IL6/adiponectin/HMGB1 feedback loop mediates adipocyte and macrophage crosstalk and M2 polarization after myocardial infarction.

Background: Differences in border zone contribute to different outcomes post-infarction, such as left ventricular aneurysm (LVA) and myocardial infarction (MI). LVA usually forms within 24 h of the onset of MI and may cause heart rupture; however, LVA surgery is best performed 3 months after MI. Few studies have investigated the LVA model, the differences in border zones between LVA and MI, and the mechanism in the border zone. Methods: The LVA, MI, and SHAM mouse models were used. Echocardiography, Masson's trichrome staining, and immunofluorescence staining were performed, and RNA sequencing of the border zone was conducted. The adipocyte-conditioned medium-treated hypoxic macrophage cell line and LVA and MI mouse models were employed to determine the effects of the hub gene, adiponectin (ADPN), on macrophages. Quantitative polymerase chain reaction (qPCR), Western blot analysis, transmission electron microscopy, and chromatin immunoprecipitation (ChIP) assays were conducted to elucidate the mechanism in the border zone. Human subepicardial adipose tissue and blood samples were collected to validate the effects of ADPN. Results: A novel, simple, consistent, and low-cost LVA mouse model was constructed. LVA caused a greater reduction in contractile functions than MI owing to reduced wall thickness and edema in the border zone. ADPN impeded cardiac edema and promoted lymphangiogenesis by increasing macrophage infiltration post-infarction. Adipocyte-derived ADPN promoted M2 polarization and sustained mitochondrial quality via the ADPN/AdipoR2/HMGB1 axis. Mechanistically, ADPN impeded macrophage HMGB1 inflammation and decreased interleukin-6 (IL6) and HMGB1 secretion. The secretion of IL6 and HMGB1 increased ADPN expression via STAT3 and the co-transcription factor, YAP, in adipocytes. Based on ChIP and Dual-Glo luciferase experiments, STAT3 promoted ADPN transcription by binding to its promoter in adipocytes. In vivo, ADPN promoted lymphangiogenesis and decreased myocardial injury after MI. These phenotypes were rescued by macrophage depletion or HMGB1 knockdown in macrophages. Supplying adipocytes overexpressing STAT3 decreased collagen disposition, increased lymphangiogenesis, and impaired myocardial injury. However, these effects were rescued after HMGB1 knockdown in macrophages. Overall, the IL6/ADPN/HMGB1 axis was validated using human subepicardial tissue and blood samples. This axis could serve as an independent factor in overweight MI patients who need coronary artery bypass grafting (CABG) treatment. Conclusion: The IL6/ADPN/HMGB1 loop between adipocytes and macrophages in the border zone contributes to different clinical outcomes post-infarction. Thus, targeting the IL6/ADPN/HMGB1 loop may be a novel therapeutic approach for cardiac lymphatic regulation and reduction of cell senescence post-infarction.

Nutritional Status and Recurrent Major Cardiovascular Events Following Acute Myocardial Infarction-A Follow-Up Study in a Primary Percutaneous Coronary Intervention Center.

BACKGROUND: Acute myocardial infarction is often accompanied by malnutrition, which is associated with an imbalance between catabolic and anabolic processes. This ultimately leads to cardiac cachexia, which worsens the patient's prognosis. We aimed to assess the correlation between nutritional status, assessed using the controlling nutritional status (CONUT) score, and the rate of major cardiovascular adverse events (MACE). METHODS: The present investigation was a non-randomized, prospective, observational study in which 108 patients with acute myocardial infarction were included. Nutritional status was assessed using the CONUT score. Based on the CONUT score, the patients were divided as follows: Group 1-normal or mild nutritional status (CONUT < 3 points, n = 76), and Group 2-moderate to severe nutritional deficiency (CONUT ≥ 3 points, n = 32). Demographic, echocardiographic, and laboratory parameters were obtained for all patients, as well as the MACE rate at 1 and 3 months of follow-up. RESULTS: The MACE occurred more frequently in patients with impaired nutritional status at both 1-month follow-up (46.9% versus 9.2%; p < 0.0001) and 3-month follow-up (68.8% versus 10.5%; p < 0.0001). In terms of cardiovascular events, patients with poor nutritional status, with a CONUT score ≥ 3, presented more frequent non-fatal myocardial infarction, stroke, revascularization procedure, and ventricular arrhythmia. Also, the number of cardiovascular deaths was higher in the undernourished group. CONCLUSIONS: This study found that patients with poor nutritional status experienced inflammatory status, frailty, and cardiovascular events more often than those with normal nutritional status at 1-month and 3-month follow-up after an acute myocardial infarction.

