coronary artery calcium ( cac ) measured by computed tomography is strongly associated with incident coronary heart disease ( chd ) and individuals with a cac score of zero have very low shortterm risk for chd ( ie , over 5 to 10 years ) . although the impact of a cac score of zero on shortterm risk is well established , its longterm implications are uncertain , particularly in the setting of high predicted lifetime risk . among individuals with low shortterm risk ( ie , low framingham risk score ) , the presence of high predicted lifetime risk is common and translates into marked elevations in longterm chd event rates . thus , individuals with zero cac and high predicted lifetime risk represent a particularly challenging subgroup with apparent discordance between shortterm and longterm risk . since there are no available data on individuals with measured cac and longterm followup ( ie , 30 + years ) , progression of subclinical atherosclerosis is a reasonable surrogate that may identify unfavorable lifetime risk trajectories . therefore , we sought to determine the association between predicted lifetime risk and cac incidence in a large sample of healthy adults with low shortterm risk and cac scores of 0 . we hypothesized that high predicted lifetime risk would be associated with greater cac incidence , identifying a group of individuals with very low shortterm risk who might benefit from more intensive risk factor modification . the design of the dallas heart study ( dhs ) and details of variable definitions have been previously described . in brief , the dhs is a multiethnic , populationbased , cohort study of dallas county adults , with deliberate oversampling of africanamericans . all participants provided written informed consent and the study protocol was approved by the institutional review board of the university of texas southwestern medical center . the first phase of the dhs took place between 2000 and 2002 when the initial cohort underwent a detailed inhome health survey ( visit 1 ) , after which participants aged 30 to 65 years returned for blood and urine collection ( visit 2 ) . visit 3 consisted of participants who returned for a detailed clinical examination and imaging studies . dhs phase2 is a longitudinal followup study of dhs phase1 participants who volunteered to undergo additional assessments between september 2007 and december 2009 . these assessments again included an extensive health survey , laboratory testing , and imaging studies . among dhs phase1 participants , 2646 had interpretable cac scans and complete data for all covariates . after excluding 285 participants with prior cardiovascular disease ( ie , prior stroke , myocardial infarction , or coronary revascularization ) or diabetes , 1560 with cac>0 and 41 with framingham risk 10% , 762 participants were eligible for inclusion in this study . of these 762 participants , 8 did not return for cac scanning in dhs phase2 resulting in a final sample of 754 individuals with low shortterm risk , baseline cac of zero and a repeat cac scan ( figure 1 ) . cac indicates coronary artery calcium ; cvd , cardiovascular disease ; dhs1 , dallas heart study phase 1 ; dhs2 , dallas heart study phase 2 ; dm , diabetes mellitus . height , weight , blood pressure , plasma lipids , and glucose were measured , and the body mass index was calculated using standard methods . in dhs phase1 , electronbeam computed tomography ( ebct ) measurements of cac were performed in duplicate 1 to 2 minutes apart on an imatron 150 xp scanner . in dhs phase2 , cac was measured by multidetector computed tomography ( mdct ) and was performed on a toshiba aquilon 64slice mdct scanner with each participant scanned in duplicate within 1 to 2 minutes . dhs phase1 and dhs phase2 cac scores were adjusted using a standard calcium phantom that was scanned with the participant . this adjusted attenuation process has been previously described and allows comparison of scores obtained across different platforms ( eg , ebct in dhs phase1 and mdct in dhs phase2 ) . the framingham risk score was determined in accordance with the third adult treatment panel risk assessment tool using age , sex , total and highdensity lipoprotein cholesterol levels , smoking , systolic blood pressure , and antihypertensive medication use . participants with diabetes or prevalent cardiovascular disease were excluded from this study . in secondary analysis , low shortterm risk was defined as < 7.5% 10year risk using the pooled cohort equations as proposed by the most recent american guidelines . predicted lifetime risk was determined based on our previously published algorithm ( table 1 ) . for the primary analysis , cac incidence was defined as a followup cac score > 0 . as sensitivity analysis , we defined cac incidence as a followup cac score > 10 agatston units ( au ) to minimize falsepositive results related to technical artifacts . risk factor stratification and predicted lifetime risk for cardiovascular disease risk factor stratification derived from lloydjones , et al . diabetes was included in the original published stratification . because all diabetics were considered to have  high shortterm risk  , this risk factor was not included in the present paper . baseline demographic and clinical variables were compared between subjects with low versus high predicted lifetime risk using the chisquare test for categorical variables and wilcoxonrank sum for continuous variables . a logistic regression