Abstract-Although cellular adhesion molecules (CAMs) are hypothesized to play an important role in atherogenesis, the relationship between CAMs and systemic atherosclerosis is uncertain. Among 92 outpatients (48 men; meanϮSD age, 65Ϯ9 years), we evaluated the association of soluble vascular CAM-1 (sVCAM-1) and intercellular adhesion molecule-1 (sICAM-1) with carotid intimal-medial thickness (IMT), an index of early atherosclerosis. All subjects underwent a 2-dimensional ultrasound examination of both carotid arteries at the distal common carotid arteries and bifurcation. sVCAM-1 and sICAM-1 levels measured by enzyme-linked immunosorbent assay were significantly correlated with mean IMT of the common carotid artery (rϭ0.34 and rϭ0.30, respectively; PϽ0.01) and carotid bifurcation (rϭ0.31 and rϭ0.26, respectively; PϽ0.05), whereas sVCAM-1 was also positively associated with maximal carotid IMT (rϭ0.35, PϽ0.01). Adjustment for age attenuated the association between sVCAM-1 and common (rϭ0.16, Pϭ0.13) and bifurcation (rϭ0.18, Pϭ0.07) carotid IMT but had minimal effect on the associations between sICAM-1 and carotid measurements (rϭ0.32, PϽ0.01; rϭ0.23, PϽ0.05; for common and bifurcation IMT, respectively). Age-adjusted sICAM-1 levels increased in a stepwise fashion across common carotid IMT tertiles (253Ϯ27 versus 275Ϯ24 versus 384Ϯ26 pg/mL for the lowest, intermediate, and highest IMT tertiles, respectively; PϽ0.01). A similar trend was also found between sVCAM-1 levels and common carotid IMT tertiles (625Ϯ60 versus 650Ϯ53 versus 714Ϯ58 pg/mL; PϽ0.15). These associations were minimally affected in analyses adjusting for hypertension, diabetes, smoking, low and high density lipoprotein cholesterol, lipoprotein(a), and homocysteine, or in a subgroup analysis limited to those with no prior history of atherothrombotic disease. These data demonstrate a positive association between serum CAMs with carotid IMT and further support the hypothesis that systemic inflammation may have a role in atherosclerotic lesion development.

Background-Genetic testing identifies sarcomere mutation carriers (Gϩ) before clinical diagnosis of hypertrophic cardiomyopathy (HCM), allowing characterization of initial disease manifestations. Previous studies demonstrated that impaired relaxation develops before left ventricular hypertrophy (LVH). The precise impact of sarcomere mutations on systolic function in early and late disease is unclear. Methods and Results-Comprehensive echocardiography with strain imaging was performed on 146 genotyped individuals with mutations in 5 sarcomere genes. Contractile parameters were compared in 68 preclinical (Gϩ/LVHϪ), 40 overt (Gϩ/LVHϩ) subjects with HCM, and 38 mutation (Ϫ) normal control relatives. All subjects had normal left ventricular ejection fraction. In preclinical HCM, global and regional peak systolic strain ( sys ) and longitudinal systolic strain rate were not significantly different from controls, but early diastolic mitral annular velocity (Ea) was reduced by 13%. In overt HCM, there was a significant 27% and 14% decrease in global longitudinal sys and systolic strain rate, respectively, compared with both preclinical HCM and controls (PϽ0.013 for all comparisons), and a 33% reduction in Ea. Conclusions-Sarcomere mutations have disparate initial effects on diastolic and systolic functions. Preclinical HCM is characterized by impaired relaxation but preserved systolic strain. In contrast, both diastolic and longitudinal systolic abnormalities are present in overt disease despite normal ejection fraction. We propose that diastolic dysfunction is an early consequence of sarcomere mutations, whereas systolic dysfunction results from mutations combined with subsequent pathological remodeling. Identifying mechanistic pathways triggered by these mutations may begin to reshape the clinical paradigm for treatment, based on early diagnosis and disease prevention. (Circ Cardiovasc Genet. 2009;2:314-321.)