FBXL8 inhibits post-myocardial infarction cardiac fibrosis by targeting Snail1 for ubiquitin-proteasome degradation.

Abnormal cardiac fibrosis is the main pathological change of post-myocardial infarction (MI) heart failure. Although the E3 ubiquitin ligase FBXL8 is a key regulator in the cell cycle, cell proliferation, and inflammation, its role in post-MI ventricular fibrosis and heart failure remains unknown. FBXL8 was primarily expressed in cardiac fibroblasts (CFs) and remarkably decreased in CFs treated by TGFß and heart subjected to MI. The echocardiography and histology data suggested that adeno-associated viruses (AAV9)-mediated FBXL8 overexpression had improved cardiac function and ameliorated post-MI cardiac fibrosis. In vitro, FBXL8 overexpression prevented TGFß-induced proliferation, migration, contraction, and collagen secretion in CFs, while knockdown of FBXL8 demonstrated opposite effects. Mechanistically, FBXL8 interacted with Snail1 to promote Snail1 degradation through the ubiquitin-proteasome system and decreased the activation of RhoA. Moreover, the FBXL8ΔC3 binding domain was indispensable for Snail1 interaction and degradation. Ectopic Snail1 expression partly abolished the effects mediated by FBXL8 overexpression in CFs treated by TGFß. These results characterized the role of FBXL8 in regulating the ubiquitin-mediated degradation of Snail1 and revealed the underlying molecular mechanism of how MI up-regulated the myofibroblasts differentiation-inducer Snail1 and suggested that FBXL8 may be a potential curative target for improving post-MI cardiac function.

Optogenetic Stimulation of the Cardiac Vagus Nerve to Promote Heart Regenerative Repair after Myocardial Infarction.

Background: It had been shown that selective cardiac vagal activation holds great potential for heart regeneration. Optogenetics has clinical translation potential as a novel means of modulating targeted neurons. This study aimed to investigate whether cardiac vagal activation via optogenetics could improve heart regenerative repair after myocardial infarction (MI) and to identify the underlying mechanism. Methods: We used an adeno-associated virus (AAV) as the vector to deliver ChR2, a light-sensitive protein, to the left nodose ganglion (LNG). To assess the effects of the cardiac vagus nerve on cardiomyocyte (CM) proliferation and myocardial regeneration in vivo, the light-emitting diode illumination (470 nm) was applied for optogenetic stimulation to perform the gain-of-function experiment and the vagotomy was used as a loss-of-function assay. Finally, sequencing data and molecular biology experiments were analyzed to determine the possible mechanisms by which the cardiac vagus nerve affects myocardial regenerative repair after MI. Results: Absence of cardiac surface vagus nerve after MI was more common in adult hearts with low proliferative capacity, causing a poor prognosis. Gain- and loss-of-function experiments further demonstrated that optogenetic stimulation of the cardiac vagus nerve positively regulated cardiomyocyte (CM) proliferation and myocardial regeneration in vivo. More importantly, optogenetic stimulation attenuated ventricular remodeling and improved cardiac function after MI. Further analysis of sequencing results and flow cytometry revealed that cardiac vagal stimulation activated the IL-10/STAT3 pathway and promoted the polarization of cardiac macrophages to the M2 type, resulting in beneficial cardiac regenerative repair after MI. Conclusions: Targeting the cardiac vagus nerve by optogenetic stimulation induced macrophage M2 polarization by activating the IL-10/STAT3 signaling pathway, which obviously optimized the regenerative microenvironment and then improved cardiac function after MI.

Carbon Dots Derived from Curcumae Radix and Their Heartprotective Effect.

