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12. Minority Activities


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 in order to compare health status between various populations, but 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, both minority and non-minority, 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 2005 activities addressing this goal include the following:

  • Minority K–12 Initiative for Teachers and Students (MKITS): Supports research, development, and evaluation of innovative science training programs to provide minority students in grades K–12 with the exposure, skills, and knowledge that will encourage them to pursue advanced studies in biomedical and behavioral sciences.
  • Historically Black Colleges and Universities (HBCU) Research Scientist Award: Supports efforts by HBCU to recruit an established research scientist in 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.
  • Summer for Sickle Cell Science Program: Supports research training and mentoring of individuals from high school to junior investigator level as part of the Comprehensive Sickle Cell Centers program.
  • Student National Medical Association Externship in Sickle Cell Disease: Supports an 8-week clinical rotation in SCD for third- and fourth-year medical students at an NHLBI-funded medical institution engaged in sickle cell research and patient care.
  • Research Scientist Award for Minority Institutions: Strengthens the biomedical and behavioral research capabilities and resources of minority institutions by recruiting an established scientist with expertise in areas related to cardiovascular, lung, or blood health and disease; transfusion medicine; or sleep disorders.
  • Minority Undergraduate Biomedical Education Program: Encourages development of pilot demonstration programs at minority under-graduate educational institutions to recruit and retain talented undergraduate students in the biomedical sciences.

The Office of Minority Health Affairs (OMHA) within the OD 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 OMHA also coordinates activities to foster greater participation of underrepresented minorities in NHLBI research and research training programs. Selected FY 2005 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 underrepresented racial and ethnic groups or disadvantaged backgrounds or individuals with disabilities.
  • Participating in HHS-Endorsed Minority Organization Internship Programs by providing positions in NHLBI extramural divisions to students from the National Association for Equal Opportunity in Higher Education, the Hispanic Association of Colleges and Universities, and the Washington Internships for Native Students programs.
  • 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 encour-age youngsters 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 presen-tations, an introduction to NHLBI’s research training and career development programs, and a tour of several NHLBI laboratories.
  • Providing undergraduate students from the Tougaloo College Scholars program the opportunity to observe biomedical research at the NHLBI during a 3-day tour of the NIH that included learning about the NIH and available research training opportunities.
  • Conducting a workshop on “Academic and Career Guidance” for Intramural Research Training Award (IRTA) students including the Biomedical Research Training Program for Underrepresented Groups to facilitate postbaccalaureate students to phase into biomedical research careers.

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.

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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; 50 percent of the participants are black.
  • ARIC (see Chapter 10): To investigate the associ-ation of CHD risk factors with development of atherosclerosis and CVD in an adult population; 30 percent of the participants are black.
  • CHS (see Chapter 10): To examine risk factors for CHD and stroke in the elderly; 16 percent of the 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; 62 percent of the participants are minorities.
  • 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.

Several investigator-initiated epidemiologic studies are examining gene–environment interactions that increase CVD risk factors among various racial groups. Included among them are studies that compare gene–environment interactions in black populations in Africa, the Caribbean, and selected areas of the United States; determine the genes responsible for the metabolic syndrome, a risk factor for CVD, in 10,000 Chinese sibling pairs; determine the genes responsible for CVD risk factor response to dietary fat changes in blacks; investigate genes influencing changes in blood pressure in response to high- and low-salt diets in a rural Chinese population; and identify and map specific genes that contribute to CVD risk in Mexican Americans.

Scientific evidence is emerging that implicates cellular and inflammatory processes in the development and characteristics of atherosclerotic plaque and the clinical course of CVD. One study seeks to identify cellular, metabolic, and genomic correlates of atherosclerotic plaque characteristics and early changes in the vascular wall in a subset of the ARIC cohort that is predominately black. Another study is elucidating the links between socioeconomic factors, stress, inflammation and hemostasis, and cardiovascular risk in a large and diverse population-based sample.

Several drugs in four widely used classes of noncardiovascular medications (fluoroquinolone and macrolide antibiotics, antipsychotics, and antidepressants) have been shown to be pro-arrhythmic and thus increase the risk of sudden cardiac death. Investigators are conducting a study, using a large and comprehensive data set of about 800,000 people, 40 percent blacks, to understand the role of these medications on the risk of sudden cardiac death. Research findings will provide information that clinicians need to prescribe these widely used medications in a way that minimizes the risk of sudden cardiac death.

An ancillary study to MESA is seeking to determine whether impairment of myocardial perfusion reserve can serve as a marker of CHD. Scientists hypothesize that impaired myocardial perfusion reserve indicates the presence of subclinical coronary atherosclerosis and coronary microvascular disease. Developing a new measure of subclinical disease would enable early interventions and lifestyle modifications to prevent CHD. Fifty percent of the population will be Hispanic. Other ancillary studies to MESA are investigating progression of carotid atherosclerosis, association of risk factors with arteriosclerosis measured in retinal vessels, and the relationship of sex hormones to subclinical CVD and other risk factors in men and women.

The Institute is supporting additional epidemiologic investigations that include a study of Chagas’ disease— a leading cause of heart disease throughout Latin America—to identify genetic determinants of susceptibility to infection and differential disease pathogenesis in a black population residing in rural Brazil; 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 relationship, 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., Japanese American in Hawaii, and Japanese in Japan.

Treatment and Prevention

Low-dose aspirin is cost effective and efficacious for the prevention and treatment of CHD. However, some individuals, perhaps because of genetic variations across individuals, do not respond to the treatment. A genetic study in high-risk siblings of patients with premature CHD, along with their adult offspring, is seeking to determine whether low-dose aspirin responsiveness is heritable and whether it is associated with specific variations in candidate genes or defined haplotypes; 50 percent of the participants are black.

