Micro- and macrovascular function in the highest city in the world: a cross sectional study
Yann Savina, Aurélien Pichon, Lucas Lemaire, Connor A. Howe, Mathilde Ulliel‐Roche, Sarah Skinner, Élie Nader, Nicolas Guillot, Émeric Stauffer, Matthieu Roustit, Iván Hancco, Paul Robach, François Estève, Vincent Pialoux, Elisa Perger, Gianfranco Parati, Philip N. Ainslie, Stéphane Doutreleau, Philippe Connes, Samuel Vergès, Julien V. Brugniaux
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".