Hyaluronan Receptor LYVE-1-Expressing Macrophages Maintain Arterial Tone through Hyaluronan-Mediated Regulation of Smooth Muscle Cell Collagen.

The maintenance of appropriate arterial tone is critically important for normal physiological arterial function. However, the cellular and molecular mechanisms remain poorly defined. Here, we have shown that in the mouse aorta, resident macrophages prevented arterial stiffness and collagen deposition in the steady state. Using phenotyping, transcriptional profiling, and targeted deletion of Csf1r, we have demonstrated that these macrophages-which are a feature of blood vessels invested with smooth muscle cells (SMCs) in both mouse and human tissues-expressed the hyaluronan (HA) receptor LYVE-l. Furthermore, we have shown they possessed the unique ability to modulate collagen expression in SMCs by matrix metalloproteinase MMP-9-dependent proteolysis through engagement of LYVE-1 with the HA pericellular matrix of SMCs. Our study has unveiled a hitherto unknown homeostatic contribution of arterial LYVE-1+ macrophages through the control of collagen production by SMCs and has identified a function of LYVE-1 in leukocytes.

Calponin 1 inhibits agonist-induced ERK activation and decreases calcium sensitization in vascular smooth muscle.

Smooth muscle cell (SMC) contraction and vascular tone are modulated by phosphorylation and multiple modifications of the thick filament, and thin filament regulation of SMC contraction has been reported to involve extracellular regulated kinase (ERK). Previous studies in ferrets suggest that the actin-binding protein, calponin 1 (CNN1), acts as a scaffold linking protein kinase C (PKC), Raf, MEK and ERK, promoting PKC-dependent ERK activation. To gain further insight into this function of CNN1 in ERK activation and the regulation of SMC contractility in mice, we generated a novel Calponin 1 knockout mouse (Cnn1 KO) by a single base substitution in an intronic CArG box that preferentially abolishes expression of CNN1 in vascular SMCs. Using this new Cnn1 KO mouse, we show that ablation of CNN1 has two effects, depending on the cytosolic free calcium level: (1) in the presence of elevated intracellular calcium caused by agonist stimulation, Cnn1 KO mice display a reduced amplitude of stress and stiffness but an increase in agonist-induced ERK activation; and (2) during intracellular calcium depletion, in the presence of an agonist, Cnn1 KO mice exhibit increased duration of SM tone maintenance. Together, these results suggest that CNN1 plays an important and complex modulatory role in SMC contractile tone amplitude and maintenance.

Impact of arterial stiffness on cerebrovascular function: a review of evidence from humans and preclincal models.

With advancing age, the cerebral vasculature becomes dysfunctional, and this dysfunction is associated with cognitive decline. However, the initiating cause of these age-related cerebrovascular impairments remains incompletely understood. A characteristic feature of the aging vasculature is the increase in stiffness of the large elastic arteries. This increase in arterial stiffness is associated with elevated pulse pressure and blood flow pulsatility in the cerebral vasculature. Evidence from both humans and rodents supports that increases in large elastic artery stiffness are associated with cerebrovascular impairments. These impacts on cerebrovascular function are wide-ranging and include reductions in global and regional cerebral blood flow, cerebral small vessel disease, endothelial cell dysfunction, and impaired perivascular clearance. Furthermore, recent findings suggest that the relationship between arterial stiffness and cerebrovascular function may be influenced by genetics, specifically APOE and NOTCH genotypes. Given the strength of the evidence that age-related increases in arterial stiffness have deleterious impacts on the brain, interventions that target arterial stiffness are needed. The purpose of this review is to summarize the evidence from human and rodent studies, supporting the role of increased arterial stiffness in age-related cerebrovascular impairments.

Short-term vascular responses to spring and fall daylight savings time shifts.

