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Chunrui Zou,1,2 Frank Li,2,3 Jiwoong Choi,1,4 Babak Haghighi,5 Sanghun Choi,6 Prathish K Rajaraman,1,2 Alejandro P Comellas,7 John D Newell Jnr,8 Chang Hyun Lee,8,9 R Graham Barr,10 Eugene Bleecker,11 Christopher B Cooper,12 David Couper,13 Meilan Han,14 Nadia N Hansel,15 Richard E Kanner,16 Ella A Kazerooni,17 Eric C Kleerup,18 Fernando J Martinez,19 Wanda O’Neal,20 Robert Paine III,16 Stephen I Rennard,21 Benjamin M Smith,22,23 Prescott G Woodruff,24 Eirc A Hoffman,3,7,8 Ching-Long Lin1– 3,8 1Department of Mechanical Engineering, University of Iowa, Iowa City, IA, USA; 2IIHR-Hydroscience & Engineering, University of Iowa, Iowa City, IA, USA; 3Department of Biomedical Engineering, University of Iowa, Iowa City, IA, USA; 4Department of Internal Medicine, School of Medicine, University of Kansas, Kansas City, KS, USA; 5Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 6School of Mechanical Engineering, Kyungpook National University, Daegu, Republic of Korea; 7Department of Internal Medicine, University of Iowa, Iowa City, IA, USA; 8Department of Radiology, University of Iowa, Iowa City, IA, USA; 9Department of Radiology, College of Medicine, Seoul National University, Seoul, Republic of Korea; 10Mailman School of Public Health, Columbia University, New York, NY, USA; 11Department of Medicine, The University of Arizona, Tucson, AZ, USA; 12Department of Physiology, UCLA, Los Angeles, CA, USA; 13Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USA; 14Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; 15School of Medicine, Johns Hopkins, Baltimore, MD, USA; 16School of Medicine, University of Utah, Salt Lake City, UT, USA; 17Department of Radiology, University of Michigan, Ann Arbor, MI, USA; 18Department of Medicine, UCLA, Los Angeles, CA, USA; 19Weill Cornell Medicine, Cornell University, New York, NY, USA; 20School of Medicine, University of North Carolina, Chapel Hill, NC, USA; 21Department of Internal Medicine, University of Nebraska College of Medicine, Omaha, NE, USA; 22Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USA; 23Department of Medicine, McGill University Health Centre Research Institute, Montreal, Canada; 24Department of Medicine, University of California at San Francisco, San Francisco, CA, USACorrespondence: Ching-Long Lin 2406 Seamans Center for the Engineering Art and Science, Iowa City, IA, 52242, USATel +1 319 335 5673Email ching-long-lin@uiowa.eduPurpose: Quantitative computed tomography (qCT) imaging-based cluster analysis identified clinically meaningful COPD former-smoker subgroups (clusters) based on cross-sectional data. We aimed to identify progression clusters for former smokers using longitudinal data.Patients and Methods: We selected 472 former smokers from SPIROMICS with a baseline visit and a one-year follow-up visit. A total of 150 qCT imaging-based variables, comprising 75 variables at baseline and their corresponding progression rates, were derived from the respective inspiration and expiration scans of the two visits. The COPD progression clusters identified were then associated with subject demography, clinical variables and biomarkers.Results: COPD severities at baseline increased with increasing cluster number. Cluster 1 patients were an obese subgroup with rapid progression of functional small airway disease percentage (fSAD%) and emphysema percentage (Emph%). Cluster 2 exhibited a decrease of fSAD% and Emph%, an increase of tissue fraction at total lung capacity and airway narrowing over one year. Cluster 3 showed rapid expansion of Emph% and an attenuation of fSAD%. Cluster 4 demonstrated severe emphysema and fSAD and significant structural alterations at baseline with rapid progression of fSAD% over one year. Subjects with different progression patterns in the same cross-sectional cluster were identified by longitudinal clustering.Conclusion: qCT imaging-based metrics at two visits for former smokers allow for the derivation of four statistically stable clusters associated with unique progression patterns and clinical characteristics. Use of baseline variables and their progression rates enables identification of longitudinal clusters, resulting in a refinement of cross-sectional clusters.Keywords: computed tomography, emphysema, functional small airway disease, longitudinal clustering

