Long-Term Intermittent Work at High Altitude: Right Heart Functional and Morphological Status and Associated Cardiometabolic Factors

Abstract

Background: Living at high altitude or with chronic hypoxia implies functional and morphological changes in the right ventricle and pulmonary vasculature with a 10% prevalence of high-altitude pulmonary hypertension (HAPH). The implications of working intermittently (day shifts) at high altitude (hypobaric hypoxia) over the long term are still not well-defined. The aim of this study was to evaluate the right cardiac circuit status along with potentially contributory metabolic variables and distinctive responses after long exposure to the latter condition. Methods: A cross-sectional study of 120 healthy miners working at an altitude of 4,400-4,800 m for over 5 years in 7-day commuting shifts was designed. Echocardiography was performed on day 2 at sea level. Additionally, biomedical and biochemical variables, Lake Louise scores (LLSs), sleep disturbances and physiological variables were measured at altitude and at sea level. Results: The population was 41.8 ± 0.7 years old, with an average of 14 ± 0.5 (range 5-29) years spent at altitude. Most subjects still suffered from mild to moderate symptoms of acute mountain sickness (mild was an LLS of 3-5 points, including cephalea; moderate was LLS of 6-10 points) (38.3%) at the end of day 1 of the shift. Echocardiography showed a 23% mean pulmonary artery pressure (mPAP) >25 mmHg, 9% HAPH (≥30 mmHg), 85% mild increase in right ventricle wall thickness (≥5 mm), 64% mild right ventricle dilation, low pulmonary vascular resistance (PVR) and fairly good ventricle performance. Asymmetric dimethylarginine (ADMA) (OR 8.84 (1.18-66.39); p < 0.05) and insulin (OR: 1.11 (1.02-1.20); p < 0.05) were associated with elevated mPAP and were defined as a cut-off. Interestingly, the correspondence analysis identified association patterns of several other variables (metabolic, labor, and biomedical) with higher mPAP. Conclusions: Working intermittently at high altitude involves a distinctive pattern. The most relevant and novel characteristics are a greater prevalence of elevated mPAP and HAPH than previously reported at chronic intermittent hypobaric hypoxia (CIHH), which is accompanied by subsequent morphological characteristics. These findings are associated with cardiometabolic factors (insulin and ADMA). However, the functional repercussions seem to be minor or negligible. This research contributes to our understanding and surveillance of this unique model of chronic intermittent high-altitude exposure.

Keywords: altitude; chronic intermittent hypobaric hypoxia; high-altitude pulmonary hypertension; insulin and ADMA; right heart.

Figure 1

Comparison between insulin, mPAP, and HOMA-IR (A) insulin (INS; IU) according to mean pulmonary artery pressure values (mPAP; mmHg); cut-off point < ≥30 mmHg; and (B) homeostatic model assessment (HOMA-IR; Index) according to insulin values: cut-off point < ≥20 IU. Values are means ($\overline{X}$)±SE (standard error); *p < 0.01.

Figure 2

Comparison of ADMA and mPAP (cut-off point < ≥30 mmHg). Asymmetric dimethylarginine (ADMA; μmol/L); mean pulmonary artery pressures (mPAP; mmHg). Values are means ($\overline{X}$)±SE (standard error); *p < 0.01.

Figure 3

Representative echocardiographic images (A) right ventricular hypertrophy and (B) Acceleration curve of pulmonary flow at pulmonary artery outflow tract.

Figure 4

Association patterns between variables by multiple correspondence analysis. Variables and cut-off points: asymmetric dimethylarginine (ADMA; μmol/L; < ≥0.8), age (years old; < ≥40), body mass index (BMI; kg/ m²; < ≥25), high-altitude years (HAy; < ≥15 years), insulin (INS; IU; < ≥20), mean pulmonary artery pressure (PAPm, mmHg; < ≥25), waist perimeter (WP; cm; < ≥100), right ventricle wall thickness (RVT; mm; < ≥5) and triglycerides (TG; mg/dL; < ≥150). Explained proportion of total variance of dimension 1 = 57.3% and dimension 2 = 42%. Cronbach's alpha: 0.594.