A method for treating, preventing, or ameliorating cardiovascular disease in a subject involves exposing the subject for an effective duration to a condition of hypobaric normoxia or hypobaric hyperoxia. An apparatus or system useful for treating, preventing, or ameliorating cardiovascular disease includes an airtight chamber configured to accommodate and enclose a subject, and including at least one hatch to allow entry or exit of the subject; a vacuum source for adjusting pressure within the chamber to a level sufficient to maintain hypobaria; and a gas source for introducing one or more gases into the chamber, such as oxygen in an amount sufficient to produce a condition of normoxia or hyperoxia within the chamber, while maintaining hypobaria.