Goal 2: Reduce Human Disease

Vascular Origins of Cognitive Decline

A comprehensive research plan is needed to identify the vascular causes of cognitive decline, to develop early treatment options, and most ideally, develop effective measures to maintain cognitive function.

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 :

Reduction in the number of elderly with cognitive impairment would not only increase quality of life but would reduce health care costs. Research is indicating that the pathologic decline in cognitive function is complex and may involve multiple pathways of cardiovascular and metabolic origin.

Feasibility and challenges of addressing this CQ or CC :

Addressing this issue requires research on vascular biology, tools for brain imaging and measurements of cognitive decline, all of which are advancing in development and implementation. The 2013 BRAIN Initiative includes $100 million in commitments from 5 federal agencies, including $46 million from NIH in grant awards focusing on new tools and techniques.

The frequently observed cognitive decline with aging can occur in a mild state or can progress to forms of dementia that are devastating to individuals and families and require a functioning and affordable support system for the affected individual. The vascular origin of this decline is only beginning to be understood. With increasing numbers of the US population surviving to their 80s and 90s, healthy cognition is critical for these elderly to be able to live independent functioning lives. .

 

As always commitment of funds is required as well as identifying appropriate research populations and efficient study designs.

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

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30 net votes
51 up votes
21 down votes
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Goal 2: Reduce Human Disease

what endogenous anti-inflammatory mechanisms can improve vascular diseases

the role of pro-inflammatory mechanisms of vascular disease are well characterized, but we know little about potentially protective endogenous anti-inflammatory mechanisms.

Submitted by (@mautieri)

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 will identify new therapy or targets of therapy to improve our understanding of most vascular disease and lead to improved human health.

Feasibility and challenges of addressing this CQ or CC :

this is quite feasible; if we know so many pro-inflammatory mechanisms which for years we have tried to reduce or prevent, we can just as easily identify endogenous anti-inflammatory mechanisms that we can identify and enhance.

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

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10 net votes
18 up votes
8 down votes
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Goal 2: Reduce Human Disease

Novel methods to diagnose and treat microvascular ischemia

Microvascular ischemia is common, particularly in the setting of critical illness. We need better ways to evaluate, diagnose and treat these conditions, whether they relate to microvascular myocardial ischemia, as a primary diagnosis of complication of other acute illness, or non-myocardial ischemia during the course of surgery, injury, infection or acute illness.

Submitted by (@greg.martin)

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

Details on the impact of addressing this CQ or CC :

Development of effective diagnostics would lead to improved treatments for myocardial and non-myocardial microvascular ischemia, and also advance understanding to extend the advance beyond this setting.

Name of idea submitter and other team members who worked on this idea : Society of Critical Care Medicine Executive Committee/Council

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0 net votes
2 up votes
2 down votes
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Goal 2: Reduce Human Disease

Lipid apheresis as adjunct therapy in peripheral vascular disease

What is the roll of inflammation and how does lipid apheresis alter inflammation in peripheral vascular disease when added to standard therapy and/or when used alone? Does lipid apheresis result in long-term improvement with reduced morbidity, mortality, and expense compared to standard therapy?

Submitted by (@winters.jeffrey)

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 prevalence of peripheral vascular disease (PVD) in the United States is estimated to be 5.9%, affecting up to 20% of adults over the age of 65. Therapy for PVD is vascular surgical intervention for limb ischemia; combined with medical therapy and anti-platelet agents but morbidity and mortality remains high. Low density lipoprotein cholesterol (LDL-c) is associated with increased risk for development and progression of PVD. Preliminary studies of the use of lipid apheresis have demonstrated improvement in symptoms and a variety of laboratory measures with decreased morbidity when added to standard therapy. The mechanism of this treatment may go beyond reducing LDL-c as the columns also affect levels of inflammatory cytokines, alter blood rheology, and affect other lipids.