Background: Acute myocardial infarction (AMI) is a common cardiovascular disease in clinic. Currently, there is no specific treatment for AMI. Carbon dots (CDs) have been reported to show excellent biological activities, which hold promise for the development of novel nanomedicines for the treatment of cardiovascular diseases. Methods: In this study, we firstly prepared CDs from the natural herb Curcumae Radix Carbonisata (CRC-CDs) by a green, simple calcination method. The aim of this study is to investigate the cardioprotective effect and mechanism of CRC-CDs on isoproterenol (ISO) -induced myocardial infarction (MI) in rats. Results: The results showed that pretreatment with CRC-CDs significantly reduced serum levels of cardiac enzymes (CK-MB, LDH, AST) and lipids (TC, TG, LDL) and reduced st-segment elevation and myocardial infarct size on the ECG in AMI rats. Importantly, cardiac ejection fraction (EF) and shortening fraction (FS) were markedly elevated, as was ATPase activity. In addition, CRC-CDs could significantly increase the levels of superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), and reduce the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) in myocardial tissue, thereby exerting cardioprotective effect by enhancing the antioxidant capacity of myocardial tissue. Moreover, the TUNEL staining image showed that positive apoptotic cells were markedly declined after CRC-CDs treatment, which indicate that CRC-CDs could inhibit cardiomyocyte apoptosis. Importantly, The protective effect of CRC-CDs on H2O2 -pretreated H9c2 cells was also verified in vitro. Conclusion: Taken together, CRC-CDs has the potential for clinical application as an anti-myocardial ischemia drug candidate, which not only provides evidence for further broadening the biological application of cardiovascular diseases, but also offers potential hope for the application of nanomedicine to treat intractable diseases.

Pressure-Controlled Intermittent Coronary Sinus Occlusion (PiCSO) in Acute Myocardial Infarction: The PiCSO-AMI-I Trial.

BACKGROUND: Primary percutaneous coronary intervention (pPCI) has improved clinical outcomes in patients with ST-segment-elevation myocardial infarction. However, as many as 50% of patients still have suboptimal myocardial reperfusion and experience extensive myocardial necrosis. The PiCSO-AMI-I trial (Pressure-Controlled Intermittent Coronary Sinus Occlusion-Acute Myocardial Infarction-I) evaluated whether PiCSO therapy can further reduce myocardial infarct size (IS) in patients undergoing pPCI. METHODS: Patients with anterior ST-segment-elevation myocardial infarction and Thrombolysis in Myocardial Infarction flow 0-1 were randomized at 16 European centers to PiCSO-assisted pPCI or conventional pPCI. The PiCSO Impulse Catheter (8Fr balloon-tipped catheter) was inserted via femoral venous access after antegrade flow restoration of the culprit vessel and before proceeding with stenting. The primary end point was the difference in IS (expressed as a percentage of left ventricular mass) at 5 days by cardiac magnetic resonance. Secondary end points were the extent of microvascular obstruction and intramyocardial hemorrhage at 5 days and IS at 6 months. RESULTS: Among 145 randomized patients, 72 received PiCSO-assisted pPCI and 73 conventional pPCI. No differences were observed in IS at 5 days (27.2%±12.4% versus 28.3%±11.45%; P=0.59) and 6 months (19.2%±10.1% versus 18.8%±7.7%; P=0.83), nor were differences between PiCSO-treated and control patients noted in terms of the occurrence of microvascular obstruction (67.2% versus 64.6%; P=0.85) or intramyocardial hemorrhage (55.7% versus 60%; P=0.72). The study was prematurely discontinued by the sponsor with no further clinical follow-up beyond 6 months. However, up to 6 months of PiCSO use appeared safe with no device-related adverse events. CONCLUSIONS: In this prematurely discontinued randomized trial, PiCSO therapy as an adjunct to pPCI did not reduce IS when compared with conventional pPCI in patients with anterior ST-segment-elevation myocardial infarction. PiCSO use was associated with increased procedural time and contrast but no increase in adverse events up to 6 months. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03625869.

Risk Burden of Cancer in Patients Treated With Abbreviated Dual Antiplatelet Therapy After PCI: Analysis of Multicenter Controlled High-Bleeding Risk Trials.

