Harmonizing the Diagnosis of Metabolic Syndrome—Focusing on Abdominal Obesity

Abstract

In 2009, important health organizations met to construct a Joint Scientific Statement (JSS) intended to harmonize the diagnosis of metabolic syndrome worldwide. The JSS aimed to unify the diagnostic criteria of metabolic syndrome, particularly in relation to whether to include abdominal obesity as a criterion of diagnosis. A large part of the JSS is devoted to discussing the diagnosis of abdominal obesity. More specifically, 9 of the 16 papers focused on abdominal obesity. Continuing this emphasis, we discuss the harmonization of the diagnosis of metabolic syndrome worldwide, specifically focusing on the need to improve the diagnosis of abdominal obesity.

Introduction

T he combination of metabolic disorders, which is now known as metabolic syndrome, was first observed and described by the anatomist Morgagni in 1765. He linked abdominal obesity to factors consistent with the diagnosis of hypertension, atherosclerosis, dyslipidemia, sleep apnea–hypopnea, and hyperuricemia.¹ Later in 1920, Kylin² noted that hypertension, hyperglycemia, and gout tended to occur together. Some decades later, Vague³ found that central obesity was a determinant factor in predisposing patients to diabetes, atherosclerosis, gout, and uric calculi. Reaven⁴ established the clinical importance of this syndrome in 1988 and coined the term “syndrome X” to describe the joint presence of three factors—dyslipidemia, hypertension, and hyperglycemia. In the following year, Kaplan⁵ introduced the term “deadly quartet” to describe the joint presence of obesity, hypertriglyceridemia, glucose intolerance, and hypertension. Over the years, other terms were used synonymously in the study of this condition (insulin resistance, syndrome X, insulin resistance syndrome X, metabolic X syndrome, dysmetabolic syndrome X, Reaven syndrome X, metabolic cardiovascular syndrome). Although there has been awareness of metabolic syndrome for more than 2 centuries, it was not until 1998 that the first formal definition was published by a group of consultants from the World Health Organization (WHO).^6,7 In subsequent years, several other organizations proposed criteria for the diagnosis of metabolic syndrome, often focusing on discussions of abdominal obesity and always considering the clinical importance.^2,8

–12

Important health organizations (the International Diabetes Federation Task Force on Epidemiology and Prevention; the National Heart, Lung, and Blood Institute; the American Heart Association; the World Heart Federation; the International Atherosclerosis Society; and the International Association for the Study of Obesity) met to draft a Joint Scientific Statement (JSS)¹³ with the intention of harmonizing the diagnosis of metabolic syndrome worldwide. The JSS aimed to unify the diagnostic criteria of metabolic syndrome, particularly in relation to including abdominal obesity as a criterion for diagnosis. Not surprisingly, a large part of the JSS is devoted to discussing the diagnosis of abdominal obesity. As an indication of its importance, 9 of the 16 papers used for writing the JSS discussed abdominal obesity. However, the method used to diagnose abdominal obesity can affect the outcome and, consequently, the subsequent identification of metabolic syndrome. As a contribution to this dialog, we discuss the worldwide harmonization of the diagnosis of metabolic syndrome, focusing on the need to improve the diagnosis of abdominal obesity.

What is Obesity?

Before we discuss the diagnosis of abdominal obesity, it is important to understand the definition of obesity. Conceptually, obesity is defined as the excessive accumulation of body fat, including total body fat, a particular fat deposit, and even the morphology/function of adipocytes. A body mass index (BMI) ≥30.0 kg/m² is an operational definition for obesity that is useful in many contexts, but it should not be used as a conceptual definition. Obesity denotes excess body fat in a quantity large enough to cause a decrease in health and longevity. This reduction in health status will not be noticeable in all cases according to the operational definition used to measure it.¹⁴

Although BMI has been accepted by the scientific community because of its simplicity and its established relationship with the morbimortality risk, it is important highlight that BMI does not distinguish between being overweight due to lean mass or due to fat accumulation. Central obesity anthropometric indicators are also simple, and they are determined in a region where muscles stabilize the trunk. Consequently, greater waist size—particularly at the level of the lumbar spine—can be attributed almost exclusively, if not exclusively, to increased fat. This reinforces the necessity for a serious reevaluation of employing the BMI as the universal criterion for the prediction of obesity-related morbimortality risk.¹⁵

Diagnosis of Abdominal Obesity

Two problems are associated with using waist circumference as a predictor of morbimortality risk. The first is the selection of the cutoff points—a problem further compounded by the use of ethnicity-dependent cutoffs. The second problem stems from inconsistencies in the measurement of waist circumference as a result of the different methods of measurement that are actually used in practice. We discuss these problems in the following section.

