Association of C-reactive protein and homocysteine with subclinical coronary plaque subtype and stenosis using low-dose MDCT coronary angiography.

OBJECTIVES: Given the uncertainty regarding the relationship of C-reactive protein (CRP) and homocysteine (Hcy) to atherosclerotic burden, our aim was to determine whether CRP and Hcy are related to the presence of subclinical coronary plaque and stenosis. METHODS: We did a cross-sectional analysis of data gathered on 1248 consecutive, newly self-referred, middle-aged subjects who underwent health check ups at China Medical University Hospital. Participants had at least one cardiac risk factor, but no known coronary heart disease. Low-dose multidetector computed tomography coronary angiography (MDCT-CA) was used to measure coronary artery stenosis and identify plaque subtypes. RESULTS: Subjects were divided into quartiles based on levels of high-sensitivity (hs)-CRP and Hcy. hs-CRP level and Hcy level were associated with the relative proportion of plaque subtypes; Hcy level (P<0.05) but not hs-CRP level (P>0.05) was associated with prevalence of artery segment stenosis. After multivariate adjustment for traditional cardiovascular risk factors through logistic regression analysis, neither hs-CRP level nor Hcy level was independently associated with coronary plaque subtypes and stenosis (P>0.05). CONCLUSIONS: Subclinical atherosclerosis is mildly increased in subjects with higher CRP and Hcy levels, but this association is not independent of traditional cardiovascular risk factors. CRP and Hcy are poor predictors of atherosclerotic burden and coronary stenosis.

Synthesis and biological evaluation of N-heterocyclic indolyl glyoxylamides as orally active anticancer agents.

A series of N-heterocyclic indolyl glyoxylamides were synthesized and evaluated for in vitro and in vivo anticancer activities. They exhibited a broad spectrum of anticancer activity not only in murine leukemic cancer cells but also in human gastric, breast, and uterus cancer cells as well as their multidrug resistant sublines with a wide range of IC(50) values. They also induced apoptosis and caused DNA fragmentation in human gastric cancer cells. Among the compounds studied, 7 showed the most potent activity of growth inhibition (IC(50) = 17-1711 nM) in several human cancer cells. Given orally, compounds 7 and 13 dose-dependently prolonged the survival of animals inoculated with P388 leukemic cancer cells. N-Heterocyclic indolyl glyoxylamides may be useful as orally active chemotherapeutic agents against cancer and refractory cancerous diseases of multidrug resistance phenotype.