Purpose: The purpose of this study is to investigate gender differences in cardiac remodeling due to hypoxia, using cardiac magnetic resonance (CMR) in individuals living at high altitudes for extended periods. Materials and Methods: The study cohort consisted of 89 healthy high-altitude residents, categorized by sex: 49 males (55.1%) and 40 females (44.9%). We conducted comparative analyses of clinical demographics and CMR-derived structural indices within the study cohort. Single-variable logistic regression revealed significant associations, which were later confirmed using adjusted multivariable modeling to identify independent predictors. Key Results: Being female is associated with a 59.4% lower risk of cardiomegaly compared to males (OR = 0.538, 95% CI = 0.279 - 0.875, p = 0.006). BMI independently predicts the risk of cardiac enlargement (OR = 0.632, 95% CI = 1.088 - 1.536, p = 0.003). The diameter of the principal pulmonary artery showed the strongest association (OR = 0.988, 95% CI = 0.988 - 1.346, p = 0.007). Conclusions: Multivariate logistic regression analysis indicates that sex, body mass index (BMI), and primary pulmonary artery diameter are independent risk factors contributing to cardiac enlargement in high-altitude regions. Given the observed cardioprotective role of female sex in high-altitude populations, we hypothesize that female gender status, BMI range, and main pulmonary artery diameter synergistically influence susceptibility to hypoxia-induced cardiac remodeling in prolonged high-altitude residents. These findings not only provide a solid foundation for preventing chronic heart disease but also support the implementation of tailored treatment interventions in high-altitude areas.
References
[1]
Garrido, E., Botella de Maglia, J. and Castillo, O. (2021) Acute, Subacute and Chronic Mountain Sickness. RevistaClínica Española (English Edition), 221, 481-490. https://doi.org/10.1016/j.rceng.2019.12.009
[2]
Richalet, J., Hermand, E. and Lhuissier, F.J. (2023) Cardiovascular Physiology and Pathophysiology at High Altitude. Nature Reviews Cardiology, 21, 75-88. https://doi.org/10.1038/s41569-023-00924-9
[3]
Hu, X. and Zhang, L. (2021) Hypoxia and the Integrated Stress Response Promote Pulmonary Hypertension and Preeclampsia: Implications in Drug Development. Drug Discovery Today, 26, 2754-2773. https://doi.org/10.1016/j.drudis.2021.07.011
[4]
Peng, W., Li, H., Xia, C., Guo, Y., Xu, X., Zeng, W., et al. (2023) Cardiovascular Indicators Associated with Ventricular Remodeling in Chronic High-Altitude Disease: A Cardiovascular MRI Study. European Radiology, 33, 6267-6277. https://doi.org/10.1007/s00330-023-09574-4
[5]
Aggarwal, K., Pathan, M.S., Dhalani, M., Kaur, I.P., Anamika, F., Gupta, V., et al. (2025) Elevated Perspectives: Unraveling Cardiovascular Dynamics in High-Altitude Realms. Current Cardiology Reviews, 21, e1573403X308818. https://doi.org/10.2174/011573403x308818241030051249
[6]
Members, C., Gregoratos, G., Abrams, J., et al. (2002) ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices-Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/NASPE Commit-Tee to Update the 1998 Pacemaker Guidelines). Journal of the American College of Cardiology, 40, 1703-1719.
