Management of Patients with Heart Failure: Focus on New Pharmaceutical and Device Options.

Hospitalization rates and survival of patients with Heart Failure (HF) have improved. However, 5-year mortality rates remain high and the prevalence of the disease is rising likely due to aging of the population and advances in diagnosis and treatment of other acute and chronic cardiovascular diseases. Over the past three decades the therapeutic armamentarium of heart failure has improved substantially with development of medications targeting neuro-hormonal activation and devices preventing sudden cardiac death and improving cardiac synchrony. Recently, inhibition of angiotensin receptors and neprilysin as well as sinoatrial pacemaker modulating f-current, have been found safe and effective strategies that improve HF hospitalization rates and/or mortality. Antidiabetic agents inhibiting sodium-glucose co-transporters 2, result in natriuresis and osmotic diuresis and may further improve HF related outcomes. Furthermore, emerging therapies such as cardiac myosin activators, soluble guanylate cyclase stimulators and non-steroidal mineralocorticoid receptor antagonists are undergoing investigation in phase II and III studies of HF patients. Finally, rapid evolution of in the management of advanced HF has occurred with the application of second and third generation continuous flow left ventricular assist devices in clinical practice. Ongoing clinical studies will validate the safety and efficacy of emerging therapeutic strategies in HF population underrepresented in previous clinical trials.

Ateroesclerosis coronaria en pacientes hipertensos: el papel de la variabilidad genética del fibrinógeno / Coronary artery atherosclerosis in hypertensive patients: the role of fibrinogen genetic variability

Introducción y objetivos: Se examina si los polimorfismos rs180070 y rs2070011 del gen del fibrinógeno podrían afectar al riesgo de enfermedad coronaria de los pacientes hipertensos al modificar el proceso inflamatorio y la coagulación. Métodos: Se practicó una angiografía coronaria a causa de síntomas de angina estable a 744 participantes, de los que 332 tenían hipertensión. Resultados: La presencia del alelo A (rs180070) se asoció a cifras de fibrinógeno significativamente elevadas en los pacientes hipertensos (p = 0,05). En el análisis multivariable, la homocigosis para A (rs180070) (β = 0,257 ± 18,6; p < 0,001), pero no la presencia de hipertensión (β = 0,05 ± 11,9; p = 0,29), fue un factor independiente predictivo de la concentración de fibrinógeno. En los pacientes hipertensos, la concentración de fibrinógeno > 443 mg/dl (odds ratio = 3,50; intervalo de confianza del 95%, 1,14-10,90; p = 0,029), pero no la homocigosis para A (odds ratio = 3,00; intervalo de confianza del 95%, 0,78-11,90; p = 0,110), fueron un factor independiente predictivo de enfermedad coronaria. Además, los valores de interleucina 6 fueron más altos en los individuos homocigotos para el polimorfismo rs180070 que en todos los demás genotipos (p = 0,046). De hecho, este genotipo fue el único factor independiente predictivo de la concentración de interleucina 6 en el análisis ajustado (β = 0,151 ± 0,642; p = 0,032). También se asoció a cifras de dímero D superiores en la hipertensión en comparación con los portadores del alelo G (p = 0,048). Conclusiones: La presencia de homocigosis para A (rs180070) se asocia a un aumento de las concentraciones de mediadores inflamatorios y mayor incidencia de enfermedad coronaria angiográfica. Tiene importancia que el fibrinógeno es un factor independiente predictivo de la presencia angiográfica de enfermedad coronaria en los pacientes hipertensos (AU)

Introduction and objectives: We examined whether the rs180070 and rs2070011 polymorphisms of the fibrinogen gene could affect the risk of coronary artery disease in hypertensive patients by modifying the inflammatory process and coagulation. Methods: A total of 744 participants underwent coronary angiography due to symptoms of stable angina, while hypertension was present in 332 patients. Results: The presence of the A allele (rs180070) was associated with significantly high levels of fibrinogen in hypertensive patients (P = .05). On multivariate analysis, A homozygosity (rs180070) (β = 0.257 ± 18.6; P < .001), but not hypertension status (β = 0.05 ± 11.9; P = .29) was an independent predictor of fibrinogen levels. In hypertensive patients, higher fibrinogen levels > 443 mg/dL (odds ratio = 3.50; 95% confidence interval, 1.14-10.90; P = .029), but not A homozygosity (odds ratio = 3.00; 95% confidence interval, 0.78-11.90; P = .110) were independent predictors of the presence of coronary artery disease. Moreover, interleukin-6 levels were higher in A homozygotes for the rs180070 polymorphism compared with all other genotypes (P = .046). Indeed, this genotype was the only adjusted independent predictor of interleukin-6 levels (β = 0.151 ± 0.642; P = .032). It was also associated with higher D-dimer levels in hypertension compared with G allele carriers (P = .048). Conclusions: The presence of A homozygosity (rs180070) is associated with increased levels of inflammatory mediators and a higher incidence of angiographic coronary artery disease. Importantly, fibrinogen is an independent predictor of the angiographic presence of coronary artery disease in hypertensive patients (AU)

