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Abstract INTRODUCTION Hearing loss is highly prevalent among older adults and independently associated with cognitive decline. The Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study is a multicenter randomized control trial (partially nested within the infrastructure of an observational cohort study, the Atherosclerosis Risk in Communities [ARIC] study) to determine the efficacy of best‐practice hearing treatment to reduce cognitive decline over 3 years. The goal of this paper is to describe the recruitment process and baseline results. METHODS Multiple strategies were used to recruit community‐dwelling 70–84‐year‐old participants with adult‐onset hearing loss who were free of substantial cognitive impairment from the parent ARIC study and de novo from the surrounding communities into the trial. Participants completed telephone screening, an in‐person hearing, vision, and cognitive screening, and a comprehensive hearing assessment to determine eligibility. RESULTS Over a 24‐month period, 3004 telephone screenings resulted in 2344 in‐person hearing, vision, and cognition screenings and 1294 comprehensive hearing screenings. Among 1102 eligible, 977 were randomized into the trial (median age = 76.4 years; 53.5% female; 87.8% White; 53.3% held a Bachelor's degree or higher). Participants recruited through the ARIC study were recruited much earlier and were less likely to report hearing loss interfered with their quality of life relative to participants recruited de novo from the community. Minor differences in baseline hearing or health characteristics were found by recruitment route (i.e., ARIC study or de novo) and by study site. DISCUSSION The ACHIEVE study successfully completed enrollment over 2 years that met originally projected rates of recruitment. Substantial operational and scientific efficiencies during study startup were achieved through embedding this trial within the infrastructure of a longstanding and well‐established observational study. Highlights The ACHIEVE study tests the effect of hearing intervention on cognitive decline. The study is partially nested within an existing cohort study. Over 2 years, 977 participants recruited and enrolled. Eligibility assessed by telephone and in‐person for hearing, vision, and cognitive screening. The ACHIEVE study findings will have significant public health implications.

BACKGROUND: Periodontitis during pregnancy is associated with an increased risk of preterm birth (

The predictive ability of coronary heart disease (CHD) and ischemic stroke (IS) polygenic risk scores (PRS) have been evaluated individually, but whether they predict the combined outcome of atherosclerotic cardiovascular disease (ASCVD) remains insufficiently researched. It is also unclear whether associations of the CHD and IS PRS with ASCVD are independent of subclinical atherosclerosis measures. 7,286 White and 2,016 Black participants from the population-based Atherosclerosis Risk in Communities study who were free of cardiovascular disease and type 2 diabetes at baseline were included. We computed previously validated CHD and IS PRS consisting of 1,745,179 and 3,225,583 genetic variants, respectively. Cox proportional hazards models were used to test the association between each PRS and ASCVD, adjusting for traditional risk factors, ankle-brachial index, carotid intima media thickness, and carotid plaque. The hazard ratios (HR) for the CHD and IS PRS were significant with HR of 1.50 (95% CI: 1.36-1.66) and 1.31 (95% CI: 1.18-1.45) respectively for the risk of incident ASCVD per standard deviation increase in CHD and IS PRS among White participants after adjusting for traditional risk factors. The HR for the CHD PRS was not significant with an HR of 0.95 (95% CI: 0.79-1.13) for the risk of incident ASCVD in Black participants. The HR for the IS PRS was significant with an HR of 1.26 (95%CI: 1.05-1.51) for the risk of incident ASCVD in Black participants. The association of the CHD and IS PRS with ASCVD was not attenuated in White participants after adjustment for ankle-brachial index, carotid intima media thickness, and carotid plaque. The CHD and IS PRS do not cross-predict well, and predict better the outcome for which they were created than the composite ASCVD outcome. Thus, the use of the composite outcome of ASCVD may not be ideal for genetic risk prediction.

