Catecholamine levels with use of electronic and combustible cigarettes.

INTRODUCTION: Smoking elevates catecholamines that increase the risk for cardiovascular disease. Sparse evidence exists about the effects of e-cigarettes and catecholamines. Higher levels of catecholamines could trigger the increased heart rate, blood pressure, and decreased vascular function reported with the use of e-cigarettes. We investigated the difference in urinary catecholamines and their metabolites before and after the use of an e-cigarette containing nicotine or cigarettes compared to no tobacco use. METHODS: In our observational cohort exposure study, healthy adults aged 21-45 years who were currently using e-cigarettes, cigarettes, or had never used tobacco, participated in an acute exposure visit using their most common tobacco product. Urine was collected before, 1, and 2 hours after a 3-second puff every 30 seconds for 10 minutes on an e-cigarette or straw or use of 1 cigarette. Urinary catecholamines and their metabolites were measured by ultra-high-performance liquid chromatography. Participants (n=323) were grouped by the product used at the visit. We compared levels of creatinine normalized log-transformed urinary catecholamines and their metabolites across groups using Dunn's test following a Kruskal-Wallis test in unadjusted and demographically adjusted models. RESULTS: Prior to use, individuals who used cigarettes (n=70) had lower urinary metabolites from epinephrine, serotonin, and norepinephrine. No differences were seen in those who used e-cigarettes (n=171) and those who did not use tobacco (n=82). In fully adjusted models, 1 h after the use of a combustible or e-cigarette, log-transformed urinary metabolites from norepinephrine (ß=1.22; 95% CI: 0.39-2.05, p=0.004 and ß=1.06; 95% CI: 0.39-1.74, p=0.002), dopamine (ß=0.37; 95% CI: 0.24-0.5, p<0.001 and ß=0.15; 95% CI: 0.05-0.26, p<0.001), and epinephrine (ß=1.89; 95% CI: 0.51-3.27, p=0.008 and ß=1.49; 95% CI: 0.38-2.61, p=0.009) were elevated. In fully adjusted models, combustible cigarette use was associated with elevated urinary norepinephrine (ß=0.46; 95% CI: 0.13-0.81, p=0.007) and dopamine (ß=0.19; 95% CI: 0.06-0.31, p=0.003) 1 h after use. CONCLUSIONS: We found that the use of both e-cigarettes and cigarettes was associated with elevated urinary catecholamines or their metabolites. Catecholamines could be useful as a biomarker of harm for tobacco use and considered by tobacco regulatory scientists in future research.

Cardiovascular Health Effects and Synthetic Cooling Agents in E-cigarettes Labeled as 'clear' Marketed in Massachusetts After the Tobacco Product Flavoring Ban.

Introduction: Massachusetts (MA) enacted statewide regulation on all flavored tobacco products in June 2020. Thereafter, electronic cigarettes (e-cigarettes) labeled 'clear' emerged on the market. We aimed to combine cardiovascular health effects with chemical analysis of 'clear' e-cigarettes. Methods: We measured acute changes in blood pressure and heart rate following a 10-minute structured use of participants' own e-cigarette, comparing 'clear' e-cigarette users with other flavored e-cigarette users and non-users. Chemical characterization and quantification of relevant flavorings and cooling agents (WS-3, WS-23) of 19 'clear'-labeled disposable e-cigarette liquids was carried out by GC/MS. Results: After the ban, participants that used 'clear' labeled e-cigarettes increased from 0% to 21%. Increase in diastolic blood pressure and heart rate was significantly greater in 'clear' e-cigarettes users (n=22) compared to both non-'clear' flavored e-cigarette users (n=114) and non-users (n=72). We saw similar results in heart rate when comparing Juul e-cigarette and 'clear' users; Juul was used as a reference as synthetic coolants WS-3 or WS-23 were not detected in these.All (19/19) 'clear' e-liquids were found to contain synthetic cooling agents WS-23 and/or WS-3, menthol (18/19), as well as other flavorings (12/19). Discussion: The detected presence of menthol alongside other flavorings in tested 'clear' products is a direct violation of the MA flavored tobacco product regulation, warranting stricter monitoring for new products and constituents. 'clear' e-cigarette use led to greater hemodynamic effects compared to other flavored e-cigarettes and Juul, which raises questions about the effect of cooling agents on users.

