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.

Association of Aortic Stiffness and Pressure Pulsatility With Noninvasive Estimates of Hepatic Steatosis and Fibrosis: The Framingham Heart Study.

BACKGROUND: Arterial stiffening may contribute to the pathogenesis of metabolic dysfunction-associated steatotic liver disease. We aimed to assess relations of vascular hemodynamic measures with measures of hepatic steatosis and fibrosis in the community. METHODS: Our sample was drawn from the Framingham Offspring, New Offspring Spouse, Third Generation, Omni-1, and Omni-2 cohorts (N=3875; mean age, 56 years; 54% women). We used vibration-controlled transient elastography to assess controlled attenuation parameter and liver stiffness measurements as measures of liver steatosis and liver fibrosis, respectively. We assessed noninvasive vascular hemodynamics using arterial tonometry. We assessed cross-sectional relations of vascular hemodynamic measures with continuous and dichotomous measures of hepatic steatosis and fibrosis using multivariable linear and logistic regression. RESULTS: In multivariable models adjusting for cardiometabolic risk factors, higher carotid-femoral pulse wave velocity (estimated ß per SD, 0.05 [95% CI, 0.01-0.09]; P=0.003), but not forward pressure wave amplitude and central pulse pressure, was associated with more liver steatosis (higher controlled attenuation parameter). Additionally, higher carotid-femoral pulse wave velocity (ß=0.11 [95% CI, 0.07-0.15]; P<0.001), forward pressure wave amplitude (ß=0.05 [95% CI, 0.01-0.09]; P=0.01), and central pulse pressure (ß=0.05 [95% CI, 0.01-0.09]; P=0.01) were associated with more hepatic fibrosis (higher liver stiffness measurement). Associations were more prominent among men and among participants with obesity, diabetes, and metabolic syndrome (interaction P values, <0.001-0.04). Higher carotid-femoral pulse wave velocity, but not forward pressure wave amplitude and central pulse pressure, was associated with higher odds of hepatic steatosis (odds ratio, 1.16 [95% CI, 1.02-1.31]; P=0.02) and fibrosis (odds ratio, 1.40 [95% CI, 1.19-1.64]; P<0.001). CONCLUSIONS: Elevated aortic stiffness and pressure pulsatility may contribute to hepatic steatosis and fibrosis.

Uncovering Unrecognized Heart Failure With Preserved Ejection Fraction Among Individuals With Obesity and Dyspnea.

BACKGROUND: Although heart failure with preserved ejection fraction (HFpEF) has become the predominant heart failure subtype, it remains clinically under-recognized. HFpEF diagnosis is particularly challenging in the setting of obesity given the limitations of natriuretic peptides and resting echocardiography. We examined invasive and noninvasive HFpEF diagnostic criteria among individuals with obesity and dyspnea without known cardiovascular disease to determine the prevalence of hemodynamic HFpEF in the community. METHODS: Research volunteers with dyspnea and obesity underwent resting echocardiography; participants with possible pulmonary hypertension qualified for invasive cardiopulmonary exercise testing. HFpEF was defined using rest or exercise pulmonary capillary wedge pressure criteria (≥15 mm Hg or Δpulmonary capillary wedge pressure/Δcardiac output slope, >2.0 mm Hg·L-1·min-1). RESULTS: Among n=78 participants (age, 53±13 years; 65% women; body mass index, 37.3±6.8 kg/m2), 40 (51%) met echocardiographic criteria to undergo invasive cardiopulmonary exercise testing. In total, 24 participants (60% among the cardiopulmonary exercise testing group, 31% among the total sample) were diagnosed with HFpEF by rest or exercise pulmonary capillary wedge pressure (n=12) or exercise criteria (n=12). There were no differences in NT-proBNP (N-terminal pro-B-type natriuretic peptide; 79 [62-104] versus 73 [57-121] pg/mL) or resting echocardiography (mitral E/e' ratio, 9.1±3.1 versus 8.0±2.7) among those with versus without HFpEF (P>0.05 for all). Distributions of HFpEF diagnostic scores were similar, with the majority classified as intermediate risk (100% versus 93.75% [H2FPEF] and 87.5% versus 68.75% [HFA-PEFF (Heart Failure Association Pretest assessment, echocardiography and natriuretic peptide, functional testing, and final etiology)] in those with versus without HFpEF). CONCLUSIONS: Among adults with obesity and dyspnea without known cardiovascular disease, at least a third had clinically unrecognized HFpEF uncovered on invasive cardiopulmonary exercise testing. Clinical, biomarker, resting echocardiography, and diagnostic scores were similar among those with and without HFpEF. These results suggest clinical underdiagnosis of HFpEF among individuals with obesity and dyspnea and highlight limitations of noninvasive testing in the identification of HFpEF.