Abstract Background Soluble receptor for advanced glycation end products (sRAGE) is a proposed emphysema and airflow obstruction biomarker; however, previous publications have shown inconsistent associations and only one study has investigate the association between sRAGE and emphysema. No cohorts have examined the association between sRAGE and progressive decline of lung function. There have also been no evaluation of assay compatibility, receiver operating characteristics, and little examination of the effect of genetic variability in non-white population. This manuscript addresses these deficiencies and introduces novel data from Pittsburgh COPD SCCOR and as well as novel work on airflow obstruction. A meta-analysis is used to quantify sRAGE associations with clinical phenotypes. Methods sRAGE was measured in four independent longitudinal cohorts on different analytic assays: COPDGene (n = 1443); SPIROMICS (n = 1623); ECLIPSE (n = 2349); Pittsburgh COPD SCCOR (n = 399). We constructed adjusted linear mixed models to determine associations of sRAGE with baseline and follow up forced expiratory volume at one second (FEV1) and emphysema by quantitative high-resolution CT lung density at the 15th percentile (adjusted for total lung capacity). Results Lower plasma or serum sRAGE values were associated with a COPD diagnosis (P

Abstract Background Millions of Americans are living in food deserts in the United States, however the role of the local food environment on COPD has not been studied. The aim of this study is to determine the association between food deserts and COPD-related outcomes. Method In this cross-sectional analysis we linked data collected from SPIROMICS (SubPopulations and InteRmediate Outcome Measures in COPD Study) between 2010 and 2015 and food desert data, defined as an underserved area that lacks access to affordable healthy foods, from the Food Access Research Atlas. COPD outcomes include percentage of predicted forced expiratory volume in one second (FEV1%), St. George’s Respiratory Questionnaire (SGRQ), COPD Assessment Test (CAT), 6-min walk distance test (6MWD), exacerbations, and air trapping. We used generalized linear mixed models to evaluate the association between living in food deserts and respiratory outcomes, adjusting for age, gender, race, education, income, marital status, BMI, smoking status, pack years, and urban status Results Among 2713 participants, 22% lived in food deserts. Participants living in food deserts were less likely to be white and more likely to have a lower income than those who did not live in food deserts. In the adjusted model controlling for demographics and individual income, living in food deserts was associated lower FEV1% (β = – 2.51, P = 0.046), higher air trapping (β = 2.47, P = 0.008), worse SGRQ (β = 3.48, P = 0.001) and CAT (β = 1.20, P = 0.003) scores, and 56% greater odds of severe exacerbations (P = 0.004). Results were consistent when looking at food access alone, regardless of whether participants lived in low income areas. Conclusions Findings suggest an independent association between food desert and food access alone with COPD outcomes. Health program planning may benefit from addressing disparities in access to food.

Abstract Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and the traditional variables extracted from computed tomography (CT) images may not be sufficient to describe all the topological features of lung tissues in COPD patients. We employed an unsupervised three-dimensional (3D) convolutional autoencoder (CAE)-feature constructor (FC) deep learning network to learn from CT data and derive tissue pattern-clusters jointly. We then applied exploratory factor analysis (EFA) to discover the unobserved latent traits (factors) among pattern-clusters. CT images at total lung capacity (TLC) and residual volume (RV) of 541 former smokers and 59 healthy non-smokers from the cohort of the SubPopulations and Intermediate Outcome Measures in the COPD Study (SPIROMICS) were analyzed. TLC and RV images were registered to calculate the Jacobian (determinant) values for all the voxels in TLC images. 3D Regions of interest (ROIs) with two data channels of CT intensity and Jacobian value were randomly extracted from training images and were fed to the 3D CAE-FC model. 80 pattern-clusters and 7 factors were identified. Factor scores computed for individual subjects were able to predict spirometry-measured pulmonary functions. Two factors which correlated with various emphysema subtypes, parametric response mapping (PRM) metrics, airway variants, and airway tree to lung volume ratio were discriminants of patients across all severity stages. Our findings suggest the potential of developing factor-based surrogate markers for new COPD phenotypes.

