heart failure ( hf ) represents an increasing clinical and public health burden in the united states as its prevalence and incidence continue to rise , especially among elderly americans . hf has emerged as the single leading diagnosis for hospitalization in the elderly and hospitalization rates are higher among blacks than among whites , with 83% of hf patients hospitalized at least once and 43% hospitalized at least 4 times over a mean duration of 4.7 years . the burden of hf is likely to increase because of the increasing age of the american population , earlier age of onset of hf and improved treatment and survival from cardiovascular ( cv ) diseases , including myocardial infarction ( mi ) and hypertension . carotid imt is a well established marker of subclinical atherosclerosis , which indicates early manifestation of atherosclerosis in the carotid arteries , and is associated with future cv events , asymptomatic myocardial ischemia , and changes in risk factors induced by therapeutic interventions . there is evidence of a direct relationship between increased carotid imt and reduced left ventricular ( lv ) systolic and diastolic function assessed by myocardial strain in asymptomatic individuals without previous clinical cv disease . elderly patients with hf differ from younger patients with hf in terms of several biologic characteristics , including the relatively large proportion of elderly patients with hf who have preserved systolic function . using data from the cardiovascular health study , which included subjects 65 years or older , atherosclerosis as measured by carotid imt was shown to predict overt systolic and diastolic hf . the association of carotid imt with incident hf in middleaged adults , who are at a lower risk of hf than older adults , is not well known . previous crosssectional analysis using data from the aric cohort showed that participants with hf had a higher mean carotid imt than participants without hf . subclinical vascular disease as determined by an increase in carotid imt may be a determinant of risk for future hf , but this has not been studied . in the present study , we examine the hypothesis that subclinical atherosclerosis , assessed by mean carotid imt , is associated with incident hf beyond what is explained by major cvd risk factors in middleaged whites and blacks . we tested this hypothesis using data from the atherosclerosis risk in communities ( aric ) study cohort . the aric study is communitybased prospective study which enrolled 15 792 participants aged 45 to 64 years at the time of their baseline assessment ( 19871989 ) from 4 communities : forsyth county , north carolina ; suburban minneapolis , minnesota ; washington county , maryland ; and jackson , mississippi . in the cohort , response rates at baseline were 46% in jackson and 65% to 67% for the other communities . successful contact with living cohort members through an annual phone interview was above 93% . during the followup period , annual phone interviews were conducted with participants to inquire about events ( including hf ) , and hospital records were surveyed for identification and classification of hf events . the institutional review boards from each site approved the aric study . our analysis involved the use of data from the baseline examination . excluded from the sample were : ( 1 ) participants who were missing all far wall values of carotid imt at baseline ( n=607 ) ; ( 2 ) racial groups other than black or white because of their limited numbers ( n=48 ) ; ( 3 ) participants with missing criteria needed to define baseline glucose status ( n=148 ) ; ( 4 ) participants with missing data needed to define hf at baseline ( n=287 ) ; ( 5 ) prevalent cases of hf at baseline , either by selfreported current intake of hf medication , or those with stage 3 or manifest hf by gothenburg criteria ( n=752 ) . the gothenburg criterion ( table 1 ) is composed of 3 scores , ( 1 ) cardiac , ( 2 ) pulmonary , and ( 3 ) therapy . to have stage 3 or manifest hf all current medications ( taken within the last 2 weeks ) were brought into the clinic and documented . atrial fibrillation was diagnosed by visual inspection of a 2minute rhythm strip from leads v1 , ii , and v5 using standardized methodology . aric study participants provided information on demographic and behavioral variables and medical history to a trained interviewer at each visit . race , gender , educational level , current alcohol use , and smoking status were determined by selfreport at baseline . atherosclerosis of the common carotid arteries was measured by noninvasive , highresolution bmode ultrasound . in this study , technicians scanned 3 specified segments of the extra cranial carotid arteries bilaterally : the common carotid , the bifurcation , and the internal carotid . the common carotid intima and media was assessed in a 1cm segment proximal to the dilatation of the carotid bulb . the intima and media of the bifurcation and internal carotid were assessed over the 1cm segments proximal and distal to the flow divider , respectively . the mean intimalmedial thickness of the far wall of the 6 segments was used as a general indicator of atherosclerosis in the carotid artery . the ultrasound examinations were performed according to a standardized protocol by trained , certified sonographers subject to semiannual evaluation . ultrasound images were recorded on a videotape and forwarded to a central reading center for interpretation . for each of the 6 images , the imt was measured over a 1cm segment at 1mm