One mechanism to regulate pathological vascular calcification (VC) is its active inhibition. Loss or inactivation of endogenic inhibitors is a major inductor of VC. Such inhibitors are proteins rich in gamma-glutamyl residues (Gla-proteins), whose function strongly depends on vitamin K. The current narrative review is focused on discussing the role of extrahepatic vitamin K-dependent Gla-proteins (osteocalcin, OC; matrix Gla-protein, MGP; Gla-rich protein, GRP) in cardio-vascular pathology. Gla-proteins possess several functionally active forms whose role in the pathogenesis of VC is still unclear. It is assumed that low circulating non-phosphorylated MGP is an indicator of active calcification and could be a novel biomarker of prevalent VC. High circulating completely inactive MGP is proposed as a novel risk factor for cardio-vascular events, disease progression, mortality, and vitamin K deficiency. The ratio between uncarboxylated (ucOC) and carboxylated (cOC) OC is considered as an indicator of vitamin K status indirectly reflecting arterial calcium. Despite the evidence that OC is an important energy metabolic regulator, its role on global cardio-vascular risk remains unclear. GRP acts as a molecular mediator between inflammation and calcification and may emerge as a novel biomarker playing a key role in these processes. Gla-proteins benefit clinical practice as inhibitors of VC, modifiable by dietary factors.

Introduction: Cardiac fibrosis is the hallmark of atrial remodeling in atrial fibrillation. Galectin-3 (Gal-3) is a biomarker of fibrosis. It is well studied in heart failure, but the data about its role in atrial fibrillation are sparse.Aim: The aim of the study was to evaluate the levels of Gal-3 in patients with atrial fibrillation after sinus rhythm restoration, to examine the association between this biomarker and other factors for developing atrial fibrillation and to assess its prognostic role.Materials and methods: We included 67 patients (35 male) at the mean age of 67.36±7.25 years, with Gal-3 test after sinus rhythm restoration, a subgroup of participants in placebo-controlled randomized clinical trial of treatment with spironolactone. They were followed up for atrial fibrillation recurrence and hospitalizations. The effect of demographic parameters and other factors on Gal-3 levels were evaluated before and one year after treatment.Results: Mean Gal-3 at baseline was 16.9±6.8 ng/ml. Higher levels of Gal-3 were associated with female gender (р=0.008), increasing age (р=0.005), renal dysfunction (p<0.0001) and gout (р=0.002). Higher thromboembolic risk as assessed by CHA2DS2-VASc score was significantly related to Gal-3. The levels of biomarker did not affect the number of atrial fibrillation recurrences (p=0.9) and hospitalizations. No correlation was found with treatment with spironolactone, antiarrhythmic and antihypertensive drugs.Conclusions: Higher Gal-3 in atrial fibrillation was associated with female sex, renal dysfunction, and history of gout. The levels of Gal-3 were not related to rhythm control. Treatment with spironolactone did not affect the biomarker of fibrosis Gal-3 in AF patients. Higher Gal-3 was related to high embolic risk.

Transthyretin cardiac amyloidosis is a restrictive cardiomyopathy ((ATTR-CM), caused by an extracellular deposition of insoluble amyloid fibrils in the myocardium. It is a life threatening disease with life expectancy of 2 to 6 years after diagnosis. There are two types – hereditary and wild type. Recent data reveal that the wild type ATTR-CM is a common cause of heart failure with preserved ejection fraction, especially in elderly men. Hereditary ATTR amyloidosis is not so rare in Bulgaria. Five different mutations have been diagnosed, the most common being p.Glu89Gln, identified in 62 unrelated families with 117 patients and 72 mutation carriers. ATTR-CM diagnosis is often delayed or even missed, however its early recognition has become very important as a new drug, which is a transthyretin stabilizer is now available and other drugs are under development. Updated knowledge about the clinical presentation, diagnostic algorithm, available and future therapeutic options for ATTR-CM are a prerequisite for an early identification, timely treatment and better prognosis of the affected patients. The diagnosis requires a multidisciplinary approach with the participation of experienced specialists, multimodality imaging, well equipped histopathological and genetic laboratories. Establishing centres of expertise could improve the management of the patients with ATTR-CM.

