Micro- and macrovascular function in the highest city in the world: a cross sectional study

IF 7 Q1 HEALTH CARE SCIENCES & SERVICES Lancet Regional Health-Americas Pub Date : 2024-09-25 DOI:10.1016/j.lana.2024.100887
Yann Savina , Aurélien P. Pichon , Lucas Lemaire , Connor A. Howe , Mathilde Ulliel-Roche , Sarah Skinner , Elie Nader , Nicolas Guillot , Émeric Stauffer , Matthieu Roustit , Ivan Hancco , Paul Robach , François Esteve , Vincent Pialoux , Elisa Perger , Gianfranco Parati , Philip N. Ainslie , Stéphane Doutreleau , Philippe Connes , Samuel Verges , Julien V. Brugniaux
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Abstract

Background

Since vascular responses to hypoxia in both healthy high-altitude natives and chronic mountain sickness (a maladaptive high-altitude pathology characterised by excessive erythrocytosis and the presence of symptoms—CMS) remain unclear, the role of inflammation and oxidative/nitrosative stress on the endothelium-dependent and -independent responses in both the micro- and macrocirculation, in healthy Andeans at different altitudes and in CMS patients, was examined.

Methods

94 men were included: 18 lowlanders (LL), 38 healthy highlanders permanently living at 3800 m (n = 21—HL-3800) or in La Rinconada, the highest city in the world (5100–5300 m) (n = 17—HL-5100/No CMS). Moreover, 14 participants with mild (Mild CMS) and 24 with moderate to severe CMS (Mod/Sev CMS) were recruited. All undertook two reactivity tests: i) local thermal hyperaemia (microcirculation) and ii) flow-mediated dilation (macrocirculation). Endothelium-independent function (glyceryl trinitrate) was also assessed only in La Rinconada.

Findings

Conductance and skin blood flow velocity during the microcirculation test, as well as macrocirculation progressively decreased with altitude (LL > HL-3800 > HL-5100/No CMS). CMS also induced a decrease in macrocirculation (HL-5100/No CMS > Mild CMS = Mod/Sev CMS), while glyceryl trinitrate restored vascular function. Both oxidative stress and nitric oxide metabolites increased with altitude only. Principal component analysis revealed that increasing inflammation with altitude was associated with a progressive decline in both micro- and macrovascular function in healthy highlanders.

Interpretation

Both micro and macrovascular function are affected by chronic exposure to hypoxia, the latter being further compounded by CMS.

Funding

The “Fonds de dotation AGIR pour les maladies chroniques”, the “Air Liquide Foundation”, and the “French National Research Agency”.
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世界海拔最高城市的微血管和大血管功能:一项横断面研究
背景由于健康的高海拔当地人和慢性高山病(一种适应不良的高海拔病理,以红细胞增多和出现症状为特征--CMS)患者的血管对低氧的反应仍不清楚,因此研究了不同海拔的健康安第斯人和慢性高山病患者的炎症和氧化/亚硝基应激对微循环和大循环中内皮依赖性和非依赖性反应的作用:研究对象包括 94 名男性:18 名低地人(LL)、38 名长期生活在海拔 3800 米(n = 21-HL-3800)或世界上海拔最高的城市拉林科纳达(5100-5300 米)的健康高地人(n = 17-HL-5100/无 CMS)。此外,还招募了 14 名轻度(Mild CMS)和 24 名中度至重度(Mod/Sev CMS)CMS 患者。所有人都进行了两项反应性测试:i)局部热高血压(微循环)和 ii)血流介导的扩张(大循环)。结果微循环测试中的传导性和皮肤血流速度以及大循环随着海拔高度的升高而逐渐降低(LL > HL-3800 > HL-5100/无 CMS)。CMS 也会导致大循环减少(HL-5100/无 CMS >;轻度 CMS = 中度/重度 CMS),而三硝酸甘油则可恢复血管功能。氧化应激和一氧化氮代谢物仅随海拔升高而增加。主成分分析表明,随着海拔的升高,炎症的增加与健康高原人微血管和大血管功能的逐渐衰退有关。
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期刊介绍: The Lancet Regional Health – Americas, an open-access journal, contributes to The Lancet's global initiative by focusing on health-care quality and access in the Americas. It aims to advance clinical practice and health policy in the region, promoting better health outcomes. The journal publishes high-quality original research advocating change or shedding light on clinical practice and health policy. It welcomes submissions on various regional health topics, including infectious diseases, non-communicable diseases, child and adolescent health, maternal and reproductive health, emergency care, health policy, and health equity.
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