External Generalizability of Clinical Trials to Developing Countries.

In this edition of Journal of Pediatric Gastroenterology and Nutrition, Winderman et al (2) sought to establish a method to measure microvascular health and responsiveness in pediatric patients with IBD. Utilizing EndoPAT2000 which has similarly been studied in adult cardiovascular patients, this study measured vascular reactivity in pediatric patients with IBD compared with healthy controls. The test is rapid, noninvasive, and previously demonstrated to be reliable to measure microvascular flow by plethysmography. The test is based upon the normal hyperemia response of endothelium when encountering ischemia. In chronic inflammatory conditions, this hyperemia response is dampened, indicating endothelial dysfunction and possible future microvascular risk. In this study of 32 pediatric patients, 11 patients had Crohn disease, 5 had ulcerative colitis, and all were age matched to 16 healthy controls. Mean reactive hyperemic index (RHI) was significantly decreased among the IBD group, indicating endothelial dysfunction and increased vascular risk among those patients. The pediatric IBD mean RHI level was decreased into the range seen in adult patients with cardiovascular risk, although 43% (7/16) fell within the normal range. All patients with IBD were noted to be in remission as per disease activity indices; however, mucosal healing was not assessed at the time by endoscopy or histology. Patients were excluded if on vasoactive medications, oral contraceptives, smoking status, pregnant, or with history of thromboembolic events or hypercoagulable states. The IBD group did have an elevated erythrocyte sedimentation rate compared to the control group; however, the study noted no significant decrease in RHI in this subgroup. Nevertheless, the results indicate that in this small series, this new technology EndoPAT2000, can identify specific pediatric patients with IBD with potential microvascular risk. This study demonstrates the feasibility of using this screening test in a pediatric IBD population to identify patients potentially at risk for future thromboembolic complications and cardiovascular disease. As with any screening test, it will need to demonstrate adequate number needed to treat, as current modalities to test for cardiovascular risk and thromboembolic events are costly and not entirely standardized. However, longitudinal studies, as suggested by the authors, with relevant outcomes are essential to not only clarify the risk of cardiovascular disease of children and adolescents with IBD as they become adults, but also the value of the RHI to predict this outcome. In future larger, prospective studies it will be of interest to note if there are indeed diagnosis-related differences in microvascular risk as preliminarily suggested by lower mean RHI in the patients with Crohn disease. Furthermore, it will help elucidate whether there are pediatric specific risk factors that may be modulated. Thus far, disease duration does not appear to contribute to cardiovascular risk in adult patients with IBD (3). This information eventually will enable clinicians to target these IBD-specific risk factors to prevent cardiovascular and thromboembolic events. It is not yet entirely known whether current medical IBD therapies modulate this cardiovascular risk. Early cardiovascular disease was recently implicated in a large, population-based study assessing risk of myocardial infarction (MI) in adult patients with IBD (4). This study identified a higher prevalence of MI in younger patients (30–34 years) with an odds ratio of 12.05 (11.16–13.01) when compared to older adults. In addition, IBD as an independent risk factor, lead to higher odds of MI in adult patients with IBD. This observation has been independently shown in other studies revealing IBD to be a risk factor for premature coronary artery disease (5). As we learn more about the possible risks of developing cardiovascular disease during the course of pediatric IBD, increasing awareness among IBD providers will be vital so that early detection of vascular risk may start in the pediatric IBD population. Winderman’s study brings to light an important and highly relevant issue that will need further investigation.