Background: Menaquinone-7 (MK-7), also known as vitamin K2, is a cofactor for the carboxylation of proteins involved in the inhibition of arterial calcification and has been suggested to reduce the progression rate of aortic valve calcification (AVC) in patients with aortic stenosis. Methods: In a randomized, double-blind, multicenter trial, men from the community with an AVC score >300 arbitrary units (AU) on cardiac noncontrast computer tomography were randomized to daily treatment with tablet 720 μg MK-7 plus 25 μg vitamin D or matching placebo for 24 months. The primary outcome was the change in AVC score. Selected secondary outcomes included change in aortic valve area and peak aortic jet velocity on echocardiography, heart valve surgery, change in aortic and coronary artery calcification, and change in dp-ucMGP (dephosphorylated-undercarboxylated matrix Gla-protein). Safety outcomes included all-cause death and cardiovascular events. Results: From February 1, 2018, to March 21, 2019, 365 men were randomized. Mean age was 71.0 (±4.4) years. The mean (95% CI) increase in AVC score was 275 AU (95% CI, 225-326 AU) and 292 AU (95% CI, 246-338 AU) in the intervention and placebo groups, respectively. The mean difference on AVC progression was 17 AU (95% CI, -86 to 53 AU; P=0.64). The mean change in aortic valve area was 0.02 cm2 (95% CI, -0.09 to 0.12 cm2; P=0.78) and in peak aortic jet velocity was 0.04 m/s (95% CI, -0.11 to 0.02 m/s; P=0.21). The progression in aortic and coronary artery calcification score was not significantly different between patients treated with MK-7 plus vitamin D and patients receiving placebo. There was no difference in the rate of heart valve surgery (1 versus 2 patients; P=0.99), all-cause death (1 versus 4 patients; P=0.37), or cardiovascular events (10 versus 10 patients; P=0.99). Compared with patients in the placebo arm, a significant reduction in dp-ucMGP was observed with MK-7 plus vitamin D (-212 pmol/L versus 45 pmol/L; P<0.001). Conclusions: In elderly men with an AVC score >300 AU, 2 years MK-7 plus vitamin D supplementation did not influence AVC progression.

Background and aims Vitamin K antagonists (VKA) remain the most frequently prescribed oral anticoagulants worldwide despite the introduction of non-vitamin K antagonist oral anticoagulants (NOAC). VKA interfere with the regeneration of Vitamin K1 and K2, essential to the activation of coagulation factors and activation of matrix-Gla protein, a strong inhibitor of arterial calcifications. This study aimed to clarify whether VKA treatment was associated with the extent of coronary artery calcification (CAC) in a population with no prior cardiovascular disease (CVD). Methods We collected data on cardiovascular risk factors and CAC scores from cardiac CT scans performed as part of clinical examinations (n = 9,672) or research studies (n = 14,166) in the period 2007–2017. Data on use of anticoagulation were obtained from the Danish National Health Service Prescription Database. The association between duration of anticoagulation and categorized CAC score (0, 1–99, 100–399, ≥400) was investigated by ordered logistic regression adjusting for covariates. Results The final study population consisted of 17,254 participants with no prior CVD, of whom 1,748 and 1,144 had been treated with VKA or NOAC, respectively. A longer duration of VKA treatment was associated with higher CAC categories. For each year of VKA treatment, the odds of being in a higher CAC category increased (odds ratio (OR) = 1.032, 95%CI 1.009–1.057). In contrast, NOAC treatment duration was not associated with CAC category (OR = 1.002, 95%CI 0.935–1.074). There was no significant interaction between VKA treatment duration and age on CAC category. Conclusions Adjusted for cardiovascular risk factors, VKA treatment–contrary to NOAC—was associated to higher CAC category.

Aims  Vitamin K antagonists (VKAs) are suspected of causing aortic valve calcification (AVC). The objective of this study was to clarify whether patients undergoing VKA treatment have increased AVC scores compared to patients treated with new oral anticoagulants (NOACs) and patients who never have been treated with VKA/NOAC. Methods and results  We included participants from the population-based DANCAVAS trial (n = 15 048). Information on confounders was collected, and the AVC scores were measured on non-contrast computed tomography scans. The participants’ medication data, including VKA and NOAC data, were collected from the Danish National Health Service Prescription Database. The final population consisted of 14 604 participants (67.4 years, 95% men) of whom 873 had been treated with VKA and 602 with NOAC. The association between AVC score and duration of anticoagulant use was investigated in an adjusted zero-inflated negative binomial regression model. For every year treated with VKA, the AVC score increased, on average, by 6% [ratio of expected counts (RECs) = 1.06; 95% confidence interval (CI) 1.02–1.10] compared to non-use. The results were consistent in sensitivity analyses excluding patients with known cardiovascular disease and statin users (REC = 1.07; 95% CI 1.02–1.11 and REC = 1.10; 95% CI 1.03–1.17, respectively). NOAC treatment was not significantly associated with AVC score in any of the corresponding models (REC = 1.03, 1.02, and 0.96). Conclusion  Compared to no treatment with anticoagulants, VKA use was associated with increased AVC score, while a similar association could not be established for NOAC.

