Can Patients with Coronary Heart Disease Go to High Altitude?

Abstract

Dehnert, Christoph, and Peter Bärtsch. Can patients with coronary heart disease go to high altitude? High Alt. Med. Biol. 11:183–187, 2010.—Tourism to high altitude is very popular and includes elderly people with both manifest and subclinical coronary heart disease (CHD). Thus, risk assessment regarding high altitude exposure of patients with CHD is of increasing interest, and individual recommendations are expected despite the lack of sufficient scientific evidence. The major factor increasing cardiac stress is hypoxia. At rest and for a given external workload, myocardial oxygen demand is increased at altitude, particularly in nonacclimatized individuals, and there is some evidence that blood-flow reserve is reduced in atherosclerotic coronary arteries even in the absence of severe stenosis. Despite a possible imbalance between oxygen demand and oxygen delivery, studies on selected patients have shown that exposure and exercise at altitudes of 3000 to 3500 m is generally safe for patients with stable CHD and sufficient work capacity. During the first days at altitude, patients with stable angina may develop symptoms of myocardial ischemia at slightly lower heart rate × blood-pressure products. Adverse cardiac events, however, such as unstable angina coronary syndromes, do not occur more frequently compared with sea level except for those who are unaccustomed to exercise. Therefore, training should start before going to altitude, and the altitude-related decrease in exercise capacity should be considered. Travel to 3500 m should be avoided unless patients have stable disease, preserved left ventricular function without residual capacity, and above-normal exercise capacity. CHD patients should avoid travel to elevations above 4500 m owing to severe hypoxia at these altitudes. The risk assessment of CHD patients at altitude should always consider a possible absence of medical support and that cardiovascular events may turn into disaster.

Introduction

Development of infrastructure makes access to high altitude regions easy today, which offers the opportunity for many people to travel to high altitude, including patients with preexisting coronary heart disease (CHD). At high altitude, ambient oxygen partial pressure and consequently arterial oxygen partial pressure is reduced, which in turn may reduce oxygen supply to the myocardium. High altitude-related hypoxia is additionally associated with physiological changes in the cardiovascular system, in particular the activation of the sympathetic system (Hansen and Sander, 2003). Most of these changes increase cardiac work, which in turn may increase cardiac risk in CHD patients.

If CHD patients are going to high altitude, they may ask for advice. Bcause of the paucity of studies, counseling these patients is not simple, and evidence-based recommendations are rarely possible. Nevertheless, CHD patients expect individual advice from their physicians. This paper should help the clinician who is advising CHD patients who wish to travel to high altitude to make reasonable decisions on an individual basis. It specifically addresses question like who can go how high, what type of pretravel evaluation is necessary, what kind of precautions or additional measures need to be taken during the trip, and how does exercise capacity change at altitude.

Acute Exposure to High Altitude

Physiological changes in the cardiovascular system are most pronounced during the first days at altitude, and most of them increase cardiac work. These changes are described in detail elsewhere (Bärtsch and Gibbs, 2007) and briefly summarized here. Because of the S-shape of the hemoglobin dissociation curve, patients will experience oxygen desaturation at elevations above 3000 m. During exercise, however, desaturation may occur at much lower altitudes, particularly in the elderly patient (Burtscher et al., 2001). Total oxygen demand for a given workload is independent of altitude (Lundby et al., 2007). Therefore, owing to the reduced arterial oxygen content of the blood, cardiac output must increase to maintain oxygen delivery for a given workload. This increase in cardiac output is mainly caused by an increase of heart rate, since stroke volume does not change significantly compared with sea level, at least with acute exposure. Additionally, cardiac work is increased owing to the increased afterload for the left ventricle because of an increased sympathetic tone, arterial hypertension, and cold, as well as for the right ventricle because of hypoxic pulmonary vasoconstriction and cold. Further, an altitude- related decrease of exercise capacity is of importance. This decrease amounts to about a 1% reduction for Vo₂max per 100 m above 1500 m of altitude in healthy individuals (Fulco et al., 1998) and in CHD patients (Schmid et al., 2006). In patients with reduced left ventricular function, the decrease in exercise capacity is even more pronounced (Agostoni et al., 2000).

