this is a retrospective cross - sectional study . there were 4,377 participants , all of whom underwent cardiac ct in a health promotion center at gangnam severance hospital ( seoul , korea ) between january 2008 and february 2013 . from 4,377 participants , we excluded men ( n  =  2,584 ) and premenopausal women ( n  =  748 ) . postmenopausal women 50 years or older with no menstrual periods for more than 12 consecutive months and women with elevated follicle - stimulating hormone levels ( > 30 iu / l ) were included in this study ( n  =  1,045 ) . women with diabetes mellitus ( n  =  59 ) , excessive alcohol consumption ( n  =  7 ) , viral hepatitis ( positive results for hepatitis b surface antigen or anti  hepatitis c virus ; n  =  19 ) , liver cirrhosis or malignancy on ultrasonography ( n  =  6 ) , and self - reported or medically verified history of cvd ( n  =  35 ) were excluded from this study . height and weight were measured , and body mass index ( bmi ) was calculated by dividing weight ( kg ) by the square of height ( m ) . lifestyle , personal medical history of acute and chronic diseases , and medication history were assessed using a standard questionnaire . systolic blood pressure ( sbp ) and diastolic blood pressure ( dbp ) were measured after a 5-minute rest . fasting plasma glucose ( fpg ) , aspartate aminotransferase , alanine aminotransferase , total cholesterol ( tc ) , high - density lipoprotein cholesterol ( hdl - c ) , triglycerides ( tg ) , and c - reactive protein ( crp ) levels were determined by enzymatic methods using a hitachi 7600 - 120 automated chemistry analyzer ( hitachi , tokyo , japan ) . low - density lipoprotein cholesterol ( ldl - c ) was calculated according to the friedewald equation . hepatitis b surface antigen levels and antibodies to hepatitis c virus were measured with a roche e-170 device ( roche diagnostics , mannheim , germany ) . fasting serum insulin was determined by chemiluminescence ( radioimmunoassay kit ; daiichi , kyoto , japan ) , and insulin resistance was estimated using the homeostasis model assessment of insulin resistance ( homa - ir ) index calculated from the following formula : homa - ir  =  fasting insulin ( u / ml )    fpg ( mmol / l ) / 22.5 . diagnosis of fatty liver disease was based on an abdominal ultrasonography scan obtained with a 3.5-mhz transducer ( hdi 5000 ; philips , bothell , wa ) . abdominal ultrasonographic examination was performed by one of three experienced radiologists , all of whom were blinded to the laboratory and clinical details of participants at the time of the procedure . in the present study , liver with any degree of fat accumulation the number of participants with severe fatty liver disease was too small ( n  =  29 ) ; thus , the presence and severity of nafld were classified into three groups according to hyperechogenicity of liver tissue , degree of discrepancy between the liver and the right kidney , and visibility of vascular structures . the three groups were as follows : group i , no fatty liver disease ; group ii , mild fatty liver disease ; group iii , moderate to severe fatty liver disease . cac was determined with a multidetector ct scanner ( philips brilliance 64 ; philips medical system , best , the netherlands ) . we used a standard prospective electrocardiogram gating protocol with a step - and - shoot technique . the scanning protocol included a slice section collimation of 64    0.625  mm , rotation time of 420 milliseconds , tube voltage of 120  kv , and tube current of 210  mas . quantitative cac score ( cacs ) was calculated with dedicated software and expressed as agatston score . continuous variables with normal distribution were expressed as mean ( sd ) , whereas continuous variables with skewed distribution were presented as median ( interquartile range ) and log - transformed for analysis . logistic regression analysis was used to analyze the association between nafld and presence of cac while controlling for potential confounders . covariates in the multivariable model , such as age , bmi , sbp , dbp , fpg , tc , ldl - c , tg , hdl - c , crp , and homa - ir , were chosen for clinical importance and statistical significance . spss statistical package version 20.0 ( spss inc , chicago , il ) was used for all statistical analyses . this is a retrospective cross - sectional study . there were 4,377 participants , all of whom underwent cardiac ct in a health promotion center at gangnam severance hospital ( seoul , korea ) between january 2008 and february 2013 . from 4,377 participants , we excluded men ( n  =  2,584 ) and premenopausal women ( n  =  748 ) . postmenopausal women 50 years or older with no menstrual periods for more than 12 consecutive months and women with elevated follicle - stimulating hormone levels ( > 30 iu / l ) were included in this study ( n  =  1,045 ) . women with diabetes mellitus ( n  =  59 ) , excessive alcohol consumption ( n  =  7 ) , viral hepatitis ( positive results for hepatitis b surface antigen or anti  hepatitis c virus ; n  =  19 ) , liver cirrhosis or malignancy on ultrasonography ( n  =  6 ) , and self - reported or medically verified history of cvd ( n  =  35 ) were excluded from this study . height and weight were measured , and body mass index ( bmi ) was calculated by dividing weight ( kg ) by the square of height ( m ) . lifestyle , personal medical history of acute and chronic diseases , and medication history were assessed