Reference values for high attenuation areas on chest CT in a healthy, never-smoker, multi-ethnic sample: The MESA study.

BACKGROUND AND OBJECTIVE: Normative values for HAA-a quantitative, CT-based measure of subclinical ILD-in healthy adults are needed to improve interpretability in clinical and research settings. METHODS: HAA was measured on full-lung CT in 3110 participants in the MESA study. Clinical prediction models were developed using a healthy never-smoker subset with normal spirometry (n = 696). RMSE on cross-validation was used as the primary criterion for model selection. Parametric and non-parametric methods were considered. z-Scores were calculated for the entire study sample. Associations between z-scores and several ILD features were estimated. RESULTS: In the healthy never-smoker subset, the mean age was 69 years with a range of 54-93 years. The median HAA was 4.3% with a range of 2.7-17.8%. Linear regression had better predictive performance than other methods. The final model included race, height, weight, age and sex. The standard error of the estimate was 1.62 with a cross-validated RMSE of 1.64 and an adjusted R2 of 0.139. z-Scores were associated with several ILD outcomes in adjusted models, including ILA (OR: 1.40 per z-unit; 95% CI: 1.30, 1.52), exertional dyspnoea (OR: 1.08 per z-unit; 95% CI: 1.02, 1.15) and FVC (expected increase per z-unit: -2.49; 95% CI: -2.95, - 2.03). CONCLUSION: We present a reference equation and z-scores to define expected values of HAA on full-lung CT to aid HAA interpretation in middle-aged and older adults.

High-Attenuation Areas on Chest Computed Tomography and Clinical Respiratory Outcomes in Community-Dwelling Adults.

RATIONALE: Areas of increased lung attenuation visualized by computed tomography are associated with all-cause mortality in the general population. It is uncertain whether this association is attributable to interstitial lung disease (ILD). OBJECTIVES: To determine whether high-attenuation areas are associated with the risk of ILD hospitalization and mortality in the general population. METHODS: We performed a cohort study of 6,808 adults aged 45-84 years sampled from six communities in the United States. High-attenuation areas were defined as the percentage of imaged lung volume with attenuation values between -600 and -250 Hounsfield units. An adjudication panel determined ILD hospitalization and death. MEASUREMENTS AND MAIN RESULTS: After adjudication, 52 participants had a diagnosis of ILD during 75,232 person-years (median, 12.2 yr) of follow-up. There were 48 hospitalizations attributable to ILD (crude rate, 6.4 per 10,000 person-years). Twenty participants died as a result of ILD (crude rate, 2.7 per 10,000 person-years). High-attenuation areas were associated with an increased rate of ILD hospitalization (adjusted hazard ratio, 2.6 per 1-SD increment in high-attenuation areas; 95% confidence interval, 1.9-3.5; P < 0.001), a finding that was stronger among men, African Americans, and Hispanics. High-attenuation areas were also associated with an increased rate of ILD-specific death (adjusted hazard ratio, 2.3; 95% confidence interval, 1.7-3.0; P < 0.001). Our findings were consistent among both smokers and nonsmokers. CONCLUSIONS: Areas of increased lung attenuation are a novel risk factor for ILD hospitalization and mortality. Measurement of high-attenuation areas by screening and diagnostic computed tomography may be warranted in at-risk adults.

Occupational risk factors for COPD phenotypes in the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study.

INTRODUCTION: The contribution of occupational exposure to the risk of chronic obstructive pulmonary disease COPD in population-based studies is of interest. We compared the performance of self-reported exposure to a newly developed JEM in exposure-response evaluation. METHODS: We used cross-sectional data from Multi-Ethnic Study of Atherosclerosis (MESA), a population-based sample of 45-84 year olds free of clinical cardiovascular disease at baseline. MESA ascertained the most recent job and employment, and the MESA Lung Study measured spirometry, and occupational exposures for 3686 participants. Associations between health outcomes (spirometry defined airflow limitation and Medical Research Council-defined chronic bronchitis) and occupational exposure [self-reported occupational exposure to vapor-gas, dust, or fumes (VGDF), severity of exposure, and a job-exposure matrix (JEM)-derived score] were evaluated using logistic regression models adjusted for non-occupational risk factors. RESULTS: The prevalence of airflow limitation was associated with self-reported exposure to vapor-gas (OR 2.6, 95%CI 1.1-2.3), severity of VGDF exposure (P-trend < 0.01), and JEM dust exposure (OR 2.4, 95%CI 1.1-5.0), and with organic dust exposure in females; these associations were generally of greater magnitude among never smokers. The prevalence of chronic bronchitis and wheeze was associated with exposure to VGDF. The association between airflow limitation and the combined effect of smoking and VGDF exposure showed an increasing trend. Self-reported vapor-gas, dust, fumes, years and severity of exposure were associated with increased prevalence of chronic bronchitis and wheeze (P < 0.001). CONCLUSIONS: Airflow limitation was associated with self-reported VGDF exposure, its severity, and JEM-ascertained dust exposure in smokers and never-smokers in this multiethnic study.

