Showing 2 ideas for tag "agents"

Goal 2: Reduce Human Disease

Does lowering circulating lipoprotein(a) levels influence cardiovascular outcomes?

A comprehensive research strategy and plan is needed to determine the most efficient, safe, cost-effective and widely applicable strategy to decrease circulating levels of lipoprotein(a) and to determine whether lowering circulating lipoprotein(a) levels will reduce the risk of developing cardiovascular disease such as a heart attack or a stroke as well as the progression of atherosclerosis or aortic stenosis.

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

Details on the impact of addressing this CQ or CC

Approximately 20% of the population are characterized by elevated circulating levels of lipoprotein(a), regardless of age, gender or blood cholesterol levels. Estimates suggest that up to 90% of the variation in plasma lipoprotein(a) levels could be due to genetic factors, which makes lipoprotein(a) the most prevalent inherited risk factor for cardiovascular diseases (CVD). Large-scale genetic studies have shown that Lipoprotein(a) was the strongest genetic determinant of CVD such as atherosclerosis and aortic stenosis. Lipoprotein(a) is one of the strongest predictors of residual CVD risk and has been shown to improve CVD risk prediction in several population-based studies. Lipoprotein(a) is also one of the strongest known risk factors for spontaneous ischemic stroke in childhood.
A comprehensive research strategy aiming at identifying, evaluating interaction with other risk factors, treating and educating patients with elevated lipoprotein(a) levels would result in substantial reductions of health care costs in the US and around the globe by reducing the burden of CVD while simultaneously improving the quality of life of these patients.

Feasibility and challenges of addressing this CQ or CC

The list of pharmaceutical agents that reduce lipoprotein(a) levels is steadily increasing. There are approximately half a dozen strategies that have been shown to significantly and safely lower lipoprotein(a) levels. One of the challenges of this research strategy will be to determine which of these strategies represent the most efficient, safe, cost-effective and widely applicable approach to lower lipoprotein(a) levels and CVD outcomes.
Increasing awareness on lipoprotein(a) and CVD will also be of utmost importance for this effort as relatively few physicians perform lipoprotein(a) testing and even fewer patients are aware of their lipoprotein(a) level. The first sign of high lipoprotein(a) is often a heart attack or stroke. Our challenge will be to identify patients with high lipoprotein(a) that could be enrolled in trials of risk characterization and lipoprotein(a)-lowering.

Name of idea submitter and other team members who worked on this idea Sandra Revill Tremulis on behalf of the Lipoprotein(a) Foundation Scientific Advisory Board

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Goal 2: Reduce Human Disease

Treatment of Major Depression in Patients with Heart Failure

Major depression (MD) is common in patients with heart failure, and it is an independent risk marker for functional decline, hospitalization, and mortality. Two large trials have shown that it can be difficult to treat. SADHART-CHF, a double-blind, placebo-controlled RCT (n=469), found that sertraline was not efficacious for MD in HF. MOOD-HF (n=372) showed that escitalopram was not efficacious. Smaller trials of cognitive-behavioral... 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

Major depression causes considerable emotional distress and functional impairment. It follows a chronic or recurrent course in many cases, and untreated episodes can last for months or even years. When superimposed on chronic heart failure, major depression can accelerate functional decline, diminish quality of life, and increase the risks of hospitalization and mortality. Effective treatment of depression can, at minimum, improve quality of life. Treatment may also decrease the risk of adverse medical outcomes, but RCTs will be needed to evaluate the potential medical benefits of treating depression in HF.

Feasibility and challenges of addressing this CQ or CC

Cognitive behavior therapy is the most promising approach tested so far, but there have been few trials of this intervention, any other psychotherapeutic treatment for depression, or antidepressant medications other than sertraline or escitalopram for major depression in HF. Additional phase II trials may be needed in order to identify the most promising approaches for testing in larger, multicenter RCTs.

Name of idea submitter and other team members who worked on this idea Kenneth E. Freedland, PhD

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