Reviewing the JSS recommendations for diagnosing abdominal obesity,¹³ 8 of 13^{8
–10,16

–20} are derived from the study of Han et al.,²¹ in which they used the midpoint. However, the midpoint is not always recommended (see Table 1). In the study by Han et al.,²¹ the cutoff points for waist circumference were based on an earlier study of the same group,²² where the cutoff points for waist circumference represent the cutoffs for BMI. For example, ≥80 cm for women and ≥94 cm correspond to a BMI ≥25 kg/m², and ≥88 cm for women and ≥102 cm for men correspond to a BMI ≥30 kg/m². Studies designed to determine the morbimortality through anthropometric indicators of obesity show that waist circumference, waist-to-hip ratio, conicity index, and waist-to-weight ratio are more effective in explaining morbimortality than BMI.^23

–27 However, within these studies, different anatomical sites were used to measure waist circumference.

Table 1.

Operational Definitions Recommended for the Diagnosis of Abdominal Obesity in Specific Populations According to Waist Circumference by Organization

		Recommended waist circumference threshold for the diagnosis of abdominal obesity
Population	Organization (original study)	Men	Women	Point of measurement recommended
Europid	IDF^2,8 (Han et al.)²¹	≥94 cm^a	≥80 cm^a	Midpoint^b
Caucasian	WHO¹⁴ (Han et al.)²¹	≥94 cm (increased risk)^a	≥80 cm (increased risk)^a	Midpoint^b
		≥102 cm (still higher risk)^a	≥88 cm (still higher risk)^a	Midpoint^b
United States	AHA/NHLBI ATP III^11,12 (Han et al.)²¹	≥102 cm^a	≥88 cm^a	Iliac crest^c
Canada	Health Canada^18,19 (Han et al.)²¹	≥102 cm^a	≥88 cm^a	Midpoint^b
European	European Cardiovascular Societies²⁰ (Han et al.)²¹	≥102 cm^a	≥88 cm^a	None^d
Asian (including Japanese)	IDF^2,8 (Ko et al.)²⁹	≥90 cm^e,f	≥80 cm^e,f	Midpoint^c
Asian	WHO, WPRO, IOTF, IASO²⁸ (Ko et al.)²⁹	≥90 cm^e,f	≥80 cm^e,f	Midpoint^c
Japanese	Japanese Obesity Society⁶⁴ (Japanese Obesity Society)⁶⁴	≥85 cm	≥90 cm	Umbilicus^b
Chinese	Cooperative Task Force⁶⁵ (Zhou)⁶⁵	≥85 cm	≥80 cm	None^g
Brazilian	Pitanga and Lessa²³	≥88 cm	≥83 cm	Midpoint^b
Middle Eastern, Mediterranean	IDF^2,8 (absent)^h	≥94 cm^a	≥80 cm^a	Midpoint^h
Sub-Saharan African	IDF^2,8 (absent)^h	≥94 cm^a	≥80 cm^a	Midpoint^h
Ethnic Central and South American	IDF^2,8 (absent)^h	≥90 cm^f	≥80 cm^f	Midpoint^h

The cutoff point developed by Han et al.²¹

The point of waist measure recommended by the organization was similar to that used to determine the cutoff point in the original study.

The point of waist measure recommended by the organization was different than that used to determine the cutoff point in the original study.

We recommend using the midpoint for the waist measure because the midpoint was used in the original study even though the organization does not recommend a point.

The cutoff point recommended by the organization was different than that developed in the original study.

The cutoff point developed by Ko et al.²⁹

We recommend using the midpoint for the waist measure because of the absence of a waist point measure recommended by the organization and the original study.

The point of waist measure and the cutoff point for abdominal obesity recommended by the organization were according to ethnic origin.

