Cardiovascular and Inflammatory Consequences of Adverse Childhood Experiences

Abstract

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.