Current Pharmaceutical Design - Volume 23, Issue 22, 2017

Background: Cardiovascular damage is clinically manifested as coronary artery disease, heart failure, stroke and peripheral artery disease. The prevalence of these adverse conditions is higher with advancing age. Although many patients present cardiovascular damage late in their life, it is common to see patients with early atherosclerosis in cardiovascular intensive care units at ages lower than 50 years in men and 55 for women. Methods and results: In this review of the literature we identified risk factors of early vascular damage. The classic risk factors such as age, gender, diabetes mellitus, dyslipidemia, smoking, alcohol, hypertension, obesity, family history and newer biomarkers such as hs-CRP, folic acid, homocysteine, fibrinogen are neither strong nor predictive of the individual patient's risk to present early cardiovascular disease. All these risk factors have been used to propose risk scores for possible future events but we still lack a single strong marker indicating new onset of disease that will predict the future independently of the classical factors. The role of vascular imaging techniques to identify patients with subclinical atherosclerotic vascular damage before clinical disease, including the effect of known and unknown risk factors on the vascular tree, seems to be very important for intensifying preventive measures in high risk patients. Early arteriosclerosis measured from pulse wave velocity is associated with reduced arterial elasticity and is associated with future cardiovascular events. Conclusions: Vascular measurements may better represent the continuum of cardiovascular disease from a young healthy to an aged diseased vessel that is going to produce adverse clinical events.

Background: Three types of necrosis characterize MI: coagulation necrosis, typically due to a coronarogenic mechanism, coagulative myocytolysis with formation of contract bands as an effect of sympathetic nervous system and adrenergic stimulation, and colliquative myocytolysis, characterized by myocardial fiber lysis, which is a close result of hydrolytic enzyme activity deriving from the material reaching the infarct area. Methods: Although a multifactorial etiology may be identified, nevertheless coronary alterations, which are a consequence of atherosclerotic plaque formation and complications with a reduced blood flow supply to the myocardium, are the benchmark of MI. Results: Evidence indicates a close relationship between the MI and some coronary risk factors, associated with this pathologic pattern with a different, but high rate. Conclusion: Precipitating events to cause acute myocardial pathology need, however, to develop an acute myocardial infarction.

Background: Change in the architecture and composition of cardiac extracellular matrix is a key element in adverse cardiac remodeling that occurs during heart failure. Most of the times, the result is the development of fibrosis, which has a huge impact on the pathophysiology and clinical outcomes of heart failure syndromes. Several molecules related to collagen metabolism detectable in the blood have been proposed as biomarkers of myocardial fibrosis. Despite concerns regarding the true ability of these biomarkers to reflect quantitative and qualitative changes in myocardial collagen, a growing body of evidence suggests that they may play a potential role in several aspects of heart failure management. Methods: This review aimed to summarize published data regarding the role of circulating biomarkers of collagen metabolism in the assessment of prognosis in patients with heart failure with reduced or mid-range LVEF ventricular ejection fraction (LVEF < 40% or LVEF 40-49%, respectively). Medline electronic database was searched to identify relevant studies published through October 2016. Results: Most evidence regarding the prognostic value of collagen biomarkers in HF with reduced or mid-range LVEF lies on data concerning PIIINP and several MMPs and TIMP-1. Several prospective studies found that higher levels of PIIINP, several MMPs and TIMP-1 are associated with higher rates of mortality and/or HF hospital admissions in HF patients with LVEF < 50%. Conclusion: Circulating collagen biomarkers have been shown to play a role in prognostic stratification in heart failure patients with reduced or mid-range ejection fraction.

Elevated homocysteine (Hcy) levels are predictors of cardiovascular disease (CVD). Hyperhomocysteinemia has also been associated with total and CVD mortality. However, whether Hcy is just a marker or plays a causal role in CVD remains to be elucidated. In this narrative review, we discuss the associations between Hcy and non-cardiac vascular diseases, namely stroke, peripheral artery disease (PAD), carotid artery disease, chronic kidney disease (CKD), atherosclerotic renal artery stenosis (ARAS), abdominal aortic aneurysm (AAA) and erectile dysfunction (ED). The effects of several drugs on Hcy levels are also considered. Folic acid, vitamin B6 and B12 supplementation can significantly decrease circulating Hcy concentrations but their effects on CVD risk reduction are conflicting. No current guidelines recommend the routine screening of Hcy levels in patients with non-cardiac vascular diseases. Therefore, further research is needed to elucidate the use of Hcy in the clinical practice.