Christopher B Cooper,1 Robert Paine,2 Jeffrey L Curtis,3,4 Richard E Kanner,2 Carlos H Martinez,3 Catherine A Meldrum,3 Russell Bowler,5 Wanda O’Neal,6 Eric A Hoffman,7 David Couper,6 Miguel Quibrera,6 Gerald Criner,8 Mark T Dransfield,9 MeiLan K Han,3 Nadia N Hansel,10 Jerry A Krishnan,11 Stephen C Lazarus,12 Stephen P Peters,13 R Graham Barr,14 Fernando J Martinez,15 Prescott G Woodruff12 On behalf of the SPIROMICS investigators1Departments of Medicine and Physiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA; 2Section of Pulmonary and Critical Care Medicine, Department of Veterans Affairs Medical Center, University of Utah, Salt Lake City, UT, USA; 3Pulmonary and Critical Care Medicine Division, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI, USA; 4Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI, USA; 5National Jewish Health, University of Colorado School of Medicine, Denver, CO, USA; 6University of North Carolina Marisco Lung Institute, Chapel Hill, NC, USA; 7Department of Radiology, University of Iowa, Iowa City, IA, USA; 8Department of Pulmonary and Critical Care Medicine, Temple University, Philadelphia, PA, USA; 9Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; 10Johns Hopkins University School of Medicine, Baltimore, MD, USA; 11Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA; 12Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA; 13Wake Forest School of Medicine, Winston-Salem, NC, USA; 14Department of Medicine, Columbia University Medical Center, New York, NY, USA; 15Joan and Sanford I Weill Department of Medicine, Division of Pulmonary and Critical Care Medicine, Weill Cornell Medicine, New York, NY, USACorrespondence: Christopher B CooperDepartments of Medicine and Physiology,David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Avenue, 37-131 CHS, Los Angeles, CA 90095, USAEmail ccooper@mednet.ucla.eduRationale: Some COPD patients develop extreme breathlessness, decreased exercise capacity and poor health status yet respiratory disability is poorly characterized as a distinct phenotype.Objective: To define respiratory disability in COPD based on available functional measures and to determine associations with risk for exacerbations and death.Methods: We analyzed baseline data from a multi-center observational study (SPIROMICS). This analysis includes 2332 participants (472 with severe COPD, 991 with mild/moderate COPD, 726 smokers without airflow obstruction and 143 non-smoking controls).Measurements: We defined respiratory disability by ≥ 4 of 7 criteria: mMRC dyspnea scale ≥ 3; Veterans Specific Activity Questionnaire < 5; 6-minute walking distance < 250 m; St George’s Respiratory Questionnaire activity domain > 60; COPD Assessment Test > 20; fatigue (FACIT-F Trial Outcome Index) < 50; SF-12 < 20.Results: Using these criteria, respiratory disability was identified in 315 (13.5%) participants (52.1% female). Frequencies were severe COPD 34.5%; mild-moderate COPD 11.2%; smokers without obstruction 5.2% and never-smokers 2.1%. Compared with others, participants with disability had more emphysema (13.2 vs. 6.6%) and air-trapping (37.0 vs. 21.6%) on HRCT (P< 0.0001). Using principal components analysis to derive a disability score, two factors explained 71% of variance, and a cut point − 1.0 reliably identified disability. This disability score independently predicted future exacerbations (ß=0.34; CI 0.12, 0.64; P=0.003) and death (HR 2.97; CI 1.54, 5.75; P=0.001). Thus, participants with disability by this criterion had almost three times greater mortality compared to those without disability.Conclusion: Our novel SPIROMICS respiratory disability score in COPD was associated with worse airflow obstruction as well as airway wall thickening, lung parenchymal destruction and certain inflammatory biomarkers. The disability score also proved to be an independent predictor of future exacerbations and death. These findings validate disability as an important phenotype in the spectrum of COPD.Keywords: disability, frailty, exacerbation rate, mortality, SPIROMICS

