BACKGROUND: The exposome concept includes nutrition as it significantly influences human health, impacting the onset and progression of diseases. Gluten-containing wheat products are an essential source of energy for the world\'s population. However, a rising number of non-celiac healthy individuals tend to reduce or completely avoid gluten-containing cereals for health reasons.
OBJECTIVE: This prospective interventional human study aimed to investigate whether short-term gluten avoidance improves cardiovascular endpoints and quality of life (QoL) in healthy volunteers. A cohort of 27 participants followed a strict gluten-free diet (GFD) for four weeks. Endothelial function measured by flow-mediated vasodilation (FMD), blood testing, plasma proteomics (Olink®) and QoL as measured by the World Health Organisation Quality-of-Life (WHOQOL) survey were investigated.
RESULTS: GFD resulted in decreased leucocyte count and C-reactive protein levels along with a trend of reduced inflammation biomarkers determined by plasma proteomics. A positive trend indicated improvement in FMD, whereas other cardiovascular endpoints remained unchanged. In addition, no improvement in QoL was observed.
CONCLUSIONS: In healthy individuals, a short-term GFD demonstrated anti-inflammatory effects but did not result in overall cardiovascular improvement or enhanced quality of life.

UNASSIGNED: This article explored the possibility that the Mpox virus (MPXV) may initiate or stimulate the consequences of vascular inflammation. In 1970, it was discovered that Macaca cynomolgus primates infected with MPXV also infected humans in the Democratic Republic of the Congo.
UNASSIGNED: The study demonstrates that MPXV invades host cells via viral proteins and surface receptors, initiating the release of diverse inflammatory mediators such as IL-1, IL-6, TNF-α, CCL2, CXCL2, CXCL8, CXCL10, and so forth probably through endothelial dysfunction by reactive oxygen species production. In general, these mediators have been found to contribute to vascular inflammation and the formation of atherosclerotic plaque at a later stage, which may contribute to the onset of vascular inflammation.
UNASSIGNED: The discussed association between vascular inflammation and Mpox has the potential to be an important finding in the field of vascular biology research.

OBJECTIVE: To further characterize the relationship between obstructive sleep apnea (OSA) and carotid atherosclerosis, we examined the structural and metabolic features of carotid plaque using hybrid 18-F-fluorodeoxyglucose (FDG) Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) in the Multi-Ethnic Study of Atherosclerosis (MESA).
METHODS: We studied 46 individuals from the MESA-PET and MESA-Sleep ancillary studies. OSA was defined as an apnea hypopnea index [AHI] ≥ 15 events per hour (4% desaturation). PET/MRI was used to measure carotid plaque inflammation (using target-to-background-ratios [TBR]) and carotid wall thickness (CWT). Linear regression was used to assess the associations between OSA, CWT and TBR.
RESULTS: The mean age was 67.9 years (SD 8.53) and the mean BMI was 28.9 kg/m2 (SD 4.47). There was a trend toward a higher mean CWT in the OSA (n = 11) vs. non-OSA group (n = 35), 1.51 vs. 1.41 (p = 0.098). TBR did not differ by OSA groups, and there was no significant association between OSA and carotid plaque inflammation (TBR) in adjusted analyses. Although there was a significant interaction between OSA and obesity, there were no statistically significant associations between OSA and vascular inflammation in stratified analysis by obesity.
CONCLUSIONS: Despite a trend toward a higher carotid wall thickness in OSA vs. non-OSA participants, we did not find an independent association between OSA and carotid plaque inflammation using PET/MRI in MESA. Our findings suggest that simultaneous assessments of structural and metabolic features of atherosclerosis may fill current knowledge gaps pertaining to the influence of OSA on atherosclerosis prevalence and progression.

UNASSIGNED: Atherosclerosis is a chronic inflammatory disease that remains the leading cause of morbidity and mortality worldwide. Despite decades of research into the development and progression of this disease, current management and treatment approaches remain unsatisfactory and further studies are required to understand the exact pathophysiology. This review aims to provide a comprehensive assessment of currently published data utilizing single-cell and next-generation sequencing techniques to identify key cellular and molecular contributions to atherosclerosis and vascular inflammation.
UNASSIGNED: Electronic searches of Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE databases were undertaken from inception until February 2022. A narrative synthesis of all included studies was performed for all included studies. Quality assessment and risk of bias analysis was evaluated using the ARRIVE and SYRCLE checklist tools.
UNASSIGNED: Thirty-four studies were eligible for narrative synthesis, with 16 articles utilizing single-cell exclusively, 10 utilizing next-generation sequencing and 8 using a combination of these approaches. Studies investigated numerous targets, ranging from exploratory tissue and plaque analysis, cell phenotype investigation and physiological/hemodynamic contributions to disease progression at both the single-cell and whole genome level. A significant area of focus was placed on smooth muscle cell, macrophage, and stem/progenitor contributions to disease, with little focus placed on contributions of other cell types including lymphocytes and endothelial cells. A significant level of heterogeneity exists in the outcomes from single-cell sequencing of similar samples, leading to inter-sample and inter-study variation.
UNASSIGNED: Single-cell and next-generation sequencing methodologies offer novel means of elucidating atherosclerosis with significantly higher resolution than previous methodologies. These approaches also show significant potential for translatability into other vascular disease states, by facilitating cell-specific gene expression profiles between disease states. Implementation of these technologies may offer novel approaches to understanding the disease pathophysiology and improving disease prevention, management, and treatment.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021229960, identifier: CRD42021229960.