increments ( total of 11 measurements ) . a mean wall thickness for each segment this protocol produces a single index of atherosclerosis with improved precision provided by the averaging of multiple imt measurements . in a randomly selected subset of 855 participants , the betweenreader reliability coefficients ranged from 0.78 to 0.93 and coefficients of variation ranged from 13.1% to 18.3% ( 80% of duplicate scans differed by < 0.267 mm ) . incident hf was defined as the first occurrence of either ( 1 ) an hf hospitalization that included an international classification of diseases ( icd ) , ninth revision , discharge code of 428.x ( 428.0 to 428.9 ) in any position , or ( 2 ) a death certificate with a 428 ( hf ) or icd , 10th revision , code i50 ( hf ) in any position . all hospitalizations occurring in cohort participants were identified either through generated computer programs , or review of hospital discharge indexes or information elicited during the annual followup interview . hospitalizations eligible based on set criteria ( discharge codes , discharge dates , race sex , and age ) but were found upon review to have been hospitalized for less than 24 hours were not abstracted . abstractors made copies of sections of the medical record ( discharge summary , history and physical report , admission note , and imaging reports ) for use by the aric heart failure mortality and morbidity classification committee ( hf mmcc ) . the interabstractor agreement rate for determining whether or not to conduct detailed abstraction in a quality control sample was 99% . the aric community surveillance database was also searched for possible hf events occurring among cohort participants that were not reported at the annual followup visit or may be otherwise missed . beginning in 2005 , the aric study conducted continuous , retrospective surveillance of hospital discharges for hf for all residents aged 55 and older in the 4 aric communities via annual hospital discharge indices . each hospitalization eligible for full abstraction was independently reviewed by centrally trained and certified physicians on the aric hf mmcc and classified into 1 of 5 categories : definite acute decompensated hf , possible acute decompensated hf , chronic stable hf , hf unlikely , or unclassifiable . hf cases occurring prior to 2005 were not adjudicated . the % agreement between any hf event adjudicated by the hf mmcc and icd9 code 428 was 75% , similar to that with the framingham followup time for those with incident hf events was defined by the time from their baseline exam ( visit 1 ) until the incident event . the end of followup time for those without hf was ( 1 ) december 31 , 2009 , ( 2 ) date of last contact for those lost to followup , or ( 3 ) date of death , whichever occurred first . prevalent chd at baseline was defined as a selfreported history of mi , mi from adjudicated baseline ecg data , a history of physiciandiagnosed mi , a prior coronary reperfusion procedure . incident chd was defined as any case of hospitalized mi , fatal chd , or ecgdiagnosed mi by the end of the study period . three systolic and diastolic blood pressures were taken with participants in the sitting position after 5 minutes of rest using a randomzero sphygmomanometer . certified technicians measured height , weight , and waist circumference . body mass index was calculated as weight ( in kg ) divided by the square of the height ( in meters ) . fasting serum glucose was measured by the optimized direct analysis in real time ( dart ) glucose reagent method . mmol / l ( 126 mg / dl ) , selfreported previous physician diagnosis , or use of diabetes medication ( oral hypoglycemic agents and/or insulin ) , or a nonfasting glucose of 11 mmol / l ( 200 mg / dl ) . mmol / l ( 100 to 125 mg / dl ) in accordance with the 2004 american diabetes association definition . normal fasting glucose was defined as any other participant who does not meet the criteria for dm and ifg . unadjusted differences in baseline characteristics between participants with and without hf were assessed using the student 's t test ( for continuous variables ) and chisquare test ( for categorical variables ) . the association of carotid imt with incident heart failure was assessed using cox proportional hazard models with sequential adjustment for covariates . hazard ratios and 95% confidence intervals for cox regression analysis are presented per unit standard deviation increase and by quartiles of imt . in multivariable analysis , the base model ( unadjusted model ) was sequentially adjusted for covariates of interest . a second model was adjusted for age , gender , race , and level of education ( demographic model ) . a third model was further adjusted for systolic and diastolic blood pressures , bmi , waist circumference , hdl cholesterol , ldl cholesterol , triglycerides , smoking status and amount in packyears , alcohol consumption , serum creatinine , and medications for hypertension and dyslipidemia ( clinical and biologic model ) . finally , a fourth model was adjusted for prevalent and incident chd ( chd model ) . for the fourth model , covariates were chosen based on their associations in the present cohort and in prior published studies . effect modification between race , gender , and carotid imt was examined using 2way interaction . this was achieved by including the product the imtrace and imtgender terms in the model . in the presence of a significant interaction ( p for interaction < 0.05 ) separate cox regression models included carotid