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.

miR-369-3p ameliorates diabetes-associated atherosclerosis by regulating macrophage succinate-GPR91 signaling.

AIMS: Diabetes leads to dysregulated macrophage immunometabolism, contributing to accelerated atherosclerosis progression. Identifying critical factors to restore metabolic alterations and promote resolution of inflammation remains an unmet goal. MicroRNAs (miRs) orchestrate multiple signaling events in macrophages, yet their therapeutic potential in diabetes-associated atherosclerosis remains unclear. METHODS AND RESULTS: MiRNA profiling revealed significantly lower miR-369-3p expression in aortic intimal lesions from Ldlr-/- mice on a high-fat sucrose containing (HFSC) diet for 12 weeks. miR-369-3p was also reduced in peripheral blood mononuclear cells (PBMCs) from diabetic patients with coronary artery disease (CAD). Cell-type expression profiling showed miR-369-3p enrichment in aortic macrophages. In vitro, oxLDL treatment reduced miR-369-3p expression in mouse bone marrow-derived macrophages (BMDMs). Metabolic profiling in BMDMs revealed that miR-369-3p overexpression blocked the oxLDL-mediated increase in the cellular metabolite succinate and reduced mitochondrial respiration (OXPHOS) and inflammation (lL-1ß, TNF-a, IL-6). Mechanistically, miR-369-3p targeted the succinate receptor (GPR91) and alleviated the oxLDL-induced activation of inflammasome signaling pathways. Therapeutic administration of miR-369-3p mimics in HFSC-fed Ldlr-/- mice reduced GPR91 expression in lesional macrophages and diabetes-accelerated atherosclerosis, evident by a decrease in plaque size and pro-inflammatory Ly6Chi monocytes. RNA-seq analyses showed more pro-resolving pathways in plaque macrophages from miR-369-3p treated mice, consistent with an increase in macrophage efferocytosis in lesions. Finally, a GPR91 antagonist attenuated oxLDL-induced inflammation in primary monocytes from human subjects with diabetes. CONCLUSION: These findings establish a therapeutic role for miR-369-3p in halting diabetes-associated atherosclerosis by regulating GPR91 and macrophage succinate metabolism.

Association of Arterial Stiffness With Mid- to Long-Term Home Blood Pressure Variability in the Electronic Framingham Heart Study: Cohort Study.

BACKGROUND: Short-term blood pressure variability (BPV) is associated with arterial stiffness in patients with hypertension. Few studies have examined associations between arterial stiffness and digital home BPV over a mid- to long-term time span, irrespective of underlying hypertension. OBJECTIVE: This study aims to investigate if arterial stiffness traits were associated with subsequent mid- to long-term home BPV in the electronic Framingham Heart Study (eFHS). We hypothesized that higher arterial stiffness was associated with higher home BPV over up to 1-year follow-up. METHODS: At a Framingham Heart Study research examination (2016-2019), participants underwent arterial tonometry to acquire measures of arterial stiffness (carotid-femoral pulse wave velocity [CFPWV]; forward pressure wave amplitude [FWA]) and wave reflection (reflection coefficient [RC]). Participants who agreed to enroll in eFHS were provided with a digital blood pressure (BP) cuff to measure home BP weekly over up to 1-year follow-up. Participants with less than 3 weeks of BP readings were excluded. Linear regression models were used to examine associations of arterial measures with average real variability (ARV) of week-to-week home systolic (SBP) and diastolic (DBP) BP adjusting for important covariates. We obtained ARV as an average of the absolute differences of consecutive home BP measurements. ARV considers not only the dispersion of the BP readings around the mean but also the order of BP readings. In addition, ARV is more sensitive to measurement-to-measurement BPV compared with traditional BPV measures. RESULTS: Among 857 eFHS participants (mean age 54, SD 9 years; 508/857, 59% women; mean SBP/DBP 119/76 mm Hg; 405/857, 47% hypertension), 1 SD increment in FWA was associated with 0.16 (95% CI 0.09-0.23) SD increments in ARV of home SBP and 0.08 (95% CI 0.01-0.15) SD increments in ARV of home DBP; 1 SD increment in RC was associated with 0.14 (95% CI 0.07-0.22) SD increments in ARV of home SBP and 0.11 (95% CI 0.04-0.19) SD increments in ARV of home DBP. After adjusting for important covariates, there was no significant association between CFPWV and ARV of home SBP, and similarly, no significant association existed between CFPWV and ARV of home DBP (P>.05). CONCLUSIONS: In eFHS, higher FWA and RC were associated with higher mid- to long-term ARV of week-to-week home SBP and DBP over 1-year follow-up in individuals across the BP spectrum. Our findings suggest that higher aortic stiffness and wave reflection are associated with higher week-to-week variation of BP in a home-based setting over a mid- to long-term time span.