Panagis Galiatsatos,1 Han Woo,1 Laura M Paulin,2 Amy Kind,3,4 Nirupama Putcha,1 Amanda J Gassett,5 Christopher B Cooper,6 Mark T Dransfield,7 Trisha M Parekh,7 Gabriela R Oates,8 R Graham Barr,9 Alejandro P Comellas,10 Meilan K Han,11 Stephen P Peters,12 Jerry A Krishnan,13 Wassim W Labaki,11 Meredith C McCormack,1 Joel D Kaufman,14 Nadia N Hansel1 1Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 2Pulmonary and Critical Care, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA; 3University of Wisconsin School of Medicine and Public Health, Department of Medicine Health Services and Care Research Program and Division of Geriatrics, Madison, WI, USA; 4Geriatric Research Education and Clinical Center, Wm. S. Middleton Veterans Hospital, Madison, WI, USA; 5Internal Medicine, University of Washington, Seattle, WA, USA; 6Department of Medicine, University of California Los Angeles School of Medicine, Los Angeles, CA, USA; 7Department of Medicine, University of Alabama Birmingham and Birmingham Veterans Affairs Medical Center, Birmingham, AL, USA; 8Department of Medicine, University of Alabama Birmingham, Birmingham, AL, USA; 9Presbyterian Hospital, Columbia University Medical Center, New York, NY, USA; 10Internal Medicine and Pulmonary, University of Iowa, Iowa City, IA, USA; 11Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA; 12Department of Medicine, Wake Forest University Health Sciences, Winston-Salem, NC, USA; 13Department of Medicine, University of Illinois, Chicago, IL, USA; 14Office of the Dean, University of Washington School of Public Health, Seattle, WA, USACorrespondence: Panagis GaliatsatosJohns Hopkins University School of Medicine, 4940 Eastern Avenue, Asthma and Allergy Building, 4th Floor, Baltimore, MD 21224, USATel +1410 550-0522Fax +1410 550-1094Email panagis@jhmi.eduRationale: Individual socioeconomic status has been shown to influence the outcomes of patients with chronic obstructive pulmonary disease (COPD). However, contextual factors may also play a role. The objective of this study is to evaluate the association between neighborhood socioeconomic disadvantage measured by the area deprivation index (ADI) and COPD-related outcomes.Methods: Residential addresses of SubPopulations and InteRmediate Outcome Measures in COPD Study (SPIROMICS) subjects with COPD (FEV1/FVC < 0.70) at baseline were geocoded and linked to their respective ADI national ranking score at the census block group level. The associations between the ADI and COPD-related outcomes were evaluated by examining the contrast between participants living in the most-disadvantaged (top quintile) to the least-disadvantaged (bottom quintile) neighborhood. Regression models included adjustment for individual-level demographics, socioeconomic variables (personal income, education), exposures (smoking status, packs per year, occupational exposures), clinical characteristics (FEV1% predicted, body mass index) and neighborhood rural status.Results: A total of 1800 participants were included in the analysis. Participants residing in the most-disadvantaged neighborhoods had 56% higher rate of COPD exacerbation (P< 0.001), 98% higher rate of severe COPD exacerbation (P=0.001), a 1.6 point higher CAT score (P< 0.001), 3.1 points higher SGRQ (P< 0.001), and 24.6 meters less six-minute walk distance (P=0.008) compared with participants who resided in the least disadvantaged neighborhoods.Conclusion: Participants with COPD who reside in more-disadvantaged neighborhoods had worse COPD outcomes compared to those residing in less-disadvantaged neighborhoods. Neighborhood effects were independent of individual-level socioeconomic factors, suggesting that contextual factors could be used to inform intervention strategies targeting high-risk persons with COPD.Keywords: health disparities, COPD, area deprivation index

