Date Published: March 27, 2019
Publisher: Public Library of Science
Author(s): Luca Valerio, Ron J. Peters, Aeilko H. Zwinderman, Sara-Joan Pinto-Sietsma, Ivana Isgum.
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.
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.
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.
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.
The increasing burden of cardiovascular disease has led investigators to look for methods to identify atherosclerosis at an early stage. Evidence suggests that the earliest development towards atherosclerosis is structural and functional alteration of the vascular endothelium. In particular, animal and human studies have shown that atherogenic stimuli and early atherogenesis are associated with structural and functional damage of the endothelial glycocalyx, a gel-like layer of membrane-attached carbohydrate polymers and adsorbed plasma proteins at the interface of vascular endothelial cells and flowing blood . These associations have led to the hypothesis that detecting reduced glycocalyx size in a clinical setting may allow early detection of atherosclerosis .
We found that small glycocalyx size as defined by highest PBR was most strongly associated with older age, female sex, higher diastolic blood pressure, lower BMI, and diabetes. Of these associations, only those with sex and diabetes were statistically significant after correcting for possible confounders such as age, diastolic blood pressure, and BMI. These results are partly consistent with previous studies, which observed that diabetes was related to highest PBR [5, 10]. Both lower BMI and female sex have not been shown to be related to highest PBR: this is unexpected, since they are known to be inversely related to atherosclerotic disease. Although we observed slight ethnic differences, they did not confound the results. Finally, highest PBR was not associated with overall prevalent cardiovascular disease, coronary heart disease and revascularization procedures, or stroke.