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.

Environmental Impacts on Cardiovascular Health and Biology: An Overview.

Environmental stressors associated with human activities (eg, air and noise pollution, light disturbance at night) and climate change (eg, heat, wildfires, extreme weather events) are increasingly recognized as contributing to cardiovascular morbidity and mortality. These harmful exposures have been shown to elicit changes in stress responses, circadian rhythms, immune cell activation, and oxidative stress, as well as traditional cardiovascular risk factors (eg, hypertension, diabetes, obesity) that promote cardiovascular diseases. In this overview, we summarize evidence from human and animal studies of the impacts of environmental exposures and climate change on cardiovascular health. In addition, we discuss strategies to reduce the impact of environmental risk factors on current and future cardiovascular disease burden, including urban planning, personal monitoring, and mitigation measures.

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.

Coronary Microvascular Function Following Severe Preeclampsia.

Background: Preeclampsia is a pregnancy-specific hypertensive disorder associated with an imbalance in circulating pro- and anti-angiogenic 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 (PET) within 4 weeks of delivery. A control group of pre-menopausal, non-postpartum women was also included. Myocardial flow reserve (MFR), myocardial blood flow (MBF), and coronary vascular resistance (CVR) were compared across groups. Soluble fms-like tyrosine kinase receptor-1 (sFlt-1) and placental growth factor (PlGF) were measured at imaging. Results: The primary cohort included 19 women with severe preeclampsia (imaged at a mean 16.0 days postpartum), 5 with normotensive pregnancy (mean 14.4 days postpartum), and 13 non-postpartum female controls. Preeclampsia was associated with lower MFR (ß=-0.67 [95% CI -1.21 to -0.13]; P=0.016), lower stress MBF (ß=-0.68 [95% CI, -1.07 to -0.29] mL/min/g; P=0.001), and higher stress CVR (ß=+12.4 [95% CI 6.0 to 18.7] mmHg/mL/min/g; P=0.001) vs. non-postpartum controls. MFR and CVR after normotensive pregnancy were intermediate between preeclamptic and non-postpartum groups. Following preeclampsia, MFR was positively associated with time following delivery (P=0.008). The sFlt-1/PlGF ratio strongly correlated with rest MBF (r=0.71; P<0.001), independent of hemodynamics. Conclusions: In this exploratory study, we observed reduced coronary microvascular function in the early postpartum period following severe preeclampsia, suggesting that systemic microvascular dysfunction in preeclampsia involves the coronary microcirculation. Further research is needed to establish interventions to mitigate risk of preeclampsia-associated cardiovascular disease.

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.

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.

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.

Emerging Medical Therapies for the Treatment of Obesity in Women with Cardiovascular Diseases.

