12. Minority Activities

Heart and Vascular Diseases
- Risk Factors
Arrhythmias
Lung Diseases
Blood Diseases
- Sickle Cell Disease
- Cooley's Anemia

Throughout its history, the NHLBI has been a leader in conducting and supporting research to eliminate health disparities that exist between various segments of the U.S. population. The Institute has not only initiated research projects with significant minority participation to compare health status between various populations, but has also given high priority to programs that focus exclusively on minority health issues.

Since FY 1991, the Institute has had procedures in place to ensure full compliance with the NIH Policy on Inclusion of Women and Minorities as Subjects in Clinical Research. As a result, all NHLBI-supported research that involves human subjects includes minorities, with the exception of a very few projects for which a compelling justification for limited diversity in the study population exists. Thus, all segments of the population, minority and nonminority, women, and children, stand to benefit from the Institute's research programs.

It has long been a goal of the NHLBI to increase the number of individuals from underrepresented groups in biomedical and behavioral research. Selected FY 2009 activities addressing this goal include the following:

Historically Black Colleges and Universities (HBCU) Research Scientist Award and the Research Scientist Award for Minority Institutions: Strengthens the biomedical and behavioral research capabilities and resources of HBCUs or minority institutions by recruiting an established research scientist in areas related to cardiovascular, lung, or blood health and disease; transfusion medicine; or sleep disorders
Sickle Cell Scholars Program: Supports career development of young or new investigators in SCD research as part of the BTRP
Summer for Sickle Cell Science Program: Supports research training and mentoring of individuals at the high school level as part of the BTRP
Clinical Research Education and Career Development in Minority Institutions: Encourages the development and implementation of curriculum-dependent programs in minority institutions to train selected doctoral and postdoctoral candidates in clinical research leading to a Master of Science Degree in Clinical Research or Master of Public Health Degree in a clinically relevant area
Minority Undergraduate Biomedical Education Program: Encourages development of pilot demonstration programs at minority undergraduate educational institutions to recruit and retain talented undergraduate students in the biomedical sciences
Summer Institute Program To Increase Diversity in Health-Related Research: Enables faculty and scientists from underrepresented racial and ethnic groups or with disabilities to advance their research skills and knowledge in basic and applied sciences relevant to heart, lung, and blood diseases and sleep disorders, so that they can compete for funding for scientific research in the biomedical and behavioral sciences

The Office of Research Training and Minority Health (ORTMH) within the Office of the Director provides oversight for, and coordinates, supports, and evaluates Institute programs related to minority health outcomes, including research, research training and career development, public outreach, and translation of research findings. The ORTMH also coordinates activities to foster greater participation of underrepresented minorities in NHLBI research and research training and career development programs. Selected FY 2009 activities include the following:

Issuing four training and career development RFAs to increase the number of highly trained minorities conducting biomedical and behavioral research. Additional targeted groups include individuals from disadvantaged backgrounds and individuals with disabilities
Participating in HHS-Endorsed Minority Organization Internship Programs by supporting positions in NHLBI extramural and intramural divisions for students from the National Association for Equal Opportunity in Higher Education, the Hispanic Association of Colleges and Universities, the Washington Internships for Native Students programs, and the Directors of Health Promotion and Education Internship Program/CDC
Cosponsoring with the NIH, the Cherokee Elementary School Project: Out of the Box, which is designed to create awareness and interest in the importance of science, medicine, and health; eliminate gaps in quality of health among minorities by encouraging health-related careers; and encourage children to take responsibility for their own health
Supporting the African American, Hispanic, and Native American Youth Initiatives to bring minority students to the NIH campus for scientific presentations, an introduction to NHLBI research training and career development programs, and a tour of NHLBI laboratories
Providing undergraduate students from the Tougaloo College Scholars program an opportunity to learn about the NIH, biomedical research, and research training opportunities at the NHLBI during a 3-day tour of the NIH
Serving as a Web site resource for recruitment of minority individuals into the Ruth L. Kirschstein Institutional National Research Service Award (T32)
Increasing recruitment of individuals for the NHLBI intramural and extramural training programs by representing the Institute at five minority-focused research meetings to raise awareness of research and research training and career development opportunities available from the NHLBI
Coordinating the Biomedical Research Training Program for Individuals from Underrepresented Groups, which offers opportunities for underrepresented undergraduate, postbaccalaureate, and graduate students to receive training in fundamental biomedical sciences and clinical research as they relate to the etiology and treatment of heart, blood vessel, lung, and blood diseases and sleep disorders
Serving as the NHLBI contact for guidance to candidates applying for the NIH Pathway to Independence (PI) Award (K99/R00) and the NHLBI Career Transition Award (K22) for extramural programmatic issues

See Chapter 13 for additional NHLBI-supported minority research training and career development programs.

The following text describes selected current projects that focus on minority populations and reflect the Institute's research portfolio related to minority health. Additional information can be found in Chapters 9 through 11.

Heart and Vascular Diseases

Risk Factors

Epidemiology

Long-term epidemiologic studies are critical to uncovering risk factors that lead to disease. The Institute has initiated several major studies of heart disease focused significantly or completely on minority populations:

CARDIA (see Chapter 10): To determine the evolution of CHD risk factors and lifestyle characteristics in young adults that may influence development of risk factors prior to middle age. Fifty percent of participants are black.
ARIC (see Chapter 10): To investigate the association of CHD risk factors with development of atherosclerosis and CVD in an adult population. Thirty percent of participants are black.
CHS (see Chapter 10): To examine risk factors for CHD and stroke in the elderly. Sixteen percent of participants are black.
Strong Heart Study (see Chapter 9): To compare risk factor levels and morbidity and mortality from CVD among American Indians from three different geographic locations.
JHS (see Chapter 10): To identify environmental and genetic factors influencing evolution and progression of CVD in blacks.
MESA (see Chapter 10): To examine the characteristics of subclinical CVD that predict progression to clinically overt CVD and related risk factors that predict subclinical disease in blacks, whites, Hispanics, and Asians. Sixty-two percent of participants are from minority populations.
GOCADAN (see Chapter 9): To document CVD risk factors and measures of subclinical disease and to identify and characterize genes that contribute to CVD in approximately 40 extended Alaska Native families.
HCHS (see Chapter 10): To identify risk factors for cardiovascular and lung disease in Hispanic populations in the United States and determine the role of acculturation in their prevalence and development.

The Institute supports components of the NHANES that track the prevalence of disease and risk factors for cardiovascular and lung diseases by race and ethnicity in the U.S. population.

Ancillary studies to MESA are investigating subclinical CVD in ethnic minority groups. They include investigations of regional left ventricular function, progression of calcification in the aorta, abnormalities in the small vessels of the retina, association of air pollution and subclinical CVD, lung function in relation to endothelial dysfunction and biomarkers, identification of genes for subclinical CVD, and relationships of sociodemographic factors and other factors to subclinical CVD.

The Institute is supporting additional epidemiologic investigations that include a project to use pooled data from nine existing U.S. studies to compare between blacks and whites, CHD incidence and mortality rates, exposure–outcome relationships, patterns of comorbidity, and population attributable risk; and a study to evaluate and compare the extent of atherosclerosis and risk factors for CHD in three different populations: U.S. (75 percent white and 25 percent black), Japanese Americans in Hawaii, and Japanese in Japan.

