Showing 5 ideas for tag "stress"

Goal 2: Reduce Human Disease

Non-obstructive Coronary Disease

It is increasingly apparent that ischemic heart disease does not equal obstructive coronary disease. There is a large, heterogeneous population of individuals who present to the ED with chest pain syndrome with or without a troponin elevation, who on diagnostic evaluation have non-obstructive disease and who on prospective studies have increased risk for ACS and early mortality; other literature shows the same for coronary... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Patients with non-obstructive coronary disease represent a large proportion of patients who report to the ED with chest pain of cardiac origin. This hetergeneous group of patients have elevated ACS/mortality risk, yet little is known of the underlying pathophysiology or of the precipitants of chest pain and events. Research focused on characterizing distinct patient groups and associated pathways by which environmental factors precipitate chest pain and events would provide enormous benefit in the development and targeting of interventions to improve patient outcomes and reduce risk of catastrophic cardiac events.

Feasibility and challenges of addressing this CQ or CC

The challenges include assembling a sufficiently large patient sample to characterize distinct phenotypes. The technologies for this characterization are sufficiently disseminated to accomplish this. Furthermore, the technologies for ascertaining key elements of pathophysiology - e.g., vascular, autonomic - are also widely available. The recent expansion of technologies for ecological measurement of environmental factors and of physiological phenomena make this a feasible undertaking at this time

Name of idea submitter and other team members who worked on this idea Matthew Burg, PhD

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Goal 2: Reduce Human Disease

Chronic stress and cardiovascular/metabolic disease

Chronic stress is a risk factor for obesity, cardiovascular disease, atherosclerosis, and stroke. Glucocorticoid hormones are elevated chronically in stressed conditions and are thought to contribute to the pathogenesis of metabolic and cardiovascular disease. Despite strong evidence for this, non-pharmacologic therapies to reduce stress are not currently part of standard care for the prevention or treatment of metabolic... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

Understanding how stress contributes to cardiovascular and metabolic disease could lead to additional therapies targeting stress reduction for their prevention. The long-term impact of studies to establish and reduce the negative impact of stress on health could include better outcomes for stress reduction programs at work and strategies to reduce stress at home.

Feasibility and challenges of addressing this CQ or CC

Clinical trials to evaluate the efficacy of non-pharmacologic therapies targeting stress reduction are already feasible including such interventions as exercise, improved sleep, mindfulness, and social interaction. Some of these have been evaluated on a small scale, but future clinical trials should include long-term follow up and be sufficiently populated for their outcomes to influence patient care. Pharmacologic therapies targeting the stress system have not yet emerged as options for prevention and treatment, and pose a greater challenge. They will require investigation into the mechanisms of stress effects on chronic disease as well as intelligent drug design to minimize systemic side effects.

Name of idea submitter and other team members who worked on this idea Endocrine Society

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Goal 2: Reduce Human Disease

Identify Pathways of Risk Linking Psychosocial Stress to Ischemic Heart Disease in Women

Women differ from men in their manifestations of ischemic heart disease (IHD). They also differ from men with respect to prevalence of psychosocial factors and vulnerability to specific mental disorders. Young women, in particular, appear to be highly susceptible to the adverse cardiovascular effects of psychosocial stress. Those who already have clinical manifestations of IHD display high psychosocial burden which could... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

The study of young women from the community, and women with early-onset IHD, could be critical in uncovering women-specific pathways of IHD risk related to psychosocial stress. Investigations of the association between psychosocial factors and IHD should include sufficient numbers of young and middle-aged adults, and rather than only adjusting for sex, should conduct analyses stratified by sex. If psychosocial stress is a major risk factor for early-onset IHD in women, then psychosocial interventions specifically tailored to address women’s stressors and applied early in women’s lives should be especially helpful in improving or reverting IHD risk in this group. Most psychosocial or drug treatment interventions for depression have not been effective for improving IHD outcomes particularly among women, suggesting that more attention should be given to psychosocial pathways specific for women and to the identification of vulnerable subsets.

