Cocaine Use May Moderate the Associations of HIV and Female Sex with Neurocognitive Impairment in a Predominantly African American Population Disproportionately Impacted by HIV and Substance Use.

HIV-associated neurocognitive disorders (HAND) remain a major challenge for people with HIV in the antiretroviral therapy era. Cocaine use may trigger/exacerbate HAND among African American (AA) adults, especially women. Between 2018 and 2019, 922 adults, predominantly AAs, with/without HIV and with/without cocaine use in Baltimore, Maryland, were enrolled in a study investigating the association of HIV and cocaine use with neurocognitive impairment (NCI). Neurocognitive performance was assessed with the NIH Toolbox Cognition Battery (NIHTB-CB). NCI was considered to be present if the fully adjusted standard score for at least two cognitive domains was 1.0 standard deviation below the mean. Although the overall analysis showed HIV and female sex were associated with NCI, the associations were dependent on cocaine use. Neither HIV [adj prevalence ratio (PR): 1.12, confidence interval (95% CI): 0.77-1.64] nor female sex (adj PR: 1.07, 95% CI: 0.71-1.61) was associated with NCI among cocaine nonusers, while both HIV (adj PR: 1.39, 95% CI: 1.06-1.81) and female sex (adj PR: 1.53, 95% CI: 1.18-1.98) were associated with NCI in cocaine users. HIV was associated with two NIHTB-CB measures overall. In addition, HIV was associated with a lower dimensional change card sort score (an executive function measure) in cocaine users and not in nonusers. Cognitive performance was poorer in female than in male cocaine users. The adverse effect of HIV on cognitive performance predominantly affected cocaine users. However, cocaine use may moderate the impact of HIV and female sex on cognitive performance, highlighting the importance of reducing cocaine use in NCI prevention among the AA population.

High-risk Coronary Plaque Regression in Cash-based Contingency Management Intervention Among Cocaine Users With HIV-associated Subclinical Coronary Atherosclerosis.

BACKGROUND: Cocaine use exacerbates human immunodeficiency virus (HIV)-associated subclinical coronary atherosclerosis. We investigated whether cocaine abstinence or reduced use achieved with contingency management (CM) intervention would retard high-risk coronary plaque progression among cocaine users with HIV and subclinical coronary atherosclerosis. METHODS: Between March 2014 and August 2017, 76 cocaine users with HIV and coronary plaques were enrolled in a study designed to decrease cocaine use and determine whether doing so impacted progression of subclinical coronary atherosclerosis as measured by coronary artery computed tomography examinations. Of the 76, 7 did not complete the study, resulting in 69 participants. A 12-month cash-based CM intervention was implemented to promote cocaine abstinence or reduced cocaine use. Generalized estimating equation approach was used to perform longitudinal data analyses. FINDINGS: During the 12-month CM, all 69 participants reduced cocaine use, and of these, 25 (36%; 95% confidence interval, 25%-49%) achieved cocaine abstinence. After adjusting for potential confounding factors, generalized estimating equation analyses showed that (1) endothelin-1 (ET-1) levels, a proinflammatory biomarker for endothelial dysfunction, at the 6-month and 12-month visits were significantly lower compared with baseline ET-1 ( P = 0.001 and P < 0.001, respectively), and (2) low-attenuation noncalcified coronary plaque volume, a predictor for myocardial infarction, at 12-month visit was significantly lower compared with baseline low-attenuation noncalcified coronary plaque volume ( P < 0.05). CONCLUSIONS: The findings of this study have not only demonstrated that CM is effective in achieving a sustained reduction in cocaine use, but also provided compelling evidence that reduction in cocaine use leads to quantifiable cardiovascular health benefits, including concurrent decrease in high-risk plaque burden and ET-1, among cocaine users with HIV-associated coronary atherosclerosis.

Temporal assessment of lesion morphology on radiological images beyond lesion volumes-a proof-of-principle study.

