Rationale and Design for a Multicenter, randomized, double-blind, placebo-controlled, phase 2 study evaluating the safety and efficacy of the soluble Guanylate Cyclase stimulator Praliciguat over 12 weeks in patients with heart failure with preserved ejection fraction (CAPACITY HFpEF)

ConclusionThe CAPACITY HFpEF trial will provide data on short-term safety and efficacy of praliciguat on peak exercise capacity, as well as multiple secondary endpoints of submaximal functional capacity, patient-reported outcomes, and biomarkers.
Source: American Heart Journal - Category: Cardiology Source Type: research

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Authors: Selthofer-Relatić K, Kibel A, Delić-Brkljačić D, Bošnjak I Abstract Obesity is a risk factor for cardiometabolic and vascular diseases like arterial hypertension, diabetes mellitus type 2, dyslipidaemia, and atherosclerosis. A special role in obesity-related syndromes is played by cardiac visceral obesity, which includes epicardial adipose tissue and intramyocardial fat, leading to cardiac steatosis; hypertensive heart disease; atherosclerosis of epicardial coronary artery disease; and ischemic cardiomyopathy, cardiac microcirculatory dysfunction, diabetic cardiomyopathy, and atrial fibrillation...
Source: Journal of Obesity - Category: Eating Disorders & Weight Management Tags: J Obes Source Type: research
In conclusion, with study of the frailty syndrome still in its infancy, frailty analysis remains a major challenge. It is a challenge that needs to be overcome in order to shed light on the multiple mechanisms involved in the pathogenesis of this syndrome. Although several mechanisms contribute to frailty, immune system alteration seems to play a central role: this syndrome is characterized by increased levels of pro-inflammatory markers and the resulting pro-inflammatory status can have negative effects on various organs. Future studies should aim to better clarify the immune system alteration in frailty, and seek to esta...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In conclusion, the impaired in situ activity of RyR2 may also account for the poor overall cardiac outcome reported in MetS patients; hence, the SERCA pump and RyR2 are both attractive potential targets for future therapies. Introduction Metabolic syndrome (MetS) is a cluster of biochemical and physiological risk factors for cardiovascular disease and diabetes mellitus type 2 (DM2); it represents a severe public health problem around the world (Alberti et al., 2009). Risk factors for MetS include obesity (particularly central obesity), elevated triglyceride (TG) levels, low high-density lipoprotein cholesterol (HDL...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Bartolo Ferraro1,2, Maria Donniacuo3, Loredana Sodano3, Franca Ferraraccio4, Rosa Maisto3, Eliana Gulotta5, Gorizio Pieretti6, Michele D’Amico3*, Maria Consiglia Trotta3 and Barbara Rinaldi3 1Institute for Cardiovascular Prevention (IPEK), Ludwig Maximilian University of Munich, Munich, Germany 2DZHK, Partner Site Munich Heart Alliance, Munich, Germany 3Department of Experimental Medicine, Pharmacology Division, University of Campania “L. Vanvitelli”, Naples, Italy 4Department of Clinical, Public and Preventive Medicine, University of Campania “L. Vanvitelli”, Naples, Italy 5Departm...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusion Activation of the Nrf2-dependent antioxidant system plays an important role in cell defense against oxidative stress damage, whereas the insufficiency of the Nrf2 system is associated with multiple aspects of the genesis and progression of metabolic diseases, posing a great risk to the cardiovascular system (Figure 1). The systemic increase of Nrf2 activity by several activators may be beneficial in the treatment of metabolic diseases. In addition, selective upregulation of Nrf2 genes may represent a potential therapy in obesity, diabetes and atherosclerosis. Looking to the future, experimental research that el...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusion: This study observed an inverse correlation between plasma LDL cholesterol and heart function in individuals with T2DM. Patients with higher levels of plasma LDL cholesterol had worse left ventricular function. Therefore, plasma LDL cholesterol may be a modifiable risk factor of heart failure in diabetes, but prospective studies are necessary to confirm this finding. Introduction Type 2 diabetes mellitus (T2DM) is a metabolic disease that affects a considerable number of patients worldwide (1). Among diabetic individuals, cardiovascular disease (CVD) is the leading cause of morbidity and mortality (2). C...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
PARP-1 inhibition protects the diabetic heart through activation of SIRT1-PGC-1α axis. Exp Cell Res. 2018 Oct 22;: Authors: Waldman M, Nudelman V, Shainberg A, Abraham NG, Dan Aravot, Arad M, Hochhauser E Abstract Type 2 diabetes mellitus (DM2) follows impaired glucose tolerance in obesity and is frequently associated with hypertension, causing adverse myocardial remodelling and leading to heart failure. The DNA bound protein PARP (poly ADP ribose) polymerase catalyses a post translational modification (polymerization of negatively charged ADP-ribose chains) of nuclear proteins. PARP-1 activatio...
Source: Experimental Cell Research - Category: Cytology Authors: Tags: Exp Cell Res Source Type: research
Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more. This content is...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
by Jasper Tromp, Wan Ting Tay, Wouter Ouwerkerk, Tiew-Hwa Katherine Teng, Jonathan Yap, Michael R. MacDonald, Kirsten Leineweber, John J. V. McMurray, Michael R. Zile, Inder S. Anand, Carolyn S. P. Lam, ASIAN-HF authors BackgroundComorbidities are common in patients with heart failure (HF) and complicate treatment and outcomes. We identified patterns of multimorbidity in Asian patients with HF and their association with patients ’ quality of life (QoL) and health outcomes. Methods and findingsWe used data on 6,480 patients with chronic HF (1,204 with preserved ejection fraction) enrolled between 1 October 2012 and 6 ...
Source: PLoS Medicine - Category: Internal Medicine Authors: Source Type: research
Abstract Heart failure and related morbidity and mortality are increasing at an alarming rate, in large part, because of increases in aging, obesity, and diabetes mellitus. The clinical outcomes associated with heart failure are considerably worse for patients with diabetes mellitus than for those without diabetes mellitus. In people with diabetes mellitus, the presence of myocardial dysfunction in the absence of overt clinical coronary artery disease, valvular disease, and other conventional cardiovascular risk factors, such as hypertension and dyslipidemia, has led to the descriptive terminology, diabetic cardio...
Source: Circulation Research - Category: Cardiology Authors: Tags: Circ Res Source Type: research
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