This review indicates that psychosocial risk factors for CVD are associated with elevated plasma ET-1; however, the relatively small number of studies, methodological differences, and variable assessment tools preclude definitive conclusions about the strength of the association. Specific suggestions regarding the selection of psychosocial factors, optimization of acute challenge protocols, and standardization of methods and timing of the ET-1 measures are provided.

Introduction Approved pharmacological treatments for smoking cessation are modestly effective, underscoring the need for improved pharmacotherapies. Glucagon-like peptide-1 receptor (GLP-1R) agonists attenuate the rewarding effects of nicotine in preclinical studies. We examined the efficacy of extended-release exenatide, a GLP-1R agonist, combined with nicotine replacement therapy (NRT, patch) for smoking cessation, craving and withdrawal symptoms, with post-cessation body weight as secondary outcome. Methods Eighty-four prediabetic and/or overweight smokers were randomized (1:1) to once-weekly placebo or exenatide, 2 mg, subcutaneously. All participants received NRT (21 mg) and brief smoking cessation counseling. Seven-day point prevalence abstinence (expired CO level ≤5 ppm), craving, withdrawal and post-cessation body weight were assessed following 6 weeks of treatment. A Bayesian approach for analyzing generalized linear models yielded posterior probabilities (PP) to quantify the evidence favoring hypothesized effects of treatment on the study outcomes. Results Exenatide increased the risk for smoking abstinence compared to placebo (46.3% and 26.8%, respectively), (RR = 1.70; 95% credible interval = [0.96, 3.27]; PP = 96.5%). Exenatide reduced end-of-treatment craving in the overall sample and withdrawal among abstainers. Post-cessation body weight was 5.6 pounds lower in the exenatide group compared to placebo (PP=97.4%). Adverse events were reported in 9.5% and 2.3% of participants in the exenatide and placebo groups, respectively. Conclusions Exenatide, in combination with the NRT improved smoking abstinence, reduced craving and withdrawal symptoms, and decreased weight gain among abstainers. Findings suggest that the GLP-1R agonist strategy is worthy of further research in larger, longer duration studies. Implications Despite considerable progress in tobacco control, cigarette smoking remains the leading cause of preventable disease, disability, and death. In this pilot study, we showed that extended-release exenatide, a glucagon-like peptide-1 receptor agonist, added to the nicotine patch, improved abstinence and mitigated post-cessation body weight gain compared to patch alone. Further research is needed to confirm these initial positive results.

Objective To examine the effects of depressive symptoms and Endothelin (ET) -1 on 2-year prognosis in younger patients with acute coronary syndrome (ACS). Depression is associated with poor post-ACS prognosis; however, few investigations have focused on younger patients. Importantly, the studies that did emphasize younger patients suggested that the influence of depression on prognosis could be more robust in younger subgroups. The particular links between depression and poor prognosis in younger patients have yet to be definitively determined. ET-1 is a potent endogenous vasoconstrictor that has been previously linked to adverse post-ACS outcomes. Methods The sample (n=153) included male (age ≤50 years) and female (age ≤55 years) ACS patients. Blood samples for ET-1 assessment were collected within 2–3h of ACS hospital admission. Depressive symptoms were assessed with the Beck Depression Inventory (BDI) II within 2–5 days of admission. The primary outcome was defined as a composite of major adverse cardiovascular events (MACE), including recurrent myocardial infarction, emergent coronary revascularization, and all-cause mortality within 2 years after index admission. Results During the follow-up period, 23 patients experienced MACE. Neither the BDI-II score nor ET-1 predicted MACE in unadjusted analyses or in analyses adjusted for demographic characteristics, comorbidities and troponin levels. In the supplementary analyses, feeling depressed in the year preceding ACS predicted MACE. Conclusions In this cohort of younger ACS patients, feeling depressed in the year preceding ACS admission predicted MACE in the 2 years after baseline ACS event, while neither the BDI-II score, nor circulating ET-1 level predicted this outcome.

Clinicians need to be persistent in promoting the importance of weight loss and smoking cessation. Screening and treating depression in younger persons is a prudent approach. The significance of regular screening and aggressive treatment of other risk factors (i.e., diabetes, hypertension, and dyslipidemia) should not be overlooked.

