Physiological acclimatization to altitude can impose an increased workload on the cardiovascular system. At high altitudes, considered those higher than 2500 m (~8200 ft) above sea level, physiologic responses may start to represent challenges for the human body. This article reviews available evidence on the effects of high altitude among patients with cardiovascular conditions, and the risks of developing clinical cardiovascular events. The following are points to remember:

1. Physics and cardiovascular physiology at high altitude:
   • High altitude is associated with progressive reduction in barometric pressure, air temperature, and humidity. A reduction in barometric pressure results in “hypobaric hypoxia.” “Acclimatization” consists of physiological responses to help maintain adequate tissue oxygen, and includes increase in ventilation, cardiac output, red cell mass and blood oxygen-carrying capacity, and other metabolic modifications at the microvascular and cellular levels.
   • High altitude is associated with increases in systemic blood pressure (BP), both rest and exercise heart rate (HR), and minute ventilation.
   • Alveolar hypoxia and arterial hypoxemia induce pulmonary circulation vasoconstriction, resulting in increased pulmonary vascular resistance and pulmonary artery pressure (hypoxic pulmonary vasoconstriction).
   • High altitude is associated with decreases in left ventricle (LV) diastolic and systolic volumes with increased LV sphericity, and decreased LV mass.
2. Heart failure: Associated comorbidities including pulmonary hypertension, chronic obstructive lung disease, chronic kidney disease, cardiac ischemia, anemia, and thrombophilia make patients with heart failure more vulnerable to the high altitude environment.
3. Ischemic heart disease: Total oxygen demand is constant for a given workload, and myocardial oxygen extraction already is very high at sea level; acute exposure to high altitude demands that cardiac output must increase to maintain oxygen delivery despite the reduced blood arterial oxygen content. Patients with coronary artery disease (CAD) may face added difficulties with high altitude because of already increased basal coronary flow at sea level, impairment in arterial elastic properties associated with atherosclerosis, and coronary microvascular dysfunction. However, few data are available regarding altitude-induced ischemia in CAD patients.
4. Systemic arterial hypertension:
   • Patients with systemic hypertension may be more susceptible to high altitude due to pre-existing elevation in hypoxic peripheral and central chemo-reflex sensitivity, and alterations in calcium homeostasis.
   • Different antihypertensive agents may have variable effects at altitude.
     • Nonselective beta-blockade with carvedilol in normal subjects is associated with a significant reduction in the BP response to high altitude, but is associated with reduced arterial hemoglobin oxygen saturation and exercise tolerance.
     • A highly selective beta-1 adrenergic receptor blocker (nebivolol) also was effective in reducing the BP response to high altitude, with a lesser reduction in exercise tolerance.
     • Monotherapy with a long-acting angiotensin receptor blocker (telmisartan) demonstrated an impressive response on both daytime and night-time BP, but only up to an altitude of 3400 m.
5. Arrhythmias and implanted devices:
   • Although increased sympathetic activity, decreased SaO₂, and increased right ventricular (RV) work and cellular transmembrane potassium shifts associated with high altitude might predispose for arrhythmias, an increase in malignant arrhythmias at altitude has not been demonstrated.
   • Although little information is available, brief exposure to a simulated altitude of 4000 m apparently does not affect ventricular stimulation thresholds.
6. Pulmonary hypertension: In one study, patients with World Health Organization (WHO) Group 1 pulmonary artery hypertension on vasodilator treatment did not experience an acute deterioration in RV function during simulated mild altitude. However, in light of the known physiological effects of hypoxia, supplemental oxygen administration should be considered in-flight or at altitudes >1500-2000 m among patients with functional class III and IV pulmonary hypertension and for those with PaO₂ consistently <60 mm Hg.
7. Congenital heart disease: Patients with cyanotic heart conditions and right-to-left shunting are likely to develop more severe hypoxemia than healthy individuals, as the increase in pulmonary vascular resistance at high altitude can worsen the right-to-left shunt. However, reduced blood oxygen content is not dangerous by itself, because cardiac output and hematocrit increase sufficiently to maintain adequate systemic oxygen delivery.
8. Cerebrovascular conditions:
   • Ischemic stroke: Albeit with limited evidence is, high altitude exposure seems to pose a risk of cerebral ischemia for patients who already have suffered an ischemic stroke; both because of the direct effect of hypoxia, and due to a reduced cerebrovascular reactivity.
   • Hemorrhagic stroke: Arterial blood pressure elevation at high altitude increases the risk of rupture of cerebral aneurysms and arterial venous malformations, as well as carrying a theoretical risk of hypertension-related cerebral hemorrhage. However, there are no data on the incidence of intracranial hemorrhage at high altitude.

Keywords: Acclimatization, Altitude, Anemia, Angiotensin Receptor Antagonists, Antihypertensive Agents, Arrhythmias, Cardiac, Atherosclerosis, Blood Pressure, Brain Ischemia, Cerebral Hemorrhage, Comorbidity, Coronary Artery Disease, Erythrocyte Volume, Exercise Tolerance, Heart Defects, Congenital, Heart Failure, Heart Rate, Hematocrit, Hemoglobins, Homeostasis, Hypertension, Hypertension, Pulmonary, Hypoxia, Brain, Intracranial Aneurysm, Intracranial Hemorrhages, Pulmonary Disease, Chronic Obstructive, Renal Insufficiency, Chronic, Secondary Prevention, Stroke, Thrombophilia, Vascular Resistance, Vasoconstriction, Vasodilator Agents

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