Urinary Metal Levels and Coronary Artery Calcification: Longitudinal Evidence in the Multi-Ethnic Study of Atherosclerosis (MESA).

Objective: Growing evidence indicates that exposure to metals are risk factors for cardiovascular disease (CVD). We hypothesized that higher urinary levels of metals with prior evidence of an association with CVD, including non-essential (cadmium , tungsten, and uranium) and essential (cobalt, copper, and zinc) metals are associated with baseline and rate of change of coronary artery calcium (CAC) progression, a subclinical marker of atherosclerotic CVD. Methods: We analyzed data from 6,418 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) with spot urinary metal levels at baseline (2000-2002) and 1-4 repeated measures of spatially weighted coronary calcium score (SWCS) over a ten-year period. SWCS is a unitless measure of CAC highly correlated to the Agatston score but with numerical values assigned to individuals with Agatston score=0. We used linear mixed effect models to assess the association of baseline urinary metal levels with baseline SWCS, annual change in SWCS, and SWCS over ten years of follow-up. Urinary metals (adjusted to µg/g creatinine) and SWCS were log transformed. Models were progressively adjusted for baseline sociodemographic factors, estimated glomerular filtration rate, lifestyle factors, and clinical factors. Results: At baseline, the median and interquartile range (25th, 75th) of SWCS was 6.3 (0.7, 58.2). For urinary cadmium, the fully adjusted geometric mean ratio (GMR) (95%Cl) of SWCS comparing the highest to the lowest quartile was 1.51 (1.32, 1.74) at baseline and 1.75 (1.47, 2.07) at ten years of follow-up. For urinary tungsten, uranium, and cobalt the corresponding GMRs at ten years of follow-up were 1.45 (1.23, 1.71), 1.39 (1.17, 1.64), and 1.47 (1.25, 1.74), respectively. For copper and zinc, the association was attenuated with adjustment for clinical risk factors; GMRs at ten years of follow-up before and after adjustment for clinical risk factors were 1.55 (1.30, 1.84) and 1.33 (1.12, 1.58), respectively, for copper and 1.85 (1.56, 2.19) and 1.57 (1.33, 1.85) for zinc. Conclusion: Higher levels of cadmium, tungsten, uranium, cobalt, copper, and zinc, as measured in urine, were associated with subclinical CVD at baseline and at follow-up. These findings support the hypothesis that metals are pro-atherogenic factors.

Aortic Arch Calcification in Ungated Lung Computed Tomography Scans as Predictors of Atherosclerotic Cardiovascular Disease: Methodology and Reproducibility in a Multi-Ethnic Study of Atherosclerosis.

Background: Aortic arch calcium (AAC), which is frequently detected on ungated lung computed tomography (CT) due to a large field of view, can serve as a marker of subclinical atherosclerotic burden. Our study sought to validate novel cardiac screening metrics of subclinical atherosclerosis by evaluating the inter- and intra-observer reproducibility of AAC measurements with ungated lung CT. Methods: The authors randomly selected 100 ungated lung CT scans from the Multi-Ethnic Study of Atherosclerosis cohort. A Bland-Altman plot analysis was used to test inter- and intra-reader reproducibility, after measuring the total arch calcium score and arch calcium volume. Results: The intra-reader reproducibility for the total arch calcium score and arch calcium volume in all subjects was excellent at 99% and 97%, respectively. The inter-reader reproducibility for the total arch calcium score and volume in all subjects was similarly excellent at 97% and 96%, respectively. Conclusions: The high reproducibility of ungated lung CT suggests a potential new method of stratifying the atherosclerotic cardiovascular disease risk among patients undergoing lung CT without requiring additional scanning. This methodology helps promote routine reporting of AAC and coronary artery calcium based on millions of ungated CT images acquired for lung screening purposes.

Association of Quantified Costal Cartilage Calcification and Long-Term Cumulative Blood Glucose Exposure: The Multi-Ethnic Study of Atherosclerosis.

