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Objective: Our aim was to evaluate the ability of arterial stiffness parameters to predict pre-eclampsia early compared with peripheral blood pressure, uterine artery Doppler and established angiogenic biomarkers., Design: Prospective cohort study., Setting: Tertiary care antenatal clinics in Montreal, Canada., Population: Women with singleton high-risk pregnancies., Methods: In the first trimester, arterial stiffness was measured by applanation tonometry, along with peripheral blood pressure and serum/plasma angiogenic biomarkers; uterine artery Doppler was measured in the second trimester. The predictive ability of different metrics was assessed through multivariate logistic regression., Main Outcome Measures: Arterial stiffness (carotid-femoral pulse wave velocity, carotid-radial pulse wave velocity) and wave reflection (augmentation index, reflected wave start time), peripheral blood pressure, ultrasound indices of velocimetry and circulating angiogenic biomarker concentrations., Results: In this prospective study, among 191 high-risk pregnant women, 14 (7.3%) developed pre-eclampsia. A first-trimester 1 m/s increase in carotid-femoral pulse wave velocity was associated with 64% increased odds (P < 0.05), and a 1-millisecond increase in time to wave reflection with 11% decreased odds for pre-eclampsia (P < 0.01). The area under the curve of arterial stiffness, blood pressure, ultrasound indices and angiogenic biomarkers was 0.83 (95% confidence interval [CI] 0.74-0.92), 0.71 (95% CI 0.57-0.86), 0.58 (95% CI 0.39-0.77), and 0.64 (95% CI 0.44-0.83), respectively. With a 5% false-positive rate, blood pressure had a sensitivity of 14% for pre-eclampsia and arterial stiffness a sensitivity of 36%., Conclusions: Arterial stiffness predicted pre-eclampsia earlier and with greater ability than blood pressure, ultrasound indices or angiogenic biomarkers., (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Background: Several vaccines against SARS-CoV-2 have been developed and approved at an unparalleled speed. Given that SARS-CoV-2 vaccines are recommended to pregnant people, our aim was to quantify vaccination uptake, and describe vaccination hesitancy and behavioural attitudes surrounding SARS-CoV-2 vaccination in pregnancy in Canada., Methods: The CONCEPTION study is an ongoing international study started in June 2020, evaluating the impact of the COVID-19 pandemic on the health of pregnant people and their children. For this study, pregnant people recruited from Apr. 20, 2021, to Feb. 8, 2022, and residing in Canada were invited to complete a Web-based survey. In addition to all CONCEPTION variables, data on vaccine uptake as well as personal knowledge of COVID-19 severity in pregnancy and of SARS-CoV-2 vaccine safety and efficacy were collected. Marginal risk differences and adjusted odds ratios (ORs) were calculated to assess determinants of SARS-CoV-2 vaccination during pregnancy., Results: From Apr. 20, 2021, to Feb. 8, 2022, 603 pregnant people were recruited and gave consent, of which 83.7% ( n = 505) were vaccinated and 16.3% ( n = 98) were not vaccinated against SARS-CoV-2. Uptake of the influenza vaccine in 2020/21 was a significant predictor of being vaccinated against SARS-CoV-2 or intention to be vaccinated (marginal risk difference 3.2%, 95% confidence interval [CI] 3.0% to 3.3%, adjusted OR 4.43, 95% CI 2.32 to 9.25), and being employed (marginal risk difference 11.2%, 95% CI 10.6% to 11.9%, adjusted OR 2.17, 95% CI 1.03 to 4.35) increased the likelihood of being vaccinated against SARS-CoV-2. Self-assessed knowledge of COVID-19 severity and vaccine efficacy was not associated with vaccine uptake., Interpretation: Among the Canadian pregnant people who responded to this study, vaccine uptake against SARS-CoV-2 was high. However, our results underscore the importance of improving knowledge transfer about the efficacy of SARS-CoV-2 vaccines in pregnancy to guide vaccination efforts., Competing Interests: Competing interests: None declared., (© 2022 CMA Impact Inc. or its licensors.)