Short sleep duration (SD) is associated with cardiovascular disease. We investigated the relationship between objective SD and subclinical atherosclerosis employing hybrid positron emission tomography/magnetic resonance imaging with 18F-FDG tracer in the MESA cohort.
We utilized data from Multi-Ethnic Study of Atherosclerosis-SLEEP and Multi-Ethnic Study of Atherosclerosis-PET ancillary studies. SD and sleep fragmentation index (SFI) were assessed using 7-day actigraphy. The primary and secondary outcomes were carotid inflammation, defined using target-to-background ratios, and measures of carotid wall remodeling (carotid wall thickness), summarized by SD category. Multivariable linear regression was performed to assess the association between SD and SFI with the primary/secondary outcomes, adjusting for several covariates including apnea-hypopnea index, and cardiovascular disease risk.
Our analytical sample (n = 58) was 62% female (mean age 68 ± 8.4 years). Average SD was 5.1 ± 0.9 hours in the short SD group (≤ 6 h/night, 31%), and 7.1 ± 0.8 hours in the normal SD group (69%). Prevalence of pathologic vascular inflammation (maximal target-to-background ratio > 1.6) was higher in the short SD group (89% vs 53%, P = .01). Those with short SD had a higher maximal target-to-background ratio (1.77 vs 1.71), although this was not statistically significant (P = .39). Carotid wall thickness was positively associated with SFI even after adjusting for covariates (Beta [standard error] = 0.073 ± [0.032], P = .03).
Prevalence of pathologic vascular inflammation was higher among those who slept ≤ 6 hours, and vascular inflammation was higher among those with a SD of ≤ 6 hours. Interestingly, SFI was positively associated with carotid wall thickness even after adjustment for covariates. Our results are hypothesis generating but suggest that both habitual SD and SFI should be investigated in future studies as potential risk factors for subclinical atherosclerosis.
Kundel V, Reid M, Fayad Z, et al. Sleep duration and vascular inflammation using hybrid positron emission tomography/magnetic resonance imaging: results from the Multi-Ethnic Study of Atherosclerosis. J Clin Sleep Med. 2021;17(10):2009-2018.

BACKGROUND: Postoperative delirium (POD) ranks among the most common complications in surgical patients. Blood-based biomarkers might help identify the patient at risk. This study aimed to assess how serum biomarkers with specificity for vascular and endothelial function and for inflammation are altered, prior to or following surgery in patients who subsequently develop POD.
METHODS: This was a study on a subcohort of consecutively recruited elective non-cardiac as well as cardiac surgery patients (age > 60 years) of the single-center PROPDESC trial at a German tertiary care hospital. Serum was sampled prior to and following surgery, and the samples were subjected to bead-based multiplex analysis of 17 serum proteins (IL-3, IL-8, IL-10, Cripto, CCL2, RAGE, Resistin, ANGPT2, TIE2, Thrombomodulin, Syndecan-1, E-Selectin, VCAM-1, ICAM-1, CXCL5, NSE, and uPAR). Development of POD was assessed during the first five days after surgery, using the Confusion Assessment Method for ICU (CAM-ICU), the CAM, the 4-\'A\'s test (4AT), and the Delirium Observation Scale (DOS). Patients were considered positive if POD was detected at least once during the visitation period by any of the applied methods. Non-parametric testing, as well as propensity score matching were used for statistical analysis.
RESULTS: A total of 118 patients were included in the final analysis; 69% underwent non-cardiac surgery, median overall patient age was 71 years, and 59% of patients were male. In the whole cohort, incidence of POD was 28%. The male gender was significantly associated with the development of POD (p = 0.0004), as well as a higher ASA status III (p = 0.04). Incidence of POD was furthermore significantly increased in cardiac surgery patients (p = 0.002). Surgery induced highly significant changes in serum levels of almost all biomarkers except uPAR. In preoperative serum samples, none of the analyzed parameters was significantly altered in subsequent POD patients. In postoperative samples, CCL2 was significantly increased by a factor of 1.75 in POD patients (p = 0.03), as compared to the no-POD cohort. Following propensity score matching, CCL2 remained the only biomarker that showed significant differences in postoperative values (p = 0.01). In cardiac surgery patients, postoperative CCL2 serum levels were more than 3.5 times higher than those following non-cardiac surgery (p < 0.0001). Moreover, after cardiac surgery, Syndecan-1 serum levels were significantly increased in POD patients, as compared to no-POD cardiac surgery patients (p = 0.04).
CONCLUSIONS: In a mixed cohort of elective non-cardiac as well as cardiac surgery patients, preoperative serum biomarker profiling with specificity for vascular dysfunction and for systemic inflammation was not indicative of subsequent POD development. Surgery-induced systemic inflammation-as evidenced by the significant increase in CCL2 release-was associated with POD, particularly following cardiac surgery. In those patients, postoperative glycocalyx injury might furthermore contribute to POD development.