Treatment and Prevention

Although great progress has been achieved in reducing CVD morbidity and mortality in the United States over the past 40 years, minorities have not shared fully in the progress and continue to have higher CVD morbidity. To address this problem, the Institute has initiated programs directed at reducing cardiovascular health disparities:

Cultural Competence and Health Disparities Academic Award Program: To enhance the ability of physicians and other health care professionals to address, in a culturally sensitive manner, disparities in the occurrence, management, and outcomes of cardiovascular, lung, and blood diseases and sleep disorders among various population groups in the United States. The award addresses ethnic, cultural, religious, socioeconomic, linguistic, and other factors that contribute to health disparities and seeks culturally competent approaches to mitigating them.
Community-Responsive Interventions To Reduce Cardiovascular Risk in American Indians and Alaska Natives (see Chapter 11): To test the effectiveness of culturally appropriate behavioral interventions that promote adoption of healthy lifestyles (healthy diet, regular physical activity, smoking cessation, and stress management) related to heart disease and stroke risk in American Indians and Alaska Natives.
Effect of Racial and Ethnic Discrimination/Bias on Health Care Delivery: To improve the measurement of racial/ethnic discrimination in health care delivery systems and enhance understanding of the influence of such discrimination and its association with health disparities among disadvantaged racial/ethnic minority groups. Research results should lead to the development of interventions that are focused on reducing or eliminating discrimination in health care delivery. Fifty percent of participants will be black.
Behavioral and Social Science Research on Understanding and Reducing Health Disparities: To encourage behavioral and social science research on the causes of and solutions to health and disabilities disparities in the U.S. population and to develop and test more effective interventions for reducing and eventually eliminating health disparities.

Education

The NHLBI, through the DARD, seeks to translate research findings into practice by communicating research advances effectively and disseminating health information to physicians, health care professionals, patients, and the public on ways to prevent or treat diseases within the Institute's mandate.

The Division has developed the Community Health Worker (CHW) Initiative as a community-based strategy to help improve cardiovascular health among various cultural/ethnic groups in the United States: black, Hispanic, American Indian, Alaska Native, and Filipino.

NHLBI–U.S. Department of Housing and Urban Development HOPE VI: To address cardiovascular health disparities in public housing settings. With the aid of the NHLBI heart health curriculum, residents of the black community are trained to become educators of other public housing residents.
NHLBI–Health Resources and Services Administration Bureau of Primary Care Partnership: To integrate clinical care management teams and trained community health educators to implement pilot programs for blacks, Hispanics, and Filipinos in the United States who are at high risk for CVD.
Salud para su Corazón: To develop networks to disseminate information and strategies about CVD prevention and control by promoting heart healthy behaviors in Hispanic communities.
NHLBI–Pan American Health Organization/WHO Partnership To Promote Cardiovascular Health in the Americas: To develop and evaluate community-based interventions to prevent and control CVD risk factors among low-resource communities in Argentina, Chile, and Guatemala.
Honoring the Gift of Heart Health: To develop and evaluate community-based interventions to prevent and control CVD risk factors through education and outreach using tribal community health workers and community health educators.
Healthy Heart, Healthy Family: To develop and evaluate culturally and linguistically appropriate outreach activities and information to increase community awareness of heart disease and its associated risk factors and to promote heart healthy lifestyles among the growing Filipino population in the United States.
The Heart Truth Campaign: To raise awareness of heart disease in women through community-based interventions. Special populations are especially targeted through the Heart Truth's Women of Color Initiative, a partnership with national black and Hispanic organizations.

In addition to the activities mentioned above, the Institute has prepared publications on CVD prevention for minority populations. They include the following:

With Every Heartbeat Is Life: A Community Health Worker's Manual for African Americans
On the Move to Better Heart Health for African Americans
Honoring the Gift of Heart Health: A Heart Health Educational Manual for American Indians and Alaska Natives
Your Choice for Change: Honoring the Gift of Heart Health for American Indians
Healthy Heart, Healthy Family: A Community Health Worker's Manual for the Filipino Community in English and Tagalog
Vietnamese Aspire for Healthy Hearts in Vietnamese and English
Your Heart Is Golden: Heart Health Promotion Activities for Vietnamese Communities
Your Heart, Your Life: A Health Educator's Manual for the Latino Community in English and Spanish
Healthy Homes, Healthy Hearts Series (six easy-to-read English and Spanish booklets on heart healthy living)
Bringing Heart Health to Latinos: A Guide for Building Community Programs
The Heart Truth for African American Women: An Action Plan
The Heart Truth for Latinas: An Action Plan

The educational materials listed throughout this chapter can be obtained from the NHLBI public Web site or through the NHLBI online catalog.

Arrhythmias

Arrhythmia is a disorder of the normal rhythms of the heart, whereby it beats too fast (tachycardia), too slow (bradycardia), or irregularly. The NHLBI is supporting basic and genetic research on the mechanisms that underlie cardiac arrhythmias to improve diagnosis, treatment, and prevention of arrhythmias in all racial and ethnic groups in the United States. One study is investigating the genetic basis and electrophysiological mechanisms of Ca2+ triggered arrhythmias in inherited diseases and syndromes—such as catecholaminergic polymorphic ventricular tachycardia, long QT syndrome, and hypertrophic cardiomyopathy—as a means to improve understanding of the pathogenesis of sudden cardiac arrest. Another study is evaluating variants of the gene NOS1AP that affect the QT interval in different racial populations, including blacks and Hispanics. A third study is evaluating the distributions of electrocardiographic predictors of atrial fibrillation in different ethnic groups to identify whether minority populations may have a higher risk for this arrhythmia than whites.

Scientists have identified an association between variations in certain receptors that are activated during sympathetic nervous system stimulation and an increased risk of sudden cardiac death, most often due to ventricular arrhythmia. Although significant differences in associated risk of sudden cardiac death were not found between blacks and whites, continued research is expected to advance understanding of differences in genetic predisposition for cardiac arrhythmias among racial and ethnic groups and ultimately lead to improved therapy.

Investigators identified two mutations in a gene encoding the major intracellular calcium release channel in two cases of SIDS. One mutation was identified in 1 of 50 black infants and the other in 1 of 83 white infants. Researchers reported a pathogenic mechanism for SIDS, whereby SIDS-linked mutant ion channels become “leaky” during stress and thus potentially trigger fatal cardiac arrhythmias. Importantly, researchers have found further evidence that cardiac arrhythmias of genetic origin contribute to SIDS, a concept that offers a chance to prevent some avoidable tragedies.

Heart Failure

Heart failure (heart muscle dysfunction) affects about 5 million Americans of all ethnicities and is a growing public health concern. It is frequently the end result of other conditions, such as hypertension, diabetes, and prior heart attacks.

The NHLBI is supporting basic and clinical research associated with heart failure that will benefit Americans of all ethnicities. One Institute-initiated study is facilitating the translation of basic science discoveries into clinical applications:

Heart Failure Clinical Research Network (see Chapter 9): To develop, coordinate, and conduct multiple collaborative proof-of-concept clinical protocols to improve heart failure outcomes. The Network has been expanded to include a historically black medical center with minority investigators and access to a high-risk, underserved population.

Other research targeting minority populations includes an investigation of genetic variations (especially those common in blacks) that affect individual responses to the beta blocker drugs used to treat heart failure; a study of underlying genetic variations that result in familial dilated cardiomyopathy, an inherited form of heart dysfunction; and a study on angioedema—a severe allergic reaction and a life-threatening side effect of ACE-inhibitor drugs that is more common in blacks than in whites. Investigators are determining the mechanisms that cause this side effect and are studying the genetic profile of affected individuals and their families to determine who should avoid taking the drugs.