Daylight saving time (DST) is a Western biannual time transition, setting the clock back 1 h in the fall and forward 1 h in the spring. There is an epidemiological link between DST and acute myocardial infarction risk in the first week following the spring shift; however, the mechanisms underlying the effect of DST on cardiovascular function remain unclear. The purpose of this study was to explore the short-term cardiovascular changes induced by fall and spring shifts in DST in a convenience sample of healthy adults. We hypothesized that spring, but not fall, DST shifts would acutely increase central pulse wave velocity, the gold standard measurement of central arterial stiffness. Twenty-one individuals (fall: n = 10; spring: n = 11) participated in four visits, occurring 1 wk before and at +1, +3, and +5 days after spring and fall time transitions. Central, brachial, and radial pulse wave velocity as well as carotid augmentation index were assessed with applanation tonometry. Sleep quality and memory function were assessed via questionnaire and the Mnemonic Similarities Task, respectively. Neither fall or spring transition resulted in changes to cardiovascular variables (carotid-femoral pulse wave velocity, carotid-brachial pulse wave velocity, carotid-radial pulse wave velocity, heart rate, mean arterial pressure, or augmentation index), sleep quality, or cognitive function (all P > 0.05). Our findings do not provide evidence that DST shifts influence cardiovascular outcomes in healthy adults. This study emphasizes the need for further research to determine the mechanisms of increased cardiovascular disease risk with DST that help explain epidemiological trends.NEW & NOTEWORTHY The debate of whether to abolish daylight savings time (DST) is, in part, motivated by the population-level increase in all-cause mortality and incidence of cardiovascular events following DST; however, there is an absence of data to support a physiological basis for risk. We found no changes in pulse wave velocity or augmentation index during the subacute window of DST. Large multisite trials are necessary to address the small, but meaningful, effects brought on by a societal event.

Role of the circulating milieu in age-related arterial dysfunction: a novel ex vivo approach.

The circulating milieu, bioactive molecules in the bloodstream, is altered with aging and interfaces constantly with the vasculature. This anatomic juxtaposition suggests that circulating factors may actively modulate arterial function. Here, we developed a novel, translational experimental model that allows for direct interrogation of the influence of the circulating milieu on age-related arterial dysfunction (aortic stiffening and endothelial dysfunction). To do so, we exposed young and old mouse arteries to serum from young and old mice and young and midlife/older (ML/O) adult humans. We found that old mouse and ML/O adult human, but not young, serum stiffened young mouse aortic rings, assessed via elastic modulus (mouse and human serum, P = 0.003 vs. young serum control), and impaired carotid artery endothelial function, assessed by endothelium-dependent dilation (EDD) (mouse serum, P < 0.001; human serum, P = 0.006 vs. young serum control). Furthermore, young mouse and human, but not old, serum reduced aortic elastic modulus (mouse serum, P = 0.009; human serum, P < 0.001 vs. old/MLO serum control) and improved EDD (mouse and human serum, P = 0.015 vs. old/MLO serum control) in old arteries. In human serum-exposed arteries, in vivo arterial function assessed in the human donors correlated with circulating milieu-modulated arterial function in young mouse arteries (aortic stiffness, r = 0.634, P = 0.005; endothelial function, r = 0.609, P = 0.004) and old mouse arteries (aortic stiffness, r = 0.664, P = 0.001; endothelial function, r = 0.637, P = 0.003). This study establishes novel experimental approaches for directly assessing the effects of the circulating milieu on arterial function and implicates changes in the circulating milieu as a mechanism of in vivo arterial aging.NEW & NOTEWORTHY Changes in the circulating milieu with advancing age may be a mechanism underlying age-related arterial dysfunction. Ex vivo exposure of young mouse arteries to the circulating milieu from old mice or midlife/older adults impairs arterial function whereas exposure of old mouse arteries to the circulating milieu from young mice or young adults improves arterial function. These findings establish that the circulating milieu directly influences arterial function with aging.

Effects of regular exercise on vascular function with aging: Does sex matter?

Vascular aging, featuring endothelial dysfunction and large elastic artery stiffening, is a major risk factor for the development of age-associated cardiovascular diseases (CVDs). Vascular aging is largely mediated by an excessive production of reactive oxygen species (ROS) and increased inflammation leading to reduced bioavailability of the vasodilatory molecule nitric oxide and remodeling of the arterial wall. Other cellular mechanisms (i.e., mitochondrial dysfunction, impaired stress response, deregulated nutrient sensing, cellular senescence), termed "hallmarks" or "pillars" of aging, may also contribute to vascular aging. Gonadal aging, which largely impacts women but also impacts some men, modulates the vascular aging process. Regular physical activity, including both aerobic and resistance exercise, is a first-line strategy for reducing CVD risk with aging. Although exercise is an effective intervention to counter vascular aging, there is considerable variation in the vascular response to exercise training with aging. Aerobic exercise improves large elastic artery stiffening in both middle-aged/older men and women and enhances endothelial function in middle-aged/older men by reducing oxidative stress and inflammation and preserving nitric oxide bioavailability; however, similar aerobic exercise training improvements are not consistently observed in estrogen-deficient postmenopausal women. Sex differences in adaptations to exercise may be related to gonadal aging and declines in estrogen in women that influence cellular-molecular mechanisms, disconnecting favorable signaling in the vasculature induced by exercise training. The present review will summarize the current state of knowledge on vascular adaptations to regular aerobic and resistance exercise with aging, the underlying mechanisms involved, and the moderating role of biological sex.