Associations of occupation, job control and job demands with intima-media thickness: the Multi-Ethnic Study of Atherosclerosis (MESA).

OBJECTIVES: Occupation has been linked to cardiovascular disease (CVD) incidence and mortality, but few studies have investigated occupation in relation to early atherosclerotic disease. This study examined associations between various occupational characteristics and carotid artery intima-media thickness (IMT) in a multi-ethnic sample. METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA) recruited 6814 adults aged 45-84 years and free of clinical CVD (response rate 60%, 51% female). Questionnaire data were used to determine occupational group (managerial/professional, sales/office, service, blue-collar), psychosocial job characteristics (ie, job demands, job control) and other sociodemographic information. RESULTS: Common carotid artery (CCA)-IMT was greater for blue-collar jobs than for management/professional jobs (mean difference = 0.012 mm, p = 0.049) after adjustment for age, sex, race, place of birth (US or foreign born) and CVD risk factors. Compared to management/professional jobs, internal carotid artery (ICA)-IMT was greater for sales/office, service and blue-collar jobs (mean difference = 0.071 mm, p < 0.001; 0.057 mm, p = 0.009; and 0.110 mm, p < 0.001, respectively) after adjustment for age, sex, race and place of birth. The difference between blue-collar jobs and management/professional jobs remained significant after additional adjustment for CVD risk factors, income and education (mean difference = 0.048 mm, p = 0.045). Higher levels of control at work were associated with thinner CCA-IMT (mean difference = -0.009 mm, p = 0.016, adjusted for age, sex, race and place of birth) but not with ICA-IMT. Job demands had no significant association with IMT. CONCLUSIONS: Blue-collar jobs and low levels of job control were associated with the development of subclinical atherosclerosis.

Fine particulate matter air pollution, proximity to traffic, and aortic atherosclerosis.

BACKGROUND: The initiation and acceleration of atherosclerosis is hypothesized as a physiologic mechanism underlying associations between air pollution and cardiovascular effects. Despite toxicologic evidence, epidemiologic data are limited. METHODS: In this cross-sectional analysis we investigated exposure to fine particulate matter (PM2.5) and residential proximity to major roads in relation to abdominal aortic calcification, a sensitive indicator of systemic atherosclerosis. Aortic calcification was measured by computed tomography among 1147 persons, in 5 US metropolitan areas, enrolled in the Multi-Ethnic Study of Atherosclerosis. The presence and quantity of aortic calcification were modeled using relative risk regression and linear regression, respectively, with adjustment for potential confounders. RESULTS: We observed a slightly elevated risk of aortic calcification (RR = 1.06; 95% confidence interval = 0.96-1.16) with a 10 microg/m contrast in PM2.5. The PM2.5-associated risk of aortic calcification was stronger among participants with long-term residence near a PM2.5 monitor (RR = 1.11; 1.00-1.24) and among participants not recently employed outside the home (RR = 1.10; 1.00-1.22). PM2.5 was not associated with an increase in the quantity of aortic calcification (Agatston score) and no roadway proximity effects were noted. There was indication of PM2.5 effect modification by lipid-lowering medication use, with greater effects among users, and PM2.5 associations were observed most consistently among Hispanics. CONCLUSIONS: Although we did not find persuasive associations across our full study population, associations were stronger among participants with less exposure misclassification. These findings support the hypothesis of a relationship between particulate air pollution and systemic atherosclerosis.

Angiotensin-Converting Inhibitors and Angiotensin II Receptor Blockers and Longitudinal Change in Percent Emphysema on Computed Tomography. The Multi-Ethnic Study of Atherosclerosis Lung Study.