Individuals with heart failure typically have a poor prognosis and a diminished quality of life. Depression is common, and it worsens functional impairment and quality of life, and decreases chances of survival. An investigator-initiated study is seeking to determine whether cognitive behavioral intervention is superior to supportive clinical management for depressed outpatients with heart failure. Thirty percent of participants are expected to be black.

An investigator-initiated, multicenter observational clinical study is being conducted to improve the ability of physicians to identify and treat appropriately patients who are at high risk for serious complications from heart failure. Participants will comprise individuals who visit the emergency department at one of three hospitals that treats racially and socioeconomically diverse patients.

High Blood Pressure

Etiology and Pathophysiology

High blood pressure is a serious health problem that is especially prevalent and severe among minorities. The NHLBI supports a number of investigator-initiated studies to identify genes linked to hypertension in blacks, Mexican Americans, and whites to determine if part of the disparity in prevalence can be attributed to genetic differences among the groups. Genes under investigation include those associated with the renin-angiotensin system, the autonomic nervous system, and sodium transport.

The role of dietary factors, particularly macronutrients, in the etiology of high blood pressure is another area of investigation. Scientists are conducting epidemiologic studies among participants with diverse ethnicity, SES, and dietary habits in four countries to determine the effect of selected dietary components (proteins, lipids, carbohydrates, amino acids, calcium, magnesium, sodium, potassium, antioxidants, fiber, and caffeine) on blood pressure. Another study is seeking to identify the link between healthy diet, genetic factors, and their underlying biological mechanisms.

Treatment and Prevention

An investigator-initiated ancillary study to ALLHAT, the largest hypertension clinical trial conducted by the NHLBI, is evaluating the pharmacogenetic response to antihypertensive treatment and long-term clinical complications in blacks, whites, and Hispanics. Scientists seek to determine whether pharmacogenetics is a feasible approach to personalized therapy for hypertension.

The Institute also supports a number of investigator-initiated studies to prevent hypertension and improve blood pressure control in racial and ethnic minorities. Interventions target both lay and medical communities. Strategies being tested include communication skill enhancement, organizational change, educational programs, lifestyle and nutritional counseling, use of technology, case management, pharmacy-based interventions, and provision of care by community health workers and other nontraditional providers.

Understanding racial differences in blood pressure control is an area of major interest for the Institute. Scientists are examining whether variations in genes of the renin-angiotensin-aldosterone system predict differences in blood pressure response to diuretic therapy among hypertensive blacks and whites. Research also is being focused on variations in the ACE gene between blacks and whites to explain racial differences in the antihypertensive responsiveness to ACE inhibitors.

Education

The NHLBI has developed a number of outreach activities to inform minority populations of the importance of blood pressure control. Included among them are a toll-free number that provides materials on hypertension in English or Spanish; mini telenovelas (Más vale prevenir que lamentar), “health moments” to reinforce CVD prevention for local Spanish-language television stations; a Spanish version of the High Blood Pressure Education Month Kit; and several publications and Web-based products for health professionals, patients, and the public. Some examples are:

Plan de Alimentación Saludable Contra la Hipertensión: Prevenir y Controlar la Presión Arterial Alta Siguiendo el Plan de Alimentación Conocida Como DASH (DASH to the Diet: Prevent and Control High Blood Pressure Following the DASH Eating Plan)
Presión Arterial Alta: NHLBI Health Topics
Sí se Puede: Prevenir y Controlar la Presión Arterial Alta: Lo Que Usted Debe Saber Sobre la Preventión y Control de la Presión Arterial Alta (Prevent and Control High Blood Pressure: What You Should Know)
Sí se Puede: Prevenir y Controlar la Presión Arterial Alta: Lo Que los Médicos Deben Saber (Prevent and Control High Blood Pressure. What Every Physician Should Know)
Keep the Beat: Control Your High Blood Pressure in English and Spanish
Help Your Heart: Control Your High Blood Pressure in Tagalog and English
Keep Your Heart in Check—Know Your Blood Pressure Number in Vietnamese and English
Prevent and Control High Blood Pressure: Mission Possible

High Serum Cholesterol

Etiology

The Institute supports investigator-initiated studies to identify genes that influence the lipoprotein profile within various racial and ethnic groups. Research findings could offer an explanation for differences in susceptibility to CHD found among various racial and ethnic groups. One project involving extended families of Mexican Americans in the San Antonio Family Heart Study has detected and mapped many quantitative trait loci (QTLs) for CVD risk factors, including some that influence HDL and LDL levels. Scientists will seek to determine the genes for the QTLs related to lipoproteins. Another study is focused on the variation in hepatic lipase activity that leads to differences in plasma concentrations of HDL and LDL synthesis and catabolism. Investigators are seeking to determine whether racial differences in hepatic lipase activity are responsible for the well-known differences in plasma HDL concentrations found in blacks and whites. Thirty-nine percent of participants are black.

Prevention

The NHLBI is supporting an investigator-initiated study among minority preschool children to track the long-term effectiveness of nutrition interventions on diet and blood cholesterol levels. Additional potential risk factors such as increased blood pressure, obesity, and intention to smoke, will also be monitored.

Education

The Institute has prepared the following publications on blood cholesterol for minority audiences:

Do You Know Your Cholesterol Levels? in English and Spanish
Heart-Healthy Home Cooking African American Style
Delicious Heart-Healthy Latino Recipes
American Indian and Alaska Native People: Treat Your Heart to a Healthy Celebration!
Be Heart Smart: Keep Your Cholesterol in Check in Tagalog and English
Serve Up a Healthy Life—Give the Gift of Good Nutrition in Vietnamese and English

Obesity

Etiology

Obesity is a major health concern that affects children and adults. Minorities, including blacks and Mexican Americans, are especially at risk. Data from the 2003–2006 NHANES show that 33 percent of adults and 16 percent of children (aged 2–19 years) are obese. Understanding the causes of obesity could lead to effective strategies to combat this problem.

The Institute is supporting a program to study the effects of short sleep duration on mechanisms underlying weight gain and obesity:

Mechanisms Linking Short Sleep Duration and Risk of Obesity or Overweight: To elucidate cause-and-effect relationships and mechanisms to explain associations between short sleep duration and increased risk of obesity or overweight due to altered metabolism, appetite, or inflammation. Blacks comprise 29 percent of participants in one project, and Asians comprise 100 percent of participants in another project.

Researchers have found that black and Hispanic children are especially likely to develop sleep disordered breathing (sleep apnea). A new study in Hispanic adolescents is investigating the relationship between untreated sleep disordered breathing and the likelihood of being overweight, obese, or having problems with glucose metabolism (insulin resistance)—which may indicate susceptibility to developing diabetes and hypertension.

Treatment and Prevention

The NHLBI has initiated programs to test approaches for treating or preventing obesity:

WLM (see Chapter 9): To determine the effectiveness of continuous patient contact on weight loss maintenance in adults who recently lost weight; 40 percent of the patients are black.
POWER (see Chapter 11): To test the effectiveness of interventions delivered in routine clinical practice on achieving weight loss in obese patients who have other CVD risk factors (e.g., hypertension). One study focuses on a low-income minority population.
Targeted Approaches to Weight Control for Young Adults (see Chapter 11): To develop and evaluate innovative approaches for weight control in young adults at high risk for weight gain. Participants will be ethnically and socioeconomically diverse.
Translating Basic Behavior and Social Science Discoveries Into Interventions To Reduce Obesity (see Chapter 9): To translate findings from basic research on human behavior into more effective clinical, community, and population interventions to reduce obesity and improve obesity-related behaviors. Some of the studies are expected to have 50- to 100-percent participation from minority populations.
Look AHEAD (see Chapter 11): To test the effectiveness of a lifestyle intervention in obese participants with type 2 diabetes over a long-term period. One of the clinical centers will direct its interventions toward American Indians.