BackgroundPulmonary endothelial damage has been shown to precede the development of emphysema in animals, and vascular changes in humans have been observed in COPD and emphysema.Research questionIs intraparenchymal vascular pruning associated with longitudinal progression of emphysema on CT imaging or decline in lung function over 5 years?Study design and methodsThe Genetic Epidemiology of COPD Study enrolled ever smokers with and without COPD from 2008 through 2011. The percentage of emphysema-like lung, or "percent emphysema," was assessed at baseline and after 5 years on noncontrast CT imaging as the percentage of lung voxels < -950 Hounsfield units. An automated CT imaging-based tool assessed and classified intrapulmonary arteries and veins. Spirometry measures are postbronchodilator. Pulmonary arterial pruning was defined as a lower ratio of small artery volume (< 5 mm2 cross-sectional area) to total lung artery volume. Mixed linear models included demographics, anthropomorphics, smoking, and COPD, with emphysema models also adjusting for CT imaging scanner and lung function models adjusting for clinical center and baseline percent emphysema.ResultsAt baseline, the 4,227 participants were 60 ± 9 years of age, 50% were women, 28% were Black, 47% were current smokers, and 41% had COPD. Median percent emphysema was 2.1 (interquartile range, 0.6-6.3) and progressed 0.24 percentage points/y (95% CI, 0.22-0.26 percentage points/y) over 5.6 years. Mean FEV1 to FVC ratio was 68.5 ± 14.2% and declined 0.26%/y (95% CI, -0.30 to -0.23%/y). Greater pulmonary arterial pruning was associated with more rapid progression of percent emphysema (0.11 percentage points/y per 1-SD increase in arterial pruning; 95% CI, 0.09-0.16 percentage points/y), including after adjusting for baseline percent emphysema and FEV1. Arterial pruning also was associated with a faster decline in FEV1 to FVC ratio (-0.04%/y per 1-SD increase in arterial pruning; 95% CI, -0.008 to -0.001%/y).InterpretationPulmonary arterial pruning was associated with faster progression of percent emphysema and more rapid decline in FEV1 to FVC ratio over 5 years in ever smokers, suggesting that pulmonary vascular differences may be relevant in disease progression.Trial registryClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov.

Background: As a part of the longitudinal Chronic Obstructive Pulmonary Disease (COPD) study, Subpopulations and Intermediate Outcome Measures in COPD study (SPIROMICS), blood samples are being collected from 3200 subjects with the goal of identifying bloo

A parallel physiological pathway for elastic changes is hypothesized for declines in arterial elasticity and lung function. Endothelial dysfunction and inflammation could potentially decrease elasticity of both vasculature and lung tissue. We examined biomarkers, large arterial elasticity and small arterial elasticity (SAE), and forced vital capacity (FVC) in a period cross-sectional design in the multiethnic study of atherosclerosis, which recruited 1823 women and 1803 men, age range 45 to 84 years, black, white, Hispanic, and Chinese, free of clinically recognized cardiovascular disease. Radial artery tonometric pulse waveform registration was performed and large arterial elasticity and SAE were derived from diastole. Spirometric data and markers of endothelial dysfunction and inflammation (soluble intracellular adhesion molecule-1, fibrinogen, hs-C-reactive protein, and interleukin-6) were obtained. Mean large arterial elasticity was 13.7 ± 5.5 mL/mm Hg × 10 and SAE was 4.6 ± 2.6 mL/mm Hg × 100. Mean FVC was 3192 ± 956.0 mL and forced expiratory volume in 1 second was 2386 ± 734.5 mL. FVC was about 40 ± 5 mL higher per SD of SAE, stronger in men than women. The association was slightly weaker with large arterial elasticity, with no sex interaction. After regression adjustment for demographic, anthropometric, and cardiovascular risk factors, the biomarkers tended to be related to reduced SAE and FVC, particularly in men. These biomarker associations suggest important cardiovascular disease risk alterations that occur concurrently with lower arterial elasticity and lung function. The observed positive association of SAE with FVC and with forced expiratory volume in 1 second in middle-aged to older free-living people is consistent with the hypothesis of parallel physiological pathways for elastic changes in the vasculature and in lung parenchymal tissue. [ABSTRACT FROM AUTHOR]