Aims: Anecdotal reports have suggested increased soft tissue calcification in individuals with long-term exposures to high blood glucose. The association of costal cartilage calcification (CCC), a reliably quantifiable marker obtainable from non-contrast cardiac computed tomography (CT) with cumulative fasting blood glucose (FBG) exposure, is unknown. In this study, we aimed to determine the association between quantified CCC and cumulative glucose exposure using non-contrast coronary artery calcium (CAC) scoring computed tomography (CT) images in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods: The volume of bilateral CCC was quantified in high-density pixels (threshold of Hounsfield Unit>180) using the CAC scoring CT images acquired in the 5th MESA exam. Prior long-term cumulative exposure to FBG was calculated by area under the FBG-time curve over ten years before the time of the CT exam. Results: A total of 2,305 participants (mean age: 69, female/male: 1.3) were included in this study. The median CCC volume was lower in females than males (1158 mm3 [IQR: 1751] vs. 3054 mm3 [3851], p<0.001). In cross-sectional analysis, quantified CCC was associated with FBG (9% increase per SD) and HbA1c (7% increase per SD) at the CT exam only in female participants after adjustment for age, race, BMI, and glomerular filtration rate. Only in female participants, quantified CCC was also associated with prior cumulative FBG (3% increase per decile change). In the subgroup of females with zero CAC scores, the adjusted CCC was still associated with FBG (13% increase per SD) at the time of CT exam and with prior cumulative FBG exposure (4% increase per decile change) before the CT exam. Conclusions: The CCC, a reliably quantified marker in non-contrast cardiac CT, is associated with 10-year cumulative FBG exposure only in female participants, even those with zero CAC.

The influence of social support on COPD outcomes mediated by depression.

BACKGROUND: The 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. METHODS: Subjects 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. RESULTS: Of 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. CONCLUSION: Higher 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 REGISTRATION: SPIROMICS was approved by Institutional Review Boards at each center and all participants provided written informed consent (clinicaltrials.gov: NCT01969344).

The relationship between smoking intensity and subclinical cardiovascular injury: The Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND AND AIMS: Modern tobacco regulatory science requires an understanding of which biomarkers of cardiovascular injury are most sensitive to cigarette smoking exposure. METHODS: We studied self-reported current smokers from the Multi-Ethnic Study of Atherosclerosis. Smoking intensity was defined by number of cigarettes/day and urinary cotinine levels. Subclinical cardiovascular injury was assessed using markers of inflammation [high-sensitivity C-reactive protein (hsCRP), interleukin 6 & 2 (IL-2 & IL-6), tumor necrosis factor alpha (TNF-α)], thrombosis (fibrinogen, D-dimer, homocysteine), myocardial injury (troponin T; TnT), endothelial damage (albumin: creatinine ratio), and vascular function [aortic & carotid distensibility, flow-mediated dilation (FMD)]. Biomarkers were modeled as absolute and percent change using multivariable-adjusted linear regression models adjusted for cardiovascular risk factors and smoking duration. RESULTS: Among 843 current smokers, mean age was 58 (9) years, 53% were men, 39% were African American, mean number of cigarettes per day was 13 (10), and median smoking duration was 39 (15) years. Cigarette count was significantly associated with higher hsCRP, IL-6 and fibrinogen (ß coefficients: 0.013, 0.011, 0.60 respectively), while ln-transformed cotinine was associated with the same biomarkers (ß coefficients: 0.12, 0.04, 5.3 respectively) and inversely associated with aortic distensibility (ß coefficient: -0.13). There was a limited association between smoking intensity and homocysteine, D-dimer, and albumin:creatinine ratio in partially adjusted models only, while there was no association with IL-2, TNF-α, carotid distensibility, FMD, or TnT in any model. In percent change analyses, relationships were strongest with hsCRP. CONCLUSIONS: Smoking intensity was associated with early biomarkers of CVD, particularly, markers of systemic inflammation. Of these, hsCRP may be the most sensitive.

Disability and recovery of independent function in obstructive lung disease: the cardiovascular health study.