Background: Given that pregnant women taking medications are excluded from clinical trials, real-world evidence is essential. We aimed to build a Canadian Mother-Child Cohort Active Surveillance Initiative (CAMCCO) and compare frequency of prematurity, low-birth-weight (LBW), major malformations, multiplicity, and gestational medication use across four provinces., Methods: CAMCCO is a collaborative research infrastructure that uses real-world data from large provincial health care databases in Canada; developed with standardized methods to similarly construct population-based pregnancy/child cohorts with longitudinal follow-up by linking administrative/hospital/birth databases. CAMCCO also includes a common repository to i) share algorithms and case definitions based on diagnostic and procedural codes for research/training purpose, and ii) download aggregate data relevant to primary care providers, researchers, and decision makers. For this study, data from Quebec (1998-2015), Manitoba (1995-2019), Saskatchewan (1996-2020), and Alberta (2005-2018) are compared (Chi-square tests, p-values), and trends are calculated using Cochran-Armitage trend tests., Results: Almost two-thirds (61%) of women took medications during pregnancy, mostly antibiotics (26%), asthma drugs (8%), and antidepressants (4%). Differences in the prevalence of prematurity (5.9-6.8%), LBW (4.0-5.2%), and multiplicity (1.0-2.5%) were statistically significant between provinces (p<0.001). Frequency of major malformations increased over time in Quebec (7-11%; p<0.001), Saskatchewan (5-11%; p<0.001), and Alberta (from 7-8%; p<0.001), and decreased in Manitoba (5-3%; p<0.001). Cardiovascular and musculoskeletal malformations were the most prevalent., Interpretation: Medications are often used among Canadian pregnancies but adverse pregnancy outcomes vary across provinces. Digitized health data may help researchers and care providers understand the risk-benefit ratios related to gestational medication use, as well as province-specific trends., Competing Interests: The authors have declared that no competing interests exist.

Importance and Objective: Prenatal cannabis effect on attention deficit with or without hyperactivity disorder (ADHD) remains to be determined. Our aim is to quantify the impact of in-utero exposure to cannabis on the risk of ADHD., Design: Cohort study., Setting: Questionnaires were mailed to women sampled from the Quebec Pregnancy Cohort (QPC). Data from questionnaires were then linked with their QPC (built with administrative health databases, hospital patient charts and birth certificate databases)., Participants: Respondents who gave birth to a singleton live born between January 1998 and December 2003 and were continuously enrolled in the Régie de l'assurance maladie du Québec (RAMQ) medication insurance plan for at least 12 months before the first day of gestation and during pregnancy., Exposure: In-utero cannabis exposure was based on mothers' answers to the question on cannabis use during pregnancy (yes/no) and categorised as occasionally, regularly exposed and unexposed if they chose one of these categories., Outcomes: ADHD was defined by a diagnosis of ADHD through the RAMQ medical services or MedEcho databases or a prescription filled for ADHD medication through RAMQ pharmaceutical services between birth and the end of the follow-up period. Follow-up started at the birth and ended at the index date (first diagnosis or prescription filled for ADHD), child death (censoring), end of public coverage for medications (censoring) or the end of study period, which was December 2015 (censoring), whichever event came first., Results: A total of 2408 children met the inclusion criteria. Of these children, 86 (3.6%) were exposed to cannabis in-utero and 241 (10.0%) had an ADHD diagnosis or medication filled. After adjustments for potential confounders, no significant association was found between in-utero cannabis exposure (occasional (1.22 (95% CI 0.63 to 2.19)) or regular (1.22 (95% CI 0.42 to 2.79))) and the risk of ADHD in children., Conclusions: In-utero exposure to cannabis seemed to not be associated with the risk ADHD in children., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Impaired vascular function is a central feature of pathologic processes preceding the onset of preeclampsia. Arterial stiffness, a composite indicator of vascular health and an important vascular biomarker, has been found to be increased throughout pregnancy in those who develop preeclampsia and at the time of preeclampsia diagnosis. Although sleep-disordered breathing in pregnancy has been associated with increased risk for preeclampsia, it is unknown if sleep-disordered breathing is associated with elevated arterial stiffness in pregnancy., Objective: This prospective observational cohort study aimed to evaluate arterial stiffness in pregnant women, with and without sleep-disordered breathing and assess the interaction between arterial stiffness, sleep-disordered breathing, and preeclampsia risk., Study Design: Women with high-risk singleton pregnancies were enrolled at 10 to 13 weeks' gestation and completed the Epworth Sleepiness Score, Pittsburgh Sleep Quality Index, and Restless Legs Syndrome questionnaires at each trimester. Sleep-disordered breathing was defined as loud snoring or witnessed apneas (≥3 times per week). Central arterial stiffness (carotid-femoral pulse wave velocity, the gold standard measure of arterial stiffness), peripheral arterial stiffness (carotid-radial pulse wave velocity), wave reflection (augmentation index, time to wave reflection), and hemodynamics (central blood pressures, pulse pressure amplification) were assessed noninvasively using applanation tonometry at recruitment and every 4 weeks from recruitment until delivery., Results: High-risk pregnant women (n=181) were included in the study. Women with sleep-disordered breathing (n=41; 23%) had increased carotid-femoral pulse wave velocity throughout gestation independent of blood pressure and body mass index (P=.042). Differences observed in other vascular measures were not maintained after adjustment for confounders. Excessive daytime sleepiness, defined by Epworth Sleepiness Score >10, was associated with increased carotid-femoral pulse wave velocity only in women with sleep-disordered breathing (P interaction =.001). Midgestation (first or second trimester) sleep-disordered breathing was associated with an odds ratio of 3.4 (0.9-12.9) for preeclampsia, which increased to 5.7 (1.1-26.0) in women with sleep-disordered breathing and hypersomnolence, whereas late (third-trimester) sleep-disordered breathing was associated with an odds ratio of 8.2 (1.5-39.5) for preeclampsia., Conclusion: High-risk pregnant women with midgestational sleep-disordered breathing had greater arterial stiffness throughout gestation than those without. Sleep-disordered breathing at any time during pregnancy was also associated with increased preeclampsia risk, and this effect was amplified by hypersomnolence., (Copyright © 2021. Published by Elsevier Inc.)

