Background and Purpose-Carotid intima-media thickness (IMT) is an independent predictor of vascular events in age groups Ͼ45 years. However, there is little information about the predictive value of IMT in younger individuals. Methods-In the Carotid Atherosclerosis Progression Study (CAPS; nϭ5056; age range 19 to 90 years; mean age 50.1 years), common carotid artery (CCA) IMT, bifurcation IMT, internal carotid artery IMT and vascular risk factors were evaluated at baseline. The incidence of stroke, myocardial infarction (MI), and death was determined prospectively. Data for younger (Ͻ50 years; nϭ2436) and older subjects (Ն50 years; nϭ2620) were analyzed separately using Cox proportional hazard regression models. Results-During

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Background and Purpose-Carotid intima-media thickness (IMT) progression rates are increasingly used as an intermediate outcome for vascular risk. The carotid bifurcation (BIF) and internal carotid artery (ICA) are predilection sites for atherosclerosis. IMT measures from these sites may be a better estimate of atherosclerosis than common carotid artery (CCA) IMT. The study aim was to evaluate site-specific IMT progression rates and their relationships to vascular risk factors compared with baseline IMT measurements. Methods-In a community population (nϭ3383), ICA-IMT, BIF-IMT, CCA-IMT, and vascular risk factors were evaluated at baseline and at 3-year follow-up. Only ICA-IMT progression significantly correlated with baseline vascular risk factors (age, male gender, hypertension, diabetes, and smoking). Change in risk factor profile over follow-up, estimated using the Framingham risk score, was a predictor of IMT progression only. For all arterial sites, correlations were stronger, by a factor of 2 to 3, for associations with baseline IMT compared with IMT progression. Conclusions-Progression rates at the ICA rather than the CCA yield greater absolute changes in IMT and better correlations with vascular risk factors. Vascular risk factors correlate more strongly with baseline IMT than with IMT progression. Prospective data on IMT progression and incident vascular events are required to establish the true value of progression data as a surrogate measure of vascular risk. Results-Mean

Background and Purpose— Smoking acts as a pro-inflammatory stimulus. Inflammation may provide a key mechanism by which smoking causes atherosclerosis. If so, then the degree to which an individual mounts an inflammatory response is likely to influence atherosclerosis severity. This study examined the impact of inflammatory gene polymorphisms and gene–smoking interactions on common carotid artery intima-media thickness (IMT), a measure of early atherosclerosis. Methods— In a community population (n=1000), mean IMT was determined using ultrasound. This population was genotyped for 6 polymorphisms in 4 inflammatory genes: IL-6-174 , IL-6-572 , and IL-6-597 ; IL-1-β-31 ; IL-1 receptor antagonist VNTR and CD14-159. Serum IL-6 levels were measured in the first 500 subjects. Genotypes/haplotypes associated with higher IL-6 levels were designated “inflammatory haplotypes.” A gene load score was calculated, in which 2 represented individuals homozygous for ≥2 inflammatory genotypes/haplotypes and 0 was homozygous for none. Results— Increasing gene load of inflammatory genotypes was associated with a linear increase in serum IL-6 levels ( P =0.018) and increased carotid artery IMT ( P =0.003). There was a significant interaction between gene load and smoking status on carotid IMT ( P for interaction=0.002). Specifically, in smokers, carriers of inflammatory haplotypes had significantly increased age- and sex-adjusted IMT ( IL-6-174C/IL-6-572G/IL-6-597A , P =0.005; IL-1-β-31T/IL-1RN*2 , P =0.04; CD14-159CC , P =0.028). Conclusions— These findings support the hypothesis that inflammation and cytokine responses provide a key mechanism by which smoking causes atherogenesis. Secondly, they highlight the importance of gene–environment, and gene–gene–environment interactions in the pathogenesis of atherosclerosis.