AMS is generally not related to gender, training, alcohol intake, or cigarette smoking.[31] Smoking may represent some kind of acclimatization to hypoxia and is associated with a slightly decreased risk to develop AMS.[34] However, in addition to all the well-known negative health effects, smoking will also impair long-term altitude acclimatization and

lung function.[34] Persons suffering from hypertension, coronary artery disease, and diabetes do not appear to be more prone to AMS than healthy persons.[11, 35] Richalet and colleagues recently documented in a large sample of mountaineers that a low Daporinad concentration ventilatory response to hypoxia at exercise and marked desaturation at exercise in hypoxia are strong risk factors for high-altitude illness.[29] Similarly, check details pronounced arterial oxygen desaturation during sleep has been suggested to be an important risk factor for the development of AMS.[10] Periodic breathing typically occurs during sleeping at high altitudes and may be advantageous up to about 3,000 to 3,500 m because oxygen saturation is stabilized at a relatively high level.[36] At altitudes up to 5,000 m, periodic breathing even appears to override the negative feedback loop in patients with risk of sleep-disordered breathing leading

to revolving sleep apneas. Between 4,500 and 5,500 m altitudes, periodic breathing is replaced by high-frequency breathing driven directly by hypoxia-sensitive neurons in the brain stem.[20] However, at Leukotriene-A4 hydrolase higher altitudes,

frequent arousals cause total sleep deprivation and mental and physical impairments.[36] Patients with AMS can develop HACE when SaO2 further drops, for example, by further ascent or when additionally HAPE occurs.[37] Therefore, further ascending with AMS or existing HAPE are risk factors for HACE, which is thought to be a progression of AMS representing the final encephalopathic, life-threatening stage of cerebral altitude effects.[7, 11, 37] One risk for the development of HAPE relates to individual susceptibility.[3] A genetic predisposition may lead to an exaggerated pulmonary vascular response to hypoxia and as a consequence to pulmonary hypertension.[3, 12] Pulmonary hypertension is the hallmark in the development of the disease,[12] but also other genetic defects might contribute to the pathogenesis (eg, defect of the transepithelial sodium transport[12]). Additionally, a large patent foramen ovale in the heart may contribute to exaggerated arterial hypoxemia and facilitate HAPE at high altitude.[38] Other individual risk factors include hypothermia as well as anatomical or functional abnormalities (eg, having only one lung) facilitating pulmonary hypertension.[12] Finally, men may be more susceptible to HAPE than women, although the mechanisms are probably multifactorial.