Environmental Pollution and Cardiovascular Disease: Part 1 of 2: Air Pollution.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Over the past 50 years, there has been a substantial decline in the incidence of CVD and related mortality in high-income countries, largely due to the mitigation of modifiable risk factors such as smoking, hypertension, and diabetes. However, a significant burden of CVD remains in low- to middle-income countries, despite their lower prevalence of traditional risk factors; other environmental factors, particularly pollution, play a significant role in this attributable risk. Mounting evidence underscores a strong association between pollution and adverse health effects, including CVD. This article is part 1 of a 2-part state-of-the-art review and discusses air pollution and its adverse effects on CVD, highlighting pathophysiological mechanisms and methods to reduce air pollution and exposure to these pollutants.

Association of cigarette and electronic cigarette use patterns with all-cause mortality: A national cohort study of 145,390 US adults.

OBJECTIVE: While e-cigarette use is associated with adverse cardiopulmonary health effects, the mortality risks associated with e-cigarette use alone and combined with smoking remain unexamined. METHODS: Data between 2014 and 2018 were obtained from the National Health Interview Survey (NHIS), an annual cross-sectional survey of US adults. All-cause mortality and date of death were obtained via linkage of the NHIS to the National Death Index through December 31, 2019. A 6-category composite cigarette (never, former, current) and e-cigarette (current, non-current) exposure variable was created. We examined the association of cigarette and e-cigarette use patterns with all-cause mortality using adjusted Cox models. RESULTS: Among 145,390 participants (79,294 women [51.5%]; 60,560 aged 18-44 [47.4%]), 5220 deaths were observed over a median follow-up of 3.5 years (508,545 total person-years). Dual use of cigarettes and e-cigarettes was associated with higher mortality risk compared with non-current e-cigarette use in combination with never smoking (hazard ratio [HR] 2.44; 95% CI, 1.90-3.13) and had a risk that did not differ from current exclusive smoking (HR, 1.06; 95% CI, 0.83-1.37). Current e-cigarette use in combination with former smoking was associated with a lower mortality risk than current exclusive cigarette smoking (HR 0.64; 95% CI, 0.41-0.99). CONCLUSIONS: The addition of e-cigarette use to smoking does not reduce mortality risk compared with exclusive smoking. However, transitioning completely from cigarettes to e-cigarettes may be associated with mortality risk reduction. Further research is needed to verify these findings in larger cohorts and over longer periods of follow-up.

Comparative evaluation of different modalities for measuring in vivo carnosine levels.

Carnosine is an endogenous di-peptide (ß-alanine -L- histidine) involved in maintaining tissue homeostasis. It is most abundant in skeletal muscle where its concentration has been determined in biopsy samples using tandem mass spectrometry (MS-MS). Carnosine levels can also be assessed in intact leg muscles by proton magnetic resonance spectroscopy (1H-MRS) or in blood and urine samples using mass spectrometry. Nevertheless, it remains uncertain how carnosine levels from these distinct compartments are correlated with each other when measured in the same individual. Furthermore, it is unclear which measurement modality might be most suitable for large-scale clinical studies. Hence, in 31 healthy volunteers, we assessed carnosine levels in skeletal muscle, via 1H-MRS, and in erythrocytes and urine by MS-MS. While muscle carnosine levels were higher in males (C2 peak, p = 0.010; C4 peak, p = 0.018), there was no sex-associated difference in urinary (p = 0.433) or erythrocyte (p = 0.858) levels. In a linear regression model adjusted for age, sex, race, and diet, there was a positive association between erythrocyte and urinary carnosine. However, no association was observed between 1H-MRS and erythrocytes or urinary measures. In the relationship between muscle versus urinary and erythrocyte measures, females had a positive association, while males did not show any association. We also found that 1H-MRS measures were highly sensitive to location of measurement. Thus, it is uncertain whether 1H-MRS can accurately and reliably predict endogenous carnosine levels. In contrast, urinary and erythrocyte carnosine measures may be stable and in greater synchrony, and given financial and logistical concerns, may be a feasible alternative for large-scale clinical studies.

Social media use, brand engagement, and tobacco product initiation among youth: Evidence from a prospective cohort study.

