Arterial stiffness in subclinical atherosclerosis quantified with ultrafast pulse wave velocity measurements: a comparison with a healthy population using propensity score matching.

PURPOSE: This study aimed to evaluate changes in ultrafast pulse wave velocity (ufPWV) in individuals with arterial stiffness and subclinical atherosclerosis (subAS), and to provide cutoff values. METHODS: This retrospective study recruited 231 participants, including 67 patients with subAS. The pulse wave velocity was measured at the beginning and end of systole (PWV-BS and PWVES, respectively) using ultrafast ultrasonography to assess arterial stiffness. The right and left common carotid arteries were measured separately, and laboratory metabolic parameters were also collected. Participants were balanced between groups using propensity score matching (PSM) at a 1:1 ratio, adjusting for age, sex, and waist-to-hip ratio as potential confounders. Cutoff values of ufPWV for monitoring subAS were determined via receiver operating characteristic (ROC) curve analysis. RESULTS: PWV-ES, unlike PWV-BS, was higher in the subAS subgroup than in the subAS-free group after PSM (all P<0.05). For each 1 m/s increase in left, right, and bilateral mean PWV-ES, the risk of subAS increased by 23% (95% confidence interval [CI], 1.04 to 1.46), 26% (95% CI, 1.07 to 1.52), and 38% (95% CI, 1.12 to 1.72), respectively. According to ROC analyses, predictive potential was found for left PWV-ES (cutoff value=7.910 m/s, P=0.002), right PWV-ES (cutoff value=6.615 m/s, P=0.003), and bilateral mean PWV-ES (cutoff value=7.415 m/s, P<0.001), but not for PWV-BS (all P>0.05). CONCLUSION: PWV-ES measured using ultrafast ultrasonography was significantly higher in individuals with subAS than in those without. Specific PWV-ES cutoff values showed potential for predicting an increased risk of subAS.

Quantifying carotid stiffness in chronic kidney disease using ultrafast ultrasound imaging.

Background: The mortality and disability of chronic kidney disease (CKD) are highly linked to the incidence of atherosclerotic cardiovascular events. Numerous clinical biochemical indicators of renal function often only increase in advanced stages of CKD, driving an urgent need for reliable indicators of atherosclerosis in early CKD. Ultrafast pulse wave velocity (ufPWV) can evaluate the stiffness of the straight carotid in vivo and quantitatively reflect the degree of early atherosclerosis. However, the use of ufPWV in CKD has not yet been reported. In this study, we aimed to explore the association between carotid stiffness, quantified using ufPWV, and renal function in CKD patients. Methods: This cross-sectional study enrolled a total of 582 participants between March 2017 and May 2022 in the Affiliated Hospital of Nanjing University of Traditional Chinese Medicine. Among those, 205 individuals without a history of CKD and estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m2 were included as controls. According to the Kidney Disease Outcomes Quality Initiative (K/DOQI) expert group of the American Kidney Foundation staging for CKD, 44 stages 1 and 2 CKD patients were included in the early CKD group, whereas 49 stages 3, 4, and 5 CKD patients were included in the advanced CKD group. Clinical and serum parameters, ultrasonic characteristics including carotid intima-media thickness (cIMT), and pulse wave velocity at the beginning of systole (PWV-BS) and pulse wave velocity at the end of systole (PWV-ES) of systole were analyzed. One-way analysis of variance (ANOVA) and least significant difference (LSD) tests were performed to compare cIMT, PWV-BS, and PWV-ES among subgroups in pairs. Pearson's correlation analysis, scatter plots, and subgroups correlation analysis were used to determine the relationships among ultrasound characteristics (cIMT, PWV-BS, PWV-ES), and major cardiovascular risk factors. Results: PWV-BS and PWV-ES for the early and advanced CKD groups were significantly higher than those for controls (all P<0.05). PWV-ES had the greatest correlation with age (r=0.474, P<0.001). PWV-ES had the greatest increase with age in the early CKD group (r=0.698, P<0.001). Conclusions: ufPWV can be used for the quantitative evaluation of carotid stiffness in CKD patients. PWV-ES may be more advantageous in the assessment of carotid atherosclerosis in early CKD patients.

Quantifying carotid stiffness in a pre-hypertensive population with ultrafast ultrasound imaging.