BACKGROUND: Chronic obstructive lung disease frequently leads to disability. Older patients may experience transitions between states of disability and independence over time. OBJECTIVE: To identify factors associated with transition between states of disability and independent function in obstructive lung disease. METHODS: We analyzed data on 4,394 participants in the Cardiovascular Health Study who completed prebronchodilator spirometry. We calculated the 1-year probability of developing and resolving impairment in ≥1 instrumental activity of daily living (IADL) or ≥1 activity of daily living (ADL) using transition probability analysis. We identified factors associated with resolving disability using relative risk (RR) regression. RESULTS: The prevalence of IADL impairment was higher with moderate (23.9%) and severe (36.9%) airflow obstruction compared to normal spirometry (22.5%; p < 0.001). Among participants with severe airflow obstruction, 23.5% recovered independence in IADLs and 40.5% recovered independence in ADLs. In the adjusted analyses, airflow obstruction predicted the development of IADL, but not ADL impairment. Participants with severe airflow obstruction were less likely to resolve IADL impairment [RR 0.67 and 95% confidence interval (CI) 0.49-0.94]. Compared to the most active individuals (i.e. who walked ≥28 blocks per week), walking less was associated with a decreased likelihood of resolving IADL impairment (7-27 blocks: RR 0.81 and 95% CI 0.69-0.86 and <7 blocks: RR 0.73 and 95% CI 0.61-0.86). Increased strength (RR 1.16 and 95% CI 1.05-1.29) was associated with resolving IADL impairment. CONCLUSIONS: Disability is common in older people, especially in those with severe airflow obstruction. Increased physical activity and muscle strength are associated with recovery. Research is needed on interventions to improve these factors among patients with obstructive lung disease and disability.

Unregulated gambling in South African townships: a policy conundrum?

This study was designed to explore the nature of informal or illegal gambling in South African townships, to investigate what motivates people to participate in this form of gambling and what they perceive are the associated benefits and dis-benefits. A series of focus group workshops was conducted with two groups of gamblers, all of whom had experience of some form of township gambling: one group currently lived in townships and the other had previously resided in townships. Gambling for the township residents was a far more frequent activity than for non-township residents and consumed substantially more of their time. The majority of the township residents classified themselves as unemployed, while of those who were unemployed, most people indicated that gambling was a major source of their income; some even described it as their only source of income. The most significant difference between what township and non-township residents expressed as wanting and getting from gambling was that the former indicated quite clearly and unanimously that what they sought and gained from gambling was money. Township residents were far more likely to indicate that they used gambling to balance their budgets than ex-township residents who gambled primarily at casinos. A lottery type game called "Fahfee" is the most widely spread and pervasive form of gambling and was unanimously portrayed as a necessary and beneficial form of support for the poor and unemployed. Lottery and Casino gambling were, in contrast, widely perceived by the township participants as being 'rigged' and unfair. Township Dice and cards were perceived as being 'fairer' and as allowing punters to be more in control than casino gambling. The downside of township gambling was reported to be high levels of violence, crime and insecurity surrounding, in particular, the game of Dice. There was widespread inability to calculate expected payoffs or odds, and an apparent belief that these were not particularly helpful skills for gamblers. In Fahfee, the reliance on dreams to guide choice of numbers appears to eradicate any interest in the odds, or of playing strategically. The findings of this study are preliminary but have serious policy implications for education and for gambling regulation in South Africa.

Heritability estimates of endophenotypes of long and health life: the Long Life Family Study.

BACKGROUND: Identification of gene variants that contribute to exceptional survival may provide critical biologic information that informs optimal health across the life span. METHODS: As part of phenotype development efforts for the Long Life Family Study, endophenotypes that represent exceptional survival were identified and heritability estimates were calculated. Principal components (PCs) analysis was carried out using 28 physiologic measurements from five trait domains (cardiovascular, cognition, physical function, pulmonary, and metabolic). RESULTS: The five most dominant PCs accounted for 50% of underlying trait variance. The first PC (PC1), which consisted primarily of poor pulmonary and physical function, represented 14.3% of the total variance and had an estimated heritability of 39%. PC2 consisted of measures of good metabolic and cardiovascular function with an estimated heritability of 27%. PC3 was made up of cognitive measures (h(2) = 36%). PC4 and PC5 contained measures of blood pressure and cholesterol, respectively (h(2) = 25% and 16%). CONCLUSIONS: These PCs analysis-derived endophenotypes may be used in genetic association studies to help identify underlying genetic mechanisms that drive exceptional survival in this and other populations.