imt as a continuous variable ( zscores ) and as a categorical variable ( quartiles ) . the proportional hazard assumption was assessed by visually examining the log ( log survival ) plots and timecovariate interaction terms . kaplanmeier plots were used to illustrate the overall survival probability and cumulative incidence of hf by subgroups , and group comparison was done using the logrank test . all analyses were performed using sas 9.2 ( sas institute inc , cary , nc ) . the aric study is communitybased prospective study which enrolled 15 792 participants aged 45 to 64 years at the time of their baseline assessment ( 19871989 ) from 4 communities : forsyth county , north carolina ; suburban minneapolis , minnesota ; washington county , maryland ; and jackson , mississippi . in the cohort , response rates at baseline were 46% in jackson and 65% to 67% for the other communities . successful contact with living cohort members through an annual phone interview was above 93% . during the followup period , annual phone interviews were conducted with participants to inquire about events ( including hf ) , and hospital records were surveyed for identification and classification of hf events . the institutional review boards from each site approved the aric study . our analysis involved the use of data from the baseline examination . excluded from the sample were : ( 1 ) participants who were missing all far wall values of carotid imt at baseline ( n=607 ) ; ( 2 ) racial groups other than black or white because of their limited numbers ( n=48 ) ; ( 3 ) participants with missing criteria needed to define baseline glucose status ( n=148 ) ; ( 4 ) participants with missing data needed to define hf at baseline ( n=287 ) ; ( 5 ) prevalent cases of hf at baseline , either by selfreported current intake of hf medication , or those with stage 3 or manifest hf by gothenburg criteria ( n=752 ) . the gothenburg criterion ( table 1 ) is composed of 3 scores , ( 1 ) cardiac , ( 2 ) pulmonary , and ( 3 ) therapy . to have stage 3 or manifest hf all current medications ( taken within the last 2 weeks ) were brought into the clinic and documented . atrial fibrillation was diagnosed by visual inspection of a 2minute rhythm strip from leads v1 , ii , and v5 using standardized methodology . aric study participants provided information on demographic and behavioral variables and medical history to a trained interviewer at each visit . race , gender , educational level , current alcohol use , and smoking status were determined by selfreport at baseline . atherosclerosis of the common carotid arteries was measured by noninvasive , highresolution bmode ultrasound . in this study , technicians scanned 3 specified segments of the extra cranial carotid arteries bilaterally : the common carotid , the bifurcation , and the internal carotid . the common carotid intima and media was assessed in a 1cm segment proximal to the dilatation of the carotid bulb . the intima and media of the bifurcation and internal carotid were assessed over the 1cm segments proximal and distal to the flow divider , respectively . the mean intimalmedial thickness of the far wall of the 6 segments was used as a general indicator of atherosclerosis in the carotid artery . the ultrasound examinations were performed according to a standardized protocol by trained , certified sonographers subject to semiannual evaluation . ultrasound images were recorded on a videotape and forwarded to a central reading center for interpretation . for each of the 6 images , the imt was measured over a 1cm segment at 1mm increments ( total of 11 measurements ) . a mean wall thickness for each segment this protocol produces a single index of atherosclerosis with improved precision provided by the averaging of multiple imt measurements . in a randomly selected subset of 855 participants , the betweenreader reliability coefficients ranged from 0.78 to 0.93 and coefficients of variation ranged from 13.1% to 18.3% ( 80% of duplicate scans differed by < 0.267 mm ) . incident hf was defined as the first occurrence of either ( 1 ) an hf hospitalization that included an international classification of diseases ( icd ) , ninth revision , discharge code of 428.x ( 428.0 to 428.9 ) in any position , or ( 2 ) a death certificate with a 428 ( hf ) or icd , 10th revision , code i50 ( hf ) in any position . all hospitalizations occurring in cohort participants were identified either through generated computer programs , or review of hospital discharge indexes or information elicited during the annual followup interview . hospitalizations eligible based on set criteria ( discharge codes , discharge dates , race sex , and age ) but were found upon review to have been hospitalized for less than 24 hours were not abstracted . abstractors made copies of sections of the medical record ( discharge summary , history and physical report , admission note , and imaging reports ) for use by the aric heart failure mortality and morbidity classification committee ( hf mmcc ) . the interabstractor agreement rate for determining whether or not to conduct detailed abstraction in a quality control sample was 99% . the aric community surveillance database was also searched for possible hf events occurring among cohort participants that were not reported at the annual followup visit or may be otherwise missed . beginning in 2005 , the aric study conducted continuous , retrospective surveillance of hospital discharges for hf for all residents aged 55 and older in the 4 aric communities via