12. Activities To Promote Diversity and Address Health Disparities


Throughout its history, the NHLBI has been a leader in conducting and supporting research and programs to eliminate health disparities that exist between various segments of the U.S. population. The Institute has not only initiated research projects with significant racial and ethnic 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 2011 activities addressing this goal include the following:

  • NHLBI Research Centers at Minority Serving Institutions: Supports establishment of research centers at minority serving institutions to augment and strengthen research capabilities and resources related to heart, lung, and blood diseases and disorders, with the goal of enabling the institutions and their investigators to become fully competitive
  • Sickle Cell Scholars Program: Supports career development of young or new investigators in SCD research as part of the Basic and Translational Research Program (BTRP) (see Chapter 9)
  • Summer-for-Sickle Cell-Science Program: Supports career development of young or new investigators in SCD research as part of the BTRP program
  • 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 in Clinical Research or Master of Public Health in a clinically relevant area
  • Short-Term Research Education Program To Increase Diversity in Health-Related Research: Promotes diversity in undergraduate and health professional student populations by offering short-term education support to stimulate career development in cardiovascular, lung, and blood diseases and sleep disorders research
  • Program To Increase Diversity Among Individuals Engaged in Health-Related Research (PRIDE): Encourages scientists and research-oriented faculty from diverse backgrounds to expand their research skills and gain experience in advanced methods and experimental approaches in basic and applied sciences in heart, lung, and blood diseases and sleep disorders so that they can compete for external funding for research in the biomedical and behavioral sciences
  • Mentored Career Development Award To Promote Faculty Diversity/Re-Entry in Biomedical Research: Promotes an increase in the number of highly trained investigators—from diverse backgrounds (i.e., faculty members who are from underrepresented racial and ethnic groups or who have disabilities or who are from disadvantaged backgrounds) or those who have experienced an interruption in their research careers—whose basic and clinical research interests are grounded in the advanced methods and experimental approaches needed to solve problems related to cardiovascular, lung, and blood diseases and sleep disorders
  • Mentored Career Award for Faculty at Minority Serving Institutions: Encourages eligible faculty members at institutions that promote diversity to undertake special studies and supervised research under a mentor who is an accomplished investigator in the research area proposed and who is experienced in developing independent investigators
  • Minority Institutional Research Training Program: Supports the training of pre- and postdoctoral students and certain health professional students at minority serving institutions in order to provide additional opportunities to develop research skills and to encourage the pursuit of research careers.
  • Support of Competitive Research (SCORE) Program: Fosters the development of faculty at minority serving institutions to increase their research competitiveness in the areas of heart, lung, and blood diseases and sleep disorders and to promote their transition to non-SCORE external sources of funding; and supports pilot awards for individuals at the beginning stages of a research career who are interested in testing a new idea or generating preliminary data, and for more experienced investigators who are interested in switching to a different field of research

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, individuals from disadvantaged backgrounds, and individuals with disabilities in NHLBI research and research training and career development programs. Selected FY 2011 activities include the following:

  • Issuing four training and career development RFAs to increase the number of highly trained individuals from diverse backgrounds, including individuals from underrepresented racial and ethnic groups, 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
  • Sponsoring Out of the Box, a project for the Cherokee and Smokey Mountain Elementary Schools that is designed to create awareness and interest in the importance of science, medicine, and health; eliminate gaps in quality of health among diverse groups by encouraging an interest in health-related careers; and empower children to take responsibility for their 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 with an opportunity to visit the NIH for 3 days to learn about biomedical research and research training opportunities at the NHLBI/NIH
  • Increasing recruitment of individuals for the NHLBI intramural and extramural training programs by representing the Institute at four diversity-focused research meetings to raise awareness of research and research training and career development opportunities supported by the NHLBI
  • Coordinating the Biomedical Research Training Program for Individuals From Underrepresented Groups, which offers opportunities for underrepresented health professional degree students and postbaccalaureate individuals 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
  • Serving as the NHLBI contact for guidance to candidates applying for the NIH Pathway to Independence Award and the NHLBI Career Transition Award for extramural programmatic issues

In addition, the DCVS Office of Research Training and Career Development sponsored the 18th annual Diversity Supplement Trainee Meeting prior to the American Heart Association Annual Scientific Meetings. The meeting brought together awardees, faculty mentors, and NHLBI program staff for scientific and poster presentations, discussions, and opportunities to network with colleagues.

See Chapter 13 for additional NHLBI-supported research training and career development programs for individuals from diverse backgrounds.

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, 10, and 11.

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Heart and Vascular Diseases

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 between CHD risk factors and the development of atherosclerosis and CVD in an adult population. Approximately 30 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. In 2000, the study began focusing on large, extended families on which linkage analyses and gene discovery studies could be conducted.
  • 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.
  • 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.
  • GOCADAN (see Chapter 9): To study the relative contributions of genetic and environmental factors to CVD in Eskimos in the Norton Sound region of Alaska.

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 and the National Longitudinal Mortality Study that analyzes socioeconomic, demographic, occupational, and racial differentials in mortality in the United States.

The NHLBI also supports a variety of investigator-initiated research activities across a range of racial and ethnic groups on risk factors, genetic contributors, and health disparities in heart, lung, and blood diseases and sleep disorders. Many of them are ancillary studies to NHLBI-initiated cohort studies.

Risk Factors

Investigator-initiated studies on cardiovascular risk factors in underrepresented racial and ethnic groups range in focus from biological to environmental, psychosocial, and cultural. One study among blacks in the JHS is characterizing the relationships between vascular function and CVD risk factors and indicators of subclinical CVD, and detecting gene variants that influence vascular function. A second study is investigating the effects of low vitamin D levels in blacks in the biethnic ARIC cohort. A third study involves echocardiographic examination of a subsample of adult participants in the HCHS to determine the prevalence of abnormal cardiac function, the degree of heterogeneity in cardiac function between Hispanic subgroups, and the relationship between cardiac structure and function and such factors as diabetes biomarkers, psychosocial measures, and measures of socioeconomic status in Hispanics.