Introduction: We aimed to measure the impact of the COVID-19 pandemic on maternal mental health, stratifying on pregnancy status, trimester of gestation, and pandemic period/wave. Methods: Pregnant persons and persons who delivered in Canada during the pandemic, >18 years, were recruited, and data were collected using a web-based strategy. The current analysis includes data on persons enrolled between 06/2020−08/2021. Maternal sociodemographic indicators, mental health measures (Edinburgh Perinatal Depression Scale (EPDS), Generalized Anxiety Disorders (GAD-7), stress) were self-reported. Maternal mental health in pregnant women (stratified by trimester, and pandemic period/wave at recruitment) was compared with the mental health of women who had delivered; determinants of severe depression were identified with multivariate logistic regression models. Results: 2574 persons were pregnant and 626 had already delivered at recruitment. Participants who had delivered had significantly higher mean depressive symptom scores compared to those pregnant at recruitment (9.1 (SD, 5.7) vs. 8.4 (SD, 5.3), p = 0.009). Maternal anxiety (aOR 1.51; 95%CI 1.44−1.59) and stress (aOR 1.35; 95%CI 1.24−1.48) were the most significant predictors of severe maternal depression (EDPS ˃ 13) in pregnancy. Conclusion: The COVID-19 pandemic had a significant impact on maternal depression during pregnancy and in the post-partum period. Given that gestational depression/anxiety/stress has been associated with preterm birth and childhood cognitive problems, it is essential to continue following women/children, and develop strategies to reduce COVID-19′s longer-term impact.

