Direct comparison of B-Type Natriuretic Peptide (BNP) and amino-terminal proBNP in a large population of patients with chronic and symptomatic heart failure: the Valsartan Heart Failure (Val-HeFT) data

Background: The B-type or brain natriuretic peptides (BNP) and the amino-terminal probrain natriuretic peptide (NT-proBNP) are good markers of prognosis and diagnosis in chronic heart failure (HF). It is unclear, however, whether differences in their biological characteristics modify their clinical correlates and prognostic performance in HF. This work aimed to provide a direct comparison of the prognostic value of BNP and NTproBNP in patients with chronic and stable HF. Methods: We measured BNP and NT-proBNP at baseline in 3916 patients enrolled in the Valsartan Heart Failure Trial. To identify the variables associated with both peptides, we conducted simple and multivariable linear regression analyses. We used Cox multivariable regression models to evaluate the independent prognostic value for all-cause mortality, mortality and morbidity, and hospitalization for HF. Prognostic performance was assessed by pairwise comparisons of the area under the curve of receiver-operator characteristic curves. Results: NT-proBNP and BNP had similar relationships with age, left ventrical ejection fraction, and internal diameter and creatinine clearance. Either peptide ranked as the first independent predictor of outcome after adjustment for major confounding clinical characteristics. ROC curves were almost superimposable for all-cause mortality (area under the curve (SE): BNP 0.665 (0.011) vs NT-proBNP 0.679 (0.011); P 0.0734), but NT-proBNP was superior to BNP for predicting mortality and morbidity (P 0.032) or hospitalization for HF (P 0.0143). Overall sensitivity and specificity ranged from 0.590 to 0.696. Conclusions: The natriuretic peptides BNP and NTproBNP showed subtle differences in their relation to clinical characteristics and prognostic performance in a large population of patients with chronic and stable HF. They were the most powerful independent markers of outcome in HF

Revisiting mortality deceleration patterns in a gamma-Gompertz-Makeham framework

We calculate life-table aging rates (LARs) for overall mortality by estimating a gamma-Gompertz-Makeham (G GM) model and taking advantage of LAR’s parametric representation by Vaupel and Zhang [34]. For selected HMD countries, we study how the evolution of estimated LAR patterns could explain observed 1) longevity dynamics, and 2) mortality improvement or deterioration at different ages. Surprisingly, the age of mortality deceleration x showed almost no correlation with a number of longevity measures apart from e0. In addition, as mortality concentrates at older ages with time, its characteristic bell-shaped pattern becomes more pronounced. Moreover, in a GGM framework, we identify the impact of senescent mortality on shape of the rate of population aging. We also find evidence for a strong relationship between x and the statistically significant curvilinear changes in the evolution of e0 over time. Finally, model-based LARs appear to be consistent with point b) of the “heterogeneity hypothesis” [12]: mortality deceleration, due to selection effects, should shift to older ages as the level of total adult mortality declines

Hypofibrinolysis in diabetes: a therapeutic target for the reduction of cardiovascular risk

An enhanced thrombotic environment and premature atherosclerosis are key factors for the increased cardiovascular risk in diabetes. The occlusive vascular thrombus, formed secondary to interactions between platelets and coagulation proteins, is composed of a skeleton of fibrin fibres with cellular elements embedded in this network. Diabetes is characterised by quantitative and qualitative changes in coagulation proteins, which collectively increase resistance to fibrinolysis, consequently augmenting thrombosis risk. Current long-term therapies to prevent arterial occlusion in diabetes are focussed on anti-platelet agents, a strategy that fails to address the contribution of coagulation proteins to the enhanced thrombotic milieu. Moreover, antiplatelet treatment is associated with bleeding complications, particularly with newer agents and more aggressive combination therapies, questioning the safety of this approach. Therefore, to safely control thrombosis risk in diabetes, an alternative approach is required with the fibrin network representing a credible therapeutic target. In the current review, we address diabetes-specific mechanistic pathways responsible for hypofibrinolysis including the role of clot structure, defects in the fibrinolytic system and increased incorporation of anti-fibrinolytic proteins into the clot. Future anti-thrombotic therapeutic options are discussed with special emphasis on the potential advantages of modulating incorporation of the anti-fibrinolytic proteins into fibrin networks. This latter approach carries theoretical advantages, including specificity for diabetes, ability to target a particular protein with a possible favourable risk of bleeding. The development of alternative treatment strategies to better control residual thrombosis risk in diabetes will help to reduce vascular events, which remain the main cause of mortality in this condition