Many evidence-based guidelines for treatment of risk factors or disease have been developed, but they are often not adhered to by patients—especially minority populations— or adopted in routine clinical practice. The Institute has initiated the following activities to address this important problem:

  • Trials Assessing Innovative Strategies To Improve Clinical Practice Through Guidelines in Heart, Lung, and Blood Diseases: To identify obstacles to implementing national evidence-based guidelines and test interventions to promote their use in clinical practice. Several approaches will be tested, including use of decision support tools; interactive seminars; Internet learning; a computerized patient activation tool placed in the waiting room of primary care offices; and performance feedback and practice profiling.
  • Overcoming Barriers to Treatment Adherence in Minorities and Persons Living in Poverty: To overcome barriers to treatment adherence for lifestyle changes and pharmacologic therapy in minorities and persons living in poverty. Studies are testing several approaches, such as telephone-based interventions, nurse case management and counsel-ing, and patient and physician education interven-tion in clinical and community settings designed to overcome patient, provider, and medical systems barriers that impede treatment adherence. Urban and rural blacks, Hispanics, Asians, and women are the targeted groups.

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 disparities:

  • Partnership Programs To Reduce Cardiovascular Disparities: To expand the capacity of research institutions to reduce health disparities, encourage more researchers to focus on minority health, and improve minority acceptance and community willingness to participate in research by pairing research-intensive medical centers that have a track record of NIH-supported research and patient care with minority health care serving institutions that lack a strong research program. Research will focus on the complex biological, behavioral, and societal factors that result in cardiovascular health disparities in their target populations (e.g., blacks, Hispanics, Native Hawaiians, Pacific Islanders).
  • Cultural Competence and Health Disparities Academic Award: To enhance the ability of physicians and other health care professionals to address disparities in the occurrence, management, and outcomes of cardiovascular, pulmonary, hematological, and sleep disorders among various population groups in the United States in a culturally sensitive manner. The award provides support to medical institutions in the United States to develop core curricula and other educational materials to increase the overall knowledge and skills of medical students, house staff, and other health professionals, including practicing physicians, on ethnic, cultural, religious, socioeconomic, linguistic, and other factors that contribute to health disparities, and on culturally competent approaches to mitigating them.
  • Community-Responsive Interventions To Reduce Cardiovascular Risk in American Indians and Alaska Natives: To test the effectiveness of culturally appropriate behavioral interventions that promote adoption of healthy lifestyles related to heart disease and stroke risk, including healthy diet, regular physical activity, smoking cessation, and stress management in American Indians and Alaska Natives.

Education

The NHLBI, through its education programs (see Chapter 2), disseminates health information to physicians, health care professionals, patients, and the public on ways to prevent or treat diseases within the Institute’s mandate. It has developed the following community-based programs to combat cardiovascular health disparities among four major cultural/ethnic groups: blacks, Hispanics, American Indians and Alaska Natives, and Asian Americans and Pacific Islanders.

  • Public Health in Public Housing: Improving Health, Changing Lives: To disseminate to populations residing in public housing health information about improving cardiovascular health by adopting heart healthy lifestyles.
  • Salud para su Corazón: To disseminate information on CVD prevention, intervention, and treatment and promote heart healthy behaviors in Hispanic communities through lay health educators (promotores model).
  • NHLBI–Indian Health Service Partnership To Strengthen the Heartbeat of American Indian and Alaska Native Communities: To develop and initiate in three tribal communities effective approaches to improve cardiovascular health, including implementing tailored heart health strategies, and creating a national cardiovascular health training program, “Honoring the Gift of Heart Health,” with the Indian Health Service.
  • NHLBI Asian American and Pacific Islanders Heart Health Outreach Project: To develop 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 a diverse Asian American and Pacific Islander population.

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

  • Improving Cardiovascular Health in African Americans—Package of Seven Easy-To-Read Booklets
  • Heart-Healthy Home Cooking African American Style
  • Eight Easy-to-Read Booklets in Spanish and English on Heart Health
  • Bringing Heart Health to Latinos: A Guide for Building Community Programs
  • Your Heart, Your Life: A Health Educator’s Manual for the Latino community
  • Filipinos Aspire for Healthy Hearts Fact Sheets in Tagalog and English
  • Filipinos Take It To Heart: A How-To Guide for Bringing Heart Health to Your Community
  • Vietnamese Aspire for Healthy Hearts Fact Sheets in Vietnamese and English
  • Treat Your Heart to a Healthy Celebration directed to American Indians and Alaskan Natives
  • Honoring the Gift of Heart Health: A Heart Health Educator’s Manual for Native Americans.

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

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Arrhythmias

During the past decade, research studies have shown a lower incidence of atrial fibrillation in blacks compared to whites. However, the picture for ventricular fibrillation, a more lethal disturbance of heart rhythm, is far less sanguine. Blacks with ventricular fibrillation were less likely than whites to undergo electrophysiologic testing and, when discharged from the hospital, had higher mortality rates over the next year. In addition, blacks with out-of-hospital arrest suffered more ventricular arrhythmias than whites in every age group. Survival rates after cardiac arrest were 3.25 times greater for whites than blacks.

The NHLBI is supporting basic and genetic research on cardiac arrhythmias to elucidate the mechanisms involved in control of heart beat/rhythm and to develop improved therapies for all ethnic/racial groups in the United States. One research group has found a gene variant in blacks that produces a small increase in risk of arrhythmia. In combination with certain medications, low blood potassium levels, or structural heart disease, such a gene variant might further magnify the risk of life-threatening arrhythmias. Another group is studying selected genes and their variants that are likely candidates for modulating cardiac rhythm, may contribute to variations in response to drug treatment of atrial fibrillation, and may alter healthy heart rhythm patterns.

High Blood Pressure

Etiology and Pathophysiology

High blood pressure is a serious health problem that is especially prevalent and severe among minorities. Institute-initiated studies addressing the etiology and pathophysiology of high blood pressure include:

  • Molecular Genetics of Hypertension (see Chapter 9): To determine the etiology and pathogenesis of hypertension and its complications in order to improve diagnosis and treatment. Many of the subprojects have a high percentage of minority participation; others target blacks or Hispanics exclusively.
  • Family Blood Pressure Program (see Chapter 9): To use a network of investigators to identify genes associated with high blood pressure and to examine interactions between genetic and environmental determinants of hypertension in specific minority populations: blacks, Mexican Americans, and Asians.