IDF, International Diabetes Federation; WHO, World Health Organization; AHA, American Heart Association; NHLBI, National Heart, Lung and Blood Institute; ARP III, Adult Treatment Panel III; WPRO, WHO Western Pacific Region; IOTF, International Obesity Task Force; IASO, International Association for the Study of Obesity.

It is noteworthy that the data presented by Lean et al.²² showed an association between BMI and waist circumference (r=0.89, P<0.001, for both sexes). Although the authors determined the sensitivity and specificity of waist circumference, two points need to be highlighted: (1) The statistical analysis used was a simple linear regression correlation when an receiver operating characteristic (ROC) curve should have been used; (2) the outcome should have focused on risk factors instead of an end point at the same level, e.g., BMI (using waist circumference to screen BMI as a diagnostic criteria for obesity is problematic because both are in the same surrogate end point level).

The recommendations for specific ethnic groups—Asians (including Japanese)^2,8,28—were based on previous evidence,^29,30 which showed that the increased risk associated with obesity occurs at lower BMIs for this population. This population is also predisposed to visceral or abdominal obesity. In the original article²⁹ that gave rise to the recommendations,^2,8,28 the minimum waist circumference was defined between the umbilicus and the xiphoid process and was used to select the optimal cutoff for hypertension, diabetes, dyslipidemia, and albuminuria within the Chinese subgroup. The cutoff points for the considered risk factors ranged from 74.6 to 78.4 cm for women and 80.0 to 84.0 cm for men. The recommended cutoff points^2,8,28 differed from the original study by Ko et al.²⁹ (see Table 1).

As admitted in the JSS,¹³ defining the cutoff points for abdominal obesity is complicated by a number of factors. The problems in defining the cutoff points are further compounded for groups where the points are defined by ethnic origin (e.g., Middle Eastern and Mediterranean; Sub-Saharan African; Central and South American) and not by the health risk imposed by abdominal obesity (see Table 1). To illustrate the ethnicity problem, consider the Brazilians as an example.³¹ This population is one of the most heterogeneous populations in the world, resulting from five centuries of miscegenation among people from three continents: Amerindians, Europeans, and Africans. This miscegenation was tested in the Brazilian population, where the fraction of mitochondrial DNA (mtDNA) haplotypes, specified by continent, showed high variability among people who self-identified as white. The study suggests that Brazilians have a genetic mosaic that derives from the combined genetic contributions of Amerindians (33%), Europeans (39%), and Africans (28%) in their genetic mosaic. On this basis, the cutoff points for abdominal obesity²³ for Brazilians are more appropriate than the cutoff points selected by ethnic origin (Table 1).¹³

Another important consideration is the choice of anatomical site of the waist circumference measure. The JSS¹³ shows the waist circumference cutoff points for abdominal obesity. However, it does not report at which point the waist should be measured. A systematic review³² identified 14 sites that can be chosen to measure waist circumference. Among these, the review found that the most frequently used measures were the midpoint (30%), the umbilical point (29%), and the minimal waist (27%). Additionally, the measurement protocol for minimal waist was inconsistently described within and throughout the studies. The differences between the midpoint and umbilical measures were analyzed using data from 13,131 subjects (aged between 10 and 79 years).³³ The analysis identified significant (P<0.01) mean differences between the measures of 3.2 cm [95% confidence interval (CI)=3.1–3.3 cm] in men and 6.2 cm (95% CI=6.1–6.3 cm) in women. These differences significantly (P<0.01) change the estimates of the prevalence of abdominal obesity—12.4% (95% CI=11.5%–13.2%) for men and 17.5% (95% CI=16.6%–18.4%) for women. Therefore, if abdominal obesity is defined at the midpoint, for example, no other point should be used to diagnose abdominal obesity. Therefore, we believe that the original protocol of waist measurement cannot be omitted from the studies, including guideline and consensus studies. There are two issues to be considered in selecting the best measure—consistency of diagnosis and the practical issue of obtaining consistency in the measurement itself.

Obtaining the Best Measurement of Waist Circumference

Currently, the best available evidence for measuring waist circumference is the midpoint, which is the most used and consistent measurement of waist circumference, as highlighted by Ross et al.³² in a systematic review. However, this does not indicate that the protocol for measuring waist circumference is complete.