OBJECTIVES: To develop a general framework to assess temporal changes in lesion morphology on radiological images beyond volumetric changes and to test whether cocaine abstinence changes coronary plaque structure on serial coronary CT angiography (CTA). METHODS: Chronic cocaine users with human immunodeficiency virus (HIV) infection were prospectively enrolled to undergo cash-based contingency management to achieve cocaine abstinence. Participants underwent coronary CTA at baseline and 6 and 12 months following recruitment. We segmented all coronary plaques and extracted 1103 radiomic features. We implemented weighted correlation network analysis to derive consensus eigen radiomic features (named as different colors) and used linear mixed models and mediation analysis to assess whether cocaine abstinence affects plaque morphology correcting for clinical variables and plaque volumes and whether serum biomarkers causally mediate these changes. Furthermore, we used Bayesian hidden Markov network changepoint analysis to assess the potential rewiring of the radiomic network. RESULTS: Sixty-nine PLWH (median age 55 IQR: 52-59 years, 19% female) completed the study, of whom 26 achieved total abstinence. Twenty consensus eigen radiomic features were derived. Cocaine abstinence significantly affected the pink and cyan eigen features (-0.04 CI: [-0.06; -0.02], p = 0.0009; 0.03 CI: [0.001; 0.04], p = 0.0017, respectively). These effects were mediated through changes in endothelin-1 levels. In abstinent individuals, we observed significant rewiring of the latent radiomic signature network. CONCLUSIONS: Using our proposed framework, we found 1 year of cocaine abstinence to significantly change specific latent coronary plaque morphological features and rewire the latent morphologic network above and beyond changes in plaque volumes and clinical characteristics. KEY POINTS: • We propose a general methodology to decompose the latent morphology of lesions on radiological images using a radiomics-based systems biology approach. • As a proof-of-principle, we show that 1 year of cocaine abstinence results in significant changes in specific latent coronary plaque morphologic features and rewiring of the latent morphologic network above and beyond changes in plaque volumes and clinical characteristics. • We found endothelin-1 levels to mediate these structural changes providing potential pathological pathways warranting further investigation.

HIV indirectly accelerates coronary artery disease by promoting the effects of risk factors: longitudinal observational study.

Our objective was to assess whether human immunodeficiency virus (HIV)-infection directly or indirectly promotes the progression of clinical characteristics of coronary artery disease (CAD). 300 African Americans with asymptomatic CAD (210 male; age: 48.0 ± 7.2 years; 226 HIV-infected) who underwent coronary CT angiography at two time points (mean follow-up: 4.0 ± 2.3 years) were randomly selected from 1429 participants of a prospective epidemiological study between May 2004 and August 2015. We calculated Agatston-scores, number of coronary plaques and segment stenosis score (SSS). Linear mixed models were used to assess the effects of HIV-infection, atherosclerotic cardiovascular disease (ASCVD) risk, years of cocaine use on CAD. There was no significant difference in annual progression rates between HIV-infected and-uninfected regarding Agatston-scores (10.8 ± 25.1/year vs. 7.2 ± 17.8/year, p = 0.17), the number of plaques (0.2 ± 0.3/year vs. 0.3 ± 0.5/year, p = 0.11) or SSS (0.5 ± 0.8/year vs. 0.5 ± 1.3/year, p = 0.96). Multivariately, HIV-infection was not associated with Agatston-scores (8.3, CI: [- 37.2-53.7], p = 0.72), the number of coronary plaques (- 0.1, CI: [- 0.5-0.4], p = 0.73) or SSS (- 0.1, CI: [- 1.0-0.8], p = 0.84). ASCVD risk scores and years of cocaine-use significantly increased all CAD outcomes among HIV-infected individuals, but not among HIV-uninfected. Importantly, none of the HIV-medications were associated with any of the CAD outcomes. HIV-infection is not directly associated with CAD and therefore HIV-infected are not destined to have worse CAD profiles. However, HIV-infection may indirectly promote CAD progression as risk factors may have a more prominent role in the acceleration of CAD in these patients.

Cardiovascular risk factors and illicit drug use may have a more profound effect on coronary atherosclerosis progression in people living with HIV.

