Showing 20 ideas for tag "cardiovascular"

Goal 2: Reduce Human Disease

Cardiometabolic Disease Risks Associated with Sleep Deficiency

How does insufficient sleep duration, irregular timed sleep schedules, and poor sleep quality contribute to the pathophysiology of lung, heart and blood diseases?

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

Details on the impact of addressing this CQ or CC

Sleep deficiency and untreated sleep disorders threaten the health of 20-30 percent of US adults through an increased risk of stroke, hypertension, diabetes, inflammatory disease, and all-cause mortality. Developing the scientific evidence-base of validated interventions will enhance the management of cardiometabolic and pulmonary risks to health, present new opportunities for secondary prevention, and reduce associated burden on health care systems.

Feasibility and challenges of addressing this CQ or CC

Improving sleep health through informed public recognition of decision-relevant science, and relatively low cost therapies for management of sleep disorders are available for immediate assessment of impact in appropriate clinical trials to demonstrate efficacy and effectiveness.
Discovery research advances implicate an array of cellular sleep and circadian mechanisms in pathophysiological pathways leading to cardiometabolic and pulmonary disease.

Irregular and disturbed sleep impairs cellular biological rhythm in all tissues and organs leading to oxidative stress, unfolded protein responses, and impaired cell function. The pathophysiological findings juxtaposed with epidemiological evidence of disease risk indicate that sleep deficiency contributes to an erosion of health across the lifespan over and above the effects of aging.

Name of idea submitter and other team members who worked on this idea NHLBI Staff

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94 net votes
122 up votes
28 down votes
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Goal 2: Reduce Human Disease

SLEEP DISORDERS AS A MODIFIABLE RISK FACTOR FOR CHRONIC DISEASE

There is developing evidence that sleep disorders, in particular obstructive sleep apnea and inadequate sleep, can influence the course of other chronic diseases. Observational studies show that CPAP treatment of patients with pre-diabetes who have OSA reduces the incidence of future diabetes. Moreover, animal and human data indicate that insufficient sleep and sleep apnea can affect the rate of progression of neurodegenerative... 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

This question will have considerable impact. Sleep apnea is an independent risk factor for insulin resistance. Moreover, observational studies show that treatment of OSA reduces the rate of future diabetes compared to that which occurs in untreated OSA. Therefore, identifying OSA and treating this could have a profound impact on reducing the rate of diabetes, i.e., a preventative strategy.

Both sleep loss and obstructive sleep apnea have also been shown to be risk factors for subsequent development of Alzheimer’s disease. This has been shown in mouse models and in epidemiological studies to address whether insufficient sleep and sleep apnea are independent risk factors for development of Alzheimer’s disease, in particular accelerating their onset. Determining whether this is so and whether interventions to treat these sleep disorders delay onset of diabetes and Alzheimer’s disease would have profound public health significance.

Feasibility and challenges of addressing this CQ or CC

These disorders are extremely common so that recruitment of subjects is not challenging. Moreover, new technology reduces protocol burden to assess individuals. All studies can be done in the patients’ home. There are existing cohort studies focused on diabetes and the Alzheimer’s Center program that could be used for these studies. Thus, the studies are extremely feasible in the near term.

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

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156 net votes
211 up votes
55 down votes
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Goal 2: Reduce Human Disease

RFA on EC-cardiomyocyte interactions in the mechanisms and treatments of cardiovascular diseases

Often under recognized, the cardiac endothelial cells are highly abundant in the heart, and may have important roles in modulating cardiac function, besides simply serving as structural component of blood vessels. Evidences of ours and others have indicated an emerging role of cardiac endothelial cells signaling to cardiomyocytes to mediate important pathophysiological responses. Nonetheless, detailed mechanisms of... 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

Successfully addressing this question would no double reveal novel mechanisms and ways of monitoring treatment responses of cardiovascular disease, ultimately leading to novel drug targets, valuable biomarkers and extended new directions of basic research as well.

Feasibility and challenges of addressing this CQ or CC

Tools of studying these cells are mostly available. Both adult cardiomyocytes and endothelial cells from the heart can be isolated and cultured, although cardiomyotyes need to used within 24 hrs and cannot be passaged. However successful preparation of these cells from WT and transgenic animals would permit co-culture experiments and mechanistic studies. These cells can also be studied using in-situ techniques either detecting molecular changes/events or dynamic interactions. Potential challenges would side in selective targeting of these cells, for example, either ECs or cardiomyocytes, once a potential therapeutic is in the testing. Nonetheless, PECAM-ab conjugated techniques have been employed to specifically deliver proteins to endothelial cells, so I am confident most of the challenges can be worked out, particularly within a RFA awardees group with frequent exchanges of ideas.