BACKGROUND: Oncological patients with coronary artery disease face an elevated risk of hemorrhagic and ischemic events following percutaneous coronary intervention. Despite medical guidelines recommending minimal dual antiplatelet therapy (DAPT) duration for patients with cancer, dedicated data on abbreviated DAPT in this population is lacking. This study aims to evaluate the occurrence of ischemic and hemorrhagic events in patients with cancer compared with other high-bleeding risk individuals. METHODS: Patient-level data from 4 high-bleeding risk coronary drug-eluting stent studies (ONYX One, LEADERS FREE, LEADERS FREE II, and SENIOR trials) treated with short DAPT were analyzed. The comparison focused on patients with high-bleeding risk with and without cancer, assessing 1-year rates of net adverse clinical events (all-cause death, myocardial infarction, stroke, revascularization, and Bleeding Academic Research Consortium [BARC] types 3 to 5 bleeding) and major adverse clinical events (all-cause death, myocardial infarction, stroke). RESULTS: A total of 5232 patients were included, of whom 574 individuals had cancer, and 4658 were at high-bleeding risk without previous cancer. Despite being younger with fewer risk factors, patients with cancer had higher net adverse clinical event (HR, 1.25; P=0.01) and major adverse clinical event (HR, 1.26; P=0.02), primarily driven by all-cause mortality and major bleeding (BARC 3-5), but not myocardial infarction, stroke, stent thrombosis, or repeat revascularization. Cancer was an independent predictor of net adverse clinical event (P=0.005), major adverse clinical event (P=0.01), and major bleeding (P=0.03). CONCLUSIONS: The present work is the first report on abbreviated DAPT dedicated to patients with cancer. Cancer is a major marker of adverse outcomes and these events had high lethality. Despite short DAPT, patients with cancer experienced higher rates of major bleeding compared with patients without cancer with high-bleeding risk, which occurred mainly after DAPT discontinuation. These findings reinforce the need for a more detailed and individualized stratification of those patients. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT03344653, NCT01623180, NCT02843633, NCT0284.

Stem Cell Therapy against Ischemic Heart Disease.

Ischemic heart disease, which is one of the top killers worldwide, encompasses a series of heart problems stemming from a compromised coronary blood supply to the myocardium. The severity of the disease ranges from an unstable manifestation of ischemic symptoms, such as unstable angina, to myocardial death, that is, the immediate life-threatening condition of myocardial infarction. Even though patients may survive myocardial infarction, the resulting ischemia-reperfusion injury triggers a cascade of inflammatory reactions and oxidative stress that poses a significant threat to myocardial function following successful revascularization. Moreover, despite evidence suggesting the presence of cardiac stem cells, the fact that cardiomyocytes are terminally differentiated and cannot significantly regenerate after injury accounts for the subsequent progression to ischemic cardiomyopathy and ischemic heart failure, despite the current advancements in cardiac medicine. In the last two decades, researchers have realized the possibility of utilizing stem cell plasticity for therapeutic purposes. Indeed, stem cells of different origin, such as bone-marrow- and adipose-derived mesenchymal stem cells, circulation-derived progenitor cells, and induced pluripotent stem cells, have all been shown to play therapeutic roles in ischemic heart disease. In addition, the discovery of stem-cell-associated paracrine effects has triggered intense investigations into the actions of exosomes. Notwithstanding the seemingly promising outcomes from both experimental and clinical studies regarding the therapeutic use of stem cells against ischemic heart disease, positive results from fraud or false data interpretation need to be taken into consideration. The current review is aimed at overviewing the therapeutic application of stem cells in different categories of ischemic heart disease, including relevant experimental and clinical outcomes, as well as the proposed mechanisms underpinning such observations.

Neutrophil Extracellular Traps in Cardiovascular and Aortic Disease: A Narrative Review on Molecular Mechanisms and Therapeutic Targeting.

Neutrophil extracellular traps (NETs), composed of DNA, histones, and antimicrobial proteins, are released by neutrophils in response to pathogens but are also recognized for their involvement in a range of pathological processes, including autoimmune diseases, cancer, and cardiovascular diseases. This review explores the intricate roles of NETs in different cardiovascular conditions such as thrombosis, atherosclerosis, myocardial infarction, COVID-19, and particularly in the pathogenesis of abdominal aortic aneurysms. We elucidate the mechanisms underlying NET formation and function, provide a foundational understanding of their biological significance, and highlight the contribution of NETs to inflammation, thrombosis, and tissue remodeling in vascular disease. Therapeutic strategies for preventing NET release are compared with approaches targeting components of formed NETs in cardiovascular disease. Current limitations and potential avenues for clinical translation of anti-NET treatments are discussed.

Association between Daily Dietary Calcium Intake and the Risk of Cardiovascular Disease (CVD) in Postmenopausal Korean Women.

