Dietary antioxidant vitamins intake and systemic vascular function in Bolivian highlanders with Chronic Mountain Sickness

Introduction:
Chronic mountain sickness (CMS), a high-altitude maladaptive syndrome, is a public health problem experienced primarily by Andean countries (1). Impaired systemic vascular endothelial function subsequent to a free radical-mediated reduction in nitric oxide (NO) bioavailability [oxidative-nitrosative stress (OXNOS)] may contribute to the increased cardiovascular risk observed in CMS patients (CMS+) (2, 3, 4, 5). The observation that antioxidant defences are depressed in CMS+ tentatively suggests that inadequate dietary intake may predispose to vascular dysfunction. Hence, the aim of the study was to investigate the intake of dietary antioxidant vitamins, fruit and vegetable consumption, and systemic vascular function in CMS+ and healthy, well-adapted highlanders (CMS-). We hypothesised that CMS+ will show impaired systemic vascular function subsequent to a low intake of dietary antioxidant vitamins.

Methods:
Thirty-three male Bolivian highlanders with CMS (n=20, CMS+; age 58±8 y), without CMS (n=13, CMS-; age 54±7 y), and thirteen British male lowlanders born and bred close to sea level (n=13 controls; 60±7 y) consented to the study. Participants were interviewed to collect a 48-hour structured dietary recall. Dietary data were analysed using NetWISP dietary analysis software (Version 4.0, Tinuviel Software; Anglesey, UK). Systemic vascular function was assessed using flow-mediated dilation (FMD, duplex ultrasound), arterial stiffness (applanation tonometry), the latter defined by carotid-femoral pulse wave velocity (c-f PWV), augmentation index normalised for a heart rate of 75 beats/minute (AIx@75) and carotid intima-media thickness (cIMT). Data were tested for normality using Shapiro-Wilk W tests and analysed using one-way ANOVAs and post hoc Bonferroni-adjusted independent samples t-tests. Significance level was established at P<0.05.

Results
CMS+ patients reported lower intake of vitamin C (P = 0.003 vs. CMS-; P = <0.000 vs. controls) and carotene (P = 0.050 vs. CMS-; P = 0.058 vs. controls) due to inadequate consumption of fruit (P = <0.000 vs. controls) and vegetables (P = <0.000 vs. CMS-; P = <0.000 vs. controls). CMS+ exhibited impaired FMD (P = <0.001 vs. controls) and greater c-f PWV (P = <0.001 vs. controls) and AIx@75 (P = 0.022 vs. controls) compared to lowlander controls along with increased cIMT (P = 0.027 vs. CMS-) compared to CMS-.

Conclusion
Collectively, these findings demonstrate that CMS+ are characterised by inadequate intake of dietary antioxidant vitamins due to reduced consumption of fruit and vegetables. A corresponding reduction in dietary antioxidant vitamin intake may contribute to systemic OXNOS-mediated impairments in vascular function. Public health programmes need to consider targeted dietary interventions, including nutrition education and dietary modification, that may help improve the overall health of highlanders, especially CMS+ who may be at increased cardiovascular risk.

References
1. Villafuerte, FC, Corante, N 2016, 'Chronic Mountain Sickness: Clinical Aspects, Etiology, Management, and Treatment', High Alt Med Biol, 17, 61-69.
2. Bailey, DM, Brugniaux, JV, et al. 2019, 'Exaggerated systemic oxidative-inflammatory-nitrosative stress in chronic mountain sickness is associated with cognitive decline and depression', J Physiol, 597, 611-629.
3. Bailey, DM, Rimoldi, SF, et al. 2013, 'Oxidative-nitrosative stress and systemic vascular function in highlanders with and without exaggerated hypoxemia', Chest, 143, 444-451.
4. Rimoldi, SF, Rexhaj, E, et al. 2012, 'Systemic vascular dysfunction in patients with chronic mountain sickness', Chest, 141, 139-146.
5. Corante, N, Anza-Ramirez, C, et al. 2018, 'Excessive Erythrocytosis and Cardiovascular Risk in Andean Highlanders', High Alt Med Biol, 19, 221-231.