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 Institute supports a number of projects to examine antecedents of hypertension in children to determine racial differences in blood pressure regulation. One study is determining relationships between cardiovascular reactivity in adolescent normotensive blacks and development of pathobiologic markers of hypertension risk (i.e., increased resting blood pressure, left ventricular mass, and relative wall thickness) later in life. Another is investigating the genetics of cardiovascular reactivity following stress in black youths.

Researchers also are examining the influence of SES and ethnic discrimination on stress reactivity to determine if it provides a pathophysiologic link to CVD in blacks. One group is examining the combined influence of low SES and ethnicity on development of behavioral risk factors (i.e., hostility, anxiety, and heightened cardiovascular reactivity to stress) in a group of adolescents; 50 percent of them are black. Another group is assessing the relationship between early life exposure to socioeconomic stressors, such as adverse socioeconomic conditions, low levels of social integration, and racial discrimination, and development of hypertension in blacks.

Investigators have observed that blacks have an augmented blood pressure response to salt. A study to improve understanding of the genetic basis and phenotypic characterization of salt-sensitive hypertension in blacks has located a specific region of the kidney where sodium is reabsorbed more extensively in blacks than in whites.

Impaired sodium regulation also appears to be linked to the development of hypertension. Scientists are investigating the effects of stress on salt retention and measuring hormonal variables known to influence sodium regulation. One study is seeking to determine whether the mechanisms regulating sodium retention differ between blacks and whites. Researchers found that black youths have a slower salt excretion rate in response to stress than white youths. Another study is examining the role of sodium and obesity in hypertension development among blacks living in three different environments: Nigeria, Jamaica, and Chicago. In a twin study consisting of 41 percent blacks, scientists are investigating sodium retention as a mechanism augmenting systemic vascular resistance and changes in vascular function, ventricular structure, and blood presssure.

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 impact 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

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

  • ALLHAT (see Chapter 11): To compare the combined incidence of fatal CHD and nonfatal MI among patients receiving ACE inhibitors, calcium antagonists, or alpha-1 blockers and patients in a control group receiving a diuretic. Also, in a subset of these groups, to determine whether cholesterol-lowering therapy reduces mortality in moderately hypercholesterolemic individuals compared with a control group; 32 percent of the participants are black and 19 percent are Hispanic. Research findings demonstrated that the less expensive traditional diuretics work better than newer medicines in treating high blood pressure and preventing some forms of heart disease and should be preferred as a first therapy for most patients with high blood pressure.
  • Ancillary Pharmacogenetic Studies in Heart, Lung, and Blood Diseases and Sleep Disorders: To conduct pharmacogenetic studies in ongoing or completed clinical trials/studies related to heart, lung, and blood diseases and sleep disorders to examine genetic influences on interindividual differences in prescription drug response. Understanding the genetic influences may permit improved medication choice and dosing in individuals and help avoid either serious adverse response or lack of response to therapy. Three of the studies focus on antihypertensive drugs and include 50 to 58 percent blacks.

Although it is well known that reducing hypertension will reduce CVD rates, the implementation of evidence-based guidelines for hypertension treatment in clinical practice is not very high. To address this issue, the NHLBI initiated a program to improve hypertension con-trol rates in blacks, a group with the highest prevalence and earliest onset of hypertension and with a disparately high premature cardiovascular mortality and morbidity:

  • Interventions To Improve Hypertension Control Rates in African Americans: To evaluate the feasibility of clinical interventions directed at the medical care delivery system to increase the proportion of blacks who have their blood pressure controlled to levels specified by the JNC VII guidelines.

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.

The Institute supports a number of investigator- initiated studies to evaluate various interventions to improve hypertension management. One study is testing the effectiveness of a two-staged intervention involving telemonitoring of blood pressure and telephone-based nurse care management in 12 community-based clinics that serve economically disadvantaged, largely black and Hispanic populations. Another study is evaluating two interventions compared to usual care (regular primary care clinic visits) in blacks with hypertension who have several risk factors (smoking, sedentary lifestyle, and high sodium intake) for CVD. The interventions include the following: (1) simultaneous intervention (smoking cession, increased exercise, and decreased salt intake) in a clinical session, with stage-specific telephone support and follow-up and (2) sequential intervention of each targeted behavior presented individually at a clinic session, with stage-specific telephone support and follow-up.

Anger and hostility have been demonstrated as risk factors for hypertension. Scientists are evaluating an anger management intervention in a hospital setting with 46 percent blacks to determine if it will lead to improved blood pressure and psychosocial risk factors (e.g., reduce depression).

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Education

The NHLBI (see Chapter 2) 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 for health professionals, patients, and the public. Below are some examples:

  • Sí se Puede: Prevenir y Controlar la Presión Arterial Alta con Actividad Física
  • Plan de Alimentación Saludable Contra la Hipertensión: Prevenir y Controlar la Presión Arterial Alta Siguiendo el Plan de Alimentación Conocida Como DASH
  • 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
  • Sí se Puede: Prevenir y Controlar la Presión Arterial Alta. Lo Que los Médicos Deben Saber
  • Take Steps To Prevent High Blood Pressure in English and Spanish
  • Cut Down on Salt and Sodium in English and Spanish
  • Churches as an Avenue to High Blood Pressure Control
  • Working With Religious Congregations: A Guide for Health Professionals
  • Protect Your Heart! Prevent High Blood Pressure
  • Spice Up Your Life! Eat Less Salt and Sodium
  • Keep the Harmony Within You—Check Your Blood Pressure
  • Keep Your Heart in Check—Know Your Blood Pressure Number in Tagalog and English and in Vietnamese and English
  • Prevent and Control High Blood Pressure: Mission Possible.

NHBPEP Coordinating Committee Activities

Member organizations of the NHBPEP coordinating committee have continuing education programs on the prevention and treatment of hypertension that are focused on their minority members. They also support hypertension prevention and awareness in community-based settings such as screening and church activities, community awareness campaigns, and media events.

High Serum Cholesterol

Etiology

The Institute supports a number of investigator- initiated projects 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 between various racial and ethnic groups.