The Institute supports a number of investigator-initiated studies on the effectiveness of obesity prevention and control interventions among diverse populations. One study is testing the effectiveness of weight-control interventions (involving diet, physical activity, psychosocial and familial influences) administered during the critical transition period from prepuberty to puberty in black girls at high risk for obesity. Another study in preadolescent black girls is evaluating the efficacy of an after-school dance program and a family-based intervention involving reduced use of television, videotapes, and video games to reduce weight gain. A third study is testing an integrated school- and community-based intervention that involves physical activity and diet to reduce the prevalence of obesity among Asians, Hispanics, and whites.

Blacks at high risk of CVD often have limited success in weight loss and lifestyle change programs. A study was initiated to examine the role of social support, particularly from family members and friends, to facilitate weight loss and related dietary and physical activity changes in blacks.

Hispanics are also an important population targeted for intervention programs. One project is studying the effects of physical activity and dietary behaviors in a microenvironment (i.e., home environment) and in a macroenvironment (i.e., apartment complex, schools, grocery stores, parks, restaurants). Community health workers (promotoras) are working with the families and the community to increase awareness and promote environmental change. Another project with strong Hispanic participation is evaluating how well an intervention, Planned Care for Obesity and Risk Reduction, supports primary care treatment of obesity in adults with at least one other cardiovascular risk factor. The study is seeking to improve the way primary care providers offer services to their patients who are overweight and who also have other important medical conditions or health risks such as hypertension, smoking, or high cholesterol.

Obesity is one of the major health challenges facing Native American children and has serious implications for the development of type 2 diabetes. A school-based intervention, augmented with a family intervention, is focusing on reducing excess weight gain by increasing physical activity and healthy dietary practices in kindergarten and first-grade Native American children.

Education

The NHLBI has prepared health information on losing excess weight for minorities:

Do You Need To Lose Weight? in English and Spanish
On the Move to Better Health for African Americans
Keep the Beat: Aim for a Healthy Weight in Tagalog and English
We Can!™ (Ways to Enhance Children's Activity & Nutrition): Many bilingual (English and Spanish) publications on energy balance are available on the Web site

Physical Inactivity

Despite substantial research about the positive impact of physical activity on CVD and its risk factors, physical inactivity is highly prevalent, especially among minority populations. Researchers have observed an age-related decline in physical activity or aerobic capacity in the biracial cohorts of Institute-initiated longitudinal cohort studies (National Growth and Health Study and CARDIA). Those results, when coupled with findings from MESA and HCHS, have helped to increase understanding of the interrelationships of cardiorespiratory fitness, body composition, and CVD-related risk factors and endpoints, and may provide the basis for more specific evidence-based recommendations on the role of fitness in cardiovascular health among minority children and adults.

Physical inactivity among children is often attributed to lack of open space, lack of recreational equipment, and fear by parents for the safety of children playing outdoors. A study is being conducted to determine if an intervention that changes these neighborhood features in a low-income, inner-city neighborhood will increase physical activity in children. Components of CARDIA, MESA, and HCHS are also examining the effects of the neighborhood environment on physical activity.

A longitudinal follow-up of the Trial of Activity for Adolescent Girls is examining the effects of a school–community joint intervention on physical activity among middle school girls.

A number of investigator-initiated studies are evaluating culturally appropriate interventions to increase physical activity. One study is using lay health advisors to increase moderate intensity physical activity among Mexican American women, a group with many countervailing family and community influences. Several studies are using faith-based approaches—including community-based participatory research approaches to engage church leaders and congregations— to increase activity levels in blacks. Other studies are testing culturally targeted interventions in schools or among pregnant women and mothers/parents with young children.

Several projects are using mobile phone technology to increase physical activity and decrease sedentary behaviors. These studies capitalize on recent advances in communication technologies, such as “smart phones” that offer a potentially transformative platform to deliver convenient and sustainable adherence strategies.

Education

The Institute has prepared the following publications for minorities on the importance of physical activity and ways to become more physically active:

On the Move to Better Health for African Americans
Sí se Puede: Prevenir y Controlar la Presión Arterial Alta con Actividad Física (Move To Prevent and Control High Blood Pressure With Physical Activity)
American Indian and Alaska Native People: Be Active for Your Heart!
Are You at Risk for Heart Disease? in Tagalog and English
Be Active for a Healthier Heart in Vietnamese and English

The Institute also has developed a Web-based application on physical activity for lay health educators in English and Spanish, which can be found at http://hin.nhlbi.nih.gov/salud/pa/index.htm.

Smoking

Smoking is a major risk factor for CHD, stroke, COPD, and other cardiovascular and respiratory conditions and is the leading cause of preventable death. Although considerable progress has been made in reducing smoking rates and providing effective prevention and cessation interventions, additional research is needed to extend these efforts and improve the maintenance of behavior change.

The NHLBI supports a number of investigator-initiated studies of smoking cessation in underserved populations. One study targets low-income, high-risk women from a variety of racial and ethnic backgrounds who quit smoking during pregnancy, and compares maintenance of smoking abstinence postpartum between those who received usual care and those who received intervention-based telephone counseling. Another study among women who live in public housing neighborhoods is evaluating smoking cessation interventions that use a combination of strategies, including contact with community health workers, small-group behavioral counseling, and neighborhood support groups.

Technology is increasingly being used to deliver smoking cessation interventions, particularly to young adult smokers. One study is evaluating whether WeBREATHe (Web-Based Respiratory Education About Tobacco and Health), an interactive Internet-based program, can help to augment the efforts of respiratory therapists and nurses who provide cessation interventions to parents of hospitalized pediatric patients with respiratory illness. Forty-two percent of participants are expected to be from minority populations. Another study is assessing the efficacy of telemedicine as a way to provide smoking cessation counseling to primary care patients who live in rural areas.

Smokers often have other cardiovascular risk factors, such as obesity, and some smokers are reluctant to quit because of fear of weight gain. Post-cessation weight gain in patients with hypertension is a particular concern. Two studies of smokers with hypertension will compare the effectiveness of a pharmacologic smoking cessation intervention followed by a weight gain prevention and blood pressure control program that consists of changes in dietary intake and physical activity to the same smoking cessation intervention followed by general health education. Sixty percent of participants are expected to be black.

The estimated prevalence of smoking in the HIV-seropositive population is approximately 50 percent. Evidence shows that before the onset of AIDS-related pulmonary complications, HIV-seropositive individuals are at increased risk of developing accelerated emphysema, possibly related to an increased susceptibility to cigarette smoke. A study of smokers with HIV will examine the effects of a specialized smoking cessation intervention on the natural history of emphysema. Thirty-eight percent of participants are expected to be black.

In addition to smoking cessation research, the NHLBI also supports a number of investigator-initiated studies that seek to improve understanding of the mechanisms that link smoking to cardiovascular and pulmonary diseases. Studies focus on mechanisms of smoking-induced chromatin remodeling in lung inflammation, adaptive glutathione response to smoking in individuals with COPD, genomic contributions of intrauterine smoking exposure and asthma, and the natural history of HIV-associated emphysema following smoking cessation.

