Study: Cross-Sectional Study: 33 papers
Peer-reviewed work on the endothelial glycocalyx, microvascular health and the ingredients in our formulas, newest first. Abstracts are indexed here and every paper links to the journal.
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Published paper
The role of the endothelial glycocalyx in fibrotic interstitial lung disease
This prospective observational study (PREDICT-ILD) assessed whether sublingual side-stream dark-field video-microscopy (GlycoCheck) is an acceptable way to measure endothelial glycocalyx health in patients with fibrotic interstitial lung disease, comparing them with age- and sex-matched healthy controls. Perfused boundary region (PBR) in 5–25 µm vessels was used as a surrogate for glycocalyx width, alongside same-day pulmonary function testing and an acceptability questionnaire. The abstract describes the rationale and methods; no numerical results are reported in the text provided.
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Published paper
Biomarkers of endothelial glycocalyx damage are associated with microvascular dysfunction in resuscitated septic shock patients
This cross-sectional study compared 31 resuscitated septic shock patients with 20 healthy individuals, measuring circulating and urinary markers of endothelial glycocalyx shedding alongside sublingual microcirculation imaging with GlycoCheck. Higher levels of syndecan-1, soluble CD44, thrombomodulin, and urinary sulfated glycosaminoglycans corresponded to worse measured microvascular function in the septic patients.
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Published paper
Relationship of the main indicators of systemic COVID-associated endotheliopathy with the morphofunctional state and hemodynamics of the retina and chorioid in the acute period of the disease
Russian researchers compared retinal and choroidal imaging (OCT) with sublingual microvascular glycocalyx measurements (GlycoCheck PBR) in 44 people convalescing from moderate or severe COVID-19 and 18 healthy volunteers. Patients showed thicker choroids and wider peripapillary retinal vessels in proportion to disease severity, and these ocular changes correlated with inflammatory/coagulation blood markers and with glycocalyx indices. The authors interpret this as indirect evidence linking post-COVID retinal microangiopathy to systemic endotheliopathy.
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Published paper
Differences in coronary flow reserve and flow-mediated dilation between plaque psoriasis and psoriatic arthritis
This cross-sectional study compared vascular and cardiac function in 311 patients with psoriatic disease (185 plaque psoriasis, 126 psoriatic arthritis) and 150 risk-factor-matched controls. Patients with psoriatic disease had thicker perfused boundary region (indicating a thinner, more damaged endothelial glycocalyx), lower coronary flow reserve, lower brachial flow-mediated dilation, and reduced left ventricular longitudinal strain. Glycocalyx impairment was similar in both psoriatic subgroups, whereas coronary microvascular and brachial endothelial function were worse in psoriatic arthritis.
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Published paper
Persistent capillary rarefication in long COVID syndrome
This prospective observational study used sublingual sidestream dark-field videomicroscopy with GlycoCheck software to compare microvascular structure and function in 27 long COVID patients, 15 healthy controls, and 16 historical critically ill COVID-19 patients. Long COVID patients showed a marked loss of the smallest capillaries and impaired capillary recruitment a median of ~18 months after infection, while glycocalyx thickness (PBR) was similar to healthy controls. The authors conclude that COVID-19 may leave persistent capillary rarefication, though the design cannot establish causality with symptoms.
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Published paper
Microvascular and proteomic signatures overlap in COVID-19 and bacterial sepsis: the MICROCODE study
This multi-center observational study compared sublingual microcirculation, glycocalyx dimensions (PBR by GlycoCheck) and 184 plasma proteins in 22 COVID-19 patients, 43 bacterial sepsis patients and 10 healthy controls. Microvascular and proteomic abnormalities were largely similar in the two diseases and tracked with illness severity rather than diagnosis. Two mutually opposed coregulated protein clusters were identified, and their ratio ("Microcode") predicted 28-day mortality/intubation in an independent COVID-19 cohort.
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Published paper
Endothelial glycocalyx integrity in oncological patients
This study compared sublingual microvascular glycocalyx thickness (measured as perfused boundary region, PBR) in 64 cancer patients versus 32 controls with similar cardiovascular risk profiles. Cancer patients had significantly higher PBR values, indicating a thinner/damaged glycocalyx, even though arterial stiffness and standard echocardiographic measures were largely comparable. The impairment tracked with cancer stage rather than with traditional risk factors or anticancer treatment.
