Current Pharmaceutical Biotechnology - Volume 18, Issue 6, 2017

Background: Biomarkers are indispensable tools for screening, diagnosis, and prognosis in cardiovascular diseases and their clinical application increases steadily. As cardiovascular diseases include various pathophysiological processes, no single biomarker, even natriuretic peptides, can be regarded as ideal fulfilling all necessary criteria for a comprehensive diagnostic or prognostic assessment revealing optimal clinical application. Hence, multi-marker approaches using different biomarkers reflecting different pathophysiologies were highlighted recently. Advances in biomedical technologies expanded the spectrum of novel blood-derived biomarkers, such as micro-RNA (miRNA) or “omics”- data potentially providing a more advanced knowledge about pathogenesis of cardiovascular disease. Conclusion: This review describes the advantages and limitations of blood circulating biomarkers with regard to proteins, metabolomics and transcriptional level both within single as well as multi-marker strategies. Moreover, their usefulness is focused on clinical decision-making in cardiovascular diseases.

Background: Coronary Artery Disease (CAD) is the most common reason for death in the western hemisphere. Therefore, a well-functioning risk-management has been established over the past decades with uprising interest in ‘novel’ biomarkers to predict adverse coronary events and detect patients with subclinical CAD. This review will focus on selected biomarkers belonging to the family of inflammatory markers (fibrinogen or hs-CRP) or to the family of lipid-associated markers (Lipoprotein associated PA2 or Lipoprotein a) and organ-specific biomarkers (hs-troponin, Cystatin C or NTproBNP). Methods: This review is based on a pubmed search focusing on the biomarkers fibrinogen, hs-CRP, Lipoprotein associated PA2, Lipoprotein a, hs-troponin, NT-proBNP and Cystatin C. Results: The search retrieved 149 references containing meta-analysis, prospective and retrospective studies concerning the usage of the selected biomarkers in risk prediction and detection of CAD. Despite clinical studies, current guidelines of the European Society of Cardiology (ESC), the American Heart Association (AHA) and the Canadian Cardiovascular Society (CCS) were analyzed regarding their recommendation of the implementation of biomarkers in clinical routine. The review identified promising stand-alone biomarkers and multi-marker risk models for CAD patients. Conclusion: Novel biomarkers detect patients at risk beyond established risk scores. However, an ideal biomarker fulfilling all necessary criteria does still not exist.

Background: Cardiomyopathies are a major cause of heart diseases in all age groups leading to heart failure and arrhythmias. Additionally, they are an important cause of sudden cardiac death (SCD) in young people. Major advances have been made in the understanding of the complex and manifold underlying pathomechanisms and their correlating blood measured biomarkers. The aim of this review is to outline the role of such biomarkers in non-ischemic cardiomyopathies and their role in the prediction of SCD. Methods: A search in bibliographic databases was conducted. Most relevant references focusing on blood measured biomarkers in non-ischemic cardiomyopathies and biomarkers in SCD were reviewed regarding their role in pathophysiology and clinical practice. The references contain prospective and retrospective studies as well as meta-analyses. Current guidelines were analyzed concerning the implementation of biomarkers. Results: Most research on the role of biomarkers in cardiomyopathies is focused on myocardial stress (natriuretic peptides), injury (troponins), inflammation, and remodelling (fibrosis marker). Various studies suggest a potential application of biomarkers in diagnostics, prognosis and treatment response. Further approaches include microRNAs or multimarker approaches. Biomarkers to delineate patients being at risk for SCD have demonstrated predictive ability and could improve risk stratification strategies. Conclusion: To improve the prognosis of cardiomyopathies an early onset of treatment is needed. This necessitates further research and a better integration of biomarkers in the diagnostic work-up of cardiomyopathies. Identification of patients being at risk for SCD is mandatory, however, reliable data of biomarkers are still lacking.

Background: Acute Heart Failure (AHF), owing to the difficulties in diagnosis, prognostic stratification and patient-related management, is still associated with unusually high morbidity and mortality. The advent of novel biomarkers apart from natriuretic peptides involved in myocardial injury, neuro-hormonal activation, and ventricular remodeling augurs immense hope in redefining the biomarker-based approach towards AHF. Methods: A thorough review of the available literature including latest review articles from distinguished experts, textbook references and guidelines from leading cardiological societies worldwide as well as the latest trials, encompassing various biomarkers known in AHF was conducted. The most relevant ones were chosen as references for the current review article. Results: Biomarkers such as midregional proatrial natriuretic peptide, soluble ST2, highly-sensitive troponin, and midregional proadrenomedullin are some such examples that have passed various stages of substantiation while there is an array of potential biomarkers innascent stages like osteopontin, CTGF, GDF-15 and TGF beta-1 awaiting further reiteration. Not only the diagnosis of AHF itself but the evaluation of co-morbidities using markers like PCT, hematologic markers or acute kidney injury markers like NGAL present a new perspective to the management of AHF. Conclusion: This review article outlines the current status of the most relevant cardiac biomarkers related to AHF.

