Introduction: Although "Life’s Essential 8" (LE8) is a key metric for cardiovascular health (CVH), its longitudinal association with subclinical atherosclerosis in Koreans remains unclear. We examined the association between baseline LE8 scores and the presence of coronary artery calcium (CAC). Methods: Data were obtained from the Cardiovascular and Metabolic Diseases Etiology Research Center cohort study, a prospective cohort (baseline: 2013–2018; follow-up: 2022–2024). Baseline CVH scores, comprising 8 metrics (diet, physical activity, nicotine exposure, sleep health, body mass index, blood lipids, blood glucose, and blood pressure), were categorized as low (0–<50), moderate (50–<80), and high (80–100). The main outcome was the presence of CAC at the follow-up. Multivariable logistic regression was used for statistical analysis. Results: During a mean follow-up of 7.3 years, among 1,746 participants (mean age: 52.3 years, 65.2% female), the overall prevalence of CAC was 41.4%, which decreased with increasing CVH scores (low: 64.6%, moderate: 41.5%, and high: 30.4%). Compared to the low CVH group, the fully adjusted odds ratios (95% confidence intervals) for the presence of CAC were 0.34 (0.23–0.51) in the moderate and 0.25 (0.15–0.39) in the high CVH group. Higher baseline CVH scores were log-linearly associated with lower odds of CAC presence, demonstrating a linear and dose-dependent relationship in the restricted cubic spline plot (p=0.102). The association between CVH and CAC was consistently observed across subgroups and sensitivity analyses. Conclusion: Our study showed that higher baseline CVH scores were associated with a lower risk of subsequent CAC, highlighting the importance of promoting ideal CVH early to reduce the burden of cardiovascular disease.
Introduction: DLL4-NOTCH1 signaling mediates juxtacrine communication between tip- and stalk-like endothelial cells during vascular sprouting, contributing to complementary aspects of endothelial function. Thus, simultaneous modulation of DLL4 and NOTCH1 may provide a strategy to broadly interfere with the endothelial functions involved in tumor angiogenesis. Accordingly, this study aimed to identify a novel natural compound capable of modulating DLL4-NOTCH1-mediated endothelial communication and to investigate how such modulation influences tumor angiogenesis and growth. Methods: We screened 66 natural compounds to identify those that suppress DLL4 and NOTCH1 signaling in endothelial cells. Using a dual-reporter system that combines a DLL4 promoter-driven reporter and a CSL luciferase reporter, we simultaneously assessed ligand-associated activity and downstream transcriptional output of the DLL4-NOTCH1 axis. We confirmed VEGF-induced target gene expression via Western blotting and quantitative real-time polymerase chain reaction. We further performed in vitro angiogenesis assays and in vivo Lewis lung carcinoma (LLC) allograft tumor experiments. Results: Among the 66 screened natural compounds, para-coumaric acid (p-CA) dose-dependently suppressed DLL4 transcription and NOTCH1 signaling activity in endothelial cells, with IC50 values of 4.57 and 8.34 µm, respectively. Furthermore, p-CA significantly suppressed VEGF-induced endothelial cell proliferation, migration, and tube formation. In the LLC allograft model, p-CA treatment suppressed tumor growth and vascular density, increased pericyte coverage, reduced tumor hypoxia, and enhanced CD3+ T-cell infiltration and tumor cell apoptosis. Conclusion: In summary, p-CA is a natural compound that functionally suppresses VEGF-driven DLL4-NOTCH1 signaling in endothelial cells, exhibiting strong anti-angiogenic effects and promoting functional vascular normalization, resulting in marked tumor suppression and enhanced antitumor immunity in vivo. These findings suggest that p-CA warrants further investigation as an anti-angiogenic compound for cancer therapy.
