The clustering of four components of risk factors (e.g., obesity, hypertension [HTN], insulin resistance, and hyperlipidemia) is called the metabolic syndrome (MetS) [123]. MetS is a major risk factor for diabetes and cardiovascular disease (CVD), with emerging high prevalence in both industrial and developing countries [45678]. The underlying pathophysiology of MetS is thought to be insulin resistance and obesity, both of which can be linked with other risk factors and are subclinical to CVD [91011]. Because of the clustering of these components in some individuals, a common pathogenesis has been suggested [10]. However, the exploratory factor analysis (EFA) in different populations has yielded inconsistent results [12131415]. A single-factor and two-, three-, four-, and even five-factor models have been reported [1213141516171819]. These inconsistencies of the results may be partially related to the nature and the different methods used in EFA that yield different factors in order to maximize the observed variability of data. Many of these studies used orthogonal rotation factors with varimax methods that would produce interpretable loading coefficients for observed variables, but in the real world, the underlying latent constructs are correlated. Despite the high prevalence of MetS, in the north of Iran [820], the issues of underlying associated latent factors of MetS remain controversial. An understanding of the underlying pathophysiology of MetS plays an important role in public health intervention and preventive measures. Confirmatory factor analysis, the measurement model within the structural equation modeling (SEM), is an alternative method of choice to evaluate the hypothesized conceptual model that characterizes the MetS [212223].

On the other hand, the SEM is often used to test a conceptual framework model with a graphic presentation of the relation of observed variables as independent variables and latent constructs as dependent variables [21]. This approach allows the measurement model and construct model to be considered simultaneously. While it can estimate the path coefficients of observed variables among latent constructs, the structural constructs used in the hypothesized model are often correlated and thus it takes into account this covariance [21222324]. Therefore, the observed model is a combination of the measurement model and the construct model. An attractive feature of SEM is that takes into account modeling measurement errors and the conceptual hypothesis model can be tested by applying SEM. The process of testing is often confirmatory. An application of SEM is to assess the construct validity, which means to determine the extent to which the observed variables evaluate the latent construct in a conceptual framework model [25]. This approach is a powerful method to use sophisticated data; it is a combination of factor, multiple regression, and path analyses. An example of such sophisticated data are the components of MetS involved with observed variables as indicators of latent constructs where several correlated latent constructs are present. The hypothesized modeling of components of MetS was characterized by previous EFA required to be tested by confirmatory analysis of SEM and to determine which of the competitive models best fit the observed data in different populations. Thus, the objectives of this study were to evaluate and compare the fitness of different competing models (one-, two-, three-, and four-factor models) as characterized in the literature for components of MetS in an adult Iranian population.

Study participants had an average age (±standard deviation [SD]) of 41.0±13.2 years, and 55.3% were female. The prevalence of MetS based on ATP III criteria was 35.0% (29.0% in men vs. 39.8% in women, P=0.001). Among the components of MetS, low HDL-C (82.4%), abnormal TG (42.2%), and abnormal WC (39.7%) values were the most common abnormalities in our study population. A significant difference of higher metabolic abnormality was observed in women compared with men (Table 1). Table 2 summarizes the fit statistics of the hypothesized models that were evaluated in this study according to sex. Model 1A is characterized as a single-factor model with reduced dimension of observed variables such that TG and HDL-C were replaced by single-dimension observed data as TG:HDL-C and DBP and SBP by MAP. In model 1B, all observed variables were considered as a single factor without reducing the dimension of data. All fitting indexes met the criterion of goodness of fit in both sexes in model 1A, but the other single-factor model (model 1B) used the original observed data; all fitting indexes were poor, in particular, the high value of RMSEA=0.20 was observed. Model 2 characterized by two correlated latent constructs, BP, and metabolic factors; the summary fitting statistics have improved significantly compared with model 1B. Except for the significant P value of the chi-square test, all fitting indexes met the required criteria in both sexes. However, a lower standardized regression coefficient of HDL-C on the lipid factor was observed. Model 3 (three-factor model) yielded a better improvement of fitting indexes than model 2; in particular, RMERA reached 0.023 in men and the P value of the chi-square test was not significant (i.e., the observed data are progressively fit with the hypothesized model) and a relatively high correlation was apparent between the two constructs of obesity and metabolic factors, but in women, again, all fitting statistics met the criteria except a significant P value of the chi-square test was revealed. The results show that the correlations among three underlying constructs were greater in women than in men, but, surprisingly, a low positive standardized regression coefficient between HDL-C and metabolic factor was observed in women. The standardized loading coefficients and the correlation between underlying constructs in two- and three-factor models are presented in Figs. 1 and 2 according to sex, respectively. Additionally, the standardized loading coefficients of the single-factor model are shown in Figs. 3 and 4. In all figures, one side arrow shows the standardized loading coefficients of observed variables on the latent construct as regression coefficients regardless of the scale used, and two side arrows indicate the correlation structure between different constructs. Additionally, the four-factor model was locally underidentified; the loading estimate for a factor or latent construct with only one indicator as observed variable cannot be mathematically derived because in our data insulin resistance factor had only one observed variable, FBG.