OBJECTIVE: To evaluate whether frequent social media use and liking/following tobacco brand accounts was associated with increased risk of tobacco and polytobacco initiation over approximately 1-year follow-up among youth with no prior tobacco use. METHODS: Associations between measures of social media engagement (daily social media use and liking/following tobacco brands) and tobacco initiation risk were examined using data from Waves 2 and 3 (2014-2015) of the US Population Assessment for Tobacco and Health study. Separate log-binomial models, accounting for missing data via multiple imputation and using propensity score adjustment to address confounding, estimated the adjusted relative risk (aRR) of any tobacco initiation and poly-use (2 + products) initiation at 1-year follow-up. RESULTS: Among the 8,672 youth with no prior tobacco use (49.3% female, mean [SD] age 14.1 [1.7]), 63.5% used social media at least daily, and 3.3% reported liking/following ≥ 1 tobacco brands on social media. Those reporting daily or more frequent social media use (compared to less) were at increased risk for tobacco (aRR 1.67; 95% CI 1.38-2.02) and polytobacco initiation (aRR 1.32; 95% CI 0.98-1.78). Although results were imprecise, liking/following ≥ 1 tobacco brands on social media (versus none) was associated with tobacco (aRR 1.34; 95% CI 0.95-1.89) or polytobacco initiation (aRR 1.60; 95% CI 0.99-2.60). In sensitivity analyses, liking/following cigarette or cigarillo brands was associated with polytobacco initiation. CONCLUSIONS: This study adds to a growing evidence-base describing the exposure of youth to tobacco-related social media content. Such content-often generated by tobacco companies-may contribute to youth tobacco initiation.

Smoking-associated Electrocardiographic Abnormalities Predict Cardiovascular Mortality: Insights from NHANES.

Background­: Smoking is associated with arrhythmia and sudden cardiac death, but the biological mechanisms remain unclear. Abnormal electrocardiogram (ECG) durations of ventricular repolarization (QT interval), atrial depolarization (P wave), and atrioventricular depolarization (PR interval and segment), predict cardiac arrhythmia and mortality. Objectives­: To elucidate how smoking affects cardiac excitation, we assessed in a nationally representative sample (NHANES III) associations between cotinine, abnormalities in P duration, PR interval, PR segment, rate-corrected QT (QTc), QRS duration, and JT interval, and long-term mortality. Methods­: We analyzed data from 5,633 adults using survey-weighted multinomial logistic regression to estimate associations between tobacco use (>15 ng/ml serum cotinine) and short (<5th percentile) or long (>95th percentile) ECG intervals, relative to reference (5 - 95th percentile). Results­: After adjustment for demographics, risk factors, and conduction-altering medications, smoking was associated with a higher odds of short PR interval, PR segment, and QRS, and long JT. Broader ECG effects of smoking were also assessed by survey-weighted linear regression of continuous cotinine and ECG intervals, which revealed cotinine inversely associated with PR segment and QTc. Over a 22-year follow-up, many ECG abnormalities predicted cardiovascular mortality in smokers, including long JT, QRS, and QTc, and short QRS. Conclusions­: Smoking increases likelihood for rapid atrioventricular conduction, rapid ventricular depolarization, and slow ventricular repolarization. The ventricular electrophysiologic abnormalities associated with smoking also predict cardiovascular mortality in smokers; however, traditional ECG measures of cardiac risk like QTc can overlook these ventricular defects and their independent predictive value in smokers.

Electronic cigarette use and chest pain in US adults: Evidence from the PATH study.

INTRODUCTION: Electronic cigarettes (e-cigarette) were introduced for smoking cessation/reduction but have also become popular among the youth. Although e-cigarettes contain fewer toxins than combustible cigarettes, their long-term cardiovascular and pulmonary effects remain unknown. We aimed to assess the association between self-reported chest pain and e-cigarette use. METHODS: We analyzed data from the PATH (Population Assessment of Tobacco and Health) study wave 4 (2016-2018) and wave 5 (2018-2019). Based on questionnaires from wave 4, we categorized tobacco use as: 1) non-use, 2) exclusive e-cigarette use, 3) combustible cigarette use, and 4) dual use. Presence of established cardiovascular disease was examined at wave 4, and participants aged >40 years were asked about chest pain during wave 5. We used binary logistic regression models to determine the association between tobacco exposures and self-reported chest pain. RESULTS: We evaluated a total of 11254 adults. The rates of chest pain were 1518 out of 7055 non-users, 49 from 208 exclusive e-cigarette users, 1192 from 3722 combustible cigarette users, and 99 out of 269 dual users. In the multivariable models adjusted for relevant covariates, combustible cigarette users (adjusted odds ratio, AOR=1.77; 95% CI: 1.56-2.01) and dual users (AOR=2.22; 95% CI: 1.61-3.05) had higher odds of reporting ever having chest pain, as well as having chest pain in the past 30 days. Conversely, exclusive e-cigarette users had similar odds of reporting chest pain compared to non-users (AOR=1.03; 95% CI: 0.69-1.54) and lower odds than combustible and dual users. In sensitivity analyses, categorizing individuals based on their reported history of cardiovascular disease, overall findings were similar. CONCLUSIONS: Exclusive e-cigarette use is associated with a lower rate of chest pain compared to combustible cigarette use and dual use.

Metabolic Pathways for Removing Reactive Aldehydes are Diminished in Atrophic Muscle During Heart Failure.

