Pubblicazioni recenti - cardiovascular disease
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Effectiveness and Cost-Effectiveness of Survivorship Care for Survivors of Hodgkin Lymphoma (INSIGHT Study): Protocol for a Multicenter Retrospective Cohort Study With a Quasi-Experimental Design.
JMIR Res Protoc2024 Apr;13():e55601. doi: 10.2196/55601.
Lammers Eline M J, Zijlstra Josée M, Retèl Valesca P, Aleman Berthe M P, van Leeuwen Flora E, Nijdam Annelies, ,
Abstract
BACKGROUND:
Hodgkin lymphoma (HL) occurs at young ages, with the highest incidence between 20 and 40 years. While cure rates have improved to 80%-90% over the past decades, survivors of HL are at substantial risk of late treatment-related complications, such as cardiovascular diseases, breast cancer, severe infections, and hypothyroidism. To reduce morbidity and mortality from late treatment effects, the Dutch Better care after lymphoma, Evaluation of long-term Treatment Effects and screening Recommendations (BETER) consortium developed a survivorship care program for 5-year survivors of HL that includes risk-based screening for and treatment of (risk factors for) late adverse events. Even though several cancer survivorship care programs have been established worldwide, there is a lack of knowledge about their effectiveness in clinical practice.
OBJECTIVE:
The Improving Nationwide Survivorship care Infrastructure and Guidelines after Hodgkin lymphoma Treatment (INSIGHT) study evaluates whether Dutch BETER survivorship care for survivors of HL decreases survivors' burden of disease from late adverse events after HL treatment and associated health care costs and improves their quality of life.
METHODS:
The INSIGHT study is a multicenter retrospective cohort study with a quasi-experimental design and prospective follow-up, embedded in the national BETER survivorship care infrastructure. The first BETER clinics started in 2013-2016 and several other centers started or will start BETER clinics in 2019-2024. This allows us to compare survivors who did and those who did not receive BETER survivorship care in the last decade. Survivors in the intervention group are matched to controls (n=450 per group) based on sex, age at diagnosis (±5 years), age in 2013 (±5 years), and treatment characteristics. The primary outcome is the burden of disease in disability-adjusted life years from cardiovascular disease, breast cancer, severe infections, and hypothyroidism. In a cost-effectiveness analysis, we will assess the cost of BETER survivorship care per averted or gained disability-adjusted life year and quality-adjusted life year. Secondary outcomes are BETER clinic attendance, adherence to screening guidelines, and knowledge and distress about late effects among survivors of HL. Study data are collected from a survivor survey, a general practitioner survey, medical records, and through linkages with national disease registries.
RESULTS:
The study was funded in November 2020 and approved by the institutional review board of the Netherlands Cancer Institute in July 2021. We expect to finalize recruitment by October 2024, data collection by early 2025, and data analysis by May 2025.
CONCLUSIONS:
INSIGHT is the first evaluation of a comprehensive survivorship program using real-world data; it will result in new information on the (cost-)effectiveness of survivorship care in survivors of HL in clinical practice. The results of this study will be used to improve the BETER program where necessary and contribute to more effective evidence-based long-term survivorship care for lymphoma survivors.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID):
PRR1-10.2196/55601.
©Eline M J Lammers, Josée M Zijlstra, Valesca P Retèl, Berthe M P Aleman, Flora E van Leeuwen, Annelies Nijdam, BETER consortium. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 18.04.2024.
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Racial Discrimination and Metabolic Syndrome in Young Black Adults.
JAMA Netw Open2024 Apr;7(4):e245288. doi: 10.1001/jamanetworkopen.2024.5288.
Heard-Garris Nia, Yu Tianyi, Brody Gene, Chen Edith, Ehrlich Katherine B, Miller Gregory E,
Abstract
IMPORTANCE:
Metabolic syndrome (MetS) is a common health condition that predisposes individuals to cardiovascular disease (CVD) and disproportionately affects Black and other racially and ethnically minoritized people. Concurrently, Black individuals also report more exposure to racial discrimination compared with White individuals; however, the role of discrimination in the development of MetS over time and associated mediators in these pathways remain underexplored.
OBJECTIVE:
To evaluate the association between racial discrimination and MetS in rural Black individuals transitioning from late adolescence into early adulthood and to identify potential mediating pathways.
DESIGN, SETTING, AND PARTICIPANTS:
This longitudinal cohort study included Black adolescents enrolled in the Strong African American Families Healthy Adults (SHAPE) Project between June 2009 and May 2021. Families resided in rural counties of Georgia, where poverty rates are among the highest in the nation. Analyses included 322 of the 500 participants who originally enrolled in SHAPE and who were eligible to participate. Guardians provided information about socioeconomic disadvantage. Analyses were conducted in April 2023.
EXPOSURES:
Youths reported exposure to racial discrimination annually from ages 19 to 21 years.