Polyvascular disease is common in patients undergoing carotid endarterectomy and lower extremity bypass and is associated with worse outcomes.

BACKGROUND: Polyvascular disease is strongly associated with increased risk of cardiovascular morbidity and mortality. However, its prevalence in patients undergoing carotid and lower extremity surgical revascularization and its impact on outcomes are unknown. METHODS: The Vascular Quality Initiative was queried for carotid endarterectomy (CEA) or infrainguinal lower extremity bypass (LEB), 2013-2019. Polyvascular disease was defined as presence of atherosclerotic occlusive disease in more than one arterial bed: carotid, coronary, and infrainguinal. Primary outcomes were (1) composite perioperative myocardial infarction (MI) or death and (2) 5-year survival. Patient characteristics and perioperative outcomes were evaluated using the χ2 test and multivariable logistic regression. Survival was analyzed using Kaplan-Meier method and Cox proportional hazards multivariable models. RESULTS: Polyvascular disease was identified in 47% of CEA (39.0% in 2 arterial beds, 7.6% in 3 arterial beds; n = 93,736) and 47% of LEB (41.0% in 2 arterial beds, 5.7% in 3 arterial beds; n = 25,223). For both CEA and LEB, patients with polyvascular disease had more comorbidities including hypertension, congestive heart disease, chronic obstructive pulmonary disease, smoking, diabetes mellitus, and end-stage renal disease (P < .0001). Perioperative MI/death rates increased with increasing number of vascular beds affected following CEA (0.9% in 1 bed vs 1.5% in 2 beds vs 2.7% in 3 beds; P < .001) and LEB (2.2% in 1 bed vs 5.3% in 2 beds vs 6.6% in 3 beds; P < .001). Polyvascular disease was associated independently with perioperative MI/death after CEA (odds ratio, 1.59; 95% confidence interval [CI], 1.40-1.81;P < .0001) and LEB (odds ratio, 1.78; 95% CI, 1.52-2.08; P < .0001). Five-year survival was decreased in patients with polyvascular disease after CEA (82% in 3 beds vs 88% in 2 beds vs 92% in 1 bed; P < .01) and LEB (72% in 3 beds vs 75% in 2 beds vs 84% in 1 bed; P < .01) in a dose-dependent manner, with the lowest 5-year survival observed in those with three arterial beds involved. Polyvascular disease was independently associated with 5-year mortality after CEA (hazard ratio, 1.33; 95% CI, 1.24-1.40; P = .0001) and LEB (hazard ratio, 1.30; 95% CI, 1.20-1.41; P = .0001). CONCLUSIONS: Polyvascular disease is common in patients undergoing CEA and LEB and is associated with a higher risk of perioperative MI/death and decreased long-term survival. After revascularization, patients with polyvascular disease should be considered for more aggressive cardioprotective medications and closer follow-up.

Coronary Microvascular Function Following Severe Preeclampsia.

BACKGROUND: Preeclampsia is a pregnancy-specific hypertensive disorder associated with an imbalance in circulating proangiogenic and antiangiogenic proteins. Preclinical evidence implicates microvascular dysfunction as a potential mediator of preeclampsia-associated cardiovascular risk. METHODS: Women with singleton pregnancies complicated by severe antepartum-onset preeclampsia and a comparator group with normotensive deliveries underwent cardiac positron emission tomography within 4 weeks of delivery. A control group of premenopausal, nonpostpartum women was also included. Myocardial flow reserve, myocardial blood flow, and coronary vascular resistance were compared across groups. sFlt-1 (soluble fms-like tyrosine kinase receptor-1) and PlGF (placental growth factor) were measured at imaging. RESULTS: The primary cohort included 19 women with severe preeclampsia (imaged at a mean of 15.3 days postpartum), 5 with normotensive pregnancy (mean, 14.4 days postpartum), and 13 nonpostpartum female controls. Preeclampsia was associated with lower myocardial flow reserve (ß, -0.67 [95% CI, -1.21 to -0.13]; P=0.016), lower stress myocardial blood flow (ß, -0.68 [95% CI, -1.07 to -0.29] mL/min per g; P=0.001), and higher stress coronary vascular resistance (ß, +12.4 [95% CI, 6.0 to 18.7] mm Hg/mL per min/g; P=0.001) versus nonpostpartum controls. Myocardial flow reserve and coronary vascular resistance after normotensive pregnancy were intermediate between preeclamptic and nonpostpartum groups. Following preeclampsia, myocardial flow reserve was positively associated with time following delivery (P=0.008). The sFlt-1/PlGF ratio strongly correlated with rest myocardial blood flow (r=0.71; P<0.001), independent of hemodynamics. CONCLUSIONS: In this exploratory cross-sectional study, we observed reduced coronary microvascular function in the early postpartum period following preeclampsia, suggesting that systemic microvascular dysfunction in preeclampsia involves coronary microcirculation. Further research is needed to establish interventions to mitigate the risk of preeclampsia-associated cardiovascular disease.

