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Background
Cardiovascular diseases are more prevalent in patients with chronic obstructive pulmonary disease (COPD) compared to age- and smoking-matched controls with no lung disease [1]. Vascular calcification is a major risk factor for cardiovascular morbidity and mortality. COPD patients have on average more extensive coronary artery calcification (CAC) than controls [2]. Furthermore, the burden of emphysema is related to the thoracic aortic calcification score [3]. The frequency of cardiac arrhythmias is also high in patients with COPD [1], and an inverse association has been identified between forced expiratory volume in one second and incident atrial fibrillation [4]. Atrial fibrillation and pulmonary embolism may be both cause and consequence of acute COPD exacerbations, and often necessitate prolonged anticoagulation therapy [5, 6].
Although the use of direct oral anticoagulants (DOACs) is rising, vitamin K antagonists (VKAs) are still widely used as anticoagulant drugs. VKAs inhibit vitamin K recycling thereby inducing functional vitamin K deficiency [7, 8]. Vitamin K is generally known as an activator of coagulation proteins in the liver and therefore often incorrectly regarded as a mono-functional cofactor [9]. It is much less acknowledged that vitamin K is also essential in the activation of extrahepatic key-proteins [9]. Matrix Gla protein (MGP) is vitamin K-dependent and a potent inhibitor of soft tissue calcification [10]. Furthermore, evidence suggests a potential role for MGP in the protection of extracellular matrix proteins from enzymatic degradation [11]. MGP knock-out mice die within two months after birth due to vascular calcifications leading to large blood vessel rupture, illustrating the importance of MGP [10]. Although research has mainly focused on its protective effects against arterial pathologies [12], MGP is also extensively expressed in the lungs [13].
Vitamin K status
Vitamin K cannot be produced endogenously and is exclusively obtained exogenously. Different forms of vitamin K can be discerned, including naturally occurring vitamins K1 and K2 [14]. Vitamin K2 usually comprises not more than about one-tenth of total vitamin K consumption, but it holds a much larger share in the activation of vitamin K-dependent proteins as vitamin K2 has higher bioavailability and longer half-life time than K1 [14]. Although there is no absolute tissue specificity, vitamin K1 is preferentially used in the liver to activate coagulation factors, whereas vitamin K2 has a more prominent...