Abstract Background Quantitative computed tomographic (QCT) imaging-based metrics enable to quantify smoking induced disease alterations and to identify imaging-based clusters for current smokers. We aimed to derive clinically meaningful sub-groups of former smokers using dimensional reduction and clustering methods to develop a new way of COPD phenotyping. Methods An imaging-based cluster analysis was performed for 406 former smokers with a comprehensive set of imaging metrics including 75 imaging-based metrics. They consisted of structural and functional variables at 10 segmental and 5 lobar locations. The structural variables included lung shape, branching angle, airway-circularity, airway-wall-thickness, airway diameter; the functional variables included regional ventilation, emphysema percentage, functional small airway disease percentage, Jacobian (volume change), anisotropic deformation index (directional preference in volume change), and tissue fractions at inspiration and expiration. Results We derived four distinct imaging-based clusters as possible phenotypes with the sizes of 100, 80, 141, and 85, respectively. Cluster 1 subjects were asymptomatic and showed relatively normal airway structure and lung function except airway wall thickening and moderate emphysema. Cluster 2 subjects populated with obese females showed an increase of tissue fraction at inspiration, minimal emphysema, and the lowest progression rate of emphysema. Cluster 3 subjects populated with older males showed small airway narrowing and a decreased tissue fraction at expiration, both indicating air-trapping. Cluster 4 subjects populated with lean males were likely to be severe COPD subjects showing the highest progression rate of emphysema. Conclusions QCT imaging-based metrics for former smokers allow for the derivation of statistically stable clusters associated with unique clinical characteristics. This approach helps better categorization of COPD sub-populations; suggesting possible quantitative structural and functional phenotypes.

Background Intensive systolic blood pressure treatment (

BackgroundThe purpose of this study was to explore the association between perceived social support and COPD outcomes and to determine whether the associations are mediated by depressive symptoms.MethodsSubjects with COPD who were enrolled as part of SPIROMICS were included in this analysis. Questionnaires relating to quality of life, symptom burden, and functional status were administered at annual clinic visits for over a 3 year period. In both cross-sectional and longitudinal analyses, we examined the association of social support as measured by the FACIT-F with COPD outcomes. Cross sectional analyses used multivariable linear or logistic regression, adjusting for covariates. For longitudinal analyses, generalized linear mixed models with random intercepts were used. Models were adjusted with and without depressive symptoms and mediation analyses performed.ResultsOf the 1831 subjects with COPD, 1779 completed the FACIT- F questionnaire. In adjusted cross-sectional analysis without depressive symptoms, higher perceived social support was associated with better quality of life, well-being, 6 minute walk distance, and less dyspnea. When also adjusting for depressive symptoms, all associations between social support and COPD outcomes were attenuated and no longer statistically significant. Mediation analysis suggested that depressive symptoms explained the majority (> = 85%) of the association between social support and measured COPD outcomes. Results of the longitudinal analysis were consistent with the cross-sectional analyses. There was no association between social support and odds of exacerbations.ConclusionHigher social support was associated with better COPD outcomes across several measures of morbidity including quality of life, respiratory symptoms, and functional status. In addition, these associations were largely attenuated when accounting for depressive symptoms suggesting that the beneficial association of social support with COPD outcomes may be largely mediated by the association between social support and depression.Trial registrationSPIROMICS was approved by Institutional Review Boards at each center and all participants provided written informed consent (clinicaltrials.gov: NCT01969344).

Abstract Background Classification of COPD is usually based on the severity of airflow, which may not sensitively differentiate subpopulations. Using a multiscale imaging-based cluster analysis (MICA), we aim to identify subpopulations for current smokers with COPD. Methods Among the SPIROMICS subjects, we analyzed computed tomography images at total lung capacity (TLC) and residual volume (RV) of 284 current smokers. Functional variables were derived from registration of TLC and RV images, e.g. functional small airways disease (fSAD%). Structural variables were assessed at TLC images, e.g. emphysema and airway wall thickness and diameter. We employed an unsupervised method for clustering. Results Four clusters were identified. Cluster 1 had relatively normal airway structures; Cluster 2 had an increase of fSAD% and wall thickness; Cluster 3 exhibited a further increase of fSAD% but a decrease of wall thickness and airway diameter; Cluster 4 had a significant increase of fSAD% and emphysema. Clinically, Cluster 1 showed normal FEV1/FVC and low exacerbations. Cluster 4 showed relatively low FEV1/FVC and high exacerbations. While Cluster 2 and Cluster 3 showed similar exacerbations, Cluster 2 had the highest BMI among all clusters. Conclusions Association of imaging-based clusters with existing clinical metrics suggests the sensitivity of MICA in differentiating subpopulations.