Characterization of cardiovascular serious adverse events after bypass or endovascular revascularization for limb-threatening ischemia in the BEST-CLI trial.

OBJECTIVE: Cardiovascular complications after revascularization to treat chronic limb-threatening ischemia (CLTI) are a major concern that guides treatment. Our goal was to assess periprocedural cardiac and vascular serious adverse events (SAEs) in the Best Endovascular vs Best Surgical Therapy in Patients with CLTI (BEST-CLI) trial. METHODS: BEST-CLI was a prospective randomized trial comparing surgical (OPEN) and endovascular (ENDO) revascularization for patients with CLTI. Thirty-day SAEs, classified as cardiac or vascular, were analyzed. Adverse events are defined as serious when they affect safety in the trial, require prolonged hospitalization, result in significant disability or incapacitation, are life-threatening, or result in death. Interventions were analyzed in a per protocol fashion. RESULTS: In the BEST-CLI trial, 850 OPEN and 896 ENDO interventions were evaluated. Forty (4.7%) and 34 (3.8%) patients experienced at least one cardiac SAE after OPEN and ENDO intervention, respectively (P = .35). Overall, there were 53 cardiac SAEs (0.06 per patient) after OPEN and 40 (0.045 per patient) after ENDO interventions. Cardiac SAEs in the OPEN arm were classified as related to ischemia (50.9%), arrhythmias (17%), heart failure (15.1%), arrest (13.2%), and heart block (3.8%); in the ENDO arm, they were classified as ischemia (47.5%), heart failure (17.5%), arrhythmias (15%), arrest (15%), and heart block (5%). Approximately half of SAEs were classified as severe for both OPEN and ENDO. SAEs were definitely or probably related to the procedure in 30.2% and 25% in the OPEN and ENDO arms, respectively (P = .2). Vascular SAEs occurred in 58 (6.8%) and 86 (9.6%) of patients after OPEN and ENDO revascularization, respectively (P = .19). In total, there were 59 (0.07 per patient) and 87 (0.097 per patient) vascular SAEs after OPEN and ENDO procedures. Vascular SAEs in the OPEN arm were classified as distal ischemia/infection (44.1%), bleeding (16.9%), occlusive (15.3%), thromboembolic (15.3%), cerebrovascular (5.1%), and other (3.4%); in the ENDO arm, they were distal ischemia/infection (40.2%), occlusive (31%), bleeding (12.6%), thromboembolic (8%), cerebrovascular (1.1%), and other (4.6%). SAEs were classified as severe for OPEN in 45.8% and ENDO in 46%. SAEs were definitely or probably related to the procedure in 23.7% and 35.6% in the OPEN and ENDO arms (P = .35), respectively. CONCLUSIONS: Patients undergoing OPEN and ENDO revascularization experienced similar degrees of cardiac and vascular SAEs. The majority were not related to the index intervention, but approximately half were severe.

Deficiency of lncRNA MERRICAL abrogates macrophage chemotaxis and diabetes-associated atherosclerosis.