Name of idea submitter and other team members who worked on this idea Hua Linda Cai, University of California Los Angeles

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27 net votes
30 up votes
3 down votes
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Goal 2: Reduce Human Disease

New ideas from drug-induced cardiotoxicity

What are the fundamental mechanisms of drug, chemical, or biologics-induced cardiotoxicity (e.g., which proteins or signaling targets are most vulnerable)? Would such knowledge lead to understanding of the most critical signaling systems and contribute to development of new therapeutic (cardioprotective) strategies?

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

Details on the impact of addressing this CQ or CC

Beyond helping with real-world problems (e.g., cancer drug cardiotoxicity), understanding of toxicity mechanisms in the CV system enables a different level of understanding. For example, acute toxicity testing is probably akin to crash testing of the CV system, permitting us to see where things break. Thus there is potential to lead to a fuller understanding and novel therapeutic ideas.

Feasibility and challenges of addressing this CQ or CC

As the number of newer and more powerful therapeutics grow, their risk of adverse impact on the CV system grows. This is in part due to insufficient knowledge of toxicity mechanisms and lack of effective drug-screening tools during drug development. This field primarily lacks researchers.

Name of idea submitter and other team members who worked on this idea NHLBI Staff

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19 net votes
45 up votes
26 down votes
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Goal 2: Reduce Human Disease

Diet and prevention of cardiovascular events

In the US, what kind of diet(s) is/are best for preventing hard cardiovascular events?

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

Details on the impact of addressing this CQ or CC

Provide an evidence base for public policy on diet.

Feasibility and challenges of addressing this CQ or CC

The Spaniards have shown that this kind of trial is possible. We have tools and interest in place for pragmatic trials.

The PREDIMED trial (done in Spain) randomized ~7000 adults and found that a diet supplemented with olive oil or nuts reduced cardiovascular events compared to a "low-fat" diet. However, in Spain the Mediterranean diet is arguably the norm.

Name of idea submitter and other team members who worked on this idea NHLBI Staff

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8 net votes
20 up votes
12 down votes
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Goal 2: Reduce Human Disease

Reducing Atrial Fibrillation by treating modifiable risk factors

Would better management of modifiable risk factors, including obesity, sleep apnea, hypertension, hyperglycemia, and metabolic syndrome, reduce atrial fibrillation recurrence? Furthermore, what are the best methods to reduce the onset, hospitalization, and death due to atrial fibrillation, especially that associated with aging

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

Details on the impact of addressing this CQ or CC

Identify strategies to prevent or reduce recurrence of atrial fibrillation using available lifestyle and medical therapies.

Feasibility and challenges of addressing this CQ or CC

There is a large population of patients with atrial fibrillation available to test this hypothesis along with strategies for treatment of modifiable risk factors. A challenge is to identify the good strategies to ensure adherence.

Name of idea submitter and other team members who worked on this idea NHLBI Staff

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3 net votes
18 up votes
15 down votes
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Goal 2: Reduce Human Disease

RCT of stepped-care depression treatment on CV events & death

Does treating depression improve survival and reduce major adverse cardiac events in acute coronary syndrome patients?

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

Details on the impact of addressing this CQ or CC

A substantial evidence base now exists showing that depression is associated with a two-fold increased risk of death and recurrent CV events in cardiac patients, leading to a recent AHA scientific statement recommending its elevation to the status of a risk factor for adverse medical outcomes in patients with acute coronary syndrome (Lichtman et al., 2014). Yet there is currently no clinical trial evidence that reducing depression improves cardiac morbidity and mortality. A clinical trial, using new, more effective depression treatment methods, such as collaborative care approaches that combine psychological counseling with medication in stepped-care fashion, is needed to determine whether effective treatment of depression can improve survival and reduce clinical cardiovascular events in cardiac patients.

Feasibility and challenges of addressing this CQ or CC

Newer stepped-care treatments for depression, combining medication and psychotherapy, have recently been developed and found to more effectively reduce depression than earlier treatments. By using these newer treatment methods to substantially lower depression, we can better answer the question as to whether treating the newly acknowledged risk factor of depression in ACS patients can improve clinical outcomes in these patients.