model was used to assess the association between low versus high predicted lifetime risk and incident cac in univariable and multivariable models . since blood pressure , total cholesterol , and smoking are included in the predicted lifetime risk variable , only age , sex , and race were added as additional covariates in the multivariable models . participants were further classified based on their risk factor profile at the follow up visit ( ie , dhs phase2 ) . individuals were then classified as lowrisk if both framingham and lifetime risk remained low and as highrisk if framingham risk was 10% , lifetime risk was high , or in the presence of diabetes or cardiovascular disease . cac incidence was compared across 4 mutually exclusive groups constructed based on baseline and followup risk classification ( ie , low baseline / low followup , low baseline / high followup , high baseline / low followup and high baseline / high followup ) . the design of the dallas heart study ( dhs ) and details of variable definitions have been previously described . in brief , the dhs is a multiethnic , populationbased , cohort study of dallas county adults , with deliberate oversampling of africanamericans . all participants provided written informed consent and the study protocol was approved by the institutional review board of the university of texas southwestern medical center . the first phase of the dhs took place between 2000 and 2002 when the initial cohort underwent a detailed inhome health survey ( visit 1 ) , after which participants aged 30 to 65 years returned for blood and urine collection ( visit 2 ) . visit 3 consisted of participants who returned for a detailed clinical examination and imaging studies . dhs phase2 is a longitudinal followup study of dhs phase1 participants who volunteered to undergo additional assessments between september 2007 and december 2009 . these assessments again included an extensive health survey , laboratory testing , and imaging studies . among dhs phase1 participants , 2646 had interpretable cac scans and complete data for all covariates . after excluding 285 participants with prior cardiovascular disease ( ie , prior stroke , myocardial infarction , or coronary revascularization ) or diabetes , 1560 with cac>0 and 41 with framingham risk 10% , 762 participants were eligible for inclusion in this study . of these 762 participants , 8 did not return for cac scanning in dhs phase2 resulting in a final sample of 754 individuals with low shortterm risk , baseline cac of zero and a repeat cac scan ( figure 1 ) . cac indicates coronary artery calcium ; cvd , cardiovascular disease ; dhs1 , dallas heart study phase 1 ; dhs2 , dallas heart study phase 2 ; dm , diabetes mellitus . height , weight , blood pressure , plasma lipids , and glucose were measured , and the body mass index was calculated using standard methods . in dhs phase1 , electronbeam computed tomography ( ebct ) measurements of cac were performed in duplicate 1 to 2 minutes apart on an imatron 150 xp scanner . in dhs phase2 , cac was measured by multidetector computed tomography ( mdct ) and was performed on a toshiba aquilon 64slice mdct scanner with each participant scanned in duplicate within 1 to 2 minutes . dhs phase1 and dhs phase2 cac scores were adjusted using a standard calcium phantom that was scanned with the participant . this adjusted attenuation process has been previously described and allows comparison of scores obtained across different platforms ( eg , ebct in dhs phase1 and mdct in dhs phase2 ) . the framingham risk score was determined in accordance with the third adult treatment panel risk assessment tool using age , sex , total and highdensity lipoprotein cholesterol levels , smoking , systolic blood pressure , and antihypertensive medication use . participants with diabetes or prevalent cardiovascular disease were excluded from this study . in secondary analysis , low shortterm risk was defined as < 7.5% 10year risk using the pooled cohort equations as proposed by the most recent american guidelines . predicted lifetime risk was determined based on our previously published algorithm ( table 1 ) . for the primary analysis , cac incidence was defined as a followup cac score > 0 . as sensitivity analysis , we defined cac incidence as a followup cac score > 10 agatston units ( au ) to minimize falsepositive results related to technical artifacts . risk factor stratification and predicted lifetime risk for cardiovascular disease risk factor stratification derived from lloydjones , et al . diabetes was included in the original published stratification . because all diabetics were considered to have high shortterm risk  , this risk factor was not included in the present paper . baseline demographic and clinical variables were compared between subjects with low versus high predicted lifetime risk using the chisquare test for categorical variables and wilcoxonrank sum for continuous variables . a logistic regression model was used to assess the association between low versus high predicted lifetime risk and incident cac in univariable and multivariable models . since blood pressure , total cholesterol , and smoking are included in the predicted lifetime risk variable , only age , sex , and race were added as additional covariates in the multivariable models . participants were further classified based on their risk factor profile at the follow up visit ( ie , dhs phase2 ) . individuals were then classified