) and highest ADPN, and MUO had highest WHRs (higher central adiposity) and lowest ADPN (P < .001). Among both nonobese and obese, metabolically healthy individuals had higher ADPN than metabolically unhealthy individuals (P < .05) after adjustment for age, sex, and body mass index. MHNO also had lower WHRs compared with MUNO (P < .01). Although WHRs were lower among MHO compared with MUO, the difference was not significant. In addition, nonobese and obese individuals with HA (defined using sex-specific cutoffs) had lower homeostasis model assessment and dyslipidemia compared with individuals without HA. Conclusions: Higher ADPN and lower WHRs (higher peripheral adiposity) are associated with better metabolic health in both nonobese and obese white individuals. These results suggest that ADPN and peripheral adiposity play a key role in determining the metabolic health independent of body mass index.

Download Full-text

Abstract 17843: Visceral Adipose Tissue Secretion of Adiponectin Decreases with Increased Body Mass Index

Circulation ◽

10.1161/circ.130.suppl_2.17843 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Lenore R Rengel ◽

Brittaney Obi ◽

Jon Gould ◽

Matthew Goldblatt ◽

Andrew Kastenmeier ◽

...

Keyword(s):

Adipose Tissue ◽

Visceral Adipose Tissue ◽

Metabolic Health ◽

Metabolically Healthy Obese ◽

Obese Subjects ◽

Healthy Obese ◽

Metabolically Healthy ◽

Visceral Adipose ◽

Subcutaneous Adipose

Introduction: Peripheral adiposity is associated with better metabolic health and higher plasma adiponectin (ADPN) levels. Since ADPN is secreted mainly by adipose tissue (AT), it is intriguing that higher visceral adipose tissue (VAT) is associated with lower ADPN levels and poor metabolic health. Hypothesis: We hypothesized that various AT depots differ in their ability to secrete ADPN. Methods: Paired AT samples (VAT and subcutaneous adipose tissue (SAT)) were collected from 19 subjects (10 women, 15 obese) undergoing elective abdominal surgery. The samples were cultured and the supernatant was collected after 24 hours. ADPN levels released into the supernatant from VAT and SAT were measured using multiplex methods. Subjects were defined as obese or non-obese (NO) based on BMI > or ≤ 30kg/m2 respectively. Obese subjects were further classified as metabolically unhealthy obese (MUO) or metabolically healthy obese (MHO) based on presence or absence of type 2 diabetes mellitus, hypertension, or cardiovascular disease at the time of surgery. Results: Mean ADPN secretion levels from SAT and VAT were similar in NO subjects (17.3 ± 3.4 vs. 9.8 ± 13.0 ng/mL/mg, p=0.5) whereas the mean ADPN secretion was lower from VAT among obese subjects (15.9 ± 0.8 vs. 4.5 ± 0.2 ng/mL/mg, p=0.0002). ADPN secretion decreased from VAT (r=-0.16) and increased from SAT (r=0.33) with increased BMI (Fig.1). When MHO and MUO were compared, ADPN secretion from VAT in MHO was reduced only slightly (16.1 ± 8.2 vs. 4.0 ± 2.0 ng/mL/mg, p=0.07) whereas ADPN secretion was significantly reduced in MUO (15.9 ± 5.3 vs. 4.7 ± 4.6 ng/mL/mg, p=0.003). Conclusions: Reduced ADPN secretion from VAT in subjects with increasing BMI may explain lower circulating ADPN levels in obese individuals. Higher ADPN production from SAT and the relatively preserved secretion of ADPN from VAT may explain metabolic health in some obese individuals. Futures studies will help identify factors that control ADPN secretion from AT.

Download Full-text