National Heart, Lung, and Blood Institute (NHLBI) Strategy for Addressing Health Disparities

Throughout its history, the NHLBI has been a leader in conducting and supporting research to alleviate the health disparities that exist between various segments of the U.S. population, and its outstanding efforts in this area have been publicly recognized in Congressional hearings. Projects with a strong minority component have been initiated so that comparisons may be made between various populations. These projects have produced a wealth of information that enable identification of health disparities and provide clues about their causes

Loss-of-Function Mutations in APOC3, Triglycerides, and Coronary Disease

Background—Plasma triglyceride levels are heritable and are correlated with the risk of coronary heart disease. Sequencing of the protein-coding regions of the human genome (the exome) has the potential to identify rare mutations that have a large effect on phenotype. Methods—We sequenced the protein-coding regions of 18,666 genes in each of 3734 participants of European or African ancestry in the Exome Sequencing Project. We conducted tests to determine whether rare mutations in coding sequence, individually or in aggregate within a gene, were associated with plasma triglyceride levels. For mutations associated with triglyceride levels, we subsequently evaluated their association with the risk of coronary heart disease in 110,970 persons. Results—An aggregate of rare mutations in the gene encoding apolipoprotein C3 (APOC3) was associated with lower plasma triglyceride levels. Among the four mutations that drove this result, three were loss-of-function mutations: a nonsense mutation (R19X) and two splice-site mutations (IVS2+1G→A and IVS3+1G→T). The fourth was a missense mutation (A43T). Approximately 1 in 150 persons in the study was a heterozygous carrier of at least one of these four mutations. Triglyceride levels in the carriers were 39% lower than levels in noncarriers (P<1×10−20), and circulating levels of APOC3 in carriers were 46% lower than levels in noncarriers (P = 8×10−10). The risk of coronary heart disease among 498 carriers of any rare APOC3 mutation was 40% lower than the risk among 110,472 noncarriers (odds ratio, 0.60; 95% confidence interval, 0.47 to 0.75; P = 4×10−6). Conclusions—Rare mutations that disrupt APOC3 function were associated with lower levels of plasma triglycerides and APOC3. Carriers of these mutations were found to have a reduced risk of coronary heart disease. (Funded by the National Heart, Lung, and Blood Institute and others.

Short-Term Effects of Air Pollution on Wheeze in Asthmatic Children in Fresno, California

BACKGROUND: Although studies have demonstrated that air pollution is associated with exacerbation of asthma symptoms in children with asthma, little is known about the susceptibility of subgroups, particularly those with atopy. OBJECTIVE: This study was designed to evaluate our a priori hypothesis that identifiable subgroups of asthmatic children are more likely to wheeze with exposure to ambient air pollution. METHODS: A cohort of 315 children with asthma, 6-11 years of age, was recruited for longitudinal follow-up in Fresno, California (USA). During the baseline visit, children were administered a respiratory symptom questionnaire and allergen skin-prick test. Three times a year, participants completed 14-day panels during which they answered symptom questions twice daily. Ambient air quality data from a central monitoring station were used to assign exposures to the following pollutants: particulate matter &lt;= 2.5 mu m in aerodynamic diameter, particulate matter between 2.5 and 10 mu m in aerodynamic diameter (PM(10-2.5)), elemental carbon, nitrogen dioxide (NO(2)), nitrate, and O(3). RESULTS: For the group as a whole, wheeze was significantly associated with short-term exposures to NO(2) [odds ratio (OR) = 1.10 for 8.7-ppb increase; 95% confidence interval (CI), 1.02-1.20] and PM(10-2.5) (OR = 1.11 for 14.7-mu g/m(3) increase; 95% CI, 1.01-1.22). The association with wheeze was stronger for these two pollutants in children who were skin-test positive to cat or common fungi and in boys with mild intermittent asthma. CONCLUSION: A pollutant associated with traffic emissions, NO(2), and a pollutant with bioactive constituents, PM(10-2.5), were associated with increased risk of wheeze in asthmatic children living in Fresno, California. Children with atopy to cat or common fungi and boys with mild intermittent asthma were the subgroups for which we observed the largest associations

Association of Polymorphisms in the Human IL4 and IL5 Genes With Atopic Bronchial Asthma and Severity of the Disease