as lowrisk if both framingham and lifetime risk remained low and as highrisk if framingham risk was 10% , lifetime risk was high , or in the presence of diabetes or cardiovascular disease . cac incidence was compared across 4 mutually exclusive groups constructed based on baseline and followup risk classification ( ie , low baseline / low followup , low baseline / high followup , high baseline / low followup and high baseline / high followup ) . among 754 dhs participants with low shortterm risk and cac=0 at baseline , lifetime risk stratification resulted in 2 groups of approximately equal size : low shortterm / low lifetime risk ( n=365 , 48.4% ) and low shortterm / high lifetime risk ( n=389 , 51.6% ) . participants in the high predicted lifetime risk group were older ( mean age 43.1 years versus 40.5 years ; p < 0.001 ) and had a higher burden of traditional risk factors ( ie , higher blood pressure , total cholesterol , low density lipoprotein cholesterol , triglycerides and fasting glucose with a higher prevalence of smoking and lower highdensity lipoprotein cholesterol levels ) ( table 2 ) . they also had higher bodymass indexes and were more likely to report a family history of myocardial infarction and use of statins . baseline characteristics stratified by predicted lifetime risk bmi indicates body mass index ; fhmi , family history of myocardial infarction ; hdl , highdensity lipoprotein cholesterol ; ldl , lowdensity lipoprotein cholesterol ; sbp , systolic blood pressure ; tc , total cholesterol . predicted 10 year risk of coronary heart disease events according to the adult treatment panel iii / framingham risk score , median ( interquartile range ) . after 6.9 years of followup , we observed 182 cases of incident cac , representing 24.1% of the study sample . high predicted lifetime risk was associated with a higher cac incidence ( 29.1% versus 18.9% ; p=0.001 ) , higher annualized cac incidence ( 4.2% versus 2.7% , p=0.001 ) , and higher mean followup cac scores ( 7.8 versus 2.4 au ; p < 0.001 ) ( figure 2 ) . followup cac scores > 100 au were only observed in the high lifetime risk group ( n=5 , 1.3% ) . after adjusting for age , sex , and race , high lifetime risk remained associated with higher incidence of cac ( or 1.60 , 95% ci 1.12 to 2.27 ; p=0.01 ) ( table 3 ) . coronary artery calcium incidence according to predicted lifetime risk group strata au indicates agatston units ; cac , coronary artery calcium . au indicates agatston units ; cac , coronary artery calcium ; low / low , low predicted shortterm risk and low predicted lifetime risk ; low / high , low predicted shortterm risk and high predicted lifetime risk . when cac incidence was defined as followup cac>10 au , we observed a similar pattern of results ( cac incidence 10.5% versus 6.3% ; or 1.75 , 95% ci 1.03 to 2.98 ; p=0.039 ) . applying the pooled cohort equations to define low shortterm risk as 10year risk < 7.5% , high lifetime risk remained associated with higher incidence of cac ( or 1.55 , 95% ci 1.02 to 2.37 ; p=0.04 ) . among the 365 participants classified as low lifetime risk in dhs phase1 , 160 ( 43.8% ) remained in the low predicted risk category in dhs phase2 and 205 ( 56.2% ) were newly classified as highrisk based on the development of cardiovascular disease or diabetes , framingham risk 10% or high lifetime risk ( 3 reported an interval myocardial infarction or stroke , 12 developed diabetes , 10 had framingham risk 10% , and 185 had high lifetime risk ) . in the high baseline lifetime risk group ( n=389 ) , 328 ( 84.3% ) remained in the same short and longterm risk category and 61 ( 15.7% ) were reclassified into a different group ( 27 had low lifetime risk , 30 had framingham risk 10% , 28 developed diabetes , and 6 developed cvd ) . among participants with low lifetime risk in dhs phase1 and low risk in dhs phase2 , 14.4% developed coronary calcification while , among those with high lifetime risk in dhs1 and high risk in dhs2 , 30.1% had follow up cac scores > 0 . in the group with low lifetime risk at baseline , participants with high short or longterm risk at followup account for 66.7% of incident cac . because high predicted lifetime risk is associated with the presence of at least 1 of 3 major risk factors ( ie , smoking , total cholesterol , and hypertension ) , we performed additional secondary analyses to determine the extent to which our findings were dependent upon any one risk factor . for example , after excluding smokers from the analysis , high predicted lifetime risk was associated with a higher likelihood of cac incidence when compared to individuals with low predicted lifetime risk ( adjusted or 1.70 , 95% ci 1.14 to 2.53 ; p=0.009 ) . similar findings were observed after excluding individuals with blood pressure 160/100 mm hg or on treatment with antihypertensive medications and individuals with total cholesterol  6.3 mmol / l ( 240 mg / dl ) or on treatment with a statin medication ( table 4 ) . odds ratio of cac incidence based on the presence of predicted high lifetime risk in selected subgroups stage 2 hypertension was defined as systolic blood pressure 160 mm hg or diastolic blood pressure 100 mm hg or on treatment for hypertension . in a large multiethnic populationbased cohort , we observed that , among individuals with low shortterm risk , the presence of high predicted lifetime risk is associated with a 60% increased risk of cac incidence over 6.9 years of followup . the association