In this study, SEM and confirmatory factor analysis of a set of cardiometabolic risk variables were used to evaluate the pattern of related factors to MetS. SEM correlates a set of observed variables into a single factor or latent construct involving path analysis using direct and indirect effects. This method allows evaluation of the causal pathway of observed variables in relation to defined constructs and estimation of the correlation between constructs based on conceptual framework. The objectives of SEM in this analysis were to evaluate and compare the conceptual hypothesized competitive models to determine the extent they are supported by our sample data. The latent constructs used in this analysis were obesity, HTN, and metabolic factors including lipid profiles and insulin resistance and, thus, MetS.

Within a set of defined observed variables, we found the fit of a single-factor model (model 1B) was not plausible, but the two-correlated factor model was plausible and the all fitting indexes were improved compared with the single-factor model. However, further improvement, in particular, RMSEA, was achieved significantly by fitting a three-factor oblique model rather than a two-factor oblique model. In particular, in men, all fitting indexes met the required fitting criteria, but in women, the RMSEA reached 0.08, which also is acceptable, and the all summary fitting index chi-square yielded a significant P value, perhaps due to a larger sample size. Few published studies evaluated and compared the fit indexes of different competitive models of MetS by using SEM approach, but many used only EFA to designate factors associated with MetS. Our findings are in accordance with those reported by Shah et al. [23] in a nondiabetic United States population with rather similar summary fitting indexes. Similar to our results, a single-factor model was not fit with the observed data, but a two-correlated factor model suggested by Hanley et al. [12] fit the observed data well. The four-factor model, as suggested by previous EFA, might be more plausible as shown by Shah et al. [23]. The fitting criteria were improved, but our observed data for insulin resistance were sparse and we had only one observed variable as measured by FBG as an indicator of insulin resistance and thus the SEM were unidentifiable.

In our analysis, when the dimension of observed data was reduced from seven to five by replacing TG and HDL-C with TG:HDL-C and MAP with SBP and DBP, as well as using WC as a single measure of obesity/abdominal obesity instead of BMI and WC, the single-factor model (model 1A) produced relatively fair fitting indexes. Except for NFI, the summary fitting indexes achieved the required fitting criteria, in particular for men. This shows the plausibility of the single-factor model's underlying pathophysiology of MetS. A similar result has been reported in other populations as well [11192829]. The inconsistencies of the results between single-factor and three-factor models in this analysis may be related to pooling some observed raw measures into a single measure. It seems that by this pooling, not all information for two observed variables may be conveyed to a single observed variable.

In our findings of the correlation structures between different constructs of a three-factor model designated by sex, a higher positive correlation between the three underlying constructs was observed in women. The correlation between obesity and metabolic factors in women was 0.77 but it was 0.37 in men. This might be explained by the emerging high prevalence of obesity and abdominal obesity and, thus, MetS in Iranian women compared with in Iranian men in recent decades [72030]. The standardized coefficients of observed variables on related latent constructs were rather similar between sexes, which is similar to those reported by Hanley et al. [12]. In our findings, the apparent low positive correlation of HDL-C on lipid construct was also surprising in women.

The correlation structures between three underlying factors/constructs were considerable in our SEM analysis, as one expects. The improvement in fitting indexes of three-factor models compared with a single- and two-factor models implies that MetS involves multiple physiologies. The clinical implications of this finding from preventive measures of CVD events is that any interventional program should focus simultaneously on three factors (obesity, HTN, and lipid profiles/glucose). However, our data show that the obesity component has a greater impact on MetS among women but that HTN has a greater impact in men.

This study has limitations. The casual pathway relationship may not be established with such a cross-sectional design. Also, we measured only the traditional risk factors of CVD. The homeostasis model assessment as an index of insulin sensitivity was not measured. We had only a single observed variable measured by FBG as indicator of insulin resistance and, thus, SEM was undefinable in evaluating a four-factor model. In addition, this analysis was restricted to nondiabetic individuals because of the small sample size of diabetic subjects; the estimates of SEM were undefinable. Thus, one should be cautious to generalize the results. However, this study has several advantages: it is population based with a relative homogeneous ethnic group and study participants had similar diet and physical activity behaviors. This analysis would help in the understanding of the sophisticated interrelation between unobservable constructs. The underlying constructs or latent factors involving MetS cannot be measured directly with single measure; they are a combination of several observed variables. In contrast to the traditional regression analysis, the independent and dependent variables should be observable, and it is assumed that there is no measurement error on independent observed variables, but in clinical practice such a random error is inevitable. On the other hand, the SEM method takes into account such an error in the structure of analysis. Further prospective studies with measurement of nontraditional risk variables such as inflammatory variables is required to establish the causal path relationship of related observed variables to the latent constructs.

In conclusion, the significant improvement in summary fitting indexes of a three-factor model suggested that multiple physiopathology of MetS is plausible.