MAIN OUTCOMES AND MEASURES:
MetS was the main health outcome and was measured at ages 25 and 31 years. MetS was diagnosed according to the International Diabetes Federation guidelines, which requires central adiposity (ie, waist circumference ?94 cm for males and ?80 cm for females) and at least 2 of the 4 additional components: signs of early hypertension (ie, systolic blood pressure ?130 mm Hg or diastolic blood pressure ?85 mm Hg); elevated triglyceride levels (ie, >150 mg/dL); elevated fasting glucose level (ie, ?100 mg/dL); or lowered high-density lipoprotein levels (ie,
RESULTS:
In 322 participants (210 [65.2%] female) ages 19 to 21 years, more frequent exposure to racial discrimination was associated with higher suPAR levels (b?=?0.006; 95% CI, 0.001-0.011; P?=?.01) and more sleep problems at age 25 years (b?=?0.062; 95% CI, 0.028-0.097; P?.001) as well as a 9.5% higher risk of MetS diagnosis at age 31 years (odds ratio [OR], 1.10; 95% CI, 1.01-1.20; P?=?.03). Both suPAR (b?=?0.015; 95% CI, 0.002-0.037) and sleep problems (b?=?0.020; 95% CI, 0.002-0.047) at age 25 years were significant indirect pathways. No significant interactions between sex and discrimination emerged.
CONCLUSIONS AND RELEVANCE:
This study suggests that racial discrimination in late adolescence is associated with MetS among Black young adults through biobehavioral pathways. Thus, health interventions for MetS in Black adults will need to contend with sleep behaviors and inflammatory intermediaries as well as address and reduce exposure to racial discrimination to narrow disparities and promote health equity.
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Age-related changes of interoceptive brain networks: Implications for interoception and alexithymia.
Emotion2024 Apr;():. doi: 10.1037/emo0001366.
Dobrushina Olga R, Dobrynina Larisa A, Arina Galina A, Pechenkova Ekaterina V, Kremneva Elena I, Gubanova Mariia V, Novikova Evgenia S, Kazantseva Daria A, Suslina Anastasia D, Krotenkova Marina V,
Abstract
Aging is known to be associated with a decline in interoceptive abilities and changes in emotional processing, including alexithymia. As the brain areas supporting interoceptive awareness participate in the perception of emotion, we suggested that interoceptive decline and alexithymia in older adults may share common neural ground. To test this hypothesis, we administered functional magnetic resonance imaging-based heartbeat detection task to 62 adults of diverse ages (range 18-73) and evaluated a larger sample of older and younger adults using questionnaires characterizing interoceptive sensibility, alexithymia, and depressive attitudes. We found that increasing age was linked to decreased activation during the interoceptive task, including the right insular-opercular and supplementary motor areas (SMAs). Age also affected task-based functional connectivity, with two major effects being a decrease in the connectivity of the SMA-insular network and an increase in the connectivity of the prefrontal-lateral occipital network. Path analysis performed for interoceptive accuracy as the endogenous variable revealed that the impact of age was mediated by the functional activation of the insular cortex and SMA and by the connectivity between these areas. Another path analysis using alexithymia as the endogenous variable while controlling for depressive attitudes showed that the effect of age was mediated by interoceptive decline. The study supports the role of central mechanisms in age-related interoceptive decline and shows its implications for alexithymia. Since alexithymia represents a risk factor for mental and cardiovascular diseases, the study findings may open an important direction toward maintaining older adults' well-being. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Evaluation of the efficacy of combined device strategies for long femoropopliteal artery disease.
Cardiovasc Interv Ther2024 Apr;():. doi: 10.1007/s12928-024-00997-4.
Iwata Shuko, Suzuki Riho, Hosoi Yuichiro, Tanaka Yuki, Izumi Yuichi, Tan Michinao, Urasawa Kazushi,
Abstract
One of the major problems associated with bare nitinol stent implantation is stent fracture, particularly in the popliteal artery. The purpose of this study was to determine whether drug coated balloons (DCB), interwoven stents (IWS), or plain old balloon angioplasty (POBA) would be suitable for use in distal femoropopliteal (FP) long lesions when an Eluvia stent was implanted proximal to a lesion. This was a multi-center retrospective study enrolling patients undergoing concomitant use of Eluvia with DCB, IWS or POBA for symptomatic atherosclerotic femoropopliteal disease (lesion length?>?15 cm) [Rutherford category 2-6] between January 2018 and September 2021. 79 patients with 89 femoropopliteal lesions were enrolled in this study. The mean lesion length and the percentage of the popliteal artery involvement was 24.3?±?6.4 cm vs 24.0?±?9.0 cm vs 26.6?±?6.2 cm and 65.8% vs 89.4% vs 67.8% for the Eluvia?+?DCB, Eluvia?+?IWS, and Eluvia?+?POBA groups, respectively. The 1-year Kaplan-Meier estimates of primary patency and freedom from major adverse limb events (MALEs) were 53.3% vs 44.1% vs 24.2% and 62.4% vs 51.0% vs 28.1%, respectively. Eluvia?+?POBA was associated with a lower rate for 1-year primary patency (HR 2.49; 95% confidence interval (CI): 1.28-4.87; p?=?0.007 and HR 2.38; 95% CI: 1.13-5.77; p?=?0.04). In SFA long lesions with proximal Eluvia implantation, distal implantations of either a DCB or IWS were comparable, as opposed to POBA alone which generated worse results.
