title: Cardiovascular function in healthy Himalayan high-altitude dwellers.
abstract: BACKGROUND
  Residents of the Himalayan valleys uniquely adapted to their hypoxic environment in terms of pulmonary vasculature, but their systemic vascular function is still largely unexplored. The aim of the study was to investigate vascular function and structure in rural Sherpa population, permanently living at high altitude in Nepal (HA), in comparison with control Caucasian subjects (C) living at sea level.
  
  
  RESULTS
  95 HA and 64 C were enrolled. Cardiac ultrasound, flow-mediated dilation (FMD) of the brachial artery, carotid geometry and stiffness, and aortic pulse wave velocity (PWV) were performed. The same protocol was repeated in 11 HA with reduced FMD, after 1-h 100% O2 administration. HA presented lower FMD (5.18 ± 3.10 vs. 6.44  ±  2.91%, p = 0.02) and hyperemic velocity than C (0.61 ± 0.24 vs. 0.75 ± 0.28 m/s, p = 0.008), while systolic pulmonary pressure was higher (29.4 ± 5.5 vs. 23.6 ± 4.8 mmHg, p < 0.0001). In multiple regression analysis performed in HA, hyperemic velocity remained an independent predictor of FMD, after adjustment for baseline brachial artery diameter, room temperature and pulse pressure, explaining 8.7% of its variance. On the contrary, in C brachial artery diameter remained the only independent predictor of FMD, after adjustment for confounders. HA presented also lower carotid IMT than C (0.509 ± 0.121 vs. 0.576 ± 0.122 mm, p < 0.0001), higher diameter (6.98 ± 1.07 vs. 6.81 ± 0.85 mm, p = 0.004 adjusted for body surface area) and circumferential wall stress (67.6 ± 13.1 vs. 56.4 ± 16.0 kPa, p < 0.0001), while PWV was similar. O2 administration did not modify vascular variables.
  
  
  CONCLUSIONS
  HA exhibit reduced NO-mediated dilation in the brachial artery, which is associated to reduced hyperemic response, indicating microcirculatory dysfunction. A peculiar carotid phenotype, characterized by reduced IMT and enlarged diameter, was also found.
authors.affiliation: Institute of Clinical Physiology - CNR, Pisa, Italy; Department of Clinical and Experimental Medicine, University of Pisa, Italy. Electronic address: rosam.bruno@gmail.com.
authors.forename: R M
authors.initials: RM
authors.lastname: Bruno
authors.affiliation: Biomedical Sport Studies Center, University of Ferrara, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Cogo
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Ghiadoni
authors.affiliation: Biomedical Sport Studies Center, University of Ferrara, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Duo
authors.affiliation: Biomedical Sport Studies Center, University of Ferrara, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Pomidori
authors.affiliation: Nepal International Clinic, Kathmandu, Nepal.
authors.forename: R
authors.initials: R
authors.lastname: Sharma
authors.affiliation: Nepal International Clinic, Kathmandu, Nepal.
authors.forename: G B
authors.initials: GB
authors.lastname: Thapa
authors.affiliation: Nepal International Clinic, Kathmandu, Nepal.
authors.forename: B
authors.initials: B
authors.lastname: Basnyat
authors.affiliation: Department of Experimental Medicine, Laboratory of Clinical Physiology and Sport Medicine, University of Milano-Bicocca, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Bartesaghi
authors.affiliation: Institute of Clinical Physiology - CNR, Pisa, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Picano
authors.affiliation: Institute of Clinical Physiology - CNR, Pisa, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Sicari
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Taddei
authors.affiliation: Institute of Clinical Physiology - CNR, Pisa, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Pratali
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D000293:Adolescent; D000328:Adult; D000531:Altitude; D000886:Anthropometry; D001783:Blood Flow Velocity; D001916:Brachial Artery / Q000502:physiology; D002320:Cardiovascular Physiological Phenomena; D059168:Carotid Intima-Media Thickness; D015150:Echocardiography, Doppler; D004730:Endothelium, Vascular / Q000502:physiology; D005006:Ethnicity; D005260:Female; D018056:Hemorheology; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D009390:Nepal; D009569:Nitric Oxide / Q000502:physiology; D010100:Oxygen / Q000097:blood / Q000494:pharmacology; D010641:Phenotype; D063177:Pulse Wave Analysis; D012016:Reference Values; D012424:Rural Population; D059289:Vascular Stiffness; D014664:Vasodilation / Q000502:physiology; D055815:Young Adult
chemical_list: D009569:Nitric Oxide; D010100:Oxygen
keywords: Arterial stiffness; Carotid remodeling; Echocardiography; Endothelial function; High altitude; Hypoxia