Cardiovascular & Haematological Disorders - Drug Targets - Volume 13, Issue 3, 2013

When introduced over 100 years ago, aspirin was prescribed as an analgesic drug to arthritic patients for pain relief. The prevalence of users grew quite rapidly and to this day, aspirin remains widely used in clinical practice. The popularity of aspirin resulted not only from its analgesic properties but also from a second benefit recognized later as an anti-platelet effect. It was this important activity of aspirin that made it one of the most recommended drugs for the treatment and prevention of cardiovascular diseases. The anti-platelet effect of aspirin emerged from the first few case reports published in the early 1900s and was described as a mild bleeding. The molecular mechanisms involved were described in 1971 and constituted the irreversible inhibition of cyclooxygenase-1 enzyme and prevention of platelet aggregation. Today, the contribution of aspirin to our understanding of cardiovascular health persists and remains considerable. Observations from large cohorts of aspirin users generate massive amount of valuable information used in the identification of factors influencing the potential risk for cardiovascular diseases, including sex, age and genetic predisposition. Aspirin and the path of discovery leading to its anti-platelet activity has taken a hundred years was based on manifestations of effects observed in its users, and it remains a successful strategy for the identification of new avenues to treat cardiovascular diseases associated with hyper-platelet activity. The contribution of aspirin to the understanding of cardiovascular diseases and to the design of effective treatment and prevention strategies, remains of high importance in our society.

The term peripheral arterial disease (PAD) is often used to describe atherosclerosis involving the arteries supplying the lower extremities. Risk factors that predispose to the development and progression of both symptomatic and asymptomatic PAD include age, ethnicity, smoking, diabetes mellitus, hyperlipidemia, and hypertension. In addition, emerging biomarkers of inflammation, oxidative stress, thrombosis and metabolism have also been discovered to be predictive of future PAD events. Since traditional risk factors for PAD predispose to the development of systemic atherosclerosis, identification of PAD increases the likelihood of coexistent coronary heart and cerebrovascular disease. Even after adjustment for risk factors, PAD appears to increase the risk for ischemic manifestations involving these other vascular territories with about a 2-fold increase in myocardial infarction and perhaps stroke. The most dramatic consequence of PAD is impaired survival with a 2- to 3-fold increased risk of 5- to 10-year mortality. Not only is the risk of adverse cardiovascular and cerebrovascular complications elevated in patients with severe PAD, but it is also markedly elevated in those with asymptomatic disease. The focus in the management of PAD should be on early diagnosis and efforts to reduce the risk of adverse events by risk factor modification and antiplatelet therapy.

Adrenergic mechanisms are involved in the formation of several types of pulmonary edema (PE) such as neurogenic pulmonary edema (NPE) or PE in patients with pheochromocytoma, but also in the development of pulmonary fibrosis and pulmonary hypertension. In severe cases of PE such as in the adult respiratory distress syndrome (ARDS), PE is typically accompanied by inflammation and followed by pulmonary vascular hypertrophy and pulmonary fibrosis. Norepinephrine and other adrenoceptor agonists are known to provoke activation of proinflammatory cytokines such as interleukin (IL)-1 and IL-6. These cytokines are involved both in the pathogenesis of PE and of pulmonary fibrosis. We therefore assume that adrenergic mechanisms may have an important role in the pathogenesis of pulmonary injuries characterized by edema, inflammation and fibrosis. The contribution of adrenoceptor stimulation, particularly the distinct role of α- and β-adrenergic mechanisms, to the development of PE and pulmonary fibrosis is reviewed in this paper.