annual hospital discharge indices . each hospitalization eligible for full abstraction was independently reviewed by centrally trained and certified physicians on the aric hf mmcc and classified into 1 of 5 categories : definite acute decompensated hf , possible acute decompensated hf , chronic stable hf , hf unlikely , or unclassifiable . hf cases occurring prior to 2005 were not adjudicated . the % agreement between any hf event adjudicated by the hf mmcc and icd9 code 428 was 75% , similar to that with the framingham followup time for those with incident hf events was defined by the time from their baseline exam ( visit 1 ) until the incident event . the end of followup time for those without hf was ( 1 ) december 31 , 2009 , ( 2 ) date of last contact for those lost to followup , or ( 3 ) date of death , whichever occurred first . prevalent chd at baseline was defined as a selfreported history of mi , mi from adjudicated baseline ecg data , a history of physiciandiagnosed mi , a prior coronary reperfusion procedure . incident chd was defined as any case of hospitalized mi , fatal chd , or ecgdiagnosed mi by the end of the study period . three systolic and diastolic blood pressures were taken with participants in the sitting position after 5 minutes of rest using a randomzero sphygmomanometer . certified technicians measured height , weight , and waist circumference . body mass index was calculated as weight ( in kg ) divided by the square of the height ( in meters ) . fasting serum glucose was measured by the optimized direct analysis in real time ( dart ) glucose reagent method . mmol / l ( 126 mg / dl ) , selfreported previous physician diagnosis , or use of diabetes medication ( oral hypoglycemic agents and/or insulin ) , or a nonfasting glucose of 11 mmol / l ( 200 mg / dl ) . mmol / l ( 100 to 125 mg / dl ) in accordance with the 2004 american diabetes association definition . normal fasting glucose was defined as any other participant who does not meet the criteria for dm and ifg . unadjusted differences in baseline characteristics between participants with and without hf were assessed using the student 's t test ( for continuous variables ) and chisquare test ( for categorical variables ) . the association of carotid imt with incident heart failure was assessed using cox proportional hazard models with sequential adjustment for covariates . hazard ratios and 95% confidence intervals for cox regression analysis are presented per unit standard deviation increase and by quartiles of imt . in multivariable analysis , the base model ( unadjusted model ) was sequentially adjusted for covariates of interest . a second model was adjusted for age , gender , race , and level of education ( demographic model ) . a third model was further adjusted for systolic and diastolic blood pressures , bmi , waist circumference , hdl cholesterol , ldl cholesterol , triglycerides , smoking status and amount in packyears , alcohol consumption , serum creatinine , and medications for hypertension and dyslipidemia ( clinical and biologic model ) . finally , a fourth model was adjusted for prevalent and incident chd ( chd model ) . for the fourth model , covariates were chosen based on their associations in the present cohort and in prior published studies . effect modification between race , gender , and carotid imt was examined using 2way interaction . this was achieved by including the product the imtrace and imtgender terms in the model . in the presence of a significant interaction ( p for interaction < 0.05 ) separate cox regression models included carotid imt as a continuous variable ( zscores ) and as a categorical variable ( quartiles ) . the proportional hazard assumption was assessed by visually examining the log ( log survival ) plots and timecovariate interaction terms . kaplanmeier plots were used to illustrate the overall survival probability and cumulative incidence of hf by subgroups , and group comparison was done using the logrank test . all analyses were performed using sas 9.2 ( sas institute inc , cary , nc ) . among the 13 590 participants in this study , there were 2008 ( 14.8% of total cohort ) incident cases of hf over a median followup period of 20.6 years . table 2 compares the baseline demographic and clinical characteristics of participants with and without incident hf . compared with participants without hf , participants with hf were older ( 56.6 versus 53.7 years ) , more likely to be male ( 52.5% versus 44.1% ) , and more likely to be hypertensive ( 50.3% versus 28.6% ) . participants who developed hf over the course of followup were also more likely , at baseline , to have an abnormal lipid profile , were current smokers but less likely to be current drinkers and to have completed a college education . the baseline prevalence of chd and incidence of chd were higher among subjects with hf ( p<0.0001 ) . baseline demographic and clinical characteristics by incident heart failure status of aric participants data are meanstandard deviation ( sd ) , or number ( percentages ) . bmi indicates body mass index ; chd , coronary heart disease ; hdl , high density lipoprotein ; hf , heart failure ; imt , intimamedia thickness ; ldl , low density lipoprotein ; lvh , left ventricular hypertrophy . mean carotid imt was significantly higher for subjects with hf ( 0.810.23 versus 0.710.17 ; p<0.0001 ) , table 2 . compared with subjects in the first ( lowest ) quartile of carotid imt ( imt0.61 mm ) , the unadjusted incidence rates of hf increased across the second , third , and