Integration of non-targeted metabolomics with network pharmacology deciphers the anxiolytic mechanisms of Platycladi Semen extracts in CUMS mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Platycladi Semen was recorded in Shen Nong's Herbal Classic and was considered a herbal medicine with low toxicity after long-term medication. Multiple traditional Chinese medicine prescriptions containing Platycladi Semen have been used to treat insomnia. Modern clinical practitioners commonly use Platycladi Semen to treat anxiety disorders, but there are few studies on its composition and anxiolytic mechanisms. AIM OF THE STUDY: To describe the main components of Platycladi Semen and investigate its anxiolytic effects and mechanisms. MATERIALS AND METHODS: The main components of Platycladi Semen were characterized by liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). The anxiolytic effects of oral Platycladi Semen were evaluated in chronic unpredictable mild stress (CUMS) induced mice. To explore the anxiolytic mechanisms of Platycladi Semen, serum non-targeted metabolomics combined with network pharmacology and molecular docking was performed. RESULTS: Fourteen compounds were identified in the 50% methanol extract and 11 fatty acid derivatives were identified in the methyl-esterified fatty oil of Platycladi Semen. In CUMS mice, both the aqueous extract and fatty oil of Platycladi Semen had anxiolytic effects, which were shown by the increase in the time and frequency of mice entering the open arm in the elevated plus maze (EPM) experiment. Through serum non-targeted metabolomics, 34 differential metabolites were identified, and lipid metabolic pathways such as sphingolipid metabolism, steroidogenesis, alpha-linoleic acid, and linoleic acid metabolism were enriched. Through network pharmacology, 109 targets of the main components in Platycladi Semen were identified, and the 'neuroactive ligand-receptor interaction' and 'lipid metabolism' were enriched. The molecular docking results showed that the main components in Platycladi Semen could bind to the key targets such as peroxisome proliferator-activated receptor delta (PPARD), peroxisome proliferator-activated receptor alpha (PPARA), fatty acid binding protein 5 (FABP5), fatty acid binding protein 3 (FABP3), peroxisome proliferator-activated receptor gamma (PPARG), arachidonate 5-lipoxygenase (ALOX5) and fatty acid amide hydrolase (FAAH). CONCLUSION: This study indicated that Platycladi Semen has anxiolytic effects, and the anxiolytic mechanisms may be the regulation of lipid metabolism and the neuroactive ligand-receptor interaction.

Anxiolytic effects, metabolism and plasma pharmacokinetics of 3, 6' -disinapoylsucrose.

3,6'-disinapoylsucrose (DISS) is a bioactive oligosaccharide ester derived from Polygalae Radix. This study aims to explore the anxiolytic effects of DISS and further reveal the material basis by establishing the pharmacokinetics of DISS and its metabolites. Behavioral experiments such as the open field test (OFT) and elevated plus maze test (EPM) were performed to evaluate the anxiolytic effects of DISS in mice after oral administration. By UPLC-MS/MS analysis, DISS and its metabolites both in blood and cerebrospinal fluid were identified, and the pharmacokinetics of DISS and its metabolites were characterized in SD rats after oral administration of DISS (100 mg·kg-1). Oral DISS could increase the time and frequency of mice entering the central area of the field in OFT and open arm in EPM, which indicated DISS has good anxiolytic effects. We also identified DISS and its metabolites (sinapic acid (SA), 3,4,5-trimethoxycinnamic acid (TMCA), methyl-3,4,5-trimethoxycinnamate (TMCA-CH2), p-Coumaric acid (CA) and p-methoxycinnamic acid (MA)) in rat plasma and cerebrospinal fluid. The pharmacokinetic results showed that DISS was rapidly absorbed after administration and reached its highest concentration at 12 min, SA had the highest exposure level in vivo and was probably the main active form of DISS action, TMCA could maintain at a low concentration for a long time. In brief, we reported the anxiolytic effect of DISS firstly, revealed the cerebrospinal fluid distribution and pharmacokinetics of DISS and its metabolites. Our findings provide the basis for further insight into the mechanisms involved in the anxiolytic effects of DISS.