Purpose: Preeclampsia (PrE) is a leading complication of pregnancy characterized by vascular dysfunction. Characterizing the longitudinal changes in vascular function prior to PrE onset is critical to the identification of optimal timepoints for vascular assessment and the development of effective early screening strategies., Methods: In this prospective longitudinal study of women with singleton high-risk pregnancies, arterial stiffness and wave reflection parameters were assessed using applanation tonometry at 10-13 weeks' gestation and repeated every 4 weeks throughout pregnancy. Changepoints in carotid-femoral pulse wave velocity (cfPWV), carotid-radial PWV (crPWV), augmentation index (AIx), time to wave reflection (T 1R ), pulse pressure amplification (PPA), and subendocardial viability ratio (SEVR) were compared between women who did and did not subsequently develop PrE., Results: A changepoint in cfPWV and crPWV was detected at 14-17 weeks' gestation. cfPWV then increased in women who went on to develop PrE but decreased in women who did not; a 1.2 m/s difference in cfPWV between the groups was observed at 22-25 weeks' gestation. Conversely, crPWV converged in the two groups from a baseline difference of 1.05 m/s (95% credible interval: 0.37, 1.72). Women who subsequently developed PrE demonstrated an increase in AIx at 18-21 weeks' gestation that was not seen in women who did not develop PrE until 30-33 weeks. No differences in T 1R , PPA, or SEVR were observed between the groups., Conclusions: Altered vascular adaptations were detected using measures of arterial stiffness and wave reflection in the early second trimester of pregnant women who developed PrE compared to those who did not. These findings demonstrate the potential clinical utility of arterial stiffness and wave reflection parameters as an early screening tool for PrE, which can be used to inform clinical management of high-risk pregnancies., Competing Interests: Declaration of competing interest The authors have no conflicts of interest. The funding sources had no involvement in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: Regular exercise is known to reduce arterial stiffness (AS) in hemodialysis patients. However, the impact of a more realistic intradialytic form of exercise, such as pedaling, is unclear. We aimed to examine (i) the effect of intradialytic pedaling exercise on AS over 4 months and (ii) the longer term effect of pedaling on AS 4 months after exercise cessation., Methods: Patients on stable in-center hemodialysis (3 x/week) were randomly assigned 1:1 to either intradialytic pedaling exercise (EX) or to a control group receiving usual hemodialysis (nonEX) for 4 months. At baseline and 4 months, peripheral and central blood pressure (BP) indices, heart rate (HR), augmentation index HR corrected (AIx75), and carotid-femoral pulse wave velocity (cfPWV) were assessed (applanation tonometry). Measurements were repeated in the EX group 4 months postexercise cessation., Results: As per protocol analysis was completed in 10 EX group participants (58 ± 17 years, body mass index 26 ± 4 kg/m2) and 10 nonEX group participants (53 ± 15 years, body mass index 27 ± 6 kg/m2). Peripheral and central BP was unchanged in both groups. AIx75 was unchanged in the EX group, however, a significant median increase of 3.5% [interquartile range, IQR 1.0, 8.5] was noted in the nonEX group (P = 0.009). We noted a significantly greater absolute decrease in cfPWV in the EX group compared to controls: -1.00 [IQR -1.95, 0.05] vs. 0.20 [IQR -0.10, 0.90] (P = 0.033). Interestingly, the decrease in cfPWV observed in the EX group was partially reversed 4 months after exercise cessation., Conclusion: Intradialytic pedaling exercise has a beneficial impact on AS. This relationship warrants further investigation., Clinical Trials Registration: Trial Number #NCT03027778 (clinicaltrials.gov).

The objective of this systematic review was to provide insight into the controversy that still abounds as to the impact of acute aerobic exercise on immediate changes in arterial stiffness. Electronic databases were searched to identify articles assessing the effects of acute aerobic exercise on parameters of arterial stiffness. Eligible studies included arterial stiffness measurements before and after acute aerobic exercise in healthy human subjects. Forty-three studies were included. The effect of acute aerobic exercise on arterial stiffness was found to be dependent on the anatomical segment assessed, and on the timing of the measurement post-exercise. Arterial stiffness of the central and upper body peripheral arterial segments was found to be increased relative to resting values immediately post-exercise (0-5 min), whereas, thereafter (>5 min), decreased to a level at or below resting values. In the lower limbs, proximal to the primary working muscles, arterial stiffness decreased immediately post-exercise (0-5 min), which persisted into the recovery period post-exercise (>5 min). This systematic review reveals a differential response to acute exercise in the lower and upper/central arterial segments in healthy adult subjects. We further showed that the effect of acute aerobic exercise on arterial stiffness is dependent on the timing of the measurements post-exercise. Therefore, when assessing the overall impact of exercise on arterial stiffness, it is important to consider the arterial segment being analyzed and measurement time point, as failure to contextualize the measurement can lead to conflicting results and misleading clinical inferences.