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Published paper
Mutations in the heparan sulfate backbone elongating enzymes EXT1 and EXT2 have no major effect on endothelial glycocalyx and the glomerular filtration barrier
Researchers tested whether people carrying a single defective copy of the heparan sulfate chain-elongating genes EXT1 or EXT2 (causing multiple osteochondromas) have a damaged endothelial glycocalyx or leaky glomerular filtration barrier. Using sublingual GlycoCheck measurements and urine albumin testing in 19 patients versus 19 matched controls, plus review of archived kidney biopsies from 24 osteochondroma cases, they found no meaningful differences. Only one archival case showed the rare fibrillar glomerular deposits previously described as 'glomerulopathy of hereditary multiple exostoses'.
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Published paper
Endothelial glycocalyx and microvascular perfusion are associated with carotid intima-media thickness and impaired myocardial deformation in psoriatic disease
This study compared sublingual endothelial glycocalyx and microvascular perfusion measures in 297 patients with psoriatic disease against 150 risk-factor-matched controls. Psoriatic patients showed a thinner glycocalyx (higher perfused boundary region) and poorer microvascular perfusion, and these changes tracked with disease severity, carotid intima-media thickness, coronary flow reserve, and left ventricular deformation.
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Published paper
Endothelial glycocalyx integrity and microvascular perfusion are associated with novel echocardiographic markers and carotid intima-media thickness in patients with psoriasis
Researchers used sublingual sidestream dark-field imaging (GlycoCheck) to compare endothelial glycocalyx barrier properties and microvascular perfusion in 297 psoriasis patients versus 150 risk-factor-adjusted controls. Psoriasis patients showed a thicker perfused boundary region (indicating a thinner glycocalyx) and poorer microvascular perfusion, which correlated with reduced coronary flow reserve, impaired left ventricular deformation, and greater carotid intima-media thickness.
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Published paper
Microvascular Differences in Individuals With Obesity At Risk of Developing Cardiovascular Disease
In a cross-sectional analysis of 813 middle-aged adults with overweight/obesity, sublingual microcirculation was imaged using sidestream dark-field video microscopy with new GlycoCheck software that adds red blood cell velocity analysis. Participants at high 10-year cardiovascular risk (Framingham) had fewer perfused small capillaries and faster red cell velocity than low-risk participants, whereas velocity-corrected perfused boundary region (a glycocalyx index) did not differ between risk groups.
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Published paper
Identification of novel sublingual parameters to analyze and diagnose microvascular dysfunction in sepsis: the NOSTRADAMUS study (link to Critical Care)
This single-center observational study used sublingual sidestream dark-field videomicroscopy with a new GlycoCheck software version to analyze microvessels in 1-micrometer diameter classes (4-25 um) in 34 septic ICU patients and 17 healthy controls. Sepsis was associated with loss of the very smallest capillaries, impaired capillary recruitment, and increased perfused boundary region (indicating a thinner/more permeable glycocalyx). The authors combined capillary blood volume and PBR into a composite 'Microvascular Health Score' that separated patients from controls and correlated with sepsis severity.
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Published paper
Does sublingual microscopy correlate with nailfold videocapillaroscopy in systemic sclerosis?
This single-center cross-sectional study compared automated sublingual videomicroscopy (GlycoCheck) with nailfold videocapillaroscopy (NVC), the standard test for scleroderma microvascular damage, in 39 systemic sclerosis patients on the same clinic day. Sublingual microvascular density correlated moderately with nailfold capillary number and inversely with the NVC microangiopathy evolution score. Functional measures (red blood cell fraction and glycocalyx perfused boundary region) did not correlate with NVC parameters in this mostly late-pattern cohort.