Diabetes-associated atherosclerosis involves excessive immune cell recruitment and plaque formation. However, the mechanisms remain poorly understood. Transcriptomic analysis of the aortic intima in Ldlr-/- mice on a high-fat, high-sucrose-containing (HFSC) diet identifies a macrophage-enriched nuclear long noncoding RNA (lncRNA), MERRICAL (macrophage-enriched lncRNA regulates inflammation, chemotaxis, and atherosclerosis). MERRICAL expression increases by 249% in intimal lesions during progression. lncRNA-mRNA pair genomic mapping reveals that MERRICAL positively correlates with the chemokines Ccl3 and Ccl4. MERRICAL-deficient macrophages exhibit lower Ccl3 and Ccl4 expression, chemotaxis, and inflammatory responses. Mechanistically, MERRICAL guides the WDR5-MLL1 complex to activate CCL3 and CCL4 transcription via H3K4me3 modification. MERRICAL deficiency in HFSC diet-fed Ldlr-/- mice reduces lesion formation by 74% in the aortic sinus and 86% in the descending aorta by inhibiting leukocyte recruitment into the aortic wall and pro-inflammatory responses. These findings unveil a regulatory mechanism whereby a macrophage-enriched lncRNA potently inhibits chemotactic responses, alleviating lesion progression in diabetes.

Addressing Barriers to Entry and Retention of Women in Interventional Vascular Specialties With Proposed Solutions: A Scientific Statement From the American Heart Association.

Representation of women in interventional vascular fields (interventional cardiology, interventional radiology, and vascular surgery) lags behind that in other specialties. With women representing half of all medical school graduates, encouraging parity of women in these fields needs to start in medical school. Barriers to pursuing careers in vascular intervention include insufficient exposure during core clerkships, early mentorship, visibility of women in the field, length of training, lifestyle considerations, work culture and environment, and concerns about radiation exposure. This scientific statement highlights potential solutions for both the real and perceived barriers that women may face in pursuing careers in vascular intervention, including streamlining of training (as both interventional radiology and vascular surgery have done with a resultant increase in percentage of women trainees), standardization of institutional promotion of women in leadership, and professional and industry partnerships for the retention and advancement of women.

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.

Adverse Impact of Cannabis on Human Health.

Cannabis, the most commonly used recreational drug, is illicit in many areas of the world. With increasing decriminalization and legalization, cannabis use is increasing in the United States and other countries. The adverse effects of cannabis are unclear because its status as a Schedule 1 drug in the United States restricts research. Despite a paucity of data, cannabis is commonly perceived as a benign or even beneficial drug. However, recent studies show that cannabis has adverse cardiovascular and pulmonary effects and is linked with malignancy. Moreover, case reports have shown an association between cannabis use and neuropsychiatric disorders. With growing availability, cannabis misuse by minors has led to increasing incidences of overdose and toxicity. Though difficult to detect, cannabis intoxication may be linked to impaired driving and motor vehicle accidents. Overall, cannabis use is on the rise, and adverse effects are becoming apparent in clinical data sets.

Vascular Age Assessed From an Uncalibrated, Noninvasive Pressure Waveform by Using a Deep Learning Approach: The AI-VascularAge Model.

BACKGROUND: Aortic stiffness, assessed as carotid-femoral pulse wave velocity, provides a measure of vascular age and risk for adverse cardiovascular disease outcomes, but it is difficult to measure. The shape of arterial pressure waveforms conveys information regarding aortic stiffness; however, the best methods to extract and interpret waveform features remain controversial. METHODS: We trained a convolutional neural network with fixed-scale (time and amplitude) brachial, radial, and carotid tonometry waveforms as input and negative inverse carotid-femoral pulse wave velocity as label. Models were trained with data from 2 community-based Icelandic samples (N=10 452 participants with 31 126 waveforms) and validated in the community-based Framingham Heart Study (N=7208 participants, 21 624 waveforms). Linear regression rescaled predicted negative inverse carotid-femoral pulse wave velocity to equivalent artificial intelligence vascular age (AI-VA). RESULTS: The AI-VascularAge model predicted negative inverse carotid-femoral pulse wave velocity with R2=0.64 in a randomly reserved Icelandic test group (n=5061, 16%) and R2=0.60 in the Framingham Heart Study. In the Framingham Heart Study (up to 18 years of follow-up; 479 cardiovascular disease, 200 coronary heart disease, and 213 heart failure events), brachial AI-VA was associated with incident cardiovascular disease adjusted for age and sex (model 1; hazard ratio, 1.79 [95% CI, 1.50-2.40] per SD; P<0.0001) or adjusted for age, sex, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, prevalent diabetes, hypertension treatment, and current smoking (model 2; hazard ratio, 1.50 [95% CI, 1.24-1.82] per SD; P<0.0001). Similar hazard ratios were demonstrated for incident coronary heart disease and heart failure events and for AI-VA values estimated from carotid or radial waveforms. CONCLUSIONS: Our results demonstrate that convolutional neural network-derived AI-VA is a powerful indicator of vascular health and cardiovascular disease risk in a broad community-based sample.

