Greenspaces And Cardiovascular Health.

Accumulating evidence suggests that living in areas of high surrounding greenness or even brief exposures to areas of high greenery is conducive to cardiovascular health, which may be related to the environmental, social, psychological, and physiological benefits of greenspaces. Recent data from multiple cross-sectional, longitudinal, and cohort studies suggest that living in areas of high surrounding greenness is associated with a lower risk of all-cause and cardiovascular mortality. High levels of neighborhood greenery have been linked also to a decrease in the burden of cardiovascular disease risk factors as reflected by lower rates of hypertension, dyslipidemia, and diabetes. Those who live in greener environments report better mental health and more frequent social interactions, which can benefit cardiovascular health as well. In this narrative review, we discuss evidence linking greenspaces to cardiovascular health as well as the potential mechanisms underlying the beneficial effects of greenspaces, including the impact of vegetation on air, noise and light pollution, ambient temperature, physical activity, mental health, and biodiversity. We review literature on the beneficial effects of acute and chronic exposure to nature on cardiovascular disease risk factors, inflammation and immune function, and we highlight the potential cardiovascular effects of biogenic volatile organic compounds that are emitted by trees and shrubs. We identify current knowledge gaps in this area and underscore the need for additional population studies to understand more clearly and precisely the link between greenness and health. Such understanding is urgently needed to fully redeem the promise of greenspaces in preventing adverse environmental exposures, mitigating the effects of climate change, and creating healthier living environments.

Dynamic SARS-CoV-2 surveillance model combining seroprevalence and wastewater concentrations for post-vaccine disease burden estimates.

BACKGROUND: Despite wide scale assessments, it remains unclear how large-scale severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination affected the wastewater concentration of the virus or the overall disease burden as measured by hospitalization rates. METHODS: We used weekly SARS-CoV-2 wastewater concentration with a stratified random sampling of seroprevalence, and linked vaccination and hospitalization data, from April 2021-August 2021 in Jefferson County, Kentucky (USA). Our susceptible ( S ), vaccinated ( V ), variant-specific infected ( I 1 and I 2 ), recovered ( R ), and seropositive ( T ) model ( S V I 2 R T ) tracked prevalence longitudinally. This was related to wastewater concentration. RESULTS: Here we show the 64% county vaccination rate translate into about a 61% decrease in SARS-CoV-2 incidence. The estimated effect of SARS-CoV-2 Delta variant emergence is a 24-fold increase of infection counts, which correspond to an over 9-fold increase in wastewater concentration. Hospitalization burden and wastewater concentration have the strongest correlation (r = 0.95) at 1 week lag. CONCLUSIONS: Our study underscores the importance of continuing environmental surveillance post-vaccine and provides a proof-of-concept for environmental epidemiology monitoring of infectious disease for future pandemic preparedness.

It is unclear how large-scale COVID-19 vaccination impacts wastewater concentration or overall disease burden. Here, we developed a mathematical surveillance model that allows estimation of overall vaccine impact based on the amount of SARS-CoV-2 in wastewater, seroprevalence and the number of cases admitted to hospitals between April 2021­August 2021 in Jefferson County, Kentucky USA. We found that a 64% vaccination coverage correlated to a 61% decrease in COVID-19 cases. The emergence of the SARS-CoV-2 Delta variant during the time of the surveillance directly correlated with a sharp increase in infection incidence as well as viral counts in wastewater. The hospitalization burden was closely reflected by the viral count found in the wastewater, indicating that post-vaccine environmental surveillance can be an effective method of estimating changing disease prevalence in future pandemics.

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.

Toward Heart-Healthy and Sustainable Cities: A Policy Statement From the American Heart Association.

Nearly 56% of the global population lives in cities, with this number expected to increase to 6.6 billion or >70% of the world's population by 2050. Given that cardiometabolic diseases are the leading causes of morbidity and mortality in people living in urban areas, transforming cities and urban provisioning systems (or urban systems) toward health, equity, and economic productivity can enable the dual attainment of climate and health goals. Seven urban provisioning systems that provide food, energy, mobility-connectivity, housing, green infrastructure, water management, and waste management lie at the core of human health, well-being, and sustainability. These provisioning systems transcend city boundaries (eg, demand for food, water, or energy is met by transboundary supply); thus, transforming the entire system is a larger construct than local urban environments. Poorly designed urban provisioning systems are starkly evident worldwide, resulting in unprecedented exposures to adverse cardiometabolic risk factors, including limited physical activity, lack of access to heart-healthy diets, and reduced access to greenery and beneficial social interactions. Transforming urban systems with a cardiometabolic health-first approach could be accomplished through integrated spatial planning, along with addressing current gaps in key urban provisioning systems. Such an approach will help mitigate undesirable environmental exposures and improve cardiovascular and metabolic health while improving planetary health. The purposes of this American Heart Association policy statement are to present a conceptual framework, summarize the evidence base, and outline policy principles for transforming key urban provisioning systems to heart-health and sustainability outcomes.