Additional studies are determining geographic and ethnic variations in the prevalence of CHD risk factors; investigating risk factors linked to atherosclerosis and disease progression in South Asians that live in America; and examining the effects of arsenic exposure on diabetes and CVD in American Indians.

Genetic Epidemiology

Genetic epidemiology is concerned with the role of genetic factors in the etiology of disease within groups of relatives and the interplay of genetic factors with environmental factors. NHLBI-supported studies include those focusing on gene discovery through both linkage studies in family-based samples and genome-wide association studies (GWASs) in population-based samples; the effects of gene–environment interactions on risk factors and health; and genotypic characterization in relationship to intermediate phenotypes, such as biomarkers.

Genetic epidemiologic research is also beginning to transition to predicting and assessing genetic risk and reporting genetic results to participants of research studies. The activities offer unique insights into specific populations and general observations that are relevant to all populations. Examples are studies of genetics of hypertension in populations of West African origin; the role of stress in gene–environment interaction in a multi-ethnic population; the contribution of genetic variation to obstructive sleep apnea, impaired endothelial function, and central blood pressure in Mexican Americans; salt sensitivity and blood pressure in Chinese populations; genetics of high serum triglycerides and metabolic traits in Mexican Americans; and genetic variation that underlies obesity and obesity-related phenotypes among Samoan adults.

A new study is investigating the molecular mechanisms that underlie the genetic basis of left ventricular hypertrophy. This study is leveraging epidemiological and genetic work of the NHLBI-supported Hypertension Genetic Epidemiology Network Echo Study. Fifty-five percent of participants are black.

Health Disparities

The NHLBI is committed to supporting research that will contribute to reducing health disparities among racial and ethnic minorities.

  • CPHHD (see Chapter 9): To promote transdisciplinary research in health disparities in order to improve health outcomes and quality of life for populations at high risk for CVD. The population will consist primarily of blacks and Hispanics.
  • NHLBI Centers for Cardiovascular Outcomes Research (see Chapter 9): To conduct research that focuses on measuring, evaluating, and improving outcomes of cardiovascular care. Approximately 30 percent of participants will be from racial and ethnic minority populations.

A project within the Mentored Career Development Award To Promote Faculty Diversity/Re-Entry in Biomedical Research program is conducting research on racial disparities between blacks and whites who live in the inner city by focusing on issues related to physical fitness and cardiovascular risk reduction.

Education

The NHLBI hosts Children and Clinical Studies (see http://www.ChildrenAndClinicalStudies.nhlbi.nih.gov), an educational Web site, for children and their families and health care providers, to improve understanding of pediatric research. The site offers information in English and Spanish about the importance of research on children, safety measures in clinical trials, and potential effects on a family when a child is enrolled in a study. The site also has a section about minority interests and concerns.

The NHLBI, through the DARD, translates research findings into practice by facilitating the development of clinical practice guidelines; communicating research advances; 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 Institute supports the following activities to improve cardiovascular health in racial and cultural/ethnic groups:

  • The Community Health Worker Initiative: To improve cardiovascular health among black, Hispanic, American Indian, Alaska Native, and Filipino-American communities using the community health worker model to promote evidence-based, heart health knowledge, attitudes, and behaviors.
  • 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 evidence-based, heart health curriculum, residents of the black community are trained to become health educators of other public housing residents.
  • Salud para su Corazón: To develop networks and partnerships to disseminate information and strategies and to train lay educators about evidence-based CVD prevention and control, in order to promote heart healthy knowledge, attitudes, and behaviors in Hispanic communities.
  • Honoring the Gift of Heart Health: To train community health workers to deliver culturally appropriate, evidence-based curricula to prevent and control CVD risk factors in American Indian tribal communities.
  • Healthy Heart, Healthy Family: To train community health workers to deliver culturally and linguistically appropriate curricula and to conduct outreach activities that increase community awareness of heart disease and its associated risk factors and that promote heart healthy lifestyles among the growing population of Filipino heritage in the United States.
  • The Heart Truth® Campaign: To raise awareness of heart disease in women through community-based interventions and social marketing media. Special populations are especially targeted through the Heart Truth's Women of Color Initiative, a partnership with national black and Hispanic organizations.
  • We Can!® (Ways to Enhance Children's Activity & Nutrition): To help children ages 8–13 years maintain a healthy weight by providing curricula, tools, tips, and other resources to parents, caregivers, communities, and other organizations. Special attention is directed to black, Hispanic, and American Indian/Alaska Native populations.

In addition to the activities mentioned above, the Institute has prepared and distributed 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 (and a series of picture cards)
  • On the Move to Better Heart Health for African Americans (easy-to-read booklet on heart healthy living)
  • Your Choice for Change: Honoring the Gift of Heart Health for American Indians (easy-to-read booklet on heart healthy living)
  • Healthy Heart, Healthy Family: A Community Health Worker's Manual for the Filipino Community in English and Tagalog (and a series of picture cards)
  • Healthy Heart, Healthy Family Series (six easy-to-read English and Tagalog booklets on heart healthy living for the Filipino community)
  • 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 (and a series of bilingual picture cards and a DVD)
  • Healthy Hearts, Healthy Homes Series (six easy-to-read English and Spanish booklets on heart healthy living)
  • 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 their diagnosis, treatment, and prevention in all racial and ethnic groups in the United States. One study is evaluating variants of the gene NOS1AP that affect the QT interval in various racial and ethnic populations. Another study is evaluating the distributions of electrocardiographic predictors of atrial fibrillation in racial and ethnic groups to determine whether minority populations have a higher risk for this arrhythmia than whites. A third study is investigating the role of sodium channel polymorphisms in cardiac arrhythmias in families with Long QT syndrome and Brugada Syndrome; approximately 66 percent of participants will be from racial and ethnic minority populations.