Multi-stimuli responsive molecularly imprinted nanoparticles with tailorable affinity for modulated specific recognition of human serum albumin.

A kind of novel multi-stimuli responsive molecularly imprinted polymers with bovine serum albumin (BSA) as a dummy template (MSR-BSA-MIPs) was fabricated for specific recognition of human serum albumin (HSA) with modulated affinity. The MSR-BSA-MIPs were prepared through free radical polymerization using vinyl modified magnetic nanoparticles as substrates, bovine serum albumin (BSA), with high amino acid sequence similarity but low price compared to HSA, as the dummy template, N-(3-(dimethylamino)-propyl)-methacrylamide (DMAPMA) and N-isopropylacrylamide (NIPAm) as functional monomers with ionic strength and temperature response. The conditions of polymerization, adsorption and elution were systematically investigated. As expected, the obtained MSR-BSA-MIPs exhibited rapid dispersion or separation states under magnetic control, flexible conversion of adsorption and desorption for the target protein under temperature or ionic strength adjustment. Ten adsorption-desorption cycles were carried out with a little decrease in adsorption capacity under two different elution methods, which also inspired us to combine two elution methods while considering both the stability and adsorption capacity of MSR-BSA-MIPs. The adsorption capacity (Q) and imprinting factor (IF) of MSR-BSA-MIPs for HSA are 43.01 mg g-1 and 4.26, respectively. Furthermore, the blood was opted as a realistic specimen for evaluating the adsorption capability of the proposed adsorbent, emphasizing its good practicality for target protein recognition and enrichment.

Facile synthesis of hydrophilic magnetic graphene nanocomposites via dopamine self-polymerization and Michael addition for selective enrichment of N-linked glycopeptides.

The development of methods to effectively capture N-glycopeptides from the complex biological samples is crucial to N-glycoproteome profiling. Herein, the hydrophilic chitosan-functionalized magnetic graphene nanocomposites (denoted as Fe3O4-GO@PDA-Chitosan) were designed and synthesized via a simple two-step modification (dopamine self-polymerization and Michael addition). The Fe3O4-GO@PDA-Chitosan nanocomposites exhibited good performances with low detection limit (0.4 fmol·µL-1), good selectivity (mixture of bovine serum albumin and horseradish peroxidase tryptic digests at a molar ration of 10:1), good repeatability (4 times), high binding capacity (75 mg·g-1). Moreover, Fe3O4-GO@PDA-Chitosan nanocomposites were further utilized to selectively enrich glycopeptides from human renal mesangial cell (HRMC, 200 µg) tryptic digest, and 393 N-linked glycopeptides, representing 195 different glycoproteins and 458 glycosylation sites were identified. This study provides a feasible strategy for the surface functionalized novel materials for isolation and enrichment of N-glycopeptides.

N-acetyltransferases from three different organisms displaying distinct selectivity toward hexosamines and N-terminal amine of peptides.

N-acetyltransferases are a family of enzymes that catalyze the transfer of the acetyl moiety (COCH3) from acetyl coenzyme A (Acetyl-CoA) to a primary amine of acceptor substrates from small molecules such as aminoglycoside to macromolecules of various proteins. In this study, the substrate selectivity of three N-acetyltransferases falling into different phylogenetic groups was probed against a series of hexosamines and synthetic peptides. GlmA from Clostridium acetobutylicum and RmNag from Rhizomucor miehei, which have been defined as glucosamine N-acetyltransferases, were herein demonstrated to be also capable of acetylating the free amino group on the very first glycine residue of peptide in spite of varied catalytic efficiency. The human recombinant N-acetyltransferase of Naa10p, however, prefers primary amine groups in the peptides as opposed to glucosamine. The varied preference of GlmA, RmNag and Naa10p probably arose from the divergent evolution of these N-acetyltransferases. The expanded knowledge of acceptor specificity would as well facilitate the application of these N-acetyltransferases in the acetylation of hexosamines or peptides.

Predictors and prognosis of left ventricular thrombus in post-myocardial infarction patients with left ventricular dysfunction after percutaneous coronary intervention.

