The Impact of High Altitude on Endothelial Dysfunction of Cardiovascular Patients in Saudi Arabia: A Biochemical Study

High-altitude dwellers have successfully evolved adaptive regulatory mechanisms to survive in a chronic hypoxic environment. Risk assessment regarding high altitude exposure of patients with coronary heart disease (CHD) is of increasing interest. The aim of our study, therefore, was to investigate the biochemical effect of high altitude on modulation of the adaptive response of endothelial functions in patients with cardiovascular diseases (CVD) including myocardial ischemia (MI) or CHD patients living at high altitude in Saudi Arabia. Subjects: This study included 271 subjects composed of 136 patients (84 men and 52 women) suffering from cardiovascular diseases with age range 40 - 68 (mean 54) years, and 135 apparently healthy control subjects (69 men and 66 women) with age range 40 - 65 (mean 52.5) years. All individuals selected for this study were divided into four groups: A- 68 patients suffering from CVD from the cardiology outpatient clinic of Aseer Central Hospital, Abha city, KSA (2,200 meters above sea level) representing high altitude group. B- 68 apparently healthy control volunteer subjects from Abha city, KSA. C- 68 patients suffering from CVD from the cardiology outpatient clinic of King Abdulaziz Hospital, Makkah city, representing sea level group. D- 67 apparently healthy control volunteer subjects from Makkah city. Methods: Serum biochemical measurements for patients and healthy subjects were performed including: Fasting blood sugar, kidney and liver function tests, plasma lipid profile including: total cholesterol (TC), High density lipoprotein cholesterol (HDLc), Low Density Lipoprotein (LDLc) and triglycerides (TG). In addition, parameters of vascular endothelial functions including: Nitric Oxide (NO) in the form of serum nitrite and nitrate (NO2 - /NO3 - ) concentrations, serum endothelin-1 (ET-1) and vascular cell adhesion molecule (VCAM-1) were also measured. Results: Measurements confirmed higher levels of ET-1 in high altitude control healthy subjects compared with those at sea level (P < 0.001) and also in high altitude cardiovascular patients compared with those at sea level (P < 0.001). Our results also, showed that there was a significant elevation of serum levels of ET-1 in patients group compared to the healthy control group either at high altitude (P < 0.001) or at sea level (P < 0.001). As regards VCAM-1, our results confirmed higher serum levels of VCAM-1 in high altitude control healthy subjects compared with those at sea level (P = 0.015) and also in high altitude cardiovascular patients compared with those at sea level (P = 0.013). Our results also, showed that, there are was a significant elevation of serum levels of VCAM-1 in patients group compared to the healthy control group either at high altitude (P < 0.001) or at sea level (P < 0.001). Our results confirmed higher levels of nitrite/nitrate in high altitude control healthy subjects compared with those at sea level (P = 0.003) and also in high altitude cardiovascular patients compared with those at sea level (P = 0.01). In conclusion, our data suggest that chronic hypoxia at high altitude may lead to higher circulating concentrations of these important vasoactive compounds (VCAM-1, ET-1 and NO), either as a direct result of hypoxia or as adaptive response to chronic high-altitude exposure. This process could imply a potential role for the measurement of these compounds in the prognostic evaluation of patients with CVD. Future studies with the use of ET receptor antagonists as part of a multidrug regimen are also needed especially for cardiovascular disease patients living at high altitude.