Vitamin K Status, Warfarin Use, and Arterial Stiffness in Heart Failure (Hashmath Z et al.)

The results of an important US-based observational study assessing the relationship between warfarin use, dephospho-uncarboxylated MGP (dp-ucMGP) levels, and arterial stiffness in heart failure (HF) have recently been described in Hypertension.

Large artery stiffening contributes to the pathophysiology of HF and associated comorbidities. Matrix Gla-protein (MGP), whose activation is vitamin K-dependent, is a potent inhibitor of vascular calcification. For the purpose of the study the researchers enrolled 348 subjects, including 96 with HF with preserved ejection fraction (HFpEF), 53 with HF with reduced ejection fraction (HFrEF), and 199 without HF. In order to estimate the progression of large artery stiffening among these participants, they measured their carotid-femoral pulse wave velocity using arterial tonometry. Dp-ucMGP was measured with ELISA. Dp-ucMGP levels were greater in both HFrEF (582 pmol/L; 95% CI, 444-721 pmol/L) and HFpEF (549 pmol/L; 95% CI, 455-643 pmol/L) compared with controls (426 pmol/L; 95% CI, 377-475 pmol/L; ANCOVA P=0.0067). Levels of dp-ucMGP were positively associated with carotid-femoral pulse wave velocity (standardized β, 0.31; 95% CI, 0.19-0.42; P<0.0001), which was also true in analyses restricted to patients with HF (standardized β, 0.34; 95% CI, 0.16-0.52; P=0.0002). Warfarin use was significantly associated with carotid-femoral pulse wave velocity (standardized β, 0.13; 95% CI, 0.004-0.26; P=0.043), but this relationship was eliminated after adjustment for dp-ucMGP.

According to the authors, the results of this study showing that the increased levels of dp-ucMGP in HFpEF and HFrEF are independently associated with arterial stiffness evoke the need for future investigations into therapeutic potential of vitamin K supplementation to prevent or reduce large artery stiffening in HFpEF and HFrEF.

“This study provides real insight into how we can better help patients with heart failure by correcting their vitamin K2 deficiency,” says Dr. Katarzyna Maresz, president of the International Science and Health Foundation. “Vitamin K2’s mechanism of inhibiting calcification might be particularly beneficial in reducing large artery stiffening, therefore its role as a cardiovascular support nutrient cannot be underestimated when dealing with  heart failure issues, and randomized controlled trials should be planned to evaluate this hypothesis,” Dr. Maresz emphasizes.


Hashmath Z, Lee J, Gaddam S, Ansari B, Oldland G, Javaid K, Mustafa A, Vasim I, Akers S, Chirinos JA (2019) Vitamin K Status, Warfarin Use, and Arterial Stiffness in Heart Failure, Hypertension 73(2): 364-370, doi: 10.1161/HYPERTENSIONAHA.118.12157


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