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 the 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 approximately 5 million Americans and is a growing public health concern. It is frequently the end result of other conditions, such as hypertension, diabetes, and prior heart attacks.

Findings from the CARDIA study showed that heart failure before age 50 is substantially more common in blacks than in whites. Heart failure in black participants in the study was often preceded by such risk factors as high blood pressure, obesity, and chronic kidney disease 10 to 20 years prior to the heart failure.

The Institute has initiated a study to facilitate 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 includes a historically black medical center with minority investigators and access to a high-risk, underserved population.

Investigator-initiated research is targeting heart failure among minority populations. A study is examining the role of impaired ATP synthesis and delivery in contractile dysfunction in heart failure patients; approximately 40 percent of participants are from racial minority populations. Another study is examining the underlying genetic variations that result in familial dilated cardiomyopathy, an inherited form of heart dysfunction. A study is focusing 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. Another study is focusing on drugs commonly used to treat heart failure to determine whether beta blockers are as effective in black as in white heart failure patients; researchers will study genetic and other factors that affect the difference.

Individuals with heart failure typically have a poor prognosis and a diminished quality of life. Inadequate health literacy skills, depression, and emotional stress are common and are often associated with poor health outcomes. One study is determining whether cognitive behavioral intervention is superior to supportive clinical management for depressed outpatients with heart failure; approximately 30 percent of participants are expected to be black. Another study is examining the role of emotional stress on heart failure exacerbations; a large proportion of the population is black. A third study is investigating whether an exercise intervention, such as tai chi, can increase physical function, cardiac functional capacity, and quality of life in patients with heart failure; nearly 50 percent of participants are expected to come from minority populations.

High Blood Pressure

Etiology

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, Asians, 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.

Researchers are also seeking to understand the role of obesity in the development of high blood pressure. A new study will investigate the effect of natriuretic peptides (hormones produced by the heart) in blood pressure regulation and dietary salt sensitivity, and relate findings to previous findings that obese individuals have decreased numbers of circulating natriuretic peptides. Approximately 40 percent of study participants are expected to be from minority subgroups.

Treatment and Prevention

Identifying effective treatment strategies for various populations requires large-scale studies with representative populations in sufficient numbers.

  • SPRINT (see Chapter 11): To determine whether intensive lowering of systolic blood pressure below the currently recommended standard will reduce the risk of cardiovascular and kidney diseases or age-related cognitive decline. Approximately 25 percent of participants will be from racial and ethnic populations.

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. One study is testing a church-based lifestyle intervention to reduce blood pressure using group classes and motivational interviews to help participants make and maintain therapeutic lifestyle changes; approximately 400 blacks with high blood pressure are expected to participate.

Education

The NHLBI has developed a number of outreach activities to inform minority populations of the importance of blood pressure control. Several publications and Web-based products have been developed and distributed for health professionals, patients, and the public. Some examples are:

  • Presión Arterial Alta: NHLBI Diseases and Conditions Index
  • 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
  • Your Choice for Change: Honoring the Gift of Heart Health for American Indians

High Serum Cholesterol

Etiology

The Institute supports investigator-initiated studies to identify genes that influence the lipoprotein profile in various racial and ethnic groups. Research findings could offer an explanation for differences in susceptibility to CHD found among the groups. A 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 are seeking to identify genes for QTLs that are related to lipoproteins.

Treatment

Research has shown that patients with elevated LDL levels who have been advised to make lifestyle changes and to take statins often do not comply with the prescribed regimens. An investigator-initiated study is seeking to develop and evaluate an interactive virtual environment system to increase the initiation and maintenance of medication adherence and therapeutic lifestyle change in patients who are at risk for CHD. Patients will be able to access the system to seek advice from a virtual health care provider and get assistance in developing an effective care plan that is based on clinical guidelines.

Education

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

  • Healthy Hearts, Healthy Homes—Do You Know Your Cholesterol Levels? in English and Spanish
  • Heart-Healthy Home Cooking African American Style
  • Delicious Heart-Healthy Latino Recipes in English and Spanish
  • Healthy Heart, Healthy Family—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 American Indians, blacks, and Mexican Americans—are especially at risk. Data from the 2007–2008 NHANES show that 34 percent of adults and 17 percent of children aged 2–19 years are obese. Understanding the causes of obesity could lead to effective strategies to combat it. A long-term investigator-initiated study is examining parental and extended family influences on the development of childhood obesity in Mexican American children.

An investigator-initiated study seeks to elucidate interconnected biological and social pathways associated with adolescent obesity and risk for later development of type 2 diabetes and CVD in Latin American youth. The goal of the study is to identify modifiable conditions in order to prevent obesity and related diseases.

The NHLBI funds several studies that focus on genetic risk factors for obesity in one or more minority populations. Evidence for obesity genes has been identified on chromosome 4 in American Indians, on chromosome 9 in Mexican Americans, and on chromosomes 5 and 6 in blacks. In some cases, the results confirm those found in European Americans, and in other cases, the results represent novel findings.

Researchers have found that black and Hispanic children are especially likely to develop sleep apnea. An investigator-initiated study will assess the role of obesity in the development of abnormalities that increase the likelihood of developing sleep apnea and whether the problem can be corrected with weight loss. Blacks comprise approximately 80 percent of participants. Another study with multi-ethnic participation is determining whether obese children with sleep apnea are at increased risk of cognitive impairment and vascular disease.

Treatment and Prevention

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

  • EARLY Trials (see Chapter 11): To develop and evaluate innovative approaches for weight control in young adults from ethnically and socioeconomically diverse populations who are at high risk for weight gain.
  • ORBIT (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.
  • COPTR Consortium (see Chapter 11): To test interventions to prevent excess weight gain in non-overweight and overweight youth and to reduce weight in obese and severely obese youth. More than 50 percent of participants are expected to be from racial or ethnic minority populations.

