Sex-specific association between microvascular health and coagulation parameters: the Netherlands Epidemiology of Obesity (NEO) Study

Abstract

Background

Microvascular dysfunction is a growing determinant of sex difference in coronary heart disease (CHD). The 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 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 (NEO) study (age: 56 [IQR: 51-61] years, 53% women, BMI: 27.9 [IQR: 25.1-30.9] kg/m2), associations between glycocalyx-related perfused boundary region (PBR) derived from sidestream dark-field imaging and coagulation parameters (factor VIII/IX/XI, thrombin generation parameters, and fibrinogen) were investigated using linear regression analyses, adjusting for possible confounders (including CRP, leptin, and GlycA), followed by sex-stratified analyses.

Results

There was a sex difference in the associations between PBR and coagulation parameters. Particularly in women, one 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) and plasma fibrinogen levels (5.1 mg/dL, 95% CI: 0.4-9.9, and 5.8 mg/dL, 95% CI: 1.1-10.6). Furthermore, one 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).

Conclusion

We revealed a sex-specific association between microcirculatory health and procoagulant status, which suggests considering microvascular health in the early development of CHD in women.

Keywords

coagulation factors
thrombin generation
fibrinogen
endothelial glycocalyx (EG)
perfused boundary region (PBR)
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