Introduction:Arterial stiffness, measured by brachial-ankle pulse wave velocity (baPWV), has been linked to diabetic peripheral neuropathy (DPN). However, the evidence regarding its association with large-nerve fiber dysfunction, specifically assessed by vibration perception threshold (VPT), in Chinese patients aged 18-65 years with type 2 diabetes mellitus (T2DM) is scarce. This study aimed to investigate the relationship between baPWV and VPT in this specific population. Methods:This cross-sectional study enrolled 600 inpatients with T2DM aged 18-65 years. baPWV was measured using an automated waveform analyzer. DPN was defined as a VPT ≥15 volts in at least one foot. Multivariable logistic regression models were used to assess independent association, expressed as odds ratios (ORs) and 95% confidence intervals (CIs). Restricted cubic spline and subgroup analyses were performed to evaluate the dose-response relationship and consistency of the association. Results:Among the participants, 165 (27.5%) were classified into the abnormal VPT group. After full adjustment for confounders including age, gender, diabetes duration, glycated hemoglobin, and lifestyle factors, each 100 cm/s increase in baPWV was significantly associated with increased odds of DPN (OR = 1.07, 95% CI: 1.01-1.14). When analyzed by quartiles, participants in the highest baPWV quartile (≥1,660 cm/s) had 1.29-fold higher odds of abnormal VPT (OR = 1.29, 95% CI: 1.03-3.01) compared to those in the lowest quartile (<1,380 cm/s), with a significant trend across quartiles (p for trend = 0.005). A linear dose-response relationship was confirmed without evidence of a threshold effect. Subgroup analyses showed the association was consistent across different patient characteristics. Conclusion:Elevated baPWV is independently associated with higher odds of DPN measured by VPT in Chinese patients aged 18-65 years with type 2 diabetes. This linear relationship not only underscores the pivotal role of arterial stiffness in the pathogenesis of DPN but also positions baPWV as a valuable tool for early risk stratification in clinical practice.
Introduction: The cardio-ankle vascular index (CAVI) is a noninvasive indicator used to assess arterial stiffness and predict atherosclerotic cardiovascular disease (ASCVD). CAVI represents a scale-converted form of the stiffness parameter β. Both CAVI and β reflect overall arterial stiffness from the heart to the ankle. However, there are distinct mechanistic pathways underlying the heterogeneous progression of ASCVD across the arterial tree (e.g., elastic and muscular arteries). Thus, the present study aimed to (1) examine differences in segmental β between elastic and muscular arteries at rest; (2) compare these differences between young and older adults at rest; and (3) further compare them with the segmental β responses observed after exercise. Methods: Eighty-three healthy individuals aged 18–52 years were recruited and divided into two groups: the young group (18–23 years, n = 57) and the adult group (31–52 years, n = 26). Cuffs were applied to both upper arms, the left thigh, and the right ankle. Segmental β was measured at rest as well as immediately after exercise using the Master’s two-step exercise test. Results: At rest, muscular arterial stiffness (thigh-ankle β [taβ]) was 4.7 times higher in the young group and 2.8 times higher in the adult group, compared to that of the elastic arteries (heart-thigh β [htβ]). htβ and heart-ankle β (haβ) were higher in the adult group than in the young group (p < 0.05), whereas taβ was lower in the adult group (p < 0.05). After exercise, taβ, htβ, and haβ decreased in both groups. In the young group, exercise-induced β reduction was greatest in taβ, compared with htβ and haβ. This reduction was significantly greater in the young group than in the adult group (e.g., reduction in taβ was 4.9 times greater in the young group). Conclusion: This study demonstrated distinct segmental β values between elastic and muscular arteries, suggesting that the inherent stiffness of the arterial beds should ideally be assessed separately.
Introduction:Aortic wall calcification increases arterial stiffness which is often assessed by carotid-femoral pulse wave velocity (cfPWV). However, the impact of kidney function upon the association between calcification of the aortic wall and cfPWV remains unknown. Methods:To examine the association between aortic calcification and cfPWV, we prospectively recruited chronic kidney disease (CKD) patients (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2) and patients with normal renal function, planned for invasive coronary angiography. Participants underwent a non-contrast computed tomography scan of the entire aorta with subsequent Agatston scoring of the aortic wall in addition to a standardized cfPWV measurement and biochemical markers. Results:A total of 144 patients (67.1 ± 10.3 years, 24% female), of whom 110 had CKD (26 stage 3a, 33 stage 3b, 24 stage 4, and 27 stage 5), were included. Agatston score was associated with cfPWV in a univariate regression analysis (p < 0.001). So were age (p < 0.001) and diabetes (p = 0.001), but not gender, smoking status, eGFR, office systolic blood pressure, calcium-phosphate product, C-reactive protein nor vasodilator treatment. Multiple regression analysis including all these factors did not significantly change these associations and relative weight analysis revealed Agatston score to account for 30% of the variation in cfPWV in the model (total r 2 = 0.31). Conclusion:In a cohort representing the entire spectrum of kidney function, aortic Agatston score, as well as age and diabetes, were associated with cfPWV after adjustment for other risk factors including eGFR. However, most of the variation in cfPWV remains unexplained by these factors.
