Plasma levels of vitamin K and the risk of ischemic heart disease: a Mendelian randomization study

Abstract

Essentials Vitamin K plays a role in coagulation, and deficiency may promote coronary artery calcification. The role of vitamin K1 in heart disease was assessed using Mendelian randomization in Caucasians. Genetically higher vitamin K1 was associated with a higher risk of ischemic heart disease. Further research elucidating the role of vitamin K1 in ischemic heart disease could be useful. Background Vitamin K1 is a nutrient in green leafy vegetables; deficiency may promote coronary artery calcification. Warfarin, an anticoagulant used in secondary prevention of thrombotic events, is a vitamin K antagonist. Thrombotic and coronary events may share risk factors. Objectives To clarify the role of vitamin K1 in ischemic heart disease, the risk of coronary artery disease/myocardial infarction (CAD/MI) was assessed according to genetically determined vitamin K1 levels. Given vitamin K1 is fat soluble, associations with lipids were similarly assessed to assess pleotropic effects via lipids. Methods Separate sample instrumental variable analysis with genetic instruments (Mendelian randomization) was used to obtain an unconfounded estimate of the association of vitamin K1 (based on rs2108622 [CYP4F2], rs4645543 [KCNK9] and rs2192574 [CTNNA2] from a genome-wide association study) with CAD/MI using CARDIoGRAMplusC4D (cases = 64 374; controls = 130 681) and with lipids using Global Lipids Genetics Consortium Results (n = 196 475). Results Vitamin K1 single nucleotide polymorphisms were positively associated with CAD/MI (odds ratio [OR], 1.17 per unit [nmol L(-1) ] of natural log-transformed genetically predicted vitamin K1 ; 95% confidence interval [CI], 1.08-1.26), but not with inverse normal transformed low-density lipoprotein cholesterol (-0.0003; 95% CI, -0.03 to 0.03), high-density lipoprotein cholesterol (0.02; 95% CI, -0.01 to 0.05) or triglycerides (-0.01; 95% CI, -0.04 to 0.02). Considering only rs2108622, which is functionally relevant to vitamin K1 , the association for CAD/MI was stronger (OR, 1.21; 95% CI, 1.08-1.36). Conclusions Vitamin K may cause CAD/MI; whether vitamin K or other determinants of coagulation could be relevant to primary prevention might be worth considering.