Background: Arterial stiffness, a composite indicator of vascular health and predictor of future cardiovascular (CV) disease and events, was assessed in low-risk, uncomplicated pregnancies., Methods: Women with low-risk pregnancy were recruited consecutively (recruitment across the 3 trimesters). Vessel hemodynamics and arterial stiffness were measured every 4 weeks from recruitment until delivery and at 6.5 weeks postpartum., Results: Sixty-three women (maternal age: 32.7 ± 4.9 years) with low-risk, uncomplicated pregnancy were recruited. Mean arterial pressure (P = .04) and aortic pulse pressure (P = .03) decreased during pregnancy, whereas heart rate gradually increased until delivery (P = .0002) and decreased postpartum (P = .06). Pulse pressure amplification (PPA) and carotid-to-radial pulse wave velocity initially decreased in the second trimester, followed by a steady increase until delivery (P = .01 and P = .04, respectively). Interestingly, PPA sharply decreased postpartum (P = .01). Augmentation index and the subendocardial viability ratio significantly increased postpartum (P = .03 and .02, respectively)., Conclusion: The PPA increased steadily after the second trimester and was sharply decreased postpartum in low-risk, uncomplicated pregnancy. Longer and larger longitudinal studies will evaluate changes in PPA and its potential as a marker of CV risk later in women's life., (© The Author(s) 2015.)

Introduction: Endothelin-1 (ET-1) is a potent vasoconstrictor produced by vascular endothelial cells, and a known marker of endothelial dysfunction. However, the acute and chronic effects of smoking and nicotine gum on the ET-1 response to acute physical stress in young healthy smokers have not been investigated., Methods: Healthy smokers (n=35) and non-smokers (n=35) underwent an exercise test to exhaustion (maximal oxygen consumption) on a treadmill. Smokers were assessed a) after 12h smoking abstinence (termed chronic smoking), b) immediately after smoking one cigarette (termed acute smoking), and c) immediately after chewing nicotine gum. Blood was drawn immediately pre-exercise, and 3 minutes post-exercise. During exercise, cardiorespiratory parameters were obtained breath-by-breath using an automated metabolic cart. Plasma ET-1 levels were quantified using enzyme-linked immunosorbent-assay. The above protocol was designed to incorporate exercise as a vascular stressor to reveal changes that would not be detected at rest., Results: Mean age was 28.6±7.2 years and body mass index (BMI) was 23.6±3.2 kg/m(2). Post-exercise ET-1 levels were significantly lower than pre-exercise levels in non-smokers (P<0.001) and smokers under all three conditions (P=0.005, P<0.001, P=0.001, respectively). There were no differences in post-exercise ET-1 levels between non-smokers and smokers under all three conditions, however the absolute and relative decrease in ET-1 levels was significantly smaller in chronic smokers compared with non-smokers (P=0.007 and P=0.004). Chronic smokers had a significantly lower exercise-induced change in tidal volume (P=0.050), fraction of expired CO2 (P=0.021), oxygen consumption (P=0.005), carbon dioxide elimination (P=0.004) and peak expiratory flow (P=0.003) compared with non-smokers. Furthermore, the decrease in ET-1 observed in non-smokers in response to exercise was significantly associated with exercise induced-changes in inspiratory time, time for a tidal volume cycle, respiratory frequency, inspired minute ventilation and peak inspiratory flow., Conclusions: An acute decrease of circulating ET-1 in response to acute maximal exercise in young healthy individuals was noted. Chronic smokers had a significantly diminished decrease in ET-1 compared with non-smokers, however there were no significant differences in the ET-1 response between smokers under the three smoking conditions. Smokers were not able to achieve the same exercise-induced changes in cardiorespiratory parameters as non-smokers. By incorporating exercise as a vascular stressor in our study, we have taken a novel approach to provide evidence of an altered ET-1 and cardiorespiratory response that would not otherwise be observed at rest in young active healthy smokers., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Despite progress in automated blood pressure measurement (BPM) technology, there is limited research linking hard outcomes to automated office BPM (OBPM) treatment targets and thresholds. Equivalences for automated BPM devices have been estimated from approximations of standardized manual measurements of 140/90 mmHg. Until outcome-driven targets and thresholds become available for automated measurement methods, deriving evidence-based equivalences between automated methods and standardized manual OBPM is the next best solution. The MeasureBP study group was initiated by the Canadian Hypertension Education Program to close this critical knowledge gap. MeasureBP aims to define evidence-based equivalent values between standardized manual OBPM and automated BPM methods by synthesizing available evidence using a systematic review and individual subject-level data meta-analyses. This manuscript provides a review of the literature and MeasureBP study protocol. These results will lay the evidenced-based foundation to resolve uncertainties within blood pressure guidelines which, in turn, will improve the management of hypertension.

