Introduction: Carotid-femoral pulse wave velocity (cfPWV) and brachial-ankle pulse wave velocity (baPWV) are both used to assess arterial stiffness, but their agreement in identifying elevated central arterial stiffness remains uncertain. Methods: This prospective observational study included 222 adults who underwent standardized baseline vascular function testing. The primary phenotype analysis included 205 participants with available cfPWV, maximum bilateral baPWV (baPWVmax), and minimum ankle-brachial index data. Elevated central arterial stiffness was defined as cfPWV ≥10 m/s and elevated baPWV as baPWVmax ≥14 m/s. Associations between cfPWV and baPWVmax were assessed using Spearman correlation and residual correlation after adjustment for age, sex, and systolic blood pressure. Threshold agreement, receiver operating characteristic analysis, and alternative baPWVmax thresholds were evaluated. Results: cfPWV and baPWVmax showed a moderate positive correlation (Spearman ρ = 0.36, p <0.001), but their residual correlation was no longer significant after adjustment for age, sex, and systolic blood pressure (ρ = −0.05, p = 0.456). baPWVmax showed limited discrimination for elevated cfPWV, with an area under the curve of 0.669 (95% confidence interval, 0.592–0.745). At the commonly used baPWV threshold of 14 m/s, sensitivity was 40.3%, specificity was 75.9%, and Cohen’s κ was 0.17. Overall, 75 of 205 participants (36.6%) had discordant cfPWV-baPWV classification. The most frequent discordant phenotype was cfPWV-only elevation, which accounted for 43 participants (21.0%) and 59.7% of those with elevated cfPWV. The Youden-derived baPWV threshold was 11.75 m/s, which improved sensitivity to 70.8% but reduced specificity to 60.2%. Discordance persisted using alternative baPWV thresholds and after excluding participants with an ankle-brachial index <0.90. Conclusion: cfPWV and baPWV are correlated at the group level but show limited interchangeability for individual threshold-based classification. A baPWV value below 14 m/s should not be interpreted as excluding elevated central arterial stiffness. baPWV remains a practical vascular risk assessment tool, but cfPWV is still needed when the clinical or research focus is central arterial stiffness.
Introduction: An exaggerated increase in systolic blood pressure (SBP) during exercise is associated with future hypertension. While previous studies evaluated peak SBP or two-point slopes, we aimed to identify SBP response patterns from the full SBP time-series during maximal incremental exercise and assess their value for predicting future hypertension diagnosis. Methods: In this cohort study, we analysed SBP recordings from 3,486 normotensive adults (mean age 50.6 years; 45% women) undergoing maximal cycle ergometry. Group-based trajectory modelling (GBTM) extracted sex-specific responses from the full SBP time-series. Associations with incident hypertension were evaluated using multivariable Cox analyses by sex and stratified by prehypertensive status (SBP 130–150 mm Hg or DBP 85–90 mm Hg). Results: In both sexes, GBTM identified three SBP response profiles, reflecting low, mid, and high responders. Over 7.9 years, 171 (8.8%) men and 169 (10.9%) women were diagnosed with hypertension. Incidence was markedly higher in high versus low responders (e.g., in women: 27.8 vs. 2.5 events per 1,000 follow-up years). The increased risk was independent of traditional risk factors, including resting SBP (hazard ratio relative to average risk (HRadj): 1.26 [95% confidence interval: 1.00–1.57] in men, 1.59 [1.22–2.07] in women). The association attenuated with increasing resting SBP in women (pinteraction = 0.003). Notably, high SBP response was independently associated with future hypertension diagnosis in those without prehypertension (e.g., in women, HRadj: 2.17 [1.49–3.17]), but not in those with prehypertension. Reclassification analyses indicated incremental predictive value beyond resting and peak SBP in women without prehypertension. Conclusions: Time-series analysis of exercise SBP revealed distinct response profiles predicting future hypertension diagnosis beyond resting blood pressure. Comprehensive interpretation of exercise SBP may improve risk stratification, particularly in women without prehypertension.
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.
