Immunotherapy targeting isoDGR-protein damage extends lifespan in a mouse model of protein deamidation.

Aging results from the accumulation of molecular damage that impairs normal biochemical processes. We previously reported that age-linked damage to amino acid sequence NGR (Asn-Gly-Arg) results in "gain-of-function" conformational switching to isoDGR (isoAsp-Gly-Arg). This integrin-binding motif activates leukocytes and promotes chronic inflammation, which are characteristic features of age-linked cardiovascular disorders. We now report that anti-isoDGR immunotherapy mitigates lifespan reduction of Pcmt1-/- mouse. We observed extensive accumulation of isoDGR and inflammatory cytokine expression in multiple tissues from Pcmt1-/- and naturally aged WT animals, which could also be induced via injection of isoDGR-modified plasma proteins or synthetic peptides into young WT animals. However, weekly injection of anti-isoDGR mAb (1 mg/kg) was sufficient to significantly reduce isoDGR-protein levels in body tissues, decreased pro-inflammatory cytokine concentrations in blood plasma, improved cognition/coordination metrics, and extended the average lifespan of Pcmt1-/- mice. Mechanistically, isoDGR-mAb mediated immune clearance of damaged isoDGR-proteins via antibody-dependent cellular phagocytosis (ADCP). These results indicate that immunotherapy targeting age-linked protein damage may represent an effective intervention strategy in a range of human degenerative disorders.

Childhood household dysfunction is associated with reduced left ventricular mass in young adulthood.

The effect of adverse childhood experiences (ACEs) on left ventricular mass (LVM) and left ventricular function remains largely unknown across the lifespan. This study investigated the influence of ACEs on LVM and left ventricular function and whether inflammation influences this relationship. Two hundred forty-eight healthy young adults participated and a final sample of 217 (age, 22.6 ± 0.1 yr; females, 114) had complete data. Echocardiographic assessment of LVM was indexed to height2.7 (LVMHT) and body surface area (LVMBSA). Ejection fraction (EF) and fractional shortening were also assessed. Interleukin-6 (IL-6), C-reactive protein, tumor necrosis factor-α, and matrix metalloproteinase (MMP) 1-3 were measured and ACEs exposures were assessed based on exposure and nonexposure to childhood household dysfunction and maltreatment, and quantity of adversity, (i.e., <4 ACEs and ≥4 ACEs). Individuals who experienced household dysfunction demonstrated lower LVM, LVMHT, and LVMBSA (P < 0.01) and greater IL-6 (P < 0.05) than those who did not experience household dysfunction. Reduced MMP3 was present in individuals who experienced maltreatment (P < 0.05) and ≥4 ACEs (P < 0.01) compared with no maltreatment and <4 ACEs, respectively. After controlling for covariates (i.e., sex, recent life stress, height, body mass index, smoking, physical activity, and inflammation), a significant negative effect of household dysfunction on LVM, LVMHT, and LVMBSA persisted. Likewise, a negative effect on EF independent of covariates was observed in individuals who experienced ≥4 ACEs. As such, alterations in LVM and EF may be perpetuated through a toxic home environment, promoting left ventricular underdevelopment in young adulthood. The effect of which in midlife and beyond requires additional investigation.NEW & NOTEWORTHY This is the first study to investigate the influence of adverse childhood experiences (ACEs) on left ventricular mass (LVM) and function. We identified experiencing any childhood household dysfunction was associated with lower LVM in young adults independent of sex, recent life stress, BMI and height, smoking, physical activity, and inflammation. We speculate an inflection point in LVM occurs in midlife predisposing these individuals toward a hypertrophic profile and elevated risk of heart disease in later life, although this requires longitudinal investigation.

Endothelial Damage Arising From High Salt Hypertension Is Elucidated by Vascular Bed Systematic Profiling.

