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.

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

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

Transitioning to GLP-1 RAs and SGLT2 Inhibitors as the First Choice for Managing Cardiometabolic Risk in Type 2 Diabetes.

PURPOSE OF REVIEW: This forward-looking review summarizes existing evidence from cardiovascular outcome trials on cardiometabolic risk-reduction in type 2 diabetes (T2DM) management, with attention to updating and personalizing recommendations from recent diabetes practice guidelines issued by cardiology societies. RECENT FINDINGS: T2DM management has shifted towards cardiometabolic outcome improvement rather than purely glycemic control. According to large clinical trials, sodium-glucose cotransporter-2 inhibitors showed robust results in reducing heart failure (HF) hospitalization and chronic kidney disease (CKD) progression, while glucagon-like peptide-1 receptor agonists demonstrated the largest effects on HbA1c reduction, weight loss, and atherosclerotic cardiovascular disease outcomes prevention, including stroke. Considering the distinct features of these new cardiometabolic agents, initial selection of therapy should be targeted to each individual patient, with consideration of combination therapy for the highest risk patients. Moreover, future studies should investigate the addition of obesity-predominant risk, in conjunction with coronary artery disease, stroke, CKD, and HF, as a new influential indicator for choosing the optimal cardiometabolic agent.

Coronary Calcium to Rule Out Obstructive Coronary Artery Disease in Patients With Acute Chest Pain.

OBJECTIVES: This study aimed to evaluate the ability of coronary artery calcium (CAC) as an initial diagnostic tool to rule out obstructive coronary artery disease (CAD) in a very large registry of patients presenting to the emergency department (ED) with acute chest pain (CP) who were at low to intermediate risk for acute coronary syndrome (ACS). BACKGROUND: It is not yet well established whether CAC can be used to rule out obstructive CAD in the ED setting. METHODS: We included patients from the Baptist Health South Florida Chest Pain Registry presenting to the ED with CP at low to intermediate risk for ACS (Thrombolysis In Myocardial Infarction risk score ≤2, normal/nondiagnostic electrocardiography, and troponin levels) who underwent CAC and coronary computed tomography angiography (CCTA) procedures for evaluation of ACS. To assess the diagnostic accuracy of CAC testing to diagnose obstructive CAD and identify the need for coronary revascularization during hospitalization, we estimated sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV). RESULTS: Our study included 5,192 patients (mean age: 53.5 ± 10.8 years; 46% male; 62% Hispanic). Overall, 2,902 patients (56%) had CAC = 0, of which 135 (4.6%) had CAD (114 [3.9%] nonobstructive and 21 [0.7%] obstructive). Among those with CAC >0, 23% had obstructive CAD. Sensitivity, specificity, PPV, and NPV of CAC testing to diagnose obstructive CAD were 96.2%, 62.4%, 22.4%, and 99.3%, respectively. The NPV for identifying those who needed revascularization was 99.6%. Among patients with CAC = 0, 11 patients (0.4%) underwent revascularization, and the number needed to test with CCTA to detect 1 patient who required revascularization was 264. CONCLUSIONS: In a large population presenting to ED with CP at low to intermediate risk, CAC = 0 was common. CAC = 0 ruled out obstructive CAD and revascularization in more than 99% of the patients, and <5% with CAC = 0 had any CAD. Integrating CAC testing very early in CP evaluation may be effective in appropriate triage of patients by identifying individuals who can safely defer additional testing and more invasive procedures.

Relation of Absence of Coronary Artery Calcium to Cardiovascular Disease Mortality Risk Among Individuals Meeting Criteria for Statin Therapy According to the 2018/2019 ACC/AHA Guidelines.

The 2013 American College of Cardiology and the American Heart Association (ACC/AHA) guidelines resulted in broad recommendations for preventive statin therapy allocation in patients without known cardiovascular disease (CVD). Subsequent studies demonstrated significant heterogeneity of atherosclerotic cardiovascular disease risk across the primary prevention population. In 2018/2019, the guidelines were revised to optimize risk assessment and cholesterol management. We sought to evaluate the heterogeneity of risk in statin-recommended patients, using coronary artery calcium (CAC) according to 2018/2019 ACC/AHA guidelines in a primary prevention cohort. We evaluated 5,800 statin-naive patients aged 40 to 75 years without known coronary heart disease from the Cedars-Sinai Medical Center study cohort. All participants underwent clinical CAC scoring for risk stratification and were followed for all-cause and CVD-specific mortality. A total of 181 deaths occurred including 54 CVD deaths over a follow-up of 9.5 years. Overall, 1,939 participants would have been recommended statin therapy, 32% of whom had no detectable CAC. CAC = 0 participants had the lowest all-cause and CVD mortality rates in both statin-recommended and nonrecommended groups (0.2 and 0.4 CVD deaths per 1,000 person-years, respectively). Absence of CAC in statin-naive patients portends an approximately 12-fold lower CVD mortality (0.2% vs 2.4%) in those recommended for statin therapy compared with any CAC present. In conclusion, in a cohort of patients meeting the 2018/2019 ACC/AHA guidelines for statin therapy for primary prevention, there was a marked heterogeneity of CAC scores, with about one-third of the statin recommended population having no detectable CAC (CAC = 0) with a significantly lower CVD mortality compared with CAC>0.