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Characterization of High-Altitude Pulmonary Hypertension in the Kyrgyz

Association with Angiotensin-Converting Enzyme Genotype

National Center for Cardiology and Internal Medicine, Bishkek, Kyrgyzstan; Section on Clinical Pharmacology, Hammersmith Hospital, Imperial College School of Medicine, London; and the Department of Medicine, University of Cambridge, Cambridge, United Kingdom

Correspondence and requests for reprints should be addressed to Almaz A. Aldashev, M.D., Laboratory of Molecular and Cell Biology, National Center of Cardiology and Internal Medicine, Togolok Moldo St. 3, 720040 Bishkek, Kyrgyz Republic. E-mail: cardio{at}elcat.kg; or to Nicholas W. Morrell, M.D., Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK. E-mail: nwm23{at}cam.ac.uk

Previous studies have suggested a genetic component in susceptibility to hypoxia-induced pulmonary hypertension. We therefore estimated the prevalence of high-altitude pulmonary hypertension (HAPH) in a Kyrgyz population and whether the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene associates with HAPH. An electrocardiographic survey of 741 highlanders demonstrated electrocardiogram signs of cor pulmonale in 14% of subjects. Pulmonary artery hemodynamics measured in an independent group of 136 male highlanders with symptoms of dyspnea at altitude revealed established pulmonary hypertension (mean pulmonary artery pressure [MPAP] 25 mm Hg) in 20%. However, 26% of the normal subjects demonstrated an exaggerated response (twofold or greater increase in MPAP) to inhalation of 11% oxygen, and were classified as hyperresponsive. Ten-year follow-up of this group revealed increases in the MPAP, but not in normal subjects. Comparison of ACE I/D genotypes in the catheterized group revealed a threefold higher frequency of the I/I genotype in highlanders with HAPH, compared with normal highlanders (² = 11.59, p = 0.003). In addition, MPAP was higher in highlanders with the I/I genotype (26.9 ± 4.0 mm Hg) compared with the I/D genotype (20.6 ± 1.2 mm Hg) or the D/D genotype (18.3 ± 0.9 mm Hg) (p < 0.05). We conclude that HAPH is associated with ACE I/D genotype among Kyrgyz highlanders and the development of HAPH in this population and may be predicted by hyperresponsiveness to acute hypoxia.

Key Words: altitude • angiotensin-converting enzyme • hypoxia • pulmonary hypertension

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