Abstract Background The aim of this study is to identify genetic loci associated with post-bronchodilator FEV1/FVC and FEV1, and develop a multi-gene predictive model for lung function in COPD. Methods Genome-wide association study (GWAS) of post-bronchodilator FEV1/FVC and FEV1 was performed in 1645 non-Hispanic White European descent smokers. Results A functional rare variant in SERPINA1 (rs28929474: Glu342Lys) was significantly associated with post-bronchodilator FEV1/FVC (p = 1.2 × 10− 8) and FEV1 (p = 2.1 × 10− 9). In addition, this variant was associated with COPD (OR = 2.3; p = 7.8 × 10− 4) and severity (OR = 4.1; p = 0.0036). Heterozygous subjects (CT genotype) had significantly lower lung function and higher percentage of COPD and more severe COPD than subjects with the CC genotype. 8.6% of the variance of post-bronchodilator FEV1/FVC can be explained by SNPs in 10 genes with age, sex, and pack-years of cigarette smoking (P

Myeloperoxidase (MPO) is a heme-containing peroxidase found in azurophilic granules of neutrophils and monocytes. Epidemiological studies have reported greater plasma MPO concentration to be associated with increased incidence of several cardiovascular diseases (CVD), but the association of intracellular monocyte MPO (mMPO) with CVD is unclear. The prospective population-based Atherosclerosis Risk in Communities (ARIC) cohort study measured mMPO using flow cytometry in 1,465 participants. The association of mMPO with incident cardiovascular disease (CVD, comprising incident coronary heart disease (CHD), heart failure, stroke, peripheral artery disease, and cardiovascular mortality) was examined over a median 9.6 years of follow-up (n = 290 CVD events). There was no statistically significant association between mMPO and all incident CVD events in either age, sex, and race-adjusted proportional hazards models (HR (95% CI) across tertiles of mMPO: 1, 1.09 (0.76, 1.57), and 0.78 (0.52, 1.15), P-trend = 0.21) or adjusted for other major CVD risk factors (HR (95% CI): 1, 1.17 (0.81, 1.69), and 0.87 (0.58, 1.29), P-trend = 0.50). There also was no association between mMPO tertiles and incident CHD, heart failure, or all-cause mortality, examined separately. In conclusion, intracellular monocyte myeloperoxidase was not associated with incident cardiovascular disease in this prospective population-based study.

Background: Retinol binding protein 4 (RBP4) has been described as a link between impaired glucose uptake in adipocytes and systemic insulin sensitivity. Objective: To determine whether RBP4 fasting levels predict the development of type 2 diabetes. Methods: Using a case-cohort design, we followed 543 middle-aged individuals who developed diabetes and 537 who did not over ~9 years within the population-based Atherosclerosis Risk in Communities Study. Weighted Cox proportional hazards analyses permitted statistical inference of the RBP4 – incident diabetes associations to the entire cohort. Results: Women in the highest tertile of RBP4 presented greater risk of developing diabetes (HR = 1.74; 95%CI 1.03 – 2.94) in analyses adjusted for age, ethnicity, study center, parental history of diabetes, hypertension, glomerular filtration rate, body mass index, waist-hip ratio, nonesterified fatty acids, adiponectin, leptin, triglycerides and HDL-C. When additionally adjusted for fasting insulin, this association’s significance became borderline (HR = 1.68; 95%CI 1.00 – 2.82). No association between RBP4 levels and incident diabetes was found in men. Conclusion: These findings suggest that RBP4 levels may be directly involved in the pathogenesis of type 2 diabetes in women.