OBJECTIVES: To assess whether HIV infection directly or indirectly promotes coronary artery disease (CAD) volume progression in a longitudinal study of African Americans. METHODS: We randomly selected 300 individuals with subclinical CAD (210 male; age: 48.0 ± 7.2 years; 226 HIV infected, 174 cocaine users) from 1429 cardiovascularly asymptomatic participants of a prospective epidemiological study between May 2004 and August 2015. Individuals underwent coronary CT angiography at two time points (mean follow-up: 4.0 ± 2.3 years). We quantified noncalcified (NCP: -100-350HU), low-attenuation noncalcified (LA-NCP: -100-30HU), and calcified (CP: ≥ 351 HU) plaque volumes. Linear mixed models were used to assess the effects of HIV infection, atherosclerotic cardiovascular disease (ASCVD) risk, and years of cocaine use on plaque volumes. RESULTS: There was no significant difference in annual progression rates between HIV-infected and HIV-uninfected regarding NCP (8.7 [IQR: 3.0-19.4] mm3/year vs. 4.9 [IQR: 1.5-18.3] mm3/year, p = 0.14), LA-NCP (0.2 [IQR: 0.0-1.6] mm3/year vs. 0.2 [IQR: 0.0-0.9] mm3/year, p = 0.07) or CP volumes (0.3 [IQR: 0.0-3.4] mm3/year vs. 0.1 [IQR: 0.0-3.2] mm3/year, p = 0.30). Multivariately, HIV infection was not associated with NCP (-6.9mm3, CI: [-32.8-19.0], p = 0.60), LA-NCP (-0.1mm3, CI: [-2.6-2.4], p = 0.92), or CP volumes (-0.3mm3, CI: [-9.3-8.6], p = 0.96). However, each percentage of ASCVD and each year of cocaine use significantly increased total, NCP, and CP volumes among HIV-infected individuals, but not among HIV-uninfected. Importantly, none of the HIV-associated medications had any effect on plaque volumes (p > 0.05 for all). CONCLUSIONS: The more profound adverse effect of risk factors in HIV-infected individuals may explain the accelerated progression of CAD in these people, as HIV infection was not independently associated with any coronary plaque volume. KEY POINTS: • Human immunodeficiency virus-infected individuals may have similar subclinical coronary artery disease, as the infection is not independently associated with coronary plaque volumes. • However, cardiovascular risk factors and illicit drug use may have a more profound effect on atherosclerosis progression in those with human immunodeficiency virus infection, which may explain the accelerated progression of CAD in these people. • Nevertheless, through rigorous prevention and abstinence from illicit drugs, these individuals may experience similar cardiovascular outcomes as -uninfected individuals.

Contribution of Risk Factors to the Development of Coronary Atherosclerosis as Confirmed via Coronary CT Angiography: A Longitudinal Radiomics-based Study.

Background Various cardiovascular risk factors are thought to modify atherosclerosis in a similar fashion (ie, by increasing the magnitude of coronary artery disease [CAD]). However, coronary CT angiography allows precision phenotyping of plaque characteristics through use of radiomics. Purpose To assess whether different cardiovascular risk factors have distinctive contributions to the changes in plaque morphologic features over time. Materials and Methods Individuals with or without HIV infection and cocaine use and without cardiovascular symptoms underwent coronary CT angiography between May 2004 and August 2015. In the current HIPAA-compliant study, the effects of cocaine use, HIV infection, and atherosclerotic cardiovascular disease (ASCVD) risk on the temporal changes (mean ± standard deviation, 4.0 years ± 2.3 between CT angiographic examinations) in CAD structure were analyzed by using radiomic analysis. The changes in radiomic features were analyzed by using linear mixed models, with correction for factors that may change plaque structure: high-sensitivity C-reactive protein level, statin use, positive family history of CAD, and total plaque volume to account for any potential intrinsic correlation between volume and morphologic features. Clusters among significant radiomic features were identified by using hierarchical clustering. Bonferroni-corrected P values less than .00004 (.05 divided by 1276) were considered to indicate significant differences. Results Of 1429 participants, 300 with CAD confirmed at coronary CT angiography were randomly selected (mean age, 48 years ± 7; 210 men, 226 people infected with HIV, 174 people who use cocaine) and 1276 radiomic features were quantified for each plaque. Cocaine use was significantly associated with 23.7% (303 of 1276) of the radiomic features, HIV infection was significantly associated with 1.3% (17 of 1276), and elevated ASCVD risk was significantly associated with 8.2% (104 of 1276) (P < .00004 for all). Parameters associated with elevated ASCVD risk or cocaine use and HIV infection did not overlap. There were 13 clusters among the 409 parameters, eight of which were affected only by cocaine use and three of which were affected only by ASCVD risk. Conclusion Radiomics-based precision phenotyping indicated that conventional risk factors, cocaine use, and HIV infection each had different effects on CT angiographic morphologic changes in coronary atherosclerosis over 4 years. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Schoepf and Emrich in this issue.

Long-term cocaine use is associated with increased coronary plaque burden - a pilot study.

