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 nonminority, stand to benefit from the Institutes 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 2006 activities addressing this goal include the following:
The Office of Minority Health Affairs (OMHA) 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 OMHA also coordinates activities to foster greater participation of underrepresented minorities in NHLBI research and research training and career development programs. Selected FY 2006 activities include the following:
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 Institutes research portfolio related to minority health. Additional information can be found in Chapters 9 through 11.
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.
Several investigator-initiated epidemiologic studies are examining geneenvironment interactions that increase CVD risk factors among various racial groups. Included among them are studies that compare geneenvironment 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.
Several drugs in four widely used classes of noncardiovascular medications (fluoroquinolone and macrolide antibiotics, antipsychotics, and antidepressants) have been shown to be proarrhythmic 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 persons, 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.
Ancillary studies to MESA are investigating subclinical CVD in ethnic minority groups. They include investigations of regional left ventricular function, progression of calcification in the aorta, abnormalities in the small vessels of the retina, association of air pollution and subclinical CVD, identification of genes for subclinical CVD, and relationships of sociodemographic factors and other factors to subclinical CVD.
The Institute is supporting additional epidemiologic investigations that include a study of Chagas diseasea leading cause of heart disease throughout Latin Americato 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, exposureoutcome 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 candi-date 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 patientsespecially minority populationsor adopted in routine clinical practice. The Institute has initiated the following activities to address this important problem:
Although great progress has been achieved in reducing CVD morbidity and mortality in the United States over the past 40 years, minorities have not shared fully in the progress and continue to have higher CVD morbidity. To address this problem, the Institute has initiated programs directed at reducing cardiovascular health disparities:
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 Institutes 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.
In addition to the activities mentioned above, the Institute has prepared publications on CVD prevention for minority populations. They include the following:
The educational materials listed throughout this chapter can be obtained from the NHLBI public Web site or through the NHLBI online catalog.
The NHLBI is supporting basic and genetic research on the mechanisms that underlie cardiac arrhythmias to improve diagnosis, treatment, and prevention of arrhythmias in all ethnic and racial groups in the United States. In one study examining common genetic variants that underlie variability in heart rate and rhythm, researchers have found significant ethnic and racial differences in the occurrence of sudden infant death syndrome (SIDS) associated with mutations in the same ion channel genes that cause inherited and acquired long QT syndrome (a rhythm disturbance that can be lethal). This finding, which helps to explain why SIDS occurs among blacks and Native Americans at three times its rate among whites and six times its rate among Hispanics and Asians, may lead to prospective genetic testing for SIDS and permit counseling for at-risk families.
Another study 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 no significant differences were found between blacks and whites in associated risk of sudden cardiac death, continued research in this area can be expected to advance understanding of differences in genetic predisposition for cardiac arrhythmias among ethnic and racial groups and ultimately lead to improved therapy.
Heart failure (heart muscle dysfunction) affects about 5 million Americans of all ethnicities and is a growing public health concern. It is frequently the end result of other conditions, such as hypertension, diabetes, and prior heart attacks.
The NHLBI is supporting basic and clinical research associated with heart failure that will benefit Americans of all ethnicities. One Institute-supported study within the Partnership Programs To Reduce Cardiovascular Disparities is examining heart failure disparities in Native Hawaiians:
Other research targeting minority populations includes an investigation of genetic variations (especially those common in blacks) that affect individual responses to the beta blocker drugs used to treat heart failure and identification of underlying genetic variations that result in familial dilated cardiomyopathy, an inherited form of heart dysfunction, in which five black families are participating. Another study is addressing angioedema or severe allergic reaction, 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 the side effect and studying the genetic profile of affected individuals and their families in order to detemine who should avoid taking the drugs.
Etiology and Pathophysiology
High blood pressure is a serious health problem that is especially prevalent and severe among minorities. An Institute-initiated study is seeking to determine the etiology and pathophysiology of high blood pressure:
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 reninangiotensin 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 youth.
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 largescale studies with representative populations in sufficient numbers.
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 control rates in blacks, a group with the highest prevalence and earliest onset of hypertension and with a disparately high premature cardiovascular mortality and morbidity:
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 telephonebased nurse care management in 12 community-based clinics that serve an 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).
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:
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.
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.
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.
The NCEP (see Chapter 2) has prepared the following publications on blood cholesterol for minority audiences.
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 blackwhite 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 cornary 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 are black.
Treatment and Prevention
The NHLBI has initiated several programs to test approaches for treating or preventing obesity.
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 prehypertensive 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, and 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 a study to test the efficacy of an after-school dance program and a family-based intervention involving reduced use of television, videotapes, and video games to reduce weight gain.
Obesity is one of the major health challenges facing Native American children and has serious implications for the development of type 2 diabetes. A school-based intervention, augmented with a family intervention, is focusing on reducing excess weight gain by increasing physical activity and healthy dietary practices in kindergarten and first-grade Native American children. 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.
