Research in Diseases, Disorders, and Health Conditions
Chronic Diseases and Organ Systems
Cardiovascular disease (CVD) is a broad term used to encompass many conditions, including heart diseases such as coronary heart disease, cardiomyopathy, heart failure, heart valve disease, sudden cardiac arrest, and congenital heart defects and various diseases and conditions of the blood vessels such as cerebrovascular disease (stroke), peripheral arterial disease, and deep vein thrombosis. Coronary heart disease is the most common type of heart disease and a major cause of death in the U.S. for both men and women.
As the lead institute for CVD research, NHLBI studies cover the spectrum of basic investigations, clinical and translational research, and implementation and dissemination research. About two-thirds of the nearly 4,000 CVD-related grants and research contracts funded by NHLBI involve basic research. The clinical research funded by NHLBI includes observational studies, randomized clinical trials, comparative effectiveness research, implementation and dissemination research, and clinical studies of the effect behavioral and psychosocial factors on CVD and risk.
The Institute’s strong focus on basic and early translational studies is exemplified by support for large programs, many of which provide essential resources for investigators to conduct cutting-edge studies in areas such as genomics and cell therapy. For example, the Candidate Gene Association Resource (CARe) is a shared resource for analyses of the association of genotypes with phenotypes relevant to the NHLBI mission. It comprises nine NHLBI-sponsored cohort studies—Atherosclerosis Risk in Communities (ARIC), Cardiovascular Health Study (CHS), Cleveland Family Study (CFS), Coronary Artery Risk Development in Young Adults (CARDIA), Framingham Heart Study (FHS), Jackson Heart Study (JHS), Multi-Ethnic Study of Atherosclerosis (MESA), and Sleep Heart Health Study (SHHS).
The NHLBI Pediatric Cardiac Genomics Consortium is a cooperative investigative group that conducts clinical and translational research on the genetic causes of congenital heart disease and genetic contributions to outcome in individuals with congenital heart disease. In addition, the Programs of Excellence in Nanotechnology supports multidisciplinary teams to develop nanotechnology-based tools for the diagnosis and treatment of heart, lung, and blood diseases, and to move the translation of these technologies towards clinical application. Finally, the NHLBI Gene Therapy Resource Program facilitates the translation of gene therapy research into clinical interventions via provision of resources in the form of preclinical and clinical-grade vector production, pharmacology/toxicology testing, immunology testing, clinical trials funding assistance, and regulatory support.
NHLBI supports a robust portfolio of clinical research, including clinical trials to answer key questions about therapeutic and preventive strategies for major diseases of the heart and blood vessels. Ongoing clinical trials addressing coronary heart disease examine a number of strategies including medications, stenting, revascularization, and angiography to reduce the rate of recurrent myocardial infarction (heart attack), stroke, and CVD-related death. Clinical trials are also underway to improve treatment for arrhythmia. For example, the Catheter Ablation versus Antiarrhythmic Drug Therapy for Atrial Fibrillation trial is evaluating drug therapy versus the use of catheter directed electrical impulses to control arrhythmia. To address hypertension, NHLBI is sponsoring a number of trials, including one to determine whether a target of lower blood pressure than current standards will reduce the risk of heart and kidney disease, stroke, and/or age-related decline in cognitive function. To better treatment of heart failure, NHLBI supports clinical trials to test the benefit of mechanical circulatory support therapy using ventricular assist devices, surgical intervention, and medical therapy.
NHLBI supports numerous trials to improve the treatment of pediatric heart disease. For example, The Pumps for Kids, Infants, and Neonates (PumpKIN) program is testing devices to help children born with congenital heart defects or children who develop heart failure. The Therapeutic Hypothermia after Pediatric Cardiac Arrest trial is evaluating whether regulating body temperature will improve the outcome for children after cardiac arrest.
NHLBI also supports a number of collaborative research infrastructure projects to enable the conduct of clinical trials in areas of identified need and opportunity. For example, the Cardiovascular Cell Therapy Research Network provides an infrastructure to evaluate innovative cell therapy strategies for individuals with CVD, and the Cardiothoracic Surgical Trials Network enables rigorous scientific comparisons and evaluation of newer surgical techniques, devices, and innovative pharmaceutical and bioengineered products to improve CVD outcomes in adult populations.
NHLBI supports an extensive portfolio of behavioral research, including many studies to develop and evaluate interventions for improving eating and exercise patterns to promote cardiovascular fitness, prevent weight gain, or promote weight loss. In addition, NHLBI Global Health Centers of Excellence support a worldwide network of research and training centers to prevent and control chronic diseases, including CVD. Each center is led by a research institution in a low- to middle-income developing country that is paired with at least one partner academic institution in a developed country to enhance research and training opportunities.
Other NIH institutes also support CVD research. For example, stroke research at NINDS is comprehensive and includes research to obtain a better understanding of basic disease mechanisms; epidemiology studies to assess stroke risk, occurrence and outcomes in the population; clinical research to develop effective prevention and acute treatment approaches; and development of strategies for improving recovery and rehabilitation in stroke patients. A number of NIH stroke trials are conducted through the NINDS Specialized Program of Translational Research in Stroke, a network of eight research centers across the country that is focused on improving management and outcomes of acute stroke.110
NIBIB supports a group of interdisciplinary researchers working to develop a new method of mechanical circulatory support and a total mechanical heart that may eliminate the need for anticoagulant drugs. Using cutting-edge simulation techniques to understand the blood flow through these devices and a technology called the “Device Thrombogenicity Emulator” to validate their method, the team will work with device manufacturers to improve the design of these mechanical devices.111 112 Improved designs will lead to the elimination of difficult and costly anticoagulant drug therapy and pave the way for long-term use of these mechanical devices, ultimately saving countless lives and reducing healthcare costs.
