Abstract 4136996: Co-morbid Insomnia and Obstructive Sleep Apnea (COMISA) are Related to Incident Hypertension in a 20-Year Retrospective Cohort Study of 1.3 million Younger Men and Women Veterans: Associations by Sex

Circulation, Volume 150, Issue Suppl_1, Page A4136996-A4136996, November 12, 2024. Introduction:Insomnia and obstructive sleep apnea (OSA) each increase risk for hypertension (HTN). Among older adults, there is a negative synergistic association of comorbid insomnia and OSA (i.e., COMISA) on incident cardiovascular disease (CVD) but it is unknown if this comorbidity is associated with HTN risk earlier in the lifespan.Research Questions:1) Is COMISA associated with incident HTN among younger adults? 2) Do COMISA-HTN associations differ by sex?Hypotheses:We hypothesized that 1) COMISA would be associated with a greater risk of HTN than having no sleep disorder, 2) the hazard would be larger than for insomnia and OSA alone, and 3) distinct COMISA-HTN associations would be observed among men and women, respectively.Methods:Analyses included Veterans who enrolled in Veterans Health Administration (VA) care 2001-2021, a group selected because of its early adult age distribution. We merged administrative data, including outpatient and inpatient encounters, diagnoses, (ICD-9-CM/10 codes/dates) and pharmacy records. Veterans without demographic data, a history of other sleep disorders or CVD, or

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Novembre 2024

Abstract 4115015: Hyperpolarized Carbon-13 Metabolic Imaging Detects Changes in Cardiac Mitochondrial Metabolism in Patients Before and After Coronary Artery Bypass Graft Surgery

Circulation, Volume 150, Issue Suppl_1, Page A4115015-A4115015, November 12, 2024. Background:Coronary Artery Disease (CAD) is a significant global health issue, necessitating improved diagnostic tools for visualizing cardiac energetics. Traditional imaging methods such as PET and dobutamine stress echocardiography do not directly assess mitochondrial metabolism. Hyperpolarized Carbon-13 metabolic magnetic resonance imaging (HP-13C MRI) offers a promising non-invasive method for investigating mitochondrial function in CAD. This study utilizes HP-13C MRI to detect changes in mitochondrial metabolism in patients undergoing Coronary Artery Bypass Graft (CABG) surgery (Fig.1).Methods:We conducted HP-13C MRI examinations on two patients with advanced CAD before and (~4-6 months after CABG surgery and one healthy subject (Fig. 2 A,B). Participating subjects provided informed consent according to a protocol approved by the Institutional Review Board and Protocol Review Committee. Baseline blood samples were analyzed for pyruvate, triglycerides, free fatty acids, and insulin levels. Post-glucose load, patients received an intravenous injection of an IND-approved metabolic probe, [1-13C] pyruvic acid, prepared under Good Manufacturing Practice regulations. The HP solution was administered after polarization in a clinical polarizer (SPINlab™, GE Healthcare). Imaging was performed using a GE MR750 MR system with a Helmholtz loop-pair13C coil (PulseTeq Limited, UK). Data were reconstructed and analyzed with MATLAB scripts.Results and Discussion:Baseline blood measurements were normal for the healthy subject, but those with advanced CAD showed variable and abnormal values (Fig. 2C). HP-13C MRI safely assessed cardiac metabolism in patients with advanced CAD. Patients with advanced CAD exhibited reduced pyruvate metabolism compared to healthy controls, shown by lower myocardial bicarbonate/(bicarbonate+lactate) ratios (Bic/(Bic+Lac)). Following CABG, only Patient 2 showed improved Bic/(Bic+Lac), while Patient 1 did not (Fig. 3A-B). This variability may be influenced by differences in nutrition, hormonal status, medication regimens, or other factors. Changes in % Bic/(Bic+Lac) across different coronary artery segments were observed post-CABG in CAD patients (Fig. 3C).Conclusion:HP-13C MRI non-invasively assesses cardiac metabolism in CAD patients, demonstrating the potential to evaluate post-CABG metabolic changes. Our efforts continue to recruit large cohort to understand individual variability.

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Novembre 2024

Abstract 4139672: 12,13-diHOME Attenuates Pro-Arrhythmic Effect of High-Fat Diet

Circulation, Volume 150, Issue Suppl_1, Page A4139672-A4139672, November 12, 2024. Introduction:Obesity is a risk factor for atrial fibrillation (AF) and its incidence that has tripled over the past 30 years. Obesity is associated with dramatic changes in atrial structure and electrophysiology through unclear mechanisms. The linoleic acid metabolite 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) is a signaling lipid released by brown adipose tissue that acts in an endocrine manner on myriad tissues including the heart. 12,13-diHOME enhances cardiac myocyte Ca2+cycling and overall function, though the precise mechanisms are undetermined. This study tested the hypothesis that 12,13-diHOME inhibits the pro-arrhythmic molecule Ca2+/calmodulin-dependent kinase II (CaMKII). We propose that obesity-induced loss of 12,13-diHOME promotes CaMKII dysfunction,in vitroectopy and atrial arrhythmia (AA).Methods:Adult male and female mice were fed either high fat diet (HFD, 60% kcal from fat) or normal chow (NFD) (21% kcal from fat) for 8-16 weeks. Atrial myocytes were isolated for action potential (AP) measurements using whole-cell patch clamp ±12,13-diHOME (5 μM). To test the effect of 12,13-diHOME on AA inducibility, a second cohort of mice was fed HFD and subjected to weekly tissue nanotransfection for non-viral delivery of either Ephx1/2 (HFD-TNT), enzymes responsible for production of 12,13-diHOME, or empty plasmid (HFD-con). Following treatment, mice underwent intracardiac pacing studies to determine AA inducibility. The ability of 12,13-diHOME to directly interact with and inhibit CaMKII was tested using purified components within vitroradioassay and microscale thermophoresis.Results:HFD induced atrial myocyte AP duration prolongation and a higher incidence of spontaneous depolarization compared to NFD, both of which were reversed by 12,13-diHOME (figure). HFD-TNT exhibited decreased phospho-CaMKII compared to HFD-con mice. In parallel, HFD-TNT trended toward reduced inducibility of AA (0/7 mice inducible, 0%) compared to TNT-CON mice (5/7, 58%) (p=0.07). Radioassay revealed that 12,13-diHOME inhibits CaMKII; thermophoresis demonstrated direct binding withK1/2= 19 mM.Conclusion:HFD induces dysregulation in 12,13-diHOME and CaMKII signaling together with defects in atrial myocyte excitability and AA in mice. Non-viral overexpression of 12,13-diHOME shows promise in normalizing CaMKII activity and reducing AA burden. 12,13-diHOME represents a novel avenue for direct regulation of CaMKII signaling and downstream pathology in the heart.

