Neighborhood Disadvantage Association with Sleep Apnea and Longitudinal Cardiovascular Events in a Large Clinical Cohort

Cinthya Pena-Orbea, David Bruckman, Jarrod E. Dalton, J Darryl Thornton, Jay L Alberts, Catherine M Heinzinger, Nancy Foldvary-Schaefer, Reena Mehra
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Abstract

Background The association between neighborhood socioeconomic disadvantage and poor cardiovascular outcomes is well established; however, less is known about its interplay with obstructive sleep apnea. Methods Adult cardiovascular disease-naïve patients who underwent sleep testing at Cleveland Clinic in Ohio from August of 1998 to August of 2021 were included in this cohort. The primary exposure was Area Deprivation Index (ADI) calculated by national rank, i.e. 25th, 50th, and 75th percentiles; higher quartiles reflecting greater deprivation (ADI-Q1-4) with Q1 as reference. Cox proportional hazard models were used to determine the hazard of composite outcome of major adverse cardiovascular events (MACE), i.e. including heart failure, stroke, atrial fibrillation and coronary artery disease or death, adjusted for demographics, comorbidities, cardiac medications and objective OSA-related measures including of Apnea Hypopnea Index (AHI) and sleep-related hypoxia (percentage of sleep time spent<90%SaO2,T90). Linear models were used to examine the relationship between ADI and OSA-related measures. Interaction terms were tested between ADI and OSA-related measures. Results: Of 72,443 adults age was 50.4±14.2 years, 50.5% were men, and 18.4% Black individuals. The median AHI was 14.3[5.8, 33.3] with a median follow-up of 4.39 [IQR,1.76-7.92] years. The relative incidence of initial MACE in the presence of competing risk of death was 17% higher (HR,1.17[95%CI 1.09-1.27],p<.001) for those living in ADI-Q4. Greater levels of area deprivation were associated with sleep-related hypoxia measures including higher degree of T90(p<.001); lower mean SaO2(p<.001), and lower minimum SaO2(p<.001). Significant interactions between T90 and ADI were observed with the risk of MACE(p=0.002) or death(p=0.005). T90 conferred a 37% increased risk of MACE(HR, 1.37[95%CI:1.23-1.53]) for those living in ADI-Q1; and a 26% increased risk(HR, 1.26[95%CI:1.14-1.38%]) among patients living in ADI-Q4. For individuals living in ADI-Q2 and Q3, T90 conferred a respective 56% and 51% increased risk of death (HR,1.56[95%CI:1.23 - 1.96]; HR, 1.51[95%CI:1.21-1.88]), respectively. Conclusions: Neighborhood disadvantage was associated with an increased risk for MACE or death in this clinical cohort and this association was modified by sleep-related hypoxia. Further research is needed to identify neighborhood-specific social determinants contributing to sleep-cardiovascular health disparities to develop neighborhood-specific interventions.
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大型临床队列中邻里劣势与睡眠呼吸暂停和纵向心血管事件的关系
方法 将 1998 年 8 月至 2021 年 8 月期间在俄亥俄州克利夫兰诊所接受睡眠测试的未患心血管疾病的成人患者纳入本队列。主要暴露指标是按全国排名计算的地区剥夺指数(ADI),即第 25、50 和 75 百分位数;较高的四分位数反映了较高的剥夺程度(ADI-Q1-4),Q1 为参考值。采用 Cox 比例危险模型确定主要不良心血管事件(MACE)的综合结果危险度,即包括心力衰竭、中风、心房颤动和冠状动脉疾病或死亡,并对人口统计学、合并症、心脏病药物和客观 OSA 相关指标(包括呼吸暂停低通气指数(AHI)和睡眠相关缺氧(90%SaO2、T90 的睡眠时间百分比)进行调整。线性模型用于检验 ADI 与 OSA 相关指标之间的关系。对ADI和OSA相关指标之间的交互项进行了检验:在 72,443 名成年人中,年龄为 50.4±14.2 岁,50.5% 为男性,18.4% 为黑人。AHI中位数为14.3[5.8, 33.3],中位随访时间为4.39[IQR,1.76-7.92]年。在存在死亡竞争风险的情况下,居住在 ADI-Q4 地区的患者初次 MACE 的相对发生率要高出 17%(HR,1.17[95%CI 1.09-1.27],p<.001)。区域剥夺程度越高,与睡眠相关的缺氧指标越相关,包括T90程度越高(p< .001)、平均SaO2越低(p< .001)和最低SaO2越低(p< .001)。T90 和 ADI 与 MACE(p=0.002)或死亡(p=0.005)风险之间存在显著的相互作用。T90使ADI-Q1患者的MACE风险增加37%(HR,1.37[95%CI:1.23-1.53]);使ADI-Q4患者的MACE风险增加26%(HR,1.26[95%CI:1.14-1.38%])。对于生活在ADI-Q2和Q3的患者,T90分别使其死亡风险增加56%和51%(HR,1.56[95%CI:1.23-1.96];HR,1.51[95%CI:1.21-1.88]):在该临床队列中,邻里关系不利与MACE或死亡风险增加有关,睡眠相关缺氧会改变这种关联。需要开展进一步研究,以确定导致睡眠-心血管健康差异的邻里特定社会决定因素,从而制定邻里特定干预措施。
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