Even assuming that the pathophysiology of the OHS-related hypoventilation is distinctly different than in the pure OSA, it is difficult to explain why the added burden of severe intermittent hypoxia in OHS was associated with reduced CVM. Of note, the most severe ODI group had a mean ODI of 95.8 and spent 72.7% of total sleep time with an oxygen saturation < 90% and had a mean oxygen saturation of 83.3% compared with 18.2, 58.9%, and 87.7%, respectively, in the least severe group. After excluding the possibility that the results could be accounted for by the younger age of the most severe patients, which could imply early diagnosis and treatment, the authors suggest that the inverse relationship between OSA severity and CVM in OHS might be explained by the protective effect of “ischemic preconditioning.” This adaptive mechanism, in which brief repeated sublethal ischemia and reperfusion episodes confer profound protection from the occurrences of an acute lethal ischemia/reperfusion episode such as in acute myocardial infarction (AMI), was first demonstrated in the cardiovascular system, and then was shown to occur in other organs including skeletal muscles, gut, brain, and the liver. In 2006, Lavie and Lavie hypothesized that the cycles of apneic events in OSA that resemble cycles of ischemia/reperfusion could exert protective effects from more severe ischemic events similar to ischemic preconditioning. Currently, accumulated evidence supports the Lavies’ ischemic preconditioning hypothesis in OSA. For instance, patients with sleep apnea were shown to have age decline mortality rates, and paradoxically increased longevity of elderly patients was documented in comparison with mortality rates in the general population. Additionally, lower postoperative mortality rates and less recurrent CVD events were reported in comparison with those without apnea, suggesting again that OSA may confer some protection against CVM. Moreover, evidence that patients with OSA and total coronary occlusion have more coronary collaterals than patients with similar occlusions but without OSA, and that OSA patients after an AMI have more functional endothelial progenitors cells than patients with AMI without OSA, may provide clues to some of the underlying mechanisms responsible for this protection. The Spanish results should be replicated in a well-planned study, preferably with age-matched groups, before accepting the conclusion that OSA may exert some protective effects in OHS. However, in view of the potentially important clinical implications of the present results regarding treatment and treatment prioritizing in OHS as well as in OSA patients, further research is urgently needed.