BACKGROUND: Considerable evidence links dietary salt intake with the development of hypertension, left ventricular hypertrophy, and increased risk of stroke and coronary heart disease. Despite extensive epidemiological and basic science interrogation of the relationship between high salt (HS) intake and blood pressure, it remains unclear how HS impacts endothelial cell (EC) and vascular structure in vivo. This study aims to elucidate HS-induced vascular pathology using a differential systemic decellularization in vivo approach. METHODS: We performed systematic molecular characterization of the endothelial glycocalyx and EC proteomes in mice with HS (8%) diet-induced hypertension versus healthy control animals. Isolation of eGC and EC compartments was achieved using differential systemic decellularization in vivo methodology. Altered protein expression in hypertensive compared to normal mice was characterized by liquid chromatography tandem mass spectrometry. Proteomic results were validated using functional assays, microscopic imaging, and histopathologic evaluation. RESULTS: Proteomic analysis revealed a significant downregulation of eGC and associated proteins in HS diet-induced hypertensive mice (among 1696 proteins identified in this group, 723 were markedly decreased in abundance, while only 168 were increased in abundance. Bioinformatic analysis indicated substantial derangement of the eGC layer, which was subsequently confirmed by fluorescent and electron microscopy assessment of vessel damage ex vivo. In the EC fraction, HS-induced hypertension significantly altered protein mediators of contractility, metabolism, mechanotransduction, renal function, and the coagulation cascade. In particular, we observed dysregulation of integrin subunits α2, α2b, and α5, which was associated with arterial wall inflammation and substantial infiltration of CD68+ monocyte-macrophages. Consequently, HS-induced hypertensive mice also displayed reduced vascular integrity of multiple organs including lungs, kidneys, and heart. CONCLUSIONS: These findings provide novel molecular insight into HS-induced structural changes in eGC and EC composition that may increase cardiovascular risk and potentially guide the development of new diagnostics and therapeutic interventions.

Adverse childhood experiences are associated with altered cardiovascular reactivity to head-up tilt in young adults.

Adverse childhood experiences (ACEs) are associated with greater prevalence of cardiovascular disease and altered acute stress reactivity. The current study investigated the effect of ACEs on hemodynamic and autonomic responses to orthostatic stress imposed by 60° head-up tilt (HUT) in young adults. Two-hundred twenty-six healthy young adults (age = 22.6 ± 1.5 yr; n = 116 females) without cardiovascular disease participated and had complete data. Participants underwent supine blood pressure (BP), R-R interval (RRI), cardiac output (CO), total peripheral resistance (TPR), and cardiovagal baroreflex sensitivity (cvBRS) testing followed by a transition to 60° HUT where measures were reassessed. Childhood adversity exposures were assessed based on categorical exposure and nonexposure to childhood household dysfunction and maltreatment, and <4 and ≥4 types of ACEs. Significantly greater increases in SBP (P < 0.05), DBP, MAP, and TPR (P < 0.01; all) following 60° HUT were observed in individuals with ≥4 compared with those with <4 types of ACEs. Attenuated decreases in RRI and cvBRS were observed in those with ≥4 types of ACEs (P < 0.05). Experiencing ≥4 types of ACEs was associated with augmented BP and TPR reactivity and a blunted decrease in cvBRS in response to 60° HUT in young adults. Results suggest that a reduced vagal response to orthostatic stress is present in those who have experienced ≥4 types of ACEs that may promote autonomic dysfunction. Future research examining the sympathetic and vagal baroreflex branches is warranted.

Adverse Childhood Experiences and COVID-19 Stress on Changes in Mental Health among Young Adults.

The COVID-19 pandemic has been linked to poor mental health outcomes and may be particularly damaging for young adults who may be more affected by governmental pandemic responses such as mandatory school and work closures, online schooling, and social isolation. Exposure to Adverse Childhood Experiences (ACEs) has also been shown to have a significant impact on mental health among young adults. This prospective study examined whether young adults with higher ACE profiles were more vulnerable to COVID-19 stressors. Using pre-COVID-19 data from the Niagara Longitudinal Heart Study and a follow-up online survey during COVID-19, we examined 171 young adults and found that high COVID-19-related stress, especially emotional and relationship stress, led to a greater reduction in mental health among young adults with higher levels of ACEs. Findings indicate that young adults with high ACE profiles may benefit from resources and intervention programs directed at mental health in times of crisis, such as the COVID-19 pandemic.

No Mediation Effect of Telomere Length or Mitochondrial DNA Copy Number on the Association Between Adverse Childhood Experiences (ACEs) and Central Arterial Stiffness.