PURPOSE: The aim of this study was to assess carotid stiffening in a pre-hypertensive (PHT) population using ultrafast pulse wave velocity (ufPWV). METHODS: This study retrospectively enrolled 626 individuals who underwent clinical interviews, serum tests, and assessments of the systolic blood pressure (SBP), diastolic blood pressure (DBP), carotid intima-media thickness (cIMT), pulse wave velocity-beginning of systole (PWV-BS), and pulse wave velocity-end of systole (PWV-ES) between January 2017 and December 2021. The patients were divided into three groups according to their blood pressure (BP)-normal BP (NBP): SBP <130 mmHg and DBP <80 mmHg (n=215); PHT: 130 mmHg≤SBP<140 mmHg and/or 80 mmHg≤DBP<90 mmHg (n=119); hypertensive (HT): SBP ≥140 mmHg and/or DBP ≥90 mmHg (n=292). Correlation analyses and comparisons were performed among the groups and in the cIMT subgroups (cIMT ≥0.050 cm and <0.050 cm). RESULTS: cIMT and PWV-ES significantly differed among the BP groups (P<0.05). The BP groups had similar PWV-BS when cIMT <0.050 cm or cIMT ≥0.050 cm (all P>0.05). However, the NBP group had a notably lower PWV-ES than the PHT (P<0.001 and P=0.024) and HT (all P<0.001) groups in both cIMT categories, while the PWV-ES in the PHT group were not significantly lower than in the HT group (all P>0.05). CONCLUSION: Carotid morphological and biomechanical properties in the PHT group differed from those in the NBP group. ufPWV could be used for an early evaluation of carotid stiffening linked to pre-hypertension.

Association between triglyceride-glucose index and arterial stiffness reflected by carotid pulse-wave velocity in stage 1 hypertension and individuals with normal/elevated blood pressure.

Evidence of the triglyceride-glucose (TyG) index as an independent predictor of arterial stiffness in stage 1 hypertension patients is scarce. This study aimed to explore the association between TyG index and arterial stiffness in this population. A total of 1041 individuals from 32 centers with normal/elevated blood pressure (BP, <130/80 mmHg; 345 men (33%); median age, 37 years) and 585 stage 1 hypertension patients (BP ≥130/80 and <140/90 mmHg; 305 men (52%); median age, 47 years) were prospectively enrolled. Arterial stiffness was determined by measuring carotid ultrafast pulse-wave velocity (ufPWV). TyG index was calculated as ln (fasting triglyceride (TG) × fasting blood glucose/2). Patients with a higher TyG index tended to have higher ufPWV. The TyG index was positively associated with ufPWV at the end of systole in stage 1 hypertension patients after adjusting for confounding factors (ß for per unit .48), and restricted cubic spline analysis confirmed a linear association. Subgroup analyses in terms of age, sex, and body mass index yielded similar results. However, no significant relationship was observed between the TyG index and ufPWV in the population with normal/elevated BP. The fully adjusted ß between ufPWV and the TyG index was higher than the TG/high-density lipoprotein cholesterol ratio, TG, and pulse pressure. In conclusion, patients with a higher TyG index had greater arterial stiffness, and the TyG index independently and positively correlated with arterial stiffness in stage 1 hypertension patients. The TyG index may provide a simple and reliable marker to monitor arterial stiffness in hypertensive patients.

Individualized References of Carotid Stiffening Quantified With Ultrafast Ultrasound Imaging: Model Construction and Preliminary Validation.

To establish and preliminarily validate an individualized reference of carotid stiffness quantified by ultrafast pulse wave velocity (ufPWV), our study included 225 healthy individuals in the modeling cohort and 628 individuals in the validation cohort. All participants underwent assessment of carotid intima-media thickness (cIMT), pulse wave velocity-beginning of systole and pulse wave velocity-end of systole (PWV-ES). A threshold equation of estimated PWV-ES was obtained by multiple linear regression analysis in the modeling cohort as follows: estimated PWV-ES (m/s) = 0.080 × age (y) + 0.767 × low-density lipoprotein (mmol/L) + 0.040 × systolic blood pressure (mm Hg) + 0.372 × sex (male = 1, female = 0) - 2.803. With this equation, the validation cohort was divided into the low PWV-ES (actual PWV-ES ≤ estimated PWV-ES) and high PWV-ES (actual PWV-ES > estimated PWV-ES) groups. A clear boundary was found to be present between the low PWV-ES and high PWV-ES groups in the validation cohort. Participants with increasing PWV-ES increased with age gradually. We further subdivided participants into cIMT subgroups using a cutoff thickness of 0.050 cm. Diagnostic performance analysis revealed that the sensitivity and specificity of the threshold equation were 78.9% and 73.9%, respectively. We established and validated a novel individualized reference equation for estimated PWV-ES, which can likely expand the application of prospective ufPWV assessment.

Reference Values of Carotid Ultrafast Pulse-Wave Velocity: A Prospective, Multicenter, Population-Based Study.

BACKGROUND: Ultrafast ultrasound imaging has been demonstrated to be an effective method to evaluate carotid stiffness through carotid pulse-wave velocity (PWV) with high reproducibility, but a lack of reference values has precluded its widespread use in clinical practice. The aims of this study were to establish reference values of PWV for ultrafast ultrasound imaging in a prospective, multicenter, population-based cohort study and to investigate the main determinants of carotid PWV. METHODS: A total of 1,544 healthy Han Chinese volunteers (581 men [38%]; age range, 18-95 years) were enrolled from 32 collaborating laboratories in China. The participants were categorized by age, blood pressure (BP), and body mass index (BMI). Basic clinical parameters and carotid PWV at the beginning of systole (BS) and at end-systole (ES) were measured using ultrafast ultrasound imaging techniques. RESULTS: PWV at both BS and ES was significantly higher in the left carotid artery than in the right carotid artery. PWV at BS was significantly higher in men than in women; however, no significant difference was noted in PWV at ES between men and women. Multiple linear regression analyses revealed that age, BP, and BMI were independently correlated with PWV at both BS and ES. PWV at BS and ES progressively increased with increases in age, BP, and BMI. Furthermore, age- and sex-specific reference values of carotid PWV for ultrafast ultrasound imaging were established. CONCLUSIONS: Reference values of carotid PWV for ultrafast ultrasound imaging, stratified by sex and age, were determined for the first time. Age, BP, and BMI were the dominant determinants of carotid PWV for ultrafast ultrasound imaging, which should be considered in clinical practice for assessing arterial stiffness.

