BackgroundVitamin K-antagonists (VKA) are treatment of choice and standard care for patients with venous thrombosis and thromboembolic risk. In experimental animal models as well as humans, VKA have been shown to promote medial elastocalcinosis. As vascular calcification is considered an independent risk factor for plaque instability, we here investigated the effect of VKA on coronary calcification in patients and on calcification of atherosclerotic plaques in the ApoE−/− model of atherosclerosis.Methodology/Principal FindingsA total of 266 patients (133 VKA users and 133 gender and Framingham Risk Score matched non-VKA users) underwent 64-slice MDCT to assess the degree of coronary artery disease (CAD). VKA-users developed significantly more calcified coronary plaques as compared to non-VKA users. ApoE−/− mice (10 weeks) received a Western type diet (WTD) for 12 weeks, after which mice were fed a WTD supplemented with vitamin K1 (VK1, 1.5 mg/g) or vitamin K1 and warfarin (VK1&W; 1.5 mg/g & 3.0 mg/g) for 1 or 4 weeks, after which mice were sacrificed. Warfarin significantly increased frequency and extent of vascular calcification. Also, plaque calcification comprised microcalcification of the intimal layer. Furthermore, warfarin treatment decreased plaque expression of calcification regulatory protein carboxylated matrix Gla-protein, increased apoptosis and, surprisingly outward plaque remodeling, without affecting overall plaque burden.Conclusions/SignificanceVKA use is associated with coronary artery plaque calcification in patients with suspected CAD and causes changes in plaque morphology with features of plaque vulnerability in ApoE−/− mice. Our findings underscore the need for alternative anticoagulants that do not interfere with the vitamin K cycle.

Objective-This study explored the relationship between coronary atherosclerotic plaque burden and quantifiable circulating levels of troponin measured with a recently introduced high sensitive cardiac troponin T (hs-cTnT) assay. Methods and Results-Cardiac patients suspected of having coronary artery disease (CAD) but without acute coronary syndrome were studied. Cardiac troponin T levels were assessed using the fifth-generation hs-cTnT assay. All patients (nϭ615) underwent cardiac computed tomographic angiography (CCTA). On the basis of CCTA, patients were classified as having no CAD or mild (Ͻ50% lesion), moderate (50% to 70% lesion), severe (Ͼ70% lesion), or multivessel CAD (multiple Ͼ70% lesions). As a comparison, high-sensitivity C-reactive protein levels were measured. Progressively increasing hs-cTnT levels were found in patients with mild (median, 4.5 ng/L), moderate (median, 5.5 ng/L), severe (median, 5.7 ng/L), and multivessel (median, 8.6 ng/L) CAD compared with patients without CAD (median, 3.7 ng/L) (all PϽ0.01). For high-sensitivity C-reactive protein and N-terminal pro-B-type natriuretic peptide, no such relationship was observed. In patients without CAD, 11% showed hs-cTnT levels in the highest quartile, compared with 62% in the multivessel disease group (PϽ0.05). Multivariance analysis identified hs-cTnT as an independent risk factor for the presence of CAD. Conclusion-In

Background: Although alcohol intake has been positively associated with breast cancer risk in epidemiologic studies, a causal relationship has not been established, and the mechanisms mediating this association are speculative. Alcohol may act through altered status of folate and vitamin B 12 , two vitamins required for DNA methylation and nucleotide synthesis, and thus cell integrity. Although the effects of heavy alcohol intake on folate and vitamin B 12 status have been well-documented, few studies have addressed the effects of moderate alcohol intake in a controlled setting. Objective: The objective of this study was to determine the effects of moderate alcohol intake on folate and vitamin B 12 status in healthy, well-nourished, postmenopausal women. Design: The study design was a randomized, diet-controlled crossover intervention. Postmenopausal women (n ¼ 53) received three 8-week alcohol treatments in random order: 0, 15, and 30 g/day. Treatment periods were preceded by 2-5-week washout periods. Blood collected at baseline and week 8 of each treatment period was analyzed for serum folate, vitamin B 12 , homocysteine (HCY), and methylmalonic acid (MMA) concentrations. Results: After adjusting for body mass index (BMI), a significant 5% decrease was observed in mean serum vitamin B 12 concentrations from 0 to 30 g of alcohol/day (461.45730.26 vs 440.25730.24 pg/ml; P ¼ 0.03). Mean serum HCY concentrations tended to increase by 3% from 0 to 30 g of alcohol/day (9.4470.37 vs 9.7370.37 mmol/l; P ¼ 0.05). Alcohol intake had no significant effects on serum folate or MMA concentrations. Conclusions: Among healthy, well-nourished, postmenopausal women, moderate alcohol intake may diminish vitamin B 12 status. Sponsorship: NCI, NIH and ARS, USDA.

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