Variation in hepatic lipase activity is associated with differences in plasma concentrations of HDL and LDL synthesis and catabolism. Researchers are investigating whether ethnic differences in hepatic lipase activity are responsible for the well-known differences in plasma HDL concentrations found in blacks and whites. Genetic studies are being conducted on a population that is 39 percent black.

Prevention

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

Education

The NCEP (see Chapter 2) has prepared the following publications on blood cholesterol for minority audiences.

  • Learn Your Cholesterol Number in Spanish and English
  • Protect Your Heart—Lower Your Blood Cholesterol in Spanish and English
  • Heart-Healthy Home Cooking African American Style
  • Delicious Heart-Healthy Latino Recipes
  • Cut Down on Fat—Not on Taste in Spanish and English
  • Empower Yourself! Learn Your Cholesterol Number
  • Be Heart Smart! Eat Foods Lower in Saturated Fats and Cholesterol
  • American Indian and Alaska Native People: Treat Your Heart to a Healthy Celebration
  • Serve Up a Healthy Life—Give the Gift of Good Nutrition in Tagalog and English, and in Vietnamese and English.

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Obesity

Etiology

The latest NHANES data show a continued rise in the proportion of Americans who are overweight; black women are especially at risk. To understand the reasons for the racial disparity among women, the Institute initiated a long-term program, the NHLBI Growth and Health Study (NGHS), to examine the development of obesity and CVD risk factors in a biracial cohort of young girls. The study, which ended in FY 2000, found black girls consumed more calories and a higher percentage of calories from fat and watched more television than white girls. An investigator-initiated study using the NGHS cohort, starting at ages 18 to 19 years, is examining the changes in cardiac output and total peripheral resistance that occur with developing obesity and their influence on ethnic difference in blood pressure regulation. Another project, using data from the NGHS, is examining CHD risk factors in black and white girls to identify genes involved in black–white differences in lipid metabolism and obesity.

Black women have been shown to manifest lower resting energy expenditure than white women. Scientists seeking to improve our understanding of ethnicity, genetics, energy metabolism, and obesity development will examine the relationship between two genes implicated in energy metabolism and resting energy expenditure in high-risk blacks.

Menopause-related coronary risk was previously believed to be associated with a gain in total body fat. Research, however, suggests that the location of the fat, not the total fat per se, is the key risk factor. An investigator-initiated study is seeking to determine if indices of central adiposity, particularly intra-abdominal fat, predict coronary events better than indices of total fat. The study is also examining the role of central adiposity with altered glucose and lipid metabolism and elevated blood pressure; 48 percent of the population is black.

Treatment and Prevention

The NHLBI has initiated several programs to treat or prevent obesity.

  • Overweight and Obesity Control at Worksites: To test innovative interventions that emphasize environmental approaches or the combination of environmetal and individual approaches at worksites to prevent or treat obesity in adults. Environmental strategies include programs, policies, or organizational practices (e.g., increasing the availability of, and providing access to, healthful food choices and facilities for physical activity, and creating a socially supportive climate to influence healthy behaviors).
  • POUND LOST (see Chapter 9): To evaluate the effectiveness of four diets differing in macronutrient composition to promote and sustain weight loss in overweight and obese individuals; approximately 25 percent of the participants will be black.
  • Primordial Prevention of Overweight in American Indian Children (see Chapter 9): To prevent American Indian children from becoming overweight at an early age. Culturally appropriate interventions, including family counseling to improve nutrition and physical activity in infants and toddlers, will be developed and introduced community-wide.
  • 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.

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, and psychosocial and familial influences) administered during the critical transition period from prepuberty to puberty in black girls at high risk for obesity. Two studies are evaluating the effectiveness of weight control programs to prevent weight gain in a predominately black population that has recently completed a smoking cessation program. The blood pressure status of the participants, who are prehyper-tensive or hypertensive at the beginning of the studies, will be monitored.

Hispanic parents and children are participating in a program that targets 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. Preadolescent black girls are the subject of (1) a study to test the efficacy of an after-school dance program and (2) a family-based intervention involving reduced use of television, videotapes, and video games to reduce weight gain.

Obesity is one of the major health challenges facing American Indian 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 American Indian children. A project with a subject population consisting of Asians, Hispanics, and whites is testing an integrated school- and community-based intervention involving physical activity and diet to reduce the prevalence of obesity.

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.

Education

The NHLBI OEI (see Chapter 2) has prepared health information on losing excess weight for minorities.

  • Watch Your Weight in English and Spanish
  • Embrace Your Health! Lose Weight if You Are Overweight.

Physical Inactivity

The Institute has initiated research on the effectiveness of an intervention program to encourage greater physical activity among adolescent girls.

  • TAAG (see Chapter 11): To test the effectiveness of school–community-linked interventions to reduce the decline in physical activity in adolescent girls, from grades 6 through 8. As estimated 5,000 girls, approximately 50 percent minority, from 36 schools are participating.

The NHLBI supports several investigator-initiated studies on strategies to increase physical activity among minority populations. Included among them are studies to examine the effect of vigorous exercise on reduction of childhood obesity in black girls. A school-based study is evaluating the effects of vigorous exercise programs on decreasing the accretion of general and visceral adiposity in black girls.

An ancillary study to an Institute-initiated program to reduce the decline in physical activity in adolescent girls (TAAG) is investigating the influence of community characteristics (e.g., street design, access to public transportation, facilities for physical activity, population mix, socioeconomic mix of the neighborhood) on physical activity levels and body mass index; approximately 50 percent of the girls are minority. Two other studies are seeking to determine the factors that lead to decline in physical activity in adolescent girls. They include the effects of previous exposure to physical activity intervention, race and ethnicity, weight, psychosocial influences, and the environment.

Physical inactivity among children is often attributed to the 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.

