Female sex is a significant risk factor for pulmonary arterial hypertension (PAH), yet males with PAH have worse survival – a phenomenon referred to as the “sex paradox” in PAH. All adult PAH patients in the Pulmonary Hypertension Association Registry (PHAR) with congruent sex and gender were included. Baseline differences in demographics, hemodynamics, functional parameters, and quality of life were assessed by sex. Kaplan-Meier survival analysis was used to evaluate survival by sex. Mediation analysis was conducted with Cox proportional hazards regression by comparing the unadjusted hazard ratios for sex before and after adjustment for covariates. The plausibility of collider-stratification bias was assessed by modeling how large an unmeasured factor would have to be to generate the observed sex-based mortality differences. Subgroup analysis was performed on idiopathic and incident patients. Among the 1,891 patients included, 75% were female. Compared to men, women had less favorable hemodynamics, lower six-minute walk distance, more PAH therapies, and worse functional class; however, sex-based differences were less pronounced when accounting for body surface area or expected variability by gender. On multivariate analysis, women had a 48% lower risk of death compared to men (Hazard Ratio 0.52, 95% Confidence interval 0.36 – 0.74, p<0.001). Modeling found that under reasonable assumptions collider-stratification could account for sex-based differences in mortality. In this large registry of PAH patients new to a care center, men had worse survival than women despite having more favorable baseline characteristics. Collider-stratification bias could account for the observed greater mortality among men.

中文翻译：

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调查肺动脉高压的“性别悖论”：肺动脉高压协会登记处 （PHAR） 的结果


女性是肺动脉高压 （PAH） 的重要危险因素，但患有 PAH 的男性存活率更差——这种现象被称为 PAH 中的“性别悖论”。纳入肺动脉高压协会登记处 （PHAR） 中性别和性别一致的所有成年 PAH 患者。按性别评估人口统计学、血流动力学、功能参数和生活质量的基线差异。采用 Kaplan-Meier 生存分析评估性别生存率。通过比较协变量调整前后的性别未调整风险比，使用 Cox 比例风险回归进行中介分析。通过对未测量因子必须有多大才能产生观察到的基于性别的死亡率差异进行建模，来评估碰撞器分层偏倚的合理性。对特发性和新发患者进行亚组分析。在纳入的 1,891 名患者中，75% 是女性。与男性相比，女性的血流动力学较差，6 分钟步行距离较低，PAH 治疗较多，功能等级较差;然而，在考虑体表面积或性别的预期变异性时，基于性别的差异不太明显。在多变量分析中，女性的死亡风险比男性低 48%（风险比 0.52,95% 置信区间 0.36 – 0.74，p<0.001）。建模发现，在合理的假设下，对撞机分层可以解释基于性别的死亡率差异。在这个由护理中心新加入的 PAH 患者组成的大型登记册中，尽管男性具有更有利的基线特征，但其生存率比女性差。Collider-stratification 偏倚可以解释观察到的男性死亡率较高的原因。