Background: Muscle wasting is a serious complication in heart failure patients, and oxidative stress is involved in the pathogenesis of muscle wasting. Oxidative stress leads to the formation of toxic lipid peroxidation products, such as 4-hydroxy-2-nonenal (HNE) and acrolein, which causemuscle wasting. In tissues, these toxic aldehydes are metabolically removed by enzymes such asaldo keto reductases and endogenous nucleophiles, such as glutathione and carnosine. Whether these metabolic pathways could be affected in skeletal muscle during heart failure has never been studied. Methods: Male wild-type C57BL/6J mice were subjected to a pressure overload model of hypertrophy by transaortic constriction (TAC) surgery, and echocardiography was performed after 14 weeks. Different skeletal muscle beds were weighed and analyzed for atrophic and inflammatory markers, Atrogin1 and TRIM63, TNF-α and IL-6, respectively, by RT-PCR. Levels of acrolein and HNE-protein adducts, aldehyde-removing enzymes, aldose reductase (AKR1B1) and aldehyde dehydrogenase 2 (ALDH2) were measured by Western blotting, and histidyl dipeptides and histidyl dipeptide aldehyde conjugates were analyzed by LC/MS-MS in the gastrocnemius and soleus muscles of sham- and TAC-operated mice. Furthermore, histidyl dipeptide synthesizing enzyme carnosine synthase (CARNS) and amino acid transporters (PEPT2 and TAUT)wasmeasured in the gastrocnemius muscles of the sham and TAC-operated mice. Results: TAC-induced heart failure decreases body weight and gastrocnemius and soleus muscle weights. The expression of the atrophic and inflammatory markers Atrogin1 and TNF-α, respectively, wasincreased (~1.5-2-fold), and the formation of HNE and acrolein-protein adducts was increased in the gastrocnemius muscle of TAC-operated mice. The expression of AKR1B1 remained unchanged, whereas ALDH2 was decreased, in the gastrocnemius muscle of TAC mice. Similarly, in the atrophic gastrocnemius muscle, levels of total histidyl dipeptides (carnosine and anserine) and, in particular,carnosine were decreased. Depletion of histidyl dipeptides diminished the aldehyde removal capacity of the atrophic gastrocnemius muscle. Furthermore, the expression of CARNS and TAUT wasdecreased in the atrophic gastrocnemius muscle. Conclusions: Collectively, these results show that metabolic pathways involved in the removal of lipid peroxidation products and synthesis of histidyl dipeptides are diminished in atrophic skeletal muscle during heart failure, which could contribute to muscle atrophy.

Nicotine Formulation Influences the Autonomic and Arrhythmogenic Effects of Electronic Cigarettes.

INTRODUCTION: Evidence is mounting that electronic cigarette (e-cig) use induces cardiac sympathetic dominance and electrical dysfunction conducive to arrhythmias and dependent upon nicotine. A variety of nicotine types and concentrations are available in e-cigs, but their relative cardiovascular effects remain unclear. Here we examine how different nicotine forms (racemic, free-base, and salt) and concentrations influence e-cig-evoked cardiac dysfunction and arrhythmogenesis and provide a mechanism for nicotine-salt-induced autonomic imbalance. METHODS: ECG-telemetered C57BL/6J mice were exposed to filtered air (FA) or e-cig aerosols from propylene glycol and vegetable glycerin solvents either without nicotine (vehicle) or with increasing nicotine concentrations (1%, 2.5%, and 5%) for three 9-min puff sessions per concentration. Spontaneous ventricular premature beat (VPB) incidence rates, heart rate, and heart rate variability (HRV) were compared between treatments. Subsequently, to test the role of ß1-adrenergic activation in e-cig-induced cardiac effects, mice were pretreated with atenolol and exposed to either FA or 2.5% nicotine salt. RESULTS: During puffing and washout phases, ≥ 2.5% racemic nicotine reduced heart rate and increased HRV relative to FA and vehicle controls, indicating parasympathetic dominance. Relative to both controls, 5% nicotine salt elevated heart rate and decreased HRV during washout, suggesting sympathetic dominance, and also increased VPB frequency. Atenolol abolished e-cig-induced elevations in heart rate and declines in HRV during washout, indicating e-cig-evoked sympathetic dominance is mediated by ß1-adrenergic stimulation. CONCLUSIONS: Our findings suggest that inhalation of e-cig aerosols from nicotine salt-containing e-liquids could increase the cardiovascular risks of vaping by inducing sympathetic dominance and cardiac arrhythmias. IMPLICATIONS: Exposure to e-cig aerosols containing commercially relevant concentrations of nicotine salts may increase nicotine delivery and impair cardiac function by eliciting ß1-adrenoceptor-mediated sympathoexcitation and provoking ventricular arrhythmias. If confirmed in humans, our work suggests that regulatory targeting of nicotine salts through minimum pH standards or limits on acid additives in e-liquids may mitigate the public health risks of vaping.