Background: Endothelial dysfunction is associated with left ventricular morphology and long-term cardiovascular outcomes. The purpose of this study was to assess the relationship between both baseline brachial artery diameter and peripheral endothelial function (assessed by brachial artery ultrasonography) and right ventricular (RV) mass, RV end-diastolic volume (RVEDV), and RV ejection fraction (RVEF).Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac MRI and brachial artery ultrasonography on participants without clinical cardiovascular disease. Baseline brachial artery diameter and flow-mediated dilation were assessed.Results: The mean age was 60.9 years, and 49.4% of subjects were men (n = 2,425). In adjusted models, larger brachial artery diameter was strongly associated with greater RV mass (β = 0.55 g, P < .001), larger RVEDV (β = 3.99 mL, P < .001), and decreased RVEF (β = -0.46%, P = .03). These relationships persisted after further adjustment for the respective left ventricular parameters. Flow-mediated dilation was not associated with RV mass or RVEF and was only weakly associated with RVEDV.Conclusions: Brachial artery diameter is associated with greater RV mass and RVEDV, as well as lower RVEF. Changes in the systemic arterial circulation may have pathophysiologic links to pulmonary vascular dysfunction or abnormalities in RV perfusion. [ABSTRACT FROM AUTHOR]

Background: Changes in right ventricular (RV) morphology are associated with morbidity and mortality in heart and lung disease. We examined the association of abnormal RV structure and function with the risk of heart failure or cardiovascular death in a population-based multiethnic sample free of clinical cardiovascular disease at baseline.Methods and Results: The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac magnetic resonance imaging on 5098 participants between 2000 and 2002 with follow-up for incident heart failure and cardiovascular death ("death") until January 2008. RV volumes and mass were available for 4204 participants. The study sample (n=4144) was 61.4±10.1 years old and 47.6% male. The presence of RV hypertrophy (increased RV mass) was associated with more than twice the risk of heart failure or death after adjustment for demographics, body mass index, education, C-reactive protein level, hypertension, and smoking status (hazard ratio, 2.52; 95% confidence interval, 1.55-4.10; P<0.001) and a doubling (or more) of risk with left ventricular mass at the mean value or lower (P for interaction=0.05).Conclusions: RV hypertrophy was associated with the risk of heart failure or death in a multiethnic population free of clinical cardiovascular disease at baseline. [ABSTRACT FROM AUTHOR]

Context: Annual ultrasound screening may detect small, node-negative breast cancers that are not seen on mammography. Magnetic resonance imaging (MRI) may reveal additional breast cancers missed by both mammography and ultrasound screening.Objective: To determine supplemental cancer detection yield of ultrasound and MRI in women at elevated risk for breast cancer.Design, Setting, and Participants: From April 2004-February 2006, 2809 women at 21 sites with elevated cancer risk and dense breasts consented to 3 annual independent screens with mammography and ultrasound in randomized order. After 3 rounds of both screenings, 612 of 703 women who chose to undergo an MRI had complete data. The reference standard was defined as a combination of pathology (biopsy results that showed in situ or infiltrating ductal carcinoma or infiltrating lobular carcinoma in the breast or axillary lymph nodes) and 12-month follow-up.Main Outcome Measures: Cancer detection rate (yield), sensitivity, specificity, positive predictive value (PPV3) of biopsies performed and interval cancer rate.Results: A total of 2662 women underwent 7473 mammogram and ultrasound screenings, 110 of whom had 111 breast cancer events: 33 detected by mammography only, 32 by ultrasound only, 26 by both, and 9 by MRI after mammography plus ultrasound; 11 were not detected by any imaging screen. Among 4814 incidence screens in the second and third years combined, 75 women were diagnosed with cancer. Supplemental incidence-screening ultrasound identified 3.7 cancers per 1000 screens (95% CI, 2.1-5.8; P < .001). Sensitivity for mammography plus ultrasound was 0.76 (95% CI, 0.65-0.85); specificity, 0.84 (95% CI, 0.83-0.85); and PPV3, 0.16 (95% CI, 0.12-0.21). For mammography alone, sensitivity