We aimed to evaluate the association between daily dietary calcium intake and the risk of cardiovascular disease (CVD) in postmenopausal women using data from the Korean National Health and Nutrition Examination Survey (KNHANES). This cross-sectional study included 12,348 women aged 45-70 years who had reached natural menopause. They were classified into three groups according to daily dietary calcium intake: <400 mg, 400-800 mg, and >800 mg. The risks of CVD, stroke, angina, and myocardial infarction were assessed in each group. Further, we performed subgroup analysis according to the post-menopause duration (≤10 vs. >10 postmenopausal years). We performed logistic regression analysis with adjustment for age, menopausal age, income, urban area, education, insulin use, body mass index, hypertension, diabetes mellitus, dyslipidemia, high alcohol intake, smoking, exercise, oral contraceptive use, and hormonal therapy use. Calcium intake level was not significantly associated with the risk of CVD in the total population and the ≤10 postmenopausal years subgroup. However, in the >10 postmenopausal years subgroup, daily calcium intake >800 mg was associated with significantly decreased risks of all CVD (odds ratio [OR], 0.27; 95% confidence interval [CI], 0.11-0.64), stroke (OR, 0.06; 95% CI, 0.01-0.42), and myocardial infarction (OR, 0.27; 95% CI, 0.11-0.64). Our findings suggest that a dietary calcium intake of >800 mg/day decreases the risk of CVD events in women who have been menopausal for >10 years.

Acute Myocardial Infarction in Women, a Study on Risk Factors, Angiographic Features and Outcomes.

BACKGROUND: Women with acute coronary syndrome are more likely to have cardiovascular disease risk factors and atypical symptoms as compared to men. In Nepal, there is a rising trend of Coronary Artery Disease and myocardial infarction in women. However, research on acute myocardial infarction in women is lacking. The aim of this study was to study the cardiac risk factors, clinical features, angiographic features, and outcome of acute myocardial infarction in Nepalese women admitted to Hospital. METHODS: This was a cross sectional study done at Shahid Gangalal National Heart Center Kathmandu from September 2016 to March 2017. Female patients admitted with a diagnosis of acute ST-segment elevation myocardial infarction or non-ST segment elevation myocardial infarction, who fulfilled the inclusion criteria were included in the study. The details of the patients, demographic profile, major clinical symptoms, major coronary artery disease risk factors, angiographic features and outcomes were recorded and assessed during the study period. Coronary angiography was done in 112 patients out of 178 patients. RESULTS: Out of 178 patients, 85.95 % had ST-segment elevation myocardial infarction and 14.05% had non-ST segment elevation myocardial infarction. The mean patient age was 62.53 ± 12.1. 26.4% patients were of age less than 55 years. Major risk factors were central obesity (94.61%), dyslipidemia due to low HDL (78.65%). hypertension (54.49%), smoking (54.49%) and type 2 diabetes (34.83%). The most common atypical symptoms were shortness of breath (35.39 %,) , nausea and vomiting (23. 6%) and epigastric pain (6.74%), Single vessel disease was found in 36%; double vessel disease in 26.3% and triple vessel disease in 28.9% of patients. The primary outcome of in- hospital mortality was 3.37 %. CONCLUSIONS: Our study showed that significant number of females had Coronary Artery Disease at early age. Among women with myocardial infarction in Nepal, obesity due to high waist to hip ratio was the most common risk factor followed by dyslipidemia due to low high density lipoproteins, smoking, hypertension, and diabetes. Atypical symptoms were also common findings. Single vessel disease was the most common lesion and left anterior descending artery was the most commonly involved vessel. Mortality was seen in ST-segment elevation myocardial infarction patients only.

Rare instances of concomitant acute myocardial infarction and stroke.

Cardio-cerebral infarction (CCI) is a term coined to describe concomitant myocardial infarction and acute ischemic stroke. Acute myocardial infarction and stroke, as separate events, constitute some of the most important causes for disability and mortality in aging societies. Stroke can either occur simultaneously with myocardial infarction or become a serious complication of myocardial infarction and/or its treatment. The frequency of CCI has been reported at a 0.009% incidence rate in stroke patients and is associated with an extremely high mortality. Because of the rare occurrence of CCI, there are currently no guidelines for assessing its diagnosis and optimal treatment. Therefore, currently, the management of CCI cases needs to be individualized. Hopefully, in the future, the results of large clinical trials or prospective registries are expected to enhance our understanding of managing concomitant acute MI and stroke. In this review we have focused on the current literacy in the diagnosis and treatment of CCIs. The paper illustrates potential distinct scenarios of CCI through the analysis of three patient cases (Fig. 5, Ref. 65). Text in PDF www.elis.sk Keywords: myocardial infarction, stroke, cardio-cerebral infarction, carotid artery stenting, cardiac surgery.

Engineered Exosomes with Growth Differentiation Factor-15 Overexpression Enhance Cardiac Repair After Myocardial Injury.