Myocardial Perfusion at High Altitude

When patients with CHD go to high altitude, the key question is whether the myocardium is adequately supplied with oxygen to avoid severe cardiac events, in particular during exercise. Myocardial work and myocardial oxygen demand are increased at altitude owing to increased heart rate, myocardial contractility, and right and left ventricular afterload. To increase myocardial oxygen supply, blood flow to the myocardium has to be increased, since myocardial oxygen extraction is almost maximal even at low altitude. In healthy subjects, hypoxia induces coronary vasodilatation to increase coronary and thus myocardial blood flow (Kaufmann et al., 2001). In the atherosclerotic-altered coronary arteries of CHD patients, endothelial dysfunction may lead to a paradoxical hypoxia-induced vasoconstriction, which further reduces myocardial oxygen supply (Gordon et al., 1989; Wyss et al., 2003; Arbab-Zadeh et al., 2009). At high altitude, the only way to increase blood flow to a region supplied by an atherosclerotic-altered artery is by sympathetic stimulation of collateral supply (Seiler, 2009; Rimoldi et al. 2010), which appears to be very efficient in most individuals. For example, significant ST segment depression with skiing at about 3200 m compared with exercise at sea level occurred with similar incidence (Grover et al., 1990). Further, in an unselected population and in CHD patients, exercise at 2440 and 3170 m did not show electrocardiogram (ECG) changes, suggesting ischemia more frequently than for exercise at sea level (Okin, 1970). In line with these findings, patients with stable angina report angina symptoms during treadmill exercise at the same heart rate × blood pressure product (double product) with acute altitude exposure (3100 m) compared with 1600 m (Morgan et al., 1990). Further, in CHD patients with moderately impaired left ventricular function (ejection fraction 39%), a symptom-limited exercise test at 2500 m did not cause angina, and no ECG signs of myocardial ischemia, arrhythmia, or other adverse events occurred (Erdmann et al., 1998). A similar observation is reported by Schmid and colleagues (2006) in CHD patients after revascularization undergoing symptom-limited exercise testing at the Jungfraujoch (3454 m). One study observing an increased incidence of ischemialike ECG changes during exercise at about 4600 m in soldiers without known CHD (Khanna et al., 1976) lacked convincing evidence of CHD in those with a positive exercise test. Levine and colleagues (1997), however, found a 5% lower double product at the angina threshold with acute hypobaric hypoxia equivalent to 2500 m compared with sea level. After an acclimatization period of 5 days at the same altitude, the threshold was the same again as at sea level, indicating that adaptation needs some time. In this study, no additional wall motion abnormalities could be detected by echocardiography, which is in accordance with echocardiographic measurements at 4200 m in acclimatized CHD patients (de Vries et al., 2010). There were no differences in left ventricular function and wall motion at altitude compared with sea level.

In summary, in patients with stable CHD at high altitude, signs of myocardial ischemia occur at similar or slightly reduced cardiac work, and left ventricular contractility is unaffected despite a possible reduction in coronary blood flow, suggesting that myocardial oxygenation is sufficient at least after a few days of acclimatization. There are almost no data regarding patients with unstable CHD at high altitude, because virtually all such patients have been excluded from clinical studies. However, there are strong theoretical reasons to suspect that they might have significant difficulty with ischemia at high altitude.

Adverse Cardiac Events in CHD Patients at High Altitude

There are even fewer data quantifying adverse cardiac events at high altitude, such as myocardial infarction, significant arrhythmia, or sudden death. There is a lack of sufficiently powered trials comparing CHD patients with appropriately matched control groups. Most data are from small, often uncontrolled studies, retrospective or anecdotal. Sometimes there is just opinion. Subjects examined in these studies often are self-selected, with a selection bias toward active and relatively well trained individuals. Among the individuals ascending to higher altitudes, the prevalence of CHD seems to be very rare, which explains the low number of cardiac events and cardiac deaths in this population (Dickinson et al., 1983; Shlim and Houston, 1989; Shlim and Gallie, 1992). Burtscher and colleagues (1993) analyzed sudden cardiac deaths during hiking or skiing in the Austrian alps. They found a two- to fourfold increased risk for sudden cardiac death only in men, but no increased risk in women. A more detailed analysis showed that the risk was only increased in those who were not regularly exercising, a group of patients who is already at increased risk for exercise-induced myocardial infarction (Mittleman et al., 1993; Willich et al., 1993) or sudden death (Albert et al., 2000) at sea level. The unaccustomed exercise together with altitude stress was suggested to increase the risk of sudden cardiac death. However, it remains unclear to which degree hypoxia itself contributed to this risk increase.