RATIONALE: Although emphysema on computed tomography (CT) is associated with increased morbidity and mortality in patients with and without spirometrically defined chronic obstructive pulmonary disease, no available medications target emphysema outside of alpha-1 antitrypsin deficiency. Transforming growth factor-ß and endothelial dysfunction are implicated in emphysema pathogenesis, and angiotensin II receptor blockers (ARBs) inhibit transforming growth factor-ß, improve endothelial function, and restore airspace architecture in murine models. Evidence in humans is, however, lacking. OBJECTIVES: To determine whether angiotensin-converting enzyme (ACE) inhibitor and ARB dose is associated with slowed progression of percent emphysema by CT. METHODS: The Multi-Ethnic Study of Atherosclerosis researchers recruited participants ages 45-84 years from the general population from 2000 to 2002. Medication use was assessed by medication inventory. Percent emphysema was defined as the percentage of lung regions less than -950 Hounsfield units on CTs. Mixed-effects regression models were used to adjust for confounders. RESULTS: Among 4,472 participants, 12% used an ACE inhibitor and 6% used an ARB at baseline. The median percent emphysema was 3.0% at baseline, and the rate of progression was 0.64 percentage points over a median of 9.3 years. Higher doses of ACE or ARB were independently associated with a slower change in percent emphysema (P = 0.03). Over 10 years, in contrast to a predicted mean increase in percent emphysema of 0.66 percentage points in those who did not take ARBs or ACE inhibitors, the predicted mean increase in participants who used maximum doses of ARBs or ACE inhibitors was 0.06 percentage points (P = 0.01). The findings were of greatest magnitude among former smokers (P < 0.001). Indications for ACE inhibitor or ARB drugs (hypertension and diabetes) and other medications for hypertension and diabetes were not associated independently with change in percent emphysema. There was no evidence that ACE inhibitor or ARB dose was associated with decline in lung function. CONCLUSIONS: In a large population-based study, ACE inhibitors and ARBs were associated with slowed progression of percent emphysema by chest CT, particularly among former smokers. Randomized clinical trials of ACE and ARB agents are warranted for the prevention and treatment of emphysema.

Job Strain, Occupational Category, Systolic Blood Pressure, and Hypertension Prevalence: The Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: To assess associations of occupational categories and job characteristics with prevalent hypertension. METHODS: We analyzed 2517 Multi-Ethnic Study of Atherosclerosis participants, working 20+ hours per week, in 2002 to 2004. RESULTS: Higher job decision latitude was associated with a lower prevalence of hypertension, prevalence ratio = 0.78 (95% confidence interval 0.66 to 0.91) for the top versus bottom quartile of job decision latitude. Associations, however, differed by occupation: decision latitude was associated with a higher prevalence of hypertension in health care support occupations (interaction P = 0.02). Occupation modified associations of sex with hypertension: a higher prevalence of hypertension in women (vs men) was observed in health care support and in blue-collar occupations (interaction P = 0.03). CONCLUSIONS: Lower job decision latitude is associated with hypertension prevalence in many occupations. Further research is needed to determine reasons for differential impact of decision latitude and sex on hypertension across occupations.

Associations of work hours, job strain, and occupation with endothelial function: the Multi-Ethnic Study of Atherosclerosis (MESA).

OBJECTIVE: To investigate associations of work hours, job control, job demands, job strain, and occupational category with brachial artery flow-mediated dilation (FMD) in 1499 Multi-Ethnic Study of Atherosclerosis participants. METHODS: Flow-mediated dilation was obtained using high-resolution ultrasound. Mean values of FMD were examined across categories of occupation, work hours, and the other exposures using regression analyses. RESULTS: Occupational category was significantly associated with FMD overall, with blue-collar workers showing the lowest mean values-management/professional = 4.97 ± 0.22%; sales/office = 5.19 ± 0.28%; services = 4.73 ± 0.29%; and blue-collar workers = 4.01 ± 0.26% (adjusted P < 0.001). There was evidence of effect modification by sex (interaction P = 0.031)-significant associations were observed among women (adjusted P = 0.002) and nearly significant results among men (adjusted P = 0.087). Other exposures were not significantly associated with FMD. CONCLUSIONS: Differences in endothelial function may account for some of the variation in cardiovascular disease across occupational groups.