Cardiopulmonary Impact of Electronic Cigarettes and Vaping Products: A Scientific Statement From the American Heart Association.

Vaping and electronic cigarette (e-cigarette) use have grown exponentially in the past decade, particularly among youth and young adults. Cigarette smoking is a risk factor for both cardiovascular and pulmonary disease. Because of their more limited ingredients and the absence of combustion, e-cigarettes and vaping products are often touted as safer alternative and potential tobacco-cessation products. The outbreak of e-cigarette or vaping product use-associated lung injury in the United States in 2019, which led to >2800 hospitalizations, highlighted the risks of e-cigarettes and vaping products. Currently, all e-cigarettes are regulated as tobacco products and thus do not undergo the premarket animal and human safety studies required of a drug product or medical device. Because youth prevalence of e-cigarette and vaping product use was as high as 27.5% in high school students in 2019 in the United States, it is critical to assess the short-term and long-term health effects of these products, as well as the development of interventional and public health efforts to reduce youth use. The objectives of this scientific statement are (1) to describe and discuss e-cigarettes and vaping products use patterns among youth and adults; (2) to identify harmful and potentially harmful constituents in vaping aerosols; (3) to critically assess the molecular, animal, and clinical evidence on the acute and chronic cardiovascular and pulmonary risks of e-cigarette and vaping products use; (4) to describe the current evidence of e-cigarettes and vaping products as potential tobacco-cessation products; and (5) to summarize current public health and regulatory efforts of e-cigarettes and vaping products. It is timely, therefore, to review the short-term and especially the long-term implications of e-cigarettes and vaping products on cardiopulmonary health. Early molecular and clinical evidence suggests various acute physiological effects from electronic nicotine delivery systems, particularly those containing nicotine. Additional clinical and animal-exposure model research is critically needed as the use of these products continues to grow.

A Longitudinal Study of Perceptions of the Massachusetts Menthol Ban and Its Impact on Smoking Behaviors among Marginalized Individuals.

Menthol cigarettes have had a profound adverse effect on public health. On 1 June 2020, Massachusetts became the first state to ban the sale of menthol cigarettes. We explored how perceptions of the ban and smoking behaviors changed over time among a group of 27 individuals who smoked menthol cigarettes at our safety-net hospital. In a convergent mixed methods study, we administered questionnaires and interviews simultaneously at two timepoints: 1 month pre-ban and 6 months post-ban. Pre-ban, we assessed perceptions of the ban and anticipated smoking behaviors after the ban. Post-ban, we assessed participants' actual smoking behaviors and elicited suggestions to avoid unintended consequences that might undermine intended policy effects. Several respondents perceived the Massachusetts ban as positive because it could promote smoking cessation, prevent youth initiation, and mitigate unfair targeting of socioeconomically disadvantaged populations. Others perceived the ban as an overreach of government policy, financially motivated, and unfairly targeting the Black community. Many continued to smoke menthol cigarettes obtained outside Massachusetts. Individuals suggested promoting tobacco treatment for people affected by the ban and a national ban to circumvent out-of-state purchasing of menthol cigarettes. Our findings suggest that in order to be most effective, healthcare systems must promote tobacco treatment and ensure that treatment is accessible to all individuals affected by the ban.

A modern day perspective on smoking in peripheral artery disease.

Peripheral artery disease (PAD) is associated with increased risk of cardiovascular morbidity and mortality, poor functional status, and lower quality of life. Cigarette smoking is a major preventable risk factor for PAD and is strongly associated with a higher risk of disease progression, worse post-procedural outcomes, and increased healthcare utilization. The arterial narrowing due to atherosclerotic lesions in PAD leads to decreased perfusion to the limbs and can ultimately cause arterial obstruction and limb ischemia. Endothelial cell dysfunction, oxidative stress, inflammation, and arterial stiffness are among the key events during the development of atherogenesis. In this review, we discuss the benefits of smoking cessation among patients with PAD and the use of smoking cessation methods including pharmacological treatment. Given that smoking cessation interventions remain underutilized, we highlight the importance of incorporating smoking cessation treatments as part of the medical management of patients with PAD. Regulatory approaches to reduce the uptake of tobacco product use and support smoking cessation have the potential to reduce the burden of PAD.