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Novembre 2024

Abstract 4140502: Preventive Effects of Nitric Oxide Donors in Contrast-induced Nephropathy in Patients Undergoing Coronary Artery Angiography: An updated systematic review and meta-analysis of 13 randomized controlled trials.

Circulation, Volume 150, Issue Suppl_1, Page A4140502-A4140502, November 12, 2024. Background:Contrast-induced nephropathy (CIN) is associated with increased mortality and morbidity in patients undergoing coronary angiography (CAG) and percutaneous coronary intervention (PCI). We aimed to assess the latest evidence on the preventive effects of nitric oxide (NO) donors in CIN in patients undergoing CAG/PCI.Methods:We conducted a systematic review and meta-analysis of RCTs from PubMed, Web of Science, Scopus, Embase, and Cochrane searches until May 5th, 2024. Dichotomous data were pooled using risk ratio (RR), and continuous data were pooled using mean difference (MD), both with a 95% confidence interval (CI), using (R version 4.3).Results:Our analysis included 13 RCTs encompassing 3,550 patients. NO donors were significantly associated with a decreased incidence of CIN compared to placebo either as an oral administration (RR: 0.33 with 95% CI [0.26, 0.42], P< 0.01) or IV infusions (RR: 0.56 with 95% CI [0.40, 0.78], P< 0.01). Moreover, NO donors were significantly associated with decreased serum creatinine levels compared to placebo either as an oral administration (MD: -0.07 with 95% CI [-0.10, -0.04], P< 0.01) or IV infusions (MD: -0.07 with 95% CI [-0.09, -0.04], P< 0.01). In terms of safety, NO donors were significantly associated with a decreased incidence of MACE compared to placebo as an oral administration (RR: 0.64 with 95% CI [0.45, 0.89], P< 0.01). However, there was no significant difference between NO donors as IV infusions and placebo in MACE (RR: 0.68 with 95% CI [0.38, 1.21], P= 0.18). Finally, NO donors were significantly associated with a decreased incidence of all-cause mortality compared to placebo as an oral administration (RR: 0.58 with 95% CI [0.36, 0.94], P= 0.03). However, there was no significant difference between NO donors as IV infusions and placebo in all-cause mortality (RR: 1.84 with 95% CI [0.40, 8.52], P= 0.44).Conclusion:NO donors as an adjunct therapy are associated with reduced incidence of CIN, and decreased serum creatinine levels either as an oral or IV administration. Also, it was associated with decreased incidence of MACE and all-cause mortality as an oral administration which make this simple low-cost intervention an important therapeutic option in patients undergoing CAG/PCI.

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Novembre 2024

Occupational accidents in mining workers: scoping review of studies published in the last 13 years

Objective
Mining activity represents one of the most hazardous occupations related to health, with 8% of fatal injuries concentrated in this sector worldwide. Thus, it is crucial to timely identify the factors involved in such injuries. We aimed to explore the sociodemographic and occupational/organisational factors associated with injuries, causative agents and subsequent disabilities and fatality of workers exposed to occupational injuries in the mining sector.

Design
A secondary scoping review was conducted following the Joanna Briggs Institute guidelines.

Data sources
Scopus, Embase, Virtual Health Library, SciELO and PubMed databases were searched in February 2022 and updated in October 2023. The protocol was developed in April 2022.

Eligibility criteria for selecting studies
We included observational studies published within the last 13 years (2010–2022) which provided information on injuries of the mining workers and reported associated factors as well as health consequences.

Data extraction and synthesis
Two independent reviewers examined the eligibility criteria, screened and coded the extracted information using prevalidated data extraction tools, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses—Extension for Scoping Reviews reporting guidelines.

Results
A total of 123 studies were found, of which nine were selected for inclusion in this review. Participants were between 15 and 80 years old, and the rate of injuries ranged from 4.4% to 10.6% of reported cases. Among the total selected studies, mechanical agents were identified as the leading cause of injuries in six studies. The factors associated with injuries included age, gender (female) and biochemical characteristics. On the other hand, occupational and organisational factors encompassed work shift, outsourcing (contractors) and less than 2 years of experience in the sector.

Conclusion
This review emphasises that both work-related and individual characteristics are significantly related factors of injuries. Moreover, commonly reported health consequences of injuries encompass mortality, average days lost and permanent, partial or total disability.

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Ottobre 2024