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.

Long-term exposure to air pollution and risk of stroke by ecoregions: The REGARDS study.

Several cohort studies have found associations between long-term exposure to air pollution and stroke risk. However, it is unclear whether the surrounding ecology may modify these associations. This study evaluates associations of air pollution with stroke risk by ecoregions, which are areas of similar type, quality, and quantity of environmental resources in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. We assessed the incidence of stroke in 26,792 participants (45+ yrs) from the REGARDS study, a prospective cohort recruited across the contiguous United States. One-yr and 3-yr means of PM2.5, PM10, O3, NO2, SO2, and CO were estimated at baseline using data from the Center for Air, Climate, & Energy Solution, and assigned to participants at the census block group level. Incident stroke was ascertained through September 30, 2020. Relations of air pollutants with the risk of incident stroke were estimated using Cox proportional hazards models, adjusting for relevant demographics, behavioral risk factors, and neighborhood urbanicity. Models were stratified by EPA designated ecoregions. A 5.4 µg/m3 (interquartile range) increase in 1-yr PM10 was associated with a hazard ratio (95 %CI) for incident stroke of 1.07 (1.003, 1.15) in the overall study population. We did not find evidence of positive associations for PM2.5, O3, NO2, SO2, and CO in the fully adjusted models. In our ecoregion-specific analysis, associations of PM2.5 with stroke were stronger in the Great Plains ecoregion (HR = 1.44) than other ecoregions, while associations for PM10 were strongest in the Eastern Temperate Forests region (HR = 1.15). The associations between long-term exposure to air pollution and risk of stroke varied by ecoregion. Our results suggests that the type, quality, and quantity of the surrounding ecology can modify the effects of air pollution on risk of stroke.

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.

Racial/Ethnic Discrimination and Cardiometabolic Diseases: A Systematic Review.

INTRODUCTION: Racial discrimination has been identified as a risk factor for cardiometabolic diseases, the leading cause of morbidity and mortality among racial/ethnic minority groups; however, there is no synthesis of current knowledge on the association between discrimination and cardiometabolic diseases. The objective of this systematic review was to summarize evidence linking racial/ethnic discrimination and cardiometabolic diseases. METHODS: The review was conducted based on studies identified via electronic searches of 5 databases (PubMed, Google Scholar, WorldWideScience.org, ResearchGate and Microsoft Academic) using terms related to discrimination and cardiometabolic disease. RESULTS: Of the 123 eligible studies included in the review, 87 were cross-sectional, 25 longitudinal, 8 quasi-experimental, 2 randomized controlled trials and 1 case-control. Cardiometabolic disease outcomes discussed were hypertension (n = 46), cardiovascular disease (n = 40), obesity (n = 12), diabetes (n = 11), metabolic syndrome (n = 9), and chronic kidney disease (n = 5). Although a variety of discrimination measures was employed across the studies, the Everyday Discrimination Scale was used most often (32.5%). African Americans/Blacks were the most frequently studied racial/ethnic group (53.1%), and American Indians the least (0.02%). Significant associations between racial/ethnic discrimination and cardiometabolic disease were found in 73.2% of the studies. DISCUSSION: Racial/ethnic discrimination is positively associated with increased risk of cardiometabolic disease and higher levels of cardiometabolic biomarkers. Identifying racial/ethnic discrimination as a potential key contributor to the health inequities associated with cardiometabolic diseases is important for addressing the significant burden borne by racial/ethnic minorities.

Evaluation of urinary limonene metabolites as biomarkers of exposure to greenness.

Exposure to plants is known to improve physical and mental health and living in areas of high vegetation is associated with better health. The addition of quantitative measures of greenness exposure at individual-level to other objective and subjective study measures will help establish cause-and-effect relationships between greenspaces and human health. Because limonene is one of the most abundant biogenic volatile organic compounds emitted by plants, we hypothesized that urinary metabolites of inhaled limonene can serve as biomarkers of exposure to greenness. To test our hypothesis, we analyzed urine samples collected from eight human volunteers after limonene inhalation or after greenness exposure using liquid chromatography-high resolution mass spectrometry-based profiling. Eighteen isomers of nine metabolites were detected in urine after limonene inhalation, and their kinetic parameters were estimated using nonlinear mixed effect models. Urinary levels of most abundant limonene metabolites were elevated after brief exposure to a forested area, and the ratio of urinary limonene metabolites provided evidence of recent exposure. The identities and structures of these metabolites were validated using stable isotope tracing and tandem mass spectral comparison. Together, these data suggest that urinary metabolites of limonene, especially uroterpenol glucuronide and dihydroperillic acid glucuronide, could be used as individualized biomarkers of greenness exposure.