© 2024. The Author(s) under exclusive licence to Japanese Association of Cardiovascular Intervention and Therapeutics.
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Ineffectiveness of hemoadsorption in large animals with abdominal sepsis: a randomized controlled porcine study.
Intensive Care Med Exp2024 Apr;12(1):38. doi: 10.1186/s40635-024-00622-x.
Tegl Vaclav, Horak Jan, Nalos Lukas, Horakova Michala, Stengl Milan, Matejovic Martin, Benes Jan,
Abstract
OBJECTIVES:
The use of hemoadsorption (HA) has become popular in the treatment of vasoplegic states associated with massive cytokine release, including septic shock. However, this approach does not seem to be based on robust evidence, and it does not follow international guidelines. To understand the pathophysiological rationale and timing of HA, we conducted a large animal septic shock experiment.
DESIGN:
Prospective randomized large-animal peritoneal septic shock experiment.
SETTING:
Laboratory investigation.
SUBJECTS:
Twenty-six anesthetized, mechanically ventilated, and instrumented pigs randomly assigned into (1) sham-operated group with HA (SHAM, n?=?5); (2) sepsis animals without HA (SEPSIS, n?=?5); (3) sepsis group with HA at norepinephrine initiation (EARLY, n?=?8); and (4) sepsis group with HA initiated at norepinephrine rate reaching 0.5 ?g/kg/min (LATE, n?=?8).
INTERVENTIONS:
Peritoneal sepsis was induced by cultivated autologous feces inoculation. A CytoSorb cartridge (200 g) with a blood flow rate of 200 mL/min and heparin anticoagulation was used to perform HA. The animals received sedation and intensive organ support up to 48 h or until they experienced cardiovascular collapse.
MEASUREMENTS AND MAIN RESULTS:
Systemic hemodynamics, multiple-organ functions, and immune-inflammatory response were measured at predefined periods. The HA treatment was not associated with any measurable benefit in terms of systemic hemodynamics and organ support. The systemic inflammatory markers were unaffected by any of the treatment timings. In contrast, the HA resulted in higher vasopressor load and decreased 36-h survival (5 animals in SHAM (100%), 4 (80%) in SEPSIS, 4 (57%) in EARLY, and 2 (25%) in LATE; p?=?0.041). The HA exposure in healthy animals was associated with hemodynamic deterioration, systemic inflammatory response, and cytopenia.
CONCLUSIONS:
In this large-animal-controlled fulminant sepsis study, the HA was unable to counteract the disease progression in the early or advanced septic shock phase. However, findings from the HA-exposed sham animals suggest potential safety concerns.
© 2024. The Author(s).
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Vascular endothelial dysfunction induced by 3-bromofluoranthene via MAPK-mediated-NF?B pro-inflammatory pathway and intracellular ROS generation.
Arch Toxicol2024 Apr;():. doi: 10.1007/s00204-024-03751-0.
Lee Chien-Ying, Wu Sheng-Wen, Yang Jiann-Jou, Chen Wen-Ying, Chen Chun-Jung, Chen Hsin-Hung, Lee Yi-Chia, Su Chun-Hung, Kuan Yu-Hsiang,
Abstract
3-Bromofluoranthene (3-BrFlu) is the secondary metabolite of fluoranthene, which is classified as a polycyclic aromatic hydrocarbon, through bromination and exists in the fine particulate matter of air pollutants. Endothelial dysfunction plays a critical role in the pathogenesis of cardiovascular and vascular diseases. Little is known about the molecular mechanism of 3-BrFlu on endothelial dysfunction in vivo and in vitro assay. In the present study, 3-BrFlu included concentration-dependent changes in ectopic angiogenesis of the sub-intestinal vein and dilation of the dorsal aorta in zebrafish. Disruption of vascular endothelial integrity and up-regulation of vascular endothelial permeability were also induced by 3-BrFlu in a concentration-dependent manner through pro-inflammatory responses in vascular endothelial cells, namely, SVEC4-10 cells. Generation of pro-inflammatory mediator PGE2 was induced by 3-BrFlu through COX2 expression. Expression of COX2 and generation of pro-inflammatory cytokines, including TNF? and IL-6, were induced by 3-BrFlu through phosphorylation of NF-?B p65, which was mediated by phosphorylation of MAPK, including p38 MAPK, ERK and JNK. Furthermore, generation of intracellular ROS was induced by 3-BrFlu, which is associated with the down-regulated activities of the antioxidant enzyme (AOE), including SOD and catalase. We also found that 3-BrFlu up-regulated expression of the AOE and HO-1 induced by 3-BrFlu through Nrf-2 expression. However, the 3-BrFlu-induced upregulation of AOE and HO-1 expression could not be revised the responses of vascular endothelial dysfunction. In conclusion, 3-BrFlu is a hazardous substance that results in vascular endothelial dysfunction through the MAPK-mediated-NF?B pro-inflammatory pathway and intracellular ROS generation.