Absent atherosclerotic risk factors are associated with carotid stiffening quantified with ultrafast ultrasound imaging.

OBJECTIVES: To evaluate carotid stiffening in participants without conventional cardiovascular risk factors (CVRFs) by using ultrafast pulse wave velocity (ufPWV). METHODS: The present study enrolled 517 participants without conventional CVRFs (CVRF-Free total population). Subjects in this population were defined as current non-smokers with untreated blood pressure < 140/90 mmHg, fasting blood glucose (FBG) < 7.0 mmol/L, total cholesterol (TC) < 6.2 mmol/L, low-density lipoprotein cholesterol < 4.1 mmol/L, and high-density lipoprotein cholesterol ≥ 1.0 mmol/L. Participants in the subgroup with optimal CVRFs (CVRF-Optimal subgroup; n = 188) were defined as having blood pressure < 120/80 mmHg, TC < 5.2 mmol/L, and FBG < 5.6 mmol/L. Clinical interviews, physical examinations, serum draw, carotid intima-media thickness (cIMT), and ufPWV were evaluated. Adjusted odds ratios (ORs) with 95% confidence intervals and ordinal logistic regression models were used. RESULTS: Carotid stiffening was present in 46.2-54.5% of CVRF-Free subjects. Age, male sex, and body mass index (BMI) were independently associated with carotid stiffening in both the CVRF-Free total population and CVRF-Optimal subgroup (OR for age = 1.10-1.11, OR for male sex = 2.65-7.19, OR for BMI = 1.34-1.62; p < 0.05). Carotid stiffening was associated with TC only in the CVRF-Free total population (OR for TC = 1.84; p = 0.034). CONCLUSIONS: Many CVRF-Free individuals have carotid stiffening. ufPWV for atherosclerotic stiffening aids the assessment of early atherogenesis and may further clarify the true status of healthy adults without CVRFs. KEY POINTS: • CVRF-Optimal individuals have a lower carotid stiffness than CVRF-Free populations. • ufPWV is a quantitative predictor for the early assessment of AS. • Absent major CVRFs cannot be considered low risk for carotid stiffening and atherosclerosis.

Divalent osmium complexes: synthesis, characterization, strong red phosphorescence, and electrophosphorescence.

We report new divalent osmium complexes that feature strong red metal-to-ligand-charge-transfer (MLCT) phosphorescence and electrophosphorescence. The general formula of the complexes is Os(II)(N-N)(2)L-L, where N-N is either a bipyridine or a phenanthroline and L-L is either a phosphine or an arsine. New polypyridyl ligands synthesized are 4,4'-di(biphenyl)-2,2'-bipyridine (15) and 4,4'-di(diphenyl ether)-2,2'-bipyridine (16), and the 1,10-phenanthroline derivatives synthesized are 4,7-bis(p-methoxyphenyl)-1,10-phenanthroline (17), 4,7-bis(p-bromophenyl)-1,10-phenanthroline (18), 4,7-bis(4'-phenoxybiphen-4-yl)-1,10-phenanthroline (19), and 4,7-bis(4-naphth-2-ylphenyl)-1,10-phenanthroline (20). 4,4'-Diphenyl-2,2'-bipyridine (21) and 4,7-diphenyl-1,10-phenanthroline (22) were also used in these studies. Strong pi-acid ligands used were 1,2-bis(diphenylarseno)ethane (23), cis-1,2-bis(diphenylphosphino)ethylene (24), and cis-1,2-vinylenebis(diphenylarsine) (25). Ligand 25 is used for the first time in these types of luminescent osmium complexes. These compounds feature strong MLCT absorption bands in the visible region and strong red phosphorescent emission ranging from 611 to 651 nm, with quantum efficiency up to 45% in ethanol solution at room temperature. Red organic light-emitting diodes (OLEDs) were successfully fabricated by doping the Os(II) complexes into blend of poly(N-vinylcarbazole) (PVK) and 2-tert-butylphenyl-5-biphenyl-1,3,4-oxadiazole (PBD). Brightness over 1400 cd/m(2) for a double-layer device has been reached, with a turn-on voltage of 8 V. The maximum external quantum efficiency was 0.64%. Commission Internationale de l'Eclairage (CIE) chromaticity coordinates (x, y) of the red electrophosphorescence from the complexes are (0.65, 0.34), which indicates pure red emission.