Emphysema, airflow limitation, and early age-related macular degeneration.

OBJECTIVE: To describe the associations of lung function and emphysema, measured with spirometry and computed tomography (CT), with early age-related macular degeneration (AMD) in a sample of white, black, Hispanic, and Chinese subjects. METHODS: Three thousand three hundred ninety-nine persons aged 45 to 84 years residing in 6 US communities participated in a period cross-sectional study. Age-related macular degeneration was measured from digital retinal photographs at the second Multi-Ethnic Study of Atherosclerosis (MESA) examination. Forced expiratory volume in 1 second (FEV(1)) and FEV(1) to forced vital capacity (FVC) ratio were measured at the third or fourth MESA examination. Percent emphysema was measured from cardiac CT scans at baseline. Apical and basilar lung segments were defined as the cephalad or caudal regions of the lung on the cardiac CT scan. Logistic regression models were used to examine the association of lung function and structure with AMD, controlling for age, sex, and other factors. RESULTS: The prevalence of early AMD was 3.7%. Early AMD was not associated with FEV(1) (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.58-1.15; P = .25), FEV(1):FVC ratio (OR, 0.92; 95% CI, 0.76-1.12; P = .43), percent emphysema (OR, 1.13; 95% CI, 0.91-1.40; P = .26), and apical-basilar difference in percent emphysema (OR, 1.14; 95% CI, 0.95-1.37; P = .17). Associations were stronger in smokers. Apical-basilar difference in percent emphysema was significantly associated with early AMD among those who ever smoked (OR, 1.28; 95% CI, 1.02-1.60; P = .03). Associations were not modified by race/ethnicity. CONCLUSIONS: Lung function and emphysema on CT scan were not cross-sectionally associated with AMD; this might be explained by the relatively low smoking exposure in this cohort.

Impact of DOTS expansion on tuberculosis related outcomes and costs in Haiti.

BACKGROUND: Implementation of the World Health Organization's DOTS strategy (Directly Observed Treatment Short-course therapy) can result in significant reduction in tuberculosis incidence. We estimated potential costs and benefits of DOTS expansion in Haiti from the government, and societal perspectives. METHODS: Using decision analysis incorporating multiple Markov processes (Markov modelling), we compared expected tuberculosis morbidity, mortality and costs in Haiti with DOTS expansion to reach all of the country, and achieve WHO benchmarks, or if the current situation did not change. Probabilities of tuberculosis related outcomes were derived from the published literature. Government health expenditures, patient and family costs were measured in direct surveys in Haiti and expressed in 2003 US$. RESULTS: Starting in 2003, DOTS expansion in Haiti is anticipated to cost $4.2 million and result in 63,080 fewer tuberculosis cases, 53,120 fewer tuberculosis deaths, and net societal savings of $131 million, over 20 years. Current government spending for tuberculosis is high, relative to the per capita income, and would be only slightly lower with DOTS. Societal savings would begin within 4 years, and would be substantial in all scenarios considered, including higher HIV seroprevalence or drug resistance, unchanged incidence following DOTS expansion, or doubling of initial and ongoing costs for DOTS expansion. CONCLUSION: A modest investment for DOTS expansion in Haiti would provide considerable humanitarian benefit by reducing tuberculosis-related morbidity, mortality and costs for patients and their families. These benefits, together with projected minimal Haitian government savings, argue strongly for donor support for DOTS expansion.

Modelling the economics of gaming in South Africa.

This paper considers the application of two models for determining the optimal location and characteristics of a casino in a post-apartheid South Africa. The intention in developing the models was to allow provinces a facility for considering how to maximize the return to the stakeholders in the license award process, namely society at large, as represented by the provincial government, and the casino operator. The Allocation Model works on an estimate of total potential gambling spend and how that may be best distributed amongst a number of casinos. The Profitability model takes the estimated gaming spend from the allocation model and assesses the appropriate size and characteristics of the casino best suited to this level of gaming spend. It can then simulate levels of profitability for different proposed sizes and characteristics of proposed casinos. Together these models represent a powerful assessment mechanism for a country considering the introduction or radical changing of gaming legislation.