Search Results for: Intervalli di sorveglianza per Aneurisma Aorta Addominale (AAA)

Circulation, Ahead of Print. BACKGROUND:Vascular aging is an important phenotype characterized by structural and geometric remodeling. Some individuals exhibit supernormal vascular aging, associated with improved cardiovascular outcomes; others experience early vascular aging, linked to adverse cardiovascular outcomes. The aorta is the artery that exhibits the most prominent age-related changes; however, the biological mechanisms underlying aortic aging, its genetic architecture, and its relationship with cardiovascular structure, function, and disease states remain poorly understood.METHODS:We developed sex-specific models to quantify aortic age on the basis of aortic geometric phenotypes derived from 3-dimensional tomographic imaging data in 2 large biobanks: the UK Biobank and the Penn Medicine BioBank. Convolutional neural ne2rk–assisted 3-dimensional segmentation of the aorta was performed in 56 104 magnetic resonance imaging scans in the UK Biobank and 6757 computed tomography scans in the Penn Medicine BioBank. Aortic vascular age index (AVAI) was calculated as the difference between the vascular age predicted from geometric phenotypes and the chronological age, expressed as a percent of chronological age. We assessed associations with cardiovascular structure and function using multivariate linear regression and examined the genetic architecture of AVAI through genome-wide association studies, followed by Mendelian randomization to assess causal associations. We also constructed a polygenic risk score for AVAI.RESULTS:AVAI displayed numerous associations with cardiac structure and function, including increased left ventricular mass (standardized β=0.144 [95% CI, 0.138, 0.149];P

Circulation, Ahead of Print. BACKGROUND:Abdominal aortic aneurysms (AAA) present with high morbidity and mortality when they occasionally rupture. No medical therapy has successfully been proven to reduce AAA growth, though both metformin and statins have been identified as potential treatments in multiple meta-analysis. This study aimed to investigate a potential relationship between statin use and AAA growth rates and risk of undergoing repair, rupture, or death.METHODS:The study population included all men with screening-detected AAAs (30–55 mm) from the 2 large, population-based, randomized screening trials; the Viborg Vascular Screening trial (inclusion, 2008–2011) and the Danish Cardiovascular Screening trial (inclusion, 2014–2018). The clinical database was supplemented with data from the nationwide Danish Healthcare Registries, including prescription and outcome data. Statin exposure was quantified by defined daily doses (DDD). The primary outcome was AAA growth rate, whereas secondary outcomes included the need for repair and a composite of repair, rupture, and all-cause death. Growth rates were calculated using linear regression. To evaluate the risk of repair, patients were followed from inclusion until surgery, rupture, death, 5-year follow-up, or December 31, 2021.RESULTS:A total of 998 aneurysmal men (median age, 69.5 [interquartile range (IQR), 67–72] years; median AAA diameter, 35.4 [IQR, 32–41.2] mm) were included. Statin use was significantly associated with reduced AAA growth rate; an increase of 1 DDD statin per day was associated with an adjusted change in growth rate of −0.22 mm/year [95% CI, −0.39 to −0.06];P=0.009). The 5-year adjusted hazard ratio for undergoing repair per doubling of statin dose presented a significantly reduced adjusted hazard ratio (HR) of 0.82 ([95% CI, 0.70–0.97];P=0.023), which was significant after 2.5 years. Statin use was associated with a significantly lower risk of the composite outcome (surgery, rupture, and death) in a dose-dependent manner, with an adjusted HR of 0.83 ([95% CI, 0.73–0.94];P=0.003) per doubling of statin dose. Findings were robust in a variety of sensitivity analyses.CONCLUSIONS:High-dose statin use was associated with decreased AAA growth rates and lowered risk of undergoing repair, rupture, and death. This nonrandomized study suggests that patients with AAA could benefit from high-dose statin use, beyond only targeting associated risk factors.