It is important to clarify that the waist circumference measurement does not measure visceral fat. Instead, the waist circumference is an anthropometric indicator of fat distribution, and it can be used to predict the amount of visceral fat. Most importantly, the waist circumference can be presented as a risk of morbimortality.^34,35

The midpoint measure of waist circumference should be used to diagnose abdominal obesity. We recommend that the best measure of waist circumference be performed at the midpoint for the diagnosis of abdominal obesity and for use as one of the five criteria for metabolic syndrome diagnosis, with respect to the recommendations provided by several organizations (Table 1). This recommendation is based on the fact that the midpoint must be determined between two bone markers (last rib and iliac crest), which allows greater precision in the assessment or reassessment, because the anatomical location of bone markers may change minimally with the gain or loss of fat. Therefore, measuring the waist circumference between these bone markers, instead of on or near them, may provide greater sensitivity for detecting waist circumference changes due to changes in the amount of abdominal fat.

We also recommend standardization of the equipment used to measure waist circumference. We recommend a flat, flexible, nonelastic, anthropometric measuring tape with a spring-loaded device at one end of the tape to control pressure on the skin and enough space to handle the range of measurement at the opposite end. The resolution of the scale of measurement should be 0.10 cm, with a maximum tolerance of ±0.10 mm at 1 m.³⁶ To measure waist circumference, we recommend that the subject be positioned in a standing posture with legs parallel and feet at hip width. The circumference should be obtained in the horizontal plane, perpendicular to the longitudinal axis of the body, on bare skin at the end of a normal expiration, while asking patients to keep their abdominal muscles relaxed. To determine the midpoint, it is necessary to first locate the bone markers (last rib and iliac crest). Then, touching the left and right abdominal hemisphere, draw a line to mark the midpoints between the lowest rib and the iliac crest. The evaluator should be positioned in front of the subject, wrapping the anthropometric tape around the waist from back to front in the horizontal plane and reading the measurements.

When performing research, it is noteworthy that the gold standard (direct method) for measuring fat is body dissection.³⁷ Because this is not an option in clinical practice, the gold standards (indirect methods) for measuring visceral fat volume are abdominal computed tomography (at L4–L5) and magnetic resonance imaging (MRI). However, these methods are not widely used due to the limitations of cost and risks³⁸ (e.g., radiation exposure or contrast-induced nephropathy). In addition, when measured using MRI, there is a common variation between visceral fat and waist circumference of 65.5% and a common variation between abdominal fat and waist circumference of 70.5%.³⁹

Some questions should be asked about new diagnostic methods (even the gold standards): How can they improve clinical practice? How would they change my clinical decision making process? What is the evidence level for decision making?

A good example for answering these questions focuses on overdiagnosis, as described below.⁴⁰ A young obese woman went to the cardiologist's office with atypical chest pain. The probability of obstructive coronary disease was considered low. Even so, the physician chose to ask for noninvasive screening. Cardiac computed tomography angiography (CCTA) was performed to exclude the possibility of coronary artery stenosis and to reassure her. As with any noninvasive test, there is a probability of a false-positive result. This was evidenced by the catheterization, which showed no coronary obstruction. As a result of this procedure, the left main trunk coronary artery was dissected as a consequence of an inaccurate CCTA, causing an extensive anterior infarction, leading to emergency heart surgery. Days later, the patient was readmitted for refractory heart failure and received a heart transplant as a unique solution to resolve her symptoms. It is very important to mention that we found no evidence for this diagnostic procedure. However, the physician justified the procedure as “just in case.”

“Just in case,” i.e., overdiagnosis due lack of consistent evidence, has been discussed in another paper.⁴¹ For asthma, a Canadian study suggests that 30% of people with a diagnosis may not have asthma and 66% may not require medications. For breast cancer, a systematic review suggests that up to one-third of screening-detected cancers may be overdiagnosed. Similarly, for high cholesterol, estimates project that up to 80% of people with near-normal cholesterol are treated for life and may be overdiagnosed. Last, in prostate cancer, the risk that a cancer detected by prostate-specific antigen testing is overdiagnosed may be over 60%.

