Analysis of the components for classifying Metabolic Syndrome used in older people: an integrative review

Objective : To analyze the components of Metabolic Syndrome (MetS) and the rationale for adopting the criteria used for its classification in older individuals through an integrative review. Method : an integrative review of the literature in Portuguese, English, Spanish and Bulgarian involving older people (age ≥60 years) on the electronic databases MEDLINE - via PubMed, Embase, Web of Science and Scopus, without restriction on publication date or study design, was conducted from August 2022 to January 2023. The Medical Subject Headings (MeSH) and Health Sciences Descriptors (DEcS) controlled descriptors “elderly”, “elderly 80 or older”, “metabolic syndrome”, “prevalence”, “component” and “criterion” were used. Studies that were off-topic, unavailable in full and that failed to answer the guiding question were excluded. Results : Application of the eligibility criteria led to the retrieval of 1340 studies, of which 14 were included in the integrative review. Seven sets of criteria were identified for evaluating MetS in the older population were identified and most studies used two of these criteria. The IDF criterion was cited 7 times and the NCEP - ATP III criterion 8 times in the 14 article reviewed. Conclusions : Although the searches retrieved different studies on the subject, the results suggest the criteria for MetS should be revised, with cut-off points defined according to the population studied.


INTRODUCTION
The growth in the older population, promoted by increased life expectancy and shifts in demographic, epidemiological and population transitions, is associated with significant consequences for society 1,2 .Aging favors greater vulnerability, giving rise to functional and physiological changes in the body that lead to the development of chronic non-communicable diseases (NCD), which often cooccur in this age group 3,4 .Chronic conditions, such as diabetes mellitus (DM) and systemic arterial hypertension (SAH), affect a large contingent of the older population.These conditions, when cooccurring with high triglyceride (TG) levels, low high density cholesterol (HDL-c) values and abdominal obesity, define metabolic syndrome (MetS), a highly prevalent NCD in the older population [5][6][7][8] .
The spatial distribution of MetS is widespread, although some studies show major disparities in different parts of the world.In Brazil, the rate of MetS is around 22.7%, compared with 24.3% in European countries and 34.2% in North America.The contrast in these estimates might be explained by regional differences, disparities in sample characteristics (age, sex, race/ethnicity and economic status), besides differences in diagnostic criteria used to define the syndrome 9 -13 .
Several sets of criteria, based on different definitions and cut-offs, have been suggested by the leading world health organizations for diagnosing MetS.This definition has been the focus of studies and consensus conducted by important organizations in the field of health.In 1999, the World Health Organization (WHO), with the aim of standardizing the criteria, proposed a first diagnostic criterion, modified shortly after by the EGIR (European Group for the Study of Insulin Resistance), which proposed a new definition 14 .
One of the most widely used criteria to date was devised in 2001 in the USA, namely, the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III), defining the presence of the syndrome when 3 or more of the following criteria/components are abnormal: waist circumference, TG, blood pressure and plasma fasting glucose.In 2015, the Brazilian Society of Cardiology deemed the NCEPATP III satisfactory for diagnosing MetS [15][16][17] .
In 2005, another framework widely accepted in the literature, the International Diabetes Federation (IDF) criteria, recommended waist circumference, together with the presence of 2 or more of the following for diagnosing MetS: raised fasting plasma glucose or diagnosed DM, raised HDL-cholesterol or specific treatment, raised triglycerides or specific treatment, and raised blood pressure or specific treatment.In 2017, the Brazilian Diabetes Society endorsed the use of the IDF criteria for diagnosing MetS, including adaptations for diagnosing individuals aged under 18 years given the lack of consensus on reference values 18 .
The third National Surveillance of Risk Factors of Non-Communicable Diseases in Iran, conducted in 2007, drew on the definition of MetS according to the criteria established by the NCEP -ATP III and the IDF, adapting the cut-off point for waist circumference for the local population.The Iranian National Obesity Committee adopted this cut-off point, along with the following criteria for MetS, with 3 out of 5 components: Iranian-specific waist circumference ≥ 95cm, fasting plasma glucose or previously diagnosed DM, reduced HDL-cholesterol or specific treatment, raised triglycerides or specific treatment, raised blood pressure or specific treatment 19,20 .
Generally, the diagnostic criteria for MetS take into account the presence of dyslipidemia (hypertriglyceridemia, low-HDL), systemic arterial hypertension, obesity and hyperglycemia.However, no solid consensus exists on whether DM2 (glycemia > 126 mg/dL in population-based studies without clinical diagnosis) or obesity should be obligatory criteria for MetS, and different reference values have been proposed for systemic arterial hypertension and other biochemical analyses 14 .
Given the lack of a consensus definition on the combination of risk factors that should be considered for diagnosing MetS, together with the dearth of articles in the literature on the best criteria for assessing MetS in the older population, the objective of the present study was to analyze the components of the Metabolic Syndrome (MetS) and the rationale for adopting the criteria used for classifying the syndrome in older adults through an integrative review.

