metabolic syndrome ( metsy ) is defined as a combination of adverse cardiovascular disease ( cvd ) and metabolic risk factors including abdominal obesity , dyslipidemia , hyperglycemia , and hypertension . a growing body of evidence documented that the metsy is a risk factor for atherosclerotic cvd and type 2 diabetes mellitus ( t2 dm ) incidence and mortality .
three definitions have been suggested by various organizations . the revised national cholesterol education program third adult treatment panel ( rncep : atpiii ) definition requires three or more of the following components : 
 waist circumference ( [ wc ] 102 cm for men and 88 cm for women);increased triglycerides ( [ tg ] 150 mg / dl or being under treatment);low , high - density lipoprotein cholesterol ( hdl - c < 40 mg / dl for men and < 50 mg / dl for women or being under treatment);elevated blood pressure systolic blood pressure ( [ sbp ] 130 mmhg , or diastolic blood pressure [ dbp ] 85 mmhg or receiving anti - hypertensive medications);increased fasting plasma glucose ( [ fpg ] 100 mg / dl or treatment for hyperglycemia ) . 
 
waist circumference ( [ wc ] 102 cm for men and 88 cm for women ) ; increased triglycerides ( [ tg ] 150 mg / dl or being under treatment ) ; low , high - density lipoprotein cholesterol ( hdl - c < 40 mg / dl for men and < 50 mg / dl for women or being under treatment ) ; elevated blood pressure systolic blood pressure ( [ sbp ] 130 mmhg , or diastolic blood pressure [ dbp ] 85 mmhg or receiving anti - hypertensive medications ) ; increased fasting plasma glucose ( [ fpg ] 100 mg / dl or treatment for hyperglycemia ) . in the international diabetes federation definition , central obesity is necessary as a prerequisite ( wc 94 cm for men and 80 cm for women ) and in addition at least two of the raised tg , low hdl - c , elevated blood pressure ( bp ) and fpg .
the recent joint interim statement definition requires the presence of three out of the five above mentioned components , but with considering national or regional - specific adoption for measure of the central obesity mainly wc .
the prevalence and clinical usefulness of the metsy are age , gender , and culture - dependent , augmenting with increasing age and more useful in males . in the middle east , the prevalence of the metsy is more than western countries , with higher frequency in females than males .
due to the high burden of the cvds and t2 dm , identifying individuals who are at higher risk for these disorders would be useful . as mentioned above , the metsy is a risk factor for cvd and t2 dm but during recent years using a continuous metsy risk score ( cmetsys ) is recommended instead of a yes / no definition .
recently , hsiao et al . , using data from a middle - aged cohort , published  the chinese metsy risk score .
 they have used binary logistic regression and receiver operation characteristic ( roc ) curve to construct their cmetsys . during their study follow - up 30 of the 352 participants developed metsy .
they indicated tg and dbp have highest and lowest area under curve ( auc ) .
they concluded that tg and wc are the most important variables , and their model could be useful for clinical screening for the metsy .
the aim of this study was to construct a cmetsys in an iranian adult population and to provide an evaluation of the predictive performance of the cmetsys to identify individuals with metsy .
the isfahan healthy heart program ( ihhp ) data were used in this cross - sectional analysis .
ihhp is a comprehensive , community - based healthy lifestyle program with a reference area ; the details are published elsewhere .
briefly , data were collected from three communities located in the central area of iran including : isfahan , najaf - abad , and arak .
five to 10% of households were selected using a random two - stage clustered sampling method . during survey ,
data from 8313 individuals aged 19 years ( one random selected adult within each household ) was collected in isfahan , najafabad , and arak .
the participants were interviewed to complete validated questionnaires containing questions on demography , socioeconomic status , smoking behavior , physical activity , nutritional habits , and other behavior regarding cvd . in clinics ,
participants were asked to fast for 12 h prior to the examinations . high - sensitivity c - reactive protein ( hs - crp ) for 7087 participants , fpg , total cholesterol ( t - chol ) , hdl - c , low - density lipoprotein cholesterol ( ldl - c ) , and tg were assessed .
