Myeloperoxidase: expressing inflammation and oxidative stress in cardiovascular disease.

Myeloperoxidase (MPO), a heme protein released by leukocytes, is one of the most widely studied during the last decades molecule that plays a crucial role in inflammation and oxidative stress in the cellular level. It has become increasingly recognized that MPO performs a very important role as part of the innate immune system through the formation of microbicidal reactive oxidants, whilst it affects the arterial endothelium with a number of mechanisms that include modification of net cellular cholesterol flux and impairment of Nitric Oxide (NO)-induced vascular relaxation. In that way, MPO is implicated into both the formation and propagation of atheromatosis and there is substantial evidence that it also promotes ischemia through destabilization of the vulnerable plaque. Numerous studies have added information on the notion that MPO and its oxidant products are part of the inflammatory cascade initiated by endothelial injury and they are significantly overproduced at the site of arterial inflammation. Subsequent studies achieved quantification of this observation showing significant elevations of the systemic levels of MPO in a wide spectrum of cardiovascular disease scenarios with acute coronary syndromes and heart failure being the most studied. This review highlights key-aspects of MPO's pathophysiological properties and summarizes the role of MPO as a diagnostic and prognostic tool for a number of cardiovascular pathologies.

Adiponectin: merely a bystander or the missing link to cardiovascular disease?

Adiponectin, a newly discovered adipose-tissue secreting hormone, is a major regulator of a wide spectrum of physiological processes, such as energy metabolism, inflammation and vascular homeostasis. Emerging data suggest that adiponectin is the link between obesity and obesity-related disorders with cardiovascular disease. Adiponectin is a dominant insulin-sensitive adipokine and, in contrast to other adipose-tissue derived cytokines, it has major anti-diabetic, antiatherogenic and anti-inflammatory properties. Adiponectin has been extensively studied in the context of several aspects and risk factors of cardiovascular disease such as obesity, diabetes type I and II, coronary heart disease, hypertension, heart failure, cerebrovascular disease and smoking. The aim of this article is to summarize the acquired so far knowledge on adiponectin in relation to cardiovascular disease, to review its main biological and biochemical characteristics, to highlight the main mechanisms of adiponectin-driven beneficial effects on vasculature and briefly to refer to the basic correlations of adiponectin with the important aforementioned aspects of cardiovascular disease.

Cystatin C: an emerging biomarker in cardiovascular disease.

Cystatin C (cys-C) is a small protein molecule (120 amino acid peptide chain, approximately 13kDa) produced by virtually all nucleated cells in the human body. It belongs to the family of papain-like cysteine proteases and its main biological role is the extracellular inhibition of cathepsins. It's near constant production rate, the fact that it is freely filtered from the glomerular membrane and then completely reabsorbed without being secreted from the proximal tubular cells, made it an almost perfect candidate for estimating renal function. The strong correlation between chronic kidney disease (CKD) and cardiovascular disease (CVD) along with the growing understanding of the role of cysteinyl cathepsins in the pathophysiology of CVD inspired researchers to explore the potential association of cys-C with CVD. Throughout the spectrum of CVD (peripheral arterial disease, stroke, abdominal aortic aneurysm, heart failure, coronary artery disease) adverse outcomes and risk stratification have been associated with high plasma levels of cys-C. The exact mechanisms behind the observed correlations have not been comprehensively clarified. Plausible links between high cys-C levels and poor cardiovascular outcome could be impaired renal function, atherogenesis and inflammatory mediators, remodeling of myocardial tissue and others (genetic factors, aging and social habits). The scope of the present article is to systematically review the current knowledge about cys-C biochemistry, metabolism, methods of detection and quantification and pathophysiological associations with different aspects of CVD.

High sensitivity troponin in cardiovascular disease. Is there more than a marker of myocardial death?

