Vitamin K2 and D in Patients With Aortic Valve Calcification: A Randomized Double-Blinded Clinical Trial.

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. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03243890.

Diagnostic and prognostic value of a careful symptom evaluation and high sensitive troponin in patients with suspected stable angina pectoris without prior cardiovascular disease.

BACKGROUND AND AIMS: Typical angina pectoris (AP) and high-sensitive troponin I (hs-TnI) are independently associated with coronary artery disease (CAD) and future cardiovascular events (CVE). This study aimed to assess the individual and combined diagnostic and prognostic impact of symptoms and hs-TnI in stable chest pain patients without prior cardiovascular disease. METHODS: During a one-year period, 487 patients with suspected stable AP underwent invasive or CT-coronary angiography (significant stenosis ≥50%). At study inclusion, a careful symptom evaluation was obtained, and patients were classified as having typical AP, atypical AP, or non-cardiac chest pain. Hs-TnI was measured in all patients and divided into tertiles for analysis. Follow-up was a median of 4.9 years with cardiovascular death, non-fatal myocardial infarction, unstable AP, ischemic stroke, coronary-artery-bypass-grafting, percutaneous coronary intervention, and peripheral vascular surgery as combined endpoint. RESULTS: Hs-TnI was detected in 486 patients (99.8%). By multivariate regression analysis, typical AP and hs-TnI elevation were associated with increased risk of having significant CAD (typical AP, OR: 3.46; 95% CI: 2.07-5.79; p < 0.0001, hs-TnI, OR: 1.50; 95% CI: 1.12-2.01; p = 0.007) and experiencing future CVE (typical AP, HR: 2.64; 95% CI: 1.74-3.99; p = 0.001, hs-TnI, HR: 1.26; 95% CI: 1.06-1.49; p = 0.008). Patients in the lowest hs-TnI tertile, without typical AP (n = 107) had a 1.9% absolute risk of significant CAD and a 3.7% absolute risk of long-term CVE. CONCLUSIONS: In clinical stable patients without known cardiovascular disease, a thorough chest-pain history in combination with hs-TnI testing can identify a significant low-risk group. The prognostic need for coronary angiography in these patients seems limited.

Coronary computed tomography angiography - tolerability of ß-blockers and contrast media, and temporal changes in radiation dose.

OBJECTIVE: To determine the risk in administering ß-blockers, contrast-induced nephropathy (CIN) and the trend in X-ray use, during coronary computed tomography angiography (CCTA). METHODS: A total of 416 patients were referred for elective CCTA. To achieve a resting heart rate below 60 beats per minute, oral and/or intravenous ß-blockers were administered. Using questionnaires, information on the adverse effects of ß-blockers was collected from the patients. The levels of s-creatinine and estimated GFR (eGFR) were measured before and after contrast enhanced CCTA. Radiation exposure was compared with the exposure 3 years earlier. RESULTS: There was no significant difference in the symptoms (dizziness, lipothymia and palpitations) between patients with and patients without ß-blocker pretreatment. Compared to baseline values, the decrease in s-creatinine was not significant (75.2 vs. 74.6 µmol/L, p = 0.09), while the increase in eGFR was not significant (78 vs. 79 mL/min, p = 0.17). Also, subgroups of patients with hypertension, hypercholesterolemia, diabetes or pre-existing slight impairment in renal function did not develop CIN. The mean radiation exposure decreased from 17.5 to 6.7 mSv, p < 0.0001. CONCLUSIONS: In terms of the side effects of ß-blockers and contrast media, there were no short term complications to CCTA. Furthermore, the radiation dose has been dramatically diminished over the last three years.

Lipocalin-type prostaglandin D synthase is not a biomarker of atherosclerotic manifestations.

OBJECTIVE: Over the last decades Lipocalin-type prostaglandin D synthase (L-PGDS), Osteoprotegerin (OPG), Osteopontin (OPN) and Pregnancy associated plasma protein A (PAPP-A) have been reported to be associated with coronary artery disease, and L-PGDS has been proposed as a potential new diagnostic tool in the setting of stable coronary artery disease. We set out to investigate if measurement of concentrations of these biomarkers could be used to differentiate between four groups of individuals with different atherosclerotic manifestations. METHODS: A total of 120 individuals from four equal gender- and age-matched groups were studied: (i) no previous cardiovascular disease (CVD) and no coronary calcifications [CAC-negative group], (ii) no previous CVD but evidence of severe coronary calcifications [CAC-positive group], (iii) acute coronary syndrome [ACS-group], and (iv) clinical stable patients with CVD, who were referred for cardiovascular surgery [CVD-group]. Concentrations of L-PGDS, OPG, OPN and PAPP-A were analyzed and compared between the four groups. RESULTS: We did not find any significant differences in L-PGDS concentrations between the four groups (p = 0.32). OPG concentrations differed significantly (p = 0.003), with the highest concentration observed in ACS patients. Considering OPN (p = 0.12) and PAPP-A (p = 0.53) their concentrations between groups did not differ significantly. CONCLUSION: The main message from this study is the observation that L-PGDS based on a single blood test appears to be less valuable than previously proposed in identification of patients with coronary artery disease. However, ACS patients have higher OPG concentrations than patients with different manifestations of stable atherosclerosis. Neither OPN nor PAPP-A concentrations differed between groups.