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.

Pod-based e-liquids impair human vascular endothelial cell function.

Pod-based electronic (e-) cigarettes more efficiently deliver nicotine using a protonated formulation. The cardiovascular effects associated with these devices are poorly understood. We evaluated whether pod-based e-liquids and their individual components impair endothelial cell function. We isolated endothelial cells from people who are pod users (n = 10), tobacco never users (n = 7), and combustible cigarette users (n = 6). After a structured use, pod users had lower acetylcholine-mediated endothelial nitric oxide synthase (eNOS) activation compared with never users and was similar to levels from combustible cigarette users (overall P = 0.008, P = 0.01 pod vs never; P = 0.96 pod vs combustible cigarette). The effects of pod-based e-cigarettes and their constituents on vascular cell function were further studied in commercially available human aortic endothelial cells (HAECs) incubated with flavored JUUL e-liquids or propylene glycol (PG):vegetable glycerol (VG) at 30:70 ratio with or without 60 mg/mL nicotine salt for 90 min. A progressive increase in cell death with JUUL e-liquid exposure was observed across 0.0001-1% dilutions; PG:VG vehicle with and without nicotine salt induced cell death. A23187-stimulated nitric oxide production was decreased with all JUUL e-liquid flavors, PG:VG and nicotine salt exposures. Aerosols generated by JUUL e-liquid heating similarly decreased stimulated nitric oxide production. Only mint flavored e-liquids increased inflammation and menthol flavored e-liquids enhanced oxidative stress in HAECs. In conclusion, pod e-liquids and their individual components appear to impair endothelial cell function. These findings indicate the potential harm of pod-based devices on endothelial cell function and thus may be relevant to cardiovascular injury in pod type e-cigarette users.

Association of electronic cigarette use with circulating angiogenic cell levels in healthy young adults: Evidence for chronic systemic injury.

BACKGROUND: Circulating angiogenic cells (CACs) are indicative of vascular health and repair capacity; however, their relationship with chronic e-cigarette use is unclear. This study aims to assess the association between e-cigarette use and CAC levels. METHODS: We analyzed CAC levels in 324 healthy participants aged 21-45 years from the cross-sectional Cardiovascular Injury due to Tobacco Use study in four groups: never tobacco users (n = 65), sole e-cigarette users (n = 19), sole combustible cigarette users (n = 212), and dual users (n = 28). A total of 15 CAC subpopulations with four cell surface markers were measured using flow cytometry: CD146 (endothelial), CD34 (stem), CD45 (leukocyte), and AC133 (early progenitor/stem). Generalized linear models with gamma distribution and log-link were generated to assess association between CACs and smoking status. Benjamini-Hochberg were used to adjust p-values for multiple comparisons. RESULTS: The cohort was 47% female, 51% Black/African American, with a mean (± SD) age of 31 ± 7 years. Sole cigarette use was significantly associated with higher levels of two endothelial marker CACs (Q ⩽ 0.05). Dual users had higher levels of four endothelial marker CACs and one early progenitor/stem marker CAC (Q ⩽ 0.05). Sole e-cigarette users had higher levels of one endothelial and one leukocyte marker CAC (Q ⩽ 0.05). CONCLUSION: Dual use of e-cigarettes and combustible cigarettes was associated with higher levels of endothelial origin CACs, indicative of vascular injury. Sole use of e-cigarettes was associated with higher endothelial and inflammatory CACs, suggesting ongoing systemic injury. Distinct patterns of changes in CAC subpopulations suggest that CACs may be informative biomarkers of changes in vascular health due to tobacco product use.

Chronic E-Cigarette Use Impairs Endothelial Function on the Physiological and Cellular Levels.