Reti territoriali sociosanitarie organizzano sorveglianza attiva

‘Record di infezioni alimentari dall’inizio della sorveglianza’

Introduction
Among lower extremity artery disease (LEAD), symptomatic carotid stenosis (SCS) and abdominal aortic aneurysm (AAA), the disease burden is insufficiently illuminated from a patient and societal perspective. Such knowledge is central to identifying patients at risk of poorer outcomes. Therefore, the Danish Vascular (DanVasc) survey aims to describe self-reported health status, health literacy, medication adherence and loneliness, including changes over time, and investigate characteristics associated with worse self-reported health at baseline and their associations with poorer outcomes within 1 year (healthcare utilisation and mortality) in patients with LEAD, SCS and AAA.

Methods and analysis
The DanVasc survey, a national prospective cohort study combining survey data measured at several time points with register-based data, includes validated patient-reported outcome measures (PROMs) and ancillary questions developed with patient representatives. Our baseline survey (T0) follows the index contact in vascular outpatient clinics with follow-up surveys determined by the patient’s trajectory: (1) newly referred patients in conservative treatment trajectories; the date for the outpatient visit activates 1-month (T1), 3-month (T2) and 12-month (T3) follow-ups. (2) Patients referred for vascular surgery; the surgery date activates 1-month (T1), 3-month (T2) and 12-month (T3) follow-ups. The included PROMs assess health-related quality of life (HRQoL), anxiety and depression, sleep, frailty status, health literacy, medication adherence and loneliness. For LEAD, a disease-specific PROM evaluates HRQoL. For AAA, disease-specific ancillary questions are added. Additionally, the DanVasc survey includes questions on health behaviour, preventive measures and sexual life. The DanVasc survey will be linked to national registries to obtain socio-demographic information and data on redeemed prescriptions, clinical information, healthcare utilisation, comorbidities and mortality. From December 2023 to December 2024, we aim to recruit approximately 5500 patients from all seven DanVasc surgery departments. Patient characteristics will be reported using descriptive statistics. Changes over time and factors associated with poorer health outcomes will be analysed using linear, logistic and Cox proportional hazard models, presented as univariate and multivariate regressions.

Ethics and dissemination
Approval for the collection of medical record data was granted by the Central Denmark Region, acting on behalf of all Danish regions (record 1-45-70-94-22). Consent to participate is obtained prior to answering the survey. Results will be disseminated through peer-reviewed scientific publications and conference presentations, and findings will be shared with patients and relevant stakeholders via public and social media.

Intervento su un paziente 53enne di Tempio Pausania

To the Editor A recent JAMA Clinical Challenge reported the case of a 25-year-old female with incidental thoracic aortic aneurysm and bicuspid aortic valve (BAV). I am concerned that this article missed an important teaching point related to diagnostic workflow and did not identify the cause(s) of the thoracic aortic aneurysm and BAV, needed for diagnosis, treatment, and surveillance of this condition. In this young adult female, the family history of her father having an ascending aorta dissection repaired at age 60 years indicates an autosomal dominant inheritance with a 50% risk for first-degree relatives (children, siblings, and parents).

Domani la Giornata in ricordo delle vittime del Covid-19

Circulation, Ahead of Print. Sex differences in the risk factors, diagnosis, treatment, and outcomes of patients with cardiovascular disease have been well described; however, the bulk of the literature has focused on heart disease in women. Data on sex differences in peripheral vascular disease are ill defined, and there is a need to report and understand those sex-related differences to mitigate adverse outcomes related to those disparities. Although peripheral vascular disease is a highly diverse group of disorders affecting the arteries, veins, and lymphatics, this scientific statement focuses on disorders affecting the peripheral arteries to include the aorta and its branch vessels. The purpose of this scientific statement is to report the current status of sex-based differences and disparities in peripheral vascular disease and to provide research priorities to achieve health equity for women with peripheral vascular disease.

Objectives
Women with an abdominal aortic aneurysm (AAA) are less likely to receive elective repair than men. This study explored the effect of patient sex and other attributes on vascular surgeons’ decision-making for infrarenal AAA repair.

Design
Discrete choice experiment.

Setting
Simulated environment using case scenarios with varying patient attributes.

Participants
Vascular surgeons.

Interventions
Surgical decision-making.

Main outcome measures
AAA repair versus no repair and endovascular versus open repair.

