Goal 2: Reduce Human Disease

Close the gap: Why do men die of cardiovascular disease (CVD) at an earlier age than women?

Despite evidence that women face challenges in receiving optimal CVD care, data show that men die at an earlier age than women of CVD. This health disparity remains unexplained and there are no specific interventions to address it.

Submitted by (@collerb)

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 comprehensive T1-T4 initiative is required to explore this health disparity, ranging from epidemiology to basic mechanisms , and to translate that knowledge into specific interventions.

 

Closing the gap would add ~4 years of life to men, representing a monumental health improvement.

Feasibility and challenges of addressing this CQ or CC :

Conceptually this is straightforward since so many data are already available about sex differences in cardiovascular biology. The challenge is to review the information from this frame of reference and with the specific goal of identifying interventions.

Name of idea submitter and other team members who worked on this idea : Barry Coller

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3 up votes
1 down votes
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Goal 2: Reduce Human Disease

Addressing low-level-evidence in cardiovascular guidelines

There is a need for the NHLBI to systematically assess CV guidelines that have public health importance and that can be addressed by pragmatic, government-funded trials.

Submitted by (@nhlbiforumadministrator1)

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

Details on the impact of addressing this CQ or CC :

A much greater proportion of CV guidelines which dictate practice standards would be based on high-quality scientific evidence.

Feasibility and challenges of addressing this CQ or CC :

Guidelines are already written and levels of evidence are already assessed (by others). Methods for conducting pragmatic trials exist (e.g. embedding in registries, leveraging digital resources, recognizing the importance of pragmatic trials within the clinical community).

More than 85% of active CV guideline are based on less than level 1A evidence.

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

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2 up votes
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Goal 1: Promote Human Health

What motivates adults to exercise?

Getting people to change from a sedentary to active lifestyle is difficult. What institutional supports are most effective? What is the cost benefit of prevention versus treating cardiovascular disease.

Submitted by (@heartpathacupuncture1)

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

Details on the impact of addressing this CQ or CC :

Reducing the costs of treating cardiovascular disease (and possibly some cancers)

Feasibility and challenges of addressing this CQ or CC :

Considering the money spent on treatment this strategy should be feasible.

Name of idea submitter and other team members who worked on this idea : Shoshana

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21 net votes
39 up votes
18 down votes
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Goal 3: Advance Translational Research

Greating grant mechanism for fostering collaboration with industrial partners

There is a disconnect between the cardiovascular devices industry and the basic research that is conducted in the field by biomedical engineering researchers. Technological solutions that the industry is converging to are not well informed by the advances in basic translational research. A distinct funding mechanism should be created for fostering such collaborations. To motivate for profit cardiovascular device manufacturers ...more »

Submitted by (@danny.bluestein)

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

Name of idea submitter and other team members who worked on this idea : Danny Bluestein, Ph.D.

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1 net vote
9 up votes
8 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 »

Submitted by (@hcai00)

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 3: Advance Translational Research

Identification of autoantigens that elicit pathogenic immune responses in cardiovascular diseases

Pathogenic immune responses participate in the pathogenesis of many cardiovascular diseases. However, the autoantigens and foreign antigens that elicit the pathogenic immune responses have been poorly identified. Currently, the regulatory mechanisms on immune responses associated with diseases got some attentions. But, without detailed characterizations of this wide spectrum of autoantigens and foreign antigens in patients ...more »

Submitted by (@xfyang)

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

Feasibility and challenges of addressing this CQ or CC :

1) use peptide/protein based microarray to antibody autoimmune responses associated with each major cardiovascular diseases;

2) use MHC tetra-mers or similar techniques to characterize T cell autoimmune responses associated with each major cardiovascular diseases;

3) determine autoantigen repertoire changes in patients' responses to current therapies, especially therapies with immune modulating effects;

4) develop autoantigens-based immune therapies for clinical trials

Name of idea submitter and other team members who worked on this idea : Professor Xiaofeng Yang, MD, PhD, Professor Hong Wang, MD, PhD, Professor Klaus Ley, MD

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26 net votes
28 up votes
2 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 »