between high lifetime risk and cac incidence was robust and persisted after adopting a more strict definition of incident cac and after excluding individuals with marked elevations of each risk factor group . this suggests that even among individuals with low framingham risk scores and zero cac , predicted lifetime risk identifies a subgroup that is more likely to develop subclinical atherosclerosis and in whom longterm risk likely remains elevated . although the addition of cac to traditional risk factors has been shown to provide clinically significant improvement in shortterm cardiovascular risk prediction , both methods share similar limitations . in particular , both shortterm risk and cac are highly age dependent such that the majority of adults < 50 years old have both low shortterm risk and zero cac . nevertheless , the burden of traditional risk factors in middle age is strongly associated with chd risk across the remaining lifespan . however , the contribution of cac to lifetime cardiovascular risk has not been studied and the longterm trajectory of middle age individuals with zero cac and high predicted lifetime risk remains uncertain . in the present study , we observed that lifetime risk stratification identifies a subgroup of individuals at risk for cac incidence over the nearterm , suggesting that low shortterm risk , zero cac individuals with high predicted lifetime risk may not remain low risk . these findings highlight the complementary role of lifetime risk stratification to both shortterm risk estimation and cac imaging and could have implications for preventive interventions such as lifestyle counseling and/or medical therapy . follow up cac scores were used in this study with the primary goal of identifying unfavorable risk trajectories . the study was not designed to assess the impact of serial cac scanning on cardiovascular prevention strategies . the observation that high lifetime risk is associated with the development of subclinical atherosclerosis even among individuals with low shortterm risk and cac scores of 0 suggests that this group should be counseled on strategies to minimize longterm risk . interestingly , even among individuals with low risk factor burden ( ie , low lifetime risk ) , 18.9% developed cac and 6.3% had cac scores > 10 au over a followup period of 6.9 years . in the low lifetime risk group , twothirds of cac incidence occurred among individuals who were reclassified as high risk at followup suggesting the importance of future risk factor levels on the development of atherosclerosis . although risk factor burden at middle age has a strong association with longterm cardiovascular risk , maintaining a favorable risk factor profile may be equally important and the current recommended strategy of serial assessment of risk factor burden should be applied to individuals with low predicted risk . previous studies have shown that among participants with low shortterm risk , high predicted lifetime risk is associated with a higher prevalence and progression of atherosclerosis as measured by cac and carotid intima media thickness . however , the association between high predicted lifetime risk and cac incidence among low risk adults has not been reported . the present study extends these prior observations to show that even among those without cac at middle age , high predicted lifetime risk is associated with the development of subclinical atherosclerosis and identifies an unfavorable trajectory that is likely to result in higher longterm event rates . a warranty period of 4 years has been proposed for cac scores of zero . this warranty period is based on a study by min et al where 422 individuals with no baseline coronary calcification underwent annual cac scans up to 5 years . they showed that the cumulative incidence of cac was 15% by year 4 and 25% by year 5 and that the mean time to conversion was 4.1 years . though several risk factors were associated with cac incidence , they saw no correlation between cardiovascular risk profiles and accelerated time to conversion . in an analysis of the multiethic study of atherosclerosis ( mesa ) , kronmal et al also found that several traditional risk factors such as high blood pressure , high lowdensity lipoprotein cholesterol levels , diabetes , and family history of myocardial infarction were associated with cac incidence . in line with those findings , our study suggests that cac scores of zero should to be considered in the context of risk factor burden and lifetime risk . in the present study of relatively young adults , almost 30% of individuals with low shortterm and high lifetime risk developed measurable coronary calcification by the end of the followup period ( ie , 6.9 years ) . although cac progression ( ie , increasing cac among those with cac>0 at baseline ) has been consistently associated with chd events , the shortterm impact of cac incidence on clinical outcomes remains uncertain . in a study by budoff et al , cac progression but not incidence predicted allcause mortality in 4609 patients scanned 3.12 years apart and followed for 5.43.4 years after the second cac scan . a larger study from the mesa cohort included 6778 individuals scanned 2.50.8 years apart and followed for 7.6 years after the first scan . although cac progression was a strong predictor of chd , the impact of cac incidence was more modest . the discordance between shortterm and longterm risk is well established , and therefore , the more