JVS-vascular science最新文献

Objective

We examined the associations between 25-hydroxy vitamin D (25(OH)D₃) concentration and the diagnosis and growth of abdominal aortic aneurysm (AAA).

Methods

AAA cases and healthy controls were recruited from vascular centers or the community. A subset of participants with AAA were monitored by repeat ultrasound examination to assess AAA growth. Serum 25(OH)D₃ concentration was measured using a validated mass spectrometry method and categorized into guideline-recommended cut-points after deseasonalization. The associations between deseasonalized 25(OH)D₃ concentration and AAA diagnosis and growth were examined using logistic regression and linear mixed effects modeling.

Results

A total of 4673 participants consisting of 873 (455 controls and 418 cases) from Queensland and 3800 (3588 controls and 212 cases) from Western Australia were recruited. For every 1 standard deviation increase in 25(OH)D₃ concentration, odds of AAA diagnosis was significantly reduced in both Queensland (adjusted odds ratio: 0.81; 95% confidence interval [CI]: 0.69-0.95; P = .009) and Western Australia (adjusted odds ratio: 0.80; 95% CI: 0.68-0.94; P = .005) cohorts. A subset of 310 eligible participants with small AAA from both regions were followed for a median of 4.2 (interquartile range: 2.0-5.8) years. Compared with vitamin D sufficient participants (50 to ˂75 nmol/L), annual mean AAA growth was significantly greater in those with higher vitamin D (≥75 nmol/L) (adjusted mean difference: 0.1 mm/y, 95% CI: 0.1-0.2; P < .001).

Conclusions

High 25(OH)D₃ concentration was paradoxically associated with a lower likelihood of AAA diagnosis and faster AAA growth. Further research is needed to resolve these conflicting findings.

Background

High lipoprotein (a) [Lp(a)] is associated with adverse limb events in patients undergoing lower extremity revascularization. Lp(a) levels are genetically pre-determined, with LPA gene encoding for two apolipoprotein (a) [apo(a)] isoforms. Isoform size variations are driven by the number of kringle IV type 2 (KIV-2) repeats. Lp(a) levels are inversely correlated with isoform size. In this study, we examined the role of Lp(a) levels, apo(a) size, and inflammatory markers with lower extremity revascularization outcomes.

Methods

Twenty-five subjects with chronic peripheral arterial disease (PAD) underwent open or endovascular lower extremity revascularization (mean age, 66.7 ± 9.7 years; Female = 12; Male = 13; Black = 8; Hispanic = 5; and White = 12). Pre- and postoperative medical history, self-reported symptoms, ankle-brachial indices (ABIs), and lower extremity duplex ultrasounds were obtained. Plasma Lp(a), apoB100, lipid panel, and pro-inflammatory markers (IL-6, IL-18, hs-CRP, TNFα) were assayed preoperatively. Isoform size was estimated using gel electrophoresis and weighted isoform size (wIS) calculated based on % isoform expression. Firth logistic regression was used to examine the relationship between Lp(a) levels and wIS with procedural outcomes: symptoms (better/worse), early primary patency at 2 to 4 weeks, ABIs, and reintervention within 3 to 6 months. We controlled for age, sex, history of diabetes, smoking, statin, antiplatelet, and anticoagulation use.

Results

Median plasma Lp(a) level was 108 (interrquartile range, 44-301) nmol/L. The mean apoB100 level was 168.0 ± 65.8 mg/dL. These values were not statistically different among races. We found no association between Lp(a) levels and wIS with measured plasma pro-inflammatory markers. However, smaller apo(a) wIS was associated with occlusion of the treated lesion(s) in the postoperative period (odds ratio, 1.97; 95% confidence interval, 1.01-3.86; P < .05). The relationship of smaller apo(a) wIS with reintervention was not as strong (odds ratio, 1.57; 95% confidence interval, 0.96-2.56; P = .07). We observed no association between wIS with patient reported symptoms or change in ABIs.

Conclusions

In this small study, subjects with smaller apo(a) isoform size undergoing peripheral arterial revascularization were more likely to experience occlusion in the postoperative period and/or require reintervention. Larger cohort studies identifying the mechanism and validating these preliminary data are needed to improve understanding of long-term peripheral vascular outcomes.

Background

Peripheral artery disease (PAD) impacts more than 200 million people worldwide. The understanding of the genetics of the disease and its clinical implications continue to evolve. This systematic review provides a comprehensive summary of all DNA variants that have been studied in association with the diagnosis and progression of PAD, with a meta-analysis of the ones replicated in the literature.

Methods

A systematic review of all studies examining DNA variants associated with the diagnosis and progression of PAD was performed. Candidate gene and genome-wide association studies (GWAS) were included. A meta-analysis of 13 variants derived from earlier smaller candidate gene studies of the diagnosis of PAD was performed. The literature on the progression of PAD was limited, and a meta-analysis was not feasible because of the heterogeneity in the criteria used to characterize it.

Results

A total of 231 DNA variants in 112 papers were studied for the association with the diagnosis of PAD. There were significant variations in the definition of PAD and the selection of controls in the various studies. GWAS have established 19 variants associated with the diagnosis of PAD that were replicated in several large patient cohorts. Only variants in intercellular adhesion molecule-1 (rs5498), IL-6 (rs1800795), and hepatic lipase (rs2070895) showed significant association with the diagnosis of PAD. However, these variants were not noted in the published GWAS.

Conclusions

Genetic research in the diagnosis of PAD has significant heterogeneity, but recent GWAS have demonstrated variants consistently associated with the disease. More research focusing on the progression of PAD is needed to identify patients at risk of adverse events and develop strategies that would improve their outcomes.