Background Adverse childhood experiences (ACEs) have been linked to increased cardiovascular disease (CVD) risk. Previous reports have suggested that accelerated biological aging-indexed by telomere length (TL) and mitochondrial DNA copy number (mtDNAcn)-may contribute to associations between ACEs and cardiovascular health outcomes. Here, we examine the potential mediating effects of TL and mtDNAcn on the association between ACEs and central arterial stiffness-an intermediate cardiovascular health outcome-as a novel pathway linking ACEs to CVD risk among young adults. Methods and Results One hundred and eighty-five (n=102 women; mean age, 22.5±1.5 years) individuals provided information on ACEs. TL (kb per diploid cell) and mtDNAcn (copies per diploid cell) were quantified using quantitative polymerase chain reaction techniques. Central arterial stiffness was measured as carotid-femoral pulse wave velocity (cfPWV; m/s). Multiple linear regression analyses were used to examine the associations between ACEs, TL, mtDNAcn, and cfPWV. ACEs were positively associated with cfPWV (ß=0.147, P=0.035). TL (ß=-0.170, P=0.011) and mtDNAcn (ß=-0.159, P=0.019) were inversely associated with cfPWV. Neither TL (ß=-0.027, P=0.726) nor mtDNAcn (ß=0.038, P=0.620) was associated with ACEs. Neither marker mediated the association between ACEs and cfPWV. Conclusions An increasing number of ACEs were associated with a faster cfPWV and thus, a greater degree of central arterial stiffness. ACEs were not associated with either TL or mtDNAcn, suggesting that these markers do not represent a mediating pathway linking ACEs to central arterial stiffness.

Examining the relationships between adverse childhood experiences (ACEs), cortisol, and inflammation among young adults.

Adverse childhood experiences (ACEs) are associated with dysregulation of inflammation and cortisol. The objectives of this study were to use principal component analysis to explore the inflammatory biomarker data to create inflammation composite variables; to examine the relationship between these composite measures of inflammation with ACEs and cortisol; and to assess whether these relationships were moderated by sex. The analysis included 232 young adults from the Niagara Longitudinal Heart Study (NLHS). After adjusting for covariates, higher exposure to ACEs significantly predicted higher low-grade inflammation. These results further support the use of multiple biomarkers to understand the complex relationships among ACEs, cortisol, and inflammation, which should be further examined in longitudinal studies to study biomarker trajectories.

Profit versus Quality: The Enigma of Scientific Wellness.

The "best of both worlds" is not often the case when it comes to implementing new health models, particularly in community settings. It is often a struggle between choosing or balancing between two components: depth of research or financial profit. This has become even more apparent with the recent shift to move away from a traditionally reactive model of medicine toward a predictive/preventative one. This has given rise to many new concepts and approaches with a variety of often overlapping aims. The purpose of this perspective is to highlight the pros and cons of the numerous ventures already implementing new concepts, to varying degrees, in community settings of quite differing scales-some successful and some falling short. Scientific wellness is a complex, multifaceted concept that requires integrated experimental/analytical designs that demand both high-quality research/healthcare and significant funding. We currently see the more likely long-term success of those ventures in which any profit is largely reinvested into research efforts and health/healthspan is the primary focus.

Skin Blood Flow Responses to Acetylcholine, Local Heating, and to 60% VO2max exercise with and without Nitric Oxide inhibition, in Boys vs. Girls.

PURPOSE: To determine sex-related differences in the skin blood flow (SkBF) response to exercise, local heating, and acetylcholine (ACh) in children, and to assess nitric oxide contribution to the SkBF response. METHODS: Forearm SkBF during local heating (44°C), ACh iontophoresis, and exercise (30-min cycling and 60% of maximum oxygen consumption) was assessed, using laser Doppler fluxmetry, in 12 boys and 12 girls (7-13 y old), with and without nitric oxide synthase inhibition, using Nω-nitro-L-arginine methyl ester iontophoresis. RESULTS: Local-heating-induced and ACh-induced SkBF increase were not different between boys and girls (local heating: 1445% [900%] and 1432% [582%] of baseline, P = .57; ACh: 673% [434%] and 558% [405%] of baseline, respectively, P = .18). Exercise-induced increase in SkBF was greater in boys than girls (528% [290%] and 374% [192%] of baseline, respectively, P = .03). Nω-nitro-L-arginine methyl ester blunted the SkBF response to ACh and during exercise (P < .001), with no difference between sexes. CONCLUSION: SkBF responses to ACh and local heat stimuli were similar in boys and girls, while the increase in SkBF during exercise was greater in boys. The apparent role of nitric oxide was not different between boys and girls. It is suggested that the greater SkBF response in boys during exercise was related to greater relative heat production and dissipation needs at this exercise intensity. The response to body size-related workload should be further examined.