Education

The Institute has prepared the following publications on smoking cessation for minorities:

Enjoy Living Smoke Free in English and Spanish
On the Move to Better Health for African Americans
American Indian and Alaska Native People: Help Your Heart
Be Heart Healthy: Enjoy Living Smoke Free in Tagalog and English
Don't Burn Your Life Away—Be Good to Your Heart in Tagalog and English and in Vietnamese and English

Psychosocial Factors

Etiology

A large and consistent body of evidence has demonstrated that psychosocial factors—such as depression, stress, and low social support—are associated with elevated risk for CVD and major adverse cardiac events in heart disease patients. Additionally, race/ethnicity, gender, and social class are important factors that can influence these associations in important ways.

The NHLBI is funding research to identify more precisely the nature of the relationship between depression and adverse cardiac outcomes and the conditions associated with successful treatment of depression. Research results will guide clinical care and inform future trials of depression treatment in heart patients and minority patient populations. Studies include defining the biologic pathways that link depression to physiological mechanisms in post-myocardial infarction and acute coronary syndrome patients—including inflammatory processes implicated in atherogenesis, autonomic nervous system dysfunction, and platelet aggregation and adhesion. Approximately 30 percent of participants are black.

The Institute is also supporting research among middle-aged black and white women to determine whether depression is associated with the adipocytokines adiponectin and leptin, which are bioactive molecules secreted by adipose tissue that play a critical role in atherogenesis and metabolic dysregulation. Research results will provide information on how depression affects risk for diabetes, metabolic syndrome, obesity, and CVD in women.

The Institute supports investigator-initiated research on the interactions of psychosocial factors with race and ethnicity, environmental factors, and low SES in the development of CHD. Scientists are investigating the contribution of biobehavioral factors (hostility, anxiety, and heightened cardiovascular reactivity to stress) in the etiology, pathogenesis, and course of CHD. Racial differences in stress-induced physiologic responses are also being examined. Other investigators are focused on the relationship of psychosocial stress and sleep disordered breathing with emerging risk factors for subclinical CVD in blacks.

The nature of the relationship between acute and chronic forms of stress and cardiac morbidity and mortality is particularly relevant to minority populations, because stress induced by environmental, social, and discriminatory influences can be significant. One study is investigating whether the effect of acute and chronic exposure to established risk factors (depressive symptoms, major life events, and lack of social support) for CVD over a 5-year period is related to a 2-year increase of subclinical CVD in a sample of women undergoing menopause. Fifty-four percent of participants will be black. Other studies are seeking to clarify the physiologic pathways through which stress affects cardiovascular outcomes—including hemodynamic, sympathetic nervous system and neuroendocrine mechanisms, and inflammatory processes. The ultimate goal is to determine whether stress management interventions can alter these physiological indicators and improve cardiovascular outcomes.

Additional research supported by the Institute includes studies that are addressing the genetic basis of behavioral risk factors and the relationships between risk-promoting variables (psychosocial stress, smoking, poor diet, physical inactivity, lack of adherence to cardiac medications), presumed mediating variables (sympathetic nervous system activity and insulin metabolism), and CHD risk factors.

Treatment

The Institute supports several investigator-initiated studies to develop and evaluate interventions that seek to improve cardiovascular outcomes. One study is seeking to determine the efficacy of a personalized health plan intervention that incorporates mind–body techniques targeted at reducing various risk factors for CVD—such as insulin resistance, inflammatory markers, and self-reported negative effect. Participants select their own goals on which to focus, and the intervention is tailored to their individual risk profile. Twenty-nine percent of participants will be from minority populations. Another study is evaluating the effectiveness of stress management training combined with exercise-based cardiac rehabilitation as a way to reduce stress in vulnerable cardiac patients. Approximately 25 percent of participants are black. A third study is developing and evaluating an intervention among racial minorities that reduces the impact of bias by reducing stereotypic perceptions that render patients and providers less able to communicate effectively and impair the effect of the visit to improve patient self-management behavior. Additional studies are investigating whether stress management in a high-risk population of blacks with hypertension can influence cardiovascular risk factors.

Diabetes

Etiology

Diabetes mellitus is a strong risk factor for CVD. Individuals with type 2 diabetes are 2- to 4-times more likely to be at risk for CHD than the general population. Using genome-wide association studies, investigators have identified several genetic variants for CHD in the general population. An investigator-initiated study is seeking to identify new genetic variants for excessive risk of CHD in diabetic patients, assess the genetic effects on intermediate biochemical changes, and examine gene–environment interactions. One of the data sources will come from the Costa Rica study.

Another study is investigating two key pathways that lead to diabetes and the mechanisms by which it leads to CVD in older adults. The two pathways are the adipocyte-hepatocyte axis (in the development of diabetes) and the advanced glycation endproduct profibrosis pathway (in CVD complications). Data from CHS will be used.

Two studies are determining the associations of fetuin-A with CVD mortality and diabetes. Fetuin-A is a protein that may simultaneously inhibit vascular calcification and promote insulin resistance and diabetes. One of the studies will use data from MESA.

Treatment

The NHLBI supports clinical trials to determine the benefits of various strategies to reduce CVD among patients with diabetes or treat patients with coronary artery disease and diabetes:

ACCORD (see Chapter 11): To evaluate the benefits of different therapies to reduce CVD in type 2 diabetes. More than one-third of participants are from minority populations.
BARI 2D (see Chapter 9): To evaluate whether urgent revascularization offers an advantage over medical therapy in patients with coronary artery disease and diabetes. One-third of participants are from minority populations.

Education

The Institute has prepared the following publications on diabetes for minorities:

Protect Your Heart Against Diabetes in English and Spanish
Protect Your Heart: Prevent and Control Diabetes in Tagalog and English

Women's Health Initiative

WHI (see Chapter 11) is a long-term national health program designed to address the most frequent causes of death, disability, and diminished quality of life—CVD, cancer, and osteoporosis—in postmenopausal women. The original WHI study enrolled 161,808 postmenopausal women (17 percent of whom were from minority populations) in clinical trials and an observational study, all of which have been completed. Followup studies and data analyses are ongoing.

In January 2007, WHI entered a new phase: funding investigations using blood, DNA, and other biological samples and clinical data from WHI participants. The studies will help to explain the findings from the clinical trials and will investigate the impact of genetic and biological markers on common diseases that affect postmenopausal women. Four of the 12 2-year contracts focused on minority women. A subsequent solicitation resulted in 10 awards, including one that focused on predictive modeling for CVD in multiethnic postmenopausal women.

Recently a genome-wide association study to investigate genes that predict heart disease, stroke, and breast cancer was completed in approximately 12,000 black and Hispanic WHI participants.

Lung Diseases

The NHLBI supports research on a number of lung diseases, such as asthma, COPD, sarcoidosis, TB, and HIV-related lung diseases, which disproportionately affect minorities. The following section provides examples of research to address health disparities in lung diseases; selected sleep disorders are also included.

Asthma

Asthma is a chronic lung disease that inflames and narrows the airways. It affects people of all ages, but it most often starts in childhood. In the United States, more than 22 million people are known to have asthma, and more than 6 million of them are children. Prevalence rates are especially high in blacks and Puerto Ricans.

Etiology and Pathophysiology

The NHLBI has initiated several studies to determine the etiology and pathophysiology of asthma:

Severe Asthma Research Program: To determine the mechanistic basis for severe asthma and to determine how it differs from mild-to-moderate asthma. Several of the projects have strong minority participation.
Genome-Wide Association Studies to Identify Genetic Components Related to Heart, Lung, and Blood Disorders: To identify genetic variants related to heart, lung, and blood disorders and their risk factors using existing population, family, and clinical studies. Several of the asthma-related projects have strong minority representation in the study populations.
Airway Smooth Muscle Function and Targeted Therapeutics in Human Asthma: To investigate the complex role that airway smooth muscle plays in the development of asthma and identify innovative therapeutic targets. Two projects expect 30 to 50 percent of participants to be from minority populations.