BACKGROUND: We aimed to investigate the predictors and prognosis of left ventricular thrombus (LVT) in patients admitted for post-myocardial infarction (MI) and left ventricular dysfunction after contemporary percutaneous coronary intervention (PCI). METHODS: We prospectively enrolled 267 consecutive post-MI patients with left ventricular ejection fraction (LVEF) <0.45 based on the Shanghai East Hospital PCI database since 2012. Altogether 25 (9.36%) patients were selected as the LVT group. Baseline, angiographic, procedural characteristics and 1-year clinical outcomes were compared by Chi-square test, t-test or Kaplan-Meier survival analysis as appropriate. Receiver operating characteristic (ROC) curves were plotted for the accuracy of the multivariate analysis model. A multiple logistic regression was applied to predict LVT formation. RESULTS: The independent risk factors of LVT were left ventricular aneurysm [odds ratio (OR): 1.29, 95% confidence interval (CI): 1.09-1.52, P<0.01], incomplete revascularization (OR: 0.05, 95% CI: 0.01-0.35, P<0.01), SYNTAX score (OR: 1.28, 95% CI: 1.14-1.43, P<0.01) and D-dimer (OR: 1.90, 95% CI: 1.19-3.04, P<0.01). The SYNTAX score and D-dimer effectively indicated the development of LVT with optimal cutoff values of 29.50 and 1.53 mg/L, respectively. Patients with LVT had significantly worse outcomes at 1-year clinical follow-up, especially higher incidence of ischemic or hemorrhagic stroke. CONCLUSIONS: This study indicated that the presence of left ventricular aneurysm, incomplete revascularization, higher SYNTAX score and D-dimer level were the independent predictors of LVT formation in post-MI and LV dysfunction patients, which related to worse clinical outcomes. Future studies for early intervention and complete revascularization in high-risk subgroup patients are expected.

Maltose-Functionalized Hydrophilic Magnetic Nanoparticles with Polymer Brushes for Highly Selective Enrichment of N-Linked Glycopeptides.

Efficient enrichment glycoproteins/glycopeptides from complex biological solutions are very important in the biomedical sciences, in particular biomarker research. In this work, the high hydrophilic polyethylenimine conjugated polymaltose polymer brushes functionalized magnetic Fe3O4 nanoparticles (NPs) denoted as Fe3O4-PEI-pMaltose were designed and synthesized via a simple two-step modification. The obtained superhydrophilic Fe3O4-PEI-pMaltose NPs displayed outstanding advantages in the enrichment of N-linked glycopeptides, including high selectivity (1:100, mass ratios of HRP and bovine serum albumin (BSA) digest), low detection limit (10 fmol), large binding capacity (200 mg/g), and high enrichment recovery (above 85%). The above-mentioned excellent performance of novel Fe3O4-PEI-pMaltose NPs was attributed to graft of maltose polymer brushes and efficient assembly strategy. Moreover, Fe3O4-PEI-pMaltose NPs were further utilized to selectively enrich glycopeptides from human renal mesangial cell (HRMC, 200 µg) tryptic digest, and 449 N-linked glycopeptides, representing 323 different glycoproteins and 476 glycosylation sites, were identified. It was expected that the as-synthesized Fe3O4-PEI-pMaltose NPs, possessing excellent performance (high binding capacity, good selectivity, low detection limit, high enrichment recovery, and easy magnetic separation) coupled to a facile preparation procedure, have a huge potential in N-glycosylation proteome analysis of complex biological samples.

Body surface area as a key determinant of aortic root and arch dimensions in a population-based study.

The associations between the aortic dimensions (of the aortic sinus, aortic annulus and aortic arch) and physiological variables have not been established in the Chinese population. The present study examined the associations among physiological variables to determine the aortic root and arch dimensions echocardiographically. The diameters of the aortic sinus, annulus and arch were measured in 1,010 subjects via 2-D echocardiography with a 3.5-MHz transducer in a trans-thoracic position. The images of the aortic sinus and aortic annulus were obtained from a standard parasternal long-axis view. The maximum diameter of the valve orifice was measured at the end of systole. The aortic arch dimension was visualized in the long-axis using a suprasternal notch window and the maximum transverse diameter was measured. Epidata 3.0, Excel 2007 and SPSS version 17.0 were used to collect and analyze the data. A total of 1,010 subjects were enrolled. The mean age was 55.0±17.0 years (range of 18 to 90 years). The body surface area (BSA) was the best predictor of all the studied physiological variables and may be used to predict aortic sinus, annulus and arch dimensions independently (r=0.54, 0.37 and 0.39, respectively). Gender, blood pressure, age and BSA are significant predictors of the aortic dimensions. Of these, BSA was the best predictor.