Perfectionistic Cognitions Pre-Pandemic Predict Greater Anxiety Symptoms During the Pandemic Among Emerging Adults: A Two-Wave Cross-Lagged Study.

This study employed a two-wave cross-lagged panel analysis to examine associations between perfectionistic cognitions, anxiety, and depression pre-pandemic to during the pandemic in a sample of 171 (57% female, n = 98) emerging adults. Results demonstrated that perfectionistic cognitions decreased, anxiety increased, and depressive symptoms did not change pre-pandemic to during the pandemic. Cross-lagged results indicated that pre-pandemic perfectionistic cognitions predicted higher levels of anxiety symptoms (but not depressive symptoms) during the pandemic after accounting for pre-pandemic levels of anxiety and depressive symptoms. These results held with the inclusion of covariates (i.e., sex, age, education, exposure to COVID-19, whether or not participants knew someone diagnosed with COVID-19, had lost income due to the pandemic, and how often they thought about COVID-19). Psychological distress (i.e., anxiety and depressive symptoms) pre-pandemic did not predict perfectionistic cognitions during the pandemic after accounting for pre-pandemic levels of perfectionistic cognitions. Results support assertions that individuals with heightened levels of perfectionism are at an increased risk for poorer mental health during the pandemic. Findings underscore the importance of assessing perfectionistic cognitions for the prevention and treatment of anxiety symptoms among emerging adults during and post-pandemic.

Perfectionistic cognitions, Interleukin-6, and C-Reactive protein: A test of the perfectionism diathesis stress model.

Previous research has demonstrated that perfectionism is implicated in poorer health and earlier mortality. However, to our knowledge, research has not yet determined how individual differences in perfectionistic cognitions are related to intermediary health markers such as inflammation. Thus, within the theoretical frameworks of the perfectionism diathesis-stress model (Hewitt and Flett, 1993) and the cognitive theory of perfectionism (Flett et al., 2018; Flett et al., 2016) the aims of our study were to test whether individual differences in perfectionistic cognitions were associated with low-grade inflammation via c-reactive CRP and IL-6 biomarkers and whether these relationships varied as a function perceived stress. The sample included 248 Canadian young adults (52% female, Mage â€‹= â€‹22.89, SD â€‹= â€‹1.53) who completed surveys assessing key constructs such as perfectionistic cognitions and perceived stress along with providing assessments of body fat percentage and serum samples of IL-6 and CRP. Regression analyses indicated that perfectionistic cognitions were not related to IL-6 under any conditions of stress. However, under high levels of stress perfectionistic cognitions were associated with elevated levels of CRP and these findings held after accounting for the effects of smoking status, body fat percentage, and respondent sex. The present work adds to the growing body of evidence supporting links between personality and inflammation. These findings raise the possibility that experiencing more frequent thoughts centered on the need to be perfect when coupled with higher levels of stress may set the stage for greater vulnerability for chronic inflammation.

Serum MMP-3 and its association with central arterial stiffness among young adults is moderated by smoking and BMI.

