© 2004 American Thoracic Society
Rebuttal from Dr. LavieNo one can refute that "medical science is littered with very plausible hypotheses generated from cross-sectional studies which proved to be deceiving..." It is equally true that medical science is rich with hypotheses that were ignored, or even ridiculed, for many years, only to become in time leading theories that revolutionized medicine. McCully who hypothesized in 1969 that hyperhomocysteinemia causes arteriosclerosis (1) was denied tenure in Harvard in 1979. Thirty years later this field is exploding with thousands of publications. The free-radical damage induced atherosclerosis hypothesized by Harman (2) in 1956 remained obscure until the 1970s. Today, free-radicals occupy an amazingly central role in a wide variety of diseases. Thus, it is futile to doubt the validity of the sleep apnea–cardiovascular hypothesis based on previously deceiving hypotheses.My argument that sleep apnea causes cardiovascular disease does not rely on cross-sectional studies alone. Dr. Stradling conveniently ignored the wealth of data demonstrating why sleep apnea causes cardiovascular diseases. Being cynical about the "plethora of hypotheses" by mentioning oxidative stress (3) side by side with "loosening atheromatous plaques by snoring vibrations" does not change the well established fact that oxidative stress, a key feature of sleep apnea, promotes proatherogenic mechanisms of vascular dysfunction (4). Furthermore, before refuting the role of antioxidants in preventing cardiovascular events because a meta-analysis disproved the efficacy of vitamin E, the studies limitations should be acknowledged (4). Neither vitamin E nor nasal CPAP can reverse atherosclerotic damage accumulated before the treatment onset. Moreover, the efficacious ACE inhibitors and statins, applauded by Stradling, are in fact antioxidants by virtue of preventing free-radical formation rather than just scavenging them after production like vitamin E (4). To conclude, sleep apnea was clinically described by sharp-eyed physicians in the 19th century and disappeared from the medical literature until its rediscovery in 1960 (5). Hopefully, recognizing that sleep apnea causes cardiovascular diseases will not have to wait that long. I agree with Dr. Stradling that to win the acceptance of the medical community we do not need additional cross-sectional studies but rather hypothesis-driven research to elucidate the mechanisms underlying this association as well as long-term interventional studies. REFERENCES
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