The Institute also supports investigator-initiated projects on the etiology and pathophysiology of asthma. One study will (a) identify genetic, biologic, and immunologic characteristics and environmental exposures that interact in children who experience severe bronchiolitis caused by the respiratory syncytial virus early in life and (b) determine their role in the subsequent development of asthma, airway hyperreactivity, and allergy. Forty percent of participants will be black. Another study will identify the genetic basis for differences between blacks and whites in asthma susceptibility and development (e.g., risk of exacerbations).

A new study is focused on the possible common genetic determinants for obesity and asthma. It will first identify single nucleotide polymorphisms (SNPs) that are jointly associated with asthma and obesity, using data from the CAMP study, and subsequently validate the SNPs in three independent and ethnically diverse (Hispanic, black, and white) cohorts.

Environmental factors are known to trigger asthma symptoms. An investigator-initiated study is focusing on understanding the mechanisms by which occupational or environmental factors trigger the onset of asthma among low-income, urban blacks and Hispanics. Another study is examining multiple environmental stressors in a predominantly disadvantaged population to determine the effects of maternal stressors and environmental factors in the onset of asthma in early childhood. A third study is examining the reasons why children from lower SES groups suffer from worse asthma than children from higher SES groups. The goal is to develop models of how the social environment affects the onset and severity of childhood asthma and eventually build interventions to ameliorate these effects.

Treatment and Control

The Institute has initiated research to identify optimal drug strategies for treatment and management of asthma. Because the burden of asthma disproportionately affects minority children, it is important for them to be well represented in clinical trials.

AsthmaNet (see Chapter 11): To develop and conduct multiple clinical trials to identify optimal therapies for a variety of asthma phenotypes, genotypes, and racial and ethnic backgrounds in pediatric and adult populations. Approximately 30 percent of participants will be from minority populations.
STAN (see Chapter 9): To determine whether treatment of chronic rhinitis and sinusitis with nasal steroids will improve control of asthma. One-third of participants are expected to be from minority populations.

The Institute is also supporting investigator-initiated studies focusing on finding effective treatment for various populations. One study in whites, blacks, and Hispanics is creating an asthma self-management skills training program for children and their parents. The program is being created for Web, CD–ROM, and DVD formats and focuses on improving understanding of asthma, preventing asthma attacks, and creating an asthma management plan. Another study will assess an asthma self-management intervention in Puerto Rican children, ages 8 to 16 years, delivered to families by Puerto Rican community health workers. The intervention will tailor a standard asthma core curriculum to family needs and cultural beliefs. A third study will seek to improve health among urban black adolescents with asthma. This study will use peer support—enhanced by a culturally sensitive, technology-based MP3 player platform—to increase adherence to daily controller medications. A fourth study will evaluate a Web-based intervention program that addresses asthma management and avoidance of tobacco use in rural, black adolescent boys.

Many individuals with asthma have poor disease management. A new study will determine whether a multifaceted prompting intervention, administered in urban primary care offices, reduces morbidity among urban children with asthma. Fifty percent of participants will be black. The intervention, designed to stimulate communication between caregivers and clinicians, includes information about the patient's asthma severity or level of control and individualized guideline-based recommendations for care. To improve asthma management, another study will use a highly tailored telephone counseling approach to foster a partnership between women and a clinician. Black women will be the target of this study. A third study will evaluate the efficacy of an evidence-based lifestyle weight loss intervention on asthma control among obese adults. Thirty-six percent of participants will be from minority populations.

Education

The Institute is supporting several education activities. It has developed easy-to-read materials on asthma treatment and control directed to English and Spanish audiences with low literacy:

Facts About Controlling Your Asthma
El Asma: Cómo Controlar Esta Enfermedad (Facts About Controlling Your Asthma)

The Institute also disseminates clinical practice guidelines for the treatment and monitoring of asthma, patient education materials, and information on environmental control of allergens in the United States and throughout the world. It has developed several asthma education programs that are directed at controlling asthma in black and Hispanic children. For example, A Tailored Asthma Education Program for Urban Teens II is evaluating a school-based approach to motivate black students to change negative behaviors related to asthma management. The Institute supports projects that (a) focus on innovative techniques to improve adherence to medical regimes among minorities and people living in poverty and (b) address methods to improve physician adherence to clinical practice guidelines.

Chronic Obstructive Pulmonary Disease

COPD is a disease in which the lungs are damaged, making breathing difficult. It is responsible for more than 500,000 hospitalizations and 100,000 deaths in the United States each year. The Institute has established a research network to determine effective disease management approaches for individuals with moderate-to-severe COPD:

COPD Clinical Research Network (see Chapter 11): To perform collaborative, therapeutic interventional trials of medications, devices, and disease management strategies in individuals with moderate-to-severe COPD. In addition to evaluating treatment efficacy, network studies include examinations of genetic factors, biomarkers, or genomic/proteomic profiles that may identify patients who are more or less likely to benefit from various treatments.

The NHLBI is supporting a large, investigator-initiated study of genetic factors that determine the risk of developing COPD or that influence the type and extent of damage done to the body by the disease. The COPDGene™ study will enroll approximately 3,500 blacks with a substantial history of cigarette smoking, obtain extensive baseline clinical and phenotypic data regarding the individuals, and compare the severity and character of COPD in the subjects to analyses of their DNA. Genomewide genetic assays will be performed on a substantial fraction of this cohort.

Although COPD is less common among blacks than among whites, it is nevertheless the seventh leading cause of death among blacks. Any disparity, whether higher or lower in the minority group, may reflect racial differences in the biology of the disease that would require use of different treatments or drugs for optimal disease management. If the genes found to be determinants of COPD risk differ in blacks and whites, this will provide clues to how the roles of specific pathogenetic pathways of COPD differ among races.

Sarcoidosis

Sarcoidosis is an inflammatory disease of unknown etiology characterized by persistent granulomas with damage to surrounding tissue. The Institute has initiated a program to determine the immunopathogenesis of granulomatous inflammation found in sarcoidosis, including the role of predisposing factors, the immune components involved in the formation of granulomas, and the defective regulatory immune response.

In the United States, sarcoidosis often occurs more frequently and with more severity in blacks than in whites. This may reflect the intensity of the noncaseating granuloma, the hallmark of sarcoidosis, in affected tissue. A twofold greater density of granuloma in bronchiolar lung biopsies was recently found in black patients, which correlated as a measure of disease severity.

Investigator-initiated studies supported by the Institute address the causes of sarcoidosis. They include a study to identify genes linked to sarcoidosis susceptibility in blacks and to determine whether hereditary susceptibility predisposes blacks to sarcoidosis, a study to examine the potential role of a mycobacterial etiology of sarcoidosis, and a study to elucidate the mechanisms involved in the immunologic and inflammatory processes that ultimately lead to end-stage fibrosis in progressive pulmonary sarcoidosis. Many participants are black.

A mentored research project conducted within the Black Women's Health Study is investigating potential risk factors for sarcoidosis.

Sleep Disorders

Sleep-disordered breathing (SDB), a condition characterized by repetitive interruption in breathing, is a common disorder that disproportionately affects blacks. It is associated with an increased risk of CVD, including hypertension and stroke, and is particularly prevalent in patients with heart failure. Ongoing programs are assessing the interrelationship between sleep disorders and heart failure and the mechanisms leading to cardiovascular stress when the two intersect.