Central arterial stiffness is an independent predictor of cardiovascular disease. It is characterized by a marked reduction in the elastin-collagen ratio of the arterial wall extracellular matrix (ECM), and is largely the result of degradation of various ECM components. Matrix metalloproteinase-3 (MMP-3) may contribute to central arterial stiffness via its involvement in ECM homeostasis and remodeling. This study examined the association between serum MMP-3 concentrations and central arterial stiffness and potential interactions of MMP-3 and traditional cardiovascular risk factors in a population of healthy young adults. A total of 206 participants (n = 109 females) aged 19-25 years were included in the current study. Central arterial stiffness was measured non-invasively as carotid-femoral pulse wave velocity (cfPWV) (m/s). MMP-3 concentrations (ng/ml) were measured using ELISA techniques. Regression analyses were used to examine the association between cfPWV and MMP-3, adjusting for age, sex, smoking status, body mass index (BMI), instantaneous mean arterial pressure (MAP) and heart rate, and serum C-reactive protein. Interactions between MMP-3 with smoking, BMI, sex, and MAP were analyzed in subsequent regression models. MMP-3 was an independent predictor of cfPWV (ß = 0.187, p = 0.007), and significant interactions between MMP-3 and regular smoking (ß = 0.291, p = 0.022), and MMP-3 and BMI (ß = 0.210, p = 0.013) were observed. Higher serum MMP-3 concentrations were associated with a faster cfPWV and thus, greater central arterial stiffness. Interactions between MMP-3 and smoking, and MMP-3 and BMI may, in part, drive the association between MMP-3 and central arterial stiffness.

Linking the hemodynamic consequences of adverse childhood experiences to an altered HPA axis and acute stress response.

Adverse childhood experiences (ACEs), such as maltreatment and severe household dysfunction, represent a significant threat to public health as ACEs are associated with increased prevalence of several chronic diseases. Biological embedding, believed to be rooted in dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, is the prevailing theory by which chronic diseases become imprinted in individuals following childhood adversity. A shift towards HPA axis hypoactivity occurs in response to ACEs exposure and is proposed to contribute towards altered cortisol secretion, chronic low-grade inflammation, and dysregulated hemodynamic and autonomic function. This shift in HPA axis activity may be a long-term effect of glucocorticoid receptor methylation with downstream effects on hemodynamic and autonomic function. Emerging evidence suggests syncopal tendencies are increased among those with ACEs and coincides with altered neuroimmune function. Similarly, chronic low-grade inflammation may contribute towards arterial baroreceptor desensitization through increased arterial stiffness, negatively impacting autonomic regulation following posture change and increasing rates of syncope in later life, as has been previously highlighted in the literature. Although speculative, baroreceptor desensitization may be secondary to increased arterial stiffness and changes in expression of glucocorticoid receptors and arginine vasopressin, which are chronically altered by ACEs. Several research gaps and opportunities exist in this field and represent prospective areas for future investigation. Here, we synthesize current findings in the areas of acute psychosocial stress reactivity pertaining to HPA axis function, inflammation, and hemodynamic function while suggesting ideas for future research emphasizing systemic interactions and postural stress assessments among those with ACEs. This review aims to identify specific pathways which may contribute towards orthostatic intolerance in populations with history of childhood adversity.

Adverse Childhood Experiences (ACEs) Predict Increased Arterial Stiffness from Childhood to Early Adulthood: Pilot Analysis of the Niagara Longitudinal Heart Study.

An association among adults between adverse childhood experiences (ACEs) and arterial stiffness and between arterial stiffness and cardiovascular disease has been established. Recent cross-sectional evidence suggests that ACEs is linked to the development and progression of arterial stiffness, but it remains unclear when these changes begin to manifest. We examine the relationship between ACEs and changes in arterial stiffness from childhood into adulthood using population-based longitudinal data. The Niagara Longitudinal Heart Study (NLHS) pilot data included 76 young adults (females = 44), with an average age of 21 years (SD = 1), and had a follow-up period of 9 years. Mixed effects modeling was used to examine the effect of ACEs on changes in arterial stiffness over time adjusting for sex, changes in heart rate, systolic blood pressure, body mass index, and physical activity. Individuals with four or more ACEs have a greater increase in arterial stiffness over time from childhood into young adulthood. This increase was similar for both males and females and independent of the effects of change in heart rate, systolic blood pressure, body mass index, and physical activity. Exposure to ACEs is associated with greater increase in arterial stiffness, a marker for cardiovascular disease among adults. This suggests that interventions targeted at individuals with high exposure to ACEs early on in life could lower the risk of arterial stiffness and in turn the cascade of events leading to cardiovascular disease.