© 2024. The Author(s).
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Unexplained Residual Risk In Type 2 Diabetes: How Big Is The Problem?
Curr Cardiol Rep2024 Apr;():. doi: 10.1007/s11886-024-02055-0.
Neppala Sivaram, Rajan Jemema, Yang Eric, DeFronzo Ralph A,
Abstract
PURPOSE OF REVIEW:
What is new? Cardiovascular disease (CVD) is the leading cause of mortality in type 2 diabetes (T2D) individuals. Of the major risk factors for CVD, less than 10% of T2D people meet the American Diabetes Association/American Heart Association recommended goals of therapy. The present review examines how much of the absolute cardiovascular (CV) risk in type 2 diabetes patients can be explained by major CV intervention trials.
RECENT FINDINGS:
Multiple long-term cardiovascular (CV) intervention trials have examined the effect of specific target-directed therapies on the MACE endpoint. Only one prospective study, STENO-2, has employed a multifactorial intervention comparing intensified versus conventional treatment of modifiable risk factors in T2D patients, and demonstrated a 20% absolute CV risk reduction. If the absolute CV risk reduction in these trials is added to that in the only prospective multifactorial intervention trial (STENO-2), the unexplained CV risk is 44.1%. What are the clinical implications? Potential explanations for the unaccounted-for reduction in absolute CV risk in type 2 diabetes (T2D) patients are discussed.
HYPOTHESIS:
failure to take into account synergistic interactions between major cardiovascular risk factors is responsible for the unexplained CV risk in T2D patients. Simultaneous treatment of all major CV risk factors to recommended AHA/ADA guideline goals is required to achieve the maximum reduction in CV risk.
© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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Clinical characteristics, imaging findings, management, and outcomes of patients with scimitar syndrome at a tertiary referral healthcare center in Colombia.
Int J Cardiovasc Imaging2024 Apr;():. doi: 10.1007/s10554-024-03102-1.
Aristizabal Ana M, Guzmán-Serrano Carlos A, Mondol-Villamil Nancy Vanessa, Bolaños-Vallejo Lina Maria, Mejia-Quiñones Valentina, Recio-Gómez Maria Alejandra, García-Pretelt Enrique Carlos, Mejía-González Mauricio, Alvarez Walter Mosquera, Gutiérrez-Gil Jaiber Alberto,
Abstract
Scimitar Syndrome is part of a complex spectrum of congenital cardiovascular anomalies related to anomalous pulmonary venous return. Depending on the extent of involvement, treatment can be either expectant or surgical. Prognosis and survival have been controversial, with some results supporting early surgical management. This research aims to disclose the outcomes and describe the management, clinical and imaging characteristics of patients diagnosed with Scimitar Syndrome treated in a tertiary referral healthcare center. Longitudinal descriptive observational study. The study included all patients diagnosed with scimitar syndrome in our institution between January/2011 and December/2022. A description of the sociodemographic and clinical characteristics, diagnostic tools used, treatment features, and patient outcomes is provided. Eleven patients were included, with a mean age at diagnosis of five years (CI 0-17), six of which were female (54.55%). Nine (81.82%) patients had evidence of a scimitar vein on the chest radiograph, six (54.55%) cardiac dextroposition, six (54.55%) pulmonary hypoplasia, five (45.45%) right pulmonary artery hypoplasia, and three (27.27%) had aortopulmonary collaterals. Four (36.36%) patients had horseshoe lungs, and four (36.36%) had bronchopulmonary sequestration. In the associations, two (18.18%) patients were found to have an atrial septal defect, three (27.27%) ventricular septal defect, and one (9%) had Tetralogy of Fallot. Pulmonary hypertension was demonstrated in two (18.18%) patients. Seven (63.64%) required surgical management to correct the scimitar vein, and two patients died due to unrelated complications. Scimitar syndrome presents diagnostic and treatment challenges, necessitating a multidisciplinary approach for timely care. Chest radiography and CT scans are primary diagnostic tools, with surgical intervention often warranted alongside other heart defects or significant hemodynamic repercussions. Medical management is effective for mild to moderate cases. Long-term patient outcomes remain uncertain due to study limitations, but improved life expectancy is anticipated with ongoing care.
© 2024. The Author(s).
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Health and economic impact of dapagliflozin for type 2 diabetes patients who had or were at risk for atherosclerotic cardiovascular disease in the Italian general practitioners setting: a budget impact analysis.