Background: There is a lack of research regarding whether prolonged use of cocaine would lead to increase of coronary plaque burden. Objectives: To study the effects of cocaine use on the coronary artery plaque volume. We hypothesize the longer the cocaine use, the greater the plaque burden. Methods: We used coronary computed tomography angiography to evaluate plaque volumes. The study included chronic (N = 33 with 27 HIV+) and non-cocaine users (N = 15 with 12 HIV+). Chronic cocaine use was defined as use by any route for at least 6 months, administered at least 4 times/month. The Student's t-test was used to compare the plaque volumes between chronic and non-cocaine users. Multivariable regression analysis adjusted for age, sex, body mass index, HIV status, cigarette smoking, diabetes, and total cholesterol was performed to determine the relationship between years of cocaine use and plaque volumes. Results: The total plaque volumes between groups showed no difference (p = .065). However, the total left anterior descending artery (LAD) plaque volume in the chronic cocaine group was significantly higher than that in the non-cocaine group (p = .047). For each year increase in cocaine use, total plaque volume and total LAD plaque volume increased by 7.23 mm3 (p = .013) and 4.56 mm3 (p = .001), respectively. In the multivariable analyses, both total plaque volume and total LAD plaque volume were significantly associated with years of cocaine use (p = .039 and 0.013, respectively). Conclusion: Prolonged cocaine use accelerates the development of sub-clinical atherosclerosis.

Impact of Cardiovascular Disease on Health Insurance Coverage and Healthcare Use under Economic Stress: The National Health and Nutrition Examination Survey, 2003-2012.

OBJECTIVES: Cardiovascular disease (CVD) has a substantial financial impact on healthcare systems in the US. This study aimed to examine the impact of CVD on health insurance coverage and health service use under economic stress as indicated by the Great Recession in the US (December 2007-June 2009). METHODS: Data of 26,483 adults aged ≥ 20 years from the 2003-2012 National Health and Nutrition Examination Survey were analyzed. There were 9,479 adults assigned to the group "before the Great Recession" (2003-2006), 5,674 adults assigned to "during the Great Recession" (2007-2008), and 11,330 adults assigned to "after the Great Recession" (2009-2012). RESULTS: Patients with CVD from low-income families were more likely to have health insurance during the recession (OR:1.57, 95% CI: 1.01,2.45). Those participants without CVD, who were from low-income families or < 65 years, were more likely to use the emergency room rather than primary care facilities to gain access to routine healthcare (p < 0.05). Patients with CVD from high-income families were also more likely to use the emergency room (p < 0.05). Patients with CVD but not those without CVD, who reported a high family income or were ≥ 65 years old, were less likely to use mental health services during the recession than before the recession. CONCLUSION: Effective strategies need to be developed to promote primary care use among the general adult American population. In addition, use of mental health services among patients with CVD needs to be improved when financial stress occurs.

Cocaine use modifies the association between antiretroviral therapy and endothelial dysfunction among adults with HIV infection.

Cocaine is commonly used among HIV-infected people and may worsen HIV disease progression. In addition, existing evidence suggests a link between antiretroviral regimens and endothelial dysfunction. This study aimed to examine whether the associations of antiretroviral therapy (ART) regimens with endothelial dysfunction may be modified by cocaine use in adults with HIV infection. Between 2003 and 2014, 466 HIV-positive participants residing in Baltimore, Maryland, were enrolled in a study investigating comorbidities associated with HIV/ART. The associations between various risk factors and endothelial dysfunction indicators were examined by robust regression models fitted for the overall subjects and cocaine subgroups, separately. Duration of nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based therapy was negatively associated with plasma vWF:Ag levels in cocaine non-users (ß = -.715, SE = .220, P < .05). However, cocaine users on longer-term NNRTI-based regimens had greater plasma endothelin-1 (ET-1) concentrations than their counterparts (ß = .003, SE = .001, P < .05). In addition, current cigarette smoking was significantly positively associated with ET-1 concentrations in both cocaine non-users (ß = .609, SE = .164, P < .05) and cocaine users (ß = .331, SE = .086, P < .05). In conclusion, cocaine use modified the potential effects of NNRTI-based therapy on biomarkers of endothelial dysfunction. These findings suggested that reduction in cocaine use may improve endothelial function in HIV-infected cocaine users.

Circulating levels of cardiac troponin T are associated with coronary noncalcified plaque burden in HIV-infected adults: a pilot study.