Cardiovascular disease (CVD) continues to be the major cause of death in the developed countries. Moreover, the cardiovascular risk factors leading towards the development of CVD, mainly type 2 diabetes and obesity, are on the rise. The current preventive and therapeutic management, centred on the control of traditional risk factors, is clearly not enough to stop this pandemic. Therefore, the search for new biomarkers in CVD is a priority in most clinical research programs. Currently, interest in gut microbiota has peaked due to its association with cardiovascular and non-cardiovascular diseases. The present review considers the current situation regarding the influence of gut microbiota on CVD and particularly, its influence on the main traditional risk factors that lead to CVD, such as lipids, diabetes, hypertension and obesity.

Background: Environmental factors are a major cause of poor health worldwide. The most solid evidence is for air pollution, leading to increased disability-adjusted life years. Outdoor temperature and other seasonal climate changes may also influence cardiovascular health, according to their direct modulation of air pollution. Moreover, an increasing body of evidence associates environmental exposure to noise with poor cardiovascular outcome, and in particular with hypertension. Methods: This review is aimed at reviewing current evidence about the role of these environmental factors in cardiovascular disease and specifically hypertension. In particular, the impact of air pollution, with its short-term and long-term effects, the outdoor temperature and noise pollution will be investigated. Conclusions: People belonging to low social classes, as well as children, women, older people and those with established cardiovascular diseases, seem to have a greater susceptibility to the effects of environmental stressors, recalling the concept of “environmental justice”. The accumulating strong scientific evidence may thus support public health policies aimed at reducing social inequalities in cardiovascular health.

Background: Climate change is rapidly affecting all the regions of our planet. The most relevant example is global warming, which impacts on the earth’s ecosystems, threatening human health. Other effects include extreme variations in temperature and increases in air pollution. These events may negatively impact mortality and morbidity for cardiovascular diseases. Methods: In this review, we discuss the main effects of climate changes on cardiovascular diseases, reporting the epidemiological evidences and the biological mechanisms linking climate change consequences to hypertension, diabetes, ischemic heart diseases, heart failure and stroke. Results: Up to now, findings suggest that humans acclimate under different weather conditions, even though extreme temperatures and higher levels of air pollution can influence health-related outcomes. In these cases, climate change adversely affects cardiovascular system and the high-risk subjects for cardiovascular diseases are those more exposed. Conclusion: Finally, we examine climate change implications on publich health and suggest adaptation strategies to monitor the high-risk population, and reduce the amount of hospital admissions associated to these events. Such interventions may minimize the costs of public health and reduce the mortality for cardiovascular diseases.

Background: Blood flow assessment is essential to fully understand cardiovascular function in disease pathologies and for identification of individuals at long-term risk of cardiovascular disease development. Qualitative and quantitative assessments of blood flow by imaging modalities have been limited, and much of the accurate quantification has relied on invasive measures. Methods: This review discusses how four-dimensional velocity cardiovascular magnetic resonance (4D flow CMR) offers increasing potential for the non-invasive assessment of blood flow in the heart and major blood vessels such as the aorta. 4D flow CMR refers to phase contrast CMR with flow encoding in all three spatial directions that is resolved relative to all three dimensions of space and to the dimension of time throughout the cardiac cycle. Results: It has been demonstrated that 4D flow CMR can be used to assess parameters such as flow, pressure, velocity, wall shear stress and turbulent kinetic energy throughout the heart and major vessels of the cardiovascular system. It has been possible to gain new insights into cardiovascular pathologies such as, but not limited to, hypertrophic cardiomyopathy, dilated cardiomyopathy, Marfan syndrome and aortic bicuspid valve disease. Conclusion: Future work to standardize 4D flow CMR scan acquisition parameters is required. Furthermore, the development of automated analysis tools and standardized reporting of quantitative metrics are needed to increase capacity for larger studies and for translation to clinical practice. In doing so, the potential for 4D flow CMR to disentangle complex questions related to cardiovascular function will be maximized.

Background: Among the novelties in the field of cardiovascular imaging, the construction of quantitative maps in a fast and efficient way is one of the most interesting aspects of the clinical research. Quantitative parametric maps are typically obtained by post processing dynamic images, that is, sets of images usually acquired in different temporal intervals, where several images with different contrasts are obtained. Magnetic resonance imaging, and emission tomography (positron emission and single photon emission) are the imaging techniques best suited for the formation of quantitative maps. Methods: In this review article we present several methods that can be used for obtaining parametric maps, in a fast way, starting from the acquired raw data. We describe both methods commonly used in clinical research, and more innovative methods that build maps directly from the raw data, without going through the image reconstruction. Results: We briefly described recently developed methods in magnetic resonance imaging that accelerate further the MR raw data generation, based on appropriate sub-sampling of k-space; then, we described recently developed methods for generating MR parametric maps. With regard to the emission tomography techniques, we gave an overview of both conventional methods, and more recently developed direct estimation algorithms for parametric image reconstruction from dynamic positron emission tomography data. Conclusion: We have provided an overview of the possible approaches that can be followed to realize useful parametric maps from imaging raw data. We moved from the conventional approaches to more recent and efficient methods for accelerating the raw data generation and the of parametric maps formation.