Background: Pulmonary Arterial Hypertension (PAH) is a chronic disease which may cause or result from multiple cardiopulmonary disorders. The disease has complex pathophysiological mechanisms and involves many systematic, cellular and molecular changes. Therefore, it is crucial to find out underlying mechanisms and detect biomarkers to achieve early and proper diagnosis, evaluating disease severity, for follow-up and monitor response to treatment. Many biomarkers for PAH have been investigated but yet no such biomarker has been found specific and easily accessible to use for the patients. This review aims to identify an expanding role of biomarkers in PAH. Method: We searched an expanding role of biomarkers such as asymmetric dimethylarginine (ADMA), von Willebrand factor (vWF) and endothelin for PAH in the literature. Results: Thirty-four actual papers were included in this review for searching an expanding role of biomarkers in the PAH. Conclusion: The search for a proper biomarker for PAH patients is an ongoing process. Currently we do not have a PAH-specific, easily accesible, low-priced biomarker for PAH patients. One of the reasons of that is that PAH has a complex etiology and the diesase eventually alters multiple systems. So far, only BNP/NT-proBNP has been mainly approved and widely used for risk assesment in patients with PAH. Ongoing studies, development in the technology and understanding the underlying mechanisms in the pathophysiology of PAH, will eventually lead us to find proper biomarker(s), for PAH, which will also improve patient outcomes and decrease treatment costs in PAH.

Background: Acute aortic syndromes, being mostly underdiagnosed due to unspecific symptoms, are associated with high morbidity and mortality. Diagnosis carried out by transesophageal echocardiography, computed tomography and magnetic resonance imaging. However, there are lots of biochemical assays being investigated, but none of them used reliably to identify acute aortic syndromes. Biomarkers could accelerate the diagnostic time with cost effective way and could get place in definitive diagnostic algorithm of acute aortic syndrome. This review aims to identify contribution and value of biomarkers in acute aortic syndromes. Methods: We searched the contribution and value of biomarkers such as D - Dimer, Smooth muscle myosin heavy chain (sm - MHC), Calponin, and Soluble elastin fragments (sELAF) in acute aortic syndromes at the literature. Results: Twenty two actual papers were included in this review for searching the contribution and value of biomarkers in the acute aortic syndromes. Conclusion: Biomarkers accelerate the diagnosis and direct patients to imaging modalities with a risk classification. Plenty of biomarkers have been investigated so far but none of them were used in clinical routine. Currently none of the biomarkers can reliably identify acute aortic syndromes. Each of them has some limitation in term of sensitivity or specificity. Although, there is no single biomarker that can be safely used but a combination of the assays may increase the sensitivities and specificities.

Background: Despite the extended laboratory and clinical study of sepsis, its diagnosis remains a clinical challenge. The initiation of sepsis activates many different biochemical and immunological pathways being expressed by alterations of various molecules in human tissues. The detection and measurement of the concentration of such molecules, known as biomarkers, may be a diagnostic tool of great significance for clinicians dealing with suspected sepsis. Additionally, biomarkers may predict patients ´ outcome and may play a role in monitoring response to therapy. Methods: Most relevant clinical and experimental biomarker studies on sepsis were retrieved and reviewed in this article. Results: Although many biomarkers were evaluated for the diagnosis and prognosis in sepsis, until now not one has been proven to be absolutely reliable in the clinical field. Currently C-reactive proteine (CPR) and procalcitonin (PCT) are used worldwide routinely, nevertheless their values may elevate in clinical settings without sepsis, while they often fail to provide reliable prediction of the patient outcome. Conclusion: This review outlines most relevant circulating biomarkers in sepsis.

Background: This study evaluates the association between high sensitivity troponin I (hsTnI) and T (hsTnT) in patients with suspected stable Coronary Artery Disease (CAD) undergoing Coronary Computed Tomography Angiography (CCTA). Methods: Patients undergoing CCTA were enrolled prospectively. CCTA was indicated in patients with angina and a low to intermediate pre-test probability for CAD during routine clinical care. Blood samples were taken at the time of CCTA to measure cardiac biomarkers. Results: A total of 99 patients were enrolled with 43% revealing no CAD, 30% with non-obstructive and 26% with obstructive CAD. Out of these, 61% had single-vessel and 39% had multi-vessel CAD. Both hsTnI and hsTnT levels increased significantly according to the presence and extent of CAD (p = 0.0001) and were able to discriminate the presence of both obstructive (AUC range: 0.775 - 0.785; p = 0.0001) and multi-vessel CAD (AUC range: 0.740 - 0.749; p = 0.01). In multivariate logistic regression models adjusted for cardiovascular risk factors and NT-proBNP, both hsTn were still associated significantly with obstructive CAD (range of odds ratios (OR): 8.3-32.3; p < 0.02). Discussion: This study shows that high sensitivity troponin I and T reflect the presence and extent of CAD being diagnosed by CCTA in patients with a low to intermediate pretest probability for CAD.

Purpose: The present study aimed to analyze the researches that are at the experimental phase concerning osteosarcoma treatment. The researches included drug delivery systems which allow controlled release and imbue small interfering-/micro- ribonucleic acid. Methods: Without any language preference, we searched US National Library of Medicine National Institutes of Health, Embase, OVID, Cochrane Library database of clinical trials from 1843 to May 25, 2016 and traced all the references of incorporated documents. The data were evaluated using descriptive statistics and the results are shown as frequency (%). Results: We haven't encountered any drug delivery system in which Small interfering ribonucleic acid/ micro ribonucleic acid oligonucleotides were embedded successfully against osteosarcoma. There has been only one research in which hairpin-ribonucleic acid was embedded. Conclusion: It was considered that drug delivery system enabling controlled oligonucleotide release in the treatment period of osteosarcoma was not projected for the clinical use. However, it cannot be neglected that the mentioned experimental studies with regard to osteosarcoma treatment establish the basis of target therapies. The method in question looks promising regarding effective treatment of osteosarcoma in the future.