ABSTRACT: BACKGROUND:Damage to endothelial glycocalyx is thought to be an early marker of atherosclerosis and measuring reduced glycocalyx size clinically via the Perfused Boundary Region (PBR) may allow early detection of cardiovascular disease. However, the true value of the glycocalyx in estimating cardiovascular risk or detecting cardiovascular disease is uncertain. We therefore investigated whether small glycocalyx size is associated with cardiovascular risk or disease in a large multi-ethnic cohort. METHODS:In a multi-ethnic community-based sample (N = 6169, 42.4% male, mean age 43.6 ±13) we applied multiple imputation for missing data and used logistic regression and odds ratios to cross-sectionally investigate the relationship of small glycocalyx size as estimated by highest quartile of PBR with, on the one hand, classical risk factors for atherosclerosis including age, sex, diastolic and systolic blood pressure, LDL, HDL, triglycerides, BMI, diabetes, smoking status, and antihypertensive and lipid-lowering medication; on the other hand, prevalent cardiovascular disease. Analyses were additionally adjusted for ethnicity. RESULTS:With PBR divided in quartiles, the highest PBR quartile (smallest glycocalyx size) as dependent variable was independently associated with female sex (OR for male versus female: 0.61, 95% CI: 0.53, 0.70) and diabetes (OR: 1.28, 95% CI: 1.03-1.59) in a model adjusted for all classical risk factors of atherosclerosis and for ethnicity. With regard to cardiovascular disease, no association was found between the smallest glycocalyx size as independent variable and overall cardiovascular disease, coronary heart disease and revascularization procedures, or stroke. CONCLUSIONS:Small glycocalyx size as estimated by highest PBR is associated with female sex and diabetes, which do not completely reflect a high cardiovascular risk profile. At the same time, glycocalyx size is not associated with prevalent cardiovascular disease.