Acta Diabetol2024 Apr;():. doi: 10.1007/s00592-024-02276-3.
Cortesi Paolo Angelo, Antonazzo Ippazio Cosimo, Palladino Pasquale, Gnesi Marco, Mele Silvia, D'Amelio Marco, Zanzottera Ferrari Elena, Mazzaglia Giampiero, Mantovani Lorenzo Giovanni,
Abstract
AIM:
In 2022, in Italy, general practitioners (GPs) have been allowed to prescribe SGLT2i in Type 2 Diabetes (T2D) under National Health Service (NHS) reimbursement. In the pivotal clinical trial named DECLARE-TIMI 58, dapagliflozin reduced the risk of hospitalization for heart failure, CV death and kidney disease progression compared to placebo in a population of T2D patients. This study evaluated the health and economic impact of dapagliflozin for T2D patients who had or were at risk for atherosclerotic cardiovascular disease in the Italian GPs setting.
METHODS:
A budget impact model was developed to assess the health and economic impact of introducing dapagliflozin in GPs setting. The analysis was conducted by adopting the Italian NHS perspective and a 3-year time horizon. The model estimated and compared the health outcomes and direct medical costs associated with a scenario with dapagliflozin and other antidiabetic therapies available for GPs prescription (scenario B) and a scenario where only other antidiabetic therapies are available (scenario A). Rates of occurrence of cardiovascular and renal complications as well as adverse events were captured from DECLARE-TIMI 58 trial and the literature, while cost data were retrieved from the Italian tariff and the literature. One-way sensitivity analyses were conducted to test the impact of model parameters on the budget impact.
RESULTS:
The model estimated around 442.000 patients eligible for the treatment with dapagliflozin in the GPs setting for each simulated year. The scenario B compared to scenario A was associated with a reduction in the occurrence of cardiovascular and renal complication (-1.83%) over the 3 years simulated. Furthermore, the scenario A allowed for an overall cost saving of 102,692,305?: 14,521,464? in the first year, 33,007,064? in the second and 55,163,777? in the third. The cost of cost of drug acquisition, the probability of cardiovascular events and the percentage of patients potentially eligible to the treatment were the factor with largest impact on the results.
CONCLUSIONS:
The use of dapagliflozin in GPs setting reduce the number of CVD events, kidney disease progression and healthcare costs in Italy. These data should be considered to optimize the value produced for the T2D patients who had or were at risk for atherosclerotic cardiovascular disease.
© 2024. The Author(s).
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Unveiling Subclinical Cardiovascular Disease in HIV with Advanced Cardiovascular Imaging.
Radiol Cardiothorac Imaging2024 Apr;6(2):e240076. doi: 10.1148/ryct.240076.
Luetkens Julian A, Bischoff Leon M,
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Cardiac MRI after Sudden Cardiac Arrest: A Systematic Review.
Radiol Cardiothorac Imaging2024 Apr;6(2):e230216. doi: 10.1148/ryct.230216.
Scharinger Bernhard, Boxhammer Elke, Rezar Richard, Hecht Stefan, Wernly Sarah, Widhalm Tobias, Lichtenauer Michael, Hoppe Uta C, Hergan Klaus, Wernly Bernhard, Strohmer Bernhard, Kaufmann Reinhard,
Abstract
Purpose To perform a systematic review to assess the diagnostic and prognostic value of cardiac MRI after sudden cardiac arrest (SCA). Materials and Methods PubMed and Cochrane Library databases were systematically searched for studies investigating cardiac MRI after SCA in adult patients (?18 years of age). The time frame of the encompassed studies spans from January 2012 to January 2023. The study protocol was preregistered in OSF Registries , and the systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The quality of the included studies was evaluated using the Newcastle-Ottawa quality assessment scale. Results Fourteen studies involving 1367 individuals, 1257 (91.9%) of whom underwent cardiac MRI, were included. Inconsistent findings were reported on the diagnostic value of cardiac MRI-specific findings. The included studies demonstrated the following main findings: cardiac MRI led to a new or alternative diagnosis in patients with SCA; cardiac MRI identified pathologic or arrhythmogenic substrates; cardiac MRI helped detect myocardial edema (potentially reversible); cardiac MRI provided evidence for the occurrence of adverse events; and functional markers or ventricular dimensions were considered prognostically relevant in a few studies. Relevant challenges in this systematic review were the lack of comparators and reference standards relative to cardiac MRI as the index test and patient selection bias. Conclusion Cardiac MRI following SCA can contribute to the diagnostic process and offer supplementary information essential for treatment planning. Limitations of the review include studies with insufficient comparators and potential bias in patient selection. Systematic review registration link: osf.io/nxaev Cardiac MRI, Cardiovascular Disease, Cardiomyopathy, Ischemia, Myocardial Edema, Sudden Cardiac Arrest © RSNA, 2024.
