Sublingual endothelial glycocalyx and atherosclerosis. A cross-sectional study

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.

[1]  A. Zwinderman,et al.  Reproducibility of sublingual microcirculation parameters obtained from sidestream darkfield imaging , 2019, PloS one.

[2]  A. Gorshkov,et al.  Increase in perfused boundary region of endothelial glycocalyx is associated with higher prevalence of ischemic heart disease and lesions of microcirculation and vascular wall , 2018, Microcirculation.

[3]  J. Lekakis,et al.  Association of impaired endothelial glycocalyx with arterial stiffness, coronary microcirculatory dysfunction, and abnormal myocardial deformation in untreated hypertensives , 2018, Journal of clinical hypertension.

[4]  K. Stronks,et al.  Cohort profile: the Healthy Life in an Urban Setting (HELIUS) study in Amsterdam, The Netherlands , 2017, BMJ Open.

[5]  J. Staessen,et al.  Characteristics and Determinants of the Sublingual Microcirculation in Populations of Different Ethnicity , 2015, Hypertension.

[6]  J. Metsemakers,et al.  Disease or no disease? Disagreement on diagnoses between self-reports and medical records of adult patients , 2015, The European journal of general practice.

[7]  L. Vogt,et al.  Microvascular Glycocalyx Dimension Estimated by Automated SDF Imaging is not Related to Cardiovascular Disease , 2014, Microcirculation.

[8]  F. Schellevis,et al.  Disease prevalence based on older people's self-reports increased, but patient-general practitioner agreement remained stable, 1992-2009. , 2014, Journal of clinical epidemiology.

[9]  R. de Mutsert,et al.  Deeper Penetration of Erythrocytes into the Endothelial Glycocalyx Is Associated with Impaired Microvascular Perfusion , 2014, PloS one.

[10]  L. V. van Loon,et al.  Skeletal muscle capillary density and microvascular function are compromised with aging and type 2 diabetes. , 2014, Journal of applied physiology.

[11]  T. Rabelink,et al.  Association of kidney function with changes in the endothelial surface layer. , 2014, Clinical journal of the American Society of Nephrology : CJASN.

[12]  M. Nieuwdorp,et al.  Non-invasive assessment of microvascular dysfunction in families with premature coronary artery disease. , 2013, International journal of cardiology.

[13]  Jeroen J. Bax,et al.  2007 ESH-ESC Guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). , 2007, Blood pressure.

[14]  J. Staals,et al.  Sublingual Microvascular Glycocalyx Dimensions in Lacunar Stroke Patients , 2013, Cerebrovascular Diseases.

[15]  Karien Stronks,et al.  Unravelling the impact of ethnicity on health in Europe: the HELIUS study , 2013, BMC Public Health.

[16]  E. Adrario,et al.  From Macrohemodynamic to the Microcirculation , 2013, Critical care research and practice.

[17]  T. Skalak,et al.  Hemodynamic Systems Analysis of Capillary Network Remodeling During the Progression of Type 2 Diabetes , 2011, Microcirculation.

[18]  J. McNeil,et al.  Framingham risk prediction equations for incidence of cardiovascular disease using detailed measures for smoking , 2010, Heart international.

[19]  M. Nieuwdorp,et al.  Effect of sulodexide on endothelial glycocalyx and vascular permeability in patients with type 2 diabetes mellitus , 2010, Diabetologia.

[20]  Qingxia Chen,et al.  Missing covariate data in medical research: to impute is better than to ignore. , 2010, Journal of clinical epidemiology.

[21]  K. Stronks,et al.  The utility of ‘country of birth’ for the classification of ethnic groups in health research: the Dutch experience , 2009, Ethnicity & health.

[22]  Hans Vink,et al.  Endothelial glycocalyx as potential diagnostic and therapeutic target in cardiovascular disease , 2009, Current opinion in lipidology.

[23]  J. Kastelein,et al.  Perturbation of hyaluronan metabolism predisposes patients with type 1 diabetes mellitus to atherosclerosis , 2007, Diabetologia.

[24]  T. Rabelink,et al.  Endothelial function and dysfunction: testing and clinical relevance. , 2007, Circulation.

[25]  R. Heine,et al.  Endothelial glycocalyx damage coincides with microalbuminuria in type 1 diabetes. , 2006, Diabetes.

[26]  J. Kastelein,et al.  Loss of endothelial glycocalyx during acute hyperglycemia coincides with endothelial dysfunction and coagulation activation in vivo. , 2006, Diabetes.

[27]  Hans Vink,et al.  The endothelial glycocalyx: a potential barrier between health and vascular disease , 2005, Current opinion in lipidology.

[28]  J. Mckenney,et al.  National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) , 2002 .

[29]  M. Brownlee.  Biochemistry and molecular cell biology of diabetic complications , 2001, Nature.

[30]  K. Anderson,et al.  A population at risk: Prevalence of high cholesterol levels in hypertensive patients in the framingham study , 1986 .

[31]  S. Grundy,et al.  National Cholesterol Education Program Third Report of the National Cholesterol Education Program ( NCEP ) Expert Panel on Detection , Evaluation , and Treatment of High Blood Cholesterol in Adults ( Adult Treatment Panel III ) Final Report , 2022 .