From the Institute of Cardiovascular Science, University College London, United Kingdom (S.T.C., J.E.D.).
Department of Paediatrics (M.L.M., D.B.D.), University of Cambridge, United Kingdom.
Hypertension. 2020 Dec;76(6):1734-1743. doi: 10.1161/HYPERTENSIONAHA.120.15721. Epub 2020 Oct 26.
An increased albumin-creatinine ratio within the normal range can identify adolescents at higher risk of developing adverse cardio-renal outcomes as they progress into adulthood. Utilizing a parallel randomized controlled trial and observational cohort study, we characterized the progression of vascular phenotypes throughout this important period and investigated the effect of ACE (angiotensin-converting enzyme) inhibitors and statins in high-risk adolescents. Endothelial function (flow-mediated dilation and reactive hyperemia index) and arterial stiffness (carotid-femoral pulse wave velocity) were assessed in 158 high-risk participants recruited to a randomized, double-blind placebo-controlled 2×2 factorial trial (randomized, placebo-controlled trial) of ACE inhibitors and/or statins in adolescents with type 1 diabetes (AdDIT [Adolescent Type 1 Diabetes cardio-renal Intervention Trial]). Identical measures were also assessed in 215 lower-risk individuals recruited to a parallel observational study. In the randomized, placebo-controlled trial, high-risk patients randomized to ACE inhibitors had improved flow-mediated dilation after 2 to 4 years of follow-up (mean [95% CI]: 6.6% [6.0-7.2] versus 5.3% [4.7-5.9]; =0.005), whereas no effect was observed following statin use (6.2% [5.5-6.8] versus 5.8% [5.1-6.4]; =0.358). In the observational study, patients classed as high-risk based on albumin-creatinine ratio showed evidence of endothelial dysfunction at the end of follow-up (flow-mediated dilation=4.8% [3.8-5.9] versus 6.3% [5.8-6.7] for high-risk versus low-risk groups; =0.015). Neither reactive hyperemia index nor pulse wave velocity were affected by either treatment (>0.05 for both), but both were found to increase over the duration of follow-up (0.07 [0.03-0.12]; =0.001 and 0.5 m/s [0.4-0.6]; <0.001 for reactive hyperemia index and pulse wave velocity, respectively). ACE inhibitors improve endothelial function in high-risk adolescents as they transition through puberty. The longer-term protective effects of this intervention at this early age remain to be determined. Registration- URL: https://www.clinicaltrials.gov; Unique identifier NCT01581476.
在正常范围内，白蛋白-肌酐比值的增加可以识别出在成年后发生不良心肾结局风险较高的青少年。利用平行随机对照试验和观察性队列研究，我们描述了整个重要时期血管表型的进展，并研究了血管紧张素转换酶 (ACE) 抑制剂和他汀类药物在高危青少年中的作用。在招募至 ACE 抑制剂和/或他汀类药物的随机、双盲安慰剂对照 2×2 析因试验（青少年 1 型糖尿病心血管肾脏干预试验 [AdDIT]）的 158 名高危参与者中评估了内皮功能（血流介导的扩张和反应性充血指数）和动脉僵硬度（颈动脉-股动脉脉搏波速度）。在平行观察性研究中，也评估了 215 名低危个体的相同指标。在随机、安慰剂对照试验中，高危患者随机接受 ACE 抑制剂治疗 2 至 4 年后血流介导的扩张得到改善（平均[95%CI]：6.6%[6.0-7.2]比 5.3%[4.7-5.9]；=0.005），而他汀类药物使用后无影响（6.2%[5.5-6.8]比 5.8%[5.1-6.4]；=0.358）。在观察性研究中，根据白蛋白-肌酐比值分类为高危的患者在随访结束时显示内皮功能障碍的证据（血流介导的扩张=4.8%[3.8-5.9]比高危与低危组的 6.3%[5.8-6.7]；=0.015）。反应性充血指数和脉搏波速度均不受任何治疗的影响（两者均>0.05），但在随访期间均发现增加（0.07[0.03-0.12]；=0.001 和 0.5 m/s[0.4-0.6]；反应性充血指数和脉搏波速度分别为<0.001）。ACE 抑制剂可改善青春期过渡期间高危青少年的内皮功能。这种干预措施在这个早期年龄的长期保护作用仍有待确定。注册-网址：https://www.clinicaltrials.gov；唯一标识符 NCT01581476。