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The relevance of intestinal barrier dysfunction, antimicrobial proteins and bacterial endotoxin in metabolic dysfunction-associated steatotic liver disease.
Eur J Clin Invest2024 Apr;():e14224. doi: 10.1111/eci.14224.
Bergheim Ina, Moreno-Navarrete José María,
Abstract
BACKGROUND:
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of end-stage liver disease associated with increased mortality and cardiovascular disease. Obesity and diabetes are the most important risk factors of MASLD. It is well-established that obesity-associated insulin resistance leads to a situation of tissue lipotoxicity characterized by an accumulation of excess fat in non-fat tissues such as the liver, promoting the development of MASLD, and its progression into metabolic dysfunction-associated steatohepatitis.
METHODS:
Here, we aimed to review the impact of disrupted intestinal permeability, antimicrobial proteins and bacterial endotoxin in the development and progression of MASLD.
RESULTS AND CONCLUSION:
Recent studies demonstrated that obesity- and obesogenic diets-associated alterations of intestinal microbiota along with the disruption of intestinal barrier integrity, the alteration in antimicrobial proteins and, in consequence, an enhanced translocation of bacterial endotoxin into bloodstream might contribute to this pathological process through to impacting liver metabolism and inflammation.
© 2024 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.
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Gliflozins in the Treatment of Non-diabetic Experimental Cardiovascular Diseases.
Physiol Res2024 Apr;():.
Van??ková I, Zicha J,
Abstract
A new class of antidiabetic drugs - gliflozins (inhibitors of sodium glucose cotransporter-2; SGLT-2i) stimulate glucose and sodium excretion, thereby contributing to improved glycemic control, weight loss and blood pressure reduction in diabetic patients. Large clinical trials in patients with type 2 diabetes treated with empagliflozin, canagliflozin or dapagliflozin have demonstrated their excellent efficacy in improving many cardiovascular outcomes, including the reduction of death from cardiovascular diseases, non-fatal myocardial infarction or stroke, and hospitalization for heart failure. Moreover, the beneficial effects of SGLT-2i were also demonstrated in the decrease in proteinuria, which leads to a lower risk of progression to end-stage renal disease and thus a delay in initiation of the renal replacement therapy. Unexpectedly, their cardioprotective and renoprotective effects have been demonstrated not only in patients with diabetes but also in those without diabetes. Recently, much effort has been focused on patients with heart failure (either with reduced or preserved ejection fraction) or liver disease. Experimental studies have highlighted pleiotropic effects of SGLT-2 inhibitors beyond their natriuretic and glycosuric effects, including reduction of fibrosis, inflammation, reactive oxygen species, and others. Our results in experimental non-diabetic models of hypertension, chronic kidney disease and heart failure are partially consistent with these findings. This raises the question of whether the same mechanisms are at work in diabetic and non-diabetic conditions, and which mechanisms are responsible for the beneficial effects of gliflozins under non-diabetic conditions. Are these effects cardio-renal, metabolic, or others? This review will focus on the effects of gliflozins under different pathophysiological conditions, namely in hypertension, chronic kidney disease, and heart failure, which have been evaluated in non-diabetic rat models of these diseases. Key words: SGLT-2 inhibitor, hypertension, chronic kidney disease, heart failure, liver disease, rat.
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Circadian Disruption as a Risk Factor for Development of Cardiovascular and Metabolic Disorders - From Animal Models to Human Population.
Physiol Res2024 Apr;():.
Sumová A, Sládek M,
Abstract
The lifestyle of human society is drifting apart from the natural environmental cycles that have influenced it since its inception. These cycles were fundamental in structuring the daily lives of people in the pre-industrial era, whether they were seasonal or daily. Factors that disrupt the regularity of human behaviour and its alignment with solar cycles, such as late night activities accompanied with food intake, greatly disturb the internal temporal organization in the body. This is believed to contribute to the rise of the so-called diseases of civilization. In this review, we discuss the connection between misalignment in daily (circadian) regulation and its impact on health, with a focus on cardiovascular and metabolic disorders. Our aim is to review selected relevant research findings from laboratory and human studies to assess the extent of evidence for causality between circadian clock disruption and pathology. Keywords: Circadian clock, Chronodisruption, Metabolism, Cardiovascular disorders, Spontaneously hypertensive rat, Human, Social jetlag, Chronotype.
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Muscarinic Receptors in Cardioprotection and Vascular Tone Regulation.
Physiol Res2024 Apr;():.