Results
182 surgeons completed 2987 scenarios. When all other attributes were equal, a woman was more likely to be offered an AAA repair (marginal rate of substitution (MRS) 3.86 (95% CI 2.93, 4.79)), while very high anaesthetic risk (MRS –4.33 (95% CI –5.63, –3.03)) and hostile anatomy (MRS –3.28 (95% CI –4.55, –2.01)) were deterrents. Increasing age did not adversely affect the likelihood of offering repair to men but decreased the likelihood for women, which negated women’s selection advantage from the age of 83 years. Women were also more likely to be offered endovascular repair (MRS 2.57 (95% CI 1.30, 3.84)).

Conclusions
Patient sex alone did not account for real-world disparity observed in selection for surgery. Rather, being a woman was associated with a higher likelihood of being offered AAA repair but also a higher likelihood of being offered less invasive endovascular repair. Increased age decreased the likelihood of surgical selection for women but not men. Preference for less invasive repair, combined with inferior rates of anatomical suitability, and the comparably older age of women at the time of AAA repair selection may account for lower rates of repair for women observed.

Nessun tumore al cervello o infezione da polmonite batterica

Circulation, Ahead of Print. BACKGROUND:The developmental diversity among smooth muscle cells (SMCs) plays a crucial role in segment-specific aortic diseases. However, traditional genetic approaches are inadequate for enabling in vivo analysis of disease susceptibility associated with cellular origin. There is an urgent need to build genetic technologies that target different developmental origins to investigate the mechanisms of aortopathies, thereby facilitating the development of effective therapeutics.METHODS:To address this challenge, we developed an advanced dual recombinase-mediated intersectional genetic system, specifically designed to precisely target SMCs from various developmental origins in mice. Specifically, we usedIsl1-Dre,Wnt1-Dre,Meox1-DreER, andUpk3b-Dreto target SMC progenitors from the second heart field, cardiac neural crest, somites, and mesothelium, respectively. This system was combined with single-cell RNA sequencing to investigate the impact of TGF-β (transforming growth factor-β) signaling in different segments of the aorta by selectively knocking out Tgfbr2 in the ascending aorta and Smad4 in the aortic arch, respectively.RESULTS:Through intersectional genetic approaches, we use theMyh11-Cre(ER) driver along with origin-specific Dre drivers to trace cells of diverse developmental origins within the SMC population. We found that a deficiency of Tgfbr2 in SMCs of the ascending aorta leads to aneurysm formation in this specific region. We also demonstrate the critical role of Smad4 in preserving aortic wall integrity and homeostasis in SMCs of the aortic arch.CONCLUSIONS:Our approach to genetically targeting SMC subtypes provides a novel platform for exploring origin-dependent or location-specific aortic vascular diseases. This genetic system enables comprehensive analysis of contributions from different cell lineages to SMC behavior and pathology, thereby paving the way for targeted research and therapeutic interventions in the future.