Name of idea submitter and other team members who worked on this idea NHLBI Staff

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5 net votes
22 up votes
17 down votes
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Goal 2: Reduce Human Disease

Relevance of cardiovascular disease associated with autoimmunity research

NIH estimates up to 23.5 million Americans suffer from autoimmune disease (AD) and up to 24 million from heart diseases. As a result, NIH and AHA estimates the annual direct health care costs for AD to be in the range of $100 billion and $200 billion for heart and stroke diseases. Yet this area of research has been neglected and underfunded. The proposition is for NHLBI to partner with other NIH institutes dealing with... 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

Reduce the impact of autoimmune diseases on the heart and vascular system.

Feasibility and challenges of addressing this CQ or CC

Generate RFAs dedicated to the field of autoimmune associated cardiovascular diseases.

Name of idea submitter and other team members who worked on this idea M. Boutjdir

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11 net votes
15 up votes
4 down votes
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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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11 net votes
12 up votes
1 down votes
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Goal 2: Reduce Human Disease

Noninvasive biomarkers for characterizing cardiovascular disease

Critical Challenge

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

Details on the impact of addressing this CQ or CC

Phenotypical characterization of cardiovascular disease with computed tomography (CT) and magnetic resonance imaging (MR) to individualize targeted therapies for coronary artery and myocardial disease. Coronary artery disease is a major cause of patient death in the United States. Nonischemic myocardial disease includes entities with clinically heterogeneous presentations and is thus challenging to manage.

Feasibility and challenges of addressing this CQ or CC

Currently CT and MR technology allows dynamic evaluation of the perfusion and contractility of the heart. Quantitative measures of disease burden, such as atherosclerotic plaque composition and myocardial texture imaging biomarkers (such as T1 mapping, activation mapping, flow pattern analysis, delayed myocardial enhancement), are possible. Positron emission tomography (PET)/MR, which combines metabolic with functional evaluation, is currently available and facilitates the development of targeted molecular-imaging techniques. Metrics derived from these techniques may serve to stratify patients noninvasively and direct appropriate therapies. Such imaging methods address noninvasive evaluation of cardiovascular disease, including ischemic heart disease but also myocardial diseases that include secondary and infiltrative cardiomyopathies, hypertrophic cardiomyopathy, and organ rejection in the scenario of transplantation.

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

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8 net votes
11 up votes
3 down votes
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Goal 2: Reduce Human Disease

Understanding the Role of the Vasculature in Dementia

Dementia is traditionally grouped into vascular dementia, Alzheimer's dementia, Parkinson's dementia and other causes of dementia. Vascular dementia is generally thought to be a consequence of strokes but there are some recent studies indicating that even Alzheimer's dementia may have a vascular underpinning. Vascular permeability is increased in the early stages of Alzheimer's disease and it is possible that similar... more »

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

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The NHLBI could fund programs which enable vascular biologists to collaborate with neuroscientists and neurologists in order to understand whether the vasculature has a causal role in the progression of dementia.

 

 

Can interventions that improve vascular function prevent the progression of dementia? Instead of using broad interventions such as statins which affect numerous signaling pathways, vascular biologists could target selected aspects of vascular health such as improving vascular barrier function and vascular regeneration.

If these interventions that have been shown to be efficacious in other vascular beds outside of the brain are also effective in the brain, then important new therapies could be developed for dementia which is likely to become one of the leading cause of death in the next decades.

Feasibility and challenges of addressing this CQ or CC

A key challenge for targeting the brain vasculature will be the blood-brain barrier. Understanding the role of the blood-brain barrier in dementia will be a prerequisite to developing novel vasculature-directed therapies.

Name of idea submitter and other team members who worked on this idea Jalees Rehman

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9 net votes
13 up votes
4 down votes
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Goal 2: Reduce Human Disease

Imaging indicators of metabolic syndrome and cardiopulmonary disease

Critical Challenge

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

Details on the impact of addressing this CQ or CC

Obesity and metabolic syndrome affect a large portion of the population and affects multiple organ systems. Identifying obesity phenotypes by imaging will impact the significant healthcare issue presented by MetS and could provide a reliable, non-invasive index of disease severity, guide prevention and intervention response.

