Markers of cardiovascular risk and their reversibility with acute oxygen therapy in Kyrgyz highlanders with high altitude pulmonary hypertension

Background: High altitude pulmonary hypertension (HAPH), a chronic altitude related illness, is associated with hypoxemia, dyspnea and reduced exercise performance. We evaluated ECG and pulse wave-derived markers of cardiovascular risk in highlanders with HAPH (HAPH+) in comparison to healthy highlanders (HH) and lowlanders (LL) and the effects of hyperoxia. Methods: We studied 34 HAPH+ and 54 HH at Aksay (3250 m), and 34 LL at Bishkek (760 m), Kyrgyzstan. Mean pulmonary artery pressure by echocardiography was mean +/- SD 34 +/- 3, 22 +/- 5, 16 +/- 4 mmHg, respectively (p < 0.05 all comparisons). During quiet rest, breathing room air or oxygen in randomized order, we measured heart-rate adjusted QT interval (QTc), an ECG derived marker of increased cardiovascular mortality, and arterial stiffness index (SI), a marker of cardiovascular disease derived from pulse oximetry plethysmograms. Results: Pulse oximetry in HAPH+, HH and LL was, mean +/- SD, 88 +/- 4, 92 +/- 2 and 95 +/- 2%, respectively (p < 0.05 vs HAPH+, both comparisons). QTc in HAPH+, HH and LL was 422 +/- 24, 405 +/- 27, 400 +/- 28 ms (p < 0.05 HAPH+ vs. others); corresponding SI was 10.5 +/- 1.9, 8.4 +/- 2.6, 8.5 +/- 2.0 m/s, heart rate was 75 +/- 8, 68 +/- 8, 70 +/- 10 bpm (p < 0.05, corresponding comparisons HAPH+ vs. others). In regression analysis, HAPH+ was an independent predictor of increased QTc and SI when controlled for several confounders. Oxygen breathing increased SI in HH but not in HAPH+, and reduced QTc in all groups. Conclusions: Our data suggest that HAPH+ but not HH may be at increased risk of cardiovascular mortality and morbidity compared to LL. The lack of a further increase of the elevated SI during hyperoxia in HAPH+ may indicate dysfunctional control of vascular tone and/or remodelling. (C) 2021 Sociedade Portuguesa de Pneumologia. Published by Elsevier Espana, S.L.U.