Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Abstract Only
Publication Acceptance Date: 4/1/2017
Publication Date: 4/1/2017
Citation: Kelly, J.M., Harshman, S.G., Brensinger, C., Barger, K., Kimmel, S., Booth, S.L. 2017. A race-specific interaction between vitamin K status and statin use during warfarin therapy initiation [abstract]. Federation of American Societies for Experimental Biology Conference. 31(1):445.6. Interpretive Summary:
Technical Abstract: Vitamin K (VK) is required for the post-translational modification of several clotting factors. Warfarin is a vitamin K antagonist and anticoagulant. The most common dietary and circulating form of VK is phylloquinone (PK). PK is lipid soluble, carried by triglyceride-rich lipoproteins, and shares a metabolic pathway with cholesterol. Thus, there is biological plausibility for an interaction between serum PK and lipid-lowering medications (statins) in warfarin therapy. The objective of this study was to examine if serum PK and/or statin treatment was associated with anticoagulation control in African Americans and Caucasians initiating warfarin therapy. Warfarin sensitivity differs between African Americans and Caucasians, so analyses were race-specific. Cox proportional hazards and linear regression models were used in a cross-sectional analysis of the 2009-2013 International Normalized Ratio Adherence and Genetics II cohort of African Americans (n=331; 40% female) and Caucasians (n=140; 36% female) initiating warfarin therapy. Primary exposures included serum PK (categorized as quartiles 1: PK<0.6, 2: 0.6</=PK</=1.0, 3: 1.0<PK</=1.7, 4: PK>1.7nmol/L) and statin use. Outcomes included number of days to maintenance dose and percent time in the therapeutic range (PTTR). Covariates included age, sex, smoking status, serum triglycerides, BMI, and clinic site. A significant interaction between serum PK quartile and statin use with respect to days to maintenance was detected in Caucasians (p=0.04), but not African Americans (p=0.81). In Caucasians taking statins (n=60), the rate to reach maintenance was 88% (HR=0.12, 95% CI 0.04-0.39) and 81% (HR=0.19, 5% CI 0.06-0.53) slower for those in the second and third serum PK quartiles, respectively, compared to those in the lowest quartile. The rate to reach maintenance did not differ between the highest and lowest serum PK quartiles (HR=0.84, 95% CI 0.26-2.70) or between any quartiles among Caucasians not taking statins (n=80, p=0.67). In African Americans, serum PK was not associated with the rate to reach maintenance whether they used statins (n=140, p=0.98) or not (n=191, p=0.23). Serum PK and statin use were not associated significantly with PTTR in either race. Statin use appears to slow the rate to establish maintenance warfarin dose among Caucasians with moderate serum PK. This apparent drug-drug-nutrient interaction suggests PK status and lipid-lowering medication may influence anticoagulation for Caucasians during warfarin therapy initiation. The role of vitamin K with statin use in anticoagulation therapy in different races requires further examination.