Background-Pharmacogenetic-guided dosing of warfarin is a promising application of "personalized medicine" but has not been adequately tested in randomized trials. Methods and Results-Consenting patients (nϭ206) being initiated on warfarin were randomized to pharmacogeneticguided or standard dosing. Buccal swab DNA was genotyped for CYP2C9 *2 and CYP2C9 *3 and VKORC1 C1173T with a rapid assay. Standard dosing followed an empirical protocol, whereas pharmacogenetic-guided dosing followed a regression equation including the 3 genetic variants and age, sex, and weight.

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Background Vitamin D status has been linked to the risk of cardiovascular disease (CVD). However, the optimal 25hydroxy-vitamin D (25(OH)-vitamin D) levels for potential cardiovascular health benefits remain unclear. Methods and Results We searched MEDLINE and EMBASE from 1966 through February 2012 for prospective studies that assessed the association of 25(OH)-vitamin D concentrations with CVD risk. A total of 24 articles met our inclusion criteria, from which 19 independent studies with 6,123 CVD cases in 65,994 participants were included for a meta-analysis. Comparing the lowest to the highest 25(OH)-vitamin D categories, the pooled relative risks (RR) was 1.52 (95% CI: 1.30-1.77) for total CVD, 1.42 (95% CI: 1.19-1.71) for CVD mortality, 1.38 (95% CI: 1.21-1.57) for coronary heart disease, and 1.64 (95% CI: 1.27-2.10) for stroke. These associations remained strong and significant when analyses were limited to studies that excluded participants with baseline CVD and had better controlled for season and confounding. We used a fractional polynomial spline regression analysis to assess the linearity of dose-response association between continuous 25(OH)-vitamin D and CVD risk. The CVD risk increased monotonically across decreasing 25(OH)-vitamin D below approximately 60 nmol/L, with a RR of 1.03 (95% CI: 1.00-1.06) per 25 nmol/L decrement in 25(OH)-vitamin D. Conclusions This meta-analysis demonstrated a generally linear, inverse association between circulating 25(OH)-vitamin D in the range of 20-60 nmol/L and risk of CVD. Further research is needed to clarify the association of 25(OH)-vitamin D higher than 60 nmol/L with CVD risk and assess causality of the observed associations.