Predictive power of wastewater for nowcasting infectious disease transmission: A retrospective case study of five sewershed areas in Louisville, Kentucky.

BACKGROUND: Epidemiological nowcasting traditionally relies on count surveillance data. The availability and quality of such count data may vary over time, limiting representation of true infections. Wastewater data correlates with traditional surveillance data and may provide additional value for nowcasting disease trends. METHODS: We obtained SARS-CoV-2 case, death, wastewater, and serosurvey data for Jefferson County, Kentucky (USA), between August 2020 and March 2021, and parameterized an existing nowcasting model using combinations of these data. We assessed the predictive performance and variability at the sewershed level and compared the effects of adding or replacing wastewater data to case and death reports. FINDINGS: Adding wastewater data minimally improved the predictive performance of nowcasts compared to a model fitted to case and death data (Weighted Interval Score (WIS) 0.208 versus 0.223), and reduced the predictive performance compared to a model fitted to deaths data (WIS 0.517 versus 0.500). Adding wastewater data to deaths data improved the nowcasts agreement to estimates from models using cases and deaths data. These findings were consistent across individual sewersheds as well as for models fit to the aggregated total data of 5 sewersheds. Retrospective reconstructions of epidemiological dynamics created using different combinations of data were in general agreement (coverage >75%). INTERPRETATION: These findings show wastewater data may be valuable for infectious disease nowcasting when clinical surveillance data are absent, such as early in a pandemic or in low-resource settings where systematic collection of epidemiologic data is difficult.

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.

The Green Heart Project: Objectives, Design, and Methods.

The Green Heart Project is a community-based trial to evaluate the effects of increasing greenery on urban environment and community health. The study was initiated in 2018 in a low-to-middle-income mixed-race residential area of nearly 28,000 residents in Louisville, KY. The 4 square mile area was surveyed for land use, population characteristics, and greenness, and assigned to 8 paired clusters of demographically- and environmentally matched "target" (T) and adjacent "control" (C), clusters. Ambient levels of ultrafine particles, ozone, oxides of nitrogen, and environmental noise were measured in each cluster. Individual-level data were acquired during in-person exams of 735 participants in Wave 1 (2018-2019) and 545 participants in Wave 2 (2021) to evaluate sociodemographic and psychosocial factors. Blood, urine, nail, and hair samples were collected to evaluate standard cardiovascular risk factors, inflammation, stress, and pollutant exposure. Cardiovascular function was assessed by measuring arterial stiffness and flow-mediated dilation. After completion of Wave 2, more than 8,000 mature, mostly evergreen, trees and shrubs were planted in the T clusters in 2022. Post planting environmental and individual-level data were collected during Wave 3 (2022) from 561 participants. We plan to continue following changes in area characteristics and participant health to evaluate the long-term impact of increasing urban greenery.

Aldose Reductase (AR) Mediates and Perivascular Adipose Tissue (PVAT) Modulates Endothelial Dysfunction of Short-Term High-Fat Diet Feeding in Mice.

Increased adiposity of both visceral and perivascular adipose tissue (PVAT) depots is associated with an increased risk of diabetes and cardiovascular disease (CVD). Under healthy conditions, PVAT modulates vascular tone via the release of PVAT-derived relaxing factors, including adiponectin and leptin. However, when PVAT expands with high-fat diet (HFD) feeding, it appears to contribute to the development of endothelial dysfunction (ED). Yet, the mechanisms by which PVAT alters vascular health are unclear. Aldose reductase (AR) catalyzes glucose reduction in the first step of the polyol pathway and has been long implicated in diabetic complications including neuropathy, retinopathy, nephropathy, and vascular diseases. To better understand the roles of both PVAT and AR in HFD-induced ED, we studied structural and functional changes in aortic PVAT induced by short-term HFD (60% kcal fat) feeding in wild type (WT) and aldose reductase-null (AR-null) mice. Although 4 weeks of HFD feeding significantly increased body fat and PVAT mass in both WT and AR-null mice, HFD feeding induced ED in the aortas of WT mice but not of AR-null mice. Moreover, HFD feeding augmented endothelial-dependent relaxation in aortas with intact PVAT only in WT and not in AR-null mice. These data indicate that AR mediates ED associated with short-term HFD feeding and that ED appears to provoke 'compensatory changes' in PVAT induced by HFD. As these data support that the ED of HFD feeding is AR-dependent, vascular-localized AR remains a potential target of temporally selective intervention.

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.