Adverse childhood experiences (ACEs) and cardiovascular development from childhood to early adulthood: study protocol of the Niagara Longitudinal Heart Study.

INTRODUCTION: Recent reviews have found substantial links between a toxic childhood environment including child abuse and severe household dysfunction and adult cardiovascular disease (CVD). Collectively referred to as adverse childhood experiences (ACEs), this toxic environment is prevalent among children, with recent Canadian estimates of child abuse at 27%-32%, and severe household dysfunction at 49%. Based on these prevalence rates, the potential effect of ACEs on CVD is more significant than previously thought. Yet, how ACEs amplify the risk for later CVD remains unclear. Lifestyle risk factors only partially account for this connection, instead directing attention to the interaction between psychosocial factors and physiological mechanisms such as inflammation. The Niagara Longitudinal Heart Study (NLHS) examines how ACEs influence cardiovascular health (CVH) from childhood to early adulthood. Integrating the stress process and biological embedding models, this study examines how psychosocial and physiological factors in addition to lifestyle factors explain the relationship between ACEs and CVH. METHODS: This follow-up study combines three baseline studies from 2007 to 2012 that collected CVH measures including child blood pressure, heart rate, left ventricular structure and function, arterial stiffness indices and baroreflex sensitivity on 564 children. Baseline data also include anthropometric, biological, lifestyle, behavioural, and psychosocial measures that varied across primary studies. Now over 18 years of age, we will recruit and retest as many participants from the baseline studies as possible collecting data on ACEs, CVH, anthropometric, lifestyle and psychosocial measures as well as blood, saliva and hair for physiological biostress markers. ETHICS AND DISSEMINATION: Ethics approval has been received for the NLHS follow-up. Written consent to participate in the follow-up study is obtained from each participant. Results testing all proposed hypotheses will be submitted for publication in peer-reviewed journals.

What is the effect of ADHD stimulant medication on heart rate and blood pressure in a community sample of children?

OBJECTIVE: This study examines the effect of ADHD (attention deficit hyperactivity disorder) diagnosis and stimulant medication for ADHD treatment on child heart rate (HR) and blood pressure (BP) in a community sample compared to children without ADHD. METHODS: Data came from the HBEAT Study. From 49 schools, 2013 participants from southern Ontario in grades 5-8 were included. Linear regression analyses examined the effects of ADHD medications on systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate adjusting for age, sex and body mass index (BMI). RESULTS: Compared to non-ADHD children and adjusting for age, sex and BMI, children with ADHD on stimulant medication had a 12.3-bpm higher HR, and 3.0-mmHg higher SBP and DBP (all statistically significant). Children with ADHD on no stimulant medication had no differences in HR and BP compared to those children without a diagnosis of ADHD. CONCLUSION: Stimulant medications used to treat ADHD are associated with elevated HR and higher BP. While it is unknown whether children on ADHD medications may be at risk for longer-term cardiovascular issues, this study supports the need to examine the long-term consequences of ADHD medication.

Adverse childhood experiences are associated with self-regulation and the magnitude of the error-related negativity difference.

Trauma and stress, like that which occurs as a result of adverse childhood experiences (ACEs), can change brain structure and function, especially in medial prefrontal and hippocampal areas, and can impact self-regulatory skill. The error-related negativity (ERN) is a medial frontal negative event-related potential (ERP) component that is more negative when a participant makes an erroneous versus correct response. We investigated the association of ACEs to adolescents' ERN and self-regulation. Forty-three 12-15 year olds performed a flanker task while EEG data were recorded. We found an interaction between trial type (correct vs incorrect) and group (low, medium and high trauma groups) on the ERN. The high-trauma group showed a larger Error-Correct difference than the low- and medium-trauma groups. This appeared as trend correlations between overall trauma exposure as a continuous variable and ERN-related variables. Trauma exposure was associated with reduced self-regulatory capacity, and accounting for self-regulation decreased the associations between trauma and the ERN, suggestive of a protective effect for self-regulation.

Arterial stiffness in children with and without probable developmental coordination disorder.