modest impact of cac incidence on shortterm event rates is not inconsistent with a high lifetime risk for chd . in other words , individuals with incident cac usually have low overall cac scores , which translate into low shortterm event rates but are likely to result in high longterm risk . in contrast to shortterm risk estimation strategies that provide objective data on shortterm event rates , longterm risk estimation strategies provide insight into risk trajectories across the lifespan . we have previously shown in multiple cohorts that about half of all adults with a low framingham risk score have high predicted lifetime risk . our data are consistent with this distinction and suggest that , even among middle age individuals with zero cac , high predicted lifetime risk does identify a subgroup of low shortterm risk individuals who are on a different risk trajectory as demonstrated by a higher cac incidence in the shortterm . coronary calcium scores are subject to noise and measurement variations , which could result in imprecise estimates of cac incidence . by using duplicate scans in each visit and demonstrating the consistency of our findings with more strict cac incidence definitions , we believe that our results reflect true biological effects . ideally the impact of predicted lifetime risk in the subgroup of individuals with low framingham risk and cac scores of 0 would be assessed in cohorts with longterm followup where the measured outcome would be clinical chd events . unfortunately , since cac is a relatively new marker , these data will not be available for the foreseeable future . the dallas heart study is a relatively young cohort with a high proportion of africanamericans , which may limit the generalizability of our findings to other populations . although the addition of cac to traditional risk factors has been shown to provide clinically significant improvement in shortterm cardiovascular risk prediction , both methods share similar limitations . in particular , both shortterm risk and cac are highly age dependent such that the majority of adults < 50 years old have both low shortterm risk and zero cac . nevertheless , the burden of traditional risk factors in middle age is strongly associated with chd risk across the remaining lifespan . however , the contribution of cac to lifetime cardiovascular risk has not been studied and the longterm trajectory of middle age individuals with zero cac and high predicted lifetime risk remains uncertain . in the present study , we observed that lifetime risk stratification identifies a subgroup of individuals at risk for cac incidence over the nearterm , suggesting that low shortterm risk , zero cac individuals with high predicted lifetime risk may not remain low risk . these findings highlight the complementary role of lifetime risk stratification to both shortterm risk estimation and cac imaging and could have implications for preventive interventions such as lifestyle counseling and/or medical therapy . follow up cac scores were used in this study with the primary goal of identifying unfavorable risk trajectories . the study was not designed to assess the impact of serial cac scanning on cardiovascular prevention strategies . the observation that high lifetime risk is associated with the development of subclinical atherosclerosis even among individuals with low shortterm risk and cac scores of 0 suggests that this group should be counseled on strategies to minimize longterm risk . interestingly , even among individuals with low risk factor burden ( ie , low lifetime risk ) , 18.9% developed cac and 6.3% had cac scores > 10 au over a followup period of 6.9 years . in the low lifetime risk group , twothirds of cac incidence occurred among individuals who were reclassified as high risk at followup suggesting the importance of future risk factor levels on the development of atherosclerosis . although risk factor burden at middle age has a strong association with longterm cardiovascular risk , maintaining a favorable risk factor profile may be equally important and the current recommended strategy of serial assessment of risk factor burden should be applied to individuals with low predicted risk . previous studies have shown that among participants with low shortterm risk , high predicted lifetime risk is associated with a higher prevalence and progression of atherosclerosis as measured by cac and carotid intima media thickness . however , the association between high predicted lifetime risk and cac incidence among low risk adults has not been reported . the present study extends these prior observations to show that even among those without cac at middle age , high predicted lifetime risk is associated with the development of subclinical atherosclerosis and identifies an unfavorable trajectory that is likely to result in higher longterm event rates . a warranty period of 4 years has been proposed for cac scores of zero . this warranty period is based on a study by min et al where 422 individuals with no baseline coronary calcification underwent annual cac scans up to 5 years . they showed that the cumulative incidence of cac was 15% by year 4 and 25% by year 5 and that the mean time to conversion was 4.1 years . though several risk factors were associated with cac incidence , they saw no correlation between cardiovascular risk profiles and accelerated time to conversion . in an analysis of the multiethic study of atherosclerosis ( mesa ) , kronmal et al