The Institute supports a number of investigator-initiated studies on the effectiveness of obesity prevention and control interventions among diverse populations. They include testing an integrated school- and community-based intervention that involves physical activity and diet to reduce the prevalence of obesity among Hispanics, people of Asian heritage, and whites; evaluating, in a primarily minority population, the effect of adding environmental approaches to a standard family-based intervention to reduce overeating in obese children; exploring whether naturally occurring social support networks can help parents manage their children's weight in a population where 40 percent of the children are expected to be from racial and ethnic minority populations; and evaluating an intervention that supports primary care treatment of obesity in adults with at least one other cardiovascular risk factor; one project has strong Hispanic participation.

Many obese adults have difficulty breathing upon physical exertion and therefore are unable to exercise sufficiently. It is unclear whether this is because the individuals are in poor physical condition and could be helped with endurance exercise training, or whether obesity-related respiratory changes have occurred that necessitate weight loss before exercise training can be effective. Researchers are planning to investigate this question in obese individuals (approximately 40 percent of whom will be from minority populations) by assessing the effect of endurance exercise training (without weight loss) versus weight loss (without exercise training) on breathing difficulties after physical exertion.

Education

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

  • Healthy Hearts, Healthy Homes—Do You Need To Lose Weight? in English and Spanish
  • ¿En Qué Consiste el Sobrepeso y la Obesidad? (What are Overweight and Obesity?) in the NHLBI Diseases and Conditions Index
  • We Can!®: Many bilingual (English and Spanish) publications on energy balance are available on the Web site at http://wecan.nhlbi.nih.gov

Physical Inactivity

Despite substantial research about the benefits 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 two Institute-initiated longitudinal cohort studies.

The transition from elementary school to middle school marks a critical stage in the development of young people and the period during which physical activity tends to decline dramatically. An investigator-initiated study is investigating factors that contribute to the decline and the potential moderating effects of gender, race, socioeconomic status, and neighborhood environment on factors that influence changes in physical activity. A majority of participants will be from racial and ethnic minority populations. Another study will collect data on aspects of neighborhood environments that are most often associated with physical activity in adolescents and determine whether this information can be used, via interventions offered in the offices of pediatricians, to help children increase their physical activity. A third study will develop and evaluate policies to increase physical activity and improve nutrition during summer and afterschool programs sponsored by the YMCA; approximately 50 percent of the children in the programs being evaluated are expected to be black.

Regular physical activity is important for cardiovascular health throughout life. Investigators are designing and evaluating a long-term, multilevel physical activity intervention for sedentary residents who are living in retirement communities. The intervention uses a variety of elements, including self-monitoring with a pedometer, group sessions and peer mentoring, and such environmental components as tailored walking maps. Approximately 25 percent of participants are expected to be from racial and ethnic minority populations.

Several investigator-initiated studies are evaluating culturally appropriate interventions to increase physical activity. Projects include those that use faith-based approaches involving church leaders and congregations to increase activity levels in blacks and those that test culturally targeted interventions in schools or among pregnant women and 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 new way to deliver convenient and sustainable adherence strategies. In one study, women are receiving prompts, video clips, and individualized feedback via their cell phones to help them increase their physical activity levels; approximately 60 percent of the women are expected to be from racial and ethnic minority populations. In another study with large minority participation, researchers are assessing a program that is designed to improve diet and activity levels in sedentary people with poor quality diets; all participants use "smart phones" to monitor themselves and transmit information to a personal coach.

Education

The Institute has prepared and distributed 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
  • 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
  • We Can!®: Many bilingual (English and Spanish) publications on physical activity and energy balance are available on the Web site at http://wecan.nhlbi.nih.gov

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 Institute has initiated smoking intervention programs in specialized groups:

  • CHART (see Chapter 11): To evaluate the translation of efficacious smoking cessation strategies initiated during hospitalization and continued post-discharge into effective programs that can be widely implemented in routine clinical practice and assess the cost-effectiveness of these interventions. One of the projects will have approximately 75 percent participation from Asian, Hispanic, and black populations.
  • Longitudinal Studies of HIV-Associated Lung Infections and Complications: To develop and evaluate a specialized smoking cessation intervention for the treatment of nicotine dependence in HIV-seropositive smokers who are at high risk of developing accelerated emphysema; 40 percent of participants are black.

The NHLBI supports a number of investigator-initiated studies of smoking cessation in underserved populations. One study among predominately black 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. 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. Two studies among military personnel are testing interventions that focus on smoking cessation and subsequent abstinence; approximately 25–40 percent of participants are expected to come from racial and ethnic minority populations.

Education

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

  • Enjoy Living Smoke Free in English and Spanish
  • 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 and 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. One study is seeking to increase understanding of the mechanisms that lead to death in depressed patients with heart disease by assessing the effects of stress on heart and brain function in heart disease patients with and without depression; approximately 45 percent of participants are expected to be from minority groups. Another study is examining the potential epigenetic mechanisms that link depression and cardiovascular disease. More than 50 percent of participants are expected to be black.

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.

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 during 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. Another study is examining whether racial disparity in AMI-recovery outcomes in older individuals is partially due to stress related to age and racial stigmas. Fifty 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 goal is to determine whether stress management interventions can alter these physiological indicators and improve cardiovascular outcomes.

Treatment

The Institute supports several investigator-initiated studies to develop and evaluate interventions to improve cardiovascular outcomes. One study is seeking to determine the efficacy of a mindfulness-based personalized health plan intervention on reducing inflammation, a significant predictor of future CVD, via reductions in traditional risk factors, selected psychosocial attributes, and stress-reactivity among at-risk adults. Approximately 30 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 GWAS, 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 Rican Diabetes–CHD case-control study.