Background: Cardiac repair remains a thorny issue for survivors of acute myocardial infarction (AMI), due to the regenerative inertia of myocardial cells. Cell-free therapies, such as exosome transplantation, have become a potential strategy for myocardial injury. The aim of this study was to investigate the role of engineered exosomes in overexpressing Growth Differentiation Factor-15 (GDF-15) (GDF15-EVs) after myocardial injury, and their molecular mechanisms in cardiac repair. Methods: H9C2 cells were transfected with GDF-15 lentivirus or negative control. The exosomes secreted from H9C2 cells were collected and identified. The cellular apoptosis and autophagy of H2O2-injured H9C2 cells were assessed by Western blotting, TUNEL assay, electron microscopy, CCK-8 and caspase 3/7 assay. A rat model of AMI was constructed by ligating the left anterior descending artery. The anti-apoptotic, pro-angiogenic effects of GDF15-EVs treatment, as well as ensuing functional and histological recovery were evaluated. Then, mRNA sequencing was performed to identify the differentially expressed mRNAs after GDF15-EVs treatment. Results: GDF15-EVs inhibited apoptosis and promoted autophagy in H2O2 injured H9C2 cells. GDF15-EVs effectively decreased the infarct area and enhanced the cardiac function in rats with AMI. Moreover, GDF15-EVs hindered inflammatory cell infiltration, inhibited cell apoptosis, and promoted cardiac angiogenesis in rats with AMI. RNA sequence showed that telomerase reverse transcriptase (TERT) mRNA was upregulated in GDF15-EVs-treated H9C2 cells. AMPK signaling was activated after GDF15-EVs. Silencing TERT impaired the protective effects of GDF15-EVs on H2O2-injured H9C2 cells. Conclusion: GDF15-EVs could fulfil their protective effects against myocardial injury by upregulating the expression of TERT and activating the AMPK signaling pathway. GDF15-EVs might be exploited to design new therapies for AMI.

Key lifestyles and health outcomes across 16 prevalent chronic diseases: A network analysis of an international observational study.

Background: Central and bridge nodes can drive significant overall improvements within their respective networks. We aimed to identify them in 16 prevalent chronic diseases during the coronavirus disease 2019 (COVID-19) pandemic to guide effective intervention strategies and appropriate resource allocation for most significant holistic lifestyle and health improvements. Methods: We surveyed 16 512 adults from July 2020 to August 2021 in 30 territories. Participants self-reported their medical histories and the perceived impact of COVID-19 on 18 lifestyle factors and 13 health outcomes. For each disease subgroup, we generated lifestyle, health outcome, and bridge networks. Variables with the highest centrality indices in each were identified central or bridge. We validated these networks using nonparametric and case-dropping subset bootstrapping and confirmed central and bridge variables' significantly higher indices through a centrality difference test. Findings: Among the 48 networks, 44 were validated (all correlation-stability coefficients >0.25). Six central lifestyle factors were identified: less consumption of snacks (for the chronic disease: anxiety), less sugary drinks (cancer, gastric ulcer, hypertension, insomnia, and pre-diabetes), less smoking tobacco (chronic obstructive pulmonary disease), frequency of exercise (depression and fatty liver disease), duration of exercise (irritable bowel syndrome), and overall amount of exercise (autoimmune disease, diabetes, eczema, heart attack, and high cholesterol). Two central health outcomes emerged: less emotional distress (chronic obstructive pulmonary disease, eczema, fatty liver disease, gastric ulcer, heart attack, high cholesterol, hypertension, insomnia, and pre-diabetes) and quality of life (anxiety, autoimmune disease, cancer, depression, diabetes, and irritable bowel syndrome). Four bridge lifestyles were identified: consumption of fruits and vegetables (diabetes, high cholesterol, hypertension, and insomnia), less duration of sitting (eczema, fatty liver disease, and heart attack), frequency of exercise (autoimmune disease, depression, and heart attack), and overall amount of exercise (anxiety, gastric ulcer, and insomnia). The centrality difference test showed the central and bridge variables had significantly higher centrality indices than others in their networks (P < 0.05). Conclusion: To effectively manage chronic diseases during the COVID-19 pandemic, enhanced interventions and optimised resource allocation toward central lifestyle factors, health outcomes, and bridge lifestyles are paramount. The key variables shared across chronic diseases emphasise the importance of coordinated intervention strategies.

Depression Onset After a Spouse's Cardiovascular Event.