Background: Irisin, a recently discovered myokine, has been shown to induce browning of white adipose tissue, enhancing energy expenditure and mediating some of the beneficial effects of exercise. We aimed to estimate the time frame of changes in irisin levels after acute exercise and the effect of different exercise workloads and intensities on circulating irisin levels immediately post-exercise., Methods: In a pilot study, four healthy subjects (22.5±1.7 years) underwent maximal workload exercise (maximal oxygen consumption, VO2 max) and blood was drawn at prespecified intervals to define the time frame of pre- and post-exercise irisin changes over a 24-h period. In the main study, 35 healthy, non-smoking (23.0±3.3 years) men and women (n=20/15) underwent three exercise protocols ≥48-h apart, in random order: i) maximal workload (VO2 max); ii) relative workload (70% of VO2 max/10 min); and iii) absolute workload (75 W/10 min). Blood was drawn immediately pre-exercise and 3 min post-exercise., Results: In the pilot study, irisin levels increased by 35% 3 min post-exercise, then dropped and remained relatively constant. In the main study, irisin levels post-exercise were significantly higher than those of pre-exercise after all workloads (all, P<0.001). Post-to-pre-exercise differences in irisin levels were significantly different between workloads (P=0.001), with the greatest increase by 34% following maximal workload (P=0.004 vs relative and absolute)., Conclusions: Circulating irisin levels were acutely elevated in response to exercise, with a greater increase after maximal workload. These findings suggest that irisin release could be a function of muscle energy demand. Future studies need to determine the underlying mechanisms of irisin release and explore irisin's therapeutic potential., (© 2014 European Society of Endocrinology.)

New-onset diabetes has been observed in clinical trials and meta-analyses involving statin therapy. To explain this association, three major mechanisms have been proposed and discussed in the literature. First, certain statins affect insulin secretion through direct, indirect or combined effects on calcium channels in pancreatic β-cells. Second, reduced translocation of glucose transporter 4 in response to treatment results in hyperglycemia and hyperinsulinemia. Third, statin therapy decreases other important downstream products, such as coenzyme Q10, farnesyl pyrophosphate, geranylgeranyl pyrophosphate, and dolichol; their depletion leads to reduced intracellular signaling. Other possible mechanisms implicated in the effect of statins on new-onset diabetes are: statin interference with intracellular insulin signal transduction pathways via inhibition of necessary phosphorylation events and reduction of small GTPase action; inhibition of adipocyte differentiation leading to decreased peroxisome proliferator activated receptor gamma and CCAAT/enhancer-binding protein which are important pathways for glucose homeostasis; decreased leptin causing inhibition of β-cells proliferation and insulin secretion; and diminished adiponectin levels. Given that the magnitude of the risk of new-onset diabetes following statin use remains to be fully clarified and the well-established beneficial effect of statins in reducing cardiovascular risk, statins remain the first-choice treatment for prevention of CVD. Elucidation of the mechanisms underlying the development of diabetes in association with statin use may help identify novel preventative or therapeutic approaches to this problem and/or help design a new generation statin without such side-effects., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The discovery of endothelin (ET) in 1988 has led to considerable effort to unravel its implication in health and disease and the mechanisms evoked by ET. ET-1 and related signaling aberrancies are believed to be implicated in the pathogenesis of diverse cardiovascular diseases, such as hypertension, atherosclerosis, hypertrophy and diabetes. The endothelin system consists of three potent vasoconstrictive isopeptides, ET-1, ET-2 and ET-3, signaling through two G protein coupled receptors, ETA and ETB, which are linked to multiple signaling pathways. Activated signaling transduction pathways include the modulation of the adenylyl cyclase/cAMP pathway through stimulatory (Gs) and inhibitory (Gi) G proteins, activation of the phosphoinositide pathway through the activation of proteins Gq/11, generation of oxidative stress, growth factor receptor-related mitogenic events, such as the activation of phosphatidylinositol-3 kinase pathway, phosphoinositide pathway and activation of the mitogen-activated protein (MAP) kinase cascade. The levels of ETA and ETB receptors as well as the signaling pathways activated by these receptors are altered in several cardiovascular diseases including hypertension, hypertrophy, atherosclerosis, diabetes, etc. In this review, we provide an overview of the signaling events modulated by ET-1 in vascular smooth muscle cells in both physiological and pathological conditions.