using a standard questionnaire . systolic blood pressure ( sbp ) and diastolic blood pressure ( dbp ) were measured after a 5-minute rest . fasting plasma glucose ( fpg ) , aspartate aminotransferase , alanine aminotransferase , total cholesterol ( tc ) , high - density lipoprotein cholesterol ( hdl - c ) , triglycerides ( tg ) , and c - reactive protein ( crp ) levels were determined by enzymatic methods using a hitachi 7600 - 120 automated chemistry analyzer ( hitachi , tokyo , japan ) . low - density lipoprotein cholesterol ( ldl - c ) hepatitis b surface antigen levels and antibodies to hepatitis c virus were measured with a roche e-170 device ( roche diagnostics , mannheim , germany ) . fasting serum insulin was determined by chemiluminescence ( radioimmunoassay kit ; daiichi , kyoto , japan ) , and insulin resistance was estimated using the homeostasis model assessment of insulin resistance ( homa - ir ) index calculated from the following formula : homa - ir  =  fasting insulin ( u / ml )    fpg ( mmol / l ) / 22.5 . diagnosis of fatty liver disease was based on an abdominal ultrasonography scan obtained with a 3.5-mhz transducer ( hdi 5000 ; philips , bothell , wa ) . abdominal ultrasonographic examination was performed by one of three experienced radiologists , all of whom were blinded to the laboratory and clinical details of participants at the time of the procedure . in the present study , liver with any degree of fat accumulation was considered nafld . the number of participants with severe fatty liver disease was too small ( n  =  29 ) ; thus , the presence and severity of nafld were classified into three groups according to hyperechogenicity of liver tissue , degree of discrepancy between the liver and the right kidney , and visibility of vascular structures . the three groups were as follows : group i , no fatty liver disease ; group ii , mild fatty liver disease ; group iii , moderate to severe fatty liver disease . cac was determined with a multidetector ct scanner ( philips brilliance 64 ; philips medical system , best , the netherlands ) . we used a standard prospective electrocardiogram gating protocol with a step - and - shoot technique . the scanning protocol included a slice section collimation of 64    0.625  mm , rotation time of 420 milliseconds , tube voltage of 120  kv , and tube current of 210  mas . quantitative cac score ( cacs ) was calculated with dedicated software and expressed as agatston score . continuous variables with normal distribution were expressed as mean ( sd ) , whereas continuous variables with skewed distribution were presented as median ( interquartile range ) and log - transformed for analysis . logistic regression analysis was used to analyze the association between nafld and presence of cac while controlling for potential confounders . covariates in the multivariable model , such as age , bmi , sbp , dbp , fpg , tc , ldl - c , tg , hdl - c , crp , and homa - ir , were chosen for clinical importance and statistical significance . spss statistical package version 20.0 ( spss inc , chicago , il ) was used for all statistical analyses . a total of 919 postmenopausal women were included in this study . of these , 738 women had no cac ( cacs  =  0 ) , whereas the remaining 181 women exhibited some evidence of cac ( cacs > 0 ; 19.7% ) . among women in this study , 294 women ( 31.9% ) women were stratified into three groups by the presence and severity of fatty liver disease . age , bmi , sbp , dbp , fpg , tg , aspartate aminotransferase , alanine aminotransferase , crp , and homa - ir increased according to the severity of fatty liver disease , whereas hdl - c decreased . the prevalence of cac and the mean cac score significantly increased with the severity of fatty liver disease ( table 2 ) . the association between fatty liver disease and presence of cac ( cacs > 0 ) was further explored by categorizing the severity of nafld into three groups and by using the first group as reference ( table 3 ) . these relationships remained significant even after adjusting for well - established cardiovascular risk factors , including age , bmi , sbp , dbp , fpg , tc , ldl - c , tg , hdl - c , and crp ( model 2 ) . however , this association was attenuated after additional adjustment for insulin resistance ( model 3 ) . in this study , we investigated the relationship between nafld and prevalence of cac in postmenopausal women . we found that the prevalence of cac was significantly associated with nafld after adjustment for conventional cardiovascular risk factors , but this association was attenuated after adjustment for insulin resistance . to the best of our knowledge , this is the first study to investigate the correlation between nafld and presence of early coronary artery atherosclerosis in postmenopausal women . in this study , this prevalence was higher than that in premenopausal women ( 19.7% ) , which was determined by analyzing the subgroup of premenopausal women among 4,377 participants . hamaguchi et al reported that the prevalence of nafld in japanese postmenopausal women was higher than that in premenopausal women and concluded that postmenopause was a risk factor for nafld . although it remains unclear how estrogen deficiency increases the prevalence of nafld after menopause , several reports have suggested that estrogen deficiency affects body fat distribution , which increases accumulation of gluteofemoral fat and central fat . hepatic