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.

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.