Adverse pregnancy outcomes and renal-vascular function in the early years after delivery.

Adverse pregnancy outcomes (APOs: hypertensive disorders, gestational diabetes, preterm birth, and placental disorders) are associated with cardiovascular disease risk or blood volume abnormalities. Traditional risk factors might not identify highest risk people in the early years after APO deliveries. Test the hypothesis that vascular function is worse, and plasma volume-regulating renal hormones are lower after delivery in people who did versus did not have an APO. Adult participants 6 mo-3 years postdelivery of a singleton infant participated in this cross-sectional study. Exclusion criteria included current smoking, current use of certain medications, and diabetes outside of pregnancy. Differences in measurements between participants with versus without APOs were determined with t tests or Wilcoxon tests. Associations of renal hormones with APO history were assessed with linear regression, adjusted for age, race, body mass index (BMI), and sodium consumption. Of 86 participants, 38 (44%) had an APO history. Those with APOs were more likely to identify as Black and had a higher BMI, 34.0 kg/m2 [interquartile range (IQR), 24.6, 39.3] versus 24.2 kg/m2 [IQR, 21.2, 31.3], P < 0.05. Most brachial and all aortic blood pressures were higher in those with APOs: median aortic blood pressure was 102/74 versus 96/68 mmHg, P ≤ 0.05. There were no differences in arterial stiffness or endothelial function between groups. Aldosterone was lower (54 [IQR, 28-84] vs. 80 [IQR, 39-150] pmol/L) in participants with past APOs. Blood pressures were higher, and aldosterone was lower in participants with past APOs. Associations of aldosterone with APO history persisted after adjustment. Neither renin nor aldosterone were related to vascular function.NEW & NOTEWORTHY Adverse pregnancy outcomes (APOs) are associated with cardiovascular disease (CVD) risk. Traditional CVD risk factors may not fully capture excess CVD risk soon after APOs. Vascular dysfunction and plasma volume irregularities may be detectable. We found people with APOs had worse blood pressures, higher BMI, and lower aldosterone levels versus those without APOs in the early years after delivery. Vascular function was similar between groups. Future research should assess vascular function and renal hormones at multiple timepoints during the perinatal period.

Systemic hemodynamics and pediatric lung disease: Mechanistic links and therapeutic relevance.

Chronic lung disease, also known as bronchopulmonary dysplasia affects thousands of infants worldwide each year. The impact on resources is second only to bronchial asthma, with lung function affected well into adolescence. Diagnostic and therapeutic constructs have almost exclusively focussed on pulmonary architecture (alveoli/airways) and pulmonary hypertension. Information on systemic hemodynamics indicates major artery thickness/stiffness, elevated systemic afterload and/or primary left ventricular dysfunction may play a part in a subset of infants with severe neonatal-pediatric lung disease. Understanding the underlying principles with attendant effectors would aid in identifying the pathophysiological course where systemic afterload reduction with angiotensin converting enzyme inhibitors could become the preferred treatment strategy over conventional pulmonary artery vasodilatation.

The gut microbiome as a modulator of arterial function and age-related arterial dysfunction.

The arterial system is integral to the proper function of all other organs and tissues. Arterial function is impaired with aging, and arterial dysfunction contributes to the development of numerous age-related diseases, including cardiovascular diseases. The gut microbiome has emerged as an important regulator of both normal host physiological function and impairments in function with aging. The purpose of this review is to summarize more recently published literature demonstrating the role of the gut microbiome in supporting normal arterial development and function and in modulating arterial dysfunction with aging in the absence of overt disease. The gut microbiome can be altered due to a variety of exposures, including physiological aging processes. We explore mechanisms by which the gut microbiome may contribute to age-related arterial dysfunction, with a focus on changes in various gut microbiome-related compounds in circulation. In addition, we discuss how modulating circulating levels of these compounds may be a viable therapeutic approach for improving artery function with aging. Finally, we identify and discuss various experimental considerations and research gaps/areas of future research.