[7]
Kawel-Boehm, N., Maceira, A., Valsangiacomo-Buechel, E.R., Vogel-Claussen, J., Turkbey, E.B., Williams, R., et al. (2015) Normal Values for Cardiovascular Magnetic Resonance in Adults and Children. Journal of Cardiovascular Magnetic Resonance, 17, Article 29. https://doi.org/10.1186/s12968-015-0111-7
[8]
Petersen, S.E., Aung, N., Sanghvi, M.M., Zemrak, F., Fung, K., Paiva, J.M., et al. (2016) Reference Ranges for Cardiac Structure and Function Using Cardiovascular Magnetic Resonance (CMR) in Caucasians from the UK Biobank Population Cohort. Journal of Cardiovascular Magnetic Resonance, 19, Article 18. https://doi.org/10.1186/s12968-017-0327-9
[9]
Zhang, M., Zhu, D., Wan, Y., He, B., Ma, L., Li, H., et al. (2022) Using 7.0T Cardiac Magnetic Resonance to Investigate the Effect of Estradiol on Biventricular Structure and Function of Ovariectomized Rats Exposed to Chronic Hypobaric Hypoxia at High Altitude. Archives of Biochemistry and Biophysics, 725, Article 109294. https://doi.org/10.1016/j.abb.2022.109294
[10]
González-Candia, A., Candia, A.A., Arias, P.V., Paz, A.A., Herrera, E.A. and Castillo, R.L. (2023) Chronic Intermittent Hypobaric Hypoxia Induces Cardiovascular Dysfunction in a High-Altitude Working Shift Model. Life Sciences, 326, Article 121800. https://doi.org/10.1016/j.lfs.2023.121800
[11]
Lyen, S., Mathias, H., McAlindon, E., Trickey, A., Rodrigues, J., Bucciarelli‐Ducci, C., et al. (2015) Optimising the Imaging Plane for Right Ventricular Magnetic Resonance Volume Analysis in Adult Patients Referred for Assessment of Right Ventricular Structure and Function. Journal of Medical Imaging and Radiation Oncology, 59, 421-430. https://doi.org/10.1111/1754-9485.12303
[12]
Hundley, W.G., Bluemke, D.A., Finn, J.P., Flamm, S.D., Fogel, M.A., Friedrich, M.G., et al. (2010) ACCF/ACR/AHA/NASCI/SCMR 2010 Expert Consensus Document on Cardiovascular Magnetic Resonance. Journal of the American College of Cardiology, 55, 2614-2662. https://doi.org/10.1016/j.jacc.2009.11.011
[13]
Pennell, D.J. (2003) Cardiovascular Magnetic Resonance: Twenty-First Century Solutions in Cardiology. Clinical Medicine, 3, 273-278. https://doi.org/10.7861/clinmedicine.3-3-273
[14]
Schulz-Menger, J., Bluemke, D.A., Bremerich, J., Flamm, S.D., Fogel, M.A., Friedrich, M.G., et al. (2020) Standardized Image Interpretation and Post-Processing in Cardiovascular Magnetic Resonance-2020 Update: Society for Cardiovascular Magnetic Resonance (SCMR): Board of Trustees Task Force on Standardized Post-Processing. Journal of Cardiovascular Magnetic Resonance, 22, Article 19. https://doi.org/10.1186/s12968-020-00610-6
[15]
González-Candia, A., Candia, A.A., Paz, A., Mobarec, F., Urbina-Varela, R., del Campo, A., et al. (2022) Cardioprotective Antioxidant and Anti-Inflammatory Mechanisms Induced by Intermittent Hypobaric Hypoxia. Antioxidants, 11, Article1043. https://doi.org/10.3390/antiox11061043
[16]
Natelson, D. (2024) Strange Metals: Newly Discovered Materials Bend the Regular Rules of Physics. Scientific American, 330, Article 42. https://doi.org/10.1038/scientificamerican0424-42
[17]
Sandek, A. and Hasenfuß, G. (2023) Geschlechtsspezifische Unterschiede in der Kardiologie. Die InnereMedizin, 64, 727-735. https://doi.org/10.1007/s00108-022-01437-2
[18]
Elertson, K.M. and Morgan, L.L. (2023) Consideration of Gender in Cardiovascular Disease Prevention and Management. Nursing Clinics of North America, 58, 595-605. https://doi.org/10.1016/j.cnur.2023.06.003
[19]
Boos, C.J., Mellor, A., O’Hara, J.P., Tsakirides, C. and Woods, D.R. (2016) The Effects of Sex on Cardiopulmonary Responses to Acute Normobaric Hypoxia. High Altitude Medicine & Biology, 17, 108-115. https://doi.org/10.1089/ham.2015.0114
[20]
Jacob, D.W., Harper, J.L., Ivie, C.L., Ott, E.P. and Limberg, J.K. (2021) Sex Differences in the Vascular Response to Sympathetic Activation during Acute Hypoxaemia. Experimental Physiology, 106, 1689-1698. https://doi.org/10.1113/ep089461
[21]
Vaccarino, V., Badimon, L., Corti, R., de Wit, C., Dorobantu, M., Hall, A., et al. (2010) Ischaemic Heart Disease in Women: Are There Sex Differences in Pathophysiology and Risk Factors? Position Paper from the Working Group on Coronary Pathophysiology and Microcirculation of the European Society of Cardiology. Cardiovascular Research, 90, 9-17. https://doi.org/10.1093/cvr/cvq394
[22]
Raberin, A., Burtscher, J., Citherlet, T., Manferdelli, G., Krumm, B., Bourdillon, N., et al. (2024) Women at Altitude: Sex-Related Physiological Responses to Exercise in Hypoxia. Sports Medicine, 54, 271-287. https://doi.org/10.1007/s40279-023-01954-6
