, Germaine Cornelissen2 and Franz Halberg2
(1)
Department of Chronomics & Gerontology, Tokyo Women’s Medical University Medical Center East, Arakawa-ku, Tokyo, Japan
(2)
Halberg Chronobiology Center, University of Minnesota, Minneapolis, MN, USA
Abstract
Humans adjusted to ambient hypoxia via changes in the expression of hypoxia-related genes. Gender differences, however, have not yet been studied from the viewpoint of a glocal (combined global and local) comprehensive assessment. Using a glocal comprehensive assessment, we studied the effects of high altitude on pulse oximetry (SpO2), blood pressure (BP), heart rate (HR), aortic stiffness of cardio-ankle vascular index (CAVI), and autonomic cardiovascular and cognitive function. Subjects consisted of 25,211 Japanese (11,845 women) and 1,858 Ladakhis (1,081 women). As compared to Japanese living at low altitude, highland people showed higher CAVI values in both men and women. Highland people also had lower LF and HF components and a higher LF/HF ratio, lower SpO2, higher diastolic BP, and higher HR. Elderly residents in the high-altitude community had a poorer cognitive function, estimated by the Kohs block design test, and slept less. These findings suggest that the hypobaric hypoxic condition at high altitude induced a decrease in parasympathetic activity and an increase in sympathetic drive, which may result in an imbalance of the cardiopulmonary-vascular functions in Ladakhis. As to gender differences, systolic BP and CAVI measures were higher in Ladakhi women. Ladakhi women showed a steeper negative slope of the regression line between SpO2 and age and steeper slopes of the regression lines between systolic and diastolic BP vs. age than Ladakhi men.
Keywords
High-altitude communityGlocal comprehensive assessmentCardio-ankle vascular indexCognitive functionGender difference12.1 Introduction
Leh, Ladakh, is a strongly Buddhist district of east Kashmir, adjacent to Tibet, lying at 3,524 m above sea level between the ranges of Karakoram and the Himalayas. It was virtually unknown to the West until the 1970s, and it still has limited contacts with the outside world today. The economy is based on subsistence farmers who grow mainly barley but also legumes. Whereas physiological adjustment to high altitude has been studied in resident populations of the Andes, Tibet, Nepal, North America, and Europe, much less is known about high-altitude natives in India.
The study of human biology in the mountains began about 2,000 years ago. The Jesuit Jose de Acosta, a sixteenth century traveler in the Andes of Peru, was the first to attribute his discomfort when reaching an altitude of 4,802 m to the “thin air” [1]. Numerous physiological studies attempted to understand the effects of ambient hypoxia on humans. We have learned how humans adapted to it via changes in the expression of hypoxia-related genes [2–11]. We also noticed that the adaptation to hypobaric hypoxia at high altitude was more pronounced in men than in women. Gender differences, however, have not yet been studied from the viewpoint of a glocal (combined global and local) comprehensive assessment [12–14].
12.2 Glocal Comprehensive Assessment in High Altitude
This investigation focused on chronoecology in Ladakh, using a sleep-habit questionnaire, endpoints of the circulation, autonomic nervous function, and quality of health as a physiological test system at high altitude, for comparison with chronoecological studies in several Japanese towns (Tosa, Kochi and Uraus, Hokkaido). Individuals living permanently at high altitude must contend with chronic hypobaric hypoxia. Several compensatory mechanisms have evolved to enable them to live and work in this inhospitable environment. We examined whether Ladakhi people have acquired any kind of notable cardiovascular adaptation.
To determine any effects of high altitude on the cardiopulmonary and neurocognitive functions, physical examinations were performed on 1,858 resting Ladakhi subjects living in 119 villages at altitudes between 2,200 and 4,590 m (1,081 women and 777 men, aged from 13 to 92 years, average 51.4 years). They included the measurement of pulse oximetry (SpO2), blood pressure (BP), heart rate (HR), respiration rate (RR), and body mass index (BMI). BP and HR were measured twice in each of the sitting, supine, and standing positions using a semiautomated BP device (UA-767PC, A&D Co, Ltd, Tokyo, Japan). Orthostatic hypotension (OH) was defined when systolic (S) or diastolic (D) BP decreased by more than 20 or 10 mmHg from the supine to the standing position, respectively. Orthostatic hypertension (OHT) was defined when SBP or DBP increased by more than 20 or 10 mmHg from the supine to the standing position, respectively.
Aortic stiffness of cardio-ankle vascular index (CAVI) of right and left ankles [15, 16] was measured twice using a VaSera instrument (Fukuda Denshi, Tokyo) in the 1,858 Ladakhis as well as in 25,211 Japanese (13,366 men and 11,845 women, aged from 16 to 98 years, average 48.0 years). The average and maximal values from the four measurements were defined as CAVI-mean and CAVI-max, respectively.
Using a glocal comprehensive assessment, including a sleep-habit questionnaire, we studied the effects of high altitude on the autonomic cardiovascular function in Japanese T-town and Uraus and in several villages, including Leh, Ladakh. With continuous monitoring of the pulse-pulse interval using a newly developed pulse oximetry monitor (Konica-Minolta, Japan), we analyzed the autonomic cardiovascular activity.
12.3 Neurocognitive Functions in High Altitude
Of the 1,858 Ladakhis living at an altitude of 2,200–4,590 m, we selected middle-aged and elderly subjects over 40 years of age (1,331 citizens aged from 40 to 92 years, average 58.5 years). Any gender differences in compensatory mechanisms were investigated by comparing the cardiovascular functions, including BP, HR, ECG, and CAVI, between men and women in three groups living at different altitudes, i.e., from 2,500 to 3,000 m (66 men, average 62.7 years; 61 women, average 54.2 years), from 3,200 to 3,720 m (390 men, average 62.6 years; 635 women, average 56.2 years), and from 3,800 to 4,590 m (73 men, average 60.3 years; 110 women, average 55.5 years). We also assessed any gender-dependent effect of altitude by comparing the slopes of regression lines of BP with age between women and men.