Two polymorphisms in the IL4 (G/C 3′-UTR) and IL5 (C-703T) genes were studied in a sample of families whose probands had atopic bronchial asthma (BA) (66 families, n = 183) and in a group of non-cognate individuals with the severe form of the disease (n = 34). The samples were collected from the Russian population in the city of Tomsk (Russia). Using the transmission/disequilibrium test (TDT), a significant association of allele C-703 IL5 with BA was established (TDT = 4.923, p = 0.007 ± 0.0007). The analysis of 40 individuals with mild asthma and 49 patients with the severe form of the disease revealed a negative association of genotype GG IL4 (OR = 0.39, 95% CI = 0.15−0.99, p = 0.035), and also a trend towards a positive association of the GC IL4 genotype (OR = 2.52, 95% CI = 0.98−6.57, p = 0.052) with mild BA. There was a concordance of the clinical classification of BA severity with the ‘genotype’ (McNemar’s χ2 test with continuity correction constituted 0.03, d.f. = 1, p = 0.859). These results suggest that polymorphisms in the IL4 and IL5 genes contribute to the susceptibility to atopic BA and could determine the clinical course of the disease

A longitudinal study of adult-onset asthma incidence among HMO members

BACKGROUND: HMO databases offer an opportunity for community based epidemiologic studies of asthma incidence, etiology and treatment. The incidence of asthma in HMO populations and the utility of HMO data, including use of computerized algorithms and manual review of medical charts for determining etiologic factors has not been fully explored. METHODS: We identified adult-onset asthma, using computerized record searches in a New England HMO. Monthly, our software applied exclusion and inclusion criteria to identify an "at-risk" population and "potential cases". Electronic and paper medical records from the past year were then reviewed for each potential case. Persons with other respiratory diseases or insignificant treatment for asthma were excluded. Confirmed adult-onset asthma (AOA) cases were defined as those potential cases with either new-onset asthma or reactivated mild intermittent asthma that had been quiescent for at least one year. We validated the methods by reviewing charts of selected subjects rejected by the algorithm. RESULTS: The algorithm was 93 to 99.3% sensitive and 99.6% specific. Sixty-three percent (n = 469) of potential cases were confirmed as AOA. Two thirds of confirmed cases were women with an average age of 34.8 (SD 11.8), and 45% had no evidence of previous asthma diagnosis. The annualized monthly rate of AOA ranged from 4.1 to 11.4 per 1000 at-risk members. Physicians most commonly attribute asthma to infection (59%) and allergy (14%). New-onset cases were more likely attributed to infection, while reactivated cases were more associated with allergies. Medical charts included a discussion of work exposures in relation to asthma in only 32 (7%) cases. Twenty-three of these (72%) indicated there was an association between asthma and workplace exposures for an overall rate of work-related asthma of 4.9%. CONCLUSION: Computerized HMO records can be successfully used to identify AOA. Manual review of these records is important to confirm case status and is useful in evaluation of provider consideration of etiologies. We demonstrated that clinicians attribute most AOA to infection and tend to ignore the contribution of environmental and occupational exposures

Prospective Analysis of Traffic Exposure as a Risk Factor for Incident Coronary Heart Disease: The Atherosclerosis Risk in Communities (ARIC) Study

BackgroundFor people living close to busy roads, traffic is a major source of air pollution. Few prospective data have been published on the effects of long-term exposure to traffic on the incidence of coronary heart disease (CHD).ObjectivesIn this article, we examined the association between long-term traffic exposure and incidence of fatal and nonfatal CHD in a population-based prospective cohort study.MethodsWe studied 13,309 middle-age men and women in the Atherosclerosis Risk in Communities study, without previous CHD at enrollment, from 1987 to 1989 in four U.S. communities. Geographic information system–mapped traffic density and distance to major roads served as measures of traffic exposure. We examined the association between traffic exposure and incident CHD using proportional hazards regression models, with adjustment for background air pollution and a wide range of individual cardiovascular risk factors.ResultsOver an average of 13 years of follow-up, 976 subjects developed CHD. Relative to those in the lowest quartile of traffic density, the adjusted hazard ratio (HR) in the highest quartile was 1.32 [95% confidence interval (CI), 1.06–1.65; p-value for trend across quartiles = 0.042]. When we treated traffic density as a continuous variable, the adjusted HR per one unit increase of log-transformed density was 1.03 (95% CI, 1.01–1.05; p = 0.006). For residents living within 300 m of major roads compared with those living farther away, the adjusted HR was 1.12 (95% CI, 0.95–1.32; p = 0.189). We found little evidence of effect modification for sex, smoking status, obesity, low-density lipoprotein cholesterol level, hypertension, age, or education.ConclusionHigher long-term exposure to traffic is associated with incidence of CHD, independent of other risk factors. These prospective data support an effect of traffic-related air pollution on the development of CHD in middle-age persons

