Program in Nutritional Metabolism, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Division of Musculoskeletal Imaging and Intervention, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
J Clin Endocrinol Metab. 2018 Apr 1;103(4):1558-1565. doi: 10.1210/jc.2017-02198.
Natriuretic peptides (NPs) negatively feedback on the renin-angiotensin-aldosterone system (RAAS) and play a critical role in preserving cardiac structure and maintaining metabolic homeostasis. Well-treated HIV-infected individuals are at risk for fat redistribution and demonstrate evidence of RAAS dysregulation, which relates to metabolic dysfunction. We investigated circulating NPs in relation to RAAS physiology and metrics of body composition in HIV.
We assessed atrial natriuretic peptide, brain natriuretic peptide (BNP), and amino terminal pro B-type natriuretic peptide (NT-proBNP) during acute activation of the RAAS using a low-sodium controlled diet among 20 HIV-infected and 10 non-HIV-infected individuals well phenotyped for body composition.
BNP was significantly lower [median, 60 (interquartile range, 44, 152) pg/mL vs 196 (91, 251) pg/mL, respectively; P = 0.04], and serum aldosterone was higher, among HIV-infected than among non-HIV-infected individuals. BNP was significantly and inversely associated with body composition [waist circumference: r = -0.46 (P = 0.04); BMI: r = -0.55 (P = 0.01); body adiposity index: r = -0.49 (P = 0.03)], metabolic indices [total cholesterol: r = -0.44 (P = 0.05), insulin resistance calculated by using homeostatic model assessment: r = -0.44 (P = 0.05); mean arterial pressure: r = -0.44 (P = 0.05)], and serum aldosterone (r = -0.49; P = 0.03) among the HIV-infected group. These relationships were not demonstrated in the non-HIV-infected group. In a four-group comparison stratifying by HIV serostatus and above or below a body mass index (BMI) of 25 kg/m2, BNP decreased significantly across groups; it was highest in non-HIV-infected patients with a BMI <25 kg/m2 and lowest in HIV-infected patients with a BMI ≥25 kg/m2 (overall P = 0.01).
Relatively reduced NP, particularly BNP, among HIV-infected individuals with excess adiposity may contribute to reduced suppression of aldosterone and potentially drive aldosterone-mediated metabolic complications. Strategies that target RAAS blockade and/or augment NPs may be useful to reduce cardiometabolic disease among HIV-infected individuals in whom these systems are perturbed.
利钠肽（NPs）对肾素-血管紧张素-醛固酮系统（RAAS）产生负反馈作用，在维持心脏结构和代谢平衡方面发挥着关键作用。经充分治疗的 HIV 感染者存在脂肪重新分布的风险，并表现出 RAAS 失调的证据，这与代谢功能障碍有关。我们研究了 HIV 患者循环 NPs 与 RAAS 生理学和身体成分指标之间的关系。
我们在 20 名 HIV 感染患者和 10 名非 HIV 感染对照者中，评估了 RAAS 急性激活期间的心房利钠肽、脑利钠肽（BNP）和氨基末端 pro B 型利钠肽（NT-proBNP），这些患者的身体成分特征得到了很好的描述。
与非 HIV 感染个体相比，HIV 感染个体的 BNP 明显降低[中位数分别为 60（四分位距，44，152）pg/mL 和 196（91，251）pg/mL；P = 0.04]，血清醛固酮水平升高。BNP 与身体成分[腰围：r = -0.46（P = 0.04）；BMI：r = -0.55（P = 0.01）；体脂指数：r = -0.49（P = 0.03）]、代谢指标[总胆固醇：r = -0.44（P = 0.05），采用稳态模型评估的胰岛素抵抗：r = -0.44（P = 0.05）；平均动脉压：r = -0.44（P = 0.05）]和血清醛固酮（r = -0.49；P = 0.03）之间存在显著的负相关。在非 HIV 感染组中未观察到这些关系。在根据 HIV 血清状态和 BMI（体重指数）≥25 kg/m2 或＜25 kg/m2 进行四组比较时，BNP 在各组之间显著降低；非 HIV 感染患者中 BMI＜25 kg/m2 时 BNP 最高，HIV 感染患者中 BMI≥25 kg/m2 时 BNP 最低（总体 P = 0.01）。
在肥胖的 HIV 感染者中，相对减少的 NP，特别是 BNP，可能导致醛固酮抑制减少，并可能导致醛固酮介导的代谢并发症。针对 RAAS 阻断和/或增强 NPs 的策略可能有助于减少这些系统受到干扰的 HIV 感染者的心血管代谢疾病。
