Triglyceride-glucose (TyG) index is an emerging surrogate indicator of insulin resistance, which has been demonstrated as a risk factor for various cardiovascular diseases including coronary syndrome, in-stent restenosis, and heart failure. However, association of TyG index with incident aortic dissection (AD) and aortic aneurysm (AA) remains to be investigated. This study included 420,292 participants without baseline AD/AA from the large-scale prospective UK Biobank cohort. The primary outcome was incident AD/AA, comprising AD and AA. Multivariable-adjusted Cox proportional hazards regression models and restricted cubic spline (RCS) analyses were applied to assess the relationship between TyG index and the onset of AD/AA. In addition, the association between TyG index and incident AD/AA was examined within subgroups defined by age, gender, smoking status, drinking status, diabetes, hypertension, and BMI. Over a median follow-up period of 14.8 (14.1, 15.5) years, 3,481 AD/AA cases occurred. The incidence of AD/AA rose along with elevated TyG index. RCS curves showed a linear trend of TyG index with risk of incident AD/AA. TyG index was positively associated with risk of incident AD/AA after adjusting for age, gender, smoking status, drinking status, BMI, hypertension, LDL-c, and HbA1c, with adjusted HRs of 1.0 (reference), 1.20 (95% CI 1.08–1.35), 1.21 (95% CI 1.08–1.35), and 1.30 (95% CI 1.16–1.45) for TyG index quartiles 2, 3, and 4, respectively. Especially, participants in the highest TyG index quartile had highest risk of developing AA, with an adjusted HR of 1.35 (95% CI 1.20–1.52). TyG index is independently associated with a higher risk of incident AD/AA, indicating the importance of using TyG index for risk assessment of AD/AA, especially for AA.

Recent studies demonstrated HMGB1, an extracellular inflammation molecule, played an important role on endothelial cells. This study aimed to define the role and related mechanism of HMGB1 in endothelial cells. Endothelial-specific deletion of HMGB1(HMGB1ECKO) was generated and Akt/eNOS signaling, reactive oxygen species (ROS) production, endothelium dependent relaxation (EDR), and angiogenesis were determined in vitro and in vivo. Decreased activation of Akt/eNOS signaling, sprouting, and proliferation, and increased ROS production were evidenced in endothelial cells derived from HMGB1ECKO mice as compared with wild type controls. Decreased EDR and retarded blood flow recovery after hind limb ischemia were also demonstrated in HMGB1ECKO mice. Both impaired EDR and angiogenesis could be partly rescued by superoxide dismutase in HMGB1ECKO mice. In conclusion, intracellular HMGB1 might be a key regulator of endothelial Akt/eNOS pathway and ROS production, thus plays an important role in EDR regulation and angiogenesis.

Background: Aortic aneurysms and aortic dissections (AA/AD) are serious vascular conditions that often progress without symptoms and are associated with high mortality, highlighting the need for improved tools to predict the occurrence. This study aims to identify plasma proteins that can predict the risk of future AA/AD events and to combine these biomarkers with traditional risk factors to construct risk prediction model. Materials and methods: We analyzed plasma proteomic data from 22 416 participants in the UK Biobank, measuring 2911 proteins using the Olink Explore proximity extension assay. Plasma proteomics data were analyzed using Cox regression and machine learning techniques. Proteins significantly associated with AA/AD risk were identified, and predictive models were constructed by integrating these biomarkers with traditional risk factors such as age, sex, and blood pressure. Results: The Cox regression models identified 25 proteins significantly associated with AA/AD risk, after adjusting for demographic factors. Furthermore, light gradient-boosting machine was used to rank the importance of these proteins and applied forward stepwise selection to identify four key predictive proteins (cystatin 3 [CST3], matrix metallopeptidase 12 [MMP12], multiple EGF-like domains 9 [MEGF9], and C-X-C motif chemokine ligand 17 [CXCL17]). The protein panel demonstrated an overall predictive AUC of 0.725 for AA/AD. The demographic model achieved an AUC of 0.740. Integration of these biomarkers with demographic factors significantly enhanced predictive accuracy, achieving an AUC of 0.777 (DeLong test P <0.001). Temporal trajectory analysis revealed that elevated levels of CST3, MMP12, and CXCL17 were detectable up to 10 years prior to AA/AD diagnosis. Conclusion: Our study highlights the potential of plasma proteomics, particularly combination of four proteins (CST3, MMP12, MEGF9, and CXCL17), as a valuable strategy for predicting AA/AD risk. The integration of proteomic biomarkers with demographic factors enhances predictive accuracy and offers insights into the underlying molecular mechanisms, which could lead to improved early detection and personalized treatment for AA/AD.

The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) is a novel lipid indicator used for assessing the risk of cardiovascular diseases. This study was performed to explore the association between NHHR and the risk of ischemic heart disease (IHD) in type 2 diabetes mellitus (T2DM) patients. This large-scale prospective cohort study included 19,925 participants from the UK Biobank. Cox proportional hazards regression models were used to assess the association between the NHHR and the risk of IHD in T2DM participants and restricted cubic spline (RCS) analysis was conducted to assess the dose–response association. Subgroup analysis and several sensitivity analyses were carried out to examine the robustness of our findings. During the follow-up (median 12.7 years), 3,600 T2DM participants developed IHD. The association between the NHHR and the risk of IHD in T2DM participants was significant in the highest NHHR quartile (quartile 4), whereas this association was not stable in quartile 2 or quartile 3. Four sensitivity analyses showed similar results. RCS analysis did not reveal a significant nonlinear relationship between the NHHR indicator and the risk of IHD in T2DM participants (P for nonlinearity = 0.9490). In the subgroup analysis, drinking status was found to have a joint effect with the NHHR on the incidence of IHD in T2DM patients (P for interaction = 0.038). A high level of NHHR is associated with a high risk of IHD in T2DM patients, indicating the great importance of using NHHR in the lipid management of T2DM patients.

OBJECTIVES: To compare chest CT findings in heart failure with those of Corona Virus Disease 2019 (COVID-19) pneumonia. BACKGROUND: During epidemic period, chest computed tomography (CT) has been highly recommended for screening patients with suspected COVID-19. However, the comparison of CT imaging between heart failure and COVID-19 pneumonia has not been fully elucidated. METHODS: Patients with heart failure (n=12), COVID-19 pneumonia (n=12) and one patient with both diseases were retrospectively enrolled. Clinical information and imaging of chest CT were collected and analyzed. RESULTS: There was no difference of ground glass opacity (GGO), consolidation, crazy paving pattern, lobes affected and septal thickening between heart failure and COVID-19 pneumonia. However, less rounded morphology (8.3% vs. 67%, p=0.003), more peribronchovascular thickening (75% vs. 33%, p=0.041) and fissural thickening (33% vs. 0%, p=0.028), less peripheral distribution (33% vs. 92%, p=0.003) were found in heart failure group than that in COVID-19 group. Importantly, there were also more patients with upper pulmonary vein enlargement (75% vs. 8.3%, p=0.001), subpleural effusion and cardiac enlargement in heart failure group than that in COVID-19 group (50% vs. 0%, p=0.005, separately). Besides, more fibrous lesions were found in COVID-19 group although there was no statistical difference (25% vs. 0%, P=0.064) CONCLUSIONS: Although there are some overlaps of CT imaging between heart failure and COVID-19, CT is still a useful tool in differentiating COVID-19 pneumonia.