Goal 2: Reduce Human Disease

To extend our knowledge of the pathobiology of heart, lung, blood, and sleep disorders and enable clinical investigations that advance the prediction, prevention, preemption, treatment, and cures of human disease.

Strategic Goal: Goal 2: Reduce Human Disease

Improving understanding of heart attack mechanisms in women and targeting of treatment

There remain many differences between women and men in the risk of myocardial infarction (MI or “heart attack”), manifestations of MI and outcomes after MI. The time in which the facts about differences between the sexes were unknown or ignored has passed. However, there are many basic answers women and their physicians need, such as: a) Why are younger women with MI at such high risk of death as compared to their male ...more »

Submitted by (@harmony.reynolds)

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 of sex differences is the most fundamental aspect of personalized medicine. When considering MI, some sex differences, such as lower risk of MI and a lesser extent of coronary artery disease (CAD, plaque buildup), favor women. Others, such as the 2-fold higher risk of death in younger women with MI and sex differences in the association between diabetes and MI, favor men. Insights into these and other sex differences should provide the foundation for optimal treatment for the prevention of MI and its complications.

Feasibility and challenges of addressing this CQ or CC :

Mechanistic and descriptive studies may be needed before clinical trials can be undertaken.

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

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Strategic Goal: Goal 2: Reduce Human Disease

10. What biological variables are most influential in the development and clinical outcomes of heart disease and what can be don

Given that approximately 64 percent of women who died suddenly of CHD had no previous symptoms4 and that traditional risk factors and scores underestimate CHD risk in women, there is a need to identify unique markers for women at risk for CHD60.

 

( from 10 Report)

Submitted by (@scampbell)

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

Details on the impact of addressing this CQ or CC :

Early detection and correction of such variables as elevated cholesterol, hypertension, diabetes and cigarette smoking, can reduce atherosclerosis (the main cause of CHD) and improve outcomes. These are modifiable to some extent with changes in lifestyle, improved diet, exercise and smoking cessation. Psychosocial risk factors, such as low socioeconomic status, anxiety, and depression have also been linked to CHD and should be evaluated.

There are also biomarkers, biomediators, neurohormones, and surrogate markers which can signal CHD. Some of these can be modified, including

 

• neurohormones which are part of the renin-angiotensin-aldosterone system that directly impact angiotensin II and arginine vasopressin1, 61, 62

• markers of the inflammatory processes such as C-reactive protein which may be a useful predictor of CVD and correlates significantly with future risk of developing hypertension63, 64

• markers of heart failure such as B-type natriuretic peptide

Surrogate markers of atherosclerosis and CHD risk include left ventricular hypertrophy, intima-media arterial wall thickness, proteinuria and microalbuminuria, endothelial dysfunction, coronary calcification and anemia1, 62.

Feasibility and challenges of addressing this CQ or CC :

Research shows that a variety of treatments – from lifestyle/behavioral changes, medications, and interventional treatments – can interrupt the progression of CHD. Further research is needed to demonstrate whether lifestyle and behavioral changes in women with known or suspected CHD can improve prognosis. Innovative approaches to care management that encourage changes in lifestyle should be considered. These include customized care management and the use of multidisciplinary teams of health practitioners who coordinate care for women at risk. Further research is needed to determine whether reducing or minimizing the novel biomarkers associated with CHD will result in lower mortality rates.

Name of idea submitter and other team members who worked on this idea : Susan M. Campbell, WomenHeart Scientific Advisory Council

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Strategic Goal: Goal 2: Reduce Human Disease

Macrovascular disease in Type 1 and Type 2 diabetes mellitus

Do the etiology and vascular pathology of macrovascular disease differ in Type 1 and Type 2 diabetes?

Submitted by (@nhlbiforumadministrator)

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

Details on the impact of addressing this CQ or CC :

Large scale impact on the rethinking of the paradigm of diagnosis, delay (prevention) and potential treatment of CVD due to the high prevalence of Type 2 diabetes and the not so low prevalence of Type 1 diabetes in the nation.

