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 cm ² (95% CI, –0.09 to 0.12 cm ² ; 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 300 AU, 2 years MK-7 plus vitamin D supplementation did not influence AVC progression. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03243890.

Introduction Aortic stenosis is a common heart valve disease, and due to the growing elderly population, the prevalence is increasing. The disease is progressive with increasing calcification of the valve cusps. A few attempts with medical preventive treatment have failed; thus, presently, the only effective treatment of aortic stenosis is surgery. This study will examine the effect of menaquinone-7 (MK-7) supplementation on progression of aortic valve calcification (AVC). We hypothesise that MK-7 supplementation will slow down the calcification process. Methods and analysis In this multicenter and double-blinded, placebo-controlled study, 400 men aged 65–74 years with substantial AVC are randomised (1:1) to treatment with MK-7 (720 µg/day) supplemented by the recommended daily dose of vitamin D (25 µg/day) or placebo treatment (no active treatment) for 2 years. Exclusion criteria are treatment with vitamin K antagonist or coagulation disorders. To evaluate AVC score, a non-contrast CT scan is performed at baseline and repeated after 12 and 24 months of follow-up. Primary outcome is difference in AVC score from baseline to follow-up at 2 years. Intention-to-treat principle is used for all analyses. Ethics and dissemination There are no reported adverse effects associated with the use of MK-7. The protocol is approved by the Regional Scientific Ethical Committee for Southern Denmark (S-20170059) and the Data Protection Agency (17/19010). It is conducted in accordance with the Declaration of Helsinki. Positive as well as negative findings will be reported. Trial registration number NCT03243890.

Background: Pericoronary adipose tissue attenuation (PCATa), derived from coronary computed tomography angiography (CCTA), is a novel marker of inflammation in the coronary arteries. Patients with type 2 diabetes mellitus (T2DM) are at elevated risk of coronary artery disease (CAD), potentially due to systemic inflammation. This study evaluated whether baseline PCATa predicts changes in plaque composition and burden over 12 months. Methods: This prospective longitudinal study included 200 participants with T2DM, who had neither symptoms nor a prior diagnosis of CAD (mean age 61 ± 9.4 years, 72% male). PCATa was measured at the baseline scan along the proximal 40 mm of each major coronary artery, and the values were averaged to calculate the participant-level PCATa. High PCATa levels were determined using the validated cut-off of -70.1 Hounsfield units. Compositional plaque changes were quantified as the differences between baseline and 12-month scans, and plaque burden was calculated as the normalized atheroma volume. Multivariable regression analyses assessed the associations between baseline PCATa and compositional plaque changes and evaluated risk factors, including high PCATa, in predicting non-calcified plaque burden progression. Results: Plaque compositional volumes and burden increased over 12 months, while PCATa remained stable. After multivariable adjustments, baseline PCATa was significantly associated with changes in total plaque volume (β = 0.005, p = 0.005), non-calcified plaque volume (β = 0.006, p = 0.007), total plaque burden (β = 1.7, p = 0.007), and non-calcified plaque burden (β = 2.0, p = 0.006), but not with calcified plaque volume or burden. High baseline PCATa was observed in 44 participants (22%) and was the only independent predictor of non-calcified plaque burden progression (odds ratio 3.5, p = 0.002). Conclusions: Baseline PCATa is significantly associated with increases in total and non-calcified plaque volumes and burden over 12 months in participants with T2DM without symptoms or known CAD. High PCATa levels uniquely predict non-calcified plaque burden progression, suggesting that PCATa may serve as a marker for subclinical atherosclerosis progression. This warrants further investigation into PCATa for cardiovascular risk assessment, particularly in high-risk populations such as individuals with T2DM. Trial registration: Trial registration: NCT06644651. Graphical PCATa = Pericoronary Adipose Tissue attenuation. T2DM = Type 2 diabetes mellitus. CAD = Coronary Artery Disease. N = numbers. CCTA = Coronary CT angiography. Created in BioRender. Research insights: What is currently known about this topic? Type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) share inflammatory mechanisms. Individuals with T2DM face a two- to four-fold increased risk of CAD compared with those without T2DM. Pericoronary adipose tissue attenuation (PCATa) is a novel marker of coronary inflammation. What is the key research question? Can baseline PCATa predict compositional plaque changes over 12 months in T2DM without known CAD? What is new? Baseline PCATa relates to higher total and non-calcified plaque (NCP) volumes after adjustment. Baseline PCATa associates with increased total- and NCP burden after multivariable adjustment. High baseline PCATa (> -70.1 HU) independently predicts NCP burden progression. How might this study influence clinical practice? PCATa may be a marker for subclinical atherosclerosis progression.

Left ventricle mass (LVM) can be influenced by various conditions including hypertension and/or inherent cardiomyopathies. Dysglycemia is also thought to exert an anabolic effect on heart tissue by hyperinsulinemia and thereby promoting increased LVM. The primary aim of this study was to assess the influence of dysglycemia on LVM evaluated by an oral glucose tolerance test (OGTT) in patients admitted with a first myocardial infarction (MI) without hypertension. The secondary aim was to assess the impact of dysglycemia on major adverse cardiovascular events (MACE) and all-cause mortality during long-term follow-up. Patients admitted with a first MI without known history of hypertension were included. All patients without previously known type 2 diabetes mellitus (T2DM) had a standardized 2-hour OGTT performed and were categorized as: normal glucose tolerance (NGT), impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) and newly detected T2DM (new T2DM). LVM was measured by echocardiography using Devereaux formula and indexed by body surface area. Multivariate linear regression analysis was used to assess the impact of confounders (dysglycemia by OGTT, known T2DM, age, sex and type of MI) on LVM. Cox proportional hazard model was used to assess the impact of dysglycemia on all-cause mortality and a composite endpoint of MACE (all-cause mortality, MI, revascularisation due to stable angina, coronary artery bypass graft, ischemic stroke or hemorrhagic stroke). Two-hundred-and-five patients were included and followed up to 14 years. In multivariate regression analysis, LVM was only significantly increased in patients categorized as new T2DM (β = 25.3; 95% CI [7.5–43.0]) and known T2DM (β = 37.3; 95% CI [10.0-64.5]) compared to patients with NGT. Patients with new T2DM showed higher rates of MACE and all-cause mortality compared to patients with IFG/IGT and NGT; however no significantly increased hazard ratio was detected. Dysglycemia is associated with increasing LVM in normotensive patients with a first acute myocardial infarction and the strongest association was observed in patients with new T2DM and patients with known T2DM. Dysglycemia in normotensive patients with a first MI is not an independent predictor of neither MACE nor all-cause mortality during long-term follow-up compared to normotensive patients without dysglycemia.