all blood samples were examined in the central laboratory of the isfahan cardiovascular research center ( a collaborating center of the world health organization ) , with adherence to external national and international quality control . in this study , although binary metsy was defined according to the rncep : atpiii and its criteria for the components of the metsy , but after comparing the auc from models including each components as a categorical or continuous independent variable , we decided to use continuous values of the components of the metsy during model building . for approaching elevated bp and for reducing the number of model parameters , mean arterial pressure ( map ) was used .
it was calculated using the following equation : map = ( [ sbpdbp]/3 ) + dbp .
then , we compared model including only map with which one consists of map and sbp using likelihood ratio test ( lrt ) ( p = 0.041 ) and also auc using delong method ( p = 0.05 ) .
therefore , we used map to consider bp during modeling . using logistic regression with a binary outcome , based on modified national cholesterol education program ( ncep ) : atpiii metsy definition for asian populations , including gender and age and also one of the map , wc , t - chol , hdl - c , tg , hip circumstance ( hc ) , wc to hc ratio ( waist to hip circumferences ) , body mass index ( bmi , fpg , and 2 hpg as independent variables
then auc and its binomial 95% confidence interval ( ci ) were calculated for each model .
considering the value of auc and clinical practicability , more useful predictors were selected and modeled in different approaches . finally , we construct four different models as following list : 
 model 1 : including informative blood glucose measurement ( fbs).model 2 : including powerful nonlaboratory measurements ( wc , bmi , and map).model 3 : including main serum lipids measurements ( tg , hdl - c , and ldl - c).model 4 ( full model ) : including all components of metsy ( fpg , hdl - c , wc , map , and tg ) . 
 
model 2 : including powerful nonlaboratory measurements ( wc , bmi , and map ) . model 3 : including main serum lipids measurements ( tg , hdl - c , and ldl - c ) . model 4 ( full model ) : including all components of metsy ( fpg , hdl - c , wc , map , and tg ) .
to model building and validation , we conducted user stepwise selection ( using lrt ) and leave - one - out cross - validation methods ( using crossval macro for stata statistical software ) ( release : 11.2 ; statacorp , tx , usa ) . for each model ,
the auc and its 95% ci was calculated and compared ( delong method ) with its sub - models which were included less independent variables and also a full model .
we calculated the probability of the metsy for each person using following formula only for model 4 : pr = 1/(1 + e ) where x represent the suggested cmetsys . after constructing the cmetsys , by using multiple linear regression , we assessed linear relationship of the cmetsys with smoking status , percentiles of the crp value ( hs - crp ) ,
global dietary index , total , leisure time , homework , and workplace physical activity scores , and bmi .
we compared determinants of the metsy as a binary outcome with its determinants when it was defined as a continuous risk score . to do this , we fitted a logistic regression with statistically significant determinants of the cmetsys as its independent variables .
all statistical analyses were conducted using stata statistical software ( release : 11.2 ; statacorp , tx , usa ) .
mean and standard deviation of age for men were 38.5 ( 15.9 ) and for women were 39.3 ( 15.3 ) .
total prevalence of the metsy was 21.9% , 29.0% and 14.7% in females and males , respectively .
percentages of abnormality of each component of the metsy were estimated based on ncep : atpiii criteria .
the metabolic description of study participants gender - divided percentages of abnormality of the components of the metsy ( according to ncep : atpiii ) among study participants percentages of subjects with 0 , 1 , 2 , 3 , 4 or 5 abnormal component were calculated by gender .
these percentages were 14.7 , 29.3 , 27.0 , 19.7 , 7.7 , and 1.5 for females and 28.8 , 30.9 , 25.7 , 10.6 , 3.7 , and 0.5 for males , respectively .
the auc of the models including both gender and age and one or more independent variables and its binomial 95% ci are presented in table 3 .
it also illustrates the results of the comparison of each auc with the next one based on delong method .
the statistical significance level of lr test to assessing the goodness of fit of each model comparing with the same , but without underlined variable in the first column presented in the last column in this table .