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Published paper
Microvascular dysfunction in COVID-19: the MYSTIC study
This prospective, multi-center cross-sectional study used sublingual sidestream dark-field video microscopy (GlycoCheck) plus blood biomarkers to characterize microvascular and endothelial glycocalyx changes in 23 hospitalized COVID-19 patients versus 15 healthy controls. Patients showed marked loss of small capillaries, slower red blood cell velocity, and evidence of glycocalyx damage, most pronounced in those on mechanical ventilation. Higher perfused boundary region (thinner glycocalyx) and lower ADAMTS13 were associated with 60-day in-hospital mortality.
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Published paper
Evaluation of endothelial glycocalyx in healthy volunteers – An observational study
This observational study measured the endothelial glycocalyx in 21 young healthy adults using sublingual sidestream dark-field imaging with GlycoCheck software (perfused boundary region, PBR) and plasma syndecan-1 by ELISA. It reports reference values for both measures in a healthy cohort, with a median PBR of 1.82 um and median syndecan-1 of 0.3 ng/ml. The authors note their values do not fully agree with previously published healthy-subject data.
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Published paper
Sex-related associations of high-density lipoprotein cholesterol with aortic stiffness and endothelial glycocalyx integrity in treated hypertensive patients
This cross-sectional study of 193 treated hypertensive patients examined whether HDL cholesterol levels relate to aortic stiffness (carotid-femoral pulse wave velocity) and endothelial glycocalyx integrity (sublingual perfused boundary region measured by sidestream dark-field imaging/GlycoCheck). Higher HDL-C was weakly and inversely associated with aortic stiffness in the whole group, and with PBR5-9 (a marker where higher values indicate a thinner glycocalyx) specifically in men, regardless of smoking status. No such glycocalyx association was seen in women, despite their higher HDL-C levels.
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Published paper
In Vivo Imaging of the Buccal Mucosa Shows Loss of the Endothelial Glycocalyx and Perivascular Hemorrhages in Pediatric Plasmodium falciparum Malaria
Researchers used incident dark-field video microscopy of the inner cheek (buccal mucosa) in Tanzanian children to measure the perfused boundary region (PBR), an inverse indicator of endothelial glycocalyx thickness, alongside plasma glycocalyx shedding markers. Children with severe malaria had a significantly increased PBR and higher circulating hyaluronic acid, heparan sulfate, sulfated glycosaminoglycans, syndecan-1 and glypican-1 than healthy controls, consistent with substantial glycocalyx loss. Imaging also revealed perivascular hemorrhages and sequestering late-stage parasites, and markers of vascular instability (low angiopoietin-1, high angiopoietin-2) tracked with these changes.
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Published paper
Association of sublingual microcirculation parameters and endothelial glycocalyx dimensions in resuscitated sepsis
In 30 ICU patients with resuscitated sepsis and 10 healthy controls, researchers simultaneously measured endothelial glycocalyx dimensions (sublingual perfused boundary region, PBR, via GlycoCheck) and conventional sublingual microcirculation parameters (incident dark field imaging). Septic patients had both thicker PBR (indicating glycocalyx damage) and impaired microvascular perfusion, and both correlated with markers of illness severity, but the two sets of measures did not correlate with each other. PBR values agreed well with circulating syndecan-1 and with glycocalyx thickness measured by atomic force microscopy in endothelial cells exposed to patient serum.
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Published paper
Sublingual endothelial glycocalyx and atherosclerosis. A cross-sectional study
In the largest study of its kind, sublingual perfused boundary region (PBR, an indirect index of endothelial glycocalyx thickness) was measured once in 6,169 multi-ethnic adults and related to classical cardiovascular risk factors and self-reported cardiovascular disease. The smallest glycocalyx size (highest PBR quartile) was independently associated with female sex, older age, and diabetes, but not with prevalent cardiovascular disease, coronary heart disease/revascularization, or stroke. The authors conclude that PBR-estimated glycocalyx size does not track a high cardiovascular risk profile in a general population.
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Published paper
Early Onset Preeclampsia Is Associated With Glycocalyx Degradation and Reduced Microvascular Perfusion
This exploratory cross-sectional study used sublingual sidestream dark field imaging (GlycoCheck) plus blood markers to compare endothelial glycocalyx status in 137 third-trimester pregnant women. Women with early-onset preeclampsia (<34 weeks) showed greater glycocalyx degradation (higher perfused boundary region) and fewer capillaries filled with red blood cells than normotensive women, women with gestational diabetes, or those with late-onset preeclampsia. Circulating heparan sulfate proteoglycans and hyaluronic acid were also elevated in early-onset preeclampsia.
