Division of Cardiovascular Diseases Strategic Plan
Goals in Cardiovascular Clinical Problems or Disease States
2.4b. Reduce the morbidity and mortality of hypertensive heart failure
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Heart failure (HF) continues to be a major disease burden in the United States. Unlike the downward trend in death rates for CHD since 1968, heart failure death rates have continued to rise. Similarly, both the prevalence and hospitalization rates for heart failure show an upward trend since the 1970s. According to latest estimates, there are a total of 5 million heart failure patients in the country, with hospitalization rates approaching one million per year. Heart failure is estimated to cause as many as 58,000 deaths per year. The prevalence of most of the major risk factors for heart failure (e.g., hypertension, aging, obesity, diabetes and ischemia) has also continued to rise in recent years.
Today, there are an estimated 72 million people who suffer from hypertension. Hypertension precedes heart failure in more than 90 percent of patients. The vast majority of patients with heart failure in the absence of LV dilation (generally with a preserved ejection fraction) has myocardial (as well as vascular and renal) dysfunction on the basis of long-standing hypertension, and associated with pathologic myocardial hypertrophy and/or fibrosis. Patients with this form of cardiac remodeling, occurring in a population that is older and with a greater female predilection, have generally been excluded from large-scale outcome trials of drugs and devices. There is a compelling need to intensify our efforts towards understanding, preventing, treating and managing this type of heart disease.
Strategies to Accomplish this Goal May Entail:
- Understand the underlying genetic mechanisms that contribute to hypertensive myocardial remodeling and ultimately lead to heart failure.
- Identify genetic risk factors for hypertensive heart failure and study genetic variations associated with individual differences in therapeutic response.
- Understand the roles of microRNAs in hemodynamic overload-induced hypertrophic remodeling and heart failure.
- Explore the relationship between genes and epigenetic factors that contribute to disease progression and how they may be affected by environmental factors.
- Elucidate and identify key molecular, cellular and tissue mechanisms (e.g., autophagy) driving the pathological progression of hypertensive myocardial remodeling.
- Delineate the roles of the myocardial extracellular matrix, including fibroblasts and cytoskeletal scaffolds, in the pathological process. This includes delineating the pathways by which the major risk factors for hypertensive heart disease, such as hypertension, aging, obesity, diabetes, and ischemia contribute to hypertrophic remodeling and heart failure.
- Define the role and contribution of the vasculature during the remodeling process.
- Explore the contribution of sex differences (e.g., hormones such as estrogen), aging, exercise, nutrition, sodium intake, and diet in development of hypertrophic myocardial remodeling.
- Develop or improve cell, tissue, organ, and animal models for understanding normal and hypertension-related hypertrophic remodeling.
- Identify and validate potential molecular biomarkers (e.g., genes, proteins, and metabolites) that improve diagnosis, treatment, and prevention of hypertensive heart failure.
- Examine the potential of innovative therapeutic approaches in appropriate animal models of hypertensive heart failure.
- Develop, design, and test new pharmacologic approaches and new therapy delivery technologies for the treatment and prevention of hypertensive heart failure.
- Encourage multidisciplinary teams of researchers to develop better imaging approaches to improve the diagnosis and evaluation of therapeutic efficacy.
- Explore novel gene-based (e.g., therapeutic microRNA targets) and other therapies to reverse adverse hypertension-induced hypertrophic myocardial remodeling.
- Develop and utilize translational (e.g., whole organ and large animal) models, tools and resources to conduct preclinical studies of the effectiveness of promising therapeutic approaches.
- Evaluate dietary approaches to prevent the development and progression of hypertensive heart failure.
- Improve the phenotyping and clinical definitions of HF, and develop effective clinical methods (e.g., genetic profile, echo, and other imaging parameters that distinguish mild from severe dysfunction) for the prediction and diagnosis of impaired ventricular function in the absence of ventricular dilatation.
- Conduct clinical trials to examine pharmacologic or other approaches to improve heart failure outcomes.