Background: Lifestyle modification, including diet, is a key strategy for prevention and regression of cardiovascular disease (CVD), a leading cause of death worldwide. Traditionally, the study of the relationship between diet and CVD has focused on the analysis of single nutrients, or foods, in relation to CVD risk. Objective: In part one of this review, we present current epidemiologic and clinical evidence on nutrition and cardiovascular health with regards to specific foods and nutrients aimed at preventing CVD. Methods: The Cochrane Library database between 2006 and 2012 was searched for studies on effects of dietary factors on cardiovascular health. Discussion: Evidence is presented on soy protein, fats, fish, nuts, fruit, vegetables, electrolytes, vitamins, and carbohydrate including fibre, glycaemic index, and wholegrains. Evidence from specific foods underpins current dietary CVD prevention guidelines, that advise on replacing saturated with unsaturated fat, consuming carbohydrate foods that are wholegrain or of low glycaemic index, increased consumption of fruit, vegetables (particularly cruciferous), nuts, and oily fish. Other nutrients (such as soya protein, or reducing sodium intake) reduce CVD risk via favourable effects on disease contributors (such as LDL-cholesterol or blood pressure), but also infer/promote dietary change that impacts other nutrients (using less animal or processed foods, resulting in saturated fat reduction). The complexity and limitations of interpreting dietary epidemiologic studies is reviewed. With the general ineffectiveness of nutrient-based intervention, recently the shift has been towards the examination of associations between dietary patterns and cardiovascular health, which will be examined in the second part of this review.

The efficacy of herbal medicine has been confirmed in treatment of diabetes mellitus (DM) by amelioration of oxidative stress. The present study was designed to investigate protective effects of Cichorium intybus extract (CIE) against oxidative damage in diabetic rats. In this study, the rats were divided into the control (C), diabetic (D), D + CIE– treated (125 mg/kg/day) groups. Male Sprague–Dawley rats aged 9 weeks (160 ± 15 g) were administered with streptozotocin (STZ, 60 mg/kg) intraperitoneally (ip) to induce experimental diabetes. From 3 days after STZ administration to the end of the study (4 weeks) the ethanolic extract of CIE was administered (i.p) to diabetic rats. Body weight and blood glucose were measured weekly. At the end of the 4-week period, blood was drawn for biochemical assay, in order to determine the changes of cellular antioxidant defense system, serum oxidative damage and serum lipid were measured profile. CIE injection to diabetic rats resulted in significant reduction in blood glucose, triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) levels and significant elevation high density lipoprotein cholesterol (HDL-C) level as well as increase in the body weight as compared with the rats treated with STZ alone. In the treated diabetic group, we also observed the significant increase in reduced glutathione (GSH), superoxide dismutase (SOD), glutathione-S-transferase (GST) and catalase (CAT) with decline in malondialdehyde (MDA) level compared with the non-treated diabetic group. These results suggest that the Cichorium intybus extract has antioxidant properties and prevents diabetes complications by modulation of oxidative stress system.

Iron supplementation therapy seems almost indispensable in adequate management of the patients with end - stage renal disease on maintenance hemodialysis, since at least one and a half grams iron is considered to be required per year to keep sufficient erythropoiesis. Iron supplementation in conjunction with erythropoietic-stimulating agents is widely carried out as a standard therapy. However, definite diagnosis of iron deficiency in hemodialysis patients is often difficult since serum ferritin levels increase frequently by various reasons including inflammation and malignancy. Although several guidelines to treat anemia of the hemodialysis patients have been proposed, they seem still insufficient and careful clinical observation is required in individual patient to avoid possible complications of iron overload. We, here, reassess the adequate iron supplementation therapy in those patients, and the necessity of new guideline employing recent advances including magnetic resonance imaging – based method (FerriScan) and hemoglobin content per each reticulocyte is also discussed.

Time to reperfusion is among the strongest predictors of clinical outcome in patients who present with ST elevation acute myocardial infarction. When time to access is equivalent, primary percutaneous coronary intervention has demonstrated superior outcomes to fibrinolysis. However, where significant delays exist in accessing percutaneous intervention, fibrinolysis has an important role. The potential for fibrinolysis delivery in the pre-hospital setting means that delays to primary percutaneous intervention need to be considered from the time that the patient becomes eligible for fibrinolysis in the field. This can be particularly challenging in patients with symptom duration ofless than two hours, as some evidence suggests fibrinolysis may be particularly beneficial in this early phase. Additionally, access to primary percutaneous intervention provided by an experienced operator, in a timely manner at any time of the day or night, is not an available option in many healthcare settings. This review focuses on the current evidence and practice of pre-hospital fibrinolysis and assesses potential roles for this therapy in the future.