Scientists have observed an age-related decline in aerobic capacity, but have not been able to discern the effects of physical activity, body fat, and genetic variation on its rate of change. They also have little understanding about how the rate of change in aerobic capacity during early and middle adulthood affects CVD development. An ancillary, investigator-initiated study being conducted in conjunction with the Year 20 CARDIA examination is addressing these issues. Data from this study should increase understanding of the interrelationships of cardiorespiratory fitness, body composition, and CVD-related risk factors and endpoints, and may provide the basis for more extensive evidence-based recommendations on the role of fitness in cardiovascular health; 46 percent of the participants are black.

Education

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

  • Stay Active and Feel Better in English and Spanish
  • Energize Yourself! Stay Physically Active
  • American Indian and Alaska Native People: Be Active for Your Heart!
  • Be Active for a Healthy Heart 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.

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Smoking

Smoking among minorities has increased significantly compared with whites. To determine the causes of the increase, the Institute is supporting an investigator-initiated study in a predominately minority population to examine factors that prompt them to initiate smoking. In addition, the study seeks to identify predictors of cessation.

The Institute is also supporting a number of studies of smoking intervention and follow-up cessation mainten-ance that specifically target minorities. Two studies are evaluating the effectiveness of smoking cessation programs for smokers who seek treatment at the hospital emergency department. One study involves patients who suffer from acute respiratory illness; approximately 35 percent are minorities. The other targets Chinese American patients hospitalized with CVD, pulmonary disease, or diabetes mellitus. A third study is seeking to determine if the addition of a physical activity interven-tion improves smoking cessation; 45 percent of the participants are blacks.

Two types of pharmacologic therapies (nicotine replacement therapy and sustained-release bupropion) have been approved by the FDA for smoking cessation in the United States. Scientists are comparing the ability of each drug alone or in combination to increase initial and long-term smoking cessation rates in young low-income and minority smokers. Another study is evalu-ating the efficacy of a weight loss drug intervention to prevent weight gain in obese individuals participating in a smoking cessation program; 44 percent of the participants are black.

Education

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

  • Kick the Smoking Habit in English and Spanish
  • Refresh Yourself! Stop Smoking
  • American Indian and Alaska Native People: Help Your Heart
  • Don’t Burn Your Life Away—Be Good to Your Heart in Tagalog and English and in Vietnamese and English.

Psychosocial Factors

Major depression is a risk factor in the development of ischemic heart disease and for death after an acute MI. Investigator-initiated research is seeking to determine the pathways that link depression to physiological mechan-isms in post-MI patients. One study is examining the link between the severity of depressive symptoms to the inflammatory process implicated in atherogenesis by focusing on the basal expression of cytokines and cell adhesion molecules on blood monocytes. Another is focused on the autonomic nervous system and its link to depression. A third study is investigating the role of platelets, platelet aggregation, and adhesion in patients with major depression. Approximately a third of the population in the studies is black.

The NHLBI is interested in the effect of depression, anxiety, and lack of social support on prognosis after a CHD event. An investigator-initiated study is examining the efficacy of individual and group therapy in post-MI patients who are socially isolated or clincally depressed. Scientists will be measuring biological risk factors (e.g., lipids, adiposity, coagulation factors) and possible subclinical markers of disease (e.g. carotid intima-media thickness, coronary calcification); 34 percent of the participants are black.

The Institute supports investigator-initiated research on the role of race and ethnicity, psychosocial and 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 also are being examined. Other investigators are focused on the relationships of psychosocial stress, sleep disordered breathing, and nocturnal physiological measures with emerging risk factors and subclinical CVD; 50 percent of the participants are black.

Investigators are interested in the effects of race and psychosocial factors, such as hostility, on glucose metabolism. A study was initiated to determine how hostility is differentially related to glucose metabolism in blacks and whites. Research findings may increase understanding of the differences in the etiology of diabetes in the two groups.

Additional areas of interest include the genetic basis of aggression and the relationships between risk-promoting variables (psychosocial stress, smoking, poor diet, physical inactivity); presumed mediating variables (sympathetic nervous system activity and insulin metab-olism); and CHD risk factors. Fifty to sixty percent of the participants are black or Hispanic.

Diabetes

Diabetes mellitus is a strong risk factor for CVD. Its prevalence is increasing due to the significant increase of obesity and physical inactivity in the population, espe-cially among blacks, Hispanics, and American Indians. To address this growing problem, the Institute is sup-porting an investigator-initiated study on defining the relationship between the overall dose of endurance exer-cise training and the corresponding response of meta-bolic risk factors in an overweight and obese biracial female population. Another study will determine if adolescents with type 2 diabetes have a high risk of developing clinical CVD in their late 20s or 30s. Scien-tists are using noninvasive imaging techniques for detecting subclinical atherosclerosis to measure CVD development in a predominatly black population.

Hypertension and diabetes are major contributors to CVD and occur disproportionately in blacks. In particular, black women seem to have earlier disease onset and poorer outcomes. Scientists are investigating the link between hypertension and type 2 diabetes and the relative excess of androgen found in black women to determine whether insulin resistance, excess androgen, and endothelial dysfunction contribute to accelerated vascular injury in blacks.

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 the participants are minorities.
  • BARI 2D (see Chapter 9): To evaluate whether urgent revascularization offers an advantage over medical therapy in patients with coronary artery disease and diabetes. In addition, for a given level of glycemic control, to determine whether insulin-providing drugs offer advantages or risks compared to insulin sensitizers (drugs that enhance insulin action); 33 percent of the participants are from minority populations.
  • SANDS (see Chapter 9): To compare intensive treatment (pharmacologic agents, such as ACE inhibitors and simvastatin for high blood pressure and LDL cholesterol) to conventional treatment in 488 American Indians with diabetes, ages 40 or older. The primary outcome measure is change in carotid intimal-medial thickness.

An investigator-initiated study will evaluate the effectiveness of a multiple risk factor intervention (diet, exercise, stress management, social support, smoking cessation) targeting postmenopausal Hispanic women with type 2 diabetes.

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Lung Diseases

The NHLBI supports research on a number of lung diseases, such as asthma, sarcoidosis, and TB, which disproportionately affect minorities. The following section provides examples of research to address health disparities in lung diseases.