Objective

Biomechanical modeling of infrarenal aortic aneurysms seeks to predict ruptures in advance, thereby reducing aneurysm-related deaths. As individual methods focusing on strain and stress analysis lack adequate discretization power, this study aims to explore multifactorial characterization for progressive aneurysmal degeneration. The study’s objective is to compare stress- and strain-related parameters in infrarenal aortic aneurysms.

Methods

Twenty-two patients with abdominal aortic aneurysms (AAAs) (mean maximum diameter, 53.2 ± 7.2 mm) were included in the exploratory study, examined by computed tomography angiography (CTA) and three-dimensional real-time speckle tracking ultrasound (4D-US). The conformity of aneurysm anatomy in 4D-US and CTA was determined with the mean point-to-point distance (MPPD). CTA was employed for each AAA to characterize stress-related indices using the semi-automated A4-clinics RE software. Five segmentations from one 4D-US examination were fused into one averaged model for strain analysis using MATLAB and the Abaqus solver.

Results

The mean MPPD between the adjacent points of the 4D-US and CTA-derived geometry was 1.8 ± 0.4 mm. The interclass correlation coefficients for all raters and all measurements for the maximum AAA diameter in 2D, 4D ultrasound, and CTA indicate moderate to good reliability (interclass correlation coefficient₁ 0.69 with 95% confidence interval [CI], 0.49-0.84; P < .001). The peak wall stress (PWS) correlates fairly with the maximum AAA diameter in 2D-US (r = 0.54; P < .01) and 4D-US (r = 0.53; P < .05) and moderately strongly with the maximum exterior AAA diameter (r = 0.63; P < .01). The peak wall rupture risk index shows a strong correlation with the PWS (ρ > 0.9; P < .001) and is influenced by anatomical parameters with equal strength. Isolated observation of the intraluminal thrombus does not provide significant information in the determination of PWS. The maximum AAA diameter in 2D-US shows a fair negative correlation with the mean circumferential, longitudinal and in-plane shear strain (ρ = −0.46; r = −0.45; ρ = −0.47; P < .05 for all). The circumferential strain ratio as an indicator of wall motion heterogeneity increases with the aneurysm diameter (r = 0.47; P < .05). The direct comparison of wall strain and wall stress indices shows no quantitative correlation.

Conclusions

The strain and stress analyses provide independent biomechanical information of AAAs. At the current stage of development, the two methods are considered complementary and may optimize a more patient-specific rupture risk prediction in the future.

Abdominal aortic aneurysms (AAAs) are relatively common, primarily among older men, and, in the case of rupture, are associated with high mortality. Although procedure-related morbidity and mortality have improved with the advent of endovascular repair, noninvasive treatment and improved assessment of AAA rupture risk should still be sought. Several cellular pathways seem contributory to the histopathologic changes that drive AAA growth and rupture. Hypoxia inducible factor 1-alpha (HIF-1α) is an oxygen-sensitive protein that accumulates in the cytoplasm under hypoxic conditions and regulates a wide array of downstream effectors to hypoxia. Examining the potential role of HIF-1α in the pathogenesis of AAAs is alluring, because local hypoxia is known to be present in the AAA vessel wall. A systematic scoping review was performed to review the current evidence regarding the role of HIF-1α in AAA disease in vivo. After screening, 17 studies were included in the analysis. Experimental animal studies and human studies show increased HIF-1α activity in AAA tissue compared with healthy aorta and a correlation of HIF-1α activity with key histopathologic features of AAA disease. In vivo HIF-1α inhibition in animals protects against AAA development and growth. One study reveals a positive correlation between HIF-1α–activating genetic polymorphisms and the risk of AAA disease in humans. The main findings suggest a causal role of HIF-1α in the pathogenesis of AAAs in vivo. Further research into the HIF-1α pathway in AAA disease might reveal clinically applicable pharmacologic targets or biomarkers relevant in the treatment and monitoring of AAA disease.

Pressure-volume (PV) loop analysis is a sophisticated invasive approach to quantifying load-dependent and independent measures of cardiac function. Biventricular (BV) PV loops allow left and right ventricular function to be quantified simultaneously and independently, which is important for conditions and certain physiologic states, such as ventricular decoupling or acute physiologic changes. BV PV loops can be performed in an entirely endovascular, percutaneous, and closed-chest setting. This technique is helpful in a survival animal model, as a percutaneous monitoring system during endovascular device experiments, or in cases where chest wall compliance is being tested or may be a confounder. In this article, we describe the end-to-end implementation of a completely endovascular, totally percutaneous, and closed-chest large animal model to obtain contemporaneous BV PV loops in 40 to 70 kg swine. We describe the associated surgical and technical challenges and our solutions to obtaining endovascular BV PV loops, closed-chest cardiac output, and stroke volume (including validation of the correction factor necessary for thermodilution), as well as how to perform endovascular inferior vena cava occlusion in this swine model. We also include techniques for data acquisition and analysis that are required for this method.

The Basic Vascular Science (BVS) meeting was set up to provide a forum for researchers and clinicians in the field to exchange knowledge and ideas and to foster cross-disciplinary collaborations. The BVS 2024 meeting was held in Berlin. Attended by vascular surgeons and physicians, interventional radiologists, basic science researchers, and engineers, the meeting continues to successfully attract both early career researchers and established clinician-scientists. Here, we report on the scientific sessions encompassing keynote lectures and oral presentations.