fourth quartiles ( table 3 ) . the rate in the highest quartile of carotid imt was 15.42 cases per 1000 personyears ( about 4 times the rate in the first quartile , and twice the rate in the third quartile ) . figure 1 shows a kaplanmeier plot of the overall survival probability of hf over time as a function of carotid imt quartiles . there was a significant difference in eventfree survival between quartiles of imt ( p<0.0001 ) ( figure 1 ) . of note , participants in the fourth quartile had a significantly lower survival ; 74% of those in the fourth quartile were hffree at 20 years , compared with 92% in the first quartile . unadjusted and adjusted hrs ( 95% ci ) for incident heart failure across quartiles of carotid imt ci indicates confidence interval ; hf , heart failure ; hr , hazard ratio ; imt , intimamedia thickness ; pyrs , personyears ; q , quartile ; ref . , reference . * p<0.0001 , p=0.001 ; p<0.0001 for trend in all 4 models . for each model , the hr for q2 , q3 , and q4 are in comparison to the reference model , q1 . model 1 : unadjusted ; model 2 : adjusted for age , gender , race , education ; model 3 : model 2 plus systolic and diastolic blood pressure , bmi , waist circumference , ldl , hdl , triglycerides , smoking , alcohol , hypertension and cholesterol medication , serum creatinine ; model 4 : model 3 plus prevalent and incident chd . kaplanmeier curves illustrating the hffree survival probability over time as a function of quartiles of carotid imt . cimtquartiles indicates quartiles of carotid imt ; q1 , first quartile ; q2 , second quartile ; q3 , third quartile ; q4 , fourth quartile . hf indicates heart failure ; imt , intimamedia thickness . in the multivariable analysis , we estimated the hr of hf across quartiles of carotid imt ( table 3 ) . after adjustment for demographic factors , the second , third , and fourth quartiles of carotid imt were significantly associated with hf compared with the first quartile of imt ( hr for fourth quartile 2.59 , 95% ci : 2.23 to 2.99 ) . the strength of this association was reduced , but significantly persisted for the fourth quartile of carotid imt after further adjustments for cvd risk factors ( hr 1.65 , 95% ci : 1.42 , 1.93 , < 0.0001 ) and chd ( hr 1.60 , 95% ci : 1.37 to 1.87 , p<0.0001 ) . there was a significant trend in the relationship between carotid imt and hf across quartiles of imt ( p<0.0001 ) in all 4 models . even after accounting for death from other causes as a competing risk event , the cumulative incidence functions of hf across quartiles of carotid imt remained significant ( p<0.0001 ) ( figure 2 ) . a , analysis does not take into account death from other causes as a competing risk . quartilescimt indicates quartiles of carotid imt ; q1 , first quartile ; q2 , second quartile ; q3 , third quartile ; q4 , fourth quartile . the hazard ratios ( hrs ) and 95% confidence intervals of hf per unit sd ( 0.18 mm ) increase in imt are given in table 4 . no interactions were observed by gender or race ( the p values for the imtrace and imtgender interaction terms in the unadjusted model were 0.97 and 0.11 , respectively ) . unadjusted and adjusted hrs ( 95% ci ) for incident heart failure per 1 sd ( 0.18 mm ) increase in carotid imt bmi indicates body mass index ; chd , coronary heart disease ; ci confidence interval ; hdl , high density lipoprotein ; hr , hazard ratio ; hf , heart failure ; imt , intimamedia thickness ; ldl , low density lipoprotein . model 2 : adjusted for age , gender , race , education ; model 3 : model 2 plus systolic and diastolic blood pressure , bmi , waist circumference , ldl , hdl , triglycerides , smoking , alcohol , hypertension and cholesterol medication , serum creatinine ; model 4 : model 3 plus prevalent and incident chd . mean brachial pp was higher among those with hf than those without the condition ( 53.115.5 mm hg versus 46.312.7 mm hg ; p<0.0001 , respectively ) . in univariate analysis , carotid imt correlated directly with brachial pp ( r=0.25 , p<0.0001 ) . when brachial pp was included in multivariable models , no significant modification of hf risk was observed . overall mean carotid imt was not significantly different between blacks and whites ( 0.73 mm0.16 versus 0.72 mm0.19 , respectively , p=0.16 ) . the unadjusted incidence rate of hf was higher for blacks than whites ( 10.8 versus 7.22 cases per 1000 personyears ) ( table 5 ) . unadjusted and adjusted hrs ( 95% ci ) for incident heart failure per 1 sd ( 0.18 mm ) increase in carotid imt by race ci indicates confidence interval ; hf , heart failure ; hr , hazard ratio ; imt , intimamedia thickness . model 2 : adjusted for age , gender , race , education ; model 3 : model 2 plus systolic and diastolic blood pressure , bmi , waist circumference , ldl , hdl , triglycerides , smoking , alcohol , hypertension and cholesterol medication , serum creatinine ; model 4 : model 3 plus prevalent and incident chd . in multivariable analysis , carotid imt although the strength of the association decreased progressively in both blacks and whites with adjustment of more covariates , the association was only slightly attenuated ; for example , in blacks the hr was 1.54 per unit sd increase in imt ( 95% ci , 1.45 to 1.65 ) for the unadjusted model and 1.23 ( 95% ci , 1.12 to 1.32 ) after adjustment for demographic , clinical , and biological variables , and 1.22 ( 95% ci , 1.12 to 1.32 ) after adjustment for chd . the results of the association of increasing carotid imt and incident hf by gender paralleled that by race . among