Association between the rate of the morning surge in blood pressure and cardiovascular events and stroke.

BACKGROUND: The exaggerated surge in morning blood pressure (BP) that many patients experience upon awakening may be closely related to target organ damage and may be a predictor of cardiovascular complications. However, no previous studies have evaluated the rate of this surge independently of the evening period. It remains unclear whether the rate of increase experienced during the surge is a significant or independent determinant of cardiovascular events. METHODS: We randomly selected 340 ambulatory BP monitoring (ABPM) patients. All subjects without type 2 diabetes mellitus were divided into two groups: hypertensive group (n = 170) and normotensive group (n = 170). We analyzed ambulatory blood pressure recordings using a double logistic curve-fitting procedure to determine whether the magnitude of the surge in BP and heart rate (HR) in the morning is related to the level of BP in hypertensive individuals. We evaluated the association between the rate of the morning surge in systolic BP (SBP) and the incidence of myocardial infarction and stroke in normotensive and hypertensive subjects. RESULTS: Comparisons between hypertensive and normotensive subjects showed that the rates of the morning surges in SBP, mean BP (MBP), and diastolic BP (DBP) were greater in the hypertensive group (P < 0.05) than in the normotensive group. The rate of morning surge in BP was found to be correlated with the daytime SBP (r = 0.236, P < 0.01), the difference between the day and night plateau (r = 0.249, P < 0.01), and the night SBP (r = -0.160, P < 0.05), respectively. After controlling for age, sex, and mean systolic pressure within 24 hours (24 h SBP), the rate of morning surge in SBP was closely correlated with daytime SBP (r = 0.463, P < 0.001), night SBP (r = -0.173, P < 0.05), and the difference between the day and night plateau (r = 0.267, P < 0.001). Logistic regression analysis revealed that the rate of morning surge in SBP was an independent determinant of myocardial infarction (OR = 1.266, 95% CI = 1.153 - 1.389, P < 0.001) and stroke (OR = 1.367, 95% CI = 1.174 - 1.591, P < 0.001). CONCLUSIONS: The rate of the morning surge in BP is greater in hypertensive subjects than in normotensive subjects. Daytime SBP may be the best predictor of the rate of morning surge in SBP. The rate of the morning surge in BP is associated with cardiovascular and stroke events.

Smaller aortic dimensions do not fully account for the greater pulse pressure in elderly female hypertensives.

This study examined the importance of aortic dimensions in determining pulse pressure in elderly hypertensives participating in the 2nd Australian National Blood Pressure Study, including a substantial number not previously receiving blood pressure lowering medication. Aortic dimensions were determined by ultrasound at the transverse arch and at the insertion of the aortic valve. Unadjusted data showed negative (P<0.001) correlations between central (carotid) and (brachial) peripheral pulse pressure and both arch (-0.200, -0.181) and outflow tract (-0.238, -0.238) diameters. Correlations were similar in those previously treated with blood pressure lowering medication and in the treatment naïve. Central pulse pressure (84+/-26 versus 75+/-28 mm Hg, P<0.001) was higher and aortic dimensions (transverse arch 2.56+/-0.31 versus 2.88+/-0.35 mm, P<0.001) smaller in women than men. Women had greater aortic stiffness (beta index 29.4+/-36.1 versus 22.1+/-21.3, P<0.03). Other bivariate correlates of central pulse pressure were age, mean arterial pressure, height, heart rate, augmentation index, aortic stiffness (all P<0.001), and weight (P=0.027). In multivariate analyses gender remained a predictor of central pulse pressure (P<0.001) even with inclusion of aortic dimensions (P=0.013) height and weight. Other significant terms were age, heart rate, mean blood pressure, and aortic stiffness (all P<0.001). These findings demonstrate an independent inverse relation between aortic size and pulse pressure in older hypertensive subjects. Differences in aortic dimensions and stiffness between genders do not fully account for the observed blood pressure differences, suggesting that a contributory factor to gender differences in pulse pressure is an increased age-related mismatch in ventricular function and aortic stiffness in women compared with men.