Coronary Artery Atherosclerosis in Hypertensive Patients: The Role of Fibrinogen Genetic Variability.

INTRODUCTION AND OBJECTIVES: We examined whether the rs180070 and rs2070011 polymorphisms of the fibrinogen gene could affect the risk of coronary artery disease in hypertensive patients by modifying the inflammatory process and coagulation. METHODS: A total of 744 participants underwent coronary angiography due to symptoms of stable angina, while hypertension was present in 332 patients. RESULTS: The presence of the A allele (rs180070) was associated with significantly high levels of fibrinogen in hypertensive patients (P=.05). On multivariate analysis, A homozygosity (rs180070) (ß = 0.257 ± 18.6; P<.001), but not hypertension status (ß = 0.05 ± 11.9; P=.29) was an independent predictor of fibrinogen levels. In hypertensive patients, higher fibrinogen levels>443mg/dL (odds ratio = 3.50; 95% confidence interval, 1.14-10.90; P=.029), but not A homozygosity (odds ratio = 3.00; 95% confidence interval, 0.78-11.90; P = .110) were independent predictors of the presence of coronary artery disease. Moreover, interleukin-6 levels were higher in A homozygotes for the rs180070 polymorphism compared with all other genotypes (P=.046). Indeed, this genotype was the only adjusted independent predictor of interleukin-6 levels (ß = 0.151 ± 0.642; P=.032). It was also associated with higher D-dimer levels in hypertension compared with G allele carriers (P=.048). CONCLUSIONS: The presence of A homozygosity (rs180070) is associated with increased levels of inflammatory mediators and a higher incidence of angiographic coronary artery disease. Importantly, fibrinogen is an independent predictor of the angiographic presence of coronary artery disease in hypertensive patients.

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.

MicroRNAs and the heart: small things do matter.

MicroRNAs are small RNA molecules and constitute a relatively novel class of gene expression regulators, found in the great majority of eukaryotic cells. Their role in human physiology and pathology is actively being researched with new exciting discoveries continuously coming to the forefront. MicroRNAs play a crucial role in the biogenesis and function of the cardiovascular system and act as important regulators of various metabolic and signaling pathways in cardiovascular disease. In this review there will be a summary on current knowledge about the expression, regulation and function of microRNAs in the most common diseases of the cardiovascular system as well as a presentation of and discussion about their promising future role as new biomarkers and therapeutic targets.

Prevention and treatment of venous thromboembolism and pulmonary embolism: the role of novel oral anticoagulants.

Venous thromboembolism, encompassing deep vein thrombosis and pulmonary embolism, is the third most common cause of vascular death after myocardial infarction and stroke. Clinicians are often summoned to make challenging decisions for the prevention and treatment of high risk patients with an unpredicted outcome, often relying on data that are less than definitive. During the last decades, heparins (unfractionated and low molecular weight heparins) as well as vitamin K antagonists, such as warfarin, and indirect Xa inhibitors, such as fontaparinux, are the cornerstone for the prevention and treatment of patients with venous thromboembolism. However, the traditionally used anticoagulants have several drawbacks that may limit their efficacy and use in every day clinical practise. The newly developed oral anticoagulants, belonging to the categories of direct thrombin inhibitors (DTIs) and direct Xa inhibitors, have emerged as promising agents with remarkable efficacy, concentrating many parameters of an ideal anticoagulant. Rivaroxaban, dabigatran and apixaban are the most studied agents, while a plethora of others are investigated in clinical trials of different phases and are expected to reach the market in the following years. The purpose of this review is to summarize the so far acquired knowledge on these agents, to report briefly some of their pharmacodynamic and pharmacokinetic properties and to focus on their role in the treatment and prevention of venous thromboembolism.