Arterial stiffness tested by pulse wave velocity and augmentation index for cardiovascular risk stratification in antiphospholipid syndrome.

OBJECTIVES: Cardiovascular disease is a major cause of morbidity and mortality in Antiphospholipid syndrome (APS). Arterial stiffness (ArS) has emerged as a predictor of future cardiovascular events in the general population. We aimed to assess ArS in patients with thrombotic APS versus diabetes mellitus (DM) and healthy controls (HC) and identify predictors of increased ArS in APS. METHODS: ArS was evaluated by carotid-femoral pulse wave velocity (cfPWV) and augmentation index normalized to 75 beats/min (AIx@75) using the SphygmoCor device. Participants also underwent carotid/femoral ultrasound for atherosclerotic plaque detection. We used linear regression to compare ArS measures among groups and assess ArS determinants in the APS group. RESULTS: We included 110 patients with APS (70.9% female, mean age 45.4 years), 110 DM patients and 110 HC, all age/sex matched. After adjustment for age, sex, cardiovascular risk factors and plaque presence, APS patients exhibited similar cfPWV [ß = -0.142 (95% CI -0.514, 0.230), p = 0.454] but increased AIx@75 [ß = 4.525 (95% CI 1.372, 7.677), p = 0.005] compared with HC and lower cfPWV (p < 0.001) but similar AIx@75 (p = 0.193) versus DM patients. In the APS group, cfPWV was independently associated with age [ß = 0.056 (95% CI 0.034, 0.078), p < 0.001], mean arterial pressure (MAP) [ß = 0.070 (95% CI 0.043, 0.097), p < 0.001], atherosclerotic femoral plaques [ß = 0.732 (95% CI 0.053, 1.411), p = 0.035] and anti-ß2-glycoprotein I IgM positivity [ß = 0.696 (95% CI 0.201, 1.191), p = 0.006]. AIx@75 was associated with age [ß = 0.334 (95% CI 0.117, 0.551), p = 0.003], female sex [ß = 7.447 (95% CI 2.312, 12.581), p = 0.005] and MAP [ß = 0.425 (95% CI 0.187, 0.663), p = 0.001]. CONCLUSION: APS patients exhibit elevated AIx@75 vs HC and similar to DM patients, indicating enhanced arterial stiffening in APS. Given its prognostic value, ArS evaluation may help to improve cardiovascular risk stratification in APS.

Mean platelet volume (MPV) as new marker of diabetic macrovascular complications in patients with different glucose homeostasis : Platelets in cardiovascular risk.

BACKGROUND: Platelets play an important role in the development of cardiovascular disease (CVD). Mean platelet volume (MPV) is considered as biological marker of platelets activity and function. The aim of the present study was to evaluate MPV values and its possible correlation with arterial stiffness and subclinical myocardial damage, in normal glucose tolerance patients (NGT), in newly diagnosed type 2 diabetic (T2DM) patients and in individuals with pre-diabetes. METHODS: We enrolled 400 newly diagnosed hypertensive patients. All patients underwent an Oral Glucose Tolerance test (OGTT). Arterial stiffness (AS) was evaluated with the measurement of carotid-femoral pulse wave velocity (PWV), augmentation pressure (AP) and augmentation index (AI). Echocardiographic recordings were performed using an E-95 Pro ultrasound system. RESULTS: Among groups there was an increase in fasting plasma glucose (FPG) (p < 0.0001), fasting plasma insulin (FPI) (p < 0.0001), high sensitivity c reactive protein (hs-CRP) levels (p < 0.0001) and a decrease in renal function as demonstrated by e-GFR values (p < 0.0001). From the NGT group to the T2DM group there was a rise in MPV value (p < 0.0001). Moreover, in the evaluation of arterial stiffness and subclinical myocardial damage, MPV showed a positive correlation with these parameters. CONCLUSIONS: In the present study we highlighted that MPV is significantly increased, not only in newly diagnosed T2DM patients, but also in early stage of diabetes, indicating that subjects with pre-diabetes present increased platelets reactivity. Moreover, our results suggest that MPV is associated with increased arterial stiffness and subclinical myocardial damage, indicating MPV as new marker of CV risk.