VWF is extensively glycosylated with biantennary core fucosylated glycans. Most N-linked and O-linked glycans on VWF are sialylated. FVIII is also glycosylated, with a glycan structure similar to that of VWF. ST3GAL sialyltransferases catalyze the transfer of sialic acids in the α2,3 linkage to termini of N- and O-glycans. This sialic acid modification is critical for VWF synthesis and activity. We analyzed genetic and phenotypic data from the Atherosclerosis Risk in Communities (ARIC) study for the association of single nucleotide polymorphisms (SNPs) in the ST3GAL4 gene with plasma VWF levels and FVIII activity in 12,117 subjects. We also analyzed ST3GAL4 SNPs found in 2,535 subjects of 26 ethnicities from the 1000 Genomes (1000G) project for ethnic diversity, SNP imputation, and ST3GAL4 haplotypes. We identified 14 and 1,714 ST3GAL4 variants in the ARIC GWAS and 1000G databases respectively, with 46% being ethnically diverse in their allele frequencies. Among the 14 ST3GAL4 SNPs found in ARIC GWAS, the intronic rs2186717, rs7928391, and rs11220465 were associated with VWF levels and with FVIII activity after adjustment for age, BMI, hypertension, diabetes, ever-smoking status, and ABO. This study illustrates the power of next-generation sequencing in the discovery of new genetic variants and a significant ethnic diversity in the ST3GAL4 gene. We discuss potential mechanisms through which these intronic SNPs regulate ST3GAL4 biosynthesis and the activity that affects VWF and FVIII.

ABO blood groups are known to influence the plasma level of von Willebrand factor (VWF), but little is known about the relationship between ABO and coagulation factor VIII (FVIII). We analyzed the influence of ABO genotypes on VWF antigen, FVIII activity, and their quantitative relationship in 11,673 participants in the Atherosclerosis Risk in Communities (ARIC) study. VWF, FVIII, and FVIII/VWF levels varied significantly among O, A (A1 and A2), B and AB subjects, and the extent of which varied between Americans of European (EA) and African (AA) descent. We validated a strong influence of ABO blood type on VWF levels (15.2%), but also detected a direct ABO influence on FVIII activity (0.6%) and FVIII/VWF ratio (3.8%) after adjustment for VWF. We determined that FVIII activity changed 0.54% for every 1% change in VWF antigen level. This VWF-FVIII relationship differed between subjects with O and B blood types in EA, AA, and in male, but not female subjects. Variations in FVIII activity were primarily detected at low VWF levels. These new quantitative influences on VWF, FVIII and the FVIII/VWF ratio help understand how ABO genotypes differentially influence VWF, FVIII and their ratio, particularly in racial and gender specific manners.

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)

Previous cross-sectional studies have suggested that biomarkers of extracellular matrix remodelling are associated with atrial fibrillation (AF), but no prospective data have yet been published. Hence, we examine whether plasma matrix metalloproteinases (MMP) and their inhibitors are related to increased risk of incident AF.We used a case-cohort design in the context of the prospective Atherosclerosis Risk in Communities (ARIC) study. From 13718 eligible men and women free from AF in 1990-92, we selected a stratified random sample of 500 individuals without and 580 with incident AF over a mean follow-up of 11.8 years. Using a weighted proportional hazards regression model, the relationships between MMP-1, MMP-2, MMP-9, tissue inhibitor of matrix metalloproteinase (TIMP)-1, TIMP-2 and C-terminal propeptide of collagen type-I with incident AF were examined after adjusting for confounders.In models adjusted for age, sex and race, all biomarkers were associated with AF, but only the relationship between plasma MMP-9 remained significant in the fully-adjusted model: each one standard deviation increase in MMP-9 was associated with 27% (95% Confidence Interval: 7% to 50%) increase in risk of AF with no evidence of an interaction with race or sex. Individuals with above mean levels of MMP-9 were more likely to be male, white and current smokers.The findings suggest that elevated levels of MMP-9 are independently associated with increased risk of AF. However, given the lack of specificity of MMP-9 to atrial tissue, it remains to be determined whether the observed relationship reflects the impact of atrial fibrosis or more generalized fibrosis on risk of incident AF.

African Americans have the highest rate of mortality due to coronary heart disease (CHD). Although multiple loci have been identified influencing CHD risk in European-Americans using a genome-wide association (GWAS) approach, no GWAS of incident CHD has been reported for African Americans. We performed a GWAS for incident CHD events collected during 19 years of follow-up in 2,905 African Americans from the Atherosclerosis Risk in Communities (ARIC) study. We identified a genome-wide significant SNP (rs1859023, MAF = 31%) located at 7q21 near the PFTK1 gene (HR = 0.57, 95% CI 0.46 to 0.69, p = 1.86×10(-08)), which replicated in an independent sample of over 8,000 African American women from the Women's Health Initiative (WHI) (HR = 0.81, 95% CI 0.70 to 0.93, p = 0.005). PFTK1 encodes a serine/threonine-protein kinase, PFTAIRE-1, that acts as a cyclin-dependent kinase regulating cell cycle progression and cell proliferation. This is the first finding of incident CHD locus identified by GWAS in African Americans.

