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 (β = 0.187, p = 0.007), and significant interactions between MMP-3 and regular smoking (β = 0.291, p = 0.022), and MMP-3 and BMI (β = 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.Canadian Institutes of Health Researc

Cardiovascular and Inflammatory Consequences of Adverse Childhood Experiences

This thesis is composed of three investigations which aim to identify changes in cardiovascular and inflammatory health which are present in individuals who have experienced different types of ACEs (i.e., maltreatment, household dysfunction) and the accumulation of ACEs (i.e., <4 and ≥ 4 different ACEs). First, this thesis sought to identify the effects of adversity on change in arterial stiffness and cardiovagal baroreflex sensitivity (cvBRS) from childhood to young adulthood. Study 1 identified significant interactions between ≥ 4 ACEs and time, and maltreatment by time which were associated with a greater increase in systemic pulse wave velocity from childhood to young adulthood among those with a high ACE profile; although this effect only remained significant in maltreatment models after covariates were introduced. Study 1 also observed a significant interaction between ≥ 4 ACEs, time, and sex on the change in cvBRS from childhood to young adulthood with females driving this relationship. Study 2 aimed to determine whether childhood adversity demonstrated an effect on the heart, particularly left ventricular mass (LVM) and left ventricular function, measured as ejection fraction (EF) and fractional shortening (FS). This investigation identified a unique cardiac profile present among individuals who experienced childhood household dysfunction and was characterized by a significantly lower LVM, independent of recent life stress, smoking, physical activity, and inflammation while childhood maltreatment demonstrated a negative effect on EF independent of covariates. Whether this persists into older age is unknown. Notably, Studies 1 and 2 identified the MMP proteolytic family may be involved in subclinical cardiovascular remodeling among those with ACEs and warrants future investigation. Study 3 utilized an acute 60° head up tilt (HUT) to determine whether childhood adversity influenced the hemodynamic and autonomic responses to orthostatic stress. This thesis identified enhanced blood pressure and total peripheral resistance responses and blunted RR-interval, cardiac output, and cvBRS responses to 60° HUT in individuals who experienced ≥ 4 ACEs; suggesting a reduced vagal and likely enhanced sympathetic response to orthostatic stress. Collectively, these studies provide evidence that exposure to ACEs produce unique cardiovascular changes which occur largely in the absence of covariates and enhanced inflammation

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\ua0years (SD = 1), and had a follow-up period of 9\ua0years. 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

Role of aortic arch vascular mechanics in cardiovagal baroreflex sensitivity

© 2016 the American Physiological Society. 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

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

Exposure to moral stressors and associated outcomes in healthcare workers: prevalence, correlates, and impact on job attrition

Introduction: Healthcare workers (HCWs) often experience morally challenging situations in their workplaces that may contribute to job turnover and compromised well-being. This study aimed to characterize the nature and frequency of moral stressors experienced by HCWs during the COVID-19 pandemic, examine their influence on psychosocial-spiritual factors, and capture the impact of such factors and related moral stressors on HCWs’ self-reported job attrition intentions. Methods: A sample of 1204 Canadian HCWs were included in the analysis through a web-based survey platform whereby work-related factors (e.g. years spent working as HCW, providing care to COVID-19 patients), moral distress (captured by MMD-HP), moral injury (captured by MIOS), mental health symptomatology, and job turnover due to moral distress were assessed. Results: Moral stressors with the highest reported frequency and distress ratings included patient care requirements that exceeded the capacity HCWs felt safe/comfortable managing, reported lack of resource availability, and belief that administration was not addressing issues that compromised patient care. Participants who considered leaving their jobs (44%; N = 517) demonstrated greater moral distress and injury scores. Logistic regression highlighted burnout (AOR = 1.59; p p p = .022) as significant predictors of the intention to leave one’s job. Conclusion: While it is impossible to fully eliminate moral stressors from healthcare, especially during exceptional and critical scenarios like a global pandemic, it is crucial to recognize the detrimental impacts on HCWs. This underscores the urgent need for additional research to identify protective factors that can mitigate the impact of these stressors. This study explored the nature of moral stressors encountered by health care workers, along with impacts on moral injury and intentions to leave their jobs.Morally distressing encounters were common, with the most prevalent and distressing experiences being organizational or team-based in nature.Findings revealed that severity of moral injury, particularly related to trust violation or betrayal, was a key factor influencing healthcare workers’ intentions to leave their jobs. This study explored the nature of moral stressors encountered by health care workers, along with impacts on moral injury and intentions to leave their jobs. Morally distressing encounters were common, with the most prevalent and distressing experiences being organizational or team-based in nature. Findings revealed that severity of moral injury, particularly related to trust violation or betrayal, was a key factor influencing healthcare workers’ intentions to leave their jobs.</p