Feasibility and challenges of addressing this CQ or CC

Calls for proposals for mechanistic studies and intervention trials targeted to young women and men at risk for IHD or sampled according to different exposure levels should be a feasible starting point to investigate this area and begin identifying vulnerable subgroups and sex differences.

Name of idea submitter and other team members who worked on this idea Viola Vaccarino

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Goal 2: Reduce Human Disease

Devices to Enhance AVF Eligibility and Maturation

There are about 400,000 patients with end-stage renal disease in the U.S. who depend on hemodialysis (HD) for their survival. Creating effective and reliable vascular access sites that can connect patients to HD machines remains a major unmet clinical need. HD patients who use an arteriovenous fistula (AVF) for vascular access live longer, healthier lives and cost less to care for. However, only about 55% of HD patients... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

When a vein is connected to an artery to make an AVF, increased blood flow and wall shear stress (WSS) in the vein causes dilation, a critical element in AVF maturation and usability. However, with traditional AVF, the level of WSS cannot be controlled and small vein segments experience excessive WSS levels. Furthermore, the flow of blood from an artery is pulsatile, resulting in cyclic stretching of the vein wall, which has been shown in vitro to cause smooth muscle cell proliferation, which is linked to vein stenosis and AVF failure. A continuous flow source such as a rotary blood pump system may promote rapid vein dilation by delivering nonpulsatile blood and controlled WSS doses, potentially enabling more patients to receive AVF surgery and resulting in a large increase in the success rate from AVF surgery.

Feasibility and challenges of addressing this CQ or CC

This research would be best addressed through the NHLBI's SBIR program. Phase I would fund design and prototyping of devices, which would be tested in large animal models of peripheral vein dilation alongside a conventional AVF. Phase II would fund development of the most promising devices in a range of sizes, design for manufacturing, design verification & validation, and preparation for first-in-human studies.

Name of idea submitter and other team members who worked on this idea Howard Loree

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Goal 2: Reduce Human Disease

Redox regulation of cardiovascular and lung disease through thiols

Redox imbalance as represented by alterations in oxidative versus reductive stresses are well appreciated to occur during nearly all forms of cardiovascular and lung diseases. However, specific molecular mechanisms responsible for these changes remain largely unknown and poorly organized. Study of redox biology principals has revealed that protein cysteine thiols are a unique target for redox posttranslational modifications... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Protein cysteine thiols are recognized to be important for multiple signaling and cell biology functions due to unique properties of oxidation/reduction resulting in a 'thiol switch'. However, oxidative modifications of thiols are highly complex involving nitrosation, sulfhydration, sulfenylation, and glutathiolyation among many others. It has become increasingly clear that these posttranslational modifications are associated with cardiovascular and pulmonary pathophysiology. Yet, many important questions remain such as: how these thiol modifications occur during disease and differ from health? How do these thiol switches impact protein function involved in cellular pathophysiology? And can thiol switch manipulation be exploited for therapeutic purposes to maintain cellular and organ health or treat disease? In order to begin to answer these questions, careful and comprehensive investigations are required to understand thiol-switching principals employing a host of molecular, biochemical and pathophysiological approaches.

Feasibility and challenges of addressing this CQ or CC

Given the significant advances in quantitative analytical chemical and molecular techniques, molecular redox mediators and pathways, non-invasive imagine modalities and comprehensive translational study designs; multiple fields are uniquely poised that could provide significant insight into this critical challenge. Primary objectives would be to establish consensus analytical methodologies, chemical and molecular biology approaches, and cellular and animal models in conjunction with rigorous clinical investigations. Results from efforts at understanding the importance of ‘thiol switches’ will make significant clinical impact on cardiovascular and lung pathogenesis and would feasibly be accomplished in 5-10 years.

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