P.-H. Sung, Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan Y.-H. Yang, Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan; Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan; Health Information and Epidemiology Laboratory of Chang Gung Memorial Hospital, Chiayi, Taiwan; School of Medicine, Chang Gung University, Taoyuan, Taiwan H.-J. Chiang, Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan; and Chung Shan Medical University School of Medicine, Taichung, Taiwan J. Y. Chiang, Department of Computer Science and Engineering, National Sun Yat-Sen University, Kaohsiung, Taiwan; and the Department of Healthcare Administration and Medical Informatics, Kaohsiung Medical University, Kaohsiung, Taiwan C.-J. Chen, Center of Excellence for Chang Gung Research Datalink, Chang Gung Memorial Hospital, Chiayi, Taiwan H.-K. Yip, Division of Cardiology, Department of Internal Medicine; Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan; the Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan; the Department of Nursing, Asia University, Taichung, Taiwan; and the Department of Orthopedics, and Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan M. S. Lee, Department of Orthopedics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan; and the Department of Orthopedics, and Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Clin Orthop Relat Res. 2018 Apr;476(4):865-874. doi: 10.1007/s11999.0000000000000161.
Endothelial dysfunction has been identified as an etiologic factor for osteonecrosis of the femoral head (ONFH) and major adverse cardiovascular and cerebrovascular events (defined as major cardiovascular disease [CVD] and cerebrovascular accident [CVA]). However, the incidence of major adverse cardiovascular and cerebrovascular events in patients with nontraumatic ONFH and any association between the two diagnoses remain unclear.
QUESTIONS/PURPOSES: We compared a large cohort of patients with nontraumatic ONFH and a matched control group without this diagnosis and (1) examined the frequency and hazard ratio (HR) of major adverse cardiovascular and cerebrovascular events in both groups adjusted for age, sex, socioeconomic status, and associated comorbidities (which we defined as the adjusted HR), (2) determined whether any association of ONFH and major adverse cardiovascular and cerebrovascular events was stable after adjusting for confounding variables, and (3) compared the occurrence of major adverse cardiovascular and cerebrovascular events with time in both groups.
A population-based cohort with a 14-year dataset period (1997-2010) from the Taiwan National Health Insurance Research Database was used for this retrospective study. The database includes a greater than 99.5% Asian population randomly selected from more than 23 million citizens and foreigners residing in Taiwan for longer than 6 months. A total of 1562 patients with nontraumatic ONFH were identified from a population of one million patients in the database after excluding initially concomitant diagnoses of major CVD and CVA. The comparison group (n = 15,620) without ONFH was analyzed in a one-to-10 ratio by matching the study cohort based on age, sex, income, and urbanization.
The patients with ONFH had a higher frequency of major adverse cardiovascular and cerebrovascular events than their counterparts without ONFH (19% versus 14%; p < 0.001). The patients with ONFH had 1.34- and 1.27-fold adjusted HRs for occurrence of major CVD and CVA as compared with the normal population (95% CI, 1.11-1.61, p = 0.002, and 95% CI, 1.09-1.47, p = 0.002, respectively). Sensitivity analysis showed a consistent association between ONFH and major adverse cardiovascular and cerebrovascular events after controlling for potentially relevant confounding variables such as hypertension and diabetes. After adjusting for potential confounders including surgery and medications, ONFH remained independently associated with major CVD (adjusted HR, 1.51, 95% CI 1.09-2.03, p = 0.026) and CVA (adjusted HR, 2.44, 95% CI 1.69-3.51, p < 0.001), apart from age older than 65 years and traditional atherosclerotic risk factors. The cumulative incidence of major adverse cardiovascular and cerebrovascular events also was higher in the ONFH group than the non-ONFH group (30.3% vs 23.1% at the end of followup, p < 0.001).
Patients with ONFH have a strong association with major adverse cardiovascular and cerebrovascular events as compared with the normal population, suggesting a potential common pathway involving endothelial dysfunction. In view of this association in the relatively young population with ONFH, it is important to closely monitor these patients, treat relevant comorbidities early, and investigate preventative measures for these major adverse events.
Level III, prognostic study.
已经确定内皮功能障碍是股骨头坏死（ONFH）和主要不良心血管和脑血管事件（定义为主要心血管疾病[CVD]和脑血管意外[CVA]）的病因之一。然而，非创伤性 ONFH 患者发生主要不良心血管和脑血管事件的发生率以及这两种诊断之间的任何关联尚不清楚。
问题/目的：我们比较了一组患有非创伤性 ONFH 的大队列患者和一组无此诊断的匹配对照组，并（1）在调整年龄、性别、社会经济状况和相关合并症（我们定义为调整后的 HR）后，检查两组中主要不良心血管和脑血管事件的频率和危险比（HR），（2）确定在调整混杂变量后，ONFH 和主要不良心血管和脑血管事件之间的任何关联是否稳定，以及（3）比较两组主要不良心血管和脑血管事件随时间的发生情况。
本回顾性研究使用了来自台湾全民健康保险研究数据库的具有 14 年数据集期（1997-2010 年）的基于人群的队列。该数据库包括从居住在台湾超过 6 个月的 2300 多万公民和外国人中随机选择的大于 99.5%的亚洲人口。在排除最初伴有主要 CVD 和 CVA 的同时诊断后，从数据库中的一百万患者中确定了 1562 名患有非创伤性 ONFH 的患者。对照组（n = 15620）无 ONFH，通过基于年龄、性别、收入和城市化程度的匹配，以 1:10 的比例对研究队列进行分析。
ONFH 患者发生主要不良心血管和脑血管事件的频率高于无 ONFH 患者（19%比 14%；p <0.001）。与正常人群相比，ONFH 患者发生主要 CVD 和 CVA 的调整后 HR 分别为 1.34 倍和 1.27 倍（95%CI，1.11-1.61，p = 0.002 和 95%CI，1.09-1.47，p = 0.002）。敏感性分析表明，在控制高血压和糖尿病等潜在相关混杂变量后，ONFH 与主要不良心血管和脑血管事件之间存在一致的关联。在调整包括手术和药物在内的潜在混杂因素后，ONFH 与主要 CVD（调整后 HR，1.51，95%CI 1.09-2.03，p = 0.026）和 CVA（调整后 HR，2.44，95%CI 1.69-3.51，p <0.001）仍然独立相关，除了年龄大于 65 岁和传统的动脉粥样硬化危险因素。ONFH 组的主要不良心血管和脑血管事件累积发生率也高于非 ONFH 组（随访结束时为 30.3%比 23.1%，p <0.001）。
与正常人群相比，ONFH 患者发生主要不良心血管和脑血管事件的关联较强，提示存在涉及内皮功能障碍的潜在共同途径。鉴于 ONFH 患者中这种关联发生在相对年轻的人群中，因此密切监测这些患者、早期治疗相关合并症以及调查这些主要不良事件的预防措施非常重要。
III 级，预后研究。