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Published paper
Increase in perfused boundary region of endothelial glycocalyx is associated with higher prevalence of ischemic heart disease and lesions of microcirculation and vascular wall.
This cross-sectional study measured the perfused boundary region (PBR), an index of red blood cell penetration into the endothelial glycocalyx, using sidestream dark-field capillaroscopy in 208 middle-aged patients. Higher PBR values (above about 2 micrometers) were associated with a greater prevalence of ischemic heart disease and cerebral atherosclerosis, as well as structural and functional abnormalities of the arterial wall and skin microcirculation. The authors propose PBR as a reproducible, non-invasive candidate marker of cardiovascular disease.
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Published paper
Alterations of conjunctival glycocalyx and microcirculation in non-septic critically ill patients
This single-center prospective observational study used sidestream dark-field imaging to assess glycocalyx thickness (perfused boundary region, PBR) and microcirculatory perfusion in the sublingual mucosa and, for the first time, the ocular conjunctiva of non-septic ICU patients. Both cardiac surgical and neurocritical patients showed increased PBR (indicating glycocalyx thinning/damage) at both sites and higher blood syndecan-1 than healthy controls. Correlations between systemic glycocalyx shedding markers and local conjunctival glycocalyx measures were weak or absent.
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Published paper
HDL cholesterol levels and endothelial glycocalyx integrity in treated hypertensive patients
This cross-sectional study measured sublingual perfused boundary region (PBR 5-9 µm) with GlycoCheck sidestream dark-field imaging in 120 treated hypertensive patients over 50 and compared results across HDL-cholesterol tertiles. Patients in the highest HDL-C tertile (71-101 mg/dL) had a modestly lower PBR (thicker glycocalyx) than those with lower HDL-C. However, in multivariable analysis only BMI, not HDL-C, independently predicted PBR.
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Published paper
Sublingual functional capillary rarefaction in chronic heart failure
Researchers used sidestream dark-field sublingual videomicroscopy (with perfused boundary region as a glycocalyx measure) to compare capillary density and glycocalyx dimensions in 50 chronic heart failure patients and 35 healthy age-matched controls. Heart failure patients showed substantially fewer functional and perfused capillaries, while glycocalyx thickness differed only marginally. Within the heart failure group, larger PBR (thinner glycocalyx) correlated with inflammatory markers and worse liver/kidney function measures.
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Published paper
Automated Measurement of Microvascular Function Reveals Dysfunction in Systemic Sclerosis: A Cross-sectional Study.
Researchers used automated sidestream dark-field videomicroscopy (GlycoCheck) of sublingual microvessels to compare 40 patients with systemic sclerosis to 10 age-matched healthy controls. Patients with systemic sclerosis had fewer perfused microvessels, lower red blood cell fraction, a larger perfused boundary region (indicating deeper red-cell penetration into the glycocalyx), and thinner glycocalyx measured by a separate manual leukocyte-passage method. The study is descriptive and shows that this automated method can distinguish patients from controls.
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Published paper
Extracellular overhydration linked with endothelial dysfunction in the context of inflammation in haemodialysis dependent chronic kidney disease
This cross-sectional analysis of 72 haemodialysis patients compared fluid status (bioimpedance-derived overhydration) with macrovascular measures (pulse wave velocity, blood pressure), sublingual microvascular glycocalyx measurement (perfused boundary region by GlycoCheck), and a panel of inflammatory/endothelial biomarkers. Overhydrated patients had higher blood pressure and higher VCAM-1, thrombomodulin and IL-6 with lower leptin, while arterial stiffness and glycocalyx PBR did not differ between hydration groups. VCAM-1 was the strongest independent correlate of extracellular fluid excess.
