Nakamizo Tomoki, Misumi Munechika, Takahashi Tetsuya, Kurisu Satoshi, Matsumoto Masayasu, Tsujino Akira
Department of Clinical Studies, Radiation Effects Research Foundation (RERF), Nagasaki 850-0013, Japan.
Department of Statistics, Radiation Effects Research Foundation (RERF), Hiroshima 732-0815, Japan.
Life (Basel). 2023 May 5;13(5):1132. doi: 10.3390/life13051132.
Female sex in patients with atrial fibrillation (AF) is a controversial and paradoxical risk factor for stroke-controversial because it increases the risk of stroke only among older women of some ethnicities and paradoxical because it appears to contradict male predominance in cardiovascular diseases. However, the underlying mechanism remains unclear. We conducted simulations to examine the hypothesis that this sex difference is generated non-causally through left truncation due to competing risks (CR) such as coronary artery diseases, which occur more frequently among men than among women and share common unobserved causes with stroke. We modeled the hazards of stroke and CR with correlated heterogeneous risk. We assumed that some people died of CR before AF diagnosis and calculated the hazard ratio of female sex in the left-truncated AF population. In this situation, female sex became a risk factor for stroke in the absence of causal roles. The hazard ratio was attenuated in young populations without left truncation and in populations with low CR and high stroke incidence, which is consistent with real-world observations. This study demonstrated that spurious risk factors can be identified through left truncation due to correlated CR. Female sex in patients with AF may be a paradoxical risk factor for stroke.
心房颤动（AF）患者中的女性性别是一个存在争议且自相矛盾的中风风险因素——具有争议性是因为它仅在某些种族的老年女性中增加中风风险，自相矛盾是因为它似乎与心血管疾病中男性占主导地位相矛盾。然而，其潜在机制仍不清楚。我们进行了模拟，以检验这样一种假设，即这种性别差异是由于诸如冠状动脉疾病等竞争风险（CR）导致的左截断而无因果关系地产生的，冠状动脉疾病在男性中比在女性中更频繁发生，并且与中风有共同的未观察到的病因。我们用相关的异质性风险对中风和CR的风险进行建模。我们假设一些人在房颤诊断前死于CR，并计算了左截断的房颤人群中女性性别的风险比。在这种情况下，女性性别在没有因果作用的情况下成为中风的一个风险因素。在没有左截断的年轻人群以及CR低和中风发生率高的人群中，风险比减弱，这与现实世界的观察结果一致。这项研究表明，由于相关的CR导致的左截断可以识别出虚假的风险因素。房颤患者中的女性性别可能是中风的一个自相矛盾的风险因素。
