Obesity and the risk of heart failure

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure

Much has been published in the past 20 years on the use of measurements of arterial stiffness in animal and human research studies. This summary statement was commissioned by the American Heart Association to address issues concerning the nomenclature, methodologies, utility, limitations, and gaps in knowledge in this rapidly evolving field. The following represents an executive version of the larger online-only Data Supplement and is intended to give the reader a sense of why arterial stiffness is important, how it is measured, the situations in which it has been useful, its limitations, and questions that remain to be addressed in this field. Throughout the document, pulse-wave velocity (PWV; measured in meters per second) and variations such as carotid-femoral PWV (cfPWV; measured in meters per second) are used. PWV without modification is used in the general sense of arterial stiffness. The addition of lowercase modifiers such as “cf” is used when speaking of specific segments of the arterial circulation.

The ability to measure arterial stiffness has been present for many years, but the measurement was invasive in the early times. The improvement in technologies to enable repeated, minimal-risk, reproducible measures of this aspect of circulatory physiology led to its incorporation into longitudinal cohort studies spanning a variety of clinical populations, including those at extreme cardiovascular risk (patients on dialysis), those with comorbidities such as diabetes mellitus (DM) and hypertension, healthy elders, and general populations.

In the ≈3 decades of clinical use of PWV measures in humans, we have learned much about the importance of this parameter. PWV has proven to have independent predictive utility when evaluated in conjunction with standard risk factors for death and cardiovascular disease (CVD). However, the field of arterial stiffness investigation, which has exploded over the past 20 years, has proliferated without logistical guidance for clinical and …

Recommendations for Improving and Standardizing Vascular Research on Arterial Stiffness: A Scientific Statement From the American Heart Association

Coronary heart disease

In its classic hormonal role, erythropoietin (EPO) is produced by the kidney and regulates the number of erythrocytes within the circulation to provide adequate tissue oxygenation. EPO also mediates other effects directed towards optimizing oxygen delivery to tissues, e.g. modulating regional blood flow and reducing blood loss by promoting thrombosis within damaged vessels. Over the past 15 years, many unexpected nonhaematopoietic functions of EPO have been identified. In these more recently appreciated nonhormonal roles, locally-produced EPO signals through a different receptor isoform and is a major molecular component of the injury response, in which it counteracts the effects of pro-inflammatory cytokines. Acutely, EPO prevents programmed cell death and reduces the development of secondary, pro-inflammatory cytokine-induced injury. Within a longer time frame, EPO provides trophic support to enable regeneration and healing. As the region immediately surrounding damage is typically relatively deficient in endogenous EPO, administration of recombinant EPO can provide increased tissue protection. However, effective use of EPO as therapy for tissue injury requires higher doses than for haematopoiesis, potentially triggering serious adverse effects. The identification of a tissue-protective receptor isoform has facilitated the engineering of nonhaematopoietic, tissue-protective EPO derivatives, e.g. carbamyl EPO, that avoid these complications. Recently, regions within the EPO molecule mediating tissue protection have been identified and this has enabled the development of potent tissue-protective peptides, including some mimicking EPO's tertiary structure but unrelated in primary sequence.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2796.2008.02024.x

Erythropoietin-mediated tissue protection: reducing collateral damage from the primary injury response.

Erythropoietin (EPO) is a haematopoietic stimulatory protein that is used to treat anaemia in patients on dialysis. In addition, EPO has been shown to have anti-inflammatory properties, which may be important as dialysis patients tend to exist within a chronic, low-grade inflammatory state, and tend to be more susceptible to infections. It has been suggested that EPO has direct immunomodulatory potency on monocytes/macrophages. In this study, we aimed to clarify the effects of EPO during the inflammatory processes in human mononuclear phagocytic cells by monitoring the secretion of the following cytokines; midkine, tumour necrosis factor alpha (TNF-α), and interleukin-6 (IL-6). For this purpose, U937 human histiocytic lymphoma cell lines were used. Time-dependent effects of varying doses of EPO (0.1 to 50 IU/ml) treatment during lipopolysaccharide (LPS)-mediated cytotoxicity was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide test. LPS-stimulated midkine secretion was measured immunohistochemically and quantification of TNF-α, IL-6 and midkine secretion was achieved by ELISA. EPO treatment prevented the direct toxic effects of LPS on the U937 cells. TNF-α, IL-6 and midkine secretions were found to increase in the U937 cells in response to LPS treatment. Interleukin-6 response was varied in a doseand time-dependent manner. Treatment with EPO significantly inhibits the LPS-induced secretion of midkine and TNF-α regardless of the dosage. The data presented here provide the first evidence to indicate that EPO treatment directly reverses some of the cytotoxic and secretory effects of LPS in mononuclear cells. Inhibition of midkine secretion might be responsible for the anti-inflammatory role of EPO.

