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

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

Comparing the effectiveness of a multi-component weight loss intervention in adults with and without intellectual disabilities

&lt;p&gt;Background: The prevalence of obesity in adults with intellectual disabilities (ID) is rising, although the evidence base for its treatment in this population group is minimal. Weight management interventions that are accessible to adults with ID will reduce the inequalities that they frequently experience in health services. This short report compared the effectiveness of weight management in those with and without ID who completed nine sessions of a multi-component weight management programme.&lt;/p&gt; &lt;p&gt;Methods: TAKE 5 is a 16-week multi-component weight management intervention for adults with ID and obesity [body mass index (BMI) ≥30 kg m–2]. This intervention is an adaption of the weight management programme provided by the Glasgow &#38; Clyde Weight Management Service (GCWMS) for adults without ID and obesity (National Health Service based). Fifty-two participants of the TAKE 5 programme were individually matched by baseline characteristics (sex, age and BMI) with two participants without ID of the GCWMS programme. Comparisons in terms of weight and BMI change and rate of weight loss were made for those who attended all nine sessions.&lt;/p&gt; &lt;p&gt;Results: There were no significant differences between the groups in the amount of weight loss (median: −3.6 versus −3.8 kg, respectively, P = 0.4), change in BMI (median: −1.5 versus −1.4 kg m–2, P = 0.9), success of achieving 5% weight loss (41.3% versus 36.8%, P = 0.9) and rate of weight loss across the 16-week intervention.&lt;/p&gt; &lt;p&gt;Conclusions: A multi-component weight loss intervention can be equally effective for adults with and without ID and obesity.&lt;/p&gt

Comparison of blood pressure levels among four age groups of Chinese children matched by height

Hypertension in children is frequently undiagnosed. Normal blood pressure is currently defined as a function of two continuous variables, age and height for each gender. Applying the current cutoff values to assess a child's blood pressure is time consuming. To separate the independent effect of age from that of height on blood pressure, we conducted a multiple group matched study to investigate if blood pressure levels in children with a given height distribution vary with age. An equal number of 2539 Chinese children from each of the four age groups (7, 8, 9 and 10 years) were individually matched by height, sex and geographic region. We used the matching technique to force the four age groups to have an identical height distribution. Systolic and diastolic blood pressures significantly increased with increasing age before matching. After matching, four groups had strikingly similar levels of blood pressures, and the differences among four groups were small and not statistically significant. Once height is taken into consideration, age has little impact on blood pressure. Our findings, if confirmed in children of other ages, suggest that blood pressure percentile charts can be considerably simplified by establishing normal percentiles according to height alone for each gender

An observational study of Donor Ex Vivo Lung Perfusion in UK lung transplantation: DEVELOP-UK

Background: Many patients awaiting lung transplantation die before a donor organ becomes available. Ex vivo lung perfusion (EVLP) allows initially unusable donor lungs to be assessed and reconditioned for clinical use. Objective: The objective of the Donor Ex Vivo Lung Perfusion in UK lung transplantation study was to evaluate the clinical effectiveness and cost-effectiveness of EVLP in increasing UK lung transplant activity. Design: A multicentre, unblinded, non-randomised, non-inferiority observational study to compare transplant outcomes between EVLP-assessed and standard donor lungs. Setting: Multicentre study involving all five UK officially designated NHS adult lung transplant centres. Participants: Patients aged ≥ 18 years with advanced lung disease accepted onto the lung transplant waiting list. Intervention: The study intervention was EVLP assessment of donor lungs before determining suitability for transplantation. Main outcome measures: The primary outcome measure was survival during the first 12 months following lung transplantation. Secondary outcome measures were patient-centred outcomes that are influenced by the effectiveness of lung transplantation and that contribute to the health-care costs. Results: Lungs from 53 donors unsuitable for standard transplant were assessed with EVLP, of which 18 (34%) were subsequently transplanted. A total of 184 participants received standard donor lungs. Owing to the early closure of the study, a non-inferiority analysis was not conducted. The Kaplan–Meier estimate of survival at 12 months was 0.67 [95% confidence interval (CI) 0.40 to 0.83] for the EVLP arm and 0.80 (95% CI 0.74 to 0.85) for the standard arm. The hazard ratio for overall 12-month survival in the EVLP arm relative to the standard arm was 1.96 (95% CI 0.83 to 4.67). Patients in the EVLP arm required ventilation for a longer period and stayed longer in an intensive therapy unit (ITU) than patients in the standard arm, but duration of overall hospital stay was similar in both groups. There was a higher rate of very early grade 3 primary graft dysfunction (PGD) in the EVLP arm, but rates of PGD did not differ between groups after 72 hours. The requirement for extracorporeal membrane oxygenation (ECMO) support was higher in the EVLP arm (7/18, 38.8%) than in the standard arm (6/184, 3.2%). There were no major differences in rates of chest radiograph abnormalities, infection, lung function or rejection by 12 months. The cost of EVLP transplants is approximately £35,000 higher than the cost of standard transplants, as a result of the cost of the EVLP procedure, and the increased ECMO use and ITU stay. Predictors of cost were quality of life on joining the waiting list, type of transplant and number of lungs transplanted. An exploratory model comparing a NHS lung transplant service that includes EVLP and standard lung transplants with one including only standard lung transplants resulted in an incremental cost-effectiveness ratio of £73,000. Interviews showed that patients had a good understanding of the need for, and the processes of, EVLP. If EVLP can increase the number of usable donor lungs and reduce waiting, it is likely to be acceptable to those waiting for lung transplantation. Study limitations include small numbers in the EVLP arm, limiting analysis to descriptive statistics and the EVLP protocol change during the study. Conclusions: Overall, one-third of donor lungs subjected to EVLP were deemed suitable for transplant. Estimated survival over 12 months was lower than in the standard group, but the data were also consistent with no difference in survival between groups. Patients receiving these additional transplants experience a higher rate of early graft injury and need for unplanned ECMO support, at increased cost. The small number of participants in the EVLP arm because of early study termination limits the robustness of these conclusions. The reason for the increased PGD rates, high ECMO requirement and possible differences in lung injury between EVLP protocols needs evaluation