Importance: Although cardiovascular disease (CVD) is a known risk factor for depression, evidence is lacking regarding whether and to what extent a spouse's CVD is associated with the subsequent mental health of individuals. Objective: To examine the association between CVD onset in spouses and subsequent depression. Design, Setting, and Participants: This cohort study examined 277 142 matched married couples enrolled in the Japan Health Insurance Association health insurance program between April 2015 and March 2022, covering approximately 40% of the working-age population in Japan. Index individuals (primary insured) whose spouses (dependent) experienced incident CVD between April 2016 and March 2022 were 1:1 matched to controls whose spouses did not experience CVD. Matching was based on age, sex, income, or the onset date of the spouses' CVD. Data analysis was conducted from April 2016 to March 2022. Exposure: Spousal onset of CVD between fiscal years 2016 and 2021. The International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes were used to identify the composite CVD outcomes (stroke, heart failure, and myocardial infarction). Main Outcomes and Measures: Multivariate Cox proportional hazards models were used to investigate the association between spouses' new-onset CVD and individuals' depression, adjusting for sociodemographic characteristics and comorbidities of index individuals (diabetes, hypertension, and CVD) and spouses (diabetes, hypertension, and depression). Subgroup analyses were conducted according to sex, age, income levels, and history of CVD. Results: Among 277 142 matched pairs of married couples, 263 610 (95.1%) had a male index individual; the mean (SD) age of index individuals was 58.2 (10.2) years. A new onset of depression was observed in 4876 individuals (1.8%). In multivariable Cox models, there was an association between the spouse's CVD and the individuals' depression (hazard ratio, 1.13 [95% CI, 1.07-1.20]). The subgroup analysis found no evidence of heterogeneity in sex, age, income level, or CVD history. The results were consistent when additionally adjusted for health behaviors (smoking, alcohol consumption, physical activity, and use of antihypertensive drugs) and objectively measured physical health conditions (body mass index, blood pressure, cholesterol levels, glucose levels, and estimated glomerular filtration rate) (hazard ratio, 1.16 [95% CI, 1.06-1.28]). Conclusions and Relevance: In this nationwide cohort study of matched couples, a spouse's onset of CVD was associated with an increased risk of an individual's depression. These findings highlight the importance of preventive care for mental health disorders in individuals whose spouses experience incident CVD.

Predictors of major adverse cardiac and cerebrovascular events after percutaneous coronary intervention in older adults: a systematic review and meta-analysis.

AIM: We systematically reviewed and meta-analyzed the predictors of major adverse cardiac and cerebrovascular events (MACE/MACCE) in older adults who underwent PCI. METHODS: Three databases, PubMed, Embase, and Scopus, were searched for observational studies considering the out-of-hospital MACE/MACCE in adults ≥ 60 years old with coronary artery disease (acute or chronic) who underwent PCI. Studies were eligible if they had determined at least two statistically significant predictors of MACE/MACCE by multivariable analysis. We used the QUIPS tool to evaluate the risk of bias in the studies. Random-effects meta-analysis was utilized to pool the hazard ratios (HRs) of the most reported predictors. RESULTS: A total of 34 studies were included in the review. Older age (HR = 1.04, 95% Confidence Interval (CI): 1.03-1.06, P-value < 0.001), diabetes (HR = 1.36, 95% CI: 1.22-1.53, P < 0.001), history of myocardial infarction (MI) (HR = 1.88, 95% CI: 1.37-2.57, P < 0.001), ST-elevation MI (STEMI) at presentation (HR = 1.72, 95% CI: 1.37-2.18, P < 0.001), reduced left ventricular ejection fraction (LVEF) (HR = 2.01, 95% CI: 1.52-2.65, P < 0.001), successful PCI (HR = 0.35, 95% CI: 0.27-0.47, P < 0.001), eGFR (HR = 0.99, 95% CI: 0.97-1.00; P-value = 0.04) and left main coronary artery (LMCA) disease (HR = 2.07, 95% CI: 1.52-2.84, P < 0.001) were identified as predictors of MACE. CONCLUSION: We identified older age, diabetes, history of MI, STEMI presentation, lower LVEF, and LMCA disease increased the risk of MACE/MACCE after PCI in older adults. Meanwhile, higher eGFR and successful PCI predicted lower adverse events risk. Future studies should focus on a more robust methodology and a precise definition of MACE. REGISTRATION: PROSPERO (CRD42023480332).