METHOD
An integrative review was carried out in 6 stages: 1-identification of the topic and selection of the guiding question; 2-establishing of criteria for study inclusion/exclusion; 3-definition of the information to be extracted from the studies selected and their classification; 4-methodological assessment of the studies included; 5-interpretation of results; 6-presentation of the review and synthesis of knowledge.
The search was performed between August 2022 and January 2023 based on the guiding question: "what components are used for diagnosing Metabolic Syndrome in older people available in the literature?"The PICo framework was used to devise the question, where P denotes the population (older people), I the aspect of interest (components used) and Co the context (Metabolic Syndrome) 21 .
The search for studies was conducted on the databases MEDLINE (Medical Literature Analysis and Retrieval System Online)) -via Pubmed (U.S. National Library of Medicine), Web of Science, Scopus and Embase.The last 3 databases, with restricted access, were accessed free of charge via the Federal Academic Community (CAFe) of the National Teaching and Research Network (RNP), using the CAPES Periodicals website portal.
The following controlled descriptors from Medical Subject Headings (MeSH) and Descritores em Ciências da Saúde -Health Science Descriptors (DEcS) were employed: aged, aged 80 and over, metabolic syndrome, prevalence, component and criteria, together with the Boolean logic operators AND and OR, as per the search strategy outlined in Chart 1.
The present integrative review was registered on the OSF Registry platform under protocol code no.10.17605/OSF.IO/V7YJH.Inclusion criteria for studies were primary original articles (crosssectional, cohort study and case-control studies), addressing the different components of MetS in older adults (age ≥60 years), available in Portuguese, English, Spanish and Bulgarian.No restrictions for study design or publication date were applied.Studies were selected independently by 2 reviewers using the Rayyan selection platform by QCRI (Qatar Computing Research Institute) and all duplicate records removed.The articles were first screened by reading titles and abstracts.Articles that met the eligibility criteria and were selected by both reviewers (agreement) were read in full for inclusion or exclusion in the review.Disagreements at the full reading stage were settled by consensus by recruiting a third reviewer.
Exclusion criteria were studies that addressed other diseases besides MetS, animal studies and review articles.
The Critical Appraisal Skills Programme (CASP) tool was used to appraise the methodological rigor of the articles included (Chart 2).The original CASP contained 8 specific tools for appraising different study designs, such as reviews, cohort studies, crosssectional studies, clinical trials, among others.An adapted 10-item version of the CASP was scored in the present review: 1) clear statement of aim; 2) appropriate method; 3) presentation and discussion of theoretical and methodological procedures; 4) appropriate sample recruitment; 5) clear data collection; 6) relationship between researcher and participants; 7) ethical standards maintained; 8) rigorous data analysis; 9) clear statement and discussion of findings; and 10) contributions, limitations and identification of new areas of research.Each item was attributed a value of 0 (zero) or 1 (one), where the final result is a tally of the scores, for a maximum of 10 points.The articles selected were classified according to final scores into level A -6-10 points (good methodological quality and reduced bias) or level B -at least 5 points (satisfactory methodological quality, but with increased risk of bias) 22 .
The level of evidence of the studies was categorized using the Agency for Health Care Research and Quality (AHRQ) system.Quality of evidence is classified into 6 levels, namely: (1) systematic review or meta-analysis; (2) randomized clinical trials; (3) non-randomized clinical trials; (4) cohort and case-control studies; (5) systematic review of descriptive and qualitative studies; and (6) original descriptive or qualitative study 23 .

