Palà Elena, Bustamante Alejandro, Pagola Jorge, Juega Jesus, Francisco-Pascual Jaume, Penalba Anna, Rodriguez Maite, De Lera Alfonso Mercedes, Arenillas Juan F, Cabezas Juan Antonio, Pérez-Sánchez Soledad, Moniche Francisco, de Torres Reyes, González-Alujas Teresa, Clúa-Espuny Josep Lluís, Ballesta-Ors Juan, Ribas Domingo, Acosta Juan, Pedrote Alonso, Gonzalez-Loyola Felipe, Gentile Lorente Delicia, Ángel Muñoz Miguel, Molina Carlos A, Montaner Joan
Neurovascular Research Laboratory, Vall d'Hebron Institute of Research, Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
Stroke Unit, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
Front Cardiovasc Med. 2022 Jul 4;9:908053. doi: 10.3389/fcvm.2022.908053. eCollection 2022.
Atrial fibrillation (AF) increases the risk of ischemic stroke in asymptomatic individuals and may be the underlying cause of many cryptogenic strokes. We aimed to test the usefulness of candidate blood-biomarkers related to AF pathophysiology in two prospective cohorts representative of those populations.
Two hundred seventy-four subjects aged 65-75 years with hypertension and diabetes from the AFRICAT cohort, and 218 cryptogenic stroke patients aged >55 years from the CRYPTO-AF cohort were analyzed. AF was assessed by 4 weeks of monitoring with a wearable Holter device (NuuboTM™). Blood was collected immediately before monitoring started. 10 candidate biomarkers were measured by automated immunoassays (Roche, Penzberg) in the plasma of all patients. Univariate and logistic regression analyses were performed in each cohort separately.
Atrial fibrillation detection rate was 12.4% (AFRICAT cohort) and 22.9% (CRYPTO-AF cohort). 4 biomarkers were significantly increased in asymptomatic individuals with AF [Troponin-T, Angiopoietin-2 (Ang-2), Endocan, and total N-terminal pro-B type natriuretic peptide (NT-proBNP)] and 7 biomarkers showed significantly higher concentrations in cryptogenic stroke patients with AF detection [growth differentiation factor 15, interleukin 6, Troponin-T, Ang-2, Bone morphogenic protein 10, Dickkopf-related protein 3 (DKK-3), and total NT-proBNP]. The models including Ang-2 and total NT-proBNP [AUC 0.764 (0.665-0.863)], and Ang-2 and DKK-3 [AUC = 0.733 (0.654-0.813)], together with age and sex, showed the best performance to detect AF in high-risk asymptomatic individuals, and in cryptogenic stroke patients, respectively.
Blood-biomarkers, in particular, total NT-proBNP, DKK-3, and Ang-2, were associated with AF reflecting two mechanistically different pathways involved in AF pathophysiology (AF stretch and vascular changes). The combination of these biomarkers could be useful in AF screening strategies in the primary care setting and also for searching AF after cryptogenic stroke.
心房颤动（AF）会增加无症状个体发生缺血性卒中的风险，且可能是许多不明原因卒中的潜在病因。我们旨在检验在代表这些人群的两个前瞻性队列中，与AF病理生理学相关的候选血液生物标志物的效用。
分析了来自AFRICAT队列的274名年龄在65 - 75岁之间的高血压和糖尿病患者，以及来自CRYPTO - AF队列的218名年龄大于55岁的不明原因卒中患者。通过佩戴式动态心电图监测设备（NuuboTM™）进行4周监测来评估AF。在监测开始前立即采集血液。通过自动化免疫测定法（罗氏公司，彭茨贝格）对所有患者血浆中的10种候选生物标志物进行检测。在每个队列中分别进行单因素和逻辑回归分析。
AF检测率在AFRICAT队列中为12.4%，在CRYPTO - AF队列中为22.9%。4种生物标志物在无症状AF个体中显著升高[肌钙蛋白 - T、血管生成素 - 2（Ang - 2）、内皮糖蛋白和总N末端B型脑钠肽前体（NT - proBNP）]，7种生物标志物在检测到AF的不明原因卒中患者中浓度显著更高[生长分化因子15、白细胞介素6、肌钙蛋白 - T、Ang - 2、骨形态发生蛋白10、Dickkopf相关蛋白3（DKK - 3）和总NT - proBNP]。包含Ang - 2和总NT - proBNP [曲线下面积（AUC）为0.764（0.665 - 0.863）]，以及Ang - 2和DKK - 3 [AUC = 0.733（0.654 - 0.813）]，再加上年龄和性别，分别在高危无症状个体和不明原因卒中患者中表现出检测AF的最佳性能。
血液生物标志物，特别是总NT - proBNP、DKK - 3和Ang - 2，与AF相关，反映了AF病理生理学中涉及的两种机制不同的途径（AF牵张和血管变化）。这些生物标志物的组合可能有助于基层医疗环境中的AF筛查策略，也有助于在不明原因卒中后寻找AF。