Statins are the most powerful lipid lowering drugs in clinical practice. However, the efficacy of statin therapy, as seen in randomized control trials, is undermined by the documented non-adherence observed in clinical practice. Understanding the clinical consequences of statin non-adherence is an important step in implementing successful interventions aimed at improving adherence. Our previous systematic review included a literature search up to January 2010 on the effects of statin non-adherence or discontinuation on cardiovascular (CV) and cerebrovascular outcomes. We provide an update to this publication and a review of promising interventions that have reported a demonstrated improvement in statin adherence. Through a systematic literature search of PubMed, Ovid Medline, Ovid Embase, CINAHL, Cochrane Library and Web of Science, out of the 3440 initially identified, 13 studies were selected. Non-adherence in a primary prevention population was associated with a graded increase in CV risk. Individuals taking statins for secondary prevention were at particular risk when taking statin with highly variable adherence. Moreover, particular attention is warranted for non-adherence in diabetic and rheumatoid arthritis populations, as non-adherence is significantly associated with CV risk as early as 1 month following discontinuation. Statin adherence, therefore, represents an important modifiable risk factor. Numerous interventions to improve adherence have shown promise, including copayment reduction, automatic reminders, mail-order pharmacies, counseling with a health professional, and fixed-dose combination therapy. Given the complexity of causes underlying statin non-adherence, successful strategies will likely need to be tailored to each patient.

Background: Over 100 million women currently use oral contraceptive pills (OCPs) worldwide. However, little is known about the effects of OCPs on arterial stiffness and hemodynamics. Furthermore, whether arterial stiffness and hemodynamics vary throughout the natural menstrual cycle remains controversial. Herein, we estimated the effect of the natural menstrual cycle and OCP use on arterial stiffness and hemodynamics., Methods: Healthy, nonsmoking women, aged 18-30 years, were recruited if they had regular menstrual cycles and never used OCPs (OCP nonuser group), or were using low-dose OCPs for at least 6 months (OCP user group). Using applanation tonometry, three assessments of arterial stiffness and central and peripheral hemodynamics were performed in a randomized order: during the early follicular (days 3-6), late follicular (days 14-16), and luteal (days 22-26) phases. Within group and between group comparisons were performed using general linear models., Results: Sixty women (21.7 ± 2.8 years) were recruited. Compared with OCP nonusers, OCP users had significantly increased aortic and peripheral SBPs during the active OCP use, but not during the inert tablet phase. No differences in arterial stiffness were noted., Conclusion: OCP use was associated with significant increases in aortic and peripheral blood pressures, but not with increased arterial stiffness. Given the widespread OCP use, future longitudinal studies are needed to confirm our findings and assess the long-term effect of OCPs on arterial stiffness and hemodynamics.

Objective: Carotid endarterectomy (CEA) reduces the risk of cerebrovascular events due to the presence of atherosclerotic plaque in the internal carotid artery. Arterial stiffness is an indicator of cardiovascular risk and strongly associates with the development of atherosclerosis. This study aims to assess the short-term effect of CEA on arterial stiffness and haemodynamics., Design: Prospective observational study., Methods: Measurements of arterial stiffness and haemodynamics, including carotid-femoral pulse wave velocity (cfPWV), carotid-radial PWV (crPWV), augmentation pressure, augmentation index, subendocardial viability ratio, central pressures and pulse pressure amplification, were performed pre- and 6 weeks post-CEA on both surgical and non-surgical sides., Results: Fifty-nine patients completed the study (n = 46 men, age 68.9 ± 10.1 years). crPWV was decreased after CEA on the surgical (P = 0.01) and non-surgical side (P = 0.0008), AIx75 tended to decrease only on the surgical side (P = 0.06). cfPWV did not change significantly on either side., Conclusion: We assessed, for the first time, the short-term effect of CEA on arterial stiffness and haemodynamics. CEA improved peripheral but not central arterial stiffness. This study provides evidence for significant changes in certain arterial stiffness and haemodynamic parameters. Longer-term follow-up will assess whether these changes are sustained and whether CEA is associated with further haemodynamic benefits., (Copyright © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