The Institute also supports investigator-initiated projects to elucidate cardiovascular and other health consequences of SDB, sleep deprivation, and shift work in various community settings. Characterization of how SDB occurs within family groups is helping to identify potential genetic risk factors that may allow early identification and treatment of high-risk individuals. A community-based study of sleep in Hispanics is assessing the prevalence and awareness of sleep disorders.

Treatment and Control

The Institute initiated a clinical trial to determine whether adenotonsillectomy is an effective treatment for SDB in children:

Randomized Controlled Study of Adenotonsillectomy for Childhood Sleep Apnea (see Chapter 9): To assess the efficacy of adenotonsillectomy as a treatment for SDB in children aged 5 to 9 years. Fifty percent of participants are from various minority and ethnic populations.

Investigator-initiated research will assess treatment strategies in minorities. One study is seeking to develop in-home personalized sleep plans that can improve nightly sleep duration, neurocognitive function, and behavioral disorders in lower income minority children (ages 5 to 6 years). Another study of adults is examining the effect of a sleep apnea treatment (positive airway pressure therapy) on biological markers of CVD risk, including inflammation and metabolism. More than 50 percent of study participants are from minority populations.

Education

The NHLBI published Your Guide to Healthy Sleep, which provides the latest information about sleep apnea and other sleep disorders, including insomnia, restless legs syndrome, and narcolepsy.

HIV-Related Lung Diseases

HIV infection disproportionately affects minority populations in the United States and due to multidrug antiretroviral therapy, has become a chronic condition for many patients. Among them, HIV-associated lung complications are frequent causes of illness and death. But the long-term consequences of HIV infection and HIV-associated lung infections and complications are unknown. Little is known about drug-resistant Pneumocystis, the prevalence and pathogenesis of HIV-associated COPD, HIV-associated pulmonary hypertension, and immune reconstitution syndromes. In developing countries where millions of people are HIV-infected, many have serious or fatal lung complications including TB and bacterial pneumonias that have never been well characterized.

Etiology and Pathophysiology

In addition to supporting investigator-initiated research on the etiology and pathogenesis of HIV-associated lung diseases, the Institute has initiated research to understand their causes and impact and to identify potential therapeutic targets and preventive strategies:

The Mechanisms of HIV-Related Pulmonary Complications: To encourage innovative research on the roles of co-infections, immune factors, and genetic predisposition in the pathogenesis of HIV-related pulmonary diseases.
Longitudinal Studies of HIV-Associated Lung Infections and Complications: To accelerate research on lung complications associated with HIV-infection by characterizing lung infections, other HIV-associated lung complications, and their consequences in longitudinal studies in existing HIV-infected cohorts and other established groups of patients who are HIV-infected. Depending on the center, participation from minority populations ranges from approximately 40 to 100 percent.
Mechanisms and Management of Cardiovascular and Metabolic Complications of HIV/AIDS: To elucidate the underlying mechanisms of metabolic and anthropometric abnormalities seen in HIV infection and highly active antiretroviral therapy (HAART) and their relationship to CVD risk; to evaluate new and existing biomarkers and imaging modalities in the assessment of coronary artery disease and risk in HIV patients; and to identify treatment strategies and interventional approaches to reduce cardiovascular risk while optimizing the medical management of HIV infection. Enrollment from minority populations is expected to range from approximately 30 to more than 70 percent.
Microbiome of the Lung and Respiratory Tract in HIV-Infected Individuals and HIV-Uninfected Controls (see Chapter 9): To characterize the microbiome of the lung alone or in combination with the upper airways in HIV-infected individuals and matched HIV-uninfected controls using molecular techniques to identify bacteria and if possible other organisms (e.g., viruses, cell-wall deficient organisms, protozoa, and fungi). Enrollment from minority populations is expected to range from 35 to 76 percent.

Tuberculosis

TB is a common and often deadly infectious disease caused by the bacteria Mycobacterium tuberculosis. In the United States, an estimated 10 to 15 million people are infected with the TB bacteria. The rates among minorities and in the foreign-born remain high. In 2008, according to the CDC, more than 58 percent of all active TB cases in the United States were among the foreign born. Racial disparity in TB rates was greatest for U.S.-born blacks, whose rate was 7-times higher than the rate for U.S.-born whites.

Etiology and Pathogenesis

The immune response to TB infection is complex and involves the formation of granulomas in the lungs of infected individuals. In 2008, as part of the NHLBI Exploratory Program in Systems Biology, the Institute initiated a study that uses multiscale computational models and multisystem approaches to improve understanding of the role of granuloma formation in TB.

The Institute also supports investigator-initiated research that characterizes genes associated with TB susceptibility; investigates host lung defenses, including immune responses to infection; and studies the impact of TB on HIV disease. A new genetics study will fine-map chromosomal regions that have been linked to resistance to TB. Investigators will also analyze innate immune responses and model genetic predictors of resistance using data from a long-term household contact study conducted in Uganda.

Treatment and Control

The NHLBI supports a number of investigator-initiated studies focused on understanding the relationship between the immune system and TB. Most of the studies are being conducted among patients from minority populations. Included among them are studies to compare susceptibility to TB in populations in Mexico and Peru and examine the role of interferon-gamma in the pathogenesis of TB among Hispanics with and without HIV.

Education

Building on the foundation laid by the Tuberculosis Academic Award program, the NHLBI is supporting a consortium of five TB curriculum centers:

TB Curriculum Coordinating Center (See Chapter 10): To strengthen, expand, and increase access to the best ongoing educational and training opportunities in TB for medical, nursing, and allied health schools, especially those that provide primary care to communities where TB is endemic and the population is at high risk of developing TB

Blood Diseases

The NHLBI supports basic and clinical research on SCD and Cooley's anemia with the goal of curing the disorders and improving patient care.

Sickle Cell Disease

Basic Research

SCD is an inherited blood disorder that produces chronic anemia, periodic episodes of pain, and end organ damage. It affects about 1 in 500 blacks and 1 in 1,000 Hispanics. Since 1972, the NHLBI has supported an extensive research program to improve understanding of the pathophysiology of SCD, identify better approaches for its diagnosis and treatment, and prevent complications.

Basic and translational research currently focuses on genetic influences on disease manifestations, regulation of hemoglobin synthesis, discovery of drugs to increase fetal hemoglobin production, transplantation of blood-forming stem cells, gene therapy, and development of animal models for preclinical studies. The NHLBI supports this research through Institute-initiated and investigator-initiated projects:

BTRP (see Chapter 9): To encourage fundamental investigations and their translation into initial studies in humans, as well as community translation to promote evidence-based clinical practice. SCD Scholars programs for the career development of young investigators and Summer-for-Sickle-Cell-Science programs for research training and mentoring of high-school students also will be supported as part of a larger effort by the Institute to prepare the next generation of scientists to advance the field of SCD research. The BTRP was reconfigured from the NHLBI Comprehensive Sickle Cell Centers (CSCC) program.
Pulmonary Complications of Sickle Cell Disease: To stimulate collaborative translational research on the pulmonary complications of SCD. Researchers in hematology and pulmonary science—using a combination of basic and clinical approaches—are investigating the major known pulmonary complications of SCD due to acute chest syndrome, pulmonary hypertension, and oxyhemoglobin desaturation.