RESULTS
A total of 1340 articles were identified on the databases.After removal of duplicate articles (n=79), 1261 remained for analysis.After screening of titles and abstract, articles eligible for full reading were selected, with the exclusion of 1166 studies for being off-topic or meeting other exclusion criteria.Subsequently, a further 81 articles were excluded for not being available in the literature or because, after full reading, the methods and results failed to meet the eligibility criteria.A total sample of 14 articles met the inclusion criteria and were included in the review (Figure 1).
The articles reviewed were published in English (n=11), Spanish (n=1), Portuguese (n=1) and Bulgarian (n=1) in international journals, between 2012 and 2023.Studies were conducted in 11  All studies were rated as Level A for methodological quality by the adapted CASP.Assessment using the AHRQ revealed 2 case-control type studies (Level 4 evidence), 2 prospective cohort studies (Level 4 evidence) and 10 cross-sectional observational studies (Level 6 evidence).None of the studies adopted a qualitative approach.The main information extracted from the articles is presented in Chart 3, providing a range of characteristics of the studies included covering the parameters: author, publication year, country, study design, objective, MetS assessment instruments, sample and key results.Source: created by author.
The articles selected addressed the main criteria and components used for assessing MetS older populations worldwide.Seven sets of criteria for assessing MetS in the older population were identified in the 14 articles reviewed.The data extracted from the studies were analyzed and compiled to assess for possible differences in classification among the criteria used for diagnosing MetS (Chart4).The results showed that most studies used 2 out of the 7 criteria.The IDF criteria was used in 7 of the 14 articles reviewed, while the NCEP -ATP III and modified NCEP III were used by 8 and 1 study, respectively.The Iranian-specific criteria (both IDF and NCEP III) were used once only in the articles reviewed.The WHO criteria was cited in 3 of the articles reviewed, whereas the Harmonized Criteria for MetS was used once only in the 14 articles reviewed.
Rev. Bras.Geriatr.Gerontol.2023;26:e230077 DISCUSSION Metabolic syndrome is a condition affecting a large contingent of the population, with a high prevalence in older people 3 .No specific criteria for classifying MetS in this older group was found, with all available criteria used for adults and adolescents, extending to the older population.
A 2021 study was conducted in Finland investigating 539 older individuals, comprising 320 women and 219 men.For diagnosing MetS, 3 comparative instruments were applied: the IDF, NCEP ATP III and the modified NCEP ATP III.Overall, the prevalence of MetS was 24.7%, 35.2%, and 37.2% in men, according to the NCEP, modified NCEP, and IDF definitions, respectively.In women, the corresponding figures were 20.9%, 33.1%, and 47.8% 35 .
According to the 2016 study by O'CONNOR et al. performed in Ireland, the prevalence of MetS in the population was 41.6% when defined using the NCEP ATP III criteria versus 47.3% according to the IDF criteria.For both methods, MetS was more prevalent in men than in women and increased with age 29 .
Consistent with results of the Irish study, in a 2015 study by YOUSEFZADEH et al. in Iran of 874 individuals aged >60 using the same IDF and NCEP ATP III criteria, increased age was directly associated with the development of MetS and its prevalence was high in females for both criteria 28 .
In India, a 2023 study of 114 older adults comparing both the IDF and NCEP ATP III criteria was published.The prevalence of MetS in the diabetic population was 42.3% and 28.9% according to the IDF and NCEP ATP III, respectively.A higher prevalence was found in women than men using both criteria 33,36 .
The same two criteria were used to classify MetS in 200 older hospitalized patients in a Spanish study determining MetS prevalence with the IDF and NCEP ATP III criteria.The prevalence of MetS was 65% (NCEP-ATP III) and 67.5% (IDF), proving greater in women (NCEP-ATP III=72.8%;IDF=73.6%)than in men (NCEP-ATP III=50.7%;IDF=56.3%) 24.
In Brazil, 2 studies assessing MetS in older adults were conducted, In the first, a group of 202 institutionalized older adults diagnosed with MetS using the NCEP ATP III revealed a MetS rate of 29.2% 32 .In the second investigation, 113 older adults were randomly selected from among users of the primary care service of the Brazilian national health system (SUS) and MetS assessed using the WHO harmonized criteria.The overall prevalence of MetS was 58.65%.The rate among females was 60.5% versus 55.7% for men, with no statistically significant gender difference (p = 0.589) 26 .
The NCEP ATP III was one of the most widely used frameworks in China and Cuba for assessing MetS in older individuals.A study investigating MetS prevalence in longevity in the Guangxi Zhuang Autonomous Region, China, recruited 307 oldestold to assess the presence of MetS.Overall, 28% of the participants had MetS diagnosed using the NCEP ATP III criteria 31 .In Cuba, 103 older residents of 3 nursing homes were assessed using the same criteria, revealing that 33% of patients had MetS, with predominance in in females 30 .
A study in Iran including 598 participants aged ≥60 years found that females, the widowed/divorced, the illiterate, rural residents, the unemployed, and non-smokers showed a higher number of MetS components compared to their counterparts.The results also found that, of the sample of participants, 15.3% had no MetS components, 23.7%only one, 24.5% two, 20.3% three, 12.2% four, while 4.1% exhibited all of the components of MetS.Thus, 84.7% of the subjects had at least one MetS component 20,37 .
In another Iranian study investigating MetS components, the IDF criteria showed a higher prevalence of raised systolic blood pressure and reduced HDL cholesterol levels, while central obesity was more frequent in men.Using the NCEP ATP III definition, the study results showed that systolic and diastolic blood pressure, mean levels of plasma triglycerides and fasting glucose and reduced HDL were lower in women than in men 28 .Similar findings were reported by a study in Finland when comparing the component of elevated blood pressure using the NCEP and modified NCEP ATP III or IDF criteria (91.8% in men versus 89.0% in women).In men, the second most commonly component detected by the 3 definitions was glucose abnormality, with rates of 53.2% by NCEP and 78.4% by the modified NCEP and/or IDF criteria.In women, the second most prevalent single component was also glucose abnormality, with rates of 33.1% and 59.7% measured by the NCEP and modified NCEP, respectively 35 .
In Brazil, a study of institutionalized older individuals using the NCEP ATP III criteria showed that the most frequent MetS components were low HDLc (63.9%) and abdominal obesity (42.7%) 32 .According to Vieira et al., in another Brazilian study, of older individuals selected from users of the Unified Health System and assessed using the WHO harmonized criteria, hypertension was the Rev. Bras.Geriatr.Gerontol.2023;26:e230077 most prevalent component of the syndrome in both men (80.8%) and women (85.2%) 26 .
In Bulgaria, 1050 women, comprising 538 older adults, were explored to determine the prevalence of MetS using the IDF criteria and new WHO harmonized definition.Results showed that the 41.7% (527/1265) of participants with increased waist circumference had no data on MetS because at least 2 of the total 5 components for MetS were missing.The SAH component proved a strong predictor and was second only to obligatory waist circumference in the Bulgarian population 27 .
Give the growing prevalence of MetS in the older population, mechanisms linking MetS with neurodegenerative diseases have been investigated 38 .In 2021, FLORES Jesús et al. performed a study in Mexico of a population of 99 patients, predominantly males, with median age of 66 years that had Parkinson Disease, using the World Health Organization (WHO) criteria for diagnosing MetS.MetS was reported in 8% of the population with Parkinson Disease.Of the different components of MetS, arterial hypertension had the greatest prevalence among PD patients, with a rate of 30%.Results also showed that patients who had both PD and MetS exhibited greater motor impairments than those without MetS 34 .
In 2013, NEVAJDA used the WHO criteria to investigate the prevalence of MetS in an older population in Croatia.A total of 561 older nursing home residents in Zagreb were studied.The prevalence of MetS in the older residents was 20.8% and the most common component was hypertension, being significantly more frequent in women 25 .
The present review has some limitations, such as the small number of studies addressing MetS criteria in older people and also the dearth of studies on the Brazilian population included in the review.The weakness of the criteria regarding the cut-off point for assessing waist circumference in the population studied may hamper or introduce bias in the true diagnosis of MetS, leading to a possible overestimation of the prevalence of the syndrome in women.