E-Cigarette Use Among US Adults in the 2021 Behavioral Risk Factor Surveillance System Survey.

Importance: After the initial disruption from the COVID-19 pandemic, it is unclear how patterns of e-cigarette use in the US have changed. Objective: To examine recent patterns in current and daily e-cigarette use among US adults in 2021. Design, Setting, and Participants: This cross-sectional study used data from the 2021 Behavioral Risk Factor Surveillance System (BRFSS) database. The BRFSS is the largest national telephone-based survey of randomly sampled adults in the US. Adults aged 18 years or older, residing in 49 US states (all except Florida), the District of Columbia, and 3 US territories (Guam, Puerto Rico, and the US Virgin Islands), were included in the data set. Data analysis was performed in January 2023. Main Outcomes and Measures: The main outcome was age-adjusted prevalence of current and daily e-cigarette use overall and by participant characteristics, state, and territory. Descriptive statistical analysis was conducted, applying weights to account for population representation. Results: This study included 414 755 BRFSS participants with information on e-cigarette use. More than half of participants were women (51.3%). In terms of race and ethnicity, 0.9% of participants were American Indian or Alaska Native, 5.8% were Asian, 11.5% were Black, 17.3% were Hispanic, 0.2% were Native Hawaiian or Other Pacific Islander, 62.2% were White, 1.4% were of multiple races or ethnicities, and 0.6% were of other race or ethnicity. Individuals aged 18 to 24 years comprised 12.4% of the study population. The age-standardized prevalence of current e-cigarette use was 6.9% (95% CI, 6.7%-7.1%), with almost half of participants using e-cigarettes daily (3.2% [95% CI, 3.1%-3.4%]). Among individuals aged 18 to 24 years, there was a consistently higher prevalence of e-cigarette use, with more than 18.6% reporting current use and more than 9.0% reporting daily use. Overall, among individuals reporting current e-cigarette use, 42.2% (95% CI, 40.7%-43.7%) indicated former combustible cigarette use, 37.1% (95% CI, 35.6%-38.6%) indicated current combustible cigarette use, and 20.7% (95% CI, 19.7%-21.8%) indicated never using combustible cigarettes. Although relatively older adults (aged ≥25 years) who reported current e-cigarette use were more likely to report former or current combustible cigarette use, younger adults (aged 18-24 years) were more likely to report never using combustible cigarettes. Notably, the proportion of individuals who reported current e-cigarette use and never using combustible cigarettes was higher in the group aged 18 to 20 years (71.5% [95% CI, 66.8%-75.7%]) compared with those aged 21 to 24 years (53.0% [95% CI, 49.8%-56.1%]). Conclusion and Relevance: These findings suggest that e-cigarette use remained common during the COVID-19 pandemic, particularly among young adults aged 18 to 24 years (18.3% prevalence). Notably, 71.5% of individuals aged 18 to 20 years who reported current e-cigarette use had never used combustible cigarettes. These results underscore the rationale for the implementation and enforcement of public health policies tailored to young adults.

Investigating the association of traditional and non-traditional tobacco product use with subclinical and clinical cardiovascular disease: The Cross-Cohort Collaboration-Tobacco working group rationale, design, and methodology.

While the impact of combustible cigarette smoking on cardiovascular disease (CVD) is well-established, the longitudinal association of non-traditional tobacco products with subclinical and clinical CVD has not been fully explored due to: 1) limited data availability; and 2) the lack of well-phenotyped prospective cohorts. Therefore, there is the need for sufficiently powered well-phenotyped datasets to fully elucidate the CVD risks associated with non-cigarette tobacco products. The Cross-Cohort Collaboration (CCC)-Tobacco is a harmonized dataset of 23 prospective cohort studies predominantly in the US. A priori defined variables collected from each cohort included baseline characteristics, details of traditional and non-traditional tobacco product use, inflammatory markers, and outcomes including subclinical and clinical CVD. The definitions of the variables in each cohort were systematically evaluated by a team of two physician-scientists and a biostatistician. Herein, we describe the method of data acquisition and harmonization and the baseline sociodemographic and risk profile of participants in the combined CCC-Tobacco dataset. The total number of participants in the pooled cohort is 322782 (mean age: 59.7 ± 11.8 years) of which 76% are women. White individuals make up the majority (73.1%), although there is good representation of other race and ethnicity groups including African American (15.6%) and Hispanic/Latino individuals (6.4%). The prevalence of participants who never smoked, formerly smoked, and currently smoke combustible cigarettes is 50%, 36%, and 14%, respectively. The prevalence of current and former cigar, pipe, and smokeless tobacco is 7.3%, 6.4%, and 8.6%, respectively. E-cigarette use was measured only in follow-up visits of select studies, totaling 1704 former and current users. CCC-Tobacco is a large, pooled cohort dataset that is uniquely designed with increased power to expand knowledge regarding the association of traditional and non-traditional tobacco use with subclinical and clinical CVD, with extension to understudied groups including women and individuals from underrepresented racial-ethnic groups.