Extracellular Vesicles in Metabolic and Vascular Insulin Resistance.

BACKGROUND: Insulin resistance is a major etiological factor in obesity, type 2 diabetes, and cardiovascular disease (CVD). Endothelial dysfunction may precede impairments in insulin-stimulated glucose uptake, thereby making it a key feature in development of CVD. However, the mechanism by which vascular tissue becomes dysfunctional is not clear. SUMMARY: Extracellular vesicles (EVs) have emerged as potential mediators of insulin resistance and vascular dysfunction. EVs are membrane-bound particles released by tissues following cellular stress or activation. They carry "cargo" (e.g., insulin signaling proteins, eNOS-nitric oxide, and miRNA) that are believed to promote inter-cellular and interorgan communications. Herein, we review the underlying physiology of EVs in relation to type 2 diabetes and CVD risk. Specifically, we discuss how EVs may modulate metabolic (e.g., skeletal muscle, liver, and adipose) insulin sensitivity, and propose that EVs may modulate vascular insulin action to influence both endothelial function and arterial stiffness. We lastly identify how EVs may play a unique role following exercise to promote metabolic and vascular insulin sensitivity changes. KEY MESSAGE: Gaining insight toward insulin-mediated EV mechanism has potential to identify novel pathways regulating cardiometabolic health and provide foundation for examining EVs as unique biomarkers and targets to prevent and/or treat chronic diseases.

Maternal self-reported polycystic ovary syndrome with offspring and maternal cardiometabolic outcomes.

STUDY QUESTION: Do children born to mothers with polycystic ovary syndrome (PCOS) have an adverse cardiometabolic profile including arterial stiffness at 9 years of age compared to other children? SUMMARY ANSWER: Children of mothers with PCOS did not have differing cardiometabolic outcomes than children without exposure. WHAT IS KNOWN ALREADY: While women with PCOS themselves have higher risk of cardiometabolic conditions such as obesity and diabetes, the evidence on intergenerational impact is unclear. Given in utero sequalae of PCOS (e.g. hyperandrogenism, insulin resistance), the increased risk could be to both boys and girls. STUDY DESIGN, SIZE, DURATION: The Upstate KIDS cohort is a population-based birth cohort established in 2008-2010 to prospectively study the impact of infertility treatment on children's health. After ∼10 years of follow-up, 446 mothers and their 556 children attended clinical visits to measure blood pressure (BP), heart rate, arterial stiffness by pulse wave velocity (PWV), mean arterial pressure, lipids, high-sensitivity C-reactive protein (hsCRP), hemoglobin A1c (HbA1c), and anthropometrics. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women self-reported ever diagnoses of PCOS ∼4 months after delivery of their children in 2008-2010. Linear regression models applying generalized estimating equations to account for correlation within twins were used to examine associations with each childhood cardiometabolic outcome. MAIN RESULTS AND THE ROLE OF CHANCE: In this cohort with women oversampled on infertility treatment, ∼14% of women reported a PCOS diagnosis (n = 61). We observed similarities in BP, heart rate, PWV, lipids, hsCRP, HbA1c, and anthropometry (P-values >0.05) among children born to mothers with and without PCOS. Associations did not differ by child sex. LIMITATIONS, REASONS FOR CAUTION: The sample size of women with PCOS precluded further separation of subgroups (e.g. by hirsutism). The population-based approach relied on self-reported diagnosis of maternal PCOS even though self-report has been found to be valid. Participants were predominantly non-Hispanic White and a high proportion were using fertility treatment due to the original design. Differences in cardiometabolic health may be apparent later in age, such as after puberty. WIDER IMPLICATIONS OF THE FINDINGS: Our results provide some reassurance that cardiometabolic factors do not differ in children of women with and without self-reported PCOS during pregnancy. STUDY FUNDING/COMPETING INTEREST(S): Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, United States (contracts #HHSN275201200005C, #HHSN267200700019C, #HHSN275201400013C, #HHSN275201300026I/27500004, #HHSN275201300023I/27500017). The authors have no conflicts of interest. REGISTRATION NUMBER: NCT03106493.