Background: In the last decades, interventional cardiology has received fast and wide implementation as an effective alternative treatment to surgery for several congenital and acquired diseases. In this scenario, imaging provides solutions for most clinical needs, from diagnosis to prognosis and risk stratification, as well as anatomical and functional assessment. Methods: In this review article, we present recent innovations in medical imaging for structural heart disease and coronary artery disease, emphasizing the progress achieved in the field of multimodality imaging and the solutions proposed to some as-yet unresolved technical problems for safe and effective procedural performance. Results: Intra-procedural guidance can be facilitated by established multimodality cardiac imaging such as transesophageal 2D and 3D echocardiography and by novel techniques as echo-fluoroscopy overlay and 3D modeling/printing. Computed tomography and magnetic resonance imaging are particularly helpful for preprocedural morphology assessment and device sizing. Conclusion: Successful planning, performance, and aftercare of interventions depend heavily on accurate imaging for both structural heart disease and coronary artery disease.

The multidrug resistance (MDR) of tumor cells significantly reduces the efficiency of traditional anticancer therapy. Tumor MDR is complex and involves several mechanisms such as decreased drug uptake, increased drug efflux, enhanced drug exocytosis, increased drug detoxification and inactivation by drugmetabolizing enzymes, altered drug targets due to genetic and epigenetic modifications, altered DNA repair, and impaired apoptotic pathways. Implementation of nanoparticles can markedly improve drug delivery through increased stability in the plasma, prolonged half-life, enhanced specificity of transfer, and advanced drug accumulation and retention in the tumor cells. So far, many various types of nanocarriers have been used for the delivery of anticancer agents. These carriers greatly increase anti-tumor effects of cytotoxic agents since drug-carrying nanoparticles are able to reverse MDR. The promising integrative approach in cancer nanotherapy assumes the development of multifunctional delivery systems simultaneously transmitting various agents such as drugs, genes, imaging agents, and targeting ligands in order to enhance anti-tumor toxicity and nanoparticle tracking.

Diabetes mellitus (DM) is a metabolic disorder which is characterized by inappropriate hyperglycemia. It is becoming an epidemic disease in developing countries. Diabetic patients are frequently afflicted with a vascular dysfunction and wound healing defect. In spite of intense investigations, over the past 2-3 decades, optimal treatment options and related mechanisms are still unclear. MicroRNAs (miRNAs) are small noncoding RNAs considered as regulators of a vast number of biological processes including endothelial cell function controlling molecular signaling pathways in diabetic pathogenesis. Down regulation of microRNA-126 (miR-126) which may regulate angiogenesis and vascular integrity plays a significant role in the pathogenesis and complications of DM. This paper discusses the potential application of miR-126 as a novel therapeutic agent capable of reducing diabetic vascular complications in different types of DM based on the up-to-date reports.

Background: Loss of olfaction can cause noticeable reduction in general quality of life. Only a small portion of patients with olfactory loss respond to current medications. Thus, development of novel therapeutic strategies seems to be necessary. Looking into traditional medical knowledge can be of great value in addressing useful remedies. Traditional Persian Medicine (TPM) has been practiced in Persia for more than 2000 years. Avicenna is the most eminent Persian physician. Objective: To survey Avicennas views on etiology and management of olfactory loss and to search for relevant modern pharmacological data. Methods: Avicennas views on etiology and management (including suggested medicinal plants) of olfactory loss were obtained from “Canon of Medicine”. In addition, a detailed search in ScienceDirect, PubMed, Scopus and Google Scholar databases was performed to elucidate relevant pharmacological actions and mechanisms of the plants and their major compounds with special focus on neuroprotective activity. Results: Acorus calamus L., Allium cepa L., Allium sativum L., Aloe spp., Cinnamomum cassia (L.) J.Presl, Lavandula stoechas L., Mentha longifolia (L.) L., Nigella sativa L., Peganum harmala L., Piper nigrum L. and Zingiberci offinale Roscoe were found to be the most emphatic plants for the treatment of olfactory loss. Pharmacological studies revealed biological activities including neuroprotective, anti-inflammatory, free radical scavenging activities and promoting endogenous antioxidant capacity for these plants and their major components. Conclusion: regarding the lack of effective treatments for recruiting normal smell in many cases, treatments suggested by Avicenna worth entering pharmacologic experiments and clinical trials.