auc and its 95% binomial ci for each model and statistical significance of their auc and goodness of fit table 4 shows coefficient , odds ratio , and statistical significance level of each variable in the best - fitted logistic models [ which been bold in table 3 ] to predict the probability of presence of the metsy in iranian adults .
the cross - validated ( leave - one - out ) estimates of auc for models 1 to 4 were 0.78 , 0.88 , 0.90 , and 0.95 , respectively .
best - fitted logistic models to predict presence of the metsy in iranian adults , sorted based on the auc from lowest to highest although four separate models were fitted , but as an example we calculated the x ( where probability of presence of the metsy is pr = 1/(1 + e^x ) . ) using the best one ( model 4 ) . for calculations , we used following equation where all except gender are continuous variables with units mentioned in table 1 , gender is a binary variable with one and two codes representing female and male , respectively
. x = 14.43465 + ( 0.13*hdl - c ) + ( 0.01*tg ) + ( 0.03*fps ) + ( 0.11*wc ) + ( 0.09 * map ) + ( 0.02*age ) + ( 2.83 * gender ) .
best cut point of x for classification of the metsy ( yes / no ) was 1.15 with 89% sensitivity and 87.9% specificity and 88.2% correct classification .
the auc and roc curve for each of four models mentioned in table 4 are illustrated in figure 1 .
the receiver operation characteristic curve and area under curve for each of suggested models to construct continuous metabolic syndrome risk score for iranian adults .
model 2 : including powerful nonlaboratory measurements ( waist circumference [ wc ] , body mass index and mean arterial pressure [ map ] ) .
model 3 : including main serum lipids measurements ( triglycerides , high - density lipoprotein cholesterol [ hdl - c ] and low - density lipoprotein cholesterol ) .
model 4 : including all components of the metsy ( fasting plasma glucose , hdl - c , wc , map , and tg ) we also assessed the probable determinants of the cmetsys constructed by model 4 .
table 5 shows the determinants of the cmetsys ( x ) determined by linear regression and their coefficient , and also p - values provided by logistic regression .
in this study , we constructed and validated four cmetsys to identify the metsy in iranian adults .
this is the first study of its kind in a middle - eastern adult population . considering some circumstances in which clinicians or epidemiologists do not have values on some components of metsy ,
first , when we have only age , gender and fpg , the model had lower discriminative power but still plausible auc ( 78.1 [ 95% ci : 77.1 - 79.1 ] ) .
although 2 hpg added to this model , but it had no statistically significant added value on auc or goodness of fit .
the second ones provide cmetsys for conditions in which we have nonlaboratory variables , e.g. , bmi , wc , and map .
the next model was provided for circumstances in which only serum lipid profile and tg were considered .
if we have values of each five components of metsy , the model 4 will be the best one .
our study shows that tg and wc are the number one and two contributors in presence of the metsy .
hdl - c and map are in third and fourth order , and the last one is fpg .
hsiao et al . , found tg and wc as more important components of metsy .
based on our findings , hdl - c has the same rank as in hsiao et al .
but fpg and bp do not have the same importance as in their study . in our study ,
the predictive performance of map had no statistically significant difference with sbp . however , one probable reason for this distinction may be because of considering the bp as map in our study and as sbp and dbp in the study of hsiao et al . despite ranks for importance of bp as well as other components , the auc for bp in our study was 81.3 ( 80.4 - 0.82.2 ) and 59.5 ( 50.8 - 68.3 ) in their study . considering the follow - up nature of data that used in hsiao et al .
( provide ability to predict metsy for healthy people in the future ) and cross - sectional nature of data which we used ( provide ability to identifying peoples with metsy at this time ) , this difference could provide probable evidence on more predictive performance of bp and other components for discriminate the present metsy than for its future incidence . considering our full model
, this study provides approval evidence on independent predictive performance of tg and wc to discriminate the metsy .
