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Plasma levels of vitamin K and the risk of ischemic heart disease: a Mendelian randomization study.
J Thromb Haemost 2016; 14(6):1211-5JT

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.

SUMMARY

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.

Authors+Show Affiliations

CUNY Graduate School of Public Health and Health Policy, New York, NY, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27061505

Citation

Schooling, C M.. "Plasma Levels of Vitamin K and the Risk of Ischemic Heart Disease: a Mendelian Randomization Study." Journal of Thrombosis and Haemostasis : JTH, vol. 14, no. 6, 2016, pp. 1211-5.
Schooling CM. Plasma levels of vitamin K and the risk of ischemic heart disease: a Mendelian randomization study. J Thromb Haemost. 2016;14(6):1211-5.
Schooling, C. M. (2016). Plasma levels of vitamin K and the risk of ischemic heart disease: a Mendelian randomization study. Journal of Thrombosis and Haemostasis : JTH, 14(6), pp. 1211-5. doi:10.1111/jth.13332.
Schooling CM. Plasma Levels of Vitamin K and the Risk of Ischemic Heart Disease: a Mendelian Randomization Study. J Thromb Haemost. 2016;14(6):1211-5. PubMed PMID: 27061505.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Plasma levels of vitamin K and the risk of ischemic heart disease: a Mendelian randomization study. A1 - Schooling,C M, Y1 - 2016/05/06/ PY - 2015/10/20/received PY - 2016/4/11/entrez PY - 2016/4/12/pubmed PY - 2018/1/9/medline KW - Mendelian randomization analysis KW - heart diseases KW - lipids KW - vitamin K KW - warfarin SP - 1211 EP - 5 JF - Journal of thrombosis and haemostasis : JTH JO - J. Thromb. Haemost. VL - 14 IS - 6 N2 - UNLABELLED: 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. SUMMARY: 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. SN - 1538-7836 UR - https://www.unboundmedicine.com/medline/citation/27061505/Plasma_levels_of_vitamin_K_and_the_risk_of_ischemic_heart_disease:_a_Mendelian_randomization_study_ L2 - https://doi.org/10.1111/jth.13332 DB - PRIME DP - Unbound Medicine ER -