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Published paper
Non-invasive assessment of microvascular dysfunction in patients with microvascular angina
This prospective study compared sublingual glycocalyx barrier properties (perfused boundary region, PBR) in 13 patients with microvascular angina (MVA), 13 volunteers, and 14 patients with obstructive coronary artery disease, and additionally measured myocardial perfusion reserve by adenosine stress cardiac MRI in the MVA patients. MVA patients had a larger baseline PBR than volunteers and lacked the normal PBR increase after nitroglycerin, suggesting reduced glycocalyx integrity. The PBR response correlated strongly with the MRI-derived transmural myocardial perfusion reserve index.
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Published paper
Early detection of left ventricular dysfunction in first-degree relatives of diabetic patients by myocardial deformation imaging: The role of endothelial glycocalyx damage
Researchers compared 40 first-degree relatives of people with type 2 diabetes (normal glucose tolerance), 40 people with abnormal glucose tolerance, and 20 normoglycemic controls without a family history, measuring sublingual glycocalyx thickness (perfused boundary region) and left ventricular deformation by speckle-tracking echocardiography before and 120 minutes after an oral glucose load. Both relatives and dysglycemic subjects had thinner glycocalyx (higher PBR), lower insulin sensitivity, and impaired longitudinal strain and twisting compared with controls. Greater glycocalyx damage tracked with worse myocardial deformation both at baseline and after glucose loading.
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Published paper
Characteristics and determinants of the sublingual microcirculation in populations of different ethnicity
This population-based study used sidestream/oblique epi-illumination sublingual capillaroscopy with GlycoCheck software to measure capillary density and the perfused boundary region (PBR, an inverse proxy for glycocalyx thickness) in 252 Han Chinese, 220 She Chinese and 254 Flemish adults. Higher cardiovascular risk (age, BMI, cholesterol, Framingham score) was associated with greater functional capillary recruitment, and in perfused capillaries a higher BMI and higher blood pressure were associated with lower PBR (i.e. apparently thicker glycocalyx). Associations were consistent across the three ethnic groups, although absolute PBR and capillary density differed between Chinese and Flemish participants.
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Published paper
Non-invasive assessment of microvascular dysfunction in families with premature coronary artery disease
This brief research letter reports on the use of non-invasive imaging of the sublingual microcirculation to assess microvascular function in relatives of patients with premature coronary artery disease. The authors, who developed the sidestream dark-field perfused boundary region technique, position this approach as a way to detect microvascular/glycocalyx abnormalities in people at inherited risk of early coronary disease. No abstract text was available, so the specific numerical results cannot be reported here.
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Published paper
Association of kidney function with changes in the endothelial surface layer
This cross-sectional study used sublingual sidestream dark-field imaging (GlycoCheck) to measure the perfused boundary region (PBR), an inverse index of endothelial glycocalyx integrity, in men with end-stage renal disease, kidney transplant recipients, and healthy controls. Patients with ESRD and transplant recipients who developed interstitial fibrosis/tubular atrophy had larger PBR (worse glycocalyx) and higher circulating shed glycocalyx markers, whereas recipients with stable graft function were indistinguishable from controls. Reduced eGFR correlated with a larger PBR and higher endothelial activation markers.
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Published paper
Deeper penetration of erythrocytes into the endothelial glycocalyx is associated with impaired microvascular perfusion
In a population-based sample of 915 middle-aged Dutch adults, researchers used sidestream dark-field imaging with automated GlycoCheck software to measure the perfused boundary region (PBR, a marker of how deeply red blood cells penetrate the endothelial glycocalyx) in sublingual microvessels. Deeper red-cell penetration (higher PBR) was strongly associated with poorer microvascular perfusion, measured as the percentage of time vessel segments contained red blood cells. The authors interpret a low PBR (thicker glycocalyx) as reflecting more efficient microvascular perfusion.
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Published paper
Is the systemic microvascular endothelial glycocalyx in peritoneal dialysis patients related to peritoneal transport?
This small cross-sectional study measured the sublingual microvascular glycocalyx (perfused boundary region, PBR, and estimated blood vessel density) with sidestream dark-field imaging in 15 peritoneal dialysis patients and compared these with peritoneal membrane transport measured by a peritoneal permeability analysis. Overall, no associations were found between systemic glycocalyx measures and peritoneal transport. Some correlations appeared only in the subgroup of patients without fast peritoneal transport.
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