BACKGROUND: The harmful vascular effects of smoking are well established, but the effects of chronic use of electronic cigarettes (e-cigarettes) on endothelial function are less understood. We hypothesized that e-cigarette use causes changes in blood milieu that impair endothelial function. METHODS: Endothelial function was measured in chronic e-cigarette users, chronic cigarette smokers, and nonusers. We measured effects of participants' sera, or e-cigarette aerosol condensate, on NO and H2O2 release and cell permeability in cultured endothelial cells (ECs). RESULTS: E-cigarette users and smokers had lower flow-mediated dilation (FMD) than nonusers. Sera from e-cigarette users and smokers reduced VEGF (vascular endothelial growth factor)-induced NO secretion by ECs relative to nonuser sera, without significant reduction in endothelial NO synthase mRNA or protein levels. E-cigarette user sera caused increased endothelial release of H2O2, and more permeability than nonuser sera. E-cigarette users and smokers exhibited changes in circulating biomarkers of inflammation, thrombosis, and cell adhesion relative to nonusers, but with distinct profiles. E-cigarette user sera had higher concentrations of the receptor for advanced glycation end products (RAGE) ligands S100A8 and HMGB1 (high mobility group box 1) than smoker and nonuser sera, and receptor for advanced glycation end product inhibition reduced permeability induced by e-cigarette user sera but did not affect NO production. CONCLUSIONS: Chronic vaping and smoking both impair FMD and cause changes in the blood that inhibit endothelial NO release. Vaping, but not smoking, causes changes in the blood that increase microvascular endothelial permeability and may have a vaping-specific effect on intracellular oxidative state. Our results suggest a role for RAGE in e-cigarette-induced changes in endothelial function.

Smoking is associated with increased risk of cardiovascular events, disease severity, and mortality among patients hospitalized for SARS-CoV-2 infections.

The clinical sequalae of SARS-CoV-2 infection are in part dependent upon age and pre-existing health conditions. Although the use of tobacco products decreases cardiorespiratory fitness while increasing susceptibility to microbial infections, limited information is available on how smoking affects COVID-19 severity. Therefore, we examined whether smokers hospitalized for COVID-19 are at a greater risk for developing severe complications than non-smokers. Data were from all hospitalized adults with SARS-CoV-2 infection from the American Heart Association's Get-With-The-Guidelines COVID-19 Registry, from January 2020 to March 2021, which is a hospital-based voluntary national registry initiated in 2019 with 122 participating hospitals across the United States. Patients who reported smoking at the time of admission were classified as smokers. Severe outcome was defined as either death or the use of mechanical ventilation. Of the 31,545 patients in the cohort, 6,717 patients were 1:2 propensity matched (for age, sex, race, medical history, medications, and time-frame of hospital admission) and classified as current smokers or non-smokers according to admission data. In multivariable analyses, after adjusting for sociodemographic characteristics, medical history, medication use, and the time of hospital admission, patients self-identified as current smokers had higher adjusted odds of death (adjusted odds ratio [aOR], 1.41; 95% CI, 1.21-1.64), the use of mechanical ventilation (aOR 1.15; 95% CI 1.01-1.32), and increased risk of major adverse cardiovascular events (aOR, 1.27; 95% CI 1.05-1.52). Independent of sociodemographic characteristics and medical history, smoking was associated with a higher risk of severe COVID-19, including death.

Cardiopulmonary Consequences of Vaping in Adolescents: A Scientific Statement From the American Heart Association.

Although the US Food and Drug Administration has not approved e-cigarettes as a cessation aid, industry has at times positioned their products in that way for adults trying to quit traditional cigarettes; however, their novelty and customizability have driven them into the hands of unintended users, particularly adolescents. Most new users of e-cigarette products have never smoked traditional cigarettes; therefore, understanding the respiratory and cardiovascular consequences of e-cigarette use has become of increasing interest to the research community. Most studies have been performed on adult e-cigarette users, but the majority of these study participants are either former traditional smokers or smokers who have used e-cigarettes to switch from traditional smoking. Therefore, the respiratory and cardiovascular consequences in this population are not attributable to e-cigarette use alone. Preclinical studies have been used to study the effects of naive e-cigarette use on various organ systems; however, almost all of these studies have used adult animals, which makes translation of health effects to adolescents problematic. Given that inhalation of any foreign substance can have effects on the respiratory and cardiovascular systems, a more holistic understanding of the pathways involved in toxicity could help to guide researchers to novel therapeutic treatment strategies. The goals of this scientific statement are to provide salient background information on the cardiopulmonary consequences of e-cigarette use (vaping) in adolescents, to guide therapeutic and preventive strategies and future research directions, and to inform public policymakers on the risks, both short and long term, of vaping.