Erythropoietin reduces lipopolysaccharide-induced cell Damage and midkine secretion in U937 human histiocytic lymphoma cells

Background. Prolongation of P‐wave durations and increased P‐wave dispersion are independent predictors of atrial fibrillation (AF). AF is the most common arrhythmia of the general population. Prehypertension, including those with systolic blood pressure ranging from 120–139 mmHg or diastolic blood pressure ranging from 80–89 mmHg was described by JNC7. Prehypertension is the predictor of development of hypertension in the future. Prehypertension is associated with excess cardiovascular morbidity and mortality. In this study, we evaluated relationship between prehypertension and P‐wave dispersion. Methods. Seventy‐eight prehypertensive patients (group 1: mean age 44.6±11.2 years; 45 male) and 78 normotensive patients (group 2: mean age 43.3±7.0 years; 43 male) were enrolled in this study. Standard 12‐lead ECGs were recorded in all patients using a paper speed of 50 mm/s. In all patients, transthoracic echocardiographic examination was performed. Results. Pmax and P‐wave dispersion were significantly highe...

P‐Wave dispersion increases in prehypertension

OBJECTIVES Aortic valve stenosis is the most common valvular heart disease in the Western world. The most common cause of aortic valve stenosis in adults is calcification of a normal trileaflet or congenital bicuspid valve. Calcific aortic valve stenosis is an active disease process characterized by mechanical stress, endothelial damage, lipid accumulation, inflammation, synthesis of extracellular matrix proteins, and calcification, reminiscent of atherosclerosis in many aspects. Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase which reduces the bioavailability of nitric oxide and begets endothelial dysfunction. The goal of this study was to examine the association between ADMA activity and severity of aortic valve stenosis. METHODS One hundred and nine patients were included in this study. Patients were grouped as those with mild aortic stenosis (42 patients, group 1), moderate aortic stenosis (36 patients, group 2), and severe aortic stenosis (31 patients, group 3). ADMA activity was measured by ELISA kit. RESULTS Mean ADMA activity in group 3 was significantly higher than that in groups 1 and 2 (1.94 ± 0.45 vs. 0.87 ± 0.37 micromol/l, P < 0.001 and 1.94 ± 0.45 vs. 1.34 ± 0.52 micromol/l, P < 0.001, respectively). Serum ADMA activity was positively correlated with mean aortic gradient and maximum aortic gradient and negatively correlated with aortic valve area. CONCLUSION Our results showed that serum ADMA activity is higher in patients with severe aortic valve stenosis. ADMA activity is positively correlated with aortic valve stenosis severity. Serum ADMA level may be used as a precious marker to evaluate and follow up the severity of aortic valve stenosis.

Association between plasma asymmetrical dimethylarginine activity and severity of aortic valve stenosis.

OBJECTIVES Metabolic syndrome (MetS) has been shown to be independently associated with increased risk for incident heart failure and coronary artery disease. We investigated whether there was deterioration in right ventricular functions in MetS patients with preserved left ventricular functions and its association with the number of MetS components. STUDY DESIGN The study included 192 consecutive patients (148 women, 44 men; mean age 54.3 ± 8.5 years) with the diagnosis of MetS based on the NCEP-ATP III criteria and 20 healthy controls (12 women, 8 men; mean age 51.6 ± 8.4 years). All subjects underwent conventional and tissue Doppler (TDI) echocardiography to assess left and right ventricular functions, including right ventricular myocardial performance index (MPI) and tricuspid annular plane systolic excursion (TAPSE). RESULTS The number of MetS components were three in 43.8%, four in 31.3%, and five in 25% of the patients. Right ventricular TDI-derived MPI was higher in patients with MetS compared to controls [median 0.5 (range 0.2-3.3) vs. 0.3 (0.1-0.7), p=0.000]. This was possibly due to significantly shortened right ventricular ejection time in MetS patients (p<0.05). Although TAPSE was within the normal range in MetS patients, it was significantly decreased compared to controls (p=0.000), accompanied by significantly lower TDI-derived S wave, E wave, and E/A ratio (p=0.000). None of the MetS components were significantly correlated with right ventricular TDI-derived MPI. There was no association between the number of MetS components and echocardiographic parameters. CONCLUSION Our findings show that, despite preserved left ventricular systolic functions, both systolic and diastolic functions of the right ventricle deteriorate in MetS patients.

Impaired right ventricular functions in metabolic syndrome patients with preserved left ventricular ejection fraction.

Objectives: Thymosin beta 4 (Tβ4) plays an essential role in cardiac vessel development and is currently being developed as a therapeutic agent for the treatment of coronary artery disease (CAD) in some experimental studies. Thus, we aimed to investigate the association of serum Tβ4 levels and collateral formation in patients presenting with severely stenotic CAD. Methods: Thirteen patients with poor collateral development and 16 age- and sex-matched patients with good collateral development who had ≥ 95% stenosis in at least one major coronary artery on coronary angiogram (CAG) were enrolled in the study. The Gensini score was calculated for each patient by using CAG results. Collateral development was classified according to the Cohen-Rentrop method. Serum Tβ4 levels were measured with enzyme-linked immune sorbent assay. Results: There were no statistically significant differences between the two groups in regard to clinical and laboratory characteristics of the patients except for Tβ4 levels. T...

Özlem Karakurt

Papers

Erythropoietin reduces lipopolysaccharide-induced cell Damage and midkine secretion in U937 human histiocytic lymphoma cells

P‐Wave dispersion increases in prehypertension

Association between plasma asymmetrical dimethylarginine activity and severity of aortic valve stenosis.

Impaired right ventricular functions in metabolic syndrome patients with preserved left ventricular ejection fraction.

Thymosin beta 4 is associated with collateral development in coronary artery disease