Dolej?í E, Janou?ková A, Jakubík J,
Abstract
Muscarinic acetylcholine receptors are metabotropic G-protein coupled receptors. Muscarinic receptors in the cardiovascular system play a central role in its regulation. Particularly M2 receptors slow down the heart rate by reducing the impulse conductivity through the atrioventricular node. In general, activation of muscarinic receptors has sedative effects on the cardiovascular system, including vasodilation, negative chronotropic and inotropic effects on the heart, and cardioprotective effects, including antifibrillatory effects. First, we review the signaling of individual subtypes of muscarinic receptors and their involvement in the physiology and pathology of the cardiovascular system. Then we review age and disease-related changes in signaling via muscarinic receptors in the cardiovascular system. Finally, we review molecular mechanisms involved in cardioprotection mediated by muscarinic receptors leading to negative chronotropic and inotropic and antifibrillatory effects on heart and vasodilation, like activation of acetylcholine-gated inward-rectifier K+-currents and endothelium-dependent and -independent vasodilation. We relate this knowledge with well-established cardioprotective treatments by vagal stimulation and muscarinic agonists. It is well known that estrogen exerts cardioprotective effects against atherosclerosis and ischemia-reperfusion injury. Recently, some sex hormones and neurosteroids have been shown to allosterically modulate muscarinic receptors. Thus, we outline possible treatment by steroid-based positive allosteric modulators of acetylcholine as a novel pharmacotherapeutic tactic. Keywords: Muscarinic receptors, Muscarinic agonists, Allosteric modulation, Cardiovascular system, Cardioprotection, Steroids.
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Epitranscriptomic Regulations in the Heart.
Physiol Res2024 Apr;():.
Benak D, Kolar F, Hlavackova M,
Abstract
RNA modifications affect key stages of the RNA life cycle, including splicing, export, decay, and translation. Epitranscriptomic regulations therefore significantly influence cellular physiology and pathophysiology. Here, we selected some of the most abundant modifications and reviewed their roles in the heart and in cardiovascular diseases: N6-methyladenosine (m6A), N6,2'-O-dimethyladenosine (m6Am), N1-methyladenosine (m1A), pseudouridine (?), 5 methylcytidine (m5C), and inosine (I). Dysregulation of epitranscriptomic machinery affecting these modifications vastly changes the cardiac phenotype and is linked with many cardiovascular diseases such as myocardial infarction, cardiomyopathies, or heart failure. Thus, a deeper understanding of these epitranscriptomic changes and their regulatory mechanisms can enhance our knowledge of the molecular underpinnings of prevalent cardiac diseases, potentially paving the way for novel therapeutic strategies. Keywords: Epitranscriptomics, RNA modifications, Epigenetics, m6A, RNA, Heart.
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Inflammatory, Metabolic and Endothelial Biomarkers Before and After Pregnancy Complications.
Am J Epidemiol2024 Apr;():. doi: kwae053.
Sun Baiyang, Gunderson Erica P, Bertolet Marnie, Lopa Samia H, Bryan Samantha G, Lewis Cora E, Catov Janet M,
Abstract
Women with gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), and preterm birth (PTB) have excess cardiovascular disease compared to those with uncomplicated births, perhaps related to pre-pregnancy inflammation, dysmetabolism or endothelial dysfunction. We included 1238 women in the Coronary Artery Risk Development in Young Adults Study (1985-2011) with 2215 births classified according to outcomes (term, uncomplicated births were the referent). Repeated measures ANOVA estimated pre-pregnancy, post-pregnancy and biomarker change according to pregnancy outcomes, adjusted for confounders. GDM and HDP groups had higher pre-pregnancy hsCRP (+0.37 [0.08, 0.65]; +0.29 [0.04, 0.55] log mg/L), leptin (+0.29 [0.09, 0.50]; +0.37 [0.17, 0.56] log ng/ml), and lower adiponectin (-0.25 [-0.36, -0.13); -0.11 [-0.22, -0.01] log ng/ml) than those with uncomplicated births and these profiles persisted in magnitude post-pregnancy. Controlling for BMI attenuated most profiles, except lower pre-pregnancy adiponectin remained associated with GDM. PTB without HDP or GDM was related to lower pre-pregnancy hsCRP and sICAM-1 (-0.31 [-0.56, -0.06] log mg/L; -0.05 [-0.09, - 0.01] log ng/ml) and a larger leptin increase from pre- to post-pregnancy, (+0.20 [0.02, 0.37] log ng/ml). Pre-pregnancy inflammation and metabolic dysfunction contributed to GDM and HDP, perhaps due to higher BMI. PTB may be related to adverse metabolic changes post-pregnancy, though the unexpected endothelial biomarker profile warrants further study.
© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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Mannose Binding Lectin and C3 Serum Levels in Coronary Artery Disease: A Cross-Sectional Study.
Immunol Invest2024 Apr;():1-14. doi: 10.1080/08820139.2024.2337023.
Meneghetti da Rosa Juliana, Lidani Kárita Cláudia Freitas, Andrade Fabiana Antunes, Sena Léia, Nisihara Renato, Ambrosio Altair Rogerio, Messias-Reason Iara J,
Abstract
BACKGROUND:
The process of tissue injury in coronary artery disease (CAD) has been associated with activation of the complement system, partly due to the action of mannose-binding lectin (MBL) and C3, which are expressed in atherosclerotic lesions.