The NHLBI OEI (see Chapter 2) has prepared health information on losing excess weight for minorities.
The Institute has initiated research on the effectiveness of an intervention program to encourage greater physical activity among adolescent girls.
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, and 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.
The Institute has prepared the following publications for minorities on the importance of physical activity and ways to become more physically active.
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 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 maintenance 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 intervention improves smoking cessation; 45 percent of the participants are black.
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 evaluating 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.
The Institute has prepared the following publications on smoking cessation for minorities.
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 mechanisms 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 intimal-medial 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 metabolism); and CHD risk factors. Fifty to 60 percent of the participants are black or Hispanic.
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, especially among blacks, Hispanics, and American Indians. To address this growing problem, the Institute is supporting an investigator-initiated study on defining the relationship between the overall dose of endurance exercise training and the corresponding response of metabolic 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. Scientists 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.
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.
An investigator-initiated study will evaluate the effectiveness of a multiple risk factor intervention (diet, exercise, stress management, social support, and smoking cessation) targeting postmenopausal Hispanic women with type 2 diabetes.
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.
Etiology and Pathophysiology
The NHLBI has initiated several studies to determine the etiology and pathophysiology of asthma.
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. A new case-controlled study is seeking to identify genetic determinants of asthma risk among populations of African ancestry by performing genome-wide association studies and genegene and geneenvironment interaction studies.
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 arrest occur during sleep. Focusing 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 are 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.
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.
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 minority 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.
The NAEPP (see Chapter 2) has developed easy-to-read materials on asthma treatment and control directed to audiences with low literacy.
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; many of the participants are black.
Sleep apnea is a common disorder that disproportionately affects blacks and is associated with an increased risk of CVD, including hypertension and stroke; 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.
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 is investigating 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 identification and treatment of high-risk individuals. A community-based study of sleep in Hispanics is assessing the prevalence and awarenesss of sleep disorders.
New findings from two independent studies associate SDB with a two- to fourfold increased frequency of stroke in middle-aged adults. A 3-year prospective clinical study of 1,000 middle-aged adults found that the frequency of stroke and all-cause mortality was doubled among participants diagnosed with moderate-to-severe sleep apnea.
Treatment and Control
The NHLBI has initiated a multisite clinical trial to find effective treatments for sleep apnea.
The NHLBI published Your Guide to Healthy Sleep, which provides the latest information about sleep apnea and other sleep disorders including insomnia, restless legs syndrome, and narcolepsy.
The Institute has initiated genetic studies to characterize genes associated with TB susceptibility and host immune responses to infection.
Treatment and Control
The NHLBI supports a number of investigator-initiated studies focused on understanding the relationship between the immune system and TB. Most of the patients are from minority populations. Included among them are studies to: (1) identify the correlates of protective immunity in a Mexican population in order to aid development of anti-TB vaccines; (2) compare susceptibility to TB in populations in Mexico and Peru; (3) examine the role of interferon-gamma in the pathogenesis of TB among Hispanics with and without HIV; (4) identify and characterize host factors that predispose Asians to develop TB; and (5) determine the effectiveness of adding aerosolized interferon-gamma to the usual treatment regimen for advanced TB in predominately minority populations in the United States and South Africa.
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.
Building on the foundation laid by the Tuberculosis Academic Award program, the NHLBI is supporting a consortium of five TB curriculum centers.
The NHLBI supports basic and clinical research on SCD and Cooleys anemia with the goal of curing the disorders and improving patient care.
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.
Basic and translational research currently focuses on understanding better the expression of beta globins, elucidating the complex mechanisms of cell adhesion and vaso-occlusion, discovering genes that regulate fetal hemoglobin, describing the genetic factors that are responsible for the wide spectrum of clinical severity, and developing a prospective program for gene therapy.
Specific NHLBI initiatives include:
Basic research advances reported in FY 2006 include:
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.
The NHLBI supports several transplant-related clinical studies that seek to reach minority populations.
The Cord Blood Stem Cell Transplantation (COBLT) Study was completed in 2005. The COBLT bank contained more than 8,000 cord blood units, approximately 57 percent of them from minority donors. Approximately 30 percent of the COBLT transplant patients were minority. More than 3,500 of the COBLT cord blood units are currently available through the National Bone Marrow Donor Registry for clinical transplantation.
For the past several years the NHLBI has supported working groups and meetings to understand the health and quality-of-life obstacles and challenges faced by adults with SCD. Activities to address the needs of the adult SCD patient community in 2006 include:
The NHLBI has developed a number of publications on SCD that target minorities.
Cooleys 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 hematopoetic transplantation and gene therapy approaches to cure the disease. A registry with samples has been established to foster genomic and proteomic studies. International collaborations have also been establised.
Studies initiated within this network 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); 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 Nations blood supply.
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 hormone therapy, 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.