Factorial invariance, scale reliability, and construct validity of the job control and job demands scales for immigrant workers: the multi-ethnic study of atherosclerosis.

Immigrants have a different social context from those who stay in their home country or those who were born to the country that immigrants now live. Cultural theory of risk perception suggests that social context influences one's interpretation of questionnaire items. We examined psychometric properties of job control and job demand scales with US- and foreign-born workers who preferred English, Spanish, or Chinese (n = 3,114, mean age = 58.1). Across all groups, the job control scale had acceptable Cronbach's alpha (0.78-0.83) and equivalent factor loadings (ΔCFI < 0.01). Immigrants had low alpha (0.42-0.65) for the job demands scale regardless of language, education, or age of migration. Two job-demand items had different factor loadings across groups. Among immigrants, both scales had inconsistent associations with perceived job stress and self-rated health. For a better understanding of immigrants' job stress, the concept of job demands should be expanded and immigrants' expectations for job control explored.

Performance of American Thoracic Society-recommended spirometry reference values in a multiethnic sample of adults: the multi-ethnic study of atherosclerosis (MESA) lung study.

BACKGROUND: The American Thoracic Society recommends race-specific spirometric reference values from the National Health and Nutrition Survey (NHANES) III for clinical evaluation of pulmonary function in whites, African-Americans, and Mexican-Americans in the United States and a correction factor of 0.94 for Asian-Americans. We aimed to validate the NHANES III reference equations and the correction factor for Asian-Americans in an independent, multiethnic sample of US adults. METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA) recruited self-identified non-Hispanic white, African-American, Hispanic, and Asian-American participants aged 45 to 84 years at six US sites. The MESA-Lung Study assessed prebronchodilator spirometry among 3,893 MESA participants who performed acceptable tests, of whom 1,068 were asymptomatic healthy nonsmokers who performed acceptable spirometry. RESULTS: The 1,068 participants were mean age 65 +/- 10 years, 60% female, 25% white, 20% African-American, 23% Hispanic, and 32% Asian-American. Observed values of FEV(1), FEV(6), and FVC among whites, African-Americans, and Hispanics of Mexican origin in MESA-Lung were slightly lower than predicted values based on NHANES III. Observed values among Hispanics of non-Mexican origin were consistently lower. Agreement in classification of participants with airflow obstruction based on lower limit of normal criteria was good (overall kappa = 0.88). For Asian-Americans, a correction factor of 0.88 was more accurate than 0.94. CONCLUSIONS: The NHANES III reference equations are valid for use among older adults who are white, African-American, or Hispanic of Mexican origin. Comparison of white and Asian-American participants suggests that a correction factor of 0.88, applied to the predicted and lower limits of normal values, is more appropriate than the currently recommended value of 0.94.

Simultaneous low-density lipoprotein-C lowering and high-density lipoprotein-C elevation for optimum cardiovascular disease prevention with various drug classes, and their combinations: a meta-analysis of 23 randomized lipid trials.

PURPOSE OF REVIEW: Our analysis presents an alternative hypothesis to the prevailing view that low-density lipoprotein-C is the only important target of lipid therapy. RECENT FINDINGS: Two recently published studies showed surprising results. In the Armed Forces Regression Study, low-density lipoprotein-C was lowered only 22% with cholystyramine, niacin and gemfibrozil. Coronary stenosis regressed, however, and the primary clinical event rate was reduced by 54%. Conversely, in the FIELD trial, the primary event rate reduction was only 11% (P = NS). These differences appeared to be explained largely by the difference in high-density lipoprotein response to these regimens (38 vs. 3%). This meta-analysis of 23 trials strongly supports the notion that the sum of percent reduction in low-density lipoprotein-C plus percent increase in high-density lipoprotein-C predicts benefits much more effectively than either lipoprotein component. SUMMARY: Epidemiology suggests that the cardiovascular event rate is reduced by nearly 1% for each 1% reduction in low-density lipoprotein-C and by at least 1% for each 1% increase in high-density lipoprotein. These effects are statistically independent; thus, for moderate lipid changes, they are additive. If this simple algorithm is proven accurate, a 30% high-density lipoprotein-C increase and a 40% low-density lipoprotein-C reduction would result in a nearly 70% CHD risk reduction - and a revolution in cardiovascular prevention.