Asthma

Etiology and Pathophysiology

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

  • Cellular and Molecular Mechanisms of Asthma (see Chapter 9): To delineate the cellular and molecular mechanisms underlying acute and chronic asthma through basic and clinical investigations.
  • 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.
  • Asthma Exacerbation: Biology and Disease Progression: To elucidate the biologic mechanisms of asthma exacerbation pathobiology and resolution and to determine their effect on lung function, physiology, and disease state; 27 to 56 percent of the study participants will come from various minority populations.

The Institute also supports investigator-initiated projects on the etiology and pathophysiology of asthma. One study is using genomic screening to search for the genetic basis of asthma in a homogeneous Hispanic population in Costa Rica; another study is seeking to identify positional gene candidates for airway hyperresponsiveness and compare their association with asthma between two asthmatic groups: a white population on Tangier Island, VA, and a black population from Barbados; and a third study seeks to establish the link between specific genotypic variants and phenotypic markers, and to elucidate the immunological pathways that contribute to asthma severity in blacks from Harlem.

Latinos carry a disproportionate burden of asthma, yet few investigators studying the genetics of asthma have focused on this group, partly due to the complexity of the Latino gene pool. A recently initiated study is developing and testing new methods to correct for population stratification due to racial admixture, a key problem confounding genetic studies in the Latino population. The project focuses on data from the NHLBI-supported Genetics of Asthma in Latino Americans (GALA) to assess population stratification.

Occupational and 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 the association of early exposure to endotoxin (which appears to promote the development of the immune system), nitrogen dioxide, and aeroallergens (which trigger asthma exacerbations); obesity; physical inactivity; and environmental tobacco smoke on the prevalence, persistence, and incidence of asthma in black and Hispanic children enrolled in inner-city Head Start programs.

Circadian change in airway function is an important aspect of asthma, as more than 70 percent of deaths and 80 percent of respiratory arrests occur during sleep. Forcusing on nocturnal asthma, researchers are investigating the mechanisms that cause the changes in airway function that lead to exacerbation of symptoms; 36 percent of the population is minority.

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.

  • ACRN (see Chapter 11): To support an interactive network of asthma clinical research groups to conduct studies of new therapies for asthma and disseminate findings to the practicing community. Overall, 37 percent of the participants are from minority populations.
  • CAMP (see Chapter 11): To determine whether inhaled corticosteroids are safe and effective for long-term treatment of children with mild-to-moderate asthma. The therapy proved more effective than nonsteroidal anti-inflammatory medication and significantly reduced airway hyperresponsiveness. The only side effect was a transient slowing in growth rate during the first year of treatment; 31 percent of the participants were minorities.
  • CARE (see Chapter 11): To support a network of pediatric clinical care centers to determine optimal treatment and management strategies for children with asthma. The studies considered by the network will attempt to customize therapy based on specific asthma phenotypes and genotypes; 30 percent of the population will be minorities.
  • Centers for Reducing Asthma Disparities (see Chapter 9): To support partnerships between minority-serving institutions and research-intensive institutions to conduct studies on causes of and corrections for disparities in asthma among racial/ethnic and low SES populations. Reciprocal training is encouraged to ensure culturally sensitive projects and enhance research capabilities.

The Institute is also supporting investigator-initiated studies focusing on finding effective treatment for various populations. One study is examining the effect of steroids on enhanced alpha-adrenergic vascular responsiveness in asthma; 77 percent of the participants are minority. Another study is using preexisting, well- characterized asthma patient cohorts to identify genetic variants that can predict therapeutic response to asthma drugs. Scientists are interested in the influence of race/ethnicity on the genetic factors associated with asthma therapeutic responses.

Translational Activities

Ensuring full use of modern asthma treatment strategies is an important goal of the NHLBI. The Institute is supporting an investigator-initiated study to determine the effectiveness of an intervention that is removing barriers to preventive care to improve asthma management and lower asthma morbidity. Scientists are using a Breathmobile to deliver asthma screening to black children attending Head Start Programs and a special consultation service to communicate directly with the parents about asthma management. Another study among low-income, inner-city children with asthma attending preschool is testing a bilingual intervention program to improve asthma management; 60 percent of the participants are Hispanic and 40 percent are black.

Additional studies to improve asthma management among minority groups include a study to determine whether shared decision making in choosing asthma therapy between patients and physicians improves adherence in a patient population consisting of 82 percent minorities and a study to test whether individualized interventions will improve asthma management in a black and Hispanic population. A third study seeks to improve asthma management by teaching children with asthma to recognize symptoms of the presence of airflow obstruction; 42 percent of the participants are black and 6 percent are Hispanic.

Two randomized controlled trials are being conducted among patients recruited at the time of an emergency department visit for asthma exacerbation. One study is testing an intervention to enhance knowledge, self- efficacy, and asthma-related social support; 40 percent of the patients are minority. The other focuses on young black children recruited at the time of an emergency department visit for asthma exacerbation. Investigators are testing the effectiveness of an intervention strategy that includes case management, telephone contacts, and a monetary incentive to increase follow-up visits to primary care providers.

Three studies are evaluating the benefits of working with public school systems to improve adherence to asthma management. In Birmingham, scientists are evaluating the impact of school-based supervised asthma therapy on asthma exacerbations in a predominately black population with moderate-to-severe asthma. In New York, they are testing the ability of an intervention that includes in-school intensive asthma education to 9th- and 10th-grade students who have persistent asthma and intensive asthma education for their community physicians to improve asthma morbidity; 90 percent of the participants are black. In Detroit, investigators are developing and evaluating computer-based instructions and peer counseling for black teens with asthma.

Chronic environmental tobacco smoke exposure, particularly from parental smoking, is associated with more severe asthma, increased incidence of emergency department visits, life-threatening attacks, and prolonged time to recovery from asthma exacerbation requiring hospitalization. A study is being conducted to evaluate an intervention tailored to parental stage of change regarding smoking practice, to reduce asthma crisis care used by children with persistent asthma.

Education

The NAEPP (see Chapter 2) has developed easy-to-read materials on asthma treatment and control directed to audiences with low literacy.