Two trans-NHLBI initiatives support research in SCD:

Genome-Wide Association Studies to Identify Genetic Components Related to Heart, Lung, and Blood Disorders: To investigate common genes involved in subphenotypes of SCD and centenarians. Scientists seek to identify genetic associations with specific clinical features in the two populations and subsequently compare the two datasets for differences and similarities. Research results could lead to improved treatment for SCD and increase our understanding of the genetic components that enhance healthy aging.
Ancillary Studies in Clinical Trials: To conduct time-sensitive ancillary studies in conjunction with ongoing Phase II-III clinical trials or network clinical trials related to heart, lung, and blood diseases and sleep disorders. One study seeks to identify genetic variations underlying Rh antigenic diversity in patients who have SCD. Research findings will be used to develop high throughput microchips to screen for matching donors and recipients prior to blood transfusion. Knowledge of the genetic basis for compatibility between donors and patients who have SCD for transfusion could contribute to preventing alloimmunization and improve care for patients who have SCD. Another study employs proteomic approaches to identify biomarkers of early cerebral ischemia in children who have SCD. Identifying such circulating biomarkers could allow earlier therapeutic intervention in these children.

Clinical Research

The NHLBI is committed to finding improved treatments and ultimately a cure for SCD and other hemoglobinopathies. Institute-initiated studies have begun to yield therapies that will alleviate the symptoms of sickle cell anemia and procedures that should ultimately provide a cure.

BABY HUG (see Chapter 11): To assess the effectiveness of hydroxyurea in preventing onset of chronic organ damage in young black children who have sickle cell anemia. At baseline, the trial has demonstrated that the spleens and kidneys of 1-year-old children are already damaged.
SWITCH (see Chapter 9): To determine whether hydroxyurea and phlebotomy can maintain an acceptable stroke recurrence rate and significantly reduce hepatic iron burden compared with transfusion plus chelation in black children who have had overt stroke.
Sildenafil for Sickle Cell Disease-Associated Pulmonary Hypertension (see Chapter 11): To test the effects of 16 weeks of chronic sildenafil therapy on exercise endurance and pulmonary artery pressure in patients aged 14 years and older with pulmonary hypertension and SCD.
Sickle Cell Disease Clinical Research Network (see Chapter 11): To conduct Phase III randomized controlled clinical trials to test the efficacy and effectiveness of new therapies to treat and prevent complications of SCD and, when appropriate, thalassemia.
Adult Sickle Cell Quality of Life Measurement Information System: To develop, validate, and disseminate a sickle cell-specific quality-of-life measurement tool that is a partner with and complementary to the NIH Roadmap Patient-Reported Outcomes Measurement Information System.
Exploratory Studies in the Neurobiology of Pain in Sickle Cell Disease: To conduct basic and translational research on the neurobiology of pain in SCD. The ability to identify standardized measures (such as those reflecting pain sensitivity, pain-evoked inflammatory/immune responses, and psychosocial factors) that help to explain disease status (especially patient response to opioid therapy) will have a substantial effect on how health care providers approach pain management.
Transcranial Doppler (TCD) With Transfusions Changing to Hydroxyurea: To compare standard therapy (transfusions) to alternative therapy (hydroxyurea) for maintenance of TCD velocities in children who have sickle cell anemia and are receiving chronic transfusions for abnormal TCD velocities.

The NHLBI supports several transplant-related clinical studies that seek to reach minority populations:

Blood and Marrow Transplant Clinical Research Network (BMT CRN) (see Chapter 11): In collaboration with the NCI, to perform clinical trials to advance hematopoietic stem cell transplantation. To reach minority populations, the Network supports bilingual transplant center personnel and provides public Web pages and educational materials. In addition, the Network is working with the National Marrow Donor Program to develop strategies and implement procedures to enhance enrollment of patients from minority groups.
The Sickle Cell Unrelated Transplant Trial: To assess unrelated donor marrow and umbilical cord blood transplantation for severe SCD. The trial, supported by the BMT CRN and the Sickle Cell Disease Clinical Research Network, is the first Phase II study to assess the promise of this therapy as a curative option for patients who are severely affected by SCD.

The NIH Hydroxyurea Treatment for SCD Consensus Conference, sponsored by the NIH Office of Medical Applications of Research and the NHLBI, along with other NIH and HHS components was held in February 2008. The conference assessed the available scientific evidence and concluded that hydroxyurea treatment for patients who have sickle cell anemia is underutilized and should be increased in adolescents and adults. Research has shown that patients who have SCD and are taking hydroxyurea experience fewer pain crises and hospital admissions. The conference panel advocated increased use of the drug with appropriate monitoring, and continuing follow-up of children in ongoing clinical trials.

To build capacity for clinical research, the NHLBI is funding the Clinical Hematology Research Career Development Program, which supports the early career development of clinical researchers who are expected to become independent investigators and assume academic leadership roles in nonmalignant clinical hematology.

Recommitment to Sickle Cell Disease Research

In March 2008, after a rigorous program assessment, extensive public input, and advice from the NHLBAC, the NHLBI announced a comprehensive and innovative restructuring of its research SCD program. As a result, the NHLBI is moving forward with the following innovations to its SCD portfolio:

Basic science: Support for basic research will be expanded through funding of investigator-initiated grant applications and through NHLBI-initiated RFAs focused on the pathophysiology of SCD, the biology of pain in SCD, fetal hemoglobin switching, and genetic modifiers of disease expression and progression.
Translational and clinical research: The Institute reconfigured the CSCC program into the BTRP with dedicated training components.
Participation in clinical research: The scope of clinical research trials will be broadened to allow a greater number of people with SCD to participate in NIH-sponsored clinical research trials.
Translation and dissemination to the community: In partnership with the Sickle Cell Disease Association of America and other patient advocacy groups and professional organizations, the NHLBI is developing evidence-based guidelines for the care of people with SCD across the life-span that can be used by health care practitioners throughout the world.

Education

The NHLBI has developed a number of publications on SCD that target minorities:
Datos Sobre La Anemia Falciforme (Facts About Sickle Cell Anemia)
Fact Sheet: Hydroxyurea in Pediatric Patients With Sickle Cell Disease
Facts About Sickle Cell Anemia
Patient Fact Sheet: The Multicenter Study of Hydroxyurea in Sickle Cell Anemia (MSH)
Management and Therapy of Sickle Cell Disease

Cooley's Anemia

Cooley's anemia is an inherited disorder of red blood cells that affects primarily people of African, Asiatic Indian, Chinese, Mediterranean, and Southeast Asian origin. In 2000, the Institute initiated a program to establish a network of clinical research centers to evaluate new therapeutic agents:

Thalassemia (Cooley's anemia) Clinical Research Network (see Chapter 11): To establish a group of clinical centers to accelerate research in the management of thalassemia, standardize existing treatments, and evaluate new ones

The NHLBI supports research efforts that include developing oral chelators to remove iron overload caused by repetitive transfusion therapy, testing drugs to enhance fetal hemoglobin production, and examining hematopoetic transplantation and gene therapy approaches to cure the disease. A registry with samples has been established to foster genomic and proteomic studies. International collaborations have also been initiated.

In 2006, the Institute established the NHLBI Clinical Hematology Research Career Development Program to support career development of clinical researchers in nonmalignant clinical hematology including Cooley's anemia.

The Institute recently entered into an Interagency Agreement with the CDC to develop and implement a national data system and biospecimen repository that will provide data to describe the epidemiologic and clinical characteristics of people with SCD, thalassemia, and hemoglobin-E diseases. The program will support research, information, dissemination, policy decisions, health care planning, and provider training at the local, state, and national levels.

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