Background Coronary artery calcification (CAC) and especially progression in CAC is a strong predictor of acute myocardial infarction (AMI) and cardiovascular mortality [1]. Observational studies suggest a protective role of vitamin K2 in the development of CAC [2]. Measurement of CAC score in Agatston Units (AU) is common practice, while novel software as AutoPlaque introduces new opportunities to measure coronary plaques [3]. Purpose The aim of this double-blinded randomized multicenter trial is to investigate if vitamin K2 supplementation can reduce the progression of CAC in a population without known coronary disease. Methods AVADEC is a multicenter trial investigating 389 participants randomized to vitamin K2 (720 μg/day) and vitamin D (25 μg/day) versus placebo with a 2-year follow-up from 2018–2019 [4]. The primary endpoint of AVADEC is change in aortic valve calcification. In this substudy, we examined the progression of CAC in participants with no prior coronary disease (no myocardial infarction and/or revascularization) at baseline. Secondary, the change in CAC was evaluated in two prespecified subgroups (low-risk: CAC score &lt;400 AU and high-risk: CAC ≥400 AU at baseline). Non-contrast CT-scans were performed at baseline, 12 and 24 months of follow-up. Contrast CT-scans were performed at baseline and 24 months. CAC score was measured with established software and expressed in Agatston Units (AU). On contrast CT-scans, quantitative coronary plaque composition evaluations were performed by using Autoplaque. Moreover, events (AMI, revascularization and all cause death) were assessed. Results 304 participants (male, mean age 71 years) with no prior coronary disease were identified. The intervention and placebo groups were similar in all traditional cardiovascular risk factors except familial predisposition for cardiovascular disease (14.4% vs. 6.7%, p=0.046). We found progression of CAC in both the intervention and placebo group from baseline to 24 month follow-up (203 AU vs. 254 AU, p=0.089) (Figure 1). The patients with CAC score &lt;400 AU at baseline were equal in progression (77 AU vs. 81 AU, p=0.846). In patients with CAC score ≥400, the progression of CAC was significantly lower in the intervention group (288 AU vs. 380 AU, p=0.047). Yet, preliminary analyses of contrast CT-scans in 180 participants showed no difference in the progression of non-calcified plaque volume (10 mm3 vs. 37 mm3, p=0.276). In addition, the number of events was significantly lower in participants receiving vitamin K2 and D (1.9% vs. 6.7%, p=0.048). Conclusion Patients with no prior coronary disease randomized to vitamin K2 supplementation had a non-significant reduction in CAC development over a 2-year follow-up period. High-risk patients with CAC ≥400 AU had a significantly lower progression of CAC. Additionally, vitamin K2 supplementation significantly reduced the risk of AMI, revascularization and all-cause death. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Danish Cardiovascular Academy (2/3) and the Region of Southern Denmark (1/3).

BACKGROUND Due to its location very close to the bundle of His, mitral annulus calcification (MAC) might be associated with the development of atrioventricular (AV) conduction disturbances. This study assessed the association between MAC and AV conduction disturbances identified by cardiac implantable electronic device (CIED) use and electrocardiographic parameters. The association between MAC and traditional cardiovascular risk factors was also assessed. METHODS This cross-sectional study analyzed 14,771 participants, predominantly men aged 60–75 years, from the population-based Danish Cardiovascular Screening trial. Traditional cardiovascular risk factors were obtained. Using cardiac non-contrast computed tomography imaging, MAC scores were measured using the Agatston method and divided into absent versus present and score categories. CIED implantation data were obtained from the Danish Pacemaker and Implantable Cardioverter Defibrillator Register. A 12-lead electrocardiogram was available for 2,107 participants. Associations between MAC scores and AV conduction disturbances were assessed using multivariate regression analyses. RESULTS MAC was present in 22.4% of the study subjects. Participants with pacemakers for an AV conduction disturbance had significantly higher MAC scores (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.01–1.23) than participants without a CIED, whereas participants with a CIED for other reasons did not. Prolonged QRS-interval was significantly associated with the presence of MAC (OR, 1.45; 95% CI, 1.04–2.04), whereas prolonged PQ-interval was not. Female sex and most traditional cardiovascular risk factors were significantly associated with high MAC scores. CONCLUSIONS MAC was associated with AV conduction disturbances, which could improve our understanding of the development of AV conduction disturbances.