estrogen receptors mediate estrogen action in the liver , and estradiol has been shown to play a favorable role in chronic liver disease . thus , estrogen seems to exert a protective effect against nafld in women . in this study , we showed that most metabolic risk factors increased or decreased with the severity of nafld . cac has been shown to be an independent predictor of future cardiovascular events . moreover , several recent studies have reported the association between nafld and cac , but results have been inconsistent . as part of the diabetes heart study , mckimmie et al reported that coronary arterial calcium did not correlate with hepatic steatosis in women with type 2 diabetes . another study of 398 white and black participants by ding et al did not find associations of liver fat attenuation with calcified coronary plaque . recently , vanwagner et al showed that obesity attenuates the relationship between nafld and cac . in contrast , some studies have suggested that nafld might be an independent risk factor for cac , after accounting for conventional risk factors . only a few studies have investigated the association between nafld and carotid intima - media thickness , which is another marker for subclinical atherosclerosis , after adjusting for insulin resistance and other traditional risk factors . however , whether nafld is an independent risk factor for increased intima - media thickness remains controversial . in the present study , similar to a previous study of healthy women , we found that the presence of cac increased with the severity of nafld in postmenopausal women . however , this association was attenuated after adjusting for insulin resistance , and insulin resistance was independently associated with cac in these adjusted models . this suggests that insulin resistance may act as a mediator of the relationship between nafld and cac . although the pathogenesis of nafld and cac has not been fully elucidated , there are several explanations for the relationship between nafld and cac . one of the accepted hypotheses implicates insulin resistance as a major factor leading to nafld and cac . menopause affects body fat distribution , and the resultant increases in body weight and body fat lead to insulin resistance , which might play an important role in the pathogenesis of clinical nafld and cac . recently , rodrigues et al reported that insulin resistance , metabolic syndrome , and abdominal obesity were risk markers for the development of nafld in postmenopausal women . therefore , although the mechanism underlying the relationship between nafld and cac in postmenopausal women is not completely understood , insulin resistance might provide a link between them . first , this is a cross - sectional study that can not definitively establish causality . second , this study lacked direct measures of body fat , which affects insulin resistance . fatty liver disease was assessed by liver ultrasonography  a technique that can not detect fatty infiltration below 30% . however , ultrasonography is nonetheless a very useful noninvasive technique that is often used as the first - line imaging technique in clinical practice and epidemiological studies . finally , because participants in the current study were enrolled in the same health promotion center , generalizability may be limited . increased severity of nafld is significantly associated with cac , a marker of subclinical atherosclerosis . however , this association is attenuated after additional adjustment for insulin resistance ; thus , nafld is not an independent factor for coronary atherosclerosis in postmenopausal women . further prospective large - scale studies are required to explore these findings and to elucidate the mechanism for this association .
abstractobjective : cardiovascular disease is a leading cause of death in postmenopausal women , and nonalcoholic fatty liver disease ( nafld ) has been known to be associated with cardiovascular disease . 
 however , little information regarding the relationship between nafld and coronary artery calcification ( cac ) in postmenopausal women is available . 
 the aim of this study was to investigate the association between nafld and cac in postmenopausal women.methods:among 4,377 participants who underwent cardiac computed tomography in a health promotion center , 919 postmenopausal women were enrolled . 
 anthropometric profiles and multiple cardiovascular risk factors were measured . 
 nafld was measured by ultrasonography , and cac was evaluated by cardiac computed tomography . 
 odds ratios and 95% ci for the presence of cac , by severity of fatty liver disease , were estimated using logistic regression.results:women were stratified into three groups by severity of nafld . 
 there were significant differences in cardiovascular parameters among the groups , and prevalence of cac significantly increased with severity of nafld . on logistic regression analysis 
 after adjustment for multiple risk factors , the odds ratios for the prevalence of cac were as follows ( p  <  0.05 ) : no nafld , 1.0 ; mild nafld , 1.34 ( 95% ci , 0.92 - 2.16 ) ; moderate to severe nafld , 1.83 ( 95% ci , 1.06 - 3.16 ) . 
 however , this association was attenuated after adjustment for insulin resistance ( p  =  0.16).conclusions : there is a significant correlation between nafld and prevalence of cac , but nafld is not an independent factor for coronary atherosclerosis in postmenopausal women .