  • Facts About Controlling Your Asthma
  • El asma: Cómo Controlar Esta Enfermedad.

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.

Investigator-initiated studies on the causes of sarcoidosis include a study to identify genes linked to sarcoidosis susceptibility in blacks and to determine if hereditary susceptibility predisposes blacks to sarcoidosis, and a project to elucidate the mechanisms involved in the immunologic and inflammatory processes that ultimately lead to end-stage fibrosis in progressive pulmonary sarcoidosis; 50 percent of the participants are black.

Sleep Disorders

Etiology

Sleep apnea is a common disorder that disproportionately affects blacks and is associated with an increase risk of CVD; it is particularly prevalent in heart failure patients. An Institute-initiated program is assessing the interrelationship between sleep disorders and heart failure, and the mechanisms leading to cardiovascular stress when the two interact.

The NHLBI supports research on the etiology, pathophysiology, and consequences of sleep-disordered breathing (SDB), a condition characterized by repetitive interruptions in breathing.

  • Neurobiology of Sleep and Sleep Apnea (see Chapter 9): To integrate molecular, cellular, and genetic approaches to sleep control with clinical investigation on the etiology and pathogenesis of sleep disorders, particularly sleep apnea. One study has 39 percent minority participation.
  • Sleep Heart Health Study (see Chapter 9): To determine the degree to which sleep apnea is an independent or contributing risk factor for the develop of cardiovascular or cerebrovascular disease; 23 percent of the participants are from various minority and ethnic populations.

The Institute also supports a wide spectrum of investigator-initiated projects to elucidate cardiovascular and other health consequences of SDB. Ongoing studies in various community settings are assessing the health risks of SDB within specific ethnic populations, including blacks, Hispanics, Asians, and American Indians. A study of sleep in black families will investigate whether sleep problems contribute to diabetes, and the potential relationship to CVD. Characterization of how SDB occurs within family groups is helping to identify potential genetic risk factors that may allow early iden-tification and treatment of high-risk individuals. A community-based study of sleep in Hispanics is assessing the prevalence and awarenesss of sleep disorders.

Treatment and Control

The NHLBI has initiated a multisite clinical trial to find effective treatments for sleep apnea.

  • APPLES (see Chapter 11): To determine whether continuous positive airway pressure is an effective treatment for excessive daytime sleepiness and cognitive impairment associated with moderate-to-severe SDB; 30 percent of the participants are minority.

An investigator-initiated study will assess the impact of continuous positive airway pressure on functional outcomes in milder obstructive sleep apnea. The minority participation at U.S. sites is 46 percent, but is 13 percent of the total minority participation when Canadian sites are included.

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Tuberculosis

Etiology

The Institute has initiated genetic studies to characterize genes associated with TB susceptibility and host immune responses to infection.

  • Genetic Aspects of Tuberculosis in the Lung: To identify genes or families of genes that determine resistance and susceptibility to mycobacterial infection, virulence, latency, reactivation of TB, and resistance to antituberculous drugs. A large number of the participants being recruited are from minority populations.

Treatment and Control

The NHLBI supports a number of investigator- initiated studies focused on understanding the relationship of the immune system to TB. Most of the patients are from minority populations with HIV. One group is seeking to identify the correlates of protective immunity in a Mexican American population in order to aid development of anti-TB vaccines. Another group is conducting a Phase I safety trial on a vaccine with a patient population consisting of 85 percent minorities. A third group is examining the role of interferon-gamma in the pathogenesis of TB among Hispanics with and without HIV. A fourth group is identifying and characterizing host factors that predispose Asians to develop TB. In predominately minority populations in the United States, a new study will compare the effectiveness of adding aerosolized interferon-gamma to the usual treatment regimen for advanced TB.

The NHLBI also supports research to improve TB control among minority populations. One project is evaluating educational strategies to improve adherence to medication regimens and regular clinic visits among Hispanic adolescents infected with TB. Another study, located in the Harlem community of New York City, is testing a new strategy to promote adherence to therapy among inner-city TB patients. Both programs are outgrowths of behavioral research programs begun by the Institute in 1995.

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: 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 or 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 and identify better approaches for its diagnosis and treatment and for prevention of complications.

  • Comprehensive Sickle Cell Centers Program (see Chapter 9): To provide a multidisciplinary and multilevel research approach to expedite develop-ment and application of new knowledge into improved diagnosis and treatment of SCD and prevention of its complications.
  • Reference Laboratory To Evaluate Therapies for SCD (see Chapter 9): To use a battery of standard-ized tests for preclinical evaluation of potential new therapeutic agents for SCD.
  • Genetic Modifiers of Single Gene Defect Diseases: To identify genetic factors that predisposes patients with SCD to develop specific end-organ complications and to experience more or less severe clinical courses. Identification of such genetics factors will reveal new targets for developing therapy individualized to specific complications of SCD, thus leading to improved outcomes and increased life expectancy for patients.
  • Mechanisms of Fetal Hemoglobin Gene Silencing for Treatment of Sickle Cell Disease and Cooley’s Anemia: To identify mechanisms of fetal hemoglobin gene silencing during normal human development and mechanisms of variable silencing in adults, and to develop therapeutic approaches to inhibit silencing. A renewed effort to understand the molecular basis of fetal hemoglobin silencing will facilitate the development of new gene-based therapeutic approaches to inhibit silencing, in order to increase fetal hemoglobin in red blood cells, and thus to cure beta-chain hemoglobinopathies such as SCD and Cooley’s anemia.
  • Molecular Screening Assay Development for SCD: To support the development and adaptation of biological assays for automated, high throughput screening of compounds that can potentially be used to improve the understanding of the biology of SCD and provide inroads toward new agents for SCD treatments.
  • Pulmonary Complications of Sickle Cell Disease: To stimulate translational research on the pulmo-nary complications of SCD. The initiative will stimulate collaborative research between investi-gators in hematology and pulmonary science that combine basic and clinical approaches. It includes research on the major known pulmonary compli-cations of SCD due to acute chest syndrome, pulmonary hypertension, and oxyhemoglobin desaturation.