Feasibility and challenges of addressing this CQ or CC :

Currently two lipid apheresis devices have been cleared by the Food and Drug Administration and are in use in the United States. The presence of cleared devices, the large number of affected patients, and availability of testing for lipoproteins, fibrinogen, CRP, PAI-1, IL-6, IL-17, IL-1, IL-10, INF-γ, VEGF, PGI2, IGF-I and rheology factors make the enrollment and evaluation of patients into a clinical trial examining the use of this treatment of PVD feasible. Challenges for the performance of a clinical trial would include the limited number of centers offering lipid apheresis, the chronic nature and length of time needed to perform lipid apheresis, and the expense of the lipid apheresis devices and disposables.

Name of idea submitter and other team members who worked on this idea : Bruce Sachais on behalf of ASFA

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96 net votes
116 up votes
20 down votes
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Goal 2: Reduce Human Disease

Pulmonary Vascular Diseases

Does "goal-targeted" therapy (with adjustments/additional therapy, if certain "goals" are not achieved) improve quality of life, functional status, and survival in patients with pulmonary arterial hypertension? Trials of therapies for hepatopulmonary syndrome.

Submitted by (@nhlbiforumadministrator)

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

Feasibility and challenges of addressing this CQ or CC :

This is a view of problems in the field.

Pulmonary Hypertension Clinical Research: Current Problems and Possibilities

Current studies limited to the short term, with soft outcomes.

No mechanistic studies embedded in trials.

Control of phenotype is weak.

Small n: lumping of cohorts.

No factorial of advanced design.

No biological samples obtained for study.

Failure to study basic management issues.

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

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2 net votes
2 up votes
0 down votes
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Goal 2: Reduce Human Disease

Vascular biology and the pathophysiology of sepsis

Unravel the cellular & molecular mechanisms related to the vascular biology of sepsis and related cardiovascular collapse. The goal is to develop a new scientific framework for the prevention of sepsis related morbidity and mortality by applying novel approaches to discover new targets for biomarkers and therapy by promoting multidisciplinary research required for scientific cross-talk between complementary research disciplines ...more »

Submitted by (@greg.martin)

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

Name of idea submitter and other team members who worked on this idea : Society of Critical Care Medicine Executive Committee/Council

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4 net votes
8 up votes
4 down votes
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Goal 1: Promote Human Health

Mechanisms of Vascular Stiffness

Increased vascular stiffness has been identified as an important cardiovascular event that accompanies aging and cardiovascular disease. Although multiple vascular changes have been identified and suggested to cause increased vascular stiffness, our understanding of the underlying mechanisms needs to be refined in order to develop useful therapeutic strategies to prevent or reverse these changes. An example of critical ...more »

Submitted by (@meiningerg)

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

Details on the impact of addressing this CQ or CC :

Ultimately, addressing this CQ would impact treatment of CV disease, reduce incidence of significant and life threatening CV events and improve quality of life. This area of investigation is relevant to therapeutics and potentially lifestyle changes that will improve CV health and slow CV age related changes linked to disease.

Feasibility and challenges of addressing this CQ or CC :

Current advances in our technologies make it very feasible to address new questions to improve our knowledge of the mechanisms underlying vascular stiffness. Challenges will include developing multi-scale and cross disciplinary strategies that will, by design, facilitate an integrated understanding of the process leading to altered vascular stiffness.

Name of idea submitter and other team members who worked on this idea : Gerald A. Meininger

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55 net votes
88 up votes
33 down votes
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Goal 2: Reduce Human Disease

Pulmonary Vascular Diseases

Does treatment with spironolactone improve outcomes in patients with pulmonary arterial hypertension (and/or pulmonary hypertension associated with diffuse parenchymal lung disease or COPD)? Spironolactone has been shown beneficial in CHF and many of the same mechanisms are at plan in RV failure from pulmonary hypertension. Again, no clear evidence whether this is a useful treatment or not, and no evidence to guide ...more »

Submitted by (@nhlbiforumadministrator)

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

Feasibility and challenges of addressing this CQ or CC :

This is a view of problems in the field.

Pulmonary Hypertension Clinical Research: Current Problems and Possibilities

Current studies limited to the short term, with soft outcomes.