Paravascular fluid dynamics reveal arterial stiffness assessed using dynamic diffusion-weighted imaging.

Paravascular cerebrospinal fluid (pCSF) surrounding the cerebral arteries within the glymphatic system is pulsatile and moves in synchrony with the pressure waves of the vessel wall. Whether such pulsatile pCSF can infer pulse wave propagation-a property tightly related to arterial stiffness-is unknown and has never been explored. Our recently developed imaging technique, dynamic diffusion-weighted imaging (dynDWI), captures the pulsatile pCSF dynamics in vivo and can explore this question. In this work, we evaluated the time shifts between pCSF waves and finger pulse waves, where pCSF waves were measured by dynDWI and finger pulse waves were measured by the scanner's built-in finger pulse oximeter. We hypothesized that the time shifts reflect brain-finger pulse wave travel time and are sensitive to arterial stiffness. We applied the framework to 36 participants aged 18-82 years to study the age effect of travel time, as well as its associations with cognitive function within the older participants (N = 15, age > 60 years). Our results revealed a strong and consistent correlation between pCSF pulse and finger pulse (mean CorrCoeff = 0.66), supporting arterial pulsation as a major driver for pCSF dynamics. The time delay between pCSF and finger pulses (TimeDelay) was significantly lower (i.e., faster pulse propagation) with advanced age (Pearson's r = -0.44, p = 0.007). Shorter TimeDelay was further associated with worse cognitive function in the older participants. Overall, our study demonstrated pCSF as a viable pathway for measuring intracranial pulses and encouraged future studies to investigate its relevance with cerebrovascular functions.

Association of Lipoprotein(a) with arterial stiffness: A Mendelian randomization study.

BACKGROUND: In this study we used Mendelian randomization (MR) to investigate the potential causal association of lipoprotein (a) [Lp(a)] levels with pulse wave velocity (PWV). METHODS: Genetic variants associated with Lp(a) were retrieved from the UK Biobank GWAS (N = 290,497). A non- overlapping GWAS based on a European cohort (N = 7,000) was used to obtain genetic associations with PWV (outcome) and utilized two different measures for the same trait, brachial-ankle (baPWV) and carotid-femoral (cfPWV) PWV. We applied a two-sample MR using the inverse variance weighting method (IVW) and a series of sensitivity analyses for 170 SNPs that were selected as instrumental variables (IVs). RESULTS: Our analyses do not support a causal association between Lp(a) and PWV for neither measurement [ßiwv(baPWV) = -.0005, p = .8 and ßiwv(cfPWV) = -.006, p = .16]. The above findings were consistent across sensitivity analyses including weighted median, mode-based estimation, MR-Egger regression and MR-PRESSO. CONCLUSION: We did not find evidence indicating that Lp(a) is causally associated with PWV, the gold standard marker of arterial stiffness.

Maternal vascular indices at 36 weeks' gestation in the prediction of preeclampsia.

