K.G. Jebsen Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT-The Arctic University of Norway, Tromsø (V.M.M.).
Department of Clinical Epidemiology (V.M.M., R.d.M., A.v.H.V., F.R.R., W.M.L., S.C.C.), Leiden University Medical Center, Leiden, The Netherlands.
Arterioscler Thromb Vasc Biol. 2020 Dec;40(12):3004-3014. doi: 10.1161/ATVBAHA.120.315365. Epub 2020 Oct 29.
Whether hepatic triglyceride content (HTGC) contributes to hypercoagulability beyond total body fat (TBF) and visceral adipose tissue (VAT) is unclear. We, therefore, aimed to investigate the association between HTGC and coagulation factors (F)I (fibrinogen), VIII, IX, and XI while adjusting for TBF and VAT. Approach and Results: In this cross-sectional analysis of the NEO study (Netherlands Epidemiology of Obesity; n=6671), a random subset of participants underwent magnetic resonance imaging and magnetic resonance spectroscopy to assess VAT and HTGC (n=2580). We excluded participants without complete imaging and coagulation assessment, and with history of liver disease, venous thrombosis, or on anticoagulation. Mean differences in coagulation factor levels across HTGC quartiles were estimated by linear regression adjusted for age, sex, ethnicity, education, alcohol intake, physical activity, smoking, estrogen, and menopause, in addition to TBF and VAT. Among the 1946 participants included, median HTGC was 2.66% (interquartile range: 1.34%-6.27%). Coagulation factor levels increased dose-dependently across HTGC quartiles. Mean differences between the fourth and first quartiles were 14.7 mg/dL (95% CI, 2.1-27.2) for fibrinogen, 6.7 IU/dL (95% CI, 0.5-12.9) for FVIII, 26.1 IU/dL (95% CI, 22.4-29.8) for FIX, and 8.6 IU/dL (95% CI, 4.6-12.6) for FXI. With further adjustment for TBF and VAT, the dose-response association of HTGC with FIX persisted, whereas associations with other factors disappeared.
HTGC was associated with various coagulation factors, of which FIX remained associated with HTGC after adjustment for TBF and VAT. HTGC might contribute to venous thrombosis risk beyond total body and visceral fat through FIX levels.
目前尚不清楚肝甘油三酯含量(HTGC)是否除了全身脂肪(TBF)和内脏脂肪组织(VAT)之外还与高凝状态有关。因此,我们旨在研究 HTGC 与凝血因子(F)I(纤维蛋白原)、VIII、IX 和 XI 之间的相关性,同时调整 TBF 和 VAT。
在 NEO 研究(荷兰肥胖症流行病学研究;n=6671)的这项横断面分析中,对随机亚组参与者进行了磁共振成像和磁共振波谱检查,以评估 VAT 和 HTGC(n=2580)。我们排除了影像学和凝血评估不完整、有肝脏疾病、静脉血栓形成或正在接受抗凝治疗的参与者。在调整了年龄、性别、种族、教育、酒精摄入量、体力活动、吸烟、雌激素和绝经等因素后,通过线性回归估计了 HTGC 四分位组间凝血因子水平的差异。在纳入的 1946 名参与者中,HTGC 的中位数为 2.66%(四分位距:1.34%-6.27%)。凝血因子水平随 HTGC 四分位组呈剂量依赖性升高。第四四分位与第一四分位之间的平均差异分别为纤维蛋白原 14.7mg/dL(95%CI,2.1-27.2)、FVIII 6.7IU/dL(95%CI,0.5-12.9)、FIX 26.1IU/dL(95%CI,22.4-29.8)和 FXI 8.6IU/dL(95%CI,4.6-12.6)。在进一步调整 TBF 和 VAT 后,HTGC 与 FIX 的剂量反应关系仍然存在,而与其他因素的关联则消失。
HTGC 与各种凝血因子相关,其中 FIX 在调整 TBF 和 VAT 后与 HTGC 仍相关。HTGC 可能通过 FIX 水平对静脉血栓形成风险产生影响,超出了全身和内脏脂肪的影响。