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Objective To explore the relationship of depressive symptom severity to circulating Endothelin (ET) – 1 in younger patients with acute coronary syndrome (ACS). Younger patients report greater depressive symptom severity, which predicts poorer post-ACS prognosis. The pathways linking depression to post-ACS prognosis require further elucidation. ET-1 is a potent endogenous vasoconstrictor which has been previously linked to adverse post-ACS outcomes. Methods The sample (n=153) included males ≤50 years of age and females ≤55 years of age who participated in a larger study. Blood samples for ET-1 assessment were collected within 2–3 hours of ACS admission. Depressive symptoms were assessed with the Beck Depression Inventory (BDI) II within 2–5 days of admission. ET-1 was treated as a transformed continuous variable (ET-1T). BDI-II scores were classified into four categories using conventional thresholds demarcating mild, moderate, and severe levels of depressive symptoms. The relationship of classified BDI-II score to ET-1T was examined in simple and multivariable linear regression models. Results Classified BDI-II score was related to ET-1T in both unadjusted (χ2 = 9.469, p = 0.024) and multivariable (χ2 = 8.430, p = 0.038) models, with ET-1T being significantly higher in patients with severe depressive symptoms than in those with mild and moderate depressive symptoms. Conclusions In this sample of younger post-ACS patients, severe depressive symptoms were associated with elevated ET-1. We acknowledge that the observed association could be eliminated by the inclusion of some unmeasured variable(s). Longitudinal research should examine whether ET-1 mediates the relationship of depressive symptoms to long-term post-ACS outcomes.

Background: The response time speed-accuracy trade-off (SATO) is an established index of information processing ability, but rarely examined as a variable in association with treatment of substance use disorder (SUD). Aim: The purpose of this study was to test baseline information-processing ability differences between individuals who respond to treatment for cocaine use disorder v. those who do not. Methods: Eighty patients enrolled in a clinical trial for cocaine use disorder completed a baseline drug-specific eye-tracking (anti-saccade) assessment prior to treatment, which included trials with both cocaine-related and neutral stimuli. SATO functions were computed for treatment responders v. non-responders. Results: Unexpectedly, responders demonstrated statistically different SATO functions, showing poorer accuracy when executing faster response times. This difference was present on trials that presented cocaine stimuli only. Conclusions: SATO during performance of an eye-movement task may be useful for predicting differential response to substance use disorder treatment. However, in the present study, results were specific to cocaine cues rather than an overall SATO performance decrement.

Adherence monitoring is a vital component of clinical efficacy trials, as the regularity of medication consumption affects both efficacy and adverse effect profiles. Pill‐counts do not confirm consumption, and invasive plasma assessments can only assist post hoc assessments. We previously reported on the pharmacokinetics of a potential adherence marker to noninvasively monitor dosage consumption during a trial without breaking a blind. We reported that consumption cessation of subtherapeutic 15 mg acetazolamide (ACZ) doses showed a predictable urinary excretion decay that was quantifiable for an extended period. The current study describes the clinical implementation of 15 mg ACZ doses as an adherence marker excipient in distinct cohorts taking ACZ for different “adherence” durations. We confirm that ACZ output did not change (accumulate) during 18–20 days of adherence, and developed and assessed urinary cutoffs as nonadherence indicators. We demonstrate that whereas an absolute concentration cutoff (989 ng/mL) lacked sensitivity, a creatinine normalized equivalent (1,376 ng/mg ACZ) was highly accurate at detecting nonadherence. We also demonstrate that during nonadherent phases of three trials, creatinine‐normalized urinary ACZ elimination was reproducible within and across trials with low variability. Excretion was first order, with a decay half‐life averaging ~ 2.0 days. Further, excretion remained quantifiable for 14 days, providing a long period during which the date of last consumption might be determined. We conclude that inclusion of 15 mg ACZ as a dosage form adherence marker excipient, provides a reliable and sensitive mechanism to confirm medication consumption and detect nonadherence during clinical efficacy trials.