Cardiovascular disease is one of the leading causes of death worldwide, with approximately 17.9 million people succumbing to the disease annually (World Health Organization, 2021). In the United States, there is an estimated 18.2 million Americans (20 years and older) with coronary artery disease. Of those, an estimated 655,000 Americans die annually from heart disease. Approximately 805,000 experience myocardial infarction (i.e., heart attack); 605,000 of these are first time heart attacks, and the other 200,000 have experienced at least one in their lifetime (Centers for Disease Control, 2020). Prevention and management of myocardial infarctions is constantly evolving, and new innovations are being developed to minimize the long-term, chronic consequences one may deal with. Interestingly, it is possible that life at higher altitudes, such as in the Rocky Mountains, may provide a natural edge over life at sea level. For example, Summit County, Colorado (avg elevation ~11,113 ft) has a life expectancy of 86.83 years (Stebbins, 2019). On the contrary, Lauderdale County, Mississippi (elevation 668 ft) has a life expectancy of 75.2 years (U.S.News, 2021). When looking at data regarding heart attack deaths, Summit County experiences 7.2 per 100,000 and Lauderdale County has 334.1 per 100,000 (Centers for Disease Control, 2017-2019).
Myocardial infarction is defined by cardiac muscle death that results from prolonged ischemia. The ischemia is typically the result of an atherosclerotic plaque that ruptures and occludes an artery supplying an area of heart muscle. This leads to an imbalance between the oxygen supply and demand in the affected tissue. Additional swelling ensues, occluding microcirculation, which results in more regional ischemia (Montecucco, Carbone, & Schindler, 2016). In addition to the lack of oxygen, cardiac cells overload with calcium, which causes excess contraction, cytoskeleton digestion, excess reactive oxygen species (ROS) formation, DNA fragmentation, and the release of cytochrome C from mitochondria, which signals cellular death (Heusch & Gersh, 2017).
How might altitude play a protective role in such a complicated process? There are many hypotheses out there, and some interesting findings have been discovered in animal models. Mentioned earlier, ROS fragment the DNA within cardiac cells, which is a trigger for cellular death. With the DNA damaged, cellular function ceases. ROS exposure is a normal part of life; they result from the oxygen we breath, which form free radicals (lone oxygen atoms), the pollution in the air, and the alcohol one may consume. Surprisingly, there is a reduction of ROS formation when someone is at a high enough altitude. This leads to the cardiac cell’s ability to form new, healthy cells. This suggests that ROS are like the breaks to a car and reduces the cell’s ability to move forward in the process of cell division. By taking the breaks off, it may be possible to regenerate healthy, functional tissue (Nakada, et al., 2017).
Another issue of myocardial infarction is the process of remodeling and scar tissue formation. Depending on the extent of the damage, remodeling can be detrimental and compromise the heart’s ability to pump blood efficiently. The inflammation that results signals neutrophils to the area to form scar tissue to try and repair the damage. Neutrophils also work to prevent adverse remodeling. The goal in managing heart attacks is to minimize any sort of damage that may result, but if we are too aggressive in this process, we can cause the formation of excess ROS. These ROS play a role in prolonging the lifespan of these neutrophils, allowing them to keep working. If we do not get timely resolution of the neutrophil remodeling, then healing may not be optimized (Montecucco, Carbone, & Schindler, 2016).
One study in rats explored how the heart remodels when exposed to intermittent hypoxia. Over the course of this study, rats were gradually exposed to higher simulated altitudes, and returned to baseline elevations for periods of time. The highest elevation they were exposed to was 8000 m, or the summit of Mt. Everest. They discovered that both right and left ventricles did remodel over the course of the experiment, but the left ventricle experienced significant remodeling only at the highest altitude. They also discovered that the functionality of the left ventricle was maintained. The remodeling was explained by reoxygenation that occurred at normal elevations, which resumed the production of ROS. This mechanism was absent at altitude. There are rare adverse effects of living at high altitude, which include stunted body growth, erythrocythemia (excess red blood cell formation), pulmonary hypertension, and myocardial fibrosis (Papoušek, Sedmera, Neckár, Oštádal, & Kolár, 2020).
It is exciting to explore some of the possible benefits of being and living in higher elevations. Going forward, it will be important to see if there are clinical applications, and if these applications can be administered safely and efficiently. Just like scuba divers being treated for the bends in hyperbaric chambers, what if we can develop a hypobaric chamber for those who experienced a recent heart attack? Is it possible to minimize damage by reducing the amount of oxygen entering the body, and how long would one have to be exposed to such treatment? These are very important questions that need further investigation. For now, the best course of action is to eat healthy, stop smoking, and go for a hike. If you happen to be hiking in Colorado, it may help keep the cardiologist away.
References
Centers for Disease Control. (2017-2019). Interactive Atlas of Heart Disease and Stroke. Retrieved from Centers for Disease Control and Prevention: https://nccd.cdc.gov/DHDSPAtlas/reports.aspx?geographyType=county&state=CO&themeId=8&filterIds=9,2,3,4,7&filterOptions=1,1,1,1,1#report
Centers for Disease Control. (2020, September 8). Heart Disease Facts. Retrieved from Centers for Disease Control and Prevention: https://www.cdc.gov/heartdisease/facts.htm
Heusch, G., & Gersh, B. J. (2017). The pathophysiology of acute myocardial infarction and strategies of protection beyond reperfusion: a continual challenge. European Society of Cardiology, 774-784.
Montecucco, F., Carbone, F., & Schindler, T. H. (2016). Pathophysiology of ST-segment elevation myocardial infarction: novel mechanisms and treatments. European Society of Cardiology, 1268-1283.
Nakada, Y., Canseco, D. C., Thet, S., Abdisalaam, S., Asaithamby, A., Santos, C. X., . . . Schiattarella. (2017). Hypoxia induces heart regeneration in adult mice. Nature, 222-226.
Papoušek, F., Sedmera, D., Neckár, J., Oštádal, B., & Kolár, F. (2020). Left ventricular function and remodelling in rats exposed stepwise up to extreme chronic intermittent hypoxia. Respiratory Physiology and Neurobiology.
Stebbins, S. (2019, September 6). 50 counties with high life expectancies: Does yours make the list? Retrieved from USA Today: https://www.usatoday.com/story/money/2019/09/06/the-50-counties-where-people-live-the-longest/40072465/
U.S.News. (2021). Overview of Lauderdale County, MS. Retrieved from U.S.News: https://www.usnews.com/news/healthiest-communities/mississippi/lauderdale-county
World Health Organization. (2021, June 11). Cardiovascular Diseases (CVDs). Retrieved from World Health Organization: https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds)
Tyler Cole is a second year Physician Assistant student at Midwestern University in Glendale, Arizona. He was born and raised in Glendale, and went to The University of Arizona in Tucson, where he earned his bachelor’s in Physiology and Biochemistry in 2013. From there, he went on to serve the city of Tucson as an Emergency Medical Technician for six years. He was also an EMT instructor at Pima Community College for three years. Outside of medicine, Tyler enjoys watching hockey, fishing, traveling, and spending time with his dog, Louie.