There is controversy as to whether there are sex differences in arterial stiffness. Acute physical stress can elicit vascular abnormalities not present at rest. Our objective was to assess sex differences in arterial stiffness at rest and in response to acute physical stress. Healthy young men (n=67) and women (n=55) underwent pulse wave analysis and carotid-femoral pulse wave velocity measurements at rest and 2, 5, 10 and 15 min following an exercise test to exhaustion. At rest, aortic systolic, diastolic, pulse and mean pressures were all significantly higher in men as was aortic pulse pressure at 10 and 15 min post exercise and aortic systolic pressure at 15 min. Carotid-femoral pulse wave velocity was significantly higher in men (6.0±0.7 m s(-1) vs. 5.6±0.6 m s(-1), P=0.03) at rest and at all time points post exercise. Heart rate-adjusted augmentation index was significantly lower (-10.7±10.2% vs. -4.0±10.9, P<0.0001) and subendocardial viability ratio was significantly higher (176.2±43.8% vs. 163.4±40.9, P=0.04) in men at rest. To our knowledge, this is the first study to assess sex differences in the arterial stiffness response to acute physical stress in young men and women. Although we were not able to elicit differences in vascular function after adjustment, which were not present at rest, we found that young men and women exhibit differences in arterial stiffness at rest and after acute physical stress.

A systematic review and meta-analysis was conducted using MEDLINE, EMBASE, and the Cochrane Library to investigate the association between preeclampsia and arterial stiffness. Twenty-three relevant studies were included. A significant increase in all arterial stiffness indices combined was observed in women with preeclampsia vs. women with normotensive pregnancies [standardized mean difference 1.62, 95% confidence interval (CI) 0.73-2.50]; carotid-femoral pulse wave velocity (cfPWV) and augmentation index (AIx) were also significantly increased (weighted mean difference, WMDcfPWV 1.04, 95% CI 0.34-1.74; WMDAIx 15.10, 95% CI 5.08-25.11), whereas carotid-radial PWV (crPWV) increase did not reach significance (WMDcrPWV 0.99, 95% CI -0.07 to 2.05). Significant increases in arterial stiffness measurements were noted in women with preeclampsia compared with those with gestational hypertension. Arterial stiffness measurements may also be useful in predicting preeclampsia and may play a role in the increased risk of future cardiovascular complications seen in women with a history of preeclampsia.

We earlier showed that the increased expression of Gi proteins exhibited by vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) was attributed to the enhanced levels of endogenous endothelin. Since the levels of angiotensin II (Ang II) are also enhanced in VSMC from SHR, the present study was undertaken to examine the role of enhanced levels of endogenous Ang II in the overexpression of Giα proteins in VSMC from SHR and to further explore the underlying mechanisms responsible for this increase. The enhanced expression of Giα-2 and Giα-3 proteins in VSMC from SHR compared to WKY was attenuated by the captopril, losartan and AG1478, inhibitors of angiotensin converting enzyme, AT(1) receptor and epidermal growth factor receptor (EGFR) respectively as well as by the siRNAs of AT1, cSrc and EGFR. The enhanced inhibition of forskolin-stimulated adenylyl cyclase activity by low concentrations of GTPγS (receptor-independent functions) and of inhibitory responses of hormones on adenylyl cyclase activity (receptor-dependent functions) in VSMC from SHR was also attenuated by losartan. Furthermore, the enhanced phosphorylation of EGFR in VSMC from SHR was also restored to control levels by captopril, losartan, PP2, a c-Src inhibitor and N-acetyl-L-cysteine (NAC), superoxide anion (O(2)(-)) scavenger, whereas enhanced ERK1/2 phosphorylation was attenuated by captopril and losartan. Furthermore, NAC also restored the enhanced phosphorylation of c-Src in SHR to control levels. These results suggest that the enhanced levels of endogenous Ang II in VSMC from SHR, transactivate EGFR, which through MAP kinase signaling, enhance the expression of Giα proteins and associated adenylyl cyclase signaling., (Copyright © 2011. Published by Elsevier Inc.)