Hydroxyurea is used to treat patients with SCD. It can prevent some of the vasoocclusive complications of the disease, an effect due in part to increase fetal hemoglobin (HbF) production. The treatment can improve the clinical course of the disease and prolong survival in some patients. Investigator-initiated studies are seeking to discover genes that regulate HbF level and HbF response to hydroxyurea.

In 2005, the NHLBI cosponsored two working groups with the NIH Office of Rare Diseases and the National Human Genome Research Institute. The first, entitled “An NIH Strategic Plan for the Development of Globin Gene Therapy for Treatment of Sickle Cell Disease and Cooley’s Anemia,” brought together leading investigators in the globin gene transfer field as well as patient advocates, the FDA, and industry representatives to discuss how the NHLBI can best facilitate translation of hemoglobin gene transfer into clinical trials for SCD and beta-thalassemia. The other, “Barriers to Late-Stage Drug Development for Hemoglobinopathies,” brought together experts from the NIH, drug companies, contract research organizations, and academia to evaluate options for the best ways to expedite drug development for hemoglobin disorders and other rare diseases.

The NHLBI addressed another area of serious concern for sickle cell patients, in 2005, by supporting a meeting on the “Renal and Urologic Complications in Sickle Cell Disease.” The working group assembled hematologists, renal specialists, and urologists to discuss the research needs and opportunities associated with the renal and urologic system problems in patients with SCD.

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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.

  • Multicenter Study of Hydroxyurea (MSH) Patients’ Follow-up (see Chapter 11): To determine the toxic effects of long-term hydroxyurea use in the patients who participated in the adult hydroxyurea clinical trial that ended successfully in 1995; 100 percent of the participants were black. A significant finding of the study was that patients who took hydroxyurea for 9 years experienced a 40 percent reduction in deaths.
  • BABY HUG (see Chapter 11): To assess the effectiveness of hydroxyurea in preventing onset of chronic organ damage in young black children with sickle cell anemia. At baseline, this trial has demonstrated that spleens and kidneys are already damaged by 1 year of age.
  • SWITCH (see Chapter 9): To demonstrate that hydroxyurea and phlebotomy can maintain an acceptable stroke recurrence rate and significantly reduce hepatic iron burden in comparison to transfusion plus chelation in children who have had prior overt stroke.
  • Multicenter Neurocognitive and Neuroimaging Study in Adult Sickle Cell Disease: To assess baseline neurocognitive function and neuroimaging abnormalities in adults with SCD and to randomize patients identified with subnormal neurocognitive scores to receive 6 months of transfusion versus standard care, followed by reassessment of baseline neurocognitive function.

The NHLBI is supporting several transplant-related clinical studies that are seeking to reach minority populations. To ensure increased awareness and equitable opportunities for participation, the studies support bilingual transplant center personnel and provide public Web pages, educational materials, and informed consent documents in Spanish, Japanese, Korean, Chinese, and Vietnamese. In addition, focus groups have been held to identify barriers to participation.

  • Blood and Marrow Transplant Clinical Research Network (see Chapter 11): In collaboration with the NCI, to promote the efficient comparison of innovative treatments and management strategies for patients undergoing blood or marrow transplan-tation. The Network has developed strategies and implemented procedures to enroll patients from minority groups.

The Cord Blood Stem Cell Transplantation (COBLT) Study was just completed in 2005. The COBLT bank contained more than 8,000 cord blood units; approximately 57 percent were from minority donors. Approximately 30 percent of the COBLT transplant patients were minority.

Each year in the United States approximately 1,500 children are diagnosed with sickle cell anemia, and 30 to 50 children with thalassemia. A recent retrospective analysis of 44 children who were transplanted with sibling cord blood for SCD or thalassemia showed that matched sibling cord blood transplantation offers the potential for a cure.

Transplants for patients with sickle cell anemia are performed at many centers across the United States, with few performed at a single center. To promote a unified strategy for sharing data, the NHLBI, with support from the National Center for Minority Health and Health Disparities, awarded a grant supplement to the International Bone Marrow Transplant Registry to collect data on demographics and outcomes of patients with sickle cell anemia who received a blood or marrow transplant.

Outcomes Research

In 2002 and 2003, the NHLBI held a workshop and three working groups to address the needs of adult SCD patients. One high priority recommendation was to develop and validate a health-related quality of life instrument specifically for adults with SCD. Subsequent working groups of consumers, clinicians, and researchers identified issues that are unique to SCD patients, such as interactions with the health care system and the economic burden of living with SCD. In 2005, the Institute awarded a 3-year contract to develop a health-related quality of life questionnaire to be used in clinical studies.

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 Mediterranean, African, Southeast Asian, Chinese, and Asiatic Indian origin. In 2000, the Institute initiated a program to establish a network of clinical research centers to evaluate new therapeutic agents. Research efforts include developing oral chelators to remove iron overload caused by repetitive transfusion therapy, testing drugs to enhance fetal hemoglobin production, and examining 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 establised.

  • 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.

Investigator-initiated studies include efforts to develop oral chelators to remove the iron overload caused by repetitive transfusion therapy; exploration of hormone therapy for patients surviving into their teens; testing of drugs intended to enhance fetal hemoglobin production (hydroxyurea, butyrate, and decitabine); investigation of gene therapy approaches to cure the disease; prevention of bone diseases; optimum treatment of hepatitis; treatment of heart disease and iron overload; noninvasive ways of measuring iron burden; and efforts to improve the safety of the Nation’s blood supply.

Women’s Health Initiative

Coronary heart disease, cancer, and osteoporosis are the most common causes of death, disability, and impaired quality of life in postmenopausal women. The WHI (see Chapters 2 and 11) is addressing the benefits and risks of HT, changes in dietary patterns, and calcium/vitamin D supplements in disease prevention. Several of the centers have recruited primarily minority populations: blacks, Hispanics, Asians, Pacific Islanders, and American Indians. The Clinical Trial recruited 12,607 minorities and the Observational Study recruited 15,658. Overall, of the 161,809 postmenopausal women recruited into the WHI, 17 percent were minorities.

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