No mechanistic studies embedded in trials.

Control of phenotype is weak.

Small n: lumping of cohorts.

No factorial of advanced design.

No biological samples obtained for study.

Failure to study basic management issues.

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

Voting

2 net votes
2 up votes
0 down votes
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Goal 3: Advance Translational Research

Animal models of vascular diseases

How can we better model human vascular disease in all its complexity?

­This is key to more effective translation of both diagnostics and therapeutics. Develop improved animal models of vascular diseases including PAD, aneurysm, venous diseases, to facilitate fundamental research and preclinical development.

Submitted by (@societyforvascularsurgery)

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

Name of idea submitter and other team members who worked on this idea : Society for Vascular Surgery

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

Cause of disparity in prevalence and progression of various vascular disorders

What are the causative factors underlying the disparity in prevalence and progression of various vascular disorders (PAD, CVD, aneurysm) across populations?

Submitted by (@societyforvascularsurgery)

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

Details on the impact of addressing this CQ or CC :

­Genetic, epigenetic, biochemical, nutritional, environmental, and psychosocial factors should be characterized.

Name of idea submitter and other team members who worked on this idea : Society for Vascular Surgery

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2 net votes
2 up votes
0 down votes
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Goal 3: Advance Translational Research

Direct Upregulation of Antioxidant Defenses as a Therapeutic Strategy

Clinical trials involving administration of antioxidants such as vitamin C or vitamin E as therapeutic strategies for cardiovascular diseases associated with oxidant stress have proven to be surprisingly disappointing. A particularly attractive alternative approach is direct upregulation of endogenous antioxidant defenses such as NRF2 via dietary approaches. NRF2 is a master antioxidant and cell protective transcription ...more »

Submitted by (@jlombard)

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

Details on the impact of addressing this CQ or CC :

Direct upregulation of endogenous antioxidant defenses such as NRF2 via dietary approaches will avoid the well known caveats of drug-based approaches such as off target effects and detrimental side effects. Dietary supplements such as Protandim are already available; and beneficial effects of other NRF2 up-regulators such as resveratrol and sulforaphane are beginning to be recognized. The dietary approach is minimally invasive and has high preventative value.

Feasibility and challenges of addressing this CQ or CC :

Addressing this CQ is clearly feasible, as dietary supplements are currently available for humans, and the beneficial effects of foods containing compounds that upregulate the NRF2 system, e.g., broccoli, cauliflower, red wine, and grape juice are currently recognized. One challenge in addressing this question in animal models to date is that the only genetic model lacking NRF2 is a knockout mouse model, which have substantial limitations for in vivo physiological studies due to their small size. However, a recent R21 grant (#1R21OD018309-J. H. Lombard, P.I.) has allowed the development of a NRF2 knockout rat model which is better suited for physiological studies than the mouse model. In addition, the techniques used to develop the NRF2 knockout rat can be applied to multiple disease-sensitized strains, e.g., the Dahl salt-sensitive rat. Fawn Hooded Hypertensive rat, Obese Zucker rat, etc. Similar disease sensitized rodent genetic strains are not available in mice.

Name of idea submitter and other team members who worked on this idea : Julian H. Lombard

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-5 net votes
2 up votes
7 down votes
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Goal 2: Reduce Human Disease

National network to study the pathobiology of sepsis

Sepsis is the leading cause of death in hospitalized patients, the 3rd leading cause of death in all people in the US, the most common condition leading to widespread vascular collapse, among the most common causes of respiratory failure, and a frequent cause of acute cardiac dysfunction.

Submitted by (@greg.martin)

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

Details on the impact of addressing this CQ or CC :

Developing a national network to address important aspects of sepsis (causes and consequences of cardiac dysfunction, molecular determinants of respiratory failure) and serve as a trials group for testing novel interventions for new discoveries.

Name of idea submitter and other team members who worked on this idea : Society of Critical Care Medicine Executive Committee/Council

Voting

2 net votes
4 up votes
2 down votes
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