PURPOSE OF REVIEW: In this review, the impact of obesity on cardiovascular disease in women and emerging anti-obesity pharmacologic treatments are discussed. RECENT FINDINGS: Robust evidence demonstrates the burden of obesity across the lifespan in women and links obesity to a diverse set of cardiovascular diseases. Female-specific risk factors including sex hormones and pregnancy factors intersect with obesity and cardiovascular risk. Sustained weight loss has potential for cardiovascular benefits. Recent trials demonstrate cardiovascular benefits of emerging agents with weight loss effects including GLP-1 RA and SGLT2 inhibitors in women. Treatment and prevention strategies for cardiovascular disease in obese women should include integration of weight management strategies including the targeted use of emerging pharmacologic therapies.

Aging and Vascular Disease: A Multidisciplinary Overview.

Vascular aging, i.e., the deterioration of the structure and function of the arteries over the life course, predicts cardiovascular events and mortality. Vascular degeneration can be recognized before becoming clinically symptomatic; therefore, its assessment allows the early identification of individuals at risk. This opens the possibility of minimizing disease progression. To review these issues, a search was completed using PubMed, MEDLINE, and Google Scholar from 2000 to date. As a network of clinicians and scientists involved in vascular medicine, we here describe the structural and functional age-dependent alterations of the arteries, the clinical tools for an early diagnosis of vascular aging, and the cellular and molecular events implicated. It emerges that more studies are necessary to identify the best strategy to quantify vascular aging, and to design proper physical activity programs, nutritional and pharmacological strategies, as well as social interventions to prevent, delay, and eventually revert the disease.

Trends among platelet function, arterial calcium, and vascular function measures.

Arterial tonometry and vascular calcification measures are useful in cardiovascular disease (CVD) risk assessment. Prior studies found associations between tonometry measures, arterial calcium, and CVD risk. Activated platelets release angiopoietin-1 and other factors, which may connect vascular structure and platelet function. We analyzed arterial tonometry, platelet function, aortic, thoracic and coronary calcium, and thoracic and abdominal aorta diameters measured in the Framingham Heart Study Gen3/NOS/OMNI-2 cohorts (n = 3,429, 53.7% women, mean age 54.4 years ±9.3). Platelet reactivity in whole blood or platelet-rich plasma was assessed using 5 assays and 7 agonists. We analyzed linear mixed effects models with platelet reactivity phenotypes as outcomes, adjusting for CVD risk factors and family structure. Higher arterial calcium trended with higher platelet reactivity, whereas larger aortic diameters trended with lower platelet reactivity. Characteristic impedance (Zc) and central pulse pressure positively trended with various platelet traits, while pulse wave velocity and Zc negatively trended with collagen, ADP, and epinephrine traits. All results did not pass a stringent multiple test correction threshold (p < 2.22e-04). The diameter trends were consistent with lower shear environments invoking less platelet reactivity. The vessel calcium trends were consistent with subclinical atherosclerosis and platelet activation being inter-related.

What is the context? Prior research has reported that measures of vascular system-influencing proteins such as angiopoietin-2, arterial calcium plaque formation, and arterial stiffness assessed by tonometry are associated with CVD risk.Since activated platelets produce and release vascular proteins like angiopoietin when activated, and microparticles that interact with endothelium, release of the foregoing mediators could provide one way in which vascular structure and platelet function influence each other.To our knowledge, no prior studies have directly investigated associations between these measures in a large sample. This investigation relates platelet function to arterial tonometry, aortic and arterial diameter, and arterial calcium measures in the Framingham Heart Study (FHS) Gen3/NOS/OMNI-2 cohorts (n = 3,429).What's new? Generally, higher arterial calcium measures trended with higher platelet reactivity, whereas larger aortic diameters trended with lower platelet reactivity.Arterial tonometry measures had positive and negative trends with platelet functions, including platelet measures with opposite relations to negative-inverse carotid-femoral pulse wave velocity (niCFPWV) and characteristic impedance (Zc). All tonometry, calcium, and diameter results did not reach a more stringent multiple testing threshold (p < 2.22e-04).What's the impact? The aortic diameter trends are consistent with lower shear stress invoking less platelet reactivity.The vessel calcium trends are consistent with increased vascular calcium buildup that could provoke platelet activation, thereby contributing to increased blood clot risk. Conversely, increased platelet activation could contribute to increased inflammation and thrombosis, leading to calcification in the arterial wall.