TY - JOUR
T1 - Sex-specific association between microvascular health and coagulation parameters
T2 - the Netherlands Epidemiology of Obesity study
AU - Yuan, Lushun
AU - Han, Jihee
AU - van der Velden, Anouk I.M.
AU - Vink, Hans
AU - de Mutsert, Renée
AU - Rosendaal, Frits R.
AU - van Hylckama Vlieg, Astrid
AU - Li-Gao, Ruifang
AU - Rabelink, Ton J.
AU - van den Berg, Bernard M.
N1 - Funding Information:
We express our gratitude toward all participants of the Netherlands Epidemiology of Obesity study. Furthermore, we thank P.R. van Beelen and all research nurses for data collection, P.J. Noordijk and her team for handling and storage of the blood samples, and I. de Jonge for data management. R.d.M. and F.R.R. were involved in inclusion of participants for the Netherlands Epidemiology of Obesity (NEO) study, the study design of the NEO study, and acquisition of data of the NEO study. L.Y. J.H. R.L.-G. T.J.R. and B.M.v.d.B. conceived the study and design. L.Y. J.H. A.I.M.V.d.V. H.V. A.v.H.V. R.d.M. R.L.-G. T.J.R. and B.M.v.d.B. performed analyses and interpretation of data. L.Y. J.H. R.L.-G. T.J.R. and B.M.v.d.B. drafted the manuscript and design of figures. All authors read and approved the final manuscript. H.V. works for MicroVascular Health Solutions LLC. R.L.-G. works for Metabolon Inc. The remaining authors, including L.Y. J.H. A.I.M.v.d.V. R.d.M. F.R.R. A.v.H.V. T.J.R. and B.M.v.d.B. have no competing interests to disclose.
Funding Information:
Funding information The Netherlands Epidemiology of Obesity study was supported by the participating departments; Division and the Board of Directors of the Leiden University Medical Centre; and Leiden University, Research Profile Area “Vascular and Regenerative Medicine.” Coagulation factor analyses were funded by “Stichting De Merel.” Stichting De Merel had no role in the study design; data collection and analysis; decision to publish; or preparation, review, or approval of the manuscript. This work was supported by the China Scholarship Council grant (201806270262 to L.Y.).
Publisher Copyright:
© 2023 The Author(s)
PY - 2023/9
Y1 - 2023/9
N2 - Background: Microvascular dysfunction is a growing determinant of sex differences in coronary heart disease (CHD). Dysregulation of the coagulation system is involved in CHD pathogenesis and can be induced by endothelial glycocalyx (EG) perturbation. However, little is known about the link between EG function and coagulation parameters in population-based studies on sex specificity. Objectives: We sought to examine the sex differences in the relationship between EG function and coagulation parameters in a middle-aged Dutch population. Methods: Using baseline measurements of 771 participants from the Netherlands Epidemiology of Obesity study (age, 56 years [IQR, 51-61 years]; 53% women; body mass index, 27.9 kg/m2 [IQR, 25.1-30.9 kg/m2]), associations between glycocalyx-related perfused boundary region (PBR) derived using sidestream dark-field imaging and coagulation parameters (factor [F]VIII/IX/XI; thrombin generation parameters; and fibrinogen) were investigated using linear regression analyses, adjusting for possible confounders (including C-reactive protein, leptin, and glycoprotein acetyls), followed by sex-stratified analyses. Results: There was a sex difference in the associations between PBR and coagulation parameters. Particularly in women, 1-SD PBR (both total and feed vessel, indicating poorer glycocalyx status) was associated with higher FIX activity ([1.8%; 95% CI, 0.3%-3.3%] and [2.0%; 95% CI, 0.5%-3.4%], respectively) and plasma fibrinogen levels ([5.1 mg/dL; 95% CI, 0.4-9.9 mg/dL] and [5.8 mg/dL; 95% CI, 1.1-10.6 mg/dL], respectively). Furthermore, 1-SD PBRcapillary was associated with higher FVIII activity (3.5%; 95% CI, 0.4%-6.5%) and plasma fibrinogen levels (5.3 mg/dL; 95% CI, 0.6-10.0 mg/dL). Conclusion: We revealed a sex-specific association between microcirculatory health and procoagulant status, which suggests that microvascular health be considered during early development of CHD in women.
AB - Background: Microvascular dysfunction is a growing determinant of sex differences in coronary heart disease (CHD). Dysregulation of the coagulation system is involved in CHD pathogenesis and can be induced by endothelial glycocalyx (EG) perturbation. However, little is known about the link between EG function and coagulation parameters in population-based studies on sex specificity. Objectives: We sought to examine the sex differences in the relationship between EG function and coagulation parameters in a middle-aged Dutch population. Methods: Using baseline measurements of 771 participants from the Netherlands Epidemiology of Obesity study (age, 56 years [IQR, 51-61 years]; 53% women; body mass index, 27.9 kg/m2 [IQR, 25.1-30.9 kg/m2]), associations between glycocalyx-related perfused boundary region (PBR) derived using sidestream dark-field imaging and coagulation parameters (factor [F]VIII/IX/XI; thrombin generation parameters; and fibrinogen) were investigated using linear regression analyses, adjusting for possible confounders (including C-reactive protein, leptin, and glycoprotein acetyls), followed by sex-stratified analyses. Results: There was a sex difference in the associations between PBR and coagulation parameters. Particularly in women, 1-SD PBR (both total and feed vessel, indicating poorer glycocalyx status) was associated with higher FIX activity ([1.8%; 95% CI, 0.3%-3.3%] and [2.0%; 95% CI, 0.5%-3.4%], respectively) and plasma fibrinogen levels ([5.1 mg/dL; 95% CI, 0.4-9.9 mg/dL] and [5.8 mg/dL; 95% CI, 1.1-10.6 mg/dL], respectively). Furthermore, 1-SD PBRcapillary was associated with higher FVIII activity (3.5%; 95% CI, 0.4%-6.5%) and plasma fibrinogen levels (5.3 mg/dL; 95% CI, 0.6-10.0 mg/dL). Conclusion: We revealed a sex-specific association between microcirculatory health and procoagulant status, which suggests that microvascular health be considered during early development of CHD in women.
KW - coagulation factors
KW - endothelial glycocalyx (EG)
KW - fibrinogen
KW - perfused boundary region (PBR)
KW - thrombin generation
U2 - 10.1016/j.jtha.2023.06.001
DO - 10.1016/j.jtha.2023.06.001
M3 - Article
C2 - 37301258
SN - 1538-7933
VL - 21
SP - 2585
EP - 2595
JO - Journal of Thrombosis and Haemostasis
JF - Journal of Thrombosis and Haemostasis
IS - 9
ER -