Cardiovascular disease is the leading cause of death worldwide and coronary artery disease is its most prevalent manifestation, associated with high mortality and morbidity. In clinical practice cardiac troponins (cTn) are the cornerstone of the diagnosis, risk stratification and thus selection of the optimal treatment strategy in patients with acute coronary syndrome. According to the third update of the universal definition of myocardial infarction (MI) cTn is the preferred cardiac biomarker of myocardial necrosis in the setting of acute myocardial ischemia. Over the last years newer high sensitivity cardiac troponin (hs-cTn) assays have been developed that are more sensitive than conventional assays, have low limit of detection, low imprecision and low reference limits, but due to variability, the deployment of a standardization and harmonization method is required before their wide use in clinical practice. Recent studies have shown that their utilization seems to improve the diagnostic accuracy detecting MI in patients presenting with chest pain. However, the improved sensitivity comes along with a decreased specificity, though serial cTn measurements and the detection of early changes could improve the specificity and the overall diagnostic performance. Moreover, apart from their use in the diagnosis and risk stratification of MI and acute coronary syndromes, hs-cTn assays seem to have a key role in risk stratification and short and long-term prognosis in a variety of cardiovascular modalities such as stable coronary disease, heart failure and acute pulmonary embolism. In addition, studies have suggested that cTns may be used as a biomarker in the primary prevention of cardiovascular disease leading to the identification of high-risk populations or individuals with silent heart disease.

Novel direct factor IIa and Xa inhibitors: mechanisms of action and preclinical studies.

The need to overcome certain limitations of the existing anticoagulant agents (heparin, LMWH and VKAs) and to achieve more convenient long-term anticoagulation has fueled the quest for the "ideal anticoagulant", an agent that would exert at least similar antithrombotic effects with a substantially improved pharmacologic profile and significantly less bleeding complications. The major disadvantages of the traditional agents were the narrow therapeutic window with serious drug and food interactions and the need for regular blood monitoring. Coagulation factors IIa and Xa have proved the most attractive pharmacologic targets due to their key role in the coagulation process and the opportunity of blocking thrombin generation before the level of thrombin production that results in amplification of the anticoagulant effect while preserving some of thrombin hemostatic effect. This review summarizes the mechanism of action of some of the most promising novel oral direct factor IIa and Xa inhibitors with a focus on published preclinical trials that led to their clinical development.

Increased N-terminal-pro-B-type natriuretic peptide levels in patients with appropriate implantable defibrillator therapies.

BACKGROUND: The ability to better identify predictors of implantable defibrillator therapies in patients with heart failure would allow the optimization of patient selection. N-terminal-Pro-B-type natriuretic peptide (NT-ProBNP) is secreted by the ventricles in response to myocardial stretching and is a sensitive marker of left ventricular dysfunction and cardiac mortality in patients with heart failure. We assessed the relationship between NT-ProBNP and defibrillator therapies for primary or secondary prevention of arrhythmic death. METHODS: NT-ProBNP levels were analyzed in 45 patients with stable heart failure symptoms and defibrillator devices, with and without device therapies, and appropriate and inappropriate therapies. Univariate and multivariate analyses were used to identify predictors of appropriate defibrillator therapies. RESULTS: Device interventions occurred in 21 patients: 12 appropriate therapies and 9 inappropriate therapies. Patients with appropriate therapies had higher NT-ProBNP levels than patients with no device therapies (2469.1 +/- 2281.8 pg/mL vs 838.7 +/- 832 pg/mL; P = .0019), inappropriate therapies (730.4 +/- 503 pg/mL; P = .0046), and combined inappropriate plus no therapies (2469.1 +/- 2281.8 pg/mL vs 713.9 +/- 510.6 pg/mL; P = .0008). The NT-ProBNP level was the only independent predictor of appropriate device therapies during the observation period (P = .004). CONCLUSION: Elevated NT-ProBNP was an independent predictor of appropriate defibrillator therapies. Extensive myocardial remodeling may create the electrophysiologic conditions necessary to elicit ventricular tachyarrhythmias. Further research is necessary to clarify whether the identification of a subgroup of higher risk may benefit from a more aggressive defibrillator programming.

Hypothermia-induced J waves.

A 36 years old woman with acquired immunodeficiency syndrome was admitted to the hospital for pulmonary Mycobacterium Avis Complex infection. Seventy-two hours after the admission she became hypothermic and bradycardic. The ECG showed sinus bradycardia, J waves in leads II, III, aVF, aVR, aVL, V5 and V6 along with QT prolongation and T wave abnormalities. After rewarming the J waves and repolarization abnormalities disappeared. The proposed cellular basis of hypothermia-induced J waves is the accentuation of the spike-and-dome morphology of the action potential of M and epicardial cells.