Left ventricular free wall rupture caused by myocardial ischemia without treatable atherosclerotic coronary disease: a case series.

BACKGROUND: The clinical presentation of left ventricular free wall rupture (LVFWR) varies ranging from uneventful condition to congestive heart failure. Here we report two cases of LVFWR with different clinical presentation and notable outcome. A 53-year-old male presenting emergently with signs of myocardial infarction received immediate coronary angiography and thoracic CT-scan showing occlusion of the first marginal coronary branch without possibility of revascularization and minimal pericardial extravasation. Under ICU surveillance, LVFWR occurred 24 h later and was treated by pericardiocentesis and ECMO support followed by immediate uncomplicated surgical repair. Postoperative therapy-refractory vasoplegia and electromechanical dissociation caused fulminant deterioration and the early death of the patient. The second case is a 76-year old male brought to the emergency room after sudden syncope, clinical sings of pericardial tamponade and suspicion of a type A acute aortic dissection. Immediate CT-angiography excluded aortic dissection and revealed massive pericardial effusion and a hypoperfused myocardial area on the territory of the first marginal branch. Immediate sternotomy under mechanical resuscitation enabled removal of the massive intrapericardial clot and revealed LVFWR. After an uncomplicated surgical repair, an uneventful postoperative course, the patient was discharged with sinus rhythm and good biventricular function. One year after the operation, he is living at home, symptom free. DISCUSSION: Whereas the younger patient, who was clinically stable at hospital admission received delayed surgery and did not survive treatment, the older patient, clinically unstable at presentation, went into immediate surgery and had a flawless postoperative course. Thus, early surgical repair of LVFWR leads to best outcome and treating LVFWR as a high emergency regardless of the symptoms improve survival.

In suspected ACS, hs-cTnI- vs. c-cTnI-guided care was associated with improved outcomes at 5 y in certain subgroups.

SOURCE CITATION: Lee KK, Doudesis D, Ferry AV, et al; High-STEACS Investigators. Implementation of a high sensitivity cardiac troponin I assay and risk of myocardial infarction or death at five years: observational analysis of a stepped wedge, cluster randomised controlled trial. BMJ. 2023;383:e075009. 38011922.

Quantitative Benefit-Risk Evaluation of Rivaroxaban in Patients After Peripheral Arterial Revascularization: The VOYAGER PAD Trial.

BACKGROUND: The VOYAGER PAD (Efficacy and Safety of Rivaroxaban in Reducing the Risk of Major Thrombotic Vascular Events in Subjects With Symptomatic Peripheral Artery Disease Undergoing Peripheral Revascularization Procedures of the Lower Extremities) trial compared rivaroxaban (2.5 mg twice a day) plus aspirin with aspirin alone in patients with symptomatic peripheral artery disease requiring endovascular or surgical limb revascularization, with 50% receiving clopidogrel background therapy. The New Drug Indication application includes benefit-risk assessments using clinical judgment to balance benefits against risks. During its review, the US Food and Drug Administration requested additional quantitative benefit-risk analyses with formal weighting approaches. METHODS AND RESULTS: Benefits and risks were assessed using rate differences between treatment groups (unweighted analysis). To account for clinical importance of the end points, a multi-criteria decision analysis was conducted using health state utility values as weights. Monte Carlo simulations incorporated statistical uncertainties of the event rates and utility weights. Intent-to-treat and on-treatment analyses were conducted. For unweighted intent-to-treat analyses, rivaroxaban plus aspirin would result in 120 (95% CI, -208 to -32) fewer events of the primary composite end point (per 10 000 patient-years) compared with aspirin alone. Rivaroxaban caused an excess of 40 (95% CI, 8-72) Thrombolysis in Myocardial Infarction major bleeding events, which was largely driven by nonfatal, nonintracranial hemorrhage Thrombolysis in Myocardial Infarction major bleeding events. For weighted analyses, rivaroxaban resulted in the utility equivalent of 13.7 (95% CI, -85.3 to 52.6) and 68.1 (95% CI, 7.9-135.7) fewer deaths per 10 000 patient-years (intent-to-treat and on-treatment, respectively), corresponding to probabilities of 64.4% and 98.7%, respectively, that benefits outweigh risks favoring rivaroxaban per Monte Carlo simulation. CONCLUSIONS: These analyses show a favorable benefit-risk profile of rivaroxaban therapy in the VOYAGER PAD trial, with findings generally consistent between the unweighted and weighted approaches.