also found that several traditional risk factors such as high blood pressure , high lowdensity lipoprotein cholesterol levels , diabetes , and family history of myocardial infarction were associated with cac incidence . in line with those findings , our study suggests that cac scores of zero should to be considered in the context of risk factor burden and lifetime risk . in the present study of relatively young adults , almost 30% of individuals with low shortterm and high lifetime risk developed measurable coronary calcification by the end of the followup period ( ie , 6.9 years ) . although cac progression ( ie , increasing cac among those with cac>0 at baseline ) has been consistently associated with chd events , the shortterm impact of cac incidence on clinical outcomes remains uncertain . in a study by budoff et al , cac progression but not incidence predicted allcause mortality in 4609 patients scanned 3.12 years apart and followed for 5.43.4 years after the second cac scan . a larger study from the mesa cohort included 6778 individuals scanned 2.50.8 years apart and followed for 7.6 years after the first scan . although cac progression was a strong predictor of chd , the impact of cac incidence was more modest . the discordance between shortterm and longterm risk is well established , and therefore , the more modest impact of cac incidence on shortterm event rates is not inconsistent with a high lifetime risk for chd . in other words , individuals with incident cac usually have low overall cac scores , which translate into low shortterm event rates but are likely to result in high longterm risk . in contrast to shortterm risk estimation strategies that provide objective data on shortterm event rates , longterm risk estimation strategies provide insight into risk trajectories across the lifespan . we have previously shown in multiple cohorts that about half of all adults with a low framingham risk score have high predicted lifetime risk . our data are consistent with this distinction and suggest that , even among middle age individuals with zero cac , high predicted lifetime risk does identify a subgroup of low shortterm risk individuals who are on a different risk trajectory as demonstrated by a higher cac incidence in the shortterm . coronary calcium scores are subject to noise and measurement variations , which could result in imprecise estimates of cac incidence . by using duplicate scans in each visit and demonstrating the consistency of our findings with more strict cac incidence definitions , we believe that our results reflect true biological effects . ideally the impact of predicted lifetime risk in the subgroup of individuals with low framingham risk and cac scores of 0 would be assessed in cohorts with longterm followup where the measured outcome would be clinical chd events . unfortunately , since cac is a relatively new marker , these data will not be available for the foreseeable future . the dallas heart study is a relatively young cohort with a high proportion of africanamericans , which may limit the generalizability of our findings to other populations . in the present study we demonstrate that , among individuals with low framingham risk scores and no coronary calcification , high predicted lifetime risk identifies a group with higher incidence of cac . even in this group with very low shortterm event rates , risk factor burden is associated with higher incidence of subclinical atherosclerosis . our findings suggest that among middleaged individuals with a cac score of 0 , high predicted lifetime risk can identify a group who may benefit from more aggressive preventive interventions . future studies assessing longterm cardiovascular event rates among individuals with high risk factor burden and no cac are needed to confirm the unfavorable risk trajectory suggested by this study .
backgroundthe absence of coronary artery calcium ( cac ) in middle age is associated with very low shortterm risk for coronary events . 
 however , the longterm implications of a cac score of 0 are uncertain , particularly among individuals with high cardiovascular lifetime risk . 
 we sought to characterize the association between predicted lifetime risk and incident cac among individuals with low shortterm risk.methods and resultswe included 754 dallas heart study participants with serial cac scans ( 6.9 years apart ) and both low shortterm risk and baseline cac=0 . 
 lifetime risk for cardiovascular disease was estimated according to risk factor burden . among this group , 
 365 individuals ( 48.4% ) were at low lifetime risk and 389 ( 51.6% ) at high lifetime risk . 
 high lifetime risk was associated with higher annualized cac incidence ( 4.2% versus 2.7% ; p < 0.001 ) . 
 similarly , mean followup cac scores were higher among participants with high lifetime risk ( 7.8 versus 2.4 agatston units ) . 
 after adjustment for age , sex , and race , high lifetime risk remained independently associated with incident cac ( or 1.60 ; 95% ci 1.12 to 2.27 ; p=0.01 ) . when assessing risk factor burden at the followup visit , 66.7% of cac incidence observed in the low lifetime risk group occurred among individuals reclassified to a higher short or longterm risk category.conclusionamong individuals with low shortterm risk and cac scores of 0 , high lifetime risk is associated with a higher incidence of cac . 
 these findings highlight the importance of lifetime risk even among individuals with very low shortterm risk .