adiposity has been associated with a number of cardiovascular disease ( cvd ) risk factors , including hypertension ( htn ) and diabetes mellitus . beyond generalized adiposity , for example , larger visceral adipose tissue ( vat ) volume has a stronger adverse cvd risk profile than subcutaneous adipose tissue ( sat ) . although many studies have investigated risk profiles based on absolute fat quantity , fat quality may also play an important role in conferring cvd risk . molecular and cellular characteristics of adipose tissue , such as adipocyte size , reduced oxygenation , and dysfunctional inflammatory response , are associated with adverse metabolic risk in both animal models and humans . computed tomography ( ct ) attenuation , measured in hounsfield units ( hu ) , is a quantitative measure of radiodensity to differentiate tissue types with the range of 195 to 45 hu that is attributed to adipose tissue . we have recently shown that lower ct attenuation was associated with higher cvd risk in both men and women , independent of fat depot volumes . fat volume is adversely associated with vascular calcification , a marker for atherosclerotic burden and a predictor of future coronary events . however , thus , the aim of this study was to investigate whether lower fat attenuation is associated with the presence of coronary and abdominal aortic calcium ( cac and aac , respectively ) above and beyond other cvd risk factors and fat depot volumes . because we have previously shown that lower fat ct attenuation is associated with moreadverse cvd risk factors , we hypothesized that lower fat ct attenuation would be associated with a higher odds of subclinical atherosclerosis . participants were drawn from the multidetector computed tomography ( mdct ) substudy from the offspring and thirdgeneration cohorts of the framingham heart study , which has been described previously . briefly , between june 2002 and april 2005 , this substudy enrolled a total of 3394 participants , of which 3079 ( 1516 women ) were eligible for the study after exclusion for missing outcome and risk factor / covariate data and current cvd . for the pericardial fat analysis , a subset of 1120 individuals ( 621 women ) , who had complete data on pericardial fat volume and ct attenuation , were drawn from this overall sample . institutional review board approval was obtained from both the boston university medical center ( boston , ma ) and massachusetts general hospital ( boston , ma ) . each participant received supine 8slice mdct scans of the abdomen and chest for vat , sat , and pericardial fat and calcification measurements , as previously described ( lightspeed ultra ; general electric , milwaukee , wi ) . in the abdomen , 25 contiguous 5mm slices were imaged . a dedicated offline workstation ( aquarius ; terarecon , san mateo , ca ) was used for all radiographic measurements . vat and sat volumes and ct attenuation values were measured by manually tracing the abdominal wall separating the vat and sat depots . in the chest , scans averaging 48 contiguous 2.5mm slices of the heart were taken . pericardial fat was defined as any adipose tissue located within the pericardial sac , and fat volume and ct attenuation were measured by manual tracing . chest mdct images were captured with a ct scanning protocol that was prospectively triggered by ecg readings , which allowed images to be taken at 70% of the cardiac cycle . cac lesions were defined as any 3 consecutive pixels located in the coronary arteries with an hu value of greater than 130 units . the presence of cac was defined as an agatston score ( as ) greater than 100 , and the presence of aac was defined by age and genderspecific 90th percentile cutoffs . these threshholds were used in order to be consistent with the existing literature . this protocol has also produced high inter and intrareader correlation in previous work . risk factor data were originally obtained at offspring examination cycle 7 or the first examination of the third generation . body mass index ( bmi ) was defined as the weight in kilograms divided by the height in meters squared . serum metabolic measures , including total and highdensity lipoproteins , triglycerides ( tgs ) , and glucose , were measured from participants ' fasting samples . current smokers were defined as those who smoked , on average , 1 cigarette per day for the past year . physicianadministered questions were used to quantify alcohol use , and