A phase I study of intravenous liposomal daunorubicin (DaunoXome) in paediatric patients with relapsed or resistant solid tumours

Anthracyclines are widely used in paediatric oncology, but their use is limited by the risk of cumulative cardiac toxicity. Encapsulating anthracyclines in liposomes may reduce cardiac toxicity and possibly increase drug availability to tumours. A phase I study in paediatric patients was designed to establish the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) after a single course of liposomal daunorubicin, ‘DaunoXome', as a 1 h infusion on day 1 of a 21 day cycle. Patients were stratified into two groups according to prior treatment: Group A (conventional) and group B (heavily pretreated patients). Dose limiting toxicity was expected to be haematological, and a two-step escalation was planned, with and without G-CSF support. Pharmacokinetic studies were carried out in parallel. In all, 48 patients aged from 1 to 18 years were treated. Dose limiting toxicity was neutropenia for both groups. Maximum tolerated dose was defined as 155 mg m−2 for Group A and 100 mg m−2 for Group B. The second phase with G-CSF was interrupted because of evidence of cumulative cardiac toxicity. Cardiac toxicity was reported in a total of 15 patients in this study. DaunoXome shares the early cardiotoxicity of conventional anthracyclines in paediatric oncology. This study has successfully defined a haematological MTD for DaunoXome, but the significance of this is limited given the concerns of delayed cardiac toxicity. The importance of longer-term follow-up in patients enrolled into phase I studies has been underestimated previously, and may lead to an under-recognition of important adverse events

Cardiopulmonary and inflammatory biomarkers in heartworm disease

Abstract In heartworm disease, several biomarkers of cardiopulmonary injury and inflammatory activity have been studied during the recent years. D-dimer is a fibrin degradation product present after a clot is degraded, which has been reported to provide support for the diagnosis of pulmonary thromboembolism in heartworm disease. Furthermore, concentrations increment with increased disease severity and during the adulticide treatment. This increase in concentration has proved to be valuable. Cardiac biomarkers troponin I, myoglobin and NT-proBNP demonstrated presence of myocardial injury and heart failure, especially in chronic infections, which in some cases, slightly improve after the adulticide treatment. An acute phase response in dogs with Dirofilaria immitis, characterized by variations of acute phase proteins (APP), has been reported, indicating inflammatory processes that could contribute to disease progression. Among them, C-reactive protein (CRP) increases according to the severity of the disease; and a strong correlation between pulmonary hypertension and CRP has been observed. In cats, little work has been done to ascertain the utility of these biomarkers in feline heartworm; the only published study in D. immitis–seropositive cats reported significantly higher concentrations in positive APP serum amyloid A, haptoglobin and ceruloplasmin

Introduction

Globally, the twenty-first century will witness rapid population ageing. Already in 2050, one out of five persons in the world, and one out of three in Europe, is expected to be 60 or over (UN 2015). Moreover, we have entered into a new stage of population ageing in terms of its causes, which have altered its consequences. In the first stage, lasting until the middle of the twentieth century in developed countries, population ageing was entirely due to the decline in fertility, with Sweden being commonly used as an example (Coale 1957; Bengtsson and Scott 2010; Lee and Zhou 2017). During this stage, the increase in life expectancy was primarily driven by declines in infant and child mortality. It worked in the opposite direction to the fertility decline, making the population younger since it added more years before, than after retirement (Coale 1957; Lee 1994). In the second stage of population ageing, which is the current situation, population ageing is primarily driven by the increase in life expectancy, which is now due to declining old-age mortality. As a result, more years are added after retirement than in working ages (Lee 1994). Could immigration or an upswing in fertility stop population ageing? The short answer is most likely not. The effect of migration on population aging is generally regarded as minor (Murphy 2017), and since population ageing is a global phenomenon, it will be of no general help anyway. A rapid increase in fertility is improbable and, in any case, an increase would take some 25 years before adding to the labor force. Instead, attention has been focused on how to adapt our social systems to the increasing number of elderly per worker – more so since the increase in the elderly-per-worker ratio came in parallel with a rise in per capita costs for the institutional care, home care, and general health care for the elderly