Summarizing these available data, the risk for sudden cardiac death in apparently healthy trekkers at higher altitudes seems not to be increased, although the risk cannot be estimated reliably. But does this also apply to the patient with a preexisting cardiac condition? Roach and colleagues (1995) found an altitude of 2500 m to be safe in an elderly population (mean age 70 yr) with about 20% of patients with known CHD. In almost 40%, he observed ischemialike ECG changes at 2500 m, but neither new ECG changes nor any kind of cardiac event occurred in the following 4 days at altitude in this population. During a rehabilitation program at and above 1700 m including more than 400 patients with CHD, of whom 141 had suffered a myocardial infarction, only one new myocardial infarction occurred after ascent to 3200 m. Other severe cardiac events, particularly higher grade cardiac arrhythmia, were not reported (Hallhuber et al., 1985). Levine and colleagues (1997) reported increased angina in 1 of 20 veterans (mean age 68 yr) and myocardial infarction after exercise testing on day 5 at 2500 m in another subject with known severe CHD. Schmid and colleagues (2006), in contrast, observed no cardiac event with maximal exercise testing at 3500 m in CHD patients. It must be mentioned, however, that Schmid only examined patients with good or only slightly reduced left ventricular function who had all undergone revascularization.

Compared with healthy individuals, patients who recently experienced myocardial infarction show higher sympathetic activity at altitude despite β-blockade, as well as reduced parasympathetic tone (Messerli-Burgy et al., 2009), which in turn may theoretically increase the risk for ventricular arrhythmias. But even subjects with impaired left ventricular function (ejection fraction 39%) did not present higher grade arrhythmia with maximal exercise testing (Erdmann et al., 1998) at 2500 m. Levine and colleagues (1997) showed that the number of premature ventricular contractions increased substantially at the same altitude and returned to sea level values after 5 days of acclimatization. Higher grade arrhythmia, however, was also not observed in this study. These findings are in accordance with a previous study that reported only an increased number of extra beats, but no adverse events, even at higher altitudes (Malconian et al., 1990), suggesting that the increased ectopy at altitude is benign and not associated with life-threatening arrhythmia. The large day-to-day variability of ventricular ectopic activity further complicates interpretation of these small data sets. Patients with preexisting higher grade arrhythmia have never been studied at high altitude; therefore, no information exists as to whether altitude exposure leads to an exacerbation of these arrhythmias.

Thrombosis Risk at Altitude

Acute exposure to altitudes below 4000 m is not associated with an increased risk for thromboembolic disease in individuals without thrombophilia (Bärtsch, 2006). Resistance to activated protein C, the most frequent thrombophilia in Caucasians, does not increase in vivo thrombin formation at 2400 m unless it is combined with the use of oral contraceptives (Schreijer et al., 2006). No data are available on the combined effects of hypoxia and thrombophilia at higher altitudes. In vitro and ex vivo tests suggest that hypoxia enhances platelet activation at 4559 m (Lehmann et al., 2006), whereas there are controversial results regarding platelet adhesion and aggregation in newcomers to lower altitudes (Sharma and Singh Hoon, 1978; Chatterji et al., 1982). Possible platelet activation by hypoxia is probably of minor importance, given that patients with CHD usually take inhibitors of platelet aggregation. Since acute myocardial infarction was rarely reported in the previously discussed studies, it is unlikely that acute exposure to altitudes below 3500 m has a major effect on plaque stability.

Recommendations for CHD Patients Going to High Altitude

Because of the paucity of data, it is not possible to give evidence-based recommendations for unacclimatized CHD patients ascending to high altitude. Based on the available data, we have tried to assemble reasonable recommendations for CHD patients for a relatively safe stay at altitude. All these recommendations are considered Level C (expert opinion only).

For a valid judgement of high altitude tolerance of CHD patients, a careful assessment of the underlying disease and of accompanying diseases should be performed. In particular, diseases affecting ventilation or gas exchange are of interest. The above-cited studies suggest that, for patients with a stable disease or patients with mild stable symptoms during exercise (Canadian Cardiovascular Society functional classes I and II) with preserved left ventricular function, stays at altitudes up to 3000 to 3500 m can be considered relatively safe. Therefore, only CHD patients who have well-controlled blood pressure, preserved or only slightly impaired left ventricular function, a negative exercise test or an ischemic threshold above 6 METs, and no significant cardiac arrhythmia at sea level should ascend to high altitude. For these patients, the risk at rest for the exacerbation of CHD or for a severe cardiac event (sudden cardiac death, myocardial infarction, angina, higher grade arrhythmia, etc.) is very low, whereas it may increase during exercise. Patients with any kind of unstable disease should not go to altitude. This includes the following conditions:

Unstable angina

Uncomplicated myocardial infarction or recent myocardial revascularization within the last 4 weeks, complicated myocardial infarction within the last 3 months

Prior ventricular tachycardia or fibrillation unless maximal exercise testing has shown stable cardiac rhythm

Some additional, facts must be taken into consideration.

General considerations

CHD patients always have an increased risk for adverse cardiac events requiring medical care and/or descent. In the case of an emergency, rescue may not be available immediately since altitude regions are often remote areas. Providing medical care in some altitude regions takes a very long time or, under certain circumstances (weather conditions), may be not available at all.

