Association Between Hepatic Triglyceride Content and Coagulation Factors

Arteriosclerosis Thrombosis and Vascular Biology, vol. 40, pp. 3004–3014

Abstract

OBJECTIVE: 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. CONCLUSIONS: 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.

Authors 9

1. Vânia Maris Morelli Aachen Department of Clinical Epidemiology

   Leiden University · Leiden University Medical Center · UiT The Arctic University of Norway

   Affiliation as printed

   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

   K.G. Jebsen Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT—The Arctic University of Norway, Tromsø (V.M.M.)

2. Renée de Mutsert Aachen Department of Clinical Epidemiology

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   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

3. Albert de Roos Aachen Department of Radiology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Radiology (A.d.R., H.J.L.), Leiden University Medical Center, Leiden, The Netherlands

   Albert de Roos Department of Radiology (A.d.R., H.J.L.), Leiden University Medical Center, Leiden, The Netherlands

4. Hildo J. Lamb Aachen Department of Radiology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Radiology (A.d.R., H.J.L.), Leiden University Medical Center, Leiden, The Netherlands

   Hildo J. Lamb Department of Radiology (A.d.R., H.J.L.), Leiden University Medical Center, Leiden, The Netherlands

5. Astrid van Hylckama Vlieg Aachen Department of Clinical Epidemiology Astrid van Hylckama Vlieg Department of Clinical Epidemiology

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   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

   Astrid van Hylckama Vlieg 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

6. Mettine H.A. Bos Aachen Department of Internal Medicine Section of Thrombosis and Hemostasis Section of Thrombosis and Hemostasis

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Department of Internal Medicine, Section of Thrombosis and Hemostasis (M.H.A.B., S.C.C.), Leiden University Medical Center, Leiden, The Netherlands

   Mettine H.A. Bos https://orcid.org/0000-0002-8164-817X Department of Internal Medicine, Section of Thrombosis and Hemostasis (M.H.A.B., S.C.C.), Leiden University Medical Center, Leiden, The Netherlands

7. Frits Richard Rosendaal Aachen Department of Clinical Epidemiology Frits R. Rosendaal Department of Clinical Epidemiology

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   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

   Frits R. Rosendaal 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

8. Willem M. Lijfering Aachen Department of Clinical Epidemiology Willem M. Lijfering Department of Clinical Epidemiology

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   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

   Willem M. Lijfering 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

9. Suzanne C. Cannegieter corresponding Aachen Department of Clinical Epidemiology Department of Internal Medicine Section of Thrombosis and Hemostasis

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   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

   Department of Internal Medicine, Section of Thrombosis and Hemostasis (M.H.A.B., S.C.C.), Leiden University Medical Center, Leiden, The Netherlands