Our results show that sCD14 levels are associated with both subclinical vascular disease (carotid intima media thickness and ABI) and with risk of future clinical CVD in older adults, independently of other risk factors. The reason for the nega- tive association between sCD14 and BMI is unclear, though the inter-relationships between the CD14 system and obesity appear to be complex. sCD14 can both potentiate and down- regulate responses to LPS. For example, adipose tissue CD14 gene expression is increased in obese humans,31 whereas mice harboring CD14 mutations have decreased body fat.31,32 In con- trast, administration of exogenous recombinant human sCD14 is associated with decreased visceral fat and adipocyte inflam- matory gene expression in high-fat-fed mice. Another pos- sible explanation for the paradoxical association with sCD14 observed in CHS is that lower BMI could constitute a marker for frailty and chronic disease in older adults. Therefore, addi- tional studies of sCD14 and BMI involving younger popula- tions and longitudinal data on BMI may be required.

Sources of Funding

Research reported in this article was supported by contracts HHSN268201200036C, N01-HC-85239, N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, and grants HL080295R01 and HL71862 from the National Heart, Lung, and Blood Institute, with addi- tional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided through AG-023629,

Previous studies of sCD14 and subclinical atherosclerosis have been inconsistent, though most have included primarily

AG-15928, AG-20098, and AG-027058 from the National Institute on Aging. A full list of principal Cardiovascular Health Study investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm.

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