was 0.52 (95% CI, 0.40-0.64); specificity, 0.91 (95% CI, 0.90-0.92); and PPV3, 0.38 (95% CI, 0.28-0.49; P < .001 all comparisons). Of the MRI participants, 16 women (2.6%) had breast cancer diagnosed. The supplemental yield of MRI was 14.7 per 1000 (95% CI, 3.5-25.9; P = .004). Sensitivity for MRI and mammography plus ultrasound was 1.00 (95% CI, 0.79-1.00); specificity, 0.65 (95% CI, 0.61-0.69); and PPV3, 0.19 (95% CI, 0.11-0.29). For mammography and ultrasound, sensitivity was 0.44 (95% CI, 0.20-0.70, P = .004); specificity 0.84 (95% CI, 0.81-0.87; P < .001); and PPV3, 0.18 (95% CI, 0.08 to 0.34; P = .98). The number of screens needed to detect 1 cancer was 127 (95% CI, 99-167) for mammography; 234 (95% CI, 173-345) for supplemental ultrasound; and 68 (95% CI, 39-286) for MRI after negative mammography and ultrasound results.Conclusion: The addition of screening ultrasound or MRI to mammography in women at increased risk of breast cancer resulted in not only a higher cancer detection yield but also an increase in false-positive findings.Trial Registration: clinicaltrials.gov Identifier: NCT00072501. [ABSTRACT FROM AUTHOR]

Lung function studies in middle-aged subjects predict cardiovascular disease mortality. We studied whether greater loss of forced vital capacity (FVC) early in life predicted incident hypertension. The sample was 3205 black and white men and women in the Coronary Artery Risk Development in Young Adults Study examined between 1985 and 1986 (Coronary Artery Risk Development in Young Adults year 0, ages 18-30 years) and 2005-2006 and who were not hypertensive by year 10. FVC was assessed at years 0, 2, 5, 10, and 20. Proportional hazard ratios and linear regression models predicted incident hypertension at years 15 or 20 (n=508) from the change in FVC (FVC at year 10 - peak FVC, where peak FVC was estimated as the maximum across years 0, 2, 5, and 10). Covariates included demographics, center, systolic blood pressure, FVC maximum, smoking, physical activity, asthma, and body mass index. Unadjusted cumulative incident hypertension was 25% in the lowest FVC loss quartile (Q1; median loss: 370 mL) compared with 12% cumulative incident hypertension in those who achieved peak FVC at year 10 (Q4). Minimally adjusted hazard ratio for Q1 versus Q4 was 2.21 (95% CI: 1.73-2.83), and this association remained significant in the fully adjusted model (1.37; 95% CI: 1.05-1.80). Decline in FVC from average age at peak (29.4 years) to 35 years old predicted incident hypertension between average ages 35 and 45 years. The findings may represent a common pathway that may link low normal FVC to cardiovascular disease morbidity and mortality. [ABSTRACT FROM AUTHOR]

Background: The relationship between obesity and right ventricular (RV) morphology is not well studied. We aimed to determine the association between obesity and RV structure and function in a large multiethnic population-based cohort.Methods: The MESA-Right Ventricle Study measured RV mass and volumes by cardiac MRI in participants aged 45 to 84 years without clinical cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis (MESA). Participants were divided into three categories based on BMI: lean ( ≤ 24.9 kg/m(2)), overweight (25-29.9 kg/m(2)), and obese ( ≥ 30 kg/m(2)).Results: The study sample included 4,127 participants. After adjustment for demographics, height, education, and cardiovascular risk factors, overweight and obese participants had greater RV mass (6% and 9% greater, respectively), larger RV end-diastolic volume (8% and 18% greater, respectively), larger RV stroke volume (7% and 16% greater, respectively), and lower RV ejection fraction ( ≥ 1% lower) than lean participants (all P < .001). These findings persisted after adjusting for the respective left ventricular (LV) parameters.Conclusions: Overweight and obesity were independently associated with differences in RV morphology even after adjustment for the respective LV measure. This association could be explained by increased RV afterload, increased blood volume, hormonal effects, or direct obesity-related myocardial effects. [ABSTRACT FROM AUTHOR]