Global Profiling of Urinary Mercapturic Acids Using Integrated Library-Guided Analysis.

Urinary mercapturic acids (MAs) are often used as biomarkers for monitoring human exposures to occupational and environmental xenobiotics. In this study, we developed an integrated library-guided analysis workflow using ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry. This method includes expanded assignment criteria and a curated library of 220 MAs and addresses the shortcomings of previous untargeted approaches. We employed this workflow to profile MAs in the urine of 70 participants─40 nonsmokers and 30 smokers. We found approximately 500 MA candidates in each urine sample, and 116 MAs from 63 precursors were putatively annotated. These include 25 previously unreported MAs derived mostly from alkenals and hydroxyalkenals. Levels of 68 MAs were comparable in nonsmokers and smokers, 2 MAs were higher in nonsmokers, and 46 MAs were elevated in smokers. These included MAs of polycyclic aromatic hydrocarbons and hydroxyalkenals and those derived from toxicants present in cigarette smoke (e.g., acrolein, 1,3-butadiene, isoprene, acrylamide, benzene, and toluene). Our workflow allowed profiling of known and unreported MAs from endogenous and environmental sources, and the levels of several MAs were increased in smokers. Our method can also be expanded and applied to other exposure-wide association studies.

Comprehensive review of the national surveys that assess E-cigarette use domains among youth and adults in the United States.

Surveillance of e-cigarette use among different population groups is important for the timely implementation and evaluation of tobacco regulatory policies. In this review, we identified 13 nationally representative, repeatedly conducted epidemiologic surveys that assess e-cigarette use among U.S. youth and/or adults and have been instrumental in e-cigarette surveillance. These surveys included National Youth Tobacco Survey, Youth Risk Behavior Surveillance System, Monitoring the Future Survey, International Tobacco Control Policy Evaluation Project (ITC) Youth Tobacco and Vaping Survey, Behavioral Risk Factor Surveillance System, National Health Interview Survey, Tobacco Use Supplement of the Current Population Survey, Health Information National Trends Survey, Tobacco Products and Risk Perception Surveys, ITC Four Country Smoking and Vaping Survey, National Health and Nutrition Examination Survey, National Survey on Drug Use and Health, and Population Assessment of Tobacco and Health. These surveys vary in scope and detail, with their unique strengths and the regulatory questions that can be answered using each survey data. We also highlighted the gaps in these surveys and made recommendations for improvement.

Prevalence of electronic cigarette use and its determinants in us persons of Hispanic/Latino background: The Hispanic community health study / study of Latinos (HCHS/SOL).

Objective: To determine the prevalence and determinants of electronic nicotine delivery systems (ENDS) use among Hispanic/Latino adults from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Methods: Cross-sectional data collected between the years 2015-2017 were analyzed to assess ENDS use (ever (current: use ≤ past 30 days; former: use > past 30 days) and never) among 11,623 adults (mean age 47 years±0.3 years; 52% women). Weighted prevalence estimates were reported, and age-adjusted logistic regression models were used to examine associations between sociodemographic and clinical exposures with ENDS use. Results: The prevalence of current and former ENDS use was 2.0% and 10.4%, respectively. Having ever used ENDS was associated with prevalent coronary artery disease. Current ENDS use was higher in males and associated with higher education, English language preference, and Puerto Rican background compared with nonsmokers and cigarette-only smokers (all p<0.05). Conclusions: Hispanic/Latino individuals who are young adults, male, US-born, and have high acculturation were more likely to report current ENDS use. These findings could inform preventive and regulatory interventions targeted to Hispanics/Latinos.

Examining the association of habitual e-cigarette use with inflammation and endothelial dysfunction in young adults: The VAPORS-Endothelial function study.