HIV infection and/or antiretroviral therapy may increase the risk of subclinical coronary atherosclerosis. However, patients with chronic kidney disease (CKD) and those without IV access cannot undergo contrast-enhanced coronary CT angiography (CCTA). This study was to explore the relationship between cardiac troponin T (cTnT) levels and the extent of coronary plaque burden, as assessed by CCTA in those with HIV infection. Between June and September 2017, 58 HIV-infected participants were recruited and underwent contrast-enhanced CCTA. cTnT was measured with the Elecsys Troponin T Gen 5 STAT assay, and noncalcified plaque burden was quantified using coronary plaque analysis. Robust regression model was employed to perform primary statistical analysis. Univariate robust regression analysis indicated that male gender, cardiovascular risk score defined by the 2013 ACC/AHA cardiovascular risk score algorithm, and cTnT levels were significantly associated with noncalcified plaque volume index (NCPI). Final robust regression analyses showed that only cTnT (log scale) was independently associated with the NCPI (regression coefficient: 0.0453 with 95% CI: 0.0151, 0.0755, p = 0.003). These results of this study suggest that cTnT may be a promising marker for coronary plaque burden, especially in patients with HIV-associated CKD or without IV access.

Cocaine use may induce telomere shortening in individuals with HIV infection.

BACKGROUND: Although cocaine use may induce/accelerate HIV-associated comorbidities in HIV-infected individuals on antiretroviral therapy (ART), and that HIV itself may accelerate aging, the issue of whether cocaine use plays a role in HIV-associated aging in HIV-infected cocaine users has not been reported. The goals of this study were (1) to explore factor(s) associated with peripheral blood leukocyte telomere length, a marker of cellular replicative history, and telomere shortening in HIV-infected individuals, and (2) to assess whether cocaine use plays a role in accelerating telomere shortening in cocaine users with HIV infection. METHODS: Between June 2010 and December 2016, 147 HIV-infected participants in Baltimore, Maryland, were enrolled in a cross-sectional study investigating factor(s) associated with telomere length. Of these 147, 93 participated in a follow-up study to examine factor(s) associated with telomere shortening. Robust regression model was used to analyze cross-sectional data and the generalized estimating equation approach was used to analyze follow-up data. RESULTS: Cross-sectional analyses demonstrated that (1) both daily alcohol consumption and use of non-nucleoside reverse transcriptase inhibitors (NNRTIs) were independently associated with telomere length, and cocaine use modified the associations of daily alcohol use and NNRTI use with telomere length. Longitudinal analyses suggested that both daily alcohol consumption and duration of NNRTI use were independently associated with telomere shortening, and (2) cocaine use induced/accelerated telomere shortening in HIV-infected individuals. CONCLUSIONS: Our findings suggest that cocaine use may promote premature aging in HIV-infected individuals who are on ART. Our results emphasize the importance of cocaine abstinence/reduced use, which may retard HIV-associated premature aging.

Impact of cocaine use on protease inhibitor-associated dyslipidemia in HIV-infected adults.

Previous studies have demonstrated a link between protease inhibitor (PI)-based therapy and lipid dysregulation. The main objective of this study was to examine whether cocaine use may modify PI-associated dyslipidemia in adults. Between June 2003 and June 2014, 957 human immunodeficiency virus (HIV)-infected participants in Baltimore, Maryland were enrolled in a study that investigated HIV/antiretroviral therapy-associated comorbidities. Multiple linear and logistic regression models were fitted to examine the associations between PI therapy and lipid profiles for the pooled sample and cocaine use subgroups, respectively. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), TC/high-density lipoprotein cholesterol (HDL-C) ratio, and atherogenic index of plasma (AIP) levels were positively associated with duration of PI-based therapy in long-term cocaine users (all p < 0.05). However, longer-term PI therapy was significantly associated with increased HDL-C in non-chronic cocaine users (ß = 0.109, SE = 0.042, p < 0.05). The participants who received PI therapy ≥12 months and used cocaine ≥15 years were more likely to have hypertriglyceridemia (OR = 2.82, 95% CI = 1.63, 4.88) and abnormal AIP (OR = 1.73, 95% CI = 1.08, 2.79) as compared to their counterparts. Our findings showed that long-term cocaine use may exacerbate adverse effects of PI therapy on lipid metabolism, suggesting that reduced cocaine use may be considered an alternative approach to managing PI-associated dyslipidemia in chronic cocaine users with HIV infection.

Age and Gender Differences in the Association between Serum 25-Hydroxyvitamin D and Stroke in the General US Population: The National Health and Nutrition Examination Survey, 2001-2006.