drinks / week were dichotomized and stratified by gender using the following criteria : > 14 drinks per week in men or > 7 drinks per week in women . diabetes was defined as fasting plasma glucose of 126 mg / dl or current treatment with either a hypoglycemic agent or insulin . similarly , cac and aac were log transformed after adding 1 unit to cac and aac ( log[cac+1 ] ) and log[aac+1 ] ) , respectively . ageadjusted pearson 's correlation coefficients were computed to assess the association between pericardial fat hu and various continuous cvd risk factors . the pearson 's correlation coefficients were also calculated between logtransformed cac and aac and adiposity measures for each fat depot including hu . multivariableadjusted logistic regression models were constructed to assess the association between vat and sat hu with the presence of cac ( as>100 ) and aac ( as > age and sexspecific cutoffs ) . for each outcome , 5 models were constructed and the corresponding odds ratio ( or ) for a 5unit decrease in vat or sat hu was calculated . we opted to standardize our data to a 5unit decrease in hu because this is nearly 1 sd across all measurements . this is analogous to using a continuous scale in that the p value is identical . by standardizing the data , we are able to present it in a way that is more clinically meaningful . furthermore , the hu data were modeled per decrement to be consistent with our a priori hypothesis that lower hu levels would be associated with increased calcium risk . model 1 adjusted for age and sex , and model 2 adjusted for age , sex , lipid treatment , htn treatment , smoking status , systolic blood pressure ( sbp ) , diabetes , total / highdensity lipoprotein ( hdl ) cholesterol , and ( logtransformed ) tg . models 3 , 4 , and 5 included all covariates of model 2 with the following additional adjustments : model 3 included bmi , model 4 included the corresponding fat volume ( ie , the models for sat hu were adjusted for sat volume ) , and model 5 included the other fat depot density measure ( ie , the models for sat hu were adjusted for vat hu ) . five multivariableadjusted logistic regression models were also constructed to assess the association between a 5unit decrease in pericardial fat hu and the presence of cac and aac . the first 3 models adjusted for the same covariates as models 1 , 2 , and 3 above . the fourth model adjusted for vat volume , and the fifth model adjusted for pericardial fat volume . sas statistical software ( version 9.2 ; sas institute , cary , nc ) was used for all analyses . participants were drawn from the multidetector computed tomography ( mdct ) substudy from the offspring and thirdgeneration cohorts of the framingham heart study , which has been described previously . briefly , between june 2002 and april 2005 , this substudy enrolled a total of 3394 participants , of which 3079 ( 1516 women ) were eligible for the study after exclusion for missing outcome and risk factor / covariate data and current cvd . for the pericardial fat analysis , a subset of 1120 individuals ( 621 women ) , who had complete data on pericardial fat volume and ct attenuation , were drawn from this overall sample . institutional review board approval was obtained from both the boston university medical center ( boston , ma ) and massachusetts general hospital ( boston , ma ) . each participant received supine 8slice mdct scans of the abdomen and chest for vat , sat , and pericardial fat and calcification measurements , as previously described ( lightspeed ultra ; general electric , milwaukee , wi ) . in the abdomen , 25 contiguous 5mm slices were imaged . a dedicated offline workstation ( aquarius ; terarecon , san mateo , ca ) was used for all radiographic measurements . vat and sat volumes and ct attenuation values were measured by manually tracing the abdominal wall separating the vat and sat depots . in the chest , scans averaging 48 contiguous 2.5mm slices of the heart were taken . pericardial fat was defined as any adipose tissue located within the pericardial sac , and fat volume and ct attenuation were measured by manual tracing . chest mdct images were captured with a ct scanning protocol that was prospectively triggered by ecg readings , which allowed images to be taken at 70% of the cardiac cycle . cac lesions were defined as any 3 consecutive pixels located in the coronary arteries with an hu value of greater than 130 units . the presence of cac was defined