Treatment and Prevention

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:

  • ACCORDION (see Chapter 10): To obtain long-term (10 years on average) data on ACCORD participants. More than 33 percent of participants are from minority populations.
  • Diabetes Prevention Program Outcomes Study─Phase II (see Chapter 11): To determine the efficacy of treatments to prevent or delay the development of type 2 diabetes in a population at high risk due to the presence of impaired glucose tolerance. Forty-five percent of participants will be 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.

Education

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

  • Healthy Hearts, Healthy Homes—Protect Your Heart Against Diabetes in English and Spanish
  • Healthy Heart, Healthy Family—Protect Your Heart: Prevent and Control Diabetes in Tagalog and English

HIV-Related Cardiovascular Diseases

Use of multidrug antiretroviral therapy has improved life expectancy of HIV-infected individuals to the point that HIV/AIDS is now a chronic condition for many patients. As a result, CVD is now causing an increasing proportion of the deaths of HIV-infected individuals.

The NHLBI initiated research on the development of CVD in HIV-infected patients and potential management strategies:

  • Mechanisms and Management of Cardiovascular and Metabolic Complications of HIV/AIDS: To elucidate the underlying mechanisms of metabolic and anthropometric abnormalities found in HIV-infected patients and relate the mechanisms to CVD risk; evaluate biomarkers and imaging methods for assessing coronary artery disease and risk in HIV patients; and identify strategies and approaches that reduce cardiovascular risk and optimize the medical management of HIV infection. Approximately 30–70 percent of participants are expected to come from racial and ethnic minority populations.

Lung Diseases

The NHLBI supports research on several lung diseases—such as asthma, sarcoidosis, TB, and HIV-related lung diseases—that 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 and most often starts in childhood. In the United States, more than 24 million people are known to have asthma, and more than 7 million of them are children. Prevalence rates are especially high in blacks and Puerto Ricans.

Etiology

The NHLBI has initiated additional studies to improve understanding of the etiology and pathophysiology of asthma:

  • Severe Asthma Research Program (see Chapter 9): To define severe asthma at the molecular and cellular levels over time in order to gain an understanding of the pathogenesis of the disease and provide a basis for design of mechanism-based diagnostic, prognostic, and treatment strategies for children and adults with severe asthma. Several of the projects have strong participation from minority 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 to identify innovative therapeutic targets. Two projects expect 30–50 percent of participants to be from minority populations.

The Institute also supports investigator-initiated projects on the etiology and pathophysiology of asthma. Several projects focus on the role of genetics in the development of asthma. One study will 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 subsequently determine their role in the development of asthma, airway hyperreactivity, and allergy. Forty percent of participants will be black. Another study will improve understanding of the etiology of asthma and the response to asthma drugs by performing GWAS to determine genetic factors that are associated with asthma, asthma severity, and bronchodilator response in two Latino subgroups. Additional studies will identify the genes and structural genetic variations that contribute to childhood asthma in the major racial and ethnic groups in the United States and in Hispanic populations outside the United States.

Investigators are also interested in the role of stress in the development of asthma. One study is using a systems biology approach to determine multiple biologic pathways by which stress can contribute to asthma. Scientists are investigating whether maternal stress immediately before or after the birth of a child can adversely affect the child's risk for wheezing and impair lung function later in childhood. Scientists hypothesize that multiple stressors that are prevalent in disadvantaged populations can cumulatively influence immune system development and airway inflammation in early life, thus making the populations more susceptible to other environmental factors and genetic risk factors explaining, in part, observed asthma disparities associated with SES and race and ethnicity.

A group of scientists has speculated that vitamin D deficiency in pregnant mothers may lead to faulty immune system development in the neonate, predisposing the neonate to asthma and allergy. To test the hypothesis, scientists will determine whether supplemental vitamin D intake to increase the level of vitamin D in pregnant women will prevent asthma and allergy in their children at age 3 years. More than 50 percent of participants are from racial and ethnic minority populations.

Research findings suggest that obesity and asthma are complex disorders that may have shared genetic determinants. An investigator-initiated study is seeking to 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 diverse (Hispanic, black, and white) cohorts.

Treatment and Control

The Institute has initiated research to identify optimal 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.

The Institute also supports two investigator-initiated clinical trials to evaluate treatment strategies in asthma patients. STAN (see Chapter 9) is seeking to determine whether treatment of chronic rhinitis and sinusitis with nasal steroids will improve the control of asthma. Thirty-three percent of participants are expected to be from minority populations. SOYA (see Chapter 9) expects to determine whether supplementation with soy isoflavones among persons with poorly controlled asthma improves both lung function and markers of airway inflammation. Thirty-three percent of participants are expected to be from minority populations.

Quality of life (QOL) measures can assist health care providers in the treatment of asthma. Based on recommendations by the Asthma Related Quality of Life Subcommittee of the Asthma Outcomes Workshop held in 2010, new instruments are being developed and tested to measure more comprehensively the effects of asthma on QOL. Approximately 30 percent of participants will be from racial and ethnic minority populations.

One way to reduce asthma health disparities and reduce harm is to begin treatment in early childhood. Studies have shown that asthma education programs can improve overall management of asthma in preschool children. A study in Baltimore, Maryland, is partnering with Head Start to compare the efficacy of early intervention plus asthma education versus asthma education alone in reducing asthma morbidity. Nearly all participants will be black.

The Institute is supporting several 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 is seeking to improve health among urban black adolescents with asthma by using peer support—enhanced by a culturally sensitive, technology-based MP3 player platform—to increase adherence to daily controller medications. A third study is evaluating a Web-based intervention program that addresses asthma management and avoidance of tobacco use in rural, black adolescent boys. A fourth study is assessing the effects of heart rate variability biofeedback on airway reactivity and inflammation to determine whether biofeedback can be useful for treating asthma; approximately 35 percent of participants will be from minority groups.