It is important to highlight that a guideline based on the best available evidence may prevent overdiagnosis from guiding the decision making in clinical practice and/or research (implications for practice and implications for research). Regarding the implications for research, gold standard techniques (e.g., MRI) are useful for creating new health technologies and evaluating the accuracy of new diagnostic tests. However, in practice, they may improve clinical screening by becoming available for more citizens by being simple and low cost (e.g., waist circumference).

Considering the applicability of guiding decision making in clinical practice and/or research (e.g., a researcher using the end points of the JSS¹³ to define cutoff points of metabolic syndrome), the midpoint can be recommended as the best available evidence for measuring waist circumference to diagnose abdominal obesity.

Assessing the JSS of Metabolic Syndrome

The JSS published by Circulation has a high research impact in the scientific community (searched September 19, 2012) as shown by the 1445 retrieved citations: 675 in Web of Science and 770 in Scopus. When the databases were searched specifically for Metabolic Syndrome and Related Diseases, we found 17 articles^{42

–59} that cited the JSS.¹³ Considering metabolic syndrome as a global epidemic, our concern is the use of an operational definition based on a better level of evidence instead of expert opinion.

Health professionals are increasingly looking for guidelines to assist their clinical decisions. However, there are limitations and questions about the development of such guidelines. Therefore, some tools (AGREE II, iCAHE)^60,61 have been proposed to assess the quality of these papers.

The Appraisal of Guidelines for Research & Evaluation (AGREE II)⁶⁰ is one reliable instrument for assessing the quality of a guideline. It is composed of six domains (scope and purpose, stakeholder involvement, rigor of development, clarity of presentation, applicability, editorial independence) with a total of 23 questions on a scale varying from 1 (strongly disagree) to 7 (strongly agree).

Before applying the AGREE II, ⁶⁰ to avoid the possibility of bias in the assessment of the JSS ¹³ and because the instrument used is a 7-point Likert scale, two authors (V.S. and A.J.G.) independently assessed the JSS. A kappa with linear weighting was calculated: 0.8407 (95% CI=0.7165–0.9649).

This instrument was applied to the JSS,¹³ and we obtained a mean of 4.57 (95% CI 3.52–5.61) or 65% of the possible points. The domain of rigor of development decreased the mean drastically due to procedure limitations of planning the methods of the study. The methodological problems of the JSS¹³ consist of how they selected the original articles to write the consensus; for example, a search strategy should be described for the major databases. Additionally, an evaluation of the quality of the included studies relating the limitations and strengths should have been performed. If these items had been evaluated properly, this statement would have achieved better quality.

Another weak point of the statement is the lack of a planned update. For future publications, we recommend that the authors use the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy.⁶²

It is noteworthy that health professionals have to be more careful about generalizing guidelines because this may not be assumed as an unconditional truth. Guidelines should not be followed without a critical assessment because they may jeopardize patient health.

Final Consideration

The primary purpose of the JSS¹³ to advance the study of metabolic syndrome, as admitted by the authors of the consensus,⁶³ was the unification of diagnostic criteria by organizations to set a single global definition. Another important outcome was that abdominal obesity should not be a sole prerequisite for the diagnosis of metabolic syndrome, but one of the five criteria. However, the recommendation for a global criterion of waist circumference remains unresolved, which affects the diagnosis of metabolic syndrome. The consensus of the JSS¹³ contributed to the progress of the study of metabolic syndrome. However, it is still based on expert opinion without explicit critical evaluation of the literature. In this regard, the JSS needs to be used in tandem with a critical appraisal of the guidelines. It is important to highlight that the best available evidence shows that the midpoint is the most consistent measurement for the diagnosis of abdominal obesity.

There are still some gaps in the literature, and further studies are needed to address them. Among these, we can highlight the following questions: What is the best measure (most accurate) of waist circumference? What are the differences in cutoff points for the subgroups (disease stage, co-morbidity, risk factor, sex, age, ethnic group) identified by the JSS?¹³ Is waist circumference the most accurate measure for morbimortality? What are the differences between a real end point and surrogate end point?

In addition, future updates of the JSS¹³ will urgently need to be redrafted based on appropriate methodologies and rigorous strategies for the successful implementation of the resulting recommendations because the current version was primarily based on expert opinion. This will be important for harmonizing the diagnosis of abdominal obesity and also metabolic syndrome.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

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