as an agatston score ( as ) greater than 100 , and the presence of aac was defined by age and genderspecific 90th percentile cutoffs . these threshholds were used in order to be consistent with the existing literature . this protocol has also produced high inter and intrareader correlation in previous work . risk factor data were originally obtained at offspring examination cycle 7 or the first examination of the third generation . body mass index ( bmi ) serum metabolic measures , including total and highdensity lipoproteins , triglycerides ( tgs ) , and glucose , were measured from participants ' fasting samples . current smokers were defined as those who smoked , on average , 1 cigarette per day for the past year . physicianadministered questions were used to quantify alcohol use , and drinks / week were dichotomized and stratified by gender using the following criteria : > 14 drinks per week in men or > 7 drinks per week in women . diabetes was defined as fasting plasma glucose of 126 mg / dl or current treatment with either a hypoglycemic agent or insulin . tgs were log transformed for normalization . similarly , cac and aac were log transformed after adding 1 unit to cac and aac ( log[cac+1 ] ) and log[aac+1 ] ) , respectively . ageadjusted pearson 's correlation coefficients were computed to assess the association between pericardial fat hu and various continuous cvd risk factors . the pearson 's correlation coefficients were also calculated between logtransformed cac and aac and adiposity measures for each fat depot including hu . multivariableadjusted logistic regression models were constructed to assess the association between vat and sat hu with the presence of cac ( as>100 ) and aac ( as > age and sexspecific cutoffs ) . for each outcome , 5 models were constructed and the corresponding odds ratio ( or ) for a 5unit decrease in vat or sat hu was calculated . we opted to standardize our data to a 5unit decrease in hu because this is nearly 1 sd across all measurements . this is analogous to using a continuous scale in that the p value is identical . by standardizing the data , furthermore , the hu data were modeled per decrement to be consistent with our a priori hypothesis that lower hu levels would be associated with increased calcium risk . model 1 adjusted for age and sex , and model 2 adjusted for age , sex , lipid treatment , htn treatment , smoking status , systolic blood pressure ( sbp ) , diabetes , total / highdensity lipoprotein ( hdl ) cholesterol , and ( logtransformed ) tg . models 3 , 4 , and 5 included all covariates of model 2 with the following additional adjustments : model 3 included bmi , model 4 included the corresponding fat volume ( ie , the models for sat hu were adjusted for sat volume ) , and model 5 included the other fat depot density measure ( ie , the models for sat hu were adjusted for vat hu ) . five multivariableadjusted logistic regression models were also constructed to assess the association between a 5unit decrease in pericardial fat hu and the presence of cac and aac . the first 3 models adjusted for the same covariates as models 1 , 2 , and 3 above . the fourth model adjusted for vat volume , and the fifth model adjusted for pericardial fat volume . sas statistical software ( version 9.2 ; sas institute , cary , nc ) was used for all analyses . mean age was 50 years , and approximately half of the participants ( 49.2% ; n=1516 ) were women . approximately 17% of the participants had cac present ( as>100 ) and 23% had aac present ( as > age/sexspecific cutoffs ) . overall mean and sd of sat hu was 101.0 and 5.0 , vat hu was 93.9 and 4.6 , and pericardial fat hu was 94.4 and 3.0 . characteristics of the study sample data presented as mean ( sd ) for continuous characteristics or percentage ( count ) for categorical characteristics . aac indicates abdominal aortic calcium ; as , agatston score ; bmi , body mass index ; cac , coronary artery calcium ; hdl , highdensity lipoprotein ; hu , hounsfield units ; n / a , not available ; sat , subcutaneous adipose tissue ; tgs , triglycerides ; vat , visceral adipose tissue . defined as > 7 drinks / week ( women ) or > 14 drinks / week ( men ) . presented as median ( 25th to 75th quartiles ) . aac as age/sexspecific cutoffs : men : 7 ( < 45 years old ) , 231 ( 45 to 54 ) , 1922 ( 55 to 64 ) , 4914 ( 65 to 74 ) , and 8177 ( 75 ) ; women : 0 ( < 45 years old ) , 73 ( 45 to 54 ) , 946 ( 55 to 64 ) , 2263 ( 65 to 74 ) , and 5742 ( 75 ) . pericardial fat sample counts : 1120 ( overall ) , 621 ( women ) , and 499 ( men ) . pericardial fat hu was directly correlated with most cvd risk factors in the overall cohort ( table 2 ) . for example , pericardial fat hu was directly correlated with both sbp ( r=0.10 ; p<0.001 ) and bmi ( r=0.20 ; p<0.001 ) . we also observed direct correlations overall between pericardial fat hu and sat volume ( r=0.11 ; p<0.001 ) and vat volume ( r=0.10 ; p<0.01 ) . however , there was an inverse correlation between pericardial fat hu and pericardial fat volume ( r=0.15 ; p<0.001 ) . ageadjusted pearson 's correlation coefficients between cardiovascular risk factors and pericardial fat hu cac and aac presented as log ( cac+1 ) and log ( aac+1 ) , respectively . aac indicates abdominal aortic calcium ; bmi , body mass index ; cac , coronary artery calcium ; hdl , highdensity lipoprotein ; hu , hounsfield units ; sat , subcutaneous adipose tissue ; tgs , triglycerides ; vat , visceral adipose tissue . cac was directly correlated with sat hu ( r=0.14 ; p<0.001 ) and pericardial hu ( r=0.07 ; p<0.05 ) , but was not associated with vat hu . aac was inversely correlated with vat hu ( r=0.13 ; p<0.001 ) , but not with sat hu or pericardial fat hu . ageadjusted pearson 's correlation coefficients between adiposity measures and coronary and abdominal aortic calcium presence cac and aac presented as log(cac+1 ) and log(aac+1 ) , respectively . aac indicates abdominal aortic calcium ; bmi , body mass index ; cac , coronary artery calcium ; hu , hounsfield units ; sat , subcutaneous adipose tissue ; vat , visceral adipose tissue . * p<0.05 ; p<0.01 ; p<0.001 ; pericardial fat sample counts : 1120 ( overall ) , 621 ( women ) , and 499 ( men ) contrary to our a priori hypothesis , per 5unit decrement in vat hu , we observed an or of 0.76 for cac ( p=0.0005 ) in the multivariableadjusted model . this association persisted after adjustment for bmi ( or , 0.71 ; p<0.0001 ) , vat volume ( or , 0.60 ; p<0.0001 ) , and sat hu ( or , 0.83 ; p=0.04 ) . for sat hu , we observed an or of 0.79 for cac per 5unit decrement in sat hu ( p=0.0004 ) in the multivariable model . similarly , this association persisted after adjustment for bmi ( or , 0.76 ; p=0.0001 ) , sat volume ( or , 0.71 ; p<0.0001 ) , and vat hu ( or , 0.85 ; p=0.04 ) . multivariableadjusted logistic regression for cac and aac with cardiovascular risk factors by vat hu , sat hu , and pericardial fat hu per 5 unit decrement in vat , sat , or pericardial fat hu estimates for hu are given as odds ratio ( 95% confidence intervals ) . aac indicates abdominal aortic calcium , bmi , body mass index ; cac , coronary artery calcium ; hu , hounsfield units ; sat , subcutaneous adipose tissue ; vat , visceral adipose tissue . p values for sex interaction for cac : vat hu ( p=0.90 ) ; sat hu ( p=0.63 ) ; and pericardial fat hu ( p=0.81 ) . p values for sex interaction for aac : vat hu ( p=0.82 ) ; sat hu ( p=0.83 ) ; and pericardial fat hu ( p=0.17 ) . p values for age interaction for cac : vat hu ( p=0.73 ) ; sat hu ( p=0.17 ) ; and pericardial fat hu ( p=0.94 ) . p values for age interaction for aac : vat hu ( p=0.38 ) ; sat hu ( p=0.47 ) ; and pericardial fat hu ( p=0.47 ) . aac agatston score age/sexspecific cutoffs : men : 7 ( < 45 years old ) , 231 ( 45 to 54 ) , 1922 ( 55 to 64 ) , 4914 ( 65 to 74 ) , and 8177 ( 75 ) ; women : 0 ( < 45 years old ) , 73 ( 45 to 54 ) , 946 ( 55 to 64 ) , 2263 ( 65 to 74 ) , and 5742 ( 75 ) . adjusted for age , gender , lipid treatment , hypertension treatment , smoking status , systolic blood pressure , diabetes , total / highdensity lipoprotein cholesterol ratio , and triglycerides . for vat hu and aac , there was an 18% higher risk of calcification in the agesex adjusted model ( p<0.001 ) . this association was nonsignificant after multivariable adjustment ( or , 0.9 ; p=0.09 ) and slightly stronger after additional adjustment for vat volume ( or , 0.79 for aac ; p=0.004 ) . we observed no significant association between sat hu and aac in the multivariable or serial fatdepot adjusted models . furthermore , we did not find significant associations between pericardial fat hu and either cac or aac in any of the models performed . mean age was 50 years , and approximately half of the participants ( 49.2% ; n=1516 ) were women . approximately 17% of the participants had cac present ( as>100 ) and 23% had aac present ( as > age/sexspecific cutoffs ) . overall mean and sd of sat hu was 101.0 and 5.0 , vat hu was 93.9 and 4.6 , and pericardial fat hu was 94.4 and 3.0 . characteristics of the study sample data presented as mean ( sd ) for continuous characteristics or percentage ( count ) for categorical characteristics . aac indicates abdominal aortic calcium ; as , agatston score ; bmi , body mass index ; cac , coronary artery calcium ; hdl , highdensity lipoprotein ; hu , hounsfield units ; n / a , not available ; sat , subcutaneous adipose tissue ; tgs , triglycerides ; vat , visceral adipose tissue . defined as > 7 drinks / week ( women ) or > 14 drinks / week ( men ) . presented as median ( 25th to 75th quartiles ) . aac as age/sexspecific cutoffs : men : 7 ( < 45 years old ) , 231 ( 45 to 54 ) , 1922 ( 55 to 64 ) , 4914 ( 65 to 74 ) , and 8177 ( 75 ) ; women : 0 ( < 45 years old ) , 73 ( 45 to 54 ) , 946 ( 55 to 64 ) , 2263 ( 65 to 74 ) , and 5742 ( 75 ) . pericardial fat sample counts : 1120 ( overall ) , 621 ( women ) , and 499 ( men ) . pericardial fat hu was directly correlated with most cvd risk factors in the overall cohort ( table 2 ) . for example , pericardial fat hu was directly correlated with both sbp ( r=0.10 ; p<0.001 ) and bmi ( r=0.20 ; p<0.001 ) . we also observed direct correlations overall between pericardial fat hu and sat volume ( r=0.11 ; p<0.001 ) and vat volume ( r=0.10 ; p<0.01 ) . however , there was an inverse correlation between pericardial fat hu and pericardial fat volume ( r=0.15 ; p<0.001 ) . ageadjusted pearson 's correlation coefficients between cardiovascular risk factors and pericardial fat hu cac and aac presented as log ( cac+1 ) and log ( aac+1 ) , respectively . aac indicates abdominal aortic calcium ; bmi , body mass index ; cac , coronary artery calcium ; hdl , highdensity lipoprotein ; hu , hounsfield units ; sat , subcutaneous adipose tissue ; tgs , triglycerides ; vat , visceral adipose tissue . cac was directly correlated with sat hu ( r=0.14 ; p<0.001 ) and pericardial hu ( r=0.07 ; p<0.05 ) , but was not associated with vat hu . aac was inversely correlated with vat hu ( r=0.13 ; p<0.001 ) , but not with sat hu or pericardial fat hu . ageadjusted pearson 's correlation coefficients between adiposity measures and coronary and abdominal aortic calcium presence cac and aac presented as log(cac+1 ) and log(aac+1 ) , respectively . aac indicates abdominal aortic calcium ; bmi , body mass index ; cac , coronary artery calcium ; hu , hounsfield units ; sat , subcutaneous adipose tissue ; vat , visceral adipose tissue . * p<0.05 ; p<0.01 ; p<0.001 ; pericardial fat sample counts : 1120 ( overall ) , 621 ( women ) , and 499 ( men ) . contrary to our a priori hypothesis , per 5unit decrement in vat hu , we observed an or of 0.76 for cac ( p=0.0005 ) in the multivariableadjusted model . this association persisted after adjustment for bmi ( or , 0.71 ; p<0.0001 ) , vat volume ( or , 0.60 ; p<0.0001 ) , and sat hu ( or , 0.83 ; p=0.04 ) . for sat hu , we observed an or of 0.79 for cac per 5unit decrement in sat hu ( p=0.0004 ) in the multivariable model . similarly , this association persisted after adjustment for bmi ( or , 0.76 ; p=0.0001 ) , sat volume ( or , 0.71 ; p<0.0001 ) , and vat hu ( or , 0.85 ; p=0.04 ) . multivariableadjusted logistic regression for cac and aac with cardiovascular risk factors by vat hu , sat hu , and pericardial fat hu per 5 unit decrement in vat , sat , or pericardial fat hu estimates for hu are given as odds ratio ( 95% confidence intervals ) . aac indicates abdominal aortic calcium , bmi , body mass index ; cac , coronary artery calcium ; hu , hounsfield units ; sat , subcutaneous adipose tissue ; vat , visceral adipose tissue . p values for sex interaction for cac : vat hu ( p=0.90 ) ; sat hu ( p=0.63 ) ; and pericardial fat hu ( p=0.81 ) . p values for sex interaction for aac : vat hu ( p=0.82 ) ; sat hu ( p=0.83 ) ; and pericardial fat hu ( p=0.17 ) . p values for age interaction for cac : vat hu ( p=0.73 ) ; sat hu ( p=0.17 ) ; and pericardial fat hu ( p=0.94 ) . p values for age interaction for aac : vat hu ( p=0.38 ) ; sat hu ( p=0.47 ) ; and pericardial fat hu ( p=0.47 ) . aac agatston score age/sexspecific cutoffs : men : 7 ( < 45 years old ) , 231 ( 45 to 54 ) , 1922 ( 55 to 64 ) , 4914 ( 65 to 74 ) , and 8177 ( 75 ) ; women : 0 ( < 45 years old ) , 73 ( 45 to 54 ) , 946 ( 55 to 64 ) , 2263 ( 65 to 74 ) , and 5742 ( 75 ) . adjusted for age , gender , lipid treatment , hypertension