Wuopio Jonas, Östgren Carl Johan, Länne Toste, Lind Lars, Ruge Toralph, Carlsson Axel C, Larsson Anders, Nyström Fredrik H, Ärnlöv Johan
a Department of Medicine , Mora County Hospital , Mora , Sweden.
b Department of Medical and Health Sciences , Linköping University , Linköping , Sweden.
Blood Press. 2018 Aug;27(4):215-221. doi: 10.1080/08037051.2018.1444941. Epub 2018 Feb 28.
Endostatin, cleaved from collagen XVIII in the extracellular matrix, is a promising circulating biomarker for cardiovascular damage. It possesses anti-angiogenic and anti-fibrotic functions and has even been suggested to be involved in blood pressure regulation. Less is known if endostatin levels relate to circadian blood pressure patterns. In the present paper we studied the association between circulating levels of endostatin and nocturnal dipping in blood pressure.
We used the CARDIPP-study, a cohort of middle aged, type 2 diabetics (n = 593, 32% women), with data on both 24-hour and office blood pressure, serum-endostatin, cardiovascular risk factors, and incident major cardiovascular events. Nocturnal dipping was defined as a >10% difference between day- and night-time blood pressures.
Two-hundred four participants (34%) were classified as non-dippers. The mean endostatin levels were significantly higher in non-dippers compared to dippers (mean ± standard deviation: 62.6 ± 1.8 µg/l vs. 58.7 ± 1.6 µg/l, respectively, p = .007). Higher serum levels of endostatin were associated with a diminished decline in nocturnal blood pressure adjusted for age, sex, HbA1c, mean systolic day blood pressure, hypertension treatment, glomerular filtration rate, and prevalent cardiovascular disease (regression coefficient per SD increase of endostatin -0.01, 95% CI, -0.02-(-0.001), p = .03). Structural equation modelling analyses suggest that endostatin mediates 7% of the association between non-dipping and major cardiovascular events.
We found an independent association between higher circulating levels of endostatin and a reduced difference between day- and night-time systolic blood pressure in patients with type 2 diabetes. Yet endostatin mediated only a small portion of the association between non-dipping and cardiovascular events arguing against a clinical utility of our findings.
内皮抑素是从细胞外基质中的 XVIII 型胶原蛋白裂解而来，是一种很有前景的心血管损伤循环生物标志物。它具有抗血管生成和抗纤维化功能，甚至有人认为它参与血压调节。关于内皮抑素水平是否与昼夜血压模式相关，目前所知较少。在本文中，我们研究了内皮抑素循环水平与夜间血压下降之间的关联。
我们使用了 CARDIPP 研究，这是一组中年 2 型糖尿病患者（n = 593，32%为女性），有 24 小时和诊室血压、血清内皮抑素、心血管危险因素以及主要心血管事件发生情况的数据。夜间血压下降定义为白天和夜间血压相差>10%。
204 名参与者（34%）被归类为非勺型血压者。非勺型血压者的内皮抑素平均水平显著高于勺型血压者（均值±标准差：分别为 62.6±1.8 μg/l 和 58.7±1.6 μg/l，p = 0.007）。在调整年龄、性别、糖化血红蛋白、白天平均收缩压、高血压治疗、肾小球滤过率和心血管疾病患病率后，较高的血清内皮抑素水平与夜间血压下降减少相关（内皮抑素每增加一个标准差的回归系数为 -0.01，95%可信区间为 -0.02 - (-0.001)，p = 0.03）。结构方程模型分析表明，内皮抑素介导了非勺型血压与主要心血管事件之间 7%的关联。
我们发现 2 型糖尿病患者中，较高的内皮抑素循环水平与白天和夜间收缩压差值减小之间存在独立关联。然而，内皮抑素仅介导了非勺型血压与心血管事件之间关联的一小部分，这表明我们的研究结果在临床上的实用性存疑。
