睡眠呼吸暂停患者癌症发病率和死亡率高

F. Javier Nieto博士

旧金山(EGMN)——美国胸科学会(ATS)年会上报告的2项最新研究显示，睡眠呼吸暂停患者的癌症发病率和死亡率均更高。这印证了既往体外和动物实验中的发现：反复缺氧与癌症进展加速有关。

在其中一项研究中，经过对威斯康辛睡眠队列中1,522名受试者的20年随访，威斯康辛大学的F. Javier Nieto博士及其同事发现，患有阻塞性睡眠呼吸暂停(OSA)的人死于癌症的风险，比非OSA患者增加10%~480%(具体取决于呼吸暂停严重程度)。

威斯康辛睡眠队列研究是一项前瞻性、基于社区的睡眠障碍预测因素与自然史研究，所有受试者均接受多导睡眠图描记，睡眠障碍性呼吸定义为呼吸暂停-低通气指数(AHI)≥5分。

分析结果显示，癌症死亡风险增加与缺氧的次数和严重程度均有关，但与缺氧严重程度的关联最强。如果睡眠中多数时间内氧合血红蛋白饱和度低于90%，那么在研究期间死于癌症的几率比对照者增加近8倍。癌症死亡风险与缺氧之间呈现出剂量依赖关系：校正年龄、性别、体重指数和吸烟情况等因素之后，与无睡眠呼吸暂停者相比，轻度睡眠呼吸暂停(定义为AHI 5~14.9分)者在随访期间罹患癌症的风险增加10%，中度(定义为AHI 15~29.9分)和重度(定义为AHI≥30分)睡眠呼吸暂停者的癌症风险分别增加1倍和近4倍。

在另一项纳入5,618例OSA患者的5年前瞻性研究中，西班牙Le Fe大学的Miguel A. Martinez-Garcia博士及其同事发现，睡眠中严重低氧血症与癌症发病率显著增加有关。如果睡眠中超过30%的时间内氧合血红蛋白饱和度低于90%，那么在5年随访期间新诊断癌症的几率将增加1倍以上。不过，在校正年龄、性别和体重指数之后，睡眠呼吸暂停患者的癌症风险增加变得不再具有统计学显著性。亚组分析提示，AHI与癌症发病率之间的关联可能仅限于男性和年轻患者。

新闻发布会主持人、伦敦帝国学院的Mary J. Morrell博士指出：“对这两项研究与既往动物实验的结果进行综合考虑，我们有理由认为存在低氧诱发癌症的某种机制。”

Nieto博士、Martinez-Garcia博士和Morrell博士均报告称无相关利益冲突。

爱思唯尔  版权所有

BY SHERRY BOSCHERT
Elsevier Global Medical News
Breaking News

SAN FRANCISCO (EGMN) – The recent findings of significantly increased risk for cancer incidence and mortality in people with sleep apnea echo previous in vitro and animal studies that found repeated episodes of hypoxia were associated with accelerated cancer progression.

In one of two new studies, people with obstructive sleep apnea were 10%-480% more likely to die of cancer, depending on apnea severity, compared with people without OSA, in a 20-year follow-up study of 1,522 participants in the Wisconsin Sleep Cohort.

Both the number of dips in oxygen level during sleep and the severity of hypoxia during those episodes were associated with increased risk of cancer mortality, but the association was stronger with hypoxia severity. Patients who spent much of their sleep time getting less than 90% oxyhemoglobin saturation were nearly nine times more likely to die of cancer during the study, compared with controls, said Dr. F. Javier Nieto and his associates reported in a press briefing at the annual meeting of the American Thoracic Society.

In a separate prospective 5-year study of 5,618 patients who were referred to seven sleep clinics in Spain, severe hypoxemia during sleep was associated with significantly increased incidence of cancer. Patients with OSA who spent more than 30% of their sleep time getting less than 90% oxyhemoglobin saturation had more than twice the risk for a new diagnosis of cancer during 5 years of follow-up, compared with patients without sleep apnea, Dr. Miguel A. Martinez-Garcia and his associates reported at the briefing.

“In both studies, when they looked at the amount of low oxygen that they were getting, that’s when the incidence and mortality from cancer went up,” said Mary J. Morrell, Ph.D., who moderated the press briefing. “What it suggests is that there’s something associated with low oxygen that’s triggering the cancer, which would fit with the initial animal work that caused them to look into the two large cohorts” of people, added Dr. Morrell, professor of sleep and respiratory physiology at Imperial College, London.

The U.S. study analyzed mortality data for participants in the Wisconsin Sleep Cohort, a prospective, community-based study of the predictors and natural history of sleep disorders. All underwent polysomnography at the start of the study. Sleep-disordered breathing was defined as an apnea-hypopnea index (AHI) score of 5 or greater, representing the mean number of apnea and hypopnea events per hour of sleep.

The mortality risks were associated with the presence and severity of sleep apnea in a dose-response fashion, said Dr. Nieto, chair of the department of population health sciences at the University of Wisconsin, Madison.

Compared with participants who did not have sleep apnea, those with mild sleep apnea (defined as an AHI of 5-14.9) were 10% more likely to die of cancer during the follow-up years. People with moderate sleep apnea (an AHI of 15-29.9) were twice as likely and those with severe apnea (an AHI of 30 or greater) were nearly five times as likely to die of cancer, compared with the control group without sleep apnea. The results were adjusted for the confounding effects of age, sex, body mass index, and smoking, Dr. Nieto said.

“The key thing is that it’s the amount of low oxygen that the patients are getting, not essentially how many times it occurs, which is the apnea-hypopnea index. It’s the amount that they’re getting” that matters most, Dr. Morrell noted.

When the results of the Spanish study were analyzed according to scores on the AHI, which includes both hypopnea and hypoxemia, the increased incidence of cancer in patients with sleep apnea became statistically nonsignificant after adjusting for the confounding effects of age, gender, and body mass index, said Dr. Martinez-Garcia of Le Fe University and Polytechnic Hospital, Valencia, Spain. Subset analyses suggest that the association between the hypoxemia index and cancer incidence may be limited to males and younger patients, Dr. Martinez-Garcia said.

Dr. Nieto, Dr. Martinez-Garcia, and Dr. Morrell reported having no financial disclosures.