Objective: While metabolic syndrome (MetS) and diabetes confer greater cardiovascular disease (CVD) risk, recent evidence suggests that individuals with these conditions have a wide range of risk. We evaluated whether screening for coronary artery calcium (CAC) and carotid intimal-medial thickness (CIMT) can improve CVD risk stratification over traditional risk factors (RFs) in people with MetS and diabetes.Research Design and Methods: We assessed CAC and CIMT in 6,603 people aged 45-84 years in the Multi-Ethnic Study of Atherosclerosis (MESA). Cox regression examined the association of CAC and CIMT with coronary heart disease (CHD) and CVD over 6.4 years in MetS and diabetes.Results: Of the subjects, 1,686 (25%) had MetS but no diabetes and 881 (13%) had diabetes. Annual CHD event rates were 1.0% among MetS and 1.5% for diabetes. Ethnicity and RF-adjusted hazard ratios for CHD for CAC 1-99 to ≥400 vs. 0 in subjects with neither MetS nor diabetes ranged from 2.6 to 9.5; in those with MetS, they ranged from 3.9 to 11.9; and in those with diabetes, they ranged from 2.9 to 6.2 (all P < 0.05 to P < 0.001). Findings were similar for CVD. CAC increased the C-statistic for events (P < 0.001) over RFs and CIMT in each group while CIMT added negligibly to prediction over RFs.Conclusions: Individuals with MetS or diabetes have low risks for CHD when CAC or CIMT is not increased. Prediction of CHD and CVD events is improved by CAC more than by CIMT. Screening for CAC or CIMT can stratify risk in people with MetS and diabetes and support the latest recommendations regarding CAC screening in those with diabetes. [ABSTRACT FROM AUTHOR]

Background: Dysfunction of the interventricular septum has been implicated in right ventricular (RV) failure. However, little is known about the relationship between ventricular septal and RV function in patients without clinical cardiovascular disease. We hypothesized that better septal function would be associated with higher RV ejection fraction and lower RV mass and volume by cardiac MRI.Methods: In the Multi-Ethnic Study of Atherosclerosis (MESA), cardiac MRI was performed on community-based participants without clinical cardiovascular disease. Images were analyzed by the harmonic phase method to measure peak circumferential systolic midventricular strain for each wall (anterior, lateral, inferior, and septal). Multivariable linear regression and generalized additive models were used to assess the relationship between septal strain and RV morphology.Results: There were 917 participants (45.7% women) with a mean age of 65.7 years. Better septal function was associated with higher RV ejection fraction in a nonlinear fashion after adjustment for all covariates (P = .03). There appeared to be a threshold effect for the contribution of septal strain to RV systolic function, with an almost linear decrement in RV ejection fraction with septal strain from -18% to -10%. Septal function was not related to RV mass or volume.Conclusions: Interventricular septal function was linked to RV systolic function independent of other left ventricular regions, even in individuals without clinical cardiovascular disease. This finding confirms animal and human research suggesting the importance of septal function to the right ventricle and implies that changes in septal function could herald RV dysfunction.Trial Registry: ClinicalTrials.gov; No.: NCT00005487; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Rationale: Sex hormones have effects on the left ventricle, but hormonal influences on the right ventricle (RV) are unknown.Objectives: We hypothesized that sex hormones would be associated with RV morphology in a large cohort free of cardiovascular disease.Methods: Sex hormones were measured by immunoassay and RV ejection fraction (RVEF), stroke volume (RVSV), mass, end-diastolic volume, and end-systolic volume (RVESV) were measured by cardiac magnetic resonance imaging in 1,957 men and 1,738 postmenopausal women. The relationship between each hormone and RV parameter was assessed by multivariate linear regression.Measurements and Main Results: Higher estradiol levels were associated with higher RVEF (β per 1 ln[nmol/L], 0.88; 95% confidence interval [CI], 0.32 to 1.43; P = 0.002) and lower RVESV (β per 1 ln[nmol/L], -0.87; 95% CI, -1.67 to -0.08; P = 0.03) in women using