Many individuals with asthma have poor disease management. An investigator-initiated study is determining whether an intervention designed to stimulate communication between caregivers and clinicians and to contain individualized guideline-based recommendations for care, administered in urban primary care offices, reduces morbidity among urban children with asthma; 50 percent of participants are black. Another study is addressing asthma disparities that persist among high-risk children who live in rural, medically underserved areas by testing a school-based telemedicine approach that will deliver asthma education to rural children with asthma, their caregivers, and school nurses. The approach also prompts the children's primary care physicians with treatment recommendations. Approximately 75 percent of participants will be black.

A study in high-risk black adolescents with moderate to severe asthma is testing the effectiveness of an intensive home- and community-based psychotherapy intervention to improve asthma management and reduce the number of hospitalizations and visits to emergency departments. Black women will be the target of a study to improve asthma management by using a highly tailored telephone counseling approach to foster a partnership between women and a clinician. A study of obese adults, for which approximately 40 percent will be from minority populations, will evaluate the efficacy of an evidence-based lifestyle weight loss intervention to control asthma.

Investigators are also interested in evaluating whether cultural competency training for primary care physicians who primarily serve black or Hispanic communities will improve the asthma outcomes of their patients.

Symptoms of depression are commonly found in patients with asthma. A pilot study using an antidepressant to treat outpatients with major depression and asthma showed that patients who received treatment experience greater sustained remission of depressive symptoms and require significantly less oral corticosteroids for asthma management than the group who received placebo. Based on these findings, scientists are implementing a definitive antidepressant study in patients with asthma and major depression. Most participants will be black or Hispanic.

Education

The Institute is supporting several education activities through the National Asthma Control Initiative (NACI), which was developed by the National Asthma Education and Prevention Program (NAEPP) and is coordinated by the NHLBI. The NACI seeks to accelerate the adoption of six priority action messages from the latest asthma guidelines to improve clinical practices and outcomes. NACI Demonstration Projects, Strategic Partner Projects, and Clinical Champions Projects are implementing strategies in racial and ethnic minority communities to address asthma health disparities in diverse populations.

The Institute has developed materials on asthma treatment and control:

  • So You Have Asthma
  • My Asthma Wallet Card
  • Asthma Action Plan
  • Asthma and Physical Activity in the School

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.

Chronic Obstructive Pulmonary Disease

COPD—a disease in which the lungs are damaged, making breathing difficult—is the third leading cause of death in the United States. It is responsible for more than 500,000 hospitalizations and more than 130,000 deaths in the United States each year.

Etiology

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 has enrolled more than 3,000 blacks with a substantial history of cigarette smoking, obtained extensive baseline clinical and phenotypic data regarding the individuals, and compared the severity and character of COPD in the subjects to analyses of their DNA. Genome-wide 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.

Treatment and Control

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. Twenty-two percent of participants are minorities.

In addition, in collaboration with the Centers for Medicare and Medicaid Services, the Institute is sponsoring a clinical trial of supplemental oxygen treatment in COPD patients:

  • LOTT (see Chapter 11): To test whether long-term oxygen therapy can reduce disability and prolong life in COPD patients who have moderate resting hypoxemia or severe hypoxemia during exercise.

Education

The NHLBI has developed a number of outreach activities associated with COPD. Several publications and Web-based products have been developed and distributed for health professionals, patients, and the public. Some examples include:

Sarcoidosis

Sarcoidosis is an inflammatory disease of unknown etiology characterized by persistent granulomas with damage to surrounding tissue. The Institute supports research into the basic mechanisms of sarcoidosis and new and improved treatments for it.

Sarcoidosis occurs more frequently and with more severity in blacks than in whites, suggesting the presence of genetic determinants to disease predisposition. To increase understanding of the disease, researchers are seeking to identify genes of African ancestry that play a significant role in its etiology and pathogenesis. Other possible causes of sarcoidosis are also being investigated.

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

Diagnostic tools and treatment approaches for sarcoidosis are lacking. A new study supported by the Institute-initiated CADET Program (see Chapter 9) is seeking to develop a skin test for diagnosing sarcoidosis and to establish an approach for treating sarcoidosis with oral vaccines.

Sleep Disorders

Etiology

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. One study is testing associations between indices of sleep apnea and the quality, duration, and timing of sleep with indices of cardiovascular risk and disease to address the role of sleep disorders in CVD development in minority populations. Approximately 60 percent of participants are expected to be from racial and ethnic minority groups. Another study is measuring the association between sleep duration and nervous system, cardiovascular, and metabolic health and dysfunction and overall body inflammation; approximately 70 percent of participants are expected to be from minority populations. A third study is investigating sleep apnea in stroke patients, collecting and analyzing data on prevalence, relationship to ethnicity, and the association between stroke type and outcomes; approximately 65 percent of participants are expected to be from racial and ethnic minority groups.

In an ancillary study to the Hispanic Community Health Study, investigators are collecting measurements of sleep patterns from several Hispanic subgroups. Investigators will analyze the prevalence of altered sleep patterns and define the importance of psychosocial factors (e.g., home- and work-related factors and mood, as well as cultural factors) in predicting abnormal sleep patterns. They will also evaluate associations between poor sleep and cardiovascular health outcomes, including obesity, hypertension, diabetes, and heart disease.

Treatment and Control

The Institute initiated a pilot study to guide design of phase III clinical trials to test whether treatment of obstructive sleep apnea (OSA) with positive airway pressure (PAP) reduces CVD risk:

  • Reducing Cardiovascular Disease Risk Through Treatment of Obstructive Sleep Apnea: To evaluate the treatment of OSA using PAP. The study will provide information about the feasibility of long-term (12 to 18 months) PAP treatment of OSA in patients who are at risk of CVD. The study will also provide data about the effects of PAP on surrogate markers of cardiovascular risk. Approximately 40 percent of participants will be from minority populations.