INTRODUCTION: Acute exposure to e-cigarette aerosol has been shown to have potentially deleterious effects on the cardiovascular system. However, the cardiovascular effects of habitual e-cigarette use have not been fully elucidated. Therefore, we aimed to assess the association of habitual e-cigarette use with endothelial dysfunction and inflammation - subclinical markers known to be associated with increased cardiovascular risk. METHODS: In this cross-sectional study, we analyzed data from 46 participants (23 exclusive e-cigarette users; 23 non-users) enrolled in the VAPORS-Endothelial function study. E-cigarette users had used e-cigarettes for ≥6 consecutive months. Non-users had used e-cigarettes <5 times and had a negative urine cotinine test (<30 ng/mL). Flow-mediated dilation (FMD) and reactive hyperemia index (RHI) were used to assess endothelial dysfunction, and we assayed high-sensitivity C-reactive protein, interleukin-6, fibrinogen, p-selectin, and myeloperoxidase as serum measures of inflammation. We used multivariable linear regression to assess the association of e-cigarette use with the markers of endothelial dysfunction and inflammation. RESULTS: Of the 46 participants with mean age of 24.3 ± 4.0 years, the majority were males (78%), non-Hispanic (89%), and White (59%). Among non-users, 6 had cotinine levels <10 ng/mL while 17 had levels 10-30 ng/mL. Conversely, among e-cigarette users, the majority (14 of 23) had cotinine ≥500 ng/mL. At baseline, the systolic blood pressure was higher among e-cigarette users than non-users (p=0.011). The mean FMD was slightly lower among e-cigarette users (6.32%) compared to non-users (6.53%). However, in the adjusted analysis, current e-cigarette users did not differ significantly from non-users in their mean FMD (Coefficient=2.05; 95% CI: -2.52-6.63) or RHI (Coefficient= -0.20; 95% CI: -0.88-0.49). Similarly, the levels of inflammatory markers were generally low and did not differ between e-cigarette users and non-users. CONCLUSIONS: Our findings suggest that e-cigarette use may not be significantly associated with endothelial dysfunction and systemic inflammation in relatively young and healthy individuals. Longer term studies with larger sample sizes are needed to validate these findings.

Psychosocial stressors and current e-cigarette use in the youth risk behavior survey.

BACKGROUND: This study explores the association between psychosocial stressors and current e-cigarette use among adolescents in the United States. METHODS: We used data from 12,767 participants in the 2019 National Youth Risk Behavioral Survey to examine the association between psychosocial stressors (bullying, sexual assault, safety-related absence from school, depressive symptoms, suicidal ideation, physical altercation, and weapon threats) and past-30-day e-cigarette use using multivariable-adjusted logistic regression models. We examined the association for each stressor and then as a burden score (0-7). To compare the strength of the association between stressors and current e-cigarette use to current combustible cigarette use, we additionally examined the association between each stressor and current combustible cigarette use. RESULTS: Approximately 32.7% reported current e-cigarette use. The weighted prevalence of current e-cigarette use was higher among individuals who experienced stressors than those who did not. For example, bullying (43.9% vs. 29.0%). Similar prevalence patterns were seen among other stressors. Individuals who experienced stressors had significantly higher adjusted odds of current e-cigarette use than those who did not (OR [Odds Ratio] range: 1.47-1.75). Similarly, individuals with higher burden scores had a higher prevalence (zero [20.5%], one [32.8%], two [41.4%], three [49.6%], four to seven [60.9%]) and higher odds of current e-cigarette use (OR range: 1.43-2.73) than those with a score of zero. The strength of the association between the stressors and e-cigarette use was similar to that between the stressors and combustible cigarette use. CONCLUSION: The study demonstrates a significant association between psychosocial stressors and adolescent e-cigarette use, highlighting the potential importance of interventions, such as targeted school-based programs that address stressors and promote stress management, as possible means of reducing adolescent e-cigarette use. Future research directions include exploring underlying mechanisms linking stressors to e-cigarette use and evaluating the effectiveness of interventions addressing stressors in reducing adolescent e-cigarette use.

Patterns of tobacco product use and substance misuse among adolescents in the United States.

Among adolescents, sole use is the most common pattern of e-cigarette use. However, concurrent use of e-cigarettes with other tobacco products is not uncommon and may be associated with high-risk behaviors. We used data from 12,767 participants in the 2019 Youth Risk Behavior Survey to examine the patterns of tobacco product use among youth in the US. First, we examined the prevalence of e-cigarette-specific patterns of tobacco use (nonuse[no tobacco product use], sole use[sole e-cigarette use], dual-use[e-cigarette and one other tobacco product], and poly use[e-cigarette and two or more other tobacco products]). Then, using multivariable Poisson regression, we assessed how the tobacco use patterns were associated with the misuse of nine substances of abuse (alcohol, marijuana, cocaine, ecstasy, hallucinogens, heroin, inhalants, injectables, and methamphetamines). 62.9% of youth reported nonuse of any tobacco product. The weighted prevalence of sole e-cigarette use, dual use, and poly use was 23.2%, 4.2%, and 3.3%, respectively. Across all the substances explored, the prevalence was highest among poly users, followed by dual users, sole users, and non-users. Compared to non-users, sole, dual, and poly users had 7.8(95 %CI:6.1-10.0), 14.3(95 %CI:10.8-18.8), and 19.7(95 %CI:15.0-25.9) times higher adjusted prevalence of reporting past-30-day binge drinking, after adjusting for age, sex, race/ethnicity, sexual orientation, and depressive symptoms. This pattern was seen across all the different substances explored. These findings highlight the high prevalence of substance misuse among youth who use tobacco products and the need to educate and counsel on substances of abuse among this population, particularly among poly-tobacco users.