The Kohs block design test and the time estimation test were used to assess the overall cognitive function. Subjects were 54 Ladakhi residents older than 70 years(46 men, 73.2 years of age) living at an altitude of 3,300 to 4,600 m and 67 residents of a Japanese town (Uraus) older than 70 years (52 men, 73.2 years of age). Time estimation was performed in a supine position, 10-s and 60-s being estimated with and without counting. The Up & Go test measured, in seconds, the time it took the subject to stand up from a chair, walk a distance of 3 m, turn, walk back to the chair, and sit down again. Functional reach, used to evaluate balance, represents the maximal distance a subject can reach forward beyond arm’s length while maintaining a fixed base of support in the standing position. Manual dexterity was assessed using a panel with combinations of ten hooks (hook-on), ten big buttons (button-on-and-off), and five small buttons (button-on-and-off). The total manual dexterity time in sec., defined as the button score (Button), was calculated by adding the average times for one hook-on and one big or small button-on-and-off.
Vascular stiffness and compliance of brachial artery were measured by using a chronos instrument (A&D company, Tokyo) in 80 male Japanese (28–59 years of age, average 44.9 years) and in 45 male Ladakhis (25–67 years of age, average 47.9 years) living at an altitude of 3,524 m. This instrument can measure vascular stiffness and compliance of brachial artery as Pba (pressure of initial point assessed by pressure-area correlation curve, reflecting a difference of volume of right brachial artery vs. 10 mmHg alteration of pressure difference between arm and artery), A40 (cross-sectional area of brachial artery on 40 mmHg cuff pressure measured by color Doppler echogram), eA (estimated cross-sectional area of brachial artery), dAmax (maximum change of cross-sectional area of brachial artery), Kc/V40 (volume compliance of brachial artery normalized by vessel volume), β40 (stiffness on 40 mmHg cuff pressure), hb PWV (heart brachial PWV), and ha PWV (heart ankle PWV).
12.4 Aortic Stiffness of Cardio-Ankle Vascular Index (CAVI)
Ladakhi people showed increased aortic stiffness estimated by CAVI. Japanese and Ladakhi subjects were classified into 13 age groups, in 5-year classes from under 25 years to over 80 years, as shown in Table 12.1. CAVI values increased with age in both Ladakhi and Japanese people. Highlanders showed higher CAVI-max and also higher SBP values than lowlanders.
Table. 12.1
Comparison of age-matched CAVI-max* values between Japanese and Ladakhi people
12.5 Cardiopulmonary Autonomic Activity in High Altitude
Cardiovascular function was impaired in elderly Ladakhis compared to Japanese subjects. Autonomic cardiovascular activity was compared between 54 Ladakhi residents (46 men, 73.2 years of age) living at an altitude of 3,300–4,600 m and 67 residents of a Japanese Uraus (52 men, 73.2 years of age). High-altitude residents of Leh slept less (6.9 vs. 7.8 hours, p < 0.001), had a shorter time for falling asleep (15.5 vs. 25.6 min, p < 0.005), and had a lower SpO2 (84.4 vs. 96.0 %, p < 0.00001). Compared to Japanese subjects, they also had lower CVRR (p < 0.05), VLF (p < 0.00001), LF (p < 0.05), and HF (p < 0.001) components and a higher LF/HF ratio (2.35 vs. 1.69, p < 0.05), DBP (p < 0.05), and heart rate (p < 0.00001).
Next, we checked SpO2, respiration rate, BP, and ECG findings in the elderly in Ladakh and were surprised. Residents in Ladakh suffered less coronary artery disease, atrial fibrillation, and metabolic syndrome (3 %, 0 %, and 3 %, respectively). In Leh at 3,524 m, elderly residents had a lower SpO2 and a higher RR than elderly Japanese residents in Tosa (SpO2, 88.0 ± 4.3 % vs. 96.6 ± 1.2 %, p < 0.0001; RR, 21.1 ± 4.2 vs. 17.8 ± 4.2, p < 0.0001). All six measurements of DBP and five of the 6 HR measurements were statistically significantly higher in Leh than in Tosa. Changes in HR from the supine to the standing position were larger in Leh than in Tosa (13.8 ± 8.1 bpm vs. 9.9 ± 6.7 bpm, p < 0.001). A higher voltage of the QRS complex (SV1 + RV5) was observed in the ECG of Leh’s residents, but the so-called lifestyle-related diseases were very rare there.
12.6 Men Better Adapted to Ambient Hypoxia than Women
The Ladakhi people must have obtained some kind of characteristic adaptation to their high-altitude environment. Notably, there was a different cardiovascular adaptation between men and women; men seem to be better adapted to ambient hypoxia than women in Ladakh. Compensatory mechanisms were examined in 1,334 middle-aged and elderly Ladakhis (528 men and 806 women) by comparing cardiovascular functions among three groups living at different altitudes, namely from 2,500 to 3,000 m (66 men and 61 women), from 3,200 to 3,720 m (390 men and 635 women), and from 3,800 to 4,590 m (72 men and 110 women). Results are shown in Tables 12.2 and 12.3.
Table 12.2
Cardiovascular and other characteristics of men at different high altitudes in Ladakh, Kashmir, India (n=528)
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