A new study supported by the Institute-initiated CADET Program is seeking to develop reliable urinary biomarker measures that can be used to screen and diagnose OSA in children, thereby facilitating timely treatment and prevention of OSA-associated morbidities. Approximately 80 percent of participants are expected to be from minority populations.

Investigator-initiated research will also assess treatment strategies in minorities. One study is developing in-home personalized sleep plans to improve nightly sleep duration, neurocognitive function, and behavioral disorders in lower income minority children (ages 5 and 6 years). Another study will measure effects of continuous compliance to PAP therapy on neurocognitive function (including academic achievement, attention, working memory, decision making, and mental flexibility) in children. Parental reports of child behaviors and sleep patterns will also be assessed. Approximately 60 percent of participants will be from minority populations. A third study will advance understanding of endothelial activation processes in OSA patients and may enable early identification of OSA patients who are at risk for vascular diseases. Results may also provide the basis for developing new therapeutic strategies for preventing or reversing vascular risk in OSA patients. Approximately 90 percent of participants are expected to be from minority populations.

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 infected with HIV, many have serious or fatal lung complications, including TB and bacterial pneumonias, that have never been characterized well. Lung and cardiovascular diseases, usually more prevalent in older populations, are having an increasing effect on HIV-infected populations in the United States and other industrialized nations where the average age of HIV-infected individuals has increased due to effective antiretroviral therapy. The effect is exacerbated because lung and cardiovascular complications are occurring in relatively young age groups in HIV-infected populations.

Etiology

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:

  • 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.
  • 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 Mycobacterium tuberculosis. In the United States, an estimated 10–15 million people are infected with the TB bacterium. Although the majority of those infected remain healthy (latent TB infection), a small percentage develops active tuberculosis. The rates of both TB infection and active TB 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

The immune response to TB infection is complex and involves the formation of granulomas in the lungs of infected individuals. In 2010, the Institute began a systems biology approach to identify the mechanisms of TB latency and reactivation.

  • Systems Biology Approach to the Mechanisms of TB Latency and Reactivation: To investigate mechanisms of latency and reactivation of TB in the host using integrated systems biology approaches. A collaborative program consisting of five Tuberculosis Systems Biology Centers and a Data Coordinating Center will integrate data from humans and animal models with computational and mathematical models in a comprehensive systems biology approach to increase understanding of latent TB and the factors that lead to its reactivation. Depending on the center, minority enrollment in the U.S. populations under study is expected to range from approximately 30 to 66 percent. Several of the grants in this program will study international populations in Africa and Asia.

The Institute also supports investigator-initiated research that characterizes genes associated with TB susceptibility; investigates host lung defenses, including immune responses to infection; and examines the impact of TB on HIV disease. A genetics study will seek to fine-map chromosomal regions that have been linked to resistance to TB. The study also plans to 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 on understanding the relationship between the immune system and TB. Most of the studies are being conducted among patients from minority populations. One study is seeking new approaches to diagnosing and treating active TB in sub-Saharan Africa and other parts of the world. The study may also help to identify new markers that can predict response to TB therapy. Another study is determining whether different strains of Mycobacterium tuberculosis cause different responses in individuals from various racial and ethnic groups. Results of this study may increase understanding about tailoring vaccines to specific populations. A third study is testing the efficacy of daily vitamin D supplementation, added to multidrug therapy, to improve antimicrobial immune response to TB infection in residents of Mongolia.

Blood Diseases

The NHLBI supports basic, translational, and clinical research on SCD and thalassemia (Cooley's anemia) with the goal of curing the disorders and improving patient care. The Institute also supports a deep vein thrombosis and venous disease program and programs in transfusion medicine, blood banking and blood products safety, and such cellular therapies as bone marrow transplantation.

Sickle Cell Disease

Basic and Translational Research

SCD, the most common inherited blood disorder in the United States, affects an estimated 70,000 to 100,000 Americans, most of whom are black. SCD occurs in about 1 in 500 blacks and 1 in 36,000 Hispanics. The disease is characterized by anemia, severe infections, acute and chronic pain, and organ damage. SCD, the first molecular disease described, was shown to be due to a single amino acid substitution on the beta chain of hemoglobin.

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, pain research, and development of animal models for preclinical studies. Institute-initiated programs include:

  • BTRP (see Chapter 9): To conduct comprehensive research, training, and education efforts related to SCD. The BTRP seeks to improve understanding of SCD pathophysiology and develop cures or improved medical management of the disease.
  • 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 is using proteomic approaches to identify biomarkers of early cerebral ischemia in children with SCD. Identifying such circulating biomarkers may allow earlier therapeutic intervention in these children.
  • Exploratory Studies in the Neurobiology of Pain in Sickle Cell Disease: To conduct basic and translational research on the neurobiology of pain in SCD and to develop effective pharmacologic treatments.

Investigator-initiated studies are exploring new methods to reactivate fetal hemoglobin (HbF) expression for the treatment of SCD and thalassemia; elucidating the mechanism of hypercoagulation in SCD; examining the relationships between analgesia, biomarkers, and pain levels in adults with SCD; and investigating the mechanisms underlying pain in SCD in order to develop more effective pain therapies.

Gene therapy is another area of focus. One project is exploring lentiviral gene therapy for SCD, and another is studying the application of induced pluripotent stem cell technology to replace the defective sickle beta-globin gene with a normal gene in a SCD mouse model. Researchers are seeking to translate their results to human cells that will become the foundation for future clinical trials.