OBJECTIVE:
The aim of this study was to evaluate the serum levels of MBL and C3 in patients with CAD and to compare them with healthy controls. Additionally, we aim to assess the correlation between MBL and C3 levels and cardiometabolic parameters.
METHODS:
MBL and C3 serum concentration were determined by ELISA and immunoturbidimetry, respectively, in up to 119 patients undergoing coronary angiography for CAD evaluation, comprising 48 individuals diagnosed with acute myocardial infarction (MI) and 71 without MI. A total of 93 paired healthy controls were included in the study.
RESULTS:
Individuals with CAD had MBL serum concentration higher than controls (?=?.002), regardless of the presence of MI (?=?.006). In addition, high concentration of MBL (>2000?ng/mL) was more frequent in patients with CAD (?=?.007; OR?=?2.6; 95% CI?=?1.3-5.1). C3 levels were not significantly associated with any of the patient groups but were positively correlated with cardiometabolic parameters such as body mass index (BMI) and triglycerides levels.
CONCLUSIONS:
Higher concentrations of MBL were found to be associated with CAD, whereas C3 levels were found to be associated with cardiovascular risk factors.
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Identifying Vulnerabilities to NSAID Adverse Events in the U.S. Population: An Analysis of Preexisting Conditions and Sex.
J Womens Health (Larchmt)2024 Apr;():. doi: 10.1089/jwh.2023.1039.
Rogers Paul, Wang Dong, Lu Zhiyuan, Lyn-Cook Beverly,
Abstract
In 2005, the Food and Drug Administration (FDA) issued a decision memorandum regarding nonsteroidal anti-inflammatory drugs (NSAIDs). The memorandum recommended the withdrawal of certain NSAIDs due to potential cardiovascular adverse effects. It highlighted the issue of cardiovascular risk associated with NSAIDs as a class. The NSAID medication guide includes a wide range of adverse drug reactions (ADRs), such as increased blood pressure, liver failure, allergic reactions, heart attack, and intestinal bleeding. Although both sexes have an increased risk of ADRs with NSAID use, females have a greater risk than males due to differences in pharmacodynamics and higher medication concentrations (mg/kg). In particular, females with high blood pressure, coronary heart, kidney, and liver disease are at an additional risk of harm from NSAID ADRs. This study quantifies sex-specific differences and other factors associated with prescription NSAID use. The data for this study were obtained from the National Health and Nutrition Examination Survey (NHANES), a complex survey conducted by the Centers for Disease Control and Prevention (CDC) in two-year cycles. A survey-weighted logistic regression model was utilized to investigate potential sex differences with prescription NSAIDs in the context of other factors, including kidney disease, hypertension, liver disease, insurance status, coronary heart disease, and age, within the 2011-2018 NHANES survey data. Females reported a slightly higher percentage of high blood pressure and kidney disease than males, while males reported a slightly higher percentage of coronary heart and liver disease than females. Last, the model indicated that females were 58% more likely to have used a prescription NSAID than males. The results confirm that women and people with medical conditions, who would potentially suffer greater harm from NSAID ADRs, are more likely to use a prescription NSAID than individuals without these conditions.
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An Enhanced Postpartum Transition Program to Primary Care.
J Womens Health (Larchmt)2024 Apr;():. doi: 10.1089/jwh.2023.0465.
Cameron Natalie A, Birdsell Heather, Niznik Charlotte M, Michon Ruth, Donelan Emily, Yee Lynn M, Dolan Brigid M,
Abstract
Gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP) are risk factors for future cardiovascular disease, yet few individuals receive postpartum care with primary care clinicians (PCP). To facilitate transitions of care to PCPs and improve cardiovascular health monitoring within the first 13 months postpartum, we developed and piloted an enhanced postpartum referral pathway for patients with GDM or HDP. Eligible patients included those who received perinatal care at a large, urban, academic medical center, experienced GDM or HDP during their most recent pregnancy, and lacked an existing PCP. Resident, faculty, and advanced practitioners referred patients during antenatal, delivery-related, or postpartum visits. A dedicated scheduler contacted patients to schedule an appointment with a women's health-focused resident or faculty PCP. The percent of patients who attended a postpartum PCP visit, who had an HbA1c and cholesterol panel checked within the first 13 months postpartum, were compared between patients referred and not referred to the program using adjusted odds ratios (aOR). Of 129 individuals referred, 48.1% attended a PCP visit, 31.8% completed cholesterol screening, and 41.9% completed HbA1c screening within 13 months postpartum. After adjusting for age, parity, insurance, and referral indication, referred individuals had greater odds for each outcome (PCP visit: aOR = 6.0, 95% CI 4.0-9.0; cholesterol: aOR = 2.4, 95% 1.6-3.9; HbA1c: aOR = 2.5, 95% CI 1.7-3.7) compared with nonreferred individuals in the same time period. A enhanced postpartum PCP referral pathway pilot for birthing individuals was associated with improved follow-up in the first year postpartum.
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