Feasibility and challenges of addressing this CQ or CC :

Given the number of patients with Type 2 diabetes who undergo CABG, and the potentially increasing number of Type 1 diabetes patients who live longer and undergo diagnostic testing for CAD, the potential sources of human coronary artery tissue is expected to be sufficient to perform some initial case-control or Type 1 vs Type studies. In addition to coronary arteries, other large arteries could be studied (e.g. cerebral [autopsies], carotid, aortic, femoral, popliteal, dorsalis pedis].

Small post-mortem studies have demonstrated that the atherosclerotic plaque in patients with Type 1 diabetes mellitus is more vulnerable to rupture than the plaque in patients with Type 2 diabetes mellitus. In addition, it has been suggested that CAC score or number of plaques is not as important as the composition of the plaque in predicting cardiovascular events in patients with Type 1 diabetes, since the plaque is more unstable in Type 1 than in Type 2 diabetes mellitus. Thus, some researchers have questioned whether CAC is a good biomarker of CAD in Type 1 diabetes mellitus.

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

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Strategic Goal: Goal 2: Reduce Human Disease

Study on key product factors for optimal Bone Marrow Transplantation (BMT) graft function

Hematopoietic progenitor cells (HPC) collected by Apheresis is the most common source used for BMT. How the cells are collected and what kinds of cells are collected can affect BMT graft function. Limited studies have been done to study the key product factors in relationship to optimal graft function. Questions remain such as the optimal lymphocytes contents for reduced infection post BMT, optimal megakaryocyte precursor ...more »

Submitted by (@yanyunw)

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

Details on the impact of addressing this CQ or CC :

Optimal cell therapy products can lead to reduced post BMT complication and reduced morbidity and mortality.

Feasibility and challenges of addressing this CQ or CC :

In vitro, animal studies, clinical samples can be used for key product factors for optimal BMT graft function.

These can be achieved if funding is available, as there are many centers perform allo and auto BMT.

Funding support is critically needed in this area.

Name of idea submitter and other team members who worked on this idea : Yanyun Wu on behalf of ASFA

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Strategic Goal: 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 »

Submitted by (@mboutjdir)

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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Strategic Goal: Goal 2: Reduce Human Disease

Additional research needed to identify various contributors of obesity

What are the specific contributors of obesity that lead to chronic positive energy balance and surplus energy storage?

Submitted by (@mturner)

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 is a health crisis of epic proportions. About 34% of adults in the US have obesity, up from 31 % in 1999 and about 15% in the years 1960 to 1980. The chronic diseases that result from obesity annually cost over $150 billion in weight-related medical bills. Reduction of obesity improves cardiovascular and other health outcomes, yet what is currently known about obesity is inadequate to combat the global obesity epidemic. A comprehensive understanding about the mechanics of obesity may help in developing more effective preventive and treatment strategies, which in turn will substantially improve cardiovascular and other health measures.

Feasibility and challenges of addressing this CQ or CC :

Years of obesity research have revealed the complex nature of this disease and its multi-factorial etiology. While research has firmly established the role of energy balance in weight gain and weight loss, it is important to discover upstream factors that predispose only certain individuals to energy imbalance. This may be addressed by further focusing on newly identified putative contributors of obesity, including but not limited to the impact of sleep deprivation, ambient temperature, age at first pregnancy, intrauterine and intergenerational factors, neuro-endocrine factors, epigenetics, environmental chemicals and endocrine disruptors, gut microbes, infections and the immune system, and social and behavioral factors associated with obesogenic behaviors. These studies may provide mechanistic insight that may also lead to the development of new pharmacological approaches. It is possible that cause-specific prevention or treatment approaches may yield more effective results than generic approaches that do not necessarily consider upstream modulators of energy imbalance, or inter-individual differences.