Climate conditions, particularly cold, which is very common at high altitude even in summer, may also contribute to increased cardiac stress.

All patients traveling to high altitude should be counseled about the prevention, recognition, and treatment of acute altitude illnesses that can affect all travelers, regardless of their underlying health status.

Pretravel evaluation and planning

Above 1500 m, maximal exercise capacity is reduced by about 1% for every 100 m of altitude gain. The patient must have sufficient exercise capacity for the intended activities. Therefore, a symptom-limited exercise test (including 12-lead ECG) is mandatory in CHD patients before going to altitude. This is also recommended for elderly men and women with preexisting cardiovascular risk factors. In case of a positive result, further proof of myocardial ischemia is recommended.

Exercise limitation for the altitude stay should be prescribed based on heart rate or heart rate × blood pressure product, rather than on workload limits, since patients may become symptomatic at lower exercise workloads at altitude than at sea level.

Exercise testing in hypoxia is not required because exercise in normoxia allows predicting performance in hypoxia when the altitude-associated decrease is considered. Accordingly, the ischemic threshold occurs at the same or only slightly lower cardiac work (rate × pressure product). However, this concept has been questioned in a recent report about the additional reduction of coronary blood flow in patients with CHD because of hypoxia-induced endothelial dysfunction (Arbab-Zadeh et al., 2009). If confirmed in future studies, these findings suggest that exercise testing in hypoxia might allow a better estimation of the risk associated with hypoxic exposure in CHD patients. For now, there are no indications to perform hypoxic exercise testing prior to travel, and the clinician should simply rely on standard exercise testing in normoxia.

In-travel precautions

Patients should take time for an acclimatization period of 5 days with exercise limited to light or moderate exercise (e.g., heart rate 30% below the maximum determined in an exercise ECG). Above 2000 m, sleeping altitude should be increased by not more than 300 to 350 m per night on average. Direct transportation to an altitude above 3000 m should be avoided.

CHD patients who do not engage in exercise at sea level on a regular basis should not begin exercise at high altitude. Similar to sea-level risks, the risk for cardiac events is significantly increased in those who are not used to exercise; thus a certain degree of physical training at sea level in advance of altitude stay is strongly recommended.

Blood pressure at altitude usually rises slightly compared to sea level. This, however, shows a large interindividual variability (Luks, 2009). In some patients, arterial blood pressure may even decrease, and in others it may rise considerably at altitude. Therefore, CHD patients should check blood pressure regularly and be prepared to adjust doses of antihypertensive drugs.

CHD medication at high altitude

Medication at altitude should be taken as prescribed at sea level.

Drugs with some combined α/β blocking properties (carvedilol, labetalol) or central sympatholytic effects (clonidine, guanfacine) may be especially helpful for blood-pressure regulation at altitude because of increased sympathetic activity. Further, β-blockers may impair performance at high altitude not only by reducing maximum heart rate (Luks, 2009), but also by blunting ventilatory response to hypoxia (Agostoni et al., 2006), which theoretically may be less pronounced in drugs with combined α/β blocking activity. However, this has not yet been tested.

Patients on dual platelet antiaggregation plus concomitant oral anticoagulation should not be involved in activities with increased risk of injury, in particular not while visiting remote areas.

Only patients with stable CHD and without residual ischemia should be allowed to go above 3500 m. If trekking or mountaineering is planned, exercise capacity should match the demand at the target altitude by taking into account the hypoxia-induced decrease in performance. The general recommendations given above also apply for these patients. When assessing the risk associated with trekking in remote areas, one must consider that in most areas there is no up-to-date interventional medical support for cardiovascular events, and incidents with good prognosis at home may turn into a disaster at altitude. Patients with CHD should in general not travel to altitudes above 4500 m as hypoxia is already severe at rest and increases with moderate exercise. However, specific patients with normal ventricular function, excellent exercise capacity, and no provocable ischemia (e.g., a patient with a single vessel disease who has been stented) could potentially ascend safely, and recommendations regarding such patients should be individualized.

Summary

In this review we have tried to make reasonable recommendations. However, in light of the lack of data, we would like to emphasize that in case of doubt it is always better to err on the side of caution. CHD patients generally should not go to altitude in an unstable disease state. When stable and well compensated, the risk is not significantly increased by the altitude-related hypoxia up to 3500 m; however, patients have to account for the particular circumstances of an altitude stay. Above 3500 m, there is a considerable decrease of exercise capacity and therefore, in addition to a stable disease, a preserved left ventricular function and an exercise capacity clearly above normal are required for a safe stay. With very few exceptions, CHD patients should generally be advised not to go higher than 4500 m.

Footnotes

Disclosures

The authors have no conflicts of interest or financial ties to disclose.

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