Objective: Atrial fibrillation is progressive disease with important health consequences, in which fibrosis is a key player. The aim of our study is to assess the effect of mineralcorticoid blockade on top of standard treatment in patients with atrial fibrillation after sinus rhythm restoration on the recurrence of the arrhythmia, hospitalizations and on the changes in levels of Galectin-3 as a marker of fibrosis. Methods: We prospectively studied 101 consecutive patients (56 females) at mean age 68.2 ± 7 with atrial fibrillation and sinus rhythm restoration, who were randomized on treatment with spironolactone on top of standard treatment or “usual care”. They were followed up for recurrences, hospitalization and death. The effect of spironolactone on safety was evaluated. Results: Recurrences of AF were detected in 64% of non-spironolactone group vs 57% in spironolactone group (p = 0.44). Spironolactone reduced the hospitalizations for AF, but it was not significant (p = 0.14). A Cox regression model showed only protective effect of spironolactone on AF hospitalizations, HR = 0.48, 95%CI = 0.2–1.15, р = 0.098. The same survival model for all-cause hospitalizations reached significance, with reduction of the events in the spironolactone group, HR- 0.44, 95% CI 0.2–0.94, р = 0.035. There was no difference regarding the composite endpoint (recurrences, all cause hospitalizations and death). Treatment with spironolactone did not influence the Gal-3 levels. Treatment with spironolactone has not influenced significantly the levels of serum potassium and creatinine. Conclusion: Treatment with spironolactone has protective effect regarding hospitalization for atrial fibrillation and significantly reduces all cause hospitalizations. It does not influence the biomarker of fibrosis Gal-3 after one-year treatment. The use of spironolactone in patients with AF is safe, but regular follow up is needed and recommended. Further studies are necessary, to clarify the potential of spironolactone to improve the AF prognosis.

Cardiovascular diseases are not only the leading causes of mortality in Bulgaria but also the mortality rate is twice as high as the European Union average, so screening programmes identifying subjects with elevated blood pressure (BP) are of utmost importance. May Measurement Month (MMM) is an annual global initiative of the International Society of hypertension that began in 2017 aimed at raising awareness of high BP. Bulgaria joined the 3rd campaign of MMM in 2019 and an overview of the results of Bulgarian participation are presented in this paper. Hypertension was defined as systolic BP ≥ 140 mm Hg and diastolic BP ≥ 90 mm Hg or treatment for hypertension, statistical analysis followed the standard MMM protocol. In Bulgaria, 150 screening points were set up in primary and secondary care facilities, in pharmacies, and outdoor spaces across 21 administrative districts. Out of 3678 individuals screened, 2587 participants (70.3%) had hypertension. Of 2896 participants with hypertension, 35.6% had controlled BP. Out of 1760 participants not on antihypertensive medication, 669 (38%) had elevated BP. In the case of treated individuals (n = 1918), 997 (52%) had uncontrolled hypertension. In the untreated cohort, every 4th subject had elevated BP, whilst among patients on antihypertensive medication, every second had uncontrolled BP, the worst results in terms of diagnosis and treatment are observed in men. By identifying almost two-third of the whole screened cohort with the possibility of newly diagnosed or uncontrolled hypertension, our results confirm the importance of BP screening campaigns.

Objectives: Matrix Gla protein (MGP) is a calcification inhibitor that plays a role in preventing soft tissue calcification and local mineralization of the vascular wall. The present study aimed to assess the expression of MGP in Peripheral Blood Mononuclear Cells (PBMC) in adult patients with CVD pathologies and its association with the presence and severity of coronary artery calcium score (CACS) and conventional CVD risk factors. Methods: MGP expression was measured in 87 individuals using real time qPCR. Subgrouping was performed according etiologic and metabolic CVD risk factors. Results: A clear trend for a decreased MGP expression was observed in all subgroups with high CVD risk. This decrease was significant in abdominally obese hypertensive individuals and in those with dyslipidemia. MGP expression was significantly lower in patients representing high Total cholesterol and LDL cholesterol levels. A positive correlation between MGP expression and smoking status in patients with coronary calcium and in the CVD group was established. Atrial hypertension duration correlated negatively with MGP expression in the group without coronary calcium deposits. Conclusions: The current study supports the hypothesis that MGP expression in PBMC probably reflects CVD pathology and is related to lipid metabolism dysregulation.