Name of idea submitter and other team members who worked on this idea : The Obesity Society

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Strategic Goal: 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 »

Submitted by (@jalees)

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 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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Strategic Goal: Goal 2: Reduce Human Disease

Research priorities: Sleep disorders in women

Women are more likely to have insomnia and they develop the condition at an earlier age than men. Hormone changes and menopause are two key factors but little is known about the mechanisms, which will inform the treatment. This is an understudied area of scientific focus with vast potential public health impact.

Submitted by (@hjoffe)

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

Details on the impact of addressing this CQ or CC :

Women are more likely to have insomnia and they develop the condition at an earlier age than men. Hormone changes and menopause are two key factors but little is known about the mechanisms, which will inform the treatment. This is an understudied area of scientific focus with vast potential public health impact.

Feasibility and challenges of addressing this CQ or CC :

Systematic investigation of the hormonal basis and menopause symptom contribution to insomnia in midlife women requires skilled investigation and controlled study design given variability of symtpoms.

Name of idea submitter and other team members who worked on this idea : Hadine Joffe, MD MSc

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Strategic Goal: Goal 2: Reduce Human Disease

Severe obesity prevention in pediatric and community settings

What novel lifestyle and behavioral modification therapies are needed to prevent or treat youth with severe obesity (>99th percentile for BMI) versus those who are overweight?

 

Can we harness ongoing registries such as POWER (Pediatric Obesity Weight Evaluation Registry) in pediatric primary care (PC) settings to implement novel trials that would link PC and community settings to prevent severe obesity in youth?

Submitted by (@nhlbiforumadministrator1)

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 huge impact on obesity prevention in high risk youth. In addition to physiologic and metabolic changes, severely obese youth are stigmatized and bullied more often than those who are overweight. Self-esteem issues are also common among severely obese youth. Reduction of obesity could improve long term cardiovascular risk factors as well as quality of life and future chronic diseases.

Feasibility and challenges of addressing this CQ or CC :

This CQ is feasible because there a smaller scale RCTs that are short term and have demonstrable efficacy that could be harnessed. Chronic obstructive sleep apnea is also common in severely obese subjects. Thus this initiative could be across HL divisions.

Severe obesity is prevalent in ~6% of US youth (~ 8% in African American and Hispanic youth). But there is limited research on the effects of lifestyle modification approaches on BMI and CV risk reduction in such youth. Of the limited number of tested lifestyle interventions, results (e.g., adiposity and metabolic) have been modest and not sustained long-term. Most severely obese youth may not qualify for bariatric surgery and questions arise on long-term effects of bariatric surgery in young subjects with severe co-morbidities who might qualify for surgery but may lack the emotional maturity, family support, and motivation.

 

Research to better elucidate the underlying physiological, psychological, and environmental factors associated with severe pediatric obesity are needed. Behavioral trials are needed that intervene on multiple areas of influence (e.g., pediatric care, family, and community) and evaluate traditional and non-traditional outcomes—adiposity, cardiometabolic risk factors including vasculature and function, and inflammatory markers and oxidative stress.

 

There could be challenges in changing behaviors but these could be mitigated with novel and intensive approaches.

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

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Strategic Goal: Goal 2: Reduce Human Disease

Why does loss of endoglin in adult blood cells lead to cardiac hypertrophy in HHT patients

Liver arteriovenous venous malformations creates a high flow shunt that over time creates high output cardiac failure with no effective treatments.

Submitted by (@mariannes.clancy)

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 : Marianne Clancy MPA, Chris Hughes PhD

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Strategic Goal: Goal 2: Reduce Human Disease

COPD care

What is the standard of care for stable COPD and acute exacerbation of COPD that should constitute the reference base for clinical trials?

Submitted by (@nhlbiforumadministrator1)

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 : NHLBI Staff

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Strategic Goal: Goal 2: Reduce Human Disease

Assessing gene knockout humans more effectively

What insights can be gathered from patients with single gene functional mutations to improve our understanding of the pathobiology of human disease?

Submitted by (@nhlbiforumadministrator)

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 : NHLBI Staff

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