treatment , smoking status , systolic blood pressure , diabetes , total / highdensity lipoprotein cholesterol ratio , and triglycerides . for vat hu and aac , there was an 18% higher risk of calcification in the agesex adjusted model ( p<0.001 ) . this association was nonsignificant after multivariable adjustment ( or , 0.9 ; p=0.09 ) and slightly stronger after additional adjustment for vat volume ( or , 0.79 for aac ; p=0.004 ) . we observed no significant association between sat hu and aac in the multivariable or serial fatdepot adjusted models . furthermore , we did not find significant associations between pericardial fat hu and either cac or aac in any of the models performed . , we observed that lower vat and sat hu were associated with a lower or for cac . these associations remained after further adjustment for cvd risk factors as well as vat or sat volumes . finally , we observed no association with pericardial fat hu and the presence of either cac or aac . taken together , these findings suggest that indices of abdominal fat density are associated with subclinical atherosclerosis . we observed very few associations with pericardial fat hu , suggesting that the anatomic location of fat density measurements may be important . we also can not rule out that differences in our chest , as compared to abdominal , radiographic protocol obscured our ability to identify meaningful associations with pericardial fat hu and risk factors . finally , pericardial fat hu data were available in our offspring sample only , which is , on average , older than the thirdgeneration sample . multiple studies have investigated and established associations between obesity , adipose tissue volumes , and vascular calcification . the muscatine study , a longitudinal cohort study of 384 individuals , found that higher bmi during late childhood and early adult life was associated with cac presence in early adult life . using waist and hip girth measures , the cardia study showed that abdominal obesity , including duration of obesity , was associated with subclinical atherosclerosis in young adults . beyond anthropometric measures , the st . francis heart study used ct measures to demonstrate an association between intraabdominal adiposity and the presence of cac in adults aged 50 to 70 . similarly , our group has previously identified an association between fat volumes and subclinical atherosclerosis using multislice ct scans . our current study advances the literature by using a noninvasive technique to measure fat density . this study builds on previous work from our group regarding the association of abdominal fat density and metabolic risk , where we showed that lower ( ie , morenegative hu ) was associated with moreadverse metabolic and cvd risk , including fat quantity . second , adipose tissue that is poorly vascularized is characterized by a morenegative hu value resulting from the radiographic properties of blood . third , fibrotic adipose tissue is characterized by a lessnegative hu value , compared to nonfibrotic adipose tissue , as a result of higher tissue density from excess collagen deposition . considering these characteristics in the context of the findings from our study , our results are most consistent with adipose tissue fibrosis explaining the association between fat attenuation and vascular calcification . adipocyte hypertrophy and hyperplasia induces tissue hypoxia , because the rapid adipose tissue expansion outpaces vascular growth , ultimately progressing to excess collagen deposition and fibrosis . both tissue hypoxia and fibrosis result in adipocyte necrosis , leading to a systemic chronic inflammatory state and the development of atherosclerosis . therefore , morefibrotic adipose tissue , characterized as lessnegative hu values , would be associated with higher odds of vascular calcification , consistent with the results of the present study . additionally , adiposetissue  specific hormones , such as adiponectin and leptin , may also mediate the association between obesity , fibrosis , and subclinical atherosclerosis . low serum levels of adiponectin and/or high serum levels of leptin have fibrogenic and vascular calcification effects and could mediate an association between adipose fibrosis and subclinical atherosclerosis . in published work , higher adipose tissue density was associated with lower leptin and higher adiponectin values . taken together , there are several potential mechanisms