Intake of Vitamin K Antagonists and Worsening of Cardiac and Vascular Disease: Results From the Population-Based Gutenberg Health Study

TY - JOUR

T1 - Intake of Vitamin K Antagonists and Worsening of Cardiac and Vascular Disease: Results From the Population-Based Gutenberg Health Study

AU - Eggebrecht, Lisa

AU - Prochaska, Jürgen H

AU - Schulz, Andreas

AU - Arnold, Natalie

AU - Jünger, Claus

AU - Göbel, Sebastian

AU - Laubert-Reh, Dagmar

AU - Binder, Harald

AU - Beutel, Manfred E

AU - Pfeiffer, Nobert

AU - Blankenberg, Stefan

AU - Lackner, Karl J

AU - Spronk, Henri M

AU - Ten Cate, Hugo

AU - Münzel, Thomas

AU - Wild, Philipp S

PY - 2018/9/4

Y1 - 2018/9/4

N2 - Background Preclinical data have indicated a link between use of vitamin K antagonists ( VKA ) and detrimental effects on vascular structure and function. The objective of the present study was to determine the relationship between VKA intake and different phenotypes of subclinical cardiovascular disease in the population. Methods and Results Clinical and laboratory data, as well as medical-technical examinations were assessed from 15 010 individuals aged 35 to 74 years during a highly standardized 5-hour visit at the study center of the population-based Gutenberg Health Study. In total, the study sample comprised 287 VKA users and 14 564 VKA nonusers. Multivariable analysis revealed an independent association between VKA intake and stiffness index (β=+2.54 m/s; [0.41/4.66]; P=0.019), ankle-brachial index (β=-0.03; [-0.04/-0.01]; P<0.0001), intima-media thickness (β=+0.03 mm [0.01/0.05]; P=0.0098), left ventricular ejection fraction (β=-4.02% [-4.70/-3.33]; P<0.0001), E/E' (β=+0.04 [0.01/0.08]; P=0.014) left ventricular mass (β=+5.34 g/m2.7 [4.26/6.44]; P<0.0001), and humoral markers of cardiac function and inflammation (midregional pro-atrial natriuretic peptide: β=+0.58 pmol/L [0.50/0.65]; P<0.0001; midregional pro-adrenomedullin: β=+0.18 nmol/L [0.14/0.22]; P<0.0001; N-terminal pro B-type natriuretic peptide: β=+1.90 pg/mL [1.63/2.17]; P<0.0001; fibrinogen: β=+143 mg/dL [132/153]; P<0.0001; C-reactive protein: β=+0.31 mg/L [0.20/0.43]; P<0.0001). Sensitivity analysis in the subsample of participants with atrial fibrillation stratified by intake of VKA demonstrated consistent and robust results. Genetic variants in CYP 2C9, CYP 4F2, and VKORC 1 were modulating effects of VKA on subclinical markers of cardiovascular disease. Conclusions These data demonstrate negative effects of VKA on vascular and cardiac phenotypes of subclinical cardiovascular disease, indicating a possible influence on long-term disease development. These findings may be clinically relevant for the provision of individually tailored antithrombotic therapy.

AB - Background Preclinical data have indicated a link between use of vitamin K antagonists ( VKA ) and detrimental effects on vascular structure and function. The objective of the present study was to determine the relationship between VKA intake and different phenotypes of subclinical cardiovascular disease in the population. Methods and Results Clinical and laboratory data, as well as medical-technical examinations were assessed from 15 010 individuals aged 35 to 74 years during a highly standardized 5-hour visit at the study center of the population-based Gutenberg Health Study. In total, the study sample comprised 287 VKA users and 14 564 VKA nonusers. Multivariable analysis revealed an independent association between VKA intake and stiffness index (β=+2.54 m/s; [0.41/4.66]; P=0.019), ankle-brachial index (β=-0.03; [-0.04/-0.01]; P<0.0001), intima-media thickness (β=+0.03 mm [0.01/0.05]; P=0.0098), left ventricular ejection fraction (β=-4.02% [-4.70/-3.33]; P<0.0001), E/E' (β=+0.04 [0.01/0.08]; P=0.014) left ventricular mass (β=+5.34 g/m2.7 [4.26/6.44]; P<0.0001), and humoral markers of cardiac function and inflammation (midregional pro-atrial natriuretic peptide: β=+0.58 pmol/L [0.50/0.65]; P<0.0001; midregional pro-adrenomedullin: β=+0.18 nmol/L [0.14/0.22]; P<0.0001; N-terminal pro B-type natriuretic peptide: β=+1.90 pg/mL [1.63/2.17]; P<0.0001; fibrinogen: β=+143 mg/dL [132/153]; P<0.0001; C-reactive protein: β=+0.31 mg/L [0.20/0.43]; P<0.0001). Sensitivity analysis in the subsample of participants with atrial fibrillation stratified by intake of VKA demonstrated consistent and robust results. Genetic variants in CYP 2C9, CYP 4F2, and VKORC 1 were modulating effects of VKA on subclinical markers of cardiovascular disease. Conclusions These data demonstrate negative effects of VKA on vascular and cardiac phenotypes of subclinical cardiovascular disease, indicating a possible influence on long-term disease development. These findings may be clinically relevant for the provision of individually tailored antithrombotic therapy.

KW - Adrenomedullin/blood

KW - Adult

KW - Aged

KW - Ankle Brachial Index

KW - Anticoagulants/therapeutic use

KW - Asymptomatic Diseases

KW - Atrial Fibrillation/complications

KW - Atrial Natriuretic Factor/blood

KW - C-Reactive Protein/metabolism

KW - Cardiovascular Diseases/diagnostic imaging

KW - Carotid Intima-Media Thickness

KW - Female

KW - Fibrinogen/metabolism

KW - Germany

KW - Humans

KW - Male

KW - Middle Aged

KW - Natriuretic Peptide, Brain/blood

KW - Peptide Fragments/blood

KW - Phenprocoumon/therapeutic use

KW - Protein Precursors/blood

KW - Pulmonary Embolism/drug therapy

KW - Risk Factors

KW - Stroke/etiology

KW - Stroke Volume

KW - Vascular Stiffness

KW - Venous Thrombosis/drug therapy

KW - Warfarin/therapeutic use

U2 - 10.1161/JAHA.118.008650

DO - 10.1161/JAHA.118.008650

M3 - SCORING: Journal article

C2 - 30371151

VL - 7

SP - e008650

JO - J AM HEART ASSOC

JF - J AM HEART ASSOC

SN - 2047-9980

IS - 17

ER -