BACKGROUND: Epidemiological studies have shown that women with preeclampsia (PE) are at increased long term cardiovascular risk. This risk might be associated with accelerated vascular ageing process but data on vascular abnormalities in women with PE are scarce. OBJECTIVE: This study aimed to identify the most discriminatory maternal vascular index in the prediction of PE at 35 to 37 weeks' gestation and to examine the performance of screening for PE by combinations of maternal risk factors and biophysical and biochemical markers at 35 to 37 weeks' gestation. STUDY DESIGN: This was a prospective observational nonintervention study in women attending a routine hospital visit at 35 0/7 to 36 6/7 weeks' gestation. The visit included recording of maternal demographic characteristics and medical history, vascular indices, and hemodynamic parameters obtained by a noninvasive operator-independent device (pulse wave velocity, augmentation index, cardiac output, stroke volume, central systolic and diastolic blood pressures, total peripheral resistance, and fetal heart rate), mean arterial pressure, uterine artery pulsatility index, and serum concentration of placental growth factor and soluble fms-like tyrosine kinase-1. The performance of screening for delivery with PE at any time and at <3 weeks from assessment using a combination of maternal risk factors and various combinations of biomarkers was determined. RESULTS: The study population consisted of 6746 women with singleton pregnancies, including 176 women (2.6%) who subsequently developed PE. There were 3 main findings. First, in women who developed PE, compared with those who did not, there were higher central systolic and diastolic blood pressures, pulse wave velocity, peripheral vascular resistance, and augmentation index. Second, the most discriminatory indices were systolic and diastolic blood pressures and pulse wave velocity, with poor prediction from the other indices. However, the performance of screening by a combination of maternal risk factors plus mean arterial pressure was at least as high as that of a combination of maternal risk factors plus central systolic and diastolic blood pressures; consequently, in screening for PE, pulse wave velocity, mean arterial pressure, uterine artery pulsatility index, placental growth factor, and soluble fms-like tyrosine kinase-1 were used. Third, in screening for both PE within 3 weeks and PE at any time from assessment, the detection rate at a false-positive rate of 10% of a biophysical test consisting of maternal risk factors plus mean arterial pressure, uterine artery pulsatility index, and pulse wave velocity (PE within 3 weeks: 85.2%; 95% confidence interval, 75.6%-92.1%; PE at any time: 69.9%; 95% confidence interval, 62.5%-76.6%) was not significantly different from a biochemical test using the competing risks model to combine maternal risk factors with placental growth factor and soluble fms-like tyrosine kinase-1 (PE within 3 weeks: 80.2%; 95% confidence interval, 69.9%-88.3%; PE at any time: 64.2%; 95% confidence interval, 56.6%-71.3%), and they were both superior to screening by low placental growth factor concentration (PE within 3 weeks: 53.1%; 95% confidence interval, 41.7%-64.3%; PE at any time: 44.3; 95% confidence interval, 36.8%-52.0%) or high soluble fms-like tyrosine kinase-1-to-placental growth factor concentration ratio (PE within 3 weeks: 65.4%; 95% confidence interval, 54.0%-75.7%; PE at any time: 53.4%; 95% confidence interval, 45.8%-60.9%). CONCLUSION: First, increased maternal arterial stiffness preceded the clinical onset of PE. Second, maternal pulse wave velocity at 35 to 37 weeks' gestation in combination with mean arterial pressure and uterine artery pulsatility index provided effective prediction of subsequent development of preeclampsia.

Update on the Use of Pulse Wave Velocity to Measure Age-Related Vascular Changes.

PURPOSE OF REVIEW: Pulse wave velocity (PWV) is an important and well-established measure of arterial stiffness that is strongly associated with aging. Age-related alterations in the elastic properties and integrity of arterial walls can lead to cardiovascular disease. PWV measurements play an important role in the early detection of these changes, as well as other cardiovascular disease risk factors, such as hypertension. This review provides a comprehensive summary of the current knowledge of the effects of aging on arterial stiffness, as measured by PWV. RECENT FINDINGS: This review highlights recent findings showing the applicability of PWV analysis for investigating heart failure, hypertension, and other cardiovascular diseases, as well as cerebrovascular diseases and Alzheimer's disease. It also discusses the clinical implications of utilizing PWV to monitor treatment outcomes, various challenges in implementing PWV assessment in clinical practice, and the development of new technologies, including machine learning and artificial intelligence, which may improve the usefulness of PWV measurements in the future. Measuring arterial stiffness through PWV remains an important technique to study aging, especially as the technology continues to evolve. There is a clear need to leverage PWV to identify interventions that mitigate age-related increases in PWV, potentially improving CVD outcomes and promoting healthy vascular aging.

Association Between Arterial Stiffness and New-Onset Heart Failure: The Kailuan Study.

BACKGROUND: Arterial stiffness (AS) was associated with heart failure (HF) in previous studies based on specific populations with small samples and the effects of age and blood pressure on AS were not taken into account. Whether AS was independently associated with new-onset HF in community dwellers has not been fully investigated to date. METHODS: Individuals who participated in health evaluations and underwent synchronized brachial-ankle pulse wave velocity (baPWV) screening in 2010 to 2019 were included. They were free of HF and atrial fibrillation at baseline. The participants were allocated to 3 groups according to their baPWV values. Normal AS was defined as baPWV <1400 cm/s, borderline AS was defined as 1400≤baPWV<1800 cm/s, and elevated AS was defined as baPWV ≥1800 cm/s. Cox proportional hazard regression was used to calculate hazard ratios with 95% CIs of new-onset HF across different AS groups. RESULTS: A total of 40 064 participants were enrolled with a mean age of 48.81±12.67 years. During a mean 5.53 years of follow-up, 411 participants developed HF. Compared with the normal AS group, the hazard ratio (95% CI) for incident HF was 1.97 (1.36-2.86) for the borderline AS group and 2.24 (1.49-3.38) for the elevated AS group in the multivariable-adjusted model. For each 1 SD (359 cm/s) increase in baPWV, the hazard ratio (95% CI) for new-onset HF was 1.10 (1.02-1.20). CONCLUSIONS: AS was positively associated with a higher risk of new-onset HF independently of traditional risk factors, with a dose-responsive effect.