, our best model demonstrates independency of influence of other components of the metsy to estimate the risk of presence of the metsy .
one possible reason for this discrepancy may be a large difference between the sample size of two studies as well as the possible effects of regional and ethnical differences . in concordance with our findings , there are some evidences on the presence of gradient relationship between the cmetsys and number of abnormal components of metsy . although univariate study results showed statistically significant differences between those with metsy and healthy participants in terms of all type of physical activity , the cmetsys had significant relationships with leisure time and workplace physical activity , but the corresponding figure was not significant for homework physical activity and total physical activity score . against univariate results ,
logistic regression showed no statistical association between the metsy and all types of physical activities .
these findings demonstrate two key points : first , the importance of leisure time and workplace physical activities and second , according to more analysis ( not shown ) , probable confounding effect of gender on those effects when using yes / no definition for the metsy .
the significant association of the cmetsys with leisure time physical ( ltphya ) was shown earlier in american children .
hence , we could conclude cmetsys in adults or children has a probable relationship with ltphya activity .
linear regression also showed a significant association between the cmetsys and bmi or hs - crp percentiles .
this finding is in concordance with some other studies . although we do not have any confirmation on the association of metsy with hs - crp
if accept present evidence from other studies , comparing results of logistic regression and linear regression could provide some evidence on using the cmetsys instead of yes / no definition .
. showed there is also a relationship between obesity and hs - crp level and other authors revealed the relationship of hs - crp and the metsy .
these findings are in agreement with studies on risk factors of cvds . in this study ,
our limitation was cross - sectional context of the study although most risk score studies are cross - sectional , but the goal of risk score studies is prediction of future disorder and this need cohort designs .
however , considering the concordance of our findings with which in other studies with cohort designs , it can be suggested that this limitation had no or a very weak effect on our study conclusion .
four generalizable continuous risk score models with plausible predictive performance to identify the metsy in iranian adults were generated .
the best cmetsys provided in this study had a significant relation with hs - crp , bmi , leisure time , and workplace physical activity as well as age and gender .
although we provided a practicable cmetsys to predict the metsy in iranian adults but for better predictions follow - up studies are needed .
smh contributed in the design of the study , revising the draft and approval of the final version of the manuscript , and agreed for all aspects of the work .
rk contributed in the design of the study , revising the draft and approval of the final version of the manuscript , and agreed for all aspects of the work .
hmv contributed in the design of the study , data analysis , writhing and revising the draft and approval of the final version of the manuscript , and agreed for all aspects of the work .
mm contributed in the data analysis , revising the draft and approval of the final version of the manuscript , and agreed for all aspects of the work .
ns contributed in the design of the main study , revising the draft and approval of the final version of the manuscript , and agreed for all aspects of the work .
sa contributed in the design of the main study , revising the draft and approval of the final version of the manuscript , and agreed for all aspects of the work .
 background : metabolic syndrome ( metsy ) , an important predisposing factor for the most of noncommunicable diseases , has become a global pandemic . 
 given different definitions used for the metsy , recently using a score termed  continuous metsy risk score ( cmetsys )  is recommended . 
 the aim of this study was to provide a cmetsys in a population - based sample of iranian adults and to assess its determinants.materials and methods : we used the data of the baseline survey of a community trial entitled  the isfahan health heart program .  
 the metsy was defined according to the revised national cholesterol education program third adult treatment panel . 
 all probable predictive models and their predictive performance were provided using leave - one - out cross - validated logistic regression and the receiver operation characteristic curve methods . multiple linear regression was performed to assess factors associated with the cmetsys.results:the study population consisted of 8313 persons ( 49.9% male , mean age 38.54  15.86 years ) . 
 the metsy was documented in 1539 persons ( 21.86% ) . 
 triglycerides and waist circumference were the best predictive components , and fasting plasma glucose had the lowest area under curve ( auc ) . 
 the auc for our best model was 95.36 ( 94.83 - 95.83% ) . 
 the best predictive cutoff for this risk score was 1.151 with 89% sensitivity and 87.93% specificity.conclusion:we provided four population - based leave - one - out cross - validated risk score models , with moderate to perfect predictive performance to identify the metsy in iranian adults . 
 the cmetsys had significant associations with high sensitive c - reactive protein , body mass index , leisure time , and workplace physical activity as well as age and gender . 
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
CONCLUSION
AUTHOR'S CONTRIBUTIONS