Investments in CVD basic research have produced any number of scientific advances. For example, many genetic factors have been identified that influence blood pressure. In one study, an international team of scientists examined the genomes of 200,000 people, looking for DNA variants related to blood pressure. The study found a number of previously unsuspected variants that influence blood pressure, providing new insights into the genetics and biology of blood pressure.113 NHLBI-supported scientists have reported development of a three-dimensional model of the main protein component of HDL as it occurs naturally in the body. HDL’s nickname “good” cholesterol comes from its ability to grab artery-clogging cholesterol from cells and help dispose of it. Knowing the structure of this HDL protein should help researchers mimic its function and perhaps ultimately develop new drugs to mimic its function and prevent atherosclerosis.114
In 2011, researchers reported analysis of health outcomes in postmenopausal women participating in the Women’s Health Initiative estrogen-alone trial who had undergone a hysterectomy and had taken estrogen for an average of six years. They found that excess rates of stroke and blood clots among estrogen users – reasons for halting the trial in 2004 – disappeared during the subsequent four years. Estrogen use during the trial did not increase or decrease the risks of death, heart disease, colorectal cancer, or hip fractures but did decrease breast cancer risk.
New findings are promising revolutionary new approaches to CVD treatment. For example, a recent study promises a potential new mechanism for repairing the heart after a heart attack. The heart’s natural capacity to repair itself is limited, and even when able to recover, resulting scar tissue impairs its ability to pump blood. Recent research showed that non-muscle, "fibroblast" cells, which make up more than half the cells in the heart, can be reprogrammed into other cell types — including muscle. Scientists identified a trio of gene-controlling proteins that, when "turned on", converted these fibroblasts in an injured mouse heart into beating heart muscle cells.115
Results from a large clinical trial that compared surgical removal of artery-narrowing plaque to insertion of a metal tube or stent to reopen narrowed neck arteries showed that both are safe and effective in preventing stroke. However, younger patients (aged < 70 years) fared better with stenting and older ones (aged > 70 years) with surgery. Based in large part on these results, an FDA panel voted to widen the use of carotid stenting, which will impact patient care.116
110 For more information, see www.spotrias.org .
111Girdhar G, et al. PLoS One. 2012;7(3):e32463. PMID: 22396768.
112Rowley JW, et al. Circ Cardiovasc Interv. 2012;5(2):296–304. PMID: 22511738.
113The International Consortium for Blood Pressure Genome-Wide Association Studies. Nature. 2011; 478(7367):103–9. PMID: 21909115.
114 Huang, R. et al. Nat Struct Mol Biol. 2011;18(4):416–22. PMID: 21399642.
115 Ieda M, et al. Cell. 2010 Aug 6;142(3):375–86.PMID: 20691899.
116 Mantese VA, et al. Stroke. 2010;41(10 Suppl):S31–4. PMID: 20876500.
NIDDK supports research on CVD as a common and devastating co-morbidity of diabetes, obesity, and kidney disease. Clinical and basic studies are aimed at identifying and understanding factors and mechanisms that contribute to cardiovascular damage in these diseases, while clinical prevention trials are aimed at finding strategies to prevent CVD in people at risk. For example, the NIDDK-led Look AHEAD (Action for Health in Diabetes) clinical trial is determining whether a lifestyle intervention designed to promote weight loss can improve health outcomes, including prevention of heart disease, in obese people with type 2 diabetes. The NIDDK is also leveraging landmark diabetes clinical trials through follow-up studies that can reveal the long-term effects of trial interventions on the development of CVD and other health outcomes. Already, one such study, the Epidemiology of Diabetes Interventions and Complications Study, a follow up to the NIDDK’s landmark Diabetes Control and Complications Trial, has shown that tight glucose control prevents or delays the cardiovascular complications of type 1 diabetes. Similarly, new information about the relationship between CVD and type 2 diabetes should come from the Diabetes Prevention Program Outcomes Study, a long-term follow up to the landmark Diabetes Prevention Program clinical trial. Another large scale effort, the Chronic Renal Insufficiency Cohort study, co-sponsored by NIDDK and NHLBI, is evaluating long-term cardiovascular risk and outcomes in persons with chronic kidney disease.
Stroke research continues to make considerable advances, but there remain challenges that current and future research efforts will need to overcome, including neuroprotection strategies, disparities in stroke risk and burden, and expanding the time window for safe and effective use of tissue plasminogen activator (tPA) in breaking down blood clots. The NINDS Stroke Progress Review Group is undertaking a five year review of challenges and priorities in stroke research and a new NINDS planning effort is currently underway to identify the most promising opportunities in stroke prevention, treatment and recovery research. NHLBI is currently updating the adult clinical practice guidelines for hypertension, cholesterol, and obesity, all of which are risk factors for developing CVD. The project uses state-of-the-art methodology for systematic evidence reviews and guideline development. Following completion of these guidelines NHLBI will undertake the development of integrated CVD risk reduction guidelines.