that may explain our findings of the association between abdominal fat density and subclinical atherosclerosis . one potential reason for our disparate findings is that the crosssectional nature of our work does not allow us to classify the temporal nature of disease exposure and outcome . cvd risk factors occur before the onset of subclinical atherosclerosis , and it is possible that we are picking up relationships at different points in time . next , the histological correlates of fat density are uncertain and likely represent multiple different cellular mechanisms . ultimately , the disparate findings that we have uncovered , relative to our initial hypothesis , might provide further insights into the relationships between fat quality and subclinical atherosclerosis . further work , using longitudinal samples , will be necessary to better clarify these associations . our current observations indicate the importance of better understanding risks related to abdominal fat density above and beyond fat volume . though ct imaging provides an indirect , noninvasive marker of fat density , the underlying molecular and structural characterization of varying ct attenuation still requires elucidation . additionally , further investigation should focus on providing mechanistic insight for the association between abdominal fat density and subclinical atherosclerosis . for example , investigating the association between abdominal fat density and adiposetissue  derived inflammatory factors would help to clarify this mechanism . furthermore , associations between abdominal fat density and cardiac procedures , such as coronary artery bypass or stent implantation , could begin to elucidate the effect fat density has on clinical outcomes . however , though fat density estimation by ct imaging could provide cvd risk prediction , such is beyond the scope of this current mechanistic investigation . strengths of this current study include the large sample size , communitybased design without enrichment for adiposity , and the use of ct imaging and reproducible protocols for fat measurements . limitations include the crosssectional nature of the study , thereby precluding inferences of causality or temporality . furthermore , the framingham heart study offspring and thirdgeneration cohorts were predominantly white , impeding generalization of our findings to other ethnic groups . this work was made possible through the use of resources and data from the framingham heart study of the national heart , lung and blood institute ( nhlbi ) of the national institutes of health and boston university school of medicine .
backgroundectopic fat density is associated with cardiovascular disease ( cvd ) risk factors above and beyond fat volume . 
 volumetric measures of ectopic fat have been associated with cvd risk factors and subclinical atherosclerosis . 
 the aim of this study was to investigate the association between fat density and subclinical atherosclerosis.methods and resultsparticipants were drawn from the multidetector computed tomography ( mdct ) substudy of the framingham heart study ( n=3079 ; mean age , 50.1 years ; 49.2% women ) . 
 fat density was indirectly estimated by computed tomography attenuation ( hounsfield units [ hu ] ) on abdominal scan slices . 
 visceral fat ( vat ) , subcutaneous fat ( sat ) , and pericardial fat hu and volumes were quantified using standard protocols ; coronary and abdominal aortic calcium ( cac and aac , respectively ) were measured radiographically . 
 multivariableadjusted logistic regression models were used to evaluate the association between adipose tissue hu and the presence of cac and aac . 
 overall , 17.1% of the participants had elevated cac ( agatston score [ as]>100 ) , and 23.3% had elevated aac ( as > age/sexspecific cutoffs ) . per 5unit decrement in vat hu , the odds ratio ( or ) for elevated cac was 0.76 ( 95% confidence interval [ ci ] , 0.65 to 0.89 ; p=0.0005 ) , even after adjustment for body mass index or vat volume . 
 results were similar for sat hu . with decreasing vat hu , we also observed an or of 0.79 ( 95% ci , 0.67 to 0.92 ; p=0.004 ) for elevated aac after multivariable adjustment . 
 we found no significant associations between sat hu and aac . 
 there was no significant association between pericardial fat hu and either cac or aac.conclusionslower vat and sat hu , indirect estimates of fat quality , are associated with a lower risk of subclinical atherosclerosis .