Submitted by (@jnoel0)

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 3: Advance Translational Research

NHLBI Cardiovascular Engineering Strategy

Most impressive and impactful advances in CV diagnostics and therapies came in the last 50 years from CV engineering, including implantable devices and imaging technology. CV engineers are developing next breakthrough technology including tissue engineering and flexible electronics. However, organizational structure of NIH does not have an entity responsible for strategic development of CV engineering. NIBIB does not ...more »

Submitted by (@efimov)

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 Science produced numerous fundamental ideas, which frame our approaches to diagnostics and therapy of heart disease. However, translating these ideas to clinic very often requires engineering approaches. Examples of such breakthrough therapies are implantable pacemakers and defibrillators, stents, MRI, CT and many other imaging modalities. NIBIB supports many fields of biomedical engineering, except cardiovascular! NHLBI lacks a branch responsible for strategic development of cardiovascular engineering as a critical pathway to translation of basic science ideas. There is no study section or review group focusing on cardiovascular engineering. As a result, most of CV Engineering grants are reviewed by CV biologists, who lack engineering background and have quite different priorities and vision of the field. Next breakthrough developments will happen in tissue engineering, flexible/stretchable/biodegradable electronics, novel imaging modalities, computational physiology, and other classical biomedical engineering sub-fields. Unfortunately, they are less likely to happen in cardiovascular field, because NHLBI lacks corresponding organizational structure. A working group should be formed to frame NHLBI's vision for the future of cardiovascular engineering as an indispensable component for translation from CV biology to CV therapy.

Feasibility and challenges of addressing this CQ or CC :

Biomedical engineering has trained several generations of professionals in academia and industry, which pursue basic and translational research and development with great degree of success. CV Engineering is a standard component in numerous BME Departments. Large number of senior and junior CV engineers have been recognized for their significant contribution to CV health. There is enormous CV engineering expertise and experience, which should be leveraged by NHLBI, in order to broadly define institutional strategy not only for CV biology but also for CV engineering, which are equally important in development of future breakthrough therapies for CV disease. Currently, support for CV engineering is scattered across numerous mostly biology focused groups, lacking strategic vision and coherent policy. A number of talented CV engineers are forced to leave the field to pursue other areas of biomedical engineering, which enjoy better-organized professional group support.

Name of idea submitter and other team members who worked on this idea : Igor Efimov

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8 net votes
17 up votes
9 down votes
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Goal 2: Reduce Human Disease

Development of non-contrast alternatives in cardiac magnetic resonance imaging

Critical Challenge

Submitted by (@str0001)

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

Noninvasive biomarkers for characterizing cardiovascular disease

Critical Challenge

Submitted by (@str0001)

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 3: Advance Translational Research

Develop biomarker panel to predict CVD risk in -omics era

There is a need to utilize the vast data generated in -omics research to develop biomarker panels for better prediction of cardiovascular disease (CVD) risks. •Cardiovascular diseases develop over decades and different panels of markers may be required for different stages •Lead molecules as potential biomarkers need to be selected by a panel of experts •Standard procedures about sample preparation, data acquisition, ...more »

Submitted by (@nhlbiforumadministrator)

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

Details on the impact of addressing this CQ or CC :

•Develop specific and sensitive markers for early prevention with more predictive power. Biomarkers that can detect specific perturbations in the system, such as metabolic status and vascular integrity prior to the occurrence of the diseases can be used for early preventive treatment of cardiovascular diseases.

 

•Identify vulnerable population who cannot be identified by the current LDL-HDL profiling

 

•Allow for more personalized treatment

Feasibility and challenges of addressing this CQ or CC :

•An increase in system biology studies using –omic approaches have provided huge data to mine through and find potential biomarkers, such as microRNA, DNA, lipids, proteins, and other metabolites, which can be used to assess changes proceeding cardiovascular diseases occurrence.

 

•The NIH-wide Big Data to Knowledge (BD2K) initiative launched in 2012 may have laid out some framework.

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

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7 net votes
14 up votes
7 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.

Submitted by (@jlaakso)

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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