Similar effects of treatment on central and brachial blood pressures in older hypertensive subjects in the Second Australian National Blood Pressure Trial.

The Second Australian National Blood Pressure Trial reported better prognosis for hypertensive subjects randomly assigned to an angiotensin-converting enzyme inhibitor (ACE-I) compared with a diuretic-based regimen despite no difference in brachial blood pressure control. A possible explanation is that there was a difference in central aortic pressures despite similar brachial pressure reductions. We examined this hypothesis in a subset of the Second Australian National Blood Pressure Trial cohort evaluated both before and after 4 years of treatment. The average age of the 479 subjects was 71.6+/-4.7 years (mean+/-SD), and 56% were women. Brachial systolic and pulse pressures after treatment were 145+/-1 (mean+/-SEM), 143+/-1, 72+/-1, and 70+/-1 mm Hg for diuretic and ACE-I groups, respectively. The respective changes from pretreatment values were -17+/-2, -16+/-2, -9+/-1, and -7+/-1 mm Hg. None of the differences between diuretic and ACE-I groups were significant. Central arterial pressure waveforms were acquired from carotid tonometry and calibrated from brachial pressures. Central systolic and pulse pressures posttreatment were 144+/-2, 144+/-2, 71+/-2, and 72+/-2 mm Hg for diuretic and ACE-I groups, respectively. The respective changes from pretreatment values were -15+/-2, -17+/-2, -6+/-2, and -8+/-2 mm Hg. None of the differences between diuretic and ACE-I groups were significant. The similarity of central and brachial pressures in this cohort of older hypertensive subjects is most likely because of the influences of age and hypertension in increasing arterial stiffness. There is no evidence that the better prognosis for patients randomly assigned to ACE-I in Second Australian National Blood Pressure Trial resulted from a disproportionate lowering of central blood pressure.

[The effects of phytoestrogen on blood pressure and lipids in healthy volunteers].

OBJECTIVE: To determine the effects of dietary soy containing phytoestrogens on blood pressure and lipids in healthy volunteers. METHODS: Two hundred thirteen healthy volunteers (108 men and 105 post-menopausal women, 50 - 76 years old) received either soy protein isolate (40 g soy protein, 118 mg isoflavones) or cassin placebo for 3 months in this randomized, double-blind trial. RESULTS: There were 34 withdrawals (16%) and 179 people (96 men and 83 women) completed the study protocol. After 3 months treatment, urinary phytoestrogens was significantly increased and blood pressure was significant reduced in soy protein group than that in cassin placebo group [mean change in systolic (-7.5 +/- 1.2) mm Hg vs. (-3.6 +/- 1.1) mm Hg, P < 0.05; diastolic: -4.3 +/- 0.8) mm Hg vs (-1.9 +/- 0.7) mm Hg, P < 0.05; mean aortic blood pressure: (-5.5 +/- 1.0) mm Hg vs (-0.9 +/- 1.0) mm Hg, P < 0.008]. Low- to high-density lipoprotein ratio [(-0.33 +/- 0.10) mmol/L vs (0.04 +/- 0.10) mmol/L, P < 0.05] and triglycerides [(-0.20 +/- 0.05) mmol/L vs (-0.01 +/- 0.05) mmol/L, P < 0.05] were significantly reduced and Lp(a) lipoprotein significantly increased [42 (17 - 67) mg/L vs 4 (22 - 31) mg/L, P < 0.05] in soy protein group compared to cassin placebo group. Total, low-density lipoprotein, and high-density lipoprotein cholesterols all improved in both groups and were similar between the groups. No side-effect was observed in both groups and no effect on the hypothalamic-pituitary-gonadal axis was noted in study subjects. CONCLUSION: In normotensive men and post-menopausal women, phytoestrogens intake improved blood pressure and lipids status.