the 13 590 participants in this study , there were 2008 ( 14.8% of total cohort ) incident cases of hf over a median followup period of 20.6 years . table 2 compares the baseline demographic and clinical characteristics of participants with and without incident hf . compared with participants without hf , participants with hf were older ( 56.6 versus 53.7 years ) , more likely to be male ( 52.5% versus 44.1% ) , and more likely to be hypertensive ( 50.3% versus 28.6% ) . participants who developed hf over the course of followup were also more likely , at baseline , to have an abnormal lipid profile , were current smokers but less likely to be current drinkers and to have completed a college education . the baseline prevalence of chd and incidence of chd were higher among subjects with hf ( p<0.0001 ) . baseline demographic and clinical characteristics by incident heart failure status of aric participants data are meanstandard deviation ( sd ) , or number ( percentages ) . bmi indicates body mass index ; chd , coronary heart disease ; hdl , high density lipoprotein ; hf , heart failure ; imt , intimamedia thickness ; ldl , low density lipoprotein ; lvh , left ventricular hypertrophy . mean carotid imt was significantly higher for subjects with hf ( 0.810.23 versus 0.710.17 ; p<0.0001 ) , table 2 . compared with subjects in the first ( lowest ) quartile of carotid imt ( imt0.61 mm ) , the unadjusted incidence rates of hf increased across the second , third , and fourth quartiles ( table 3 ) . the rate in the highest quartile of carotid imt was 15.42 cases per 1000 personyears ( about 4 times the rate in the first quartile , and twice the rate in the third quartile ) . figure 1 shows a kaplanmeier plot of the overall survival probability of hf over time as a function of carotid imt quartiles . there was a significant difference in eventfree survival between quartiles of imt ( p<0.0001 ) ( figure 1 ) . of note , participants in the fourth quartile had a significantly lower survival ; 74% of those in the fourth quartile were hffree at 20 years , compared with 92% in the first quartile . unadjusted and adjusted hrs ( 95% ci ) for incident heart failure across quartiles of carotid imt ci indicates confidence interval ; hf , heart failure ; hr , hazard ratio ; imt , intimamedia thickness ; pyrs , personyears ; q , quartile ; ref . , reference . * p<0.0001 , p=0.001 ; p<0.0001 for trend in all 4 models . for each model , the hr for q2 , q3 , and q4 are in comparison to the reference model , q1 . model 1 : unadjusted ; model 2 : adjusted for age , gender , race , education ; model 3 : model 2 plus systolic and diastolic blood pressure , bmi , waist circumference , ldl , hdl , triglycerides , smoking , alcohol , hypertension and cholesterol medication , serum creatinine ; model 4 : model 3 plus prevalent and incident chd . kaplanmeier curves illustrating the hffree survival probability over time as a function of quartiles of carotid imt . cimtquartiles indicates quartiles of carotid imt ; q1 , first quartile ; q2 , second quartile ; q3 , third quartile ; q4 , fourth quartile . , we estimated the hr of hf across quartiles of carotid imt ( table 3 ) . after adjustment for demographic factors , the second , third , and fourth quartiles of carotid imt were significantly associated with hf compared with the first quartile of imt ( hr for fourth quartile 2.59 , 95% ci : 2.23 to 2.99 ) . the strength of this association was reduced , but significantly persisted for the fourth quartile of carotid imt after further adjustments for cvd risk factors ( hr 1.65 , 95% ci : 1.42 , 1.93 , < 0.0001 ) and chd ( hr 1.60 , 95% ci : 1.37 to 1.87 , p<0.0001 ) . there was a significant trend in the relationship between carotid imt and hf across quartiles of imt ( p<0.0001 ) in all 4 models . even after accounting for death from other causes as a competing risk event , the cumulative incidence functions of hf across quartiles of carotid imt remained significant ( p<0.0001 ) ( figure 2 ) . quartilescimt indicates quartiles of carotid imt ; q1 , first quartile ; q2 , second quartile ; q3 , third quartile ; q4 , fourth quartile . similar results were observed with carotid imt modeled as a continuous variable . the hazard ratios ( hrs ) and 95% confidence intervals of hf per unit sd ( 0.18 mm ) no interactions were observed by gender or race ( the p values for the imtrace and imtgender interaction terms in the unadjusted model were 0.97 and 0.11 , respectively ) . unadjusted and adjusted hrs ( 95% ci ) for incident heart failure per 1 sd ( 0.18 mm ) increase in carotid imt bmi indicates body mass index ; chd , coronary heart disease ; ci confidence interval ; hdl , high density lipoprotein ; hr , hazard ratio ; hf , heart failure ; imt , intimamedia thickness ; ldl , low density lipoprotein . model 2 : adjusted for age , gender , race , education ; model 3 : model 2 plus systolic and diastolic blood pressure , bmi , waist circumference , ldl , hdl , triglycerides , smoking , alcohol , hypertension and cholesterol medication , serum creatinine ; model 4 : model 3 plus prevalent and incident chd . mean brachial pp was higher among those with hf than those without the condition ( 53.115.5 mm hg versus 46.312.7 mm hg ; p<0.0001 , respectively ) . in univariate analysis , carotid imt correlated directly with brachial pp ( r=0.25 , p<0.0001 ) . when brachial pp was included in multivariable models , no significant modification of hf risk was observed . overall mean carotid imt was not significantly different between