Skeletal muscle analysis of cancer patients reveals a potential role for carnosine in muscle wasting.

BACKGROUND: Muscle wasting during cancer cachexia is mediated by protein degradation via autophagy and ubiquitin-linked proteolysis. These processes are sensitive to changes in intracellular pH ([pH]i ) and reactive oxygen species, which in skeletal muscle are partly regulated by histidyl dipeptides, such as carnosine. These dipeptides, synthesized by the enzyme carnosine synthase (CARNS), remove lipid peroxidation-derived aldehydes, and buffer [pH]i . Nevertheless, their role in muscle wasting has not been studied. METHODS: Histidyl dipeptides in the rectus abdominis (RA) muscle and red blood cells (RBCs) of male and female controls (n = 37), weight stable (WS: n = 35), and weight losing (WL; n = 30) upper gastrointestinal cancer (UGIC) patients, were profiled by LC-MS/MS. Expression of enzymes and amino acid transporters, involved in carnosine homeostasis, was measured by Western blotting and RT-PCR. Skeletal muscle myotubes were treated with Lewis lung carcinoma conditioned medium (LLC CM), and ß-alanine to study the effects of enhancing carnosine production on muscle wasting. RESULTS: Carnosine was the predominant dipeptide present in the RA muscle. In controls, carnosine levels were higher in men (7.87 ± 1.98 nmol/mg tissue) compared with women (4.73 ± 1.26 nmol/mg tissue; P = 0.002). In men, carnosine was significantly reduced in both the WS (5.92 ± 2.04 nmol/mg tissue, P = 0.009) and WL (6.15 ± 1.90 nmol/mg tissue; P = 0.030) UGIC patients, compared with controls. In women, carnosine was decreased in the WL UGIC (3.42 ± 1.33 nmol/mg tissue; P = 0.050), compared with WS UGIC patients (4.58 ± 1.57 nmol/mg tissue), and controls (P = 0.025). Carnosine was significantly reduced in the combined WL UGIC patients (5.12 ± 2.15 nmol/mg tissue) compared with controls (6.21 ± 2.24 nmol/mg tissue; P = 0.045). Carnosine was also significantly reduced in the RBCs of WL UGIC patients (0.32 ± 0.24 pmol/mg protein), compared with controls (0.49 ± 0.31 pmol/mg protein, P = 0.037) and WS UGIC patients (0.51 ± 0.40 pmol/mg protein, P = 0.042). Depletion of carnosine diminished the aldehyde-removing ability in the muscle of WL UGIC patients. Carnosine levels were positively associated with decreases in skeletal muscle index in the WL UGIC patients. CARNS expression was decreased in the muscle of WL UGIC patients and myotubes treated with LLC-CM. Treatment with ß-alanine, a carnosine precursor, enhanced endogenous carnosine production and decreased ubiquitin-linked protein degradation in LLC-CM treated myotubes. CONCLUSIONS: Depletion of carnosine could contribute to muscle wasting in cancer patients by lowering the aldehyde quenching abilities. Synthesis of carnosine by CARNS in myotubes is particularly affected by tumour derived factors and could contribute to carnosine depletion in WL UGIC patients. Increasing carnosine in skeletal muscle may be an effective therapeutic intervention to prevent muscle wasting in cancer patients.

Compliance With the US Food and Drug Administration's Guidelines for Health Warning Labels and Engagement in Little Cigar and Cigarillo Content: Computer Vision Analysis of Instagram Posts.

Background: Health warnings in tobacco advertisements provide health information while also increasing the perceived risks of tobacco use. However, existing federal laws requiring warnings on advertisements for tobacco products do not specify whether the rules apply to social media promotions. Objective: This study aims to examine the current state of influencer promotions of little cigars and cigarillos (LCCs) on Instagram and the use of health warnings in influencer promotions. Methods: Instagram influencers were identified as those who were tagged by any of the 3 leading LCC brand Instagram pages between 2018 and 2021. Posts from identified influencers, which mentioned one of the three brands were considered LCC influencer promotions. A novel Warning Label Multi-Layer Image Identification computer vision algorithm was developed to measure the presence and properties of health warnings in a sample of 889 influencer posts. Negative binomial regressions were performed to examine the associations of health warning properties with post engagement (number of likes and comments). Results: The Warning Label Multi-Layer Image Identification algorithm was 99.3% accurate in detecting the presence of health warnings. Only 8.2% (n=73) of LCC influencer posts included a health warning. Influencer posts that contained health warnings received fewer likes (incidence rate ratio 0.59, P<.001, 95% CI 0.48-0.71) and fewer comments (incidence rate ratio 0.46, P<.001, 95% CI 0.31-0.67). Conclusions: Health warnings are rarely used by influencers tagged by LCC brands' Instagram accounts. Very few influencer posts met the US Food and Drug Administration's health warning requirement of size and placement for tobacco advertising. The presence of a health warning was associated with lower social media engagement. Our study provides support for the implementation of comparable health warning requirements to social media tobacco promotions. Using an innovative computer vision approach to detect health warning labels in influencer promotions on social media is a novel strategy for monitoring health warning compliance in social media tobacco promotions.