[Depression before and after operation in coronary artery bypass grafting patients].

OBJECTIVE: To investigate the presence of depression in coronary artery bypass grafting (CABG) patients before and after the operation. METHODS: A questionnaire survey was conducted among 72 CABG patients, 21 of which, aged 65.30 +/- 1.15, underwent on-pump coronary artery bypass grafting (ONCAB) and 51 of which, aged 63.70 +/- 0.22, underwent off-pump CAB (OPCAB), using Beck Depression Inventory (BDI) one day before, and 3 and 6 months after the operation. RESULTS: Depressive disorders occurred in 49.2% of the patients preoperatively and 26.7% of the patients 6 months after the operation. The mean pre-operative BDI score was 5.77, and the post-operative BDI scores 3 and 6 months after operation were 4.12 and 3.06 respectively. At different post-operative time points the BDI scores of the depressive group were all lower than those of the non-depressive group, however, there was still a trend of lowering of BDI scores in the latter group. There were more patients who failed to resume their original work and more patients with angina and hypertension in the depression group. The proportion of females after operation was higher in the depression group. There was no significant difference in BDI score between the ONCAB and OPCAB groups both pre- and post-operatively. CONCLUSION: Depression at different degrees exists before CABG and can be improved post-operatively. Pre-operative BDI score is predictor of post-operative psychological outcome.

Brachial blood pressure but not carotid arterial waveforms predict cardiovascular events in elderly female hypertensives.

Central arterial waveforms and related indices of large artery properties can be determined with relative ease. This would make them an attractive adjunct in the risk stratification for cardiovascular disease. Although they have been associated with some classical risk factors and the presence of coronary disease, their prospective value in predicting cardiovascular outcomes is unknown. The present study determined the relative predictive value for cardiovascular disease-free survival of large artery properties as compared with noninvasive brachial blood pressure alone in a population of elderly female hypertensive subjects. We measured systemic arterial compliance, central systolic pressure, and carotid augmentation index in a subset of female participants in the Second Australian National Blood Pressure Study (untreated blood pressure 169/88+/-12/8 mm Hg). There were a total of 53 defined events during a median of 4.1 years of follow-up in 484 women with complete measurements. Although baseline blood pressures at the brachial artery predicted cardiovascular disease-free survival (hazard ratio [HR], 2.3; 95% CI, 1.3 to 4.1 for pulse pressure > or =81 versus <81 mm Hg; P=0.01), no such relation was found for carotid augmentation index (HR, 0.80; 95% CI, 0.44 to 1.44; P value not significant) or systemic arterial compliance (HR, 1.25; 95% CI, 0.72 to 2.16; P value not significant). Blood pressure, but not noninvasively measured central arterial waveforms, predict outcome in the older female hypertensive patient. Thus, blood pressure measurement alone is superior to measurement of arterial waveforms in predicting outcome in this group.

Large artery stiffness is not related to plasma cholesterol in older subjects with hypertension.

OBJECTIVE: Previous studies have demonstrated a prognostic role of large artery stiffness in hypertensive subjects and increased stiffness in subjects with coronary artery disease. Although plasma cholesterol is an established risk factor for cardiovascular disease, its relationship with large artery properties in a hypertensive population is unclear. METHODS AND RESULTS: Plasma cholesterol and large artery properties were measured at baseline in a subset of participants of a randomized controlled trial (ANBP2) evaluating hypertension treatment in older (65 to 84 years) subjects. Noninvasive measures of large artery behavior were central augmentation index (AI), systemic arterial compliance (SAC), and transverse expansion of the aortic arch (aortic distensibility). Arterial waveforms acceptable for analysis were obtained in approximately 80% of cases yielding valid measurements of AI in 868, SAC in 846, and aortic distensibility in 680 subjects. Mean total and high-density lipoprotein (HDL) concentrations were 5.5+/-1.0 and 1.4+/-0.5 mmol L(-1). Total and HDL cholesterol and AI were greater in females than males, whereas SAC and aortic distensibility were greater in males. In multiple regression analyses there were no significant associations between stiffness parameters and total or HDL cholesterol. Significant independent associations in such analyses were found for mean arterial blood pressure, gender, age, height, and heart rate, in keeping with previous findings. CONCLUSIONS: In the largest cohort of elderly hypertensive subjects studied to date, plasma cholesterol per se was not associated with large artery stiffness. Such independence from cholesterol increases the potential for artery stiffness measurements to additionally contribute to cardiovascular risk assessment in this population.