Estimated Pulse Wave Velocity Predicts All-Cause and Cardiovascular-Cause Mortality in Individuals With Hypertension　- Findings From a National Health and Nutrition Examination Study 1999-2018.

BACKGROUND: This study aimed to investigate the association between estimated pulse wave velocity (ePWV) and mortality outcomes among individuals with hypertension.Methods and Results: Based on the National Health and Nutrition Examination Survey (NHANES) 1999-2018, a total of 14,396 eligible participants with hypertension were enrolled. The ePWV was calculated using the equation based on blood pressure and age. The mortality outcomes of included participants were directly acquired from the National Death Index database. The multivariable Cox regression analysis was used to examine the relationship between ePWV and mortality outcomes. Moreover, the restricted cubic spline (RCS) was also used to explore this relationship. Receiver operating characteristics curves (ROC) were adopted to evaluate the prognostic ability of ePWV for predicting mortality outcomes of patients with hypertension. The median follow-up duration was 10.8 years; individuals with higher an ePWV had higher risks of mortality from both all causes (HR: 2.79, 95% CI: 2.43-3.20) and cardiovascular diseases (HR: 3.41, 95% CI: 2.50-4.64). After adjusting for confounding factors, each 1 m/s increase in ePWV was associated with a 43% increase in all-cause mortality risk (HR: 1.43, 95% CI: 1.37-1.48) and a 54% increase in cardiovascular mortality risk (HR: 1.54, 95% CI: 1.43-1.66). CONCLUSIONS: This study indicates that ePWV is a novel prognostic indicator for predicting the risks of mortality among patients with hypertension.

Maternal vascular indices at 36 weeks' gestation in small and growth restricted fetuses.

OBJECTIVE: To compare maternal vascular indices and hemodynamic parameters at 35-37 weeks' gestation, in pregnancies complicated by small for gestational age (SGA) fetuses and those with fetal growth restriction (FGR). METHODS: This was a prospective observational non-intervention study in women with singleton pregnancies attending for a routine hospital visit at 35+0 to 36+6 weeks' gestation. The visit included recording of maternal demographic characteristics and medical history, vascular indices and hemodynamic parameters obtained by a non-invasive operator independent device, including pulse wave velocity, augmention index, cardiac output, stroke volume, central systolic and diastolic blood pressure, total peripheral resistance and fetal heart rate. Hypertensive disorders of pregnancy were excluded and the values in the SGA and FGR groups were compared between them and with unaffected pregnancies. Diagnosis of SGA was based on the birth of a baby with birthweight below the 10th percentile for gestational age. In FGR, in addition to a birthweight below the 10th percentile, at the 35-37 weeks scan Doppler studies had shown that the uterine artery or umbilical artery pulsatility index (PI) was above the 95th percentile for gestational age or the fetal middle cerebral artery PI was below the 5th percentile. RESULTS: In the 6,413 women included in the study there were 605 (9.4%) cases of SGA, 133 (2.1%) of FGR and 5,675 (88.5%) unaffected by SGA or FGR. Women with SGA or FGR, compared to unaffected pregnancies, had increased peripheral vascular resistance and reduced cardiac output. Central systolic and diastolic blood pressure were also increased, whereas aortic stiffness assessed by pulse wave velocity and augmentation index did not differ between affected and unaffected pregnancies. In the FGR, compared to the SGA group, central systolic and diastolic blood pressure were higher, whereas, heart rate was lower. CONCLUSIONS: In SGA and FGR pregnancies there are deranged maternal hemodynamic responses when these are compared to normal pregnancies. Mothers with FGR babies have higher central blood pressure compared to SGA ones, but it remains unclear whether these differences are driven by the size of the fetus or pathological fetal growth. This article is protected by copyright. All rights reserved.