CONCLUSION
This integrative review showed that different organizations have developed specific criteria for assessing MetS, which were applied in different parts of the world, according to the choice of study authors.The NCEP ATP III and IDF criteria were the most used by the studies, proving more rigorous than other criteria.
The WHO criteria appears to be less commonly used given its disparate results compared to other criteria, possibly due to its use of the type 2 diabetes as an obligatory factor for MetS.The Harmonized MetS criteria was less cited in the literature, although it uses abdominal obesity as an assessment component based on country-specific cut-off points, rendering the criteria more flexible.
Overall, the NCEP ATP III set of criteria was the most cited by the articles reviewed, proving more workable in that data on the components measured are more easily collected in original studies.
Although the search retrieved different studies on the subject, the results suggest the components of MetS criteria should be investigated in more depth, with specific cut-off points defined according to the population studied.

Figure 1 .
Figure 1.Flow diagram of search and selection process and reasons for exclusion of studies selected for integrative review.Recife, Pernambuco state, 2023.Source: created by author.

Chart 4 .
Criteria/components used for diagnosing metabolic syndrome in older adults: WHO, IDF, NCEP-ATP III, modified NCEP-ATP III, IDF with cut-off point for Iran, NCEP -ATP III with cut-off point for Iran and Harmonized MetS.Recife, Pernambuco state, Brazil,2023.Health Organization; NCEP-ATP III: National Cholesterol Education Program Adult Treatment Panel III; IDF: International Federation of Diabetes; NCEP-ATP III (m): modified National Cholesterol Education Program Adult Treatment Panel III; SAH: Systemic Arterial Hypertension; WC: Waist Circumference; TG: triglycerides; HDL-c: High-density lipoprotein cholesterol; BMI: body mass index; DM2: type 2 diabetes mellitus; M: male; F: female Source: created by author.