BACKGROUND: Previous findings on the association between serum 25(OH)D level and stroke have been controversial. We aimed to examine whether these controversial findings could be possibly due to difference in study participant characteristics, especially age and gender differences in these studies, by analyzing the data from a representative sample of the general US population. METHODS: Data of 13,642 adults 20 years or older who participated in the 2001-2006 National Health and Nutrition Examination Survey were analyzed in this study. Serum 25(OH)D was used to reflect vitamin D status. Stroke history was self-reported using questionnaires. Unadjusted and adjusted logistic regression models were fitted using SAS survey procedures to investigate the associations between 25(OH)D level and stroke for the pooled sample and age-gender subgroups (men versus women, <50 years old versus ≥50 years old), respectively. RESULTS: After adjusting for demographic and lifestyle covariates, vitamin D deficiency (defined as serum 25(OH)D < 12 ng/mL) was significantly associated with increased risk of stroke (adjusted odds ratio [OR] = 1.62, 95% confidence interval [CI] = 1.11, 2.36), and higher vitamin D levels were significantly associated with reduced risk of stroke (adjusted OR = .70, 95% CI = .51, .96). The association between high levels of serum 25(OH)D and stroke was particularly evident among young females (age ≤20 years to <50 years) (adjusted OR = .26, 95% CI = .14, .49). CONCLUSIONS: The findings add to the evidence suggesting maintaining ideal 25(OH)D levels may reduce the risk of stroke among US adults, particularly in adult women younger than 50 years.

Cocaine use may modify HIV/ART-associated myocardial steatosis and hepatic steatosis.

BACKGROUND: It has been recognized that myocardial and hepatic steatosis may be more prevalent in HIV-infected individuals on antiretroviral therapy (ART); however, factors associated with these conditions have not been thoroughly investigated. The goals of this study were (1) to identify the risk factors for myocardial and hepatic steatosis in HIV-infected African Americans (AAs) and explore whether ART use is independently associated with myocardial and hepatic steatosis, and (2) to examine whether and how cocaine use influences any associations of ART use with myocardial and hepatic steatosis. METHODS: Between June 2010 and December 2013, 220 HIV-infected AAs in Baltimore, Maryland, were enrolled in a study investigating HIV/ART-associated myocardial and hepatic damage. Proton magnetic resonance spectroscopy was performed to quantify myocardial and hepatic triglyceride contents. Sociodemographic, medical and laboratory data were also obtained. Robust regression model was employed to perform primary statistical analysis. RESULTS: Robust regression analyses showed that (1) duration of protease inhibitor (PI) use was independently associated with myocardial and hepatic triglyceride contents, (2) duration of PI use was independently associated with myocardial triglyceride in cocaine users (p=0.025), but not in cocaine never-users (p=0.84), and (3) duration of PI use was independently associated with hepatic triglyceride in cocaine users, but not in cocaine never-users (p=0.52). CONCLUSIONS: Cocaine use may trigger/exacerbate the toxicity of PI in ART-associated myocardial and hepatic steatosis, suggesting that cocaine abstinence/reduced use may retard these ART-associated comorbidities. Clinical trials should be conducted to examine whether reduced cocaine use improves HIV/AIDS-associated myocardial and hepatic steatosis.

Gender differences in the associations between urinary bisphenol A and body composition among American children: The National Health and Nutrition Examination Survey, 2003-2006.

BACKGROUND: As an endocrine disruptor, bisphenol A (BPA) exposure has been implicated as a potential risk factor in childhood obesity, which is defined using percentiles of body mass index for age. We aimed to examine the associations between BPA exposure, reflected by urinary BPA concentration, and body composition in American children. METHODS: Data of 1860 children aged 8-19 years who participated in the 2003-2006 National Health and Nutrition Examination Survey (NHANES) were analyzed in this study. Urinary BPA concentration (ng/mL) was used to indicate BPA status in the body. Body composition was measured by dual-energy X-ray absorptiometry (DXA). Multivariate linear regression models were fitted using survey procedures to investigate the associations between urinary BPA level and body composition separately for boys and girls. RESULTS: After adjusting for demographic and lifestyle covariates, higher quartiled and log-transformed urinary BPA levels were significantly associated with elevated lean body mass index (LBMI) z-scores in boys (p < 0.05), and significantly associated with elevated fat mass index (FMI) z-scores in girls (p < 0.05). Lower urinary BPA concentration was associated with lower percentage of trunk fat in girls (compared to 1st quartile, 2nd-quartile: ß = 2.85, 95% CI, 0.92-4.78; 3rd-quartile: ß = 2.57, 95% CI, 0.28-4.85; 4th-quartile: ß = 2.79, 95% CI, 0.44-5.14; all p < 0.05). Such patterns were not observed in boys. CONCLUSIONS: Higher BPA levels may be associated with elevated LBM in boys, but not in girls, while higher BPA levels may be associated with elevated FM in girls, but not in boys.