An Evaluation of Asthma Interventions for Preteen Students

BACKGROUND: Asthma is a serious problem for low-income preteens living in disadvantaged communities. Among the chronic diseases of childhood and adolescence, asthma has the highest prevalence and related health care use. School-based asthma interventions have proven successful for older and younger students, but results have not been demonstrated for those in middle school. METHODS: This randomized controlled study screened students 10–13 years of age in 19 middle schools in low-income communities in Detroit, Michigan. Of the 6872 students who were screened, 1292 students were identified with asthma. Schools were matched and randomly assigned to Program 1 or 2 or control. Baseline, 12, and 24 months data were collected by telephone (parents), at school (students) and from school system records. Measures were the students' asthma symptoms, quality of life, academic performance, self-regulation, and asthma management practices. Data were analyzed using multiple imputation with sequential regression analysis. Mixed models and Poisson regressions were used to develop final models. RESULTS: Neither program produced significant change in asthma symptoms or quality of life. One produced improved school grades (p = .02). The other enhanced self-regulation (p = .01) at 24 months. Both slowed the decline in self-regulation in undiagnosed preteens at 12 months and increased self-regulation at 24 months (p = .04; p = .003). CONCLUSION: Programs had effects on academic performance and self-regulation capacities of students. More developmentally focused interventions may be needed for students at this transitional stage. Disruptive factors in the schools may have reduced both program impact and the potential for outcome assessment.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78617/1/j.1746-1561.2009.00469.x.pd

The relationship of body mass index to diabetes mellitus, hypertension and dyslipidaemia: comparison of data from two national surveys

The objectives of this study were to explore the relation between body mass index (BMI) and prevalence of diabetes mellitus, hypertension and dyslipidaemia; examine BMI distributions among patients with these conditions; and compare results from two national surveys. The Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes (SHIELD) 2004 screening questionnaire (mailed survey) and the National Health and Nutrition Examination Surveys (NHANES) 1999–2002 (interview, clinical and laboratory data) were conducted in nationally representative samples ≥ 18 years old. Responses were received from 127,420 of 200,000 households (64%, representing 211,097 adults) for SHIELD, and 4257 participants for NHANES. Prevalence of diabetes mellitus, hypertension and dyslipidaemia was estimated within BMI categories, as was distribution of BMI levels among individuals with these diseases. Mean BMI was 27.8 kg/m2 for SHIELD and 27.9 kg/m2 for NHANES. Increased BMI was associated with increased prevalence of diabetes mellitus, hypertension and dyslipidaemia in both studies (p < 0.001). For each condition, more than 75% of patients had BMI ≥ 25 kg/m2. Estimated prevalence of diabetes mellitus and hypertension was similar in both studies, while dyslipidaemia was substantially higher in NHANES than SHIELD. In both studies, prevalence of diabetes mellitus, hypertension and dyslipidaemia occurred across all ranges of BMI, but increased with higher BMI. However, not all overweight or obese patients had these metabolic diseases and not all with these conditions were overweight or obese. Except for dyslipidaemia prevalence, SHIELD was comparable with NHANES. Consumer panel surveys may be an alternative method to collect data on the relationship of BMI and metabolic diseases

Correlation between the Korean Version of Asthma Control Test and Health-Related Quality of Life in Adult Asthmatics

The Asthma Control Test (ACT) is a patient-completed questionnaire developed to assess asthma control. Health-related quality of life (HRQL) in asthmatics has shown relatively low correlations with parameters of asthma control and the relationship between the ACT and HRQL in asthmatics is yet unclear. Because revalidations of translated versions of questionnaires are critical for its utilization, we first sought to validate the Korean version of ACT and then to evaluate the relationship between the ACT and HRQL. Patients (n=117) completed the ACT and asthma-related quality of life questionnaire (AQLQ) at 3 physician visits. Pulmonary function was measured and an asthma specialist rated asthma control. The Korean version of ACT was found to be reliable, valid, and responsive to changes in asthma control over time up to three consecutive visits. ACT scores correlated significantly (p=0.001) with symptoms domain (r=0.72), activity domain (r=0.65), emotional domain (r=0.69), and environmental domain (r=0.67) of AQLQ. In conclusion, the Korean version of the ACT was found to be a reliable and valid tool for measuring asthma control, and to correlate well with AQLQ scores. Moreover, the ACT was responsive to changes in AQLQ scores over time