Department of Cardiology, Erasmus MC Cardiovascular Institute, University Medical Center Rotterdam, Room Na-316, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
Department of Biostatistics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
ESC Heart Fail. 2024 Feb;11(1):594-600. doi: 10.1002/ehf2.14578. Epub 2023 Nov 27.
This study aims to provide insight into sex-specific cardiovascular protein profiles and their associations with adverse outcomes, which may contribute to a better understanding of heart failure (HF) pathophysiology and the optimal use of circulating proteins for prognostication in women and men.
In 250 stable patients with HF with reduced ejection fraction (HFrEF), we performed trimonthly blood sampling (median follow-up: 26 [17-30] months). We selected all baseline samples and two samples closest to the primary endpoint (PEP; composite of cardiovascular death, heart transplantation, left ventricular assist device implantation, and HF hospitalization) or one sample closest to censoring and applied the Olink Cardiovascular III panel. We used linear regression to study sex-based differences in baseline levels and joint models to study differences in the prognostic value of serially measured proteins. In 66 women and 184 men (mean age of 66 and 67 years, respectively), 21% and 28% reached the PEP, respectively. Mean baseline levels of fatty acid-binding protein 4, secretoglobin family 3A member 2, paraoxonase 3, and trefoil factor 3 were higher in women (P : 0.001, 0.007, 0.018, and 0.049, respectively), while matrix metalloproteinase-3, interleukin 1 receptor-like 1, and myoglobin were higher in men (P : <0.001, 0.001, and 0.049, respectively), independent of clinical characteristics. No significant differences between sexes were observed in the longitudinal associations of proteins with the PEP. Only peptidoglycan recognition protein 1 showed a suggestive interaction with sex for the primary outcome (P = 0.028), without multiple testing correction, and was more strongly associated with adverse outcome in women {hazard ratio [HR] 3.03 [95% confidence interval (CI), 1.42 to 6.68], P = 0.008} compared with men [HR 1.18 (95% CI, 0.84 to 1.66), P = 0.347].
Although multiple cardiovascular-related proteins show sex differences at baseline, temporal associations with the adverse outcome do not differ between women and men with HFrEF.
本研究旨在深入了解性别特异性心血管蛋白谱及其与不良结局的关联，这可能有助于更好地理解心力衰竭（HF）的病理生理学，以及循环蛋白在女性和男性预后预测中的最佳应用。
在 250 例射血分数降低的心力衰竭（HFrEF）稳定患者中，我们进行了每三个月一次的采血（中位随访时间：26 [17-30] 个月）。我们选择了所有基线样本和两个最接近主要终点（PEP；心血管死亡、心脏移植、左心室辅助装置植入和心力衰竭住院的复合终点）的样本，或最接近删失的一个样本，并应用了 Olink 心血管 III 面板。我们使用线性回归研究了性别间基线水平的差异，并使用联合模型研究了连续测量蛋白的预后价值差异。在 66 名女性和 184 名男性（平均年龄分别为 66 岁和 67 岁）中，分别有 21%和 28%达到 PEP。脂肪酸结合蛋白 4、分泌球蛋白家族 3A 成员 2、对氧磷酶 3 和三叶因子 3 的平均基线水平在女性中较高（P：0.001、0.007、0.018 和 0.049，分别），而基质金属蛋白酶-3、白细胞介素 1 受体样 1 和肌红蛋白在男性中较高（P：<0.001、0.001 和 0.049，分别），独立于临床特征。在 PEP 的纵向蛋白相关性方面，男女之间没有观察到显著差异。只有肽聚糖识别蛋白 1 在主要结局方面表现出与性别相关的提示性交互作用（P=0.028），且未经多次检验校正，与女性不良结局的相关性更强[危险比（HR）3.03（95%置信区间（CI），1.42 至 6.68），P=0.008]，而与男性相比[HR 1.18（95% CI，0.84 至 1.66），P=0.347]。
尽管许多心血管相关蛋白在基线水平存在性别差异，但在射血分数降低的心力衰竭女性和男性中，其与不良结局的时间相关性没有差异。