Through the SBIR and the STTR programs, the NHLBI supports translational projects to develop therapeutics and tools that can be used to treat patients with SCD and other hemoglobinopathies. Recent projects are investigating a safer and more affordable method to correct autologous hematopoietic stem cells in SCD and other genetic disorders; identifying antisickling compounds in a mixture of botanicals that can provide leads for developing new synthetic antisickling compounds; evaluating agents to increase hemoglobin F expression; testing a humanized monoclonal antibody drug for treatment of vaso-occlusive crisis; and advancing use of small molecule organic catalysts to create a new class of drugs to prevent sickle cell hemoglobin polymerization. The NHLBI also supports a project to develop a Web interface tool that can be used to improve the quality of care received by SCD patients during hospital emergency room visits.

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 cure the disease.

  • BABY HUG (see Chapter 11): To assess the effectiveness of hydroxyurea during a 2-year treatment period in preventing onset of chronic organ damage in young black children who have sickle cell anemia. Although the primary goals of preserving spleen and renal function were not achieved, data show markedly reduced numbers of vaso-occlusive events and improved hematologic counts. An observational study is following the cohort to learn more about long-term effects of hydroxyurea.
  • Sildenafil for Sickle Cell Disease-Associated Pulmonary Hypertension (walkPHaSST) Follow-Up (see Chapter 11): To use datasets and biorepository specimens from the closed trial to assess the effects of genetic factors on hematologic, cardiopulmonary, and pain phenotypes in individuals with hemoglobin SS disease and to explore phenotypic variations in individuals with hemoglobin SC disease.
  • Planning Grants for Clinical Trials in Hemoglobinopathies: To support pilot studies to obtain data that are critical for the design of robust clinical trials, especially Phase II and III clinical trials in the major hemoglobinopathies, SCD, and the thalassemias.
  • Ancillary Studies in Clinical Trials: To conduct time-sensitive ancillary studies in conjunction with ongoing clinical trials and other large clinical studies that are related to heart, lung, and blood diseases and sleep disorders. One study is assessing the treatment response of children who are experiencing acute sickle cell pain episodes to determine the effectiveness of magnesium therapy (parent trial).

The Institute supports research to assist hematologists in their ability to assess clinical outcomes:

  • Adult Sickle Cell Quality of Life Measurement Information System (see Chapter 10): To develop, validate, and disseminate a psychometrically sound and clinically useful instrument to assess health-related quality of life among adults with SCD. This system is fully integrated into an NIH Roadmap Patient-Reported Outcomes Measurement Information System.

The Institute is supporting two investigator-initiated clinical trials for children with SCD. One trial in children with abnormal transcranial Doppler (TCD) velocities is comparing standard therapy (transfusions) with alternative therapy (hydroxyurea) for maintenance of TCD velocities. The other is seeking to determine the effect of hydroxyurea treatment on the cumulative incidence of conversion from conditional to abnormal TCD velocities.

The Institute is also supporting a follow-up study on cohorts of children from the Stroke Prevention in Sickle Cell Anemia (STOP) and STOP II trials. Although the trials had major implications for managing SCD in children, the real-world effects of the tested approach have yet to be determined. The current study uses a retrospective chart review of databases that contain trial and post-trial data to determine the effectiveness of chronic transfusion therapy and TCD screening in actual clinical practice rather than in just a randomized clinical trial. The study will gather information to support the development of treatment guidelines and improve the care of individuals with SCD.

Education

The NHLBI has developed the Sickle Cell Disease Information Center (http://www.nhlbi.nih.gov/new/sicklecell.htm), a Web site that contains information for the public and health professionals.

Thalassemia

Thalassemia is an inherited disorder in which red blood cells with abnormal forms of hemoglobin are produced. The disorder, which results in excessive destruction of red blood cells and anemia, affects primarily people of African, Asiatic Indian, Chinese, Mediterranean, and Southeast Asian origin.

Institute-initiated activities include:

  • RuSH (see Chapter 10): To test, in a pilot project, the feasibility of developing a national data system that will enable investigators to estimate the number of people who have SCD, thalassemias, and hemoglobinopathies and to describe their sociodemographic characteristics.
  • Innovators in Hemoglobinopathies Academic Career Development Award: To advance the development of clinician scientists who have implemented innovative programs for patients with SCD or thalassemia but who have not been on a research track.

An investigator-initiated study is also examining hematopoietic transplantation and gene therapy approaches to cure thalassemia.

Deep Vein Thrombosis and Venous Disease

Deep vein thrombosis (DVT) is a serious condition that can cause significant disability and death if not promptly diagnosed and effectively treated. Approximately 2–3 million individuals in the United States develop venous thromboembolism each year, and of them, 60,000 die primarily of pulmonary embolism. The Institute initiated a program to improve understanding of deep vein thrombosis and venous disease.

  • Deep Vein Thrombosis and Venous Disease: To improve diagnosis, therapy, and prevention of venous thrombotic diseases in order to enhance patient health and well-being. Several of the projects have substantial participation from minority populations.

Warfarin sodium, an anticoagulant drug, is prescribed to millions of patients each year to prevent thromboembolism. However, warfarin has an unusually narrow therapeutic range and is difficult to dose properly. To address this problem, the Institute is supporting several investigator-initiated studies to determine environmental and genetic factors that influence patient response to warfarin. Fifty to 60 percent of participants are from racial and ethnic minority populations.

Transfusion Medicine and Cellular Therapeutics

The NHLBI supports research on the use, safety, and availability of blood and blood components for transfusion and cellular therapies that are seeking 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 that advance hematopoietic stem cell transplantation. To reach minority populations, the BMT CRN 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.
  • PACT (see Chapter 10): To manufacture clinical grade mesenchymal stem cells (MSC) for a clinical trial that will examine the safety of infusing MSC during the transplantation process. Data from other studies demonstrate that MSC can facilitate the acceptance of the foreign cells being infused into a patient and help to repair blood vessels that have been damaged during the circulation of "sickled" red blood cells.

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