Mediating factors in the relationship between combat-related traumatic injury and myocardial blood flow reserve: The ADVANCE cohort study

Introduction Combat-related traumatic injury (CRTI) has been linked to reduced myocardial blood-flow- reserve (MBFR), measured using the subendocardial viability ratio (SEVR). We aimed to assess the mediating role of known cardiovascular risk factors on SEVR. Materials and Methods We examined 1018 UK servicemen (prospective ADVANCE Cohort Study) comprising 504 with CRTI (140 amputees) and 514 uninjured men, frequency-matched at sampling, by age, rank and deployment (Afghanistan 2003–2014). We examined the mediating role of cardiovascular risk factors, shown to significantly greater with CRTI at study baseline (~8 years post-injury/deployment), on SEVR, measured three-years later (FU1). The cardiovascular risk measures were heart-rate variability (HRV, root-mean-square-of-successive-differences [RMSSD]), visceral-fat-mass (VFM, using DEXA), venous-blood high-sensitivity C-reactive protein (Hs-CRP, inflammation), six-minute walk distance (6MWD, physical function) and weekly leisure-time moderate-to-vigorous physical activity (LT-MVPA, physical activity). Results At baseline, VFM was significantly greater and RMSSD, 6MWD and LT-MVPA lower with CRTI compared to the uninjured. VFM and Hs-CRP were significantly greater and RMSSD, 6MWD and LT-MVPA lower in the injured amputees versus the injured non-amputees and uninjured. The SEVR at FU1 was significantly lower in the injured (mean ± standard deviation; 187.2 ± 39.7) compared to the uninjured (194.1 ± 31.5) and lowest in the amputee sub-group (181.9 ± 30.0). The association between CRTI and SEVR was mediated by VFM (natural indirect effect −1.80: 95%CI: −2.90, −0.67), RMSSD (−1.82: −3.45, −0.19) and 6MWD (−1.79: −3.16, −0.41) but not Hs-CRP and LT-MVPA. The association between traumatic amputation and SEVR was mediated by VFM, HRV and LT-MVPA. Conclusions VFM, HRV and physical function/activity were significant mediators of the link between CRTI and SEVR. Interventions on physical activity/function could mitigate the association between CRTI and SEVR. Data from longer-term follow up are required to robustly determine the temporal effects of this relationship.