OBJECTIVE: Short sleep duration (SD) is associated with cardiovascular disease (CVD). We investigated the relationship between objective SD and subclinical atherosclerosis employing hybrid PET/MRI with 18F-FDG tracer in the MESA cohort.
METHODS: We utilized data from MESA-SLEEP and MESA-PET ancillary studies. SD and sleep fragmentation index (SFI) were assessed using 7-day actigraphy. The primary and secondary outcomes were carotid inflammation, defined using target-to-background ratios (TBR), and measures of carotid wall remodeling (carotid wall thickness [CWT]), summarized by SD category. Multivariate linear regression was performed to assess the association between SD and SFI with the primary/secondary outcomes, adjusting for several covariates including apnea-hypopnea index (AHI), and CVD risk.
RESULTS: Our analytical sample (n=58) was 62% female (mean age 68±8.4 years). Average SD was 5.1±0.9 hours in the short SD group (≤6 hours/night, 31%), and 7.1±0.8 hours in the normal SD group (69%). Prevalence of pathologic vascular inflammation (TBRmax>1.6) was higher in the short SD group (89% vs. 53%, p=0.009). Those with short SD had a higher TBRmax (1.77 vs 1.71), though this was not statistically significant (p=0.39). CWT was positively correlated with SFI even after adjusting for covariates (Beta [SE]=0.073±[0.032], p=0.025).
CONCLUSIONS: Prevalence of pathologic vascular inflammation was higher among those who slept ≤6 hours, and vascular inflammation was higher among those with a SD of ≤6 hours. Interestingly, SFI was positively correlated with CWT even after adjustment for covariates. Our results are hypothesis-generating but suggest that both habitual SD and SFI should be investigated in future studies as potential risk factors for subclinical atherosclerosis.

Cardiovascular disease (CVD) is common in peritoneal dialysis (PD) patients. This study was designed to investigate the effects of isoflavones on systemic and vascular inflammation markers and oxidative stress in PD patients. In this randomized clinical trial, 40 PD patients were randomly assigned to either the isoflavone or the placebo group. The isoflavone group received 100 mg soy isoflavones daily for 8 weeks, whereas the placebo group received corresponding placebos. At baseline and the end of eighth week, serum high sensitive C-reactive protein (hs-CRP), intercellular adhesion molecule type 1 (ICAM-1), vascular cell adhesion molecule type 1 (VCAM-1), E-selectin, and malondialdehyde were measured. Serum VCAM-1 decreased significantly in the isoflavone group at the end of Week 8 compared to baseline (p = .01), whereas no significant change was observed in the placebo group. Serum ICAM-1 decreased significantly in the isoflavone (p = .01) and placebo (p = .01) group compared to baseline. However, the reduction of ICAM-1 was significantly higher in the isoflavone group than in the placebo group (p = .02). There were no significant differences between the two groups in mean changes of serum E-selectin, malondialdehyde, and hs-CRP. This study indicates that isoflavones reduce serum VCAM-1 and ICAM-1, which are two CVD risk factors, in PD patients.

Household air pollution has been associated as a risk factor for cardiovascular diseases (CVD). Therefore, the aim of this study was to assess the expression of vascular inflammation regulators miR-126 and miR-155 in plasma from women that cook with wood and women that cook with liquid petroleum gas (LPG). A cumulative index of exposure to smoke (CIES) was estimated, urinary 1-hydroxypyrene (1-OHP) levels were quantified and miRNAs expression levels were determined by quantitative real-time PCR (qRT-PCR). Biochemical clinical parameters were also evaluated. The average values for CIES and 1-OHP were 140 ± 86.8 hours-years (12.0-270 hours-years) and 0.52 ± 0.45 µmol/mol creatinine, respectively. miR-126 and miR-155 expression levels were significantly higher (p < 0.01) in the wood users compared to LPG users. Besides, we found a significant association (p < 0.01) between miR-126 and miR-155 expression levels and CIES and urinary 1-OHP concentrations. These results contribute to the current evidence about the cardiovascular risk related to biomass smoke exposure, from an epigenetic level.

Inflammation is a critical pathway in the pathogenesis of atherosclerosis. Previous studies have shown that plasma levels of high-sensitivity C-reactive protein (hsCRP), a marker of inflammation, are associated with cardiovascular disease independent of traditional risk factors. Randomized trial data have also shown that statins reduce not only hsCRP but also cardiovascular event rates independent of their effect on low-density lipoprotein cholesterol (LDL-C) level. More recently, the CANTOS trial showed that directly reducing inflammation with canakinumab, an interleukin (IL)-1β neutralizing monoclonal antibody, could also reduce cardiovascular event rates. These mark the first phase 3 trial results validating inflammation as a viable target for preventing cardiovascular disease. In this review, we recap the role of inflammation in cardiovascular disease and highlight previous trial data showing its modulation with statins and other agents. We also detail the CANTOS trial results and discuss its implications for clinicians as well as future directions for anti-inflammatory therapy in the prevention of cardiovascular disease.