Association of Electronic Cigarette Exposure on Cardiovascular Health: A Systematic Review and Meta-Analysis.

Despite the growing use of electronic cigarettes (EC) in the Unites States, particularly among young people, and their perceived safety, current evidence suggests that EC usage may cause adverse clinical cardiovascular effects. Therefore, we aim to pool all studies evaluating the association of EC exposure with cardiovascular health. Medline, Cochrane CENTRAL, and Scopus were searched for studies from January 1, 2006 until December 31, 2022. Randomized and observational studies reporting cardiovascular outcomes, hemodynamic parameters, and biomarkers of platelet physiology, before and after acute or chronic EC exposure were pooled using a random-effects model. Overall, 27 studies (n = 863) were included. Heart rate increased significantly after acute EC exposure (weighted mean difference [WMD]: 0.76 bpm; 95% confidence interval [CI], 0.48, 1.03; P < 0.00001; I2 = 92%). Significant increases in systolic blood pressure (WMD: 0.28 mmHg; 95% CI, 0.06, 0.51; P = 0.01; I2 = 94%), diastolic blood pressure (WMD: 0.38 mmHg; 95% CI, 0.16, 0.60; P = 0.0006; I2 = 90%), and PWV (WMD: 0.38; 95% CI, 0.13, 0.63; P = 0.003; I2 = 100%) were also observed. Augmentation index increased significantly (SMD: 0.39; 95% CI, 0.11, 0.67; P = 0.007; I2 = 90%), whereas reduction in flow-mediated dilation (WMD: -1.48; 95% CI, -2.49, -0.47; P = 0.004; I2 = 45%) was observed. Moreover, significant rise in both soluble P-selectin (WMD: 4.73; 95% CI, 0.80, 8.66; P = 0.02; I2 = 98%) and CD40L (WMD: 1.14; 95% CI, 0.41, 1.87; P = 0.002; I2 = 79%) was observed. Our results demonstrate that smoking EC is associated with a significant increase in cardiovascular hemodynamic measures and biomarkers. Our findings can aid policymakers in making informed decisions regarding the regulation of EC to ensure public safety.

Exposure to Volatile Organic Compounds Is Associated with Hypertension in Black Adults: The Jackson Heart Study.

BACKGROUND: The prevalence of hypertension is higher among Black adults than among White and Hispanic adults. Nevertheless, reasons underlying the higher rates of hypertension in the Black population remain unclear but may relate to exposure to environmental chemicals such as volatile organic compounds (VOCs). METHODS: We evaluated the associations of blood pressure (BP) and hypertension with VOC exposure in non-smokers and smokers in a subgroup of the Jackson Heart Study (JHS), consisting of 778 never smokers and 416 age- and sex-matched current smokers. We measured urinary metabolites of 17 VOCs by mass spectrometry. RESULTS: After adjusting for covariates, we found that amoong non-smokers, metabolites of acrolein and crotonaldehyde were associated with a 1.6 mm Hg (95%CI: 0.4, 2.7; p = 0.007) and a 0.8 mm Hg (95%CI: 0.01, 1.6; p = 0.049) higher systolic BP, and the styrene metabolite was associated with a 0.4 mm Hg (95%CI: 0.09, 0.8, p = 0.02) higher diastolic BP. Current smokers had 2.8 mm Hg (95% CI 0.5, 5.1) higher systolic BP. They were at higher risk of hypertension (relative risk = 1.2; 95% CI, 1.1, 1.4), and had higher urinary levels of several VOC metabolites. Individuals who smoke had higher levels of the urinary metabolites of acrolein, 1,3-butadiene, and crotonaldehyde and were associated with higher systolic BP. The associations were stronger among participants who were <60 years of age and male. Using Bayesian kernel machine regression to assess the effects of multiple VOC exposures, we found that the relationship between VOCs and hypertension among non-smokers was driven primarily by acrolein and styrene in non-smokers, and crotonaldehyde in smokers. CONCLUSIONS: Hypertension in Black individuals may be attributed, in part, to VOC exposure from the environment or tobacco smoke.