Large-artery stiffness contributes to the greater prevalence of systolic hypertension in elderly women.

OBJECTIVES: To determine whether sex differences in large-artery stiffness contribute to the greater prevalence of systolic hypertension in elderly women than in elderly men. DESIGN: During a single visit arterial stiffness was assessed in the unmedicated state using four parameters. PARTICIPANTS: Three hundred seventy-four women with a mean age+/-standard deviation of 72+/-5 and 296 men aged 71+/-5 participated. SETTING: Hypertensive patients were recruited from general practice as part of the second Australian National Blood Pressure Study in Melbourne, Australia. MEASUREMENTS: Large-artery stiffness was assessed using multiple methodologies, including aortic arch stiffness (beta-index) using M-mode ultrasound and arterial compliance and augmentation index using noninvasive carotid pressure and aortic flow measurements. RESULTS: Women had greater carotid and brachial pulse pressure (PP) than men (P<.001), despite higher mean arterial pressure in men. Mean arterial compliance was lower in women (0.20+/-0.12 vs 0.28+/-0.16 mL/mmHg, P<.001) even after correction for aortic area, and aortic arch stiffness was higher (30+/-36 vs 23+/-22; P<.01). Consistent with both a stiffer proximal circulation and a shorter distance to reflection sites, women had higher augmentation index (38+/-11% vs 29+/-12%, P<.001). In multivariate analysis, sex was an independent determinant of all arterial stiffness indices. CONCLUSION: Independently of known confounders, elderly hypertensive women have stiffer large arteries, greater central wave reflection, and higher PP than elderly men. Stiffer large arteries likely contribute to the greater prevalence of systolic hypertension in elderly women and may partly explain the acceleration in postmenopausal cerebrovascular and cardiac complications.

Effects of Blood Pressure, Smoking, and Their Interaction on Carotid Artery Structure and Function.

-In the present study, we examined the relationships among carotid blood pressure, arterial geometry, and wall stress and determined the impact of hypertension, smoking status, and their interaction on these relationships. The study involved 679 subjects aged 49 to 82 years: 372 smokers (190 men and 182 women) and 307 nonsmokers (110 men and 197 women). Blood samples were taken to determine total cholesterol levels. Central pulse pressure was derived from measured brachial artery pressure with a linear regression equation from data obtained in a subgroup of 276 subjects that related brachial and carotid pulse pressures; the latter was measured with applanation tonometry. Carotid intima-media thickness (IMT), lumen diameter (D), and stiffness index (SI) were determined with high-resolution B-mode ultrasound. Mean and pulsatile circumferential stress (final sigma(C)) was calculated according to the Laplace relationship. Indexes of arterial geometry and function were adjusted for age, height, and heart rate. Hypertension (treated and/or screening blood pressure of >140/90 mm Hg) was present in 71 nonsmokers and 186 smokers. Nonsmokers and smokers did not differ in blood pressure and cholesterol levels. Hypertension and smoking individually and interactively significantly increased adjusted IMT, D, and SI. The radius-to-wall thickness ratio (R/IMT) (where R=D/2) and final sigma(C) were increased in hypertensives. SI was correlated with IMT (r=0.56, P:<0.001); radius-to-wall thickness ratio was inversely correlated with central pulse pressure (r=-0.38, P:<0.001). Smoking did not influence these relationships. In conclusion, carotid artery wall remodeling appears to follow Laplace's law but is insufficient to prevent an increase in circumferential stress in hypertensive subjects. Unlike hypertension, smoking does not influence the lumen-to-wall ratio but has a significant effect on wall stiffness.