阻塞型睡眠呼吸中止症（obstructive sleep apnea, OSA）為常見的睡眠疾病，患者常於睡眠過程中出現體內間歇性缺氧（缺氧再灌流）現象。過去已有許多細胞及動物實驗研究證實，組織缺氧會導致氧化性壓力的產生，並可能造成體內總抗氧化能力下降，進而產生DNA adduct與脂質過氧化等氧化性傷害。此外，過去許多流行病學研究指出OSA與罹患心血管疾病具高度相關性。然而，過去並未有研究探討罹患OSA嚴重程度與氧化性傷害及心血管疾病指標間的相關性。因此，本研究的目的為探討：(1) OSA嚴重程度與體內總抗氧化能力及氧化性傷害間之關係；(2) 探討心血管疾病生物指標—高敏感度反應性C蛋白（high sensitivity C-reactive protein, hs-CRP）及同半胱胺酸（total homocysteine, tHcy）之含量與OSA嚴重程度間的相關性；(3) 探討氧化性壓力與心血管疾病之生物指標間的相關性。
本研究以83位長途客運駕駛及行政人員為研究對象，分別進行多項睡眠生理腦波檢查（polysomnography, PSG），血液、尿液樣本採集及健康、飲食問卷調查。血液樣本用以分析體內總抗氧化能力、脂質過氧化代謝產物—丙二醛（malondialdehyde, MDA）、hs-CRP及Hcy。尿液樣本則分析DNA adduct代謝產物— 8-hydroxy-2-deoxyguanosine（8-OHdG）之含量。
依據PSG檢查之結果，將受檢人員依OSA嚴重程度分為正常-輕度（AHI值為7.5 ± 3.2 events/hr）、中度（23.7 ± 4.7 events/hr）、重度OSA（46.8 ± 12.0 events/hr）。問卷資料分析結果顯示，客運駕駛/行政人員之比例、BMI、年資、教育程度、輪班型態、平均一週開車時數及生活習慣（如抽煙、喝酒等）在三組間均無統計上顯著差異，但年齡、罹患心臟相關疾病之比例、維他命C服用習慣卻有顯著差異（p < 0.05）。經校正干擾因子後發現，年齡為OSA最重要之影響因子（p = 0.009），年齡每增加1歲，AHI則增加0.295 counts/hr。
關於氧化性壓力部分，僅有MDA含量於三組間具統計上顯著差異（重度OSA之組別顯著高於正常-輕度、中度），且與AHI值間具有顯著相關（r = 0.257）。但經校正干擾因子後發現，OSA並不是造成體內MDA含量增加之主因（p = 0.120），可能與年齡及其他影響因子（如生活及飲食習慣等）有關。
關於心血管疾病生物指標部分， hs-CRP含量於三組間具統計上顯著差異（中度及重度OSA顯著高於正常-輕度之組別），但其含量與各因子間均無顯著相關。因此，hs-CRP含量於三組間之差異可能與極端值有關。tHcy含量於三組間並無統計上顯著差異，但有6位受試者疑似罹患hyperhomocysteinemia。
本研究雖因樣本數過少導致無法釐清氧化性壓力與心血管疾病生物指標間之相關性，但仍印證OSA與脂質過氧化間之相關性，且經校正可能之干擾因子後，發現年齡及生活飲食習慣可能是導致脂質過氧化之主因。因此，未來仍須進一步探討作用機制。

Obstructive sleep apnea (OSA) is the most common form of sleep-disordered breathing. Reoxygenation/reperfusion derived by OSA is thought to result in the elevation of oxidative stress and the decrease of antioxidant capacity, and then caused the oxidative stress and damages including DNA adduct production and lipid peroxidation. Furthermore, a recent study revealed that OSA is associated with an elevated risk for cardiovascular diseases. However, the relationship between OSA levels, oxidative damage and markers of cardiovascular diseases has not been postulated yet. Thus, the aims of this study are to investigate (1) the relationship between OSA levels, alteration of antioxidant capacity, lipid peroxidation metabolites and DNA adduct metabolites; (2) the relationship between OSA levels and cardiovascular diseases biomarkers such as high sensitivity C-reactive protein (hs-CRP) and total homocysteine (tHcy); (3) the relationship between oxidative stress and cardiovascular disease biomarkers.
83 transportation business drivers and administrators were recruited in this study to examine overnight polysomnography (PSG) in order to group the subjects into three groups according to the OSA levels. Questionnaire investigations were administered by sleep supervisors during the PSG investigation. Blood and urine samples were collected to determine their total antioxidant capacity, DNA adduct metabolite (8-hydroxy-2-deoxyguanosine, 8-OHdG), lipid peroxidation metabolite (malondialdehyde, MDA), hs-CRP and tHcy levels for each participant. Finally, all the data will be integrated to discuss the relationships between biomarkers of oxidative damage, cardiovascular diseases and OSA levels.
According to PSG investigation, the subjects were grouped to control-mild (AHI: 7.5 ± 3.2 events/hr), moderate (AHI: 23.7 ± 4.7 events/hr) and severe OSA (AHI: 46.8 ± 12.0 events/hr) groups. No significant differences were found in ratio of transportation business drivers to administrators, BMI, working period, work sheet among three groups; while significant differences were found in age, vitamin C consumption and heart disease events among three groups. After adjusting the confounders, age is probably the most important factor for OSA (p = 0.009).
The MDA levels of severe OSA group were significantly higher than control-mild and moderate OSA groups. A significantly positive correlation existed between the levels of MDA and OSA (r = 0.257). However, OSA was not the major risk factor for the elevation of MDA levels after adjusting confounders.
Significant difference of hs-CRP levels were found among three groups, but no significant correlation was found. Consequently, the difference of hs-CRP levels among three groups was associated with pinnacle values. In addition, no significant difference was found in tHcy levels among three groups. However, 6 subjects with elevated tHcy levels probably had hyperhomocysteinemia disease.
Although the sample size was insufficient to clarify the relationship between oxidative stress and cardiovascular disease in this study, we still found the positive correlation between the levels of MDA and OSA. Furthermore, OSA was not the major risk factor for the elevation of MDA levels. Future research should be conducted to investigate the mechanism of MDA formation in OSA patients.

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交通部，交通統計資料http://www.motc.gov.tw/mocwebGIP/wSite/ct?xItem=4881&ctNode=169&mp=1
衛生署，統計資訊網http://www.doh.gov.tw/statistic/index.htm