Total white blood cell (WBC) and neutrophil counts are lower among individuals of African descent due to the common African-derived "null" variant of the Duffy Antigen Receptor for Chemokines (DARC) gene. Additional common genetic polymorphisms were recently associated with total WBC and WBC sub-type levels in European and Japanese populations. No additional loci that account for WBC variability have been identified in African Americans. In order to address this, we performed a large genome-wide association study (GWAS) of total WBC and cell subtype counts in 16,388 African-American participants from 7 population-based cohorts available in the Continental Origins and Genetic Epidemiology Network. In addition to the DARC locus on chromosome 1q23, we identified two other regions (chromosomes 4q13 and 16q22) associated with WBC in African Americans (P

We report the first genome-wide association study of habitual caffeine intake. We included 47,341 individuals of European descent based on five population-based studies within the United States. In a meta-analysis adjusted for age, sex, smoking, and eigenvectors of population variation, two loci achieved genome-wide significance: 7p21 (P = 2.4 × 10(-19)), near AHR, and 15q24 (P = 5.2 × 10(-14)), between CYP1A1 and CYP1A2. Both the AHR and CYP1A2 genes are biologically plausible candidates as CYP1A2 metabolizes caffeine and AHR regulates CYP1A2.

The authors performed a case-cohort study nested within the Atherosclerosis Risk in Communities (ARIC) Study to determine the association between plasma ferritin level and risk of type 2 diabetes mellitus. Persons with incident cases of type 2 diabetes diagnosed over an average follow-up period of 7.9 years (n = 599) were compared with a random sample of the cohort (n = 690). After adjustment for age, gender, menopausal status, ethnicity, center, smoking, and alcohol intake, the hazard ratio for diabetes, comparing the fifth quintile of ferritin with the first quintile, was 1.74 (95% confidence interval: 1.14, 2.65; p-trend < 0.001). After further adjustment for body mass index and components of the metabolic syndrome, the hazard ratio was 0.81 (95% confidence interval: 0.49, 1.34; p-trend = 0.87). From a causal perspective, there are two alternative interpretations of these findings. Elevated iron stores, reflected in elevated plasma ferritin levels, may induce baseline metabolic abnormalities that ultimately result in diabetes. Alternatively, elevated ferritin may be just one of several metabolic abnormalities related to the underlying process that ultimately results in diabetes, rather than a causal factor for diabetes. Longitudinal studies with repeated measurements of glucose and iron metabolism parameters are needed to establish the role of iron stores and plasma ferritin in diabetes development. [ABSTRACT FROM AUTHOR]

The authors examined the association between lung function, as measured by forced expiratory volume in 1 second (FEV1) and forced vital capacity, and the 10-year incidence of coronary heart disease among 14,480 participants in the Atherosclerosis Risk in Communities Study (1987-1998). Separate proportional hazards models were used for FEV1 and forced vital capacity, with gender-specific lung function quartiles and lung function × gender interaction terms. An association between lung function and coronary heart disease was observed in both genders and was stronger among women. After adjustment for age, race, study center, height, height squared, smoking, and cardiovascular disease risk factors, the hazard ratios for the first (lowest), second, and third quartiles of FEV1 were 3.70 (95% confidence interval (CI): 2.19, 6.24), 2.54 (95% CI: 1.49, 4.32), and 2.25 (95% CI: 1.31, 3.87) for women and 1.51 (95% CI: 1.07, 2.13), 1.59 (95% CI: 1.15, 2.20), and 1.52 (95% CI: 1.10, 2.09) for men. After stratification by smoking status, associations were observed in each smoking group for women, while those in men were weaker and less consistent. Similar results were obtained for forced vital capacity. This analysis indicates an association between lung function and incident coronary heart disease that may be stronger in women than in men. [ABSTRACT FROM AUTHOR]