Department of Surgical Sciences, Orthopaedics, Uppsala University, Sweden.
Department of Medical Sciences, Uppsala University, Sweden.
Eur J Prev Cardiol. 2019 Nov;26(17):1865-1873. doi: 10.1177/2047487319868033. Epub 2019 Aug 14.
We aimed to discover and replicate associations between leisure-time physical activity and cardiovascular candidate plasma protein biomarkers and to examine whether the associations were independent of body fat.
We used cross-sectional data from two population-based cohorts, the EpiHealth (discovery cohort; = 2239) and the Swedish Mammography Cohort - Clinical (SMCC; replication cohort; = 4320). Physical activity during leisure time was assessed using questionnaires, and plasma concentrations of 184 proteins were assayed using the Olink Proseek Multiplex Cardiovascular 2 and 3 kits. We applied adjusted linear regression models using the False Discovery Rate to control for multiple testing in discovery.
In EpiHealth, physical activity was associated with 75 cardiovascular plasma biomarkers, of which 28 associations were verified (replicated) in SMCC. Findings include seven novel associations in human: paraoxonase 3, cystatin B, cathepsin Z, alpha-L-iduronidase, prostasin, growth differentiation factor 2 and tumour necrosis factor alpha receptor superfamily member 11A. Estimates for associations were similar across tertiles of body fat and physical activity was associated with four biomarkers independent of body fat percentage: paraoxonase 3, cystatin B, fatty acid-binding protein 4 and interleukin-1 receptor antagonist.
Leisure-time physical activity was associated with 28 cardiovascular-specific proteins; four associations were independent of body fat. Biomarkers in novel associations are involved in several atherosclerotic processes including regulation of low-density lipoprotein oxidation, protein degradation and immune cell adhesion and migration. Further research into these pathways may yield new insights into how physical activity affects cardiovascular health.
我们旨在发现并复制休闲时间体力活动与心血管候选血浆蛋白生物标志物之间的关联，并检验这些关联是否独立于体脂肪。
我们使用了两个基于人群的队列的横断面数据，EpiHealth（发现队列；n=2239）和瑞典乳腺摄影队列-临床（SMCC；复制队列；n=4320）。使用问卷评估休闲时间的体力活动，使用 Olink Proseek Multiplex Cardiovascular 2 和 3 试剂盒测定 184 种蛋白质的血浆浓度。我们应用调整后的线性回归模型和 False Discovery Rate 进行多重检验控制，以进行发现。
在 EpiHealth 中，体力活动与 75 种心血管血浆生物标志物相关，其中 28 种关联在 SMCC 中得到验证（复制）。研究结果包括人类的七个新关联：对氧磷酶 3、胱抑素 B、组织蛋白酶 Z、α-L-艾杜糖苷酸酶、前蛋白酶、生长分化因子 2 和肿瘤坏死因子受体超家族成员 11A。在体脂肪的三分位数中，关联的估计值相似，且体力活动与四个独立于体脂肪百分比的生物标志物相关：对氧磷酶 3、胱抑素 B、脂肪酸结合蛋白 4 和白细胞介素-1 受体拮抗剂。
休闲时间体力活动与 28 种心血管特异性蛋白质相关；有四个关联独立于体脂肪。在新关联中的生物标志物涉及几个动脉粥样硬化过程，包括调节低密度脂蛋白氧化、蛋白质降解以及免疫细胞黏附和迁移。对这些途径的进一步研究可能为体力活动如何影响心血管健康提供新的见解。