blacks and whites ( 0.73 mm0.16 versus 0.72 mm0.19 , respectively , p=0.16 ) . the unadjusted incidence rate of hf was higher for blacks than whites ( 10.8 versus 7.22 cases per 1000 personyears ) ( table 5 ) . unadjusted and adjusted hrs ( 95% ci ) for incident heart failure per 1 sd ( 0.18 mm ) increase in carotid imt by race ci indicates confidence interval ; hf , heart failure ; hr , hazard ratio ; imt , intimamedia thickness . model 2 : adjusted for age , gender , race , education ; model 3 : model 2 plus systolic and diastolic blood pressure , bmi , waist circumference , ldl , hdl , triglycerides , smoking , alcohol , hypertension and cholesterol medication , serum creatinine ; model 4 : model 3 plus prevalent and incident chd . in multivariable analysis , carotid imt although the strength of the association decreased progressively in both blacks and whites with adjustment of more covariates , the association was only slightly attenuated ; for example , in blacks the hr was 1.54 per unit sd increase in imt ( 95% ci , 1.45 to 1.65 ) for the unadjusted model and 1.23 ( 95% ci , 1.12 to 1.32 ) after adjustment for demographic , clinical , and biological variables , and 1.22 ( 95% ci , 1.12 to 1.32 ) after adjustment for chd . the results of the association of increasing carotid imt and incident hf by gender paralleled that by race . the objective of this study was to investigate the association of carotid imt with incident hf among middleaged adults . carotid imt was significantly associated with incident hf among whites and blacks , after adjusting for demographic and major cvd risk factors , and chd . this relationship was comparable in both blacks and whites , as well as in males and females . carotid imt is a well validated measure of preclinical atherosclerotic lesions . in this populationbased study similar mean far wall estimates have been reported in other populations of similar age groups ; in the carotid atherosclerosis progression study and malmo diet and cancer study , mean far wall imt was 0.730.16 mm and 0.770.15 mm , respectively . the present study has shown that carotid imt is associated with incident hf , with imt modeled as both a continuous and categorical variable , even after taking into account associations explained by age , gender , race , blood pressure , bmi , waist circumference , hdl cholesterol , ldl cholesterol , triglycerides , cigarette smoking , alcohol , and serum creatinine , as well as medications for dyslipidemia and hypertension . our result is consistent with that described by engstrom et al , who reported a significant association of increased imt and hf hospitalizations in a sample of 4691 subjects with 75 cases of hf . moreover , our results remained significant even after adjustment for prevalent and incident cases of chd , which has been reported to be a major cause of hf . our study 's finding that the association of carotid imt with hf remained significant after adjustment for prevalent and incident chd , as well as blood pressure , and other traditional cvd risk factors suggests that carotid imt may be associated with hf through a mechanism that is different from that causing discrete clinical episodes of myocardial ischemia or infarction . this concept is strengthened by demonstrating that results were only slightly attenuated after adjustment for chd . first , increasing carotid imt leads to structural changes of the artery wall , which result in the deposition of collagen in the intracellular matrix and a decrease in arterial distensibility , causing increased pressure afterload , pressure wave propagation , and eventually diastolic dysfunction . we found carotid imt to be directly correlated with brachial pulse pressure ( pp ) , but no significant change was observed when brachial pp was added to the multivariable models . boutouyrie et al reported a similar correlation between brachial pp and carotid pp with carotid imt . however , only carotid pp significantly influenced carotid wall thickness , indicating that carotid pp ( a measure of arterial stiffening ) may be superior to brachial pp in exploring the mechanistic relationship between imt and hf . a second potential mechanism relates to the finding from prior studies that increasing common carotid imt was associated with reduced myocardial flow reserve in adults with and without chd . some prospective and crosssectional studies have established an association between increasing carotid imt and regional lv myocardial systolic and diastolic dysfunction , a subclinical marker and strong predictor of hf . it may be necessary to further characterize hf cases ( hfpef versus hfref ) in their relation to carotid imt to fully understand the different mechanisms that could contribute to hf in subjects with increased carotid imt . baseline echocardiographic data is not available in the aric study and cardiac ultrasound data at the time of incident hf ( obtained by review of medical records ) is available only for events occurring after january 2005 . as such , hf type in our sample bourassa et al , using data from the studies of left ventricular dysfunction ( solvd ) , reported that ischemic heart disease accounts for a majority of hf cases ( 73% ) in whites than in blacks ( 36% ) . another third of cases in blacks was due to hypertensive heart disease , compared with only 4% in whites . despite these known racial differences in the etiology of hf , we found that an association of increasing carotid imt with incident hf was observed in both whites and blacks , and to comparable degrees . to the best of our knowledge , our study is the first to investigate the association of carotid imt with incident hf in a large middleaged cohort with more than 2 decades of followup and more than 2000 cases of incident hf . the use of a middleaged population that is at a lower risk of hf compared with the elderly is particularly important . first , we did not adjust our analyses for novel biomarkers that could potentially influence the relationship between carotid imt and hf , such as nterminal probrain natriuretic peptide ( ntprobnp ) and highsensitivity creactive protein . however , in a prior published study , the association of carotid imt with hf remained significant , even after adjustment for these markers . second , the use of hospital discharge codes and death registers to recruit hf cases may have underestimated hf incidence in the population . however , the fact that increased carotid imt has been shown to be associated with reduced systolic and diastolic myocardial strain in asymptomatic individuals suggests an association of carotid imt with less severe cases of hf . our analyses included both adjudicated and nonadjudicated cases of hf . in a separate sensitivity analysis ( data not shown ) , there was no significant difference in the hazard ratios of hf prior to and after the adjudication process . third , our cohort comprised of only blacks and whites , so caution should be made when generalizing these results to other race / ethnic groups . finally , in our study , carotid imt estimates used were based on mean far wall measurements only . depending on the segment of the carotid artery measured ( common , bifurcation , or internal carotid ) , the portion of the artery wall measured ( far or near wall ) , or the variable used ( mean or maximum imt ) , different studies may report conflicting results on the association between imt and cvd risk . therefore caution should be exercised when comparing our findings to other studies employing a different ultrasound protocol . in this cohort of middleaged blacks and whites , we have demonstrated that increasing thickness of the carotid intima and media is associated with the incidence of hf even beyond the risks accounted for by traditional cvd risk factors and chd . carotid imt is appealing because it has been shown in several populationbased studies to predict future risk of myocardial infarction and stroke , and our study shows that hf is also predicted by increasing carotid imt . carotid imt is a reliable , lowcost , lowrisk indicator of early atherosclerosis currently used in cardiovascular research . measurement of carotid imt can be quickly and easily accomplished in a clinical setting , and with modern ultrasound scanners this procedure becomes more efficient and reproducible . findings from our study indicate that carotid imt may mediate hf through a mechanism that is different from myocardial ischemia or infarction . carotid imt may be useful in future hf risk prediction among middleaged blacks and whites . carotid imt is appealing because it has been shown in several populationbased studies to predict future risk of myocardial infarction and stroke , and our study shows that hf is also predicted by increasing carotid imt . carotid imt is a reliable , lowcost , lowrisk indicator of early atherosclerosis currently used in cardiovascular research . measurement of carotid imt can be quickly and easily accomplished in a clinical setting , and with modern ultrasound scanners this procedure becomes more efficient and reproducible . findings from our study indicate that carotid imt may mediate hf through a mechanism that is different from myocardial ischemia or infarction . carotid imt may be useful in future hf risk prediction among middleaged blacks and whites . the authors thank the staff and participants of the aric study for their important contributions .
backgroundincreased carotid intimamedia thickness ( imt ) is associated with subclinical left ventricular myocardial dysfunction , suggesting a possible role of carotid imt in heart failure ( hf ) risk determination.methods and resultsmean far wall carotid imt , measured by bmode ultrasound , was available for 13 590 atherosclerosis risk in communities study participants aged 45 to 64 years and free of hf at baseline . 
 hf was defined using icd9 428 and icd10 i50 codes from hospitalization records and death certificates . 
 the association between carotid imt and incident hf was assessed using cox proportional hazards analysis with models adjusted for demographic variables , major cvd risk factors , and interim chd . 
 there were 2008 incident hf cases over a median followup of 20.6 years ( 8.1 cases per 1000 personyears ) . 
 mean imt was higher in those with hf than in those without ( 0.81 mm0.23 versus 0.71 mm0.17 , p<0.001 ) . 
 unadjusted rate of hf for the fourth compared with the first quartile of imt was 15.4 versus 3.9 per 1000 personyears ; p<0.001 . in multivariable analysis , after adjustment , each standard deviation increase in imt was associated with incident hf ( hr 1.20 [ 95% ci : 1.16 to 1.25 ] ) . after adjustment , 
 the top quartile of imt was associated with hf ( hr 1.60 [ 95% ci : 1.37 to 1.87 ] ) . 
 results were similar across race and gender groups.conclusionsincreasing carotid imt is associated with incident hf in middleaged whites and blacks , beyond risks explained by major cvd risk factors and chd . 
 this suggests that carotid imt may be associated with hf through mechanisms different from myocardial ischemia or infarction .