Circulation, Ahead of Print. BACKGROUND:The activation and polarization of T cells play a crucial role in atherosclerosis and dictate athero-inflammation. The epigenetic enzyme EZH2 (enhancer of zeste homolog 2) mediates the H3K27me3 (trimethylation of histone H3 lysine 27) and is pivotal in controlling T cell responses.METHODS:To detail the role of T cell EZH2 in atherosclerosis, we used human carotid endarterectomy specimens to reveal plaque expression and geography of EZH2. Atherosclerosis-proneApoe(apolipoprotein E)–deficient mice with CD (cluster of differentiation) 4+or CD8+T cell–specificEzh2deletion (Ezh2cd4-knockout [KO], Ezh2cd8-KO) were analyzed to unravel the role of T cell Ezh2 in atherosclerosis and T cell–associated immune status.RESULTS:EZH2expression is elevated in advanced human atherosclerotic plaques and primarily expressed in the T cell nucleus, suggesting the importance of canonical EZH2 function in atherosclerosis. Ezh2cd4-KO, but not Ezh2cd8-KO, mice showed reduced atherosclerosis with fewer advanced plaques, which contained less collagen and macrophages, indicating that Ezh2 in CD4+T cells drives atherosclerosis. In-depth analysis of CD4+T cells of Ezh2cd4-KO mice revealed that absence of Ezh2 results in a type 2 immune response with increased Il-4 (interleukin 4) gene and protein expression in the aorta and lymphoid organs. In vitro,Ezh2-deficient T cells polarized macrophages toward an anti-inflammatory phenotype. Single-cell RNA-sequencing of splenic T cells revealed thatEzh2deficiency reduced naive, Ccl5+(C-C motif chemokine ligand 5) and regulatory T cell populations and increased the frequencies of memory T cells and invariant natural killer T (iNKT) cells. Flow cytometric analysis identified a shift toward Th2 (type 2 T helper) effector CD4+T cells in Ezh2cd4-KO mice and confirmed a profound increase in splenic iNKT cells with increased expression of Plzf (promyelocytic leukemia zinc finger), which is the characteristic marker of the iNKT2 subset. Likewise,Zbtb16([zinc finger and BTB domain containing 16], a Plzf-encoding gene) transcripts were elevated in the aorta of Ezh2cd4-KO mice, suggesting an accumulation of iNKT2 cells in the plaque. H3K27me3–chromatin immunoprecipitation followed by quantitative polymerase chain reaction showed that T cell–Ezh2 regulates the transcription of theIl-4andZbtb16genes.CONCLUSIONS:Our study uncovers the importance of T cell EZH2 in human and mouse atherosclerosis. Inhibition of Ezh2 in CD4+T cells drives type 2 immune responses, resulting in an accumulation of iNKT2 and Th2 cells, memory T cells and anti-inflammatory macrophages that limit the progression of atherosclerosis.

Circulation, Ahead of Print. BACKGROUND:Although combination antiretroviral therapy has increased life expectancy in people living with HIV, it has led to a marked increase in the prevalence of hypertension, the cause of which is unknown. Despite combination antiretroviral therapy, HIV-derived proteins remain expressed and produced by CD4+T lymphocytes in people living with HIV. However, their contribution to HIV-associated hypertension and impaired endothelium-dependent relaxation remains ill defined.METHODS:Here, we tested the hypothesis that CD4+T cells expressing viral proteins contribute to endothelial dysfunction and hypertension using the Tg26 mouse model of HIV that expresses 7 of the 9 HIV proteins under the long terminal repeat promoter. We used male and female mice, bone marrow transplantation (BMT), adoptive transfer of CD4+T cells, and aorta specimen discarded from people living with HIV.RESULTS:We reported that intact Tg26 mice and mice receiving BMT (Tg26→WT) or CD4+T cells from Tg26 mice display impaired endothelium-dependent relaxation and hypertension. Conversely, BMT from WT mice into Tg26 mice, inhibition of T cell activation, and CD4+T cell depletion restored endothelial function and blood pressure in Tg26 mice. Cytokine profiling revealed that Tg26 mice, Tg26→WT, and Tg26 CD4+T cells consistently exhibit high interleukin 1α (IL-1α) levels with no significant increase in other cytokines, whereas BMT from WT mice into Tg26 mice reduced IL-1α levels. IL-1α neutralization reduced blood pressure and restored endothelial function in Tg26 mice. To investigate the role of CD4+T cells and IL-1α in endothelial dysfunction, we developed an aorta-immune cell coculture system. Exposure of WT aortas to Tg26 CD4+T cells impaired endothelium-dependent relaxation, which was blocked by IL-1α–neutralizing antibody. While investigating the mechanisms of endothelial dysfunction, we reported that Tg26 mice, Tg26→WT aorta exhibit high NADPH oxidase (NOX) 1 expression. IL-1α exposure increased NOX1 in human microvascular endothelial cells, and NOX1 blockade restored endothelial function in Tg26 and Tg26→WT arteries, whereas NOX1 deficiency protected against Tg26 BMT-induced impaired endothelium-dependent relaxation and hypertension. Aortas from people living with HIV exhibit high NOX1 levels, and exposure of human aorta to Tg26 T cells increased NOX1 expression.CONCLUSIONS:We provide the first evidence that CD4+T cells expressing HIV viral proteins induced hypertension through IL-1α–mediated increases in vascular NOX1, which impairs endothelial function in males and females.