Coronary Plaque Progression and Regression in Asymptomatic African American Chronic Cocaine Users With Obstructive Coronary Stenoses: A Preliminary Study.

OBJECTIVE: Although rapid progression of coronary atherosclerosis was observed in chronic cocaine users, it is unknown whether reduced cocaine use retards the progression of atherosclerosis. We investigated whether reduced cocaine use over a 12-month period was associated with coronary plaque regression in cocaine users. METHODS: Fifteen African American chronic cocaine users with previously coronary computed tomography angiography (CCTA)-confirmed >50% coronary stenosis in Baltimore, Maryland, were enrolled in a study to investigate whether reduced cocaine use is associated with changes in coronary plaque burden over a 12-month period of cash-based incentive intervention, which was implemented to systematically reinforce cocaine abstinence. In addition to previous CCTA (preintervention), CCTA was performed at the intervention baseline and at postintervention. Plaque analyses were performed to determine the trajectory of plaque changes in the absence of intervention by comparing the preintervention with the intervention baseline studies; the trajectory of plaque changes associated with the intervention by comparing the intervention baseline with the postintervention studies; and (3) whether reduced cocaine use was independently associated with changes in coronary plaque burden. RESULTS: During the 12-month cash-based incentive intervention period, cocaine use in participants was lower. The medians of noncalcified plaque indices were 37.8 (interquartile range [IQR] 29.3-44.0), 43.1 (IQR 38.3-49.0), and 38.7 (IQR 31.2-46.8) mm at preintervention, intervention baseline, and postintervention, respectively. Multivariable generalized estimating equation analysis showed that both total plaque and noncalcified plaque indices at preintervention were significantly lowered as compared with intervention baseline levels; both total plaque and noncalcified plaque indices after intervention were significantly lowered as compared with intervention baseline levels; and reduced cocaine use was independently associated with lower total plaque volume index (P < 0.0001) and noncalcified plaque volume index (P = 0.010). CONCLUSIONS: Our findings suggest that continued cocaine use may be associated with noncalcified plaque progression, whereas reduced cocaine use may be associated with noncalcified plaque regression. Larger studies are needed to confirm these findings.

Interaction of sex steroid hormones and obesity on insulin resistance and type 2 diabetes in men: the Third National Health and Nutrition Examination Survey.

AIMS: We examined interaction of sex steroid hormones and obesity with regard to insulin resistance (IR) and type 2 diabetes (T2D) by using nationally representative data from the US. METHODS: Data of 1461 men aged ≥20years who participated in the Third National Health and Nutrition Examination Survey were analyzed. Multiplicative interaction was calculated by cross-product interaction terms in multivariable logistic regression models. Additive interaction was assessed by the relative excess risk due to interaction (RERI). RESULTS: After adjusting for demographic and lifestyle covariates, the odds of IR were greatest among obese men with low free testosterone and high androstanediol glucuronide. Multiplicative interactions for total testosterone, free testosterone, and free estradiol index (FEI) were statistically significant with central obesity but not with overweight and obesity regarding to T2D (P<0.05). Significant additive interactions with obesity or central obesity were detected for total testosterone (RERI=2.75, 95% CI=0.92,4.59), SHBG (RERI=5.71, 95% CI=0.77,10.64), and FEI (RERI=-9.96, 95% CI=-19.18,-0.74) with regard to IR, beta-cell dysfunction, and T2D. CONCLUSIONS: Our findings add to the evidence suggesting that low testosterone and high estradiol may be associated greater risks of IR and T2D by interacting with overall and central obesity in adult men.

Outstanding Elastic Limit of a Thin Film Composed of Nickel Nanosprings.

