Endothelial dysfunction (ED) is a generalized disorder responsible for the reduction of nitric oxide (NO) bioavailability, which leads to the development of atherosclerotic cardiovascular diseases (CVD) directly, and through NO-soluble guanylate cyclase-protein kinase G (sGCPKG) signaling pathway, to impaired remodeling cardiomyocytes indirectly with left ventricular diastolic dysfunction (LVDD) as the earliest change. Lower extremity arterial disease (LEAD) is one of the atherosclerotic CVDs that can be suspected with the Ankle-Brachial Indeks (ABI), a technique that is relatively easy to perform in clinical practice. Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of NO synthase (NOS), an intracellular enzyme responsible for the production of NO, and one of the biomarkers of ED which can be measured from a plasma sample. A number of studies have reported ADMA as a novel risk marker of CVDs, increased levels of which have been shown to be the strongest risk predictor of CV events, all-cause and CV mortality. Although a specific ADMA-lowering agent has not yet been found, many drugs have been reported to lower ADMA levels in clinical studies by either increasing the activity/ expression of the enzyme responsible for ADMA degradation or by decreasing the expression of the enzyme responsible for the formation of ADMA in cells or via some other unknown method.  We conducted a cross-sectional study which included 165 subjects from general population in whom we observed the relationship between ADMA, incidence of LVDD and LEAD. Subjects with LVDD and LEAD had significantly lower plasma ADMA values compared to those without LVDD and LEAD. Using multivariate regression, we confirmed that variations of ADMA values in plasma were significantly influenced by the therapy that our subjects used. In this context, ADMA can serve as a good biomarker of treatment effectiveness.

Livija Susic is a doctor of medicine, cardiologist and the Head of the Department for Specialist-Council Health Care of the Osijek-Baranja County Health Center. Her speciality is echocardiography. She is also a postgraduate student at the post-graduate doctoral study of Biomedicine and Health Care at the Faculty of Medicine in Osijek and will soon defend her doctoral dissertation on the relationship between endothelial dysfunction and left ventricular diastolic dysfunction. She is a member of the Croatian Medical Chamber, the Croatian Medical Association, Croatian Society of Cardiology and the European Society of Cardiology. Since 2015, she has been regularly organizing courses in the basics of cardiopulmonary resuscitation and emergency situations intended for healthcare professionals of the Health Center of Osijek-Baranja County. She has more than 10 publications related to the field of cardiology.