Department of Cardiology, University of Groningen, University Medical Centre Groningen, Groningen, Hanzeplein 1, 9713 GZ, The Netherlands.
Department of Cardiology, Maastricht University Medical Centre+, Maastricht, The Netherlands.
Europace. 2022 Feb 2;24(2):193-201. doi: 10.1093/europace/euab179.
The clinical risk profile of atrial fibrillation (AF) patients is different in men and women. Our aim was to identify sex differences in blood biomarkers in patients with paroxysmal AF.
Sex differences in 92 blood biomarkers were measured in 364 patients included in our discovery cohort, the identification of a risk profile to guide atrial fibrillation therapy (AF-RISK) study, assessed by multivariable logistic regression and enrichment pathway analysis. Findings were subsequently confirmed in 213 patients included in our validation cohort, the Reappraisal of Atrial Fibrillation: Interaction between HyperCoagulability, Electrical remodelling, and Vascular Destabilisation in the Progression of AF (RACE V) study. In the discovery cohort, mean age was 59 ± 12 years, 41% were women. CHA2DS2-VASc-score was 1.6 ± 1.4. A total of 46% had hypertension, 10% diabetes, and 50% had heart failure, predominantly with preserved ejection fraction (47%). In women, activated leucocyte cell adhesion molecule (ALCAM) and fatty acid binding protein-4 (FABP-4) were higher. In men, matrix metalloproteinase-3 (MMP-3), C-C motif chemokine-16 (CCL-16), and myoglobin were higher. In the validation cohort, four out of five biomarkers could be confirmed: levels of ALCAM (P = 1.73 × 10-4) and FABP-4 (P = 2.46 × 10-7) and adhesion biological pathways [false discovery rate (FDR) = 1.23 × 10-8] were higher in women. In men, levels of MMP-3 (P = 4.31 × 10-8) and myoglobin (P = 2.10 × 10-4) and markers for extracellular matrix degradation biological pathways (FDR = 3.59 × 10-9) were higher.
In women with paroxysmal AF, inflammatory biomarkers were more often higher, while in men with paroxysmal AF, biomarkers for vascular remodelling were higher. Our data support the clinical notion that pathophysiological mechanisms in women and men with AF may differ.
Clinicaltrials.gov identifier NCT01510210 for AF-RISK; Clinicaltrials.gov NCT02726698 for RACE V.
心房颤动（AF）患者的临床风险特征在男性和女性中有所不同。我们的目的是确定阵发性 AF 患者血液生物标志物中的性别差异。
在我们的发现队列（识别房颤风险谱以指导治疗的研究，AF-RISK）中，对 364 名患者的 92 种血液生物标志物进行了性别差异测量，通过多变量逻辑回归和富集途径分析进行评估。在我们的验证队列（再评估房颤：在 AF 进展过程中介导高凝状态、电重构和血管不稳定之间相互作用的研究，RACE V）中，对 213 名患者进行了后续确认。在发现队列中，平均年龄为 59±12 岁，41%为女性。CHA2DS2-VASc 评分为 1.6±1.4。共有 46%患有高血压，10%患有糖尿病，50%患有心力衰竭，主要为射血分数保留型（47%）。在女性中，活化白细胞细胞黏附分子（ALCAM）和脂肪酸结合蛋白-4（FABP-4）较高。在男性中，基质金属蛋白酶-3（MMP-3）、C 型趋化因子配体 16（CCL-16）和肌红蛋白较高。在验证队列中，有五个生物标志物中的四个可以得到证实：ALCAM（P=1.73×10-4）和 FABP-4（P=2.46×10-7）水平以及黏附生物途径[假发现率（FDR）=1.23×10-8]在女性中更高。在男性中，MMP-3（P=4.31×10-8）和肌红蛋白（P=2.10×10-4）以及细胞外基质降解生物途径的标志物（FDR=3.59×10-9）水平较高。
在阵发性 AF 的女性中，炎症生物标志物更为常见，而在阵发性 AF 的男性中，血管重塑的生物标志物更高。我们的数据支持这样一种临床观点，即 AF 女性和男性的病理生理机制可能不同。
AF-RISK 的 Clinicaltrials.gov 标识符 NCT01510210；RACE V 的 Clinicaltrials.gov 标识符 NCT02726698。