Feasibility and challenges of addressing this CQ or CC

Metabolic syndrome, abnormal metabolism, may be potentially linked to obesity and cardiopulmonary disease. Theories exist but are in need of clarification. The relationship between metabolic syndrome and multiple other diseases including chronic obstructive lung disease, coronary atherosclerosis, and obesity warrants further investigation and can be elucidated through imaging. Advances in computed tomography (CT) and magnetic resonance imaging (MR) enable assessment of the cardiopulmonary manifestations, with promising MR techniques to complement high-resolution imaging data achievable with chest CT and coronary CT angiography. Assessment of CT and MR techniques in combination with three-dimensional quantitative analysis of manifestations of metabolic syndrome such as fat deposits derived from different adipocytes (white fat versus brown fat) such as in the subcutaneous, visceral, epicardial, and perivascular regions is feasible with current technology and may enable differentiation of those with varying risks of cardiovascular and pulmonary disease. The association of imaging parameters, metabolic syndrome, and associated diseases are in need of investigation, and knowledge gained may prove crucial for identifying those at risk for metabolic syndrome and at higher risk for complications in the large population of our country affected by obesity.

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

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6 net votes
10 up votes
4 down votes
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Goal 2: Reduce Human Disease

Development of non-contrast alternatives in cardiac magnetic resonance imaging

Critical Challenge

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

Details on the impact of addressing this CQ or CC

Late gadolinium-enhancement cardiac magnetic resonance imaging (MR) plays a crucial role in the evaluation of patients with suspected myocardial scar tissue. Alternative methods to contrast-enhanced MR however are in need, given the number of patients who have concomitant compromised renal function and concern for nephrogenic systemic fibrosis. Noncontrast MR techniques such as diffusion-weighted imaging would complement and eventually replace gadolinium administration thus impacting the evaluation of those with suspected and confirmed infiltrative cardiac processes and systemic diseases.

Feasibility and challenges of addressing this CQ or CC

Late gadolinium enhancement technique characterizes enhancement patterns of heart disease, identifies areas amenable to ablation, and aids in decisions pertaining to workup and therapy. The underlying mechanism of Brownian motion/diffusion in the expanded extracellular space makes diffusion weighted imaging a potential gadolinium-saving modality. Diffusion MR, applied primarily in the brain and abdominal imaging, is underutilized in the heart given respiratory and cardiac motion. A need exists to further develop and apply noncontrast MR techniques towards cardiovascular applications. Such methods are promising noncontrast alternatives to characterize patients with myocardial disease, determine those with differing prognoses, and direct appropriate therapies to subgroups.

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

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3 net votes
6 up votes
3 down votes
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Goal 2: Reduce Human Disease

Short comprehensive cardiac MR imaging in post-chemotherapy cancer patients

Critical Challenge

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

Details on the impact of addressing this CQ or CC

Cardiovascular disease and cancer are frequently identified in the same patient. Both diseases are highly prevalent in the United States population, and cancer or its therapies can result in cardiovascular disease. Early diagnosis and prediction of cardiovascular disease in patients to undergo therapy will identify patients at higher risk for cardiac dysfunction and enable earlier diagnosis of subclinical cardiac dysfunction.

Feasibility and challenges of addressing this CQ or CC

Cardiovascular magnetic resonance imaging (MR) is a powerful imaging modality for evaluating the heart function. Specifically, MR techniques allow for quantifying regional heart function, e.g. strain and strain rate, and may provide earlier markers of cardiovascular disease development than global measures of heart function, e.g. left ventricular ejection fraction, as estimated by echocardiography. Early identification of subclinical heart failure of post-chemotherapy cancer patients will allow for early and on-time chemotherapy change and personalized treatment.

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

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3 net votes
6 up votes
3 down votes
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Goal 2: Reduce Human Disease

Hormonal influences on atherosclerotic cardiovascular disease (ASCVD)

Cardiovascular diseases are the leading cause of morbidity and mortality for both men and women worldwide. It has been established that post-menopausal women have decreased protection from ASCVD relative to premenopausal women and men. However, the hormonal basis of protection (or lack thereof) is not clear.

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

Details on the impact of addressing this CQ or CC

By addressing this question, we will gain a greater understanding of hormone-based risk factors for ASCVD in women and men. Beyond expanding our fundamental knowledge of how hormones interact with cardiovascular systems, we could develop or improve therapeutic strategies for addressing risk factors for cardiovascular disease.

Feasibility and challenges of addressing this CQ or CC

Addressing this question is feasible and could be most effectively addressed through strategic initiatives sponsored by the institute. It will require a systematic approach to investigating differences in hormonal status between pre and post-menopausal women, as well as comparing them to male hormonal status. At the level of basic research, progress in this area may be slowed because researchers are not currently required to balance the studies of males and females in preclinical research involving animal models.

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

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2 net votes
6 up votes
4 down votes
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