BACKGROUND: Children with cardiovascular disease risk factors demonstrate adverse arterial alterations that are predictive of cardiovascular morbidity and mortality in adults. Children with developmental coordination disorder (DCD) are at cardiovascular risk as they are more likely to be obese and inactive. AIM: The purpose of this study was to assess arterial structure and function in children with and without probable DCD (p-DCD). METHODS: A cross-sectional study of 33 children with p-DCD (22 male) and 53 without (30 male). The Movement Assessment Battery for Children was used to classify those with p-DCD. Adiposity was assessed using the BOD POD. Compliance, distensibility, and intima-media thickness were measured at the common carotid artery (CCA). ECG R-wave-to-toe pulse wave velocity (PWV) was also measured. RESULTS: Compared to controls, males with p-DCD had lower CCA distensibility (p=0.034) and higher PWV (p=0.001). No differences were evident in females. Body fat percent was a significant predictor of CCA distensibility and removed the effect of p-DCD on PWV in males. CONCLUSIONS: The present study demonstrates augmented arterial stiffness in males with p-DCD, likely attributed to body fat. These findings underscore the importance of targeted interventions in children with p-DCD, specifically males, in order to prevent future cardiovascular risk.

Role of aortic arch vascular mechanics in cardiovagal baroreflex sensitivity.

Cardiovagal baroreflex sensitivity (cvBRS) measures the efficiency of the cardiovagal baroreflex to modulate heart rate in response to increases or decreases in systolic blood pressure (SBP). Given that baroreceptors are located in the walls of the carotid sinuses (CS) and aortic arch (AA), the arterial mechanics of these sites are important contributors to cvBRS. However, the relative contribution of CS and AA mechanics to cvBRS remains unclear. This study employed sex differences as a model to test the hypothesis that differences in cvBRS between groups would be explained by the vascular mechanics of the AA but not the CS. Thirty-six young, healthy, normotensive individuals (18 females; 24 ± 2 yr) were recruited. cvBRS was measured using transfer function analysis of the low-frequency region (0.04-0.15 Hz). Ultrasonography was performed at the CS and AA to obtain arterial diameters for the measurement of distensibility. Local pulse pressure (PP) was taken at the CS using a hand-held tonometer, whereas AA PP was estimated using a transfer function of brachial PP. Both cvBRS (25 ± 11 vs. 19 ± 7 ms/mmHg, P = 0.04) and AA distensibility (16.5 ± 6.0 vs. 10.5 ± 3.8 mmHg(-1) × 10(-3), P = 0.02) were greater in females than males. Sex differences in cvBRS were eliminated after controlling for AA distensibility (P = 0.19). There were no sex differences in CS distensibility (5.32 ± 2.3 vs. 4.63 ± 1.3 mmHg(-1) × 10(-3), P = 0.32). The present data demonstrate that AA mechanics are an important contributor to differences in cvBRS.

Linking systemic arterial stiffness among adolescents to adverse childhood experiences.

Adverse childhood experiences (ACEs) have been linked with cardiovascular disease and early mortality among adults. Most research examines this relationship retrospectively. Examining the association between ACEs and children's cardiovascular health is required to understand the time course of this association. We examined the relationship between ACEs exposure and ECG-to-toe pulse wave velocity (PWV), a measure of systemic arterial stiffness that is strongly related to cardiovascular mortality among adults. PWV (distance/transit time; m/s) was calculated using transit times from the ECG R-wave to the pulse wave contour at the toe. Transit times were collected over 15 heartbeats and the distance from the sternal notch to the left middle toe was used. A total of 221 children (119 females) aged 10-14 years participated in data collection of PWV, hemodynamic and anthropometric variables. Parents of these children completed a modified inventory of ACEs taken from the Childhood Trust Events Survey. Multivariable regression assessed the relationship between ACEs group (<4 ACEs versus ≥4 ACEs) and PWV. Analyses yielded an ACEs group by sex interaction, with males who experienced four or more ACEs having higher PWV (p<0.01). This association was independent of hemodynamic, anthropometric and sociodemographic variables (R(2)=0.346; p<0.01). Four or more ACEs is associated with greater arterial stiffness in male children aged 10-14 years. Addressing stress and trauma exposure in childhood is an important target for public health interventions to reduce early cardiovascular risk.