hormone therapy. In men, higher bioavailable testosterone levels were associated with higher RVSV (β per 1 ln[nmol/L], 1.97; 95% CI, 0.20 to 3.73; P = 0.03) and greater RV mass and volumes (P ≤ 0.01). Higher dehydroepiandrosterone levels were associated with higher RVSV (β per 1 ln[nmol/L], 1.37; 95% CI, 0.15 to 2.59; P = 0.03) and greater RV mass (β per 1 ln[nmol/L], 0.25; 95% CI, 0.00 to 0.49; P = 0.05) and volumes (P ≤ 0.001) in women.Conclusions: Higher estradiol levels were associated with better RV systolic function in women using hormone therapy. Higher levels of androgens were associated with greater RV mass and volumes in both sexes. [ABSTRACT FROM AUTHOR]

Rationale: Intense exercise in elite athletes is associated with increased left ventricular (LV) and right ventricular (RV) mass and volumes. However, the effect of physical activity on the RV in an older community-based population is unknown.Objectives: We studied the association between levels of physical activity in adults and RV mass and volumes.Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac magnetic resonance imaging on community-based participants without clinical cardiovascular disease. RV volumes were determined from manually contoured endocardial margins. RV mass was determined from the difference between epicardial and endocardial volumes multiplied by the specific gravity of myocardium. Metabolic equivalent-minutes/day were calculated from the self-reported frequency, duration, and intensity of physical activity.Measurements and Main Results: The study sample (n = 1,867) was aged 61.8 ± 10 years, 48% male, 44% white, 27% African American, 20% Hispanic, and 9% Chinese. Higher levels of moderate and vigorous physical activity were linearly associated with higher RV mass (P = 0.02) after adjusting for demographics, anthropometrics, smoking, cholesterol, diabetes mellitus, hypertension, and LV mass. Higher levels of intentional exercise (physical activity done for the sole purpose of conditioning or fitness) were nonlinearly associated with RV mass independent of LV mass (P = 0.03). There were similar associations between higher levels of physical activity and larger RV volumes.Conclusions: Higher levels of physical activity in adults were associated with greater RV mass independent of the associations with LV mass; similar results were found for RV volumes. Exercise-associated RV remodeling may have important clinical implications. [ABSTRACT FROM AUTHOR]

Objective: Many studies have documented associations between inflammation and type 2 diabetes incidence. We assessed potential variability in this association in the major U.S. racial/ethnic groups.Research Design and Methods: Incident type 2 diabetes was assessed among men and women aged 45-84 years without prior clinical cardiovascular disease or diabetes in the prospective Multi-Ethnic Study of Atherosclerosis. Interleukin (IL)-6, fibrinogen, and C-reactive protein (CRP) were measured at baseline (2000-2002); fasting glucose and diabetes medication use was assessed at baseline and three subsequent in-person exams through 2007. Type 2 diabetes was defined as use of diabetes drugs or glucose > or =126 mg/dl. Covariates included baseline demographics, clinic, smoking, alcohol, exercise, hypertension medication, systolic blood pressure, insulin resistance, and BMI. Cox proportional hazards regression was used to calculate hazard ratios (HRs) by quartiles of CRP, IL-6, and fibrinogen.Results: Among 5,571 participants (mean age 61.6 years, 53% female, 42.1% white, 11.5% Chinese, 25.7% black, and 20.7% Hispanic), 410 developed incident diabetes during a median follow-up time of 4.7 years (incidence 16.8 per 1,000 person-years). CRP, IL-6, and fibrinogen levels were associated with incident diabetes in the entire sample. After adjustment, the associations were attenuated; however, quartile 4 (versus quartile 1) of IL-6 (HR 1.5 [95% CI 1.1-2.2]) and CRP (1.7 [1.3-2.4]) remained associated with incident diabetes. In stratified analyses, similar associations were observed among white, black, and Hispanic participants.Conclusions: Higher levels of inflammation predict short-term incidence of type 2 diabetes in a multiethnic American sample. [ABSTRACT FROM AUTHOR]