This paper presents experimental results of vertical loading using an atomic force microscope (AFM) performed on a thin film consisting of nickel helical nanoelements (nanosprings) formed by glancing angle deposition (GLAD) technique. As a helical element has large reversible deformation limit in general, a characteristic behavior is expected on the yielding of the film. From the load versus displacement curves, we find the outstanding elastic limit of nickel nanosprings film. The apparent yield strain is evaluated as ε' Y = 5.2˜6.2 × 10−2, which is around 200 times of that in bulk nickel (ε Y = 0.29˜0.44 × 10−3). However, comparing the maximum shear stress in the helical spring and the solid film, the shape effect (helical shape) is only around 10˜20 times stemmed from the difference in the stress condition (torsion). The origin of difference is attributed to the size effect of nanosprings, as nano-scale metals have higher yield strain than that of bulk counterpart because of the difference in the understructure morphology. The combination of shape effect and size effect brings about the giant elastic limit on the film.

HIV Infection Itself May Not Be Associated With Subclinical Coronary Artery Disease Among African Americans Without Cardiovascular Symptoms.

BACKGROUND: The key objectives of this study were to examine whether HIV infection itself is associated with subclinical coronary atherosclerosis and the potential contributions of cocaine use and antiretroviral therapies (ARTs) to subclinical coronary artery disease (CAD) in HIV-infected persons. METHODS AND RESULTS: Between June 2004 and February 2015, 1429 African American (AA) adults with/without HIV infection in Baltimore, Maryland, were enrolled in an observational study of the effects of HIV infection, exposure to ART, and cocaine use on subclinical CAD. The prevalence of subclinical coronary atherosclerosis was 30.0% in HIV-uninfected and 33.7% in HIV-infected (P=0.17). Stratified analyses revealed that compared to HIV-uninfected, HIV-infected ART naïve were at significantly lower risk for subclinical coronary atherosclerosis, whereas HIV-infected long-term ART users (≥36 months) were at significantly higher risk. Thus, an overall nonsignificant association between subclinical coronary atherosclerosis and HIV was found. Furthermore, compared to those who were ART naïve, long-term ART users (≥36 months) were at significantly higher risk for subclinical coronary atherosclerosis in chronic cocaine users, but not in those who never used cocaine. Cocaine use was independently associated with subclinical coronary atherosclerosis. CONCLUSIONS: Overall, HIV infection, per se, was not associated with subclinical coronary atherosclerosis in this population. Cocaine use was prevalent in both HIV-infected and -uninfected individuals and itself was associated with subclinical disease. In addition, cocaine significantly elevated the risk for ART-associated subclinical coronary atherosclerosis. Treating cocaine addiction must be a high priority for managing HIV disease and preventing HIV/ART-associated subclinical and clinical CAD in individuals with HIV infection.

Cocaine Abstinence and Reduced Use Associated With Lowered Marker of Endothelial Dysfunction in African Americans: A Preliminary Study.

OBJECTIVES: Clinical and epidemiological evidence suggests that cocaine use is associated with an increased risk of premature atherosclerosis. The objectives of this study were to explore (1) whether cocaine abstinence is associated with a reduced marker of endothelial dysfunction, (2) whether cocaine abstinence is associated with a slower coronary plaque progression, and (3) whether reduction in cocaine use is associated with a reduced marker of endothelial dysfunction in African American chronic cocaine users with contrast-enhanced coronary CT angiography-confirmed less than 50% coronary stenosis. METHODS: Between March and June 2014, a total of 57 African American cocaine users with contrast-enhanced CT angiography-confirmed less than 50% coronary stenosis in Baltimore, Maryland, were enrolled in a 6-month follow-up study to investigate whether cocaine abstinence or reduction in cocaine use is associated with decreased endothelin-1 (ET-1) levels and coronary plaque progression at the 6-month follow-up. A voucher-based incentive approach was used to systematically reinforce cocaine abstinence, and urine benzoylecgonine test was implemented to confirm cocaine use. RESULTS: Among the 57 participants, 44 were HIV-infected. The median of duration of cocaine use was 18 (interquartile range, 7-30) years. According to generalized estimating equation analyses, both cocaine abstinence and reduction in cocaine use in the 6 months were independently associated with decreased ET-1. The incidence of coronary plaque progression was 7.4/100 person-years and 23.1/100 person-years in those who were totally abstinent from cocaine and those who continued to use cocaine, respectively. However, the difference in the incidence between these 2 groups was not significant (exact P = 0.30). CONCLUSIONS: The findings of this study revealed a possible association of cocaine abstinence/reduction with lowered ET levels, which suggests that such changes in cocaine use might be beneficial for preventing endothelial damage. Further studies should be conducted to investigate whether ET-1 could be used as a marker for cocaine abstinence and reduction in cocaine use.