Background: Cerebral small vessel disease is thought to result from endothelial dysfunction. The glycocalyx, lining the endothelium, is a major determinant of endothelial function. The glycocalyx is partially accessible to flowing red blood cells at its luminal side, called the perfused boundary region (PBR). Glycocalyx damage results in increased PBR, which can be measured in the sublingual microvasculature. We tested whether PBR is increased in patients with cerebral small vessel disease, i.e. lacunar stroke patients, and further distinguished patients with presence of white matter lesions as a sign of extensive cerebral small vessel disease. Methods: We used sidestream dark field imaging of the sublingual microcirculation in 31 lacunar stroke patients (6 with and 25 without white matter lesions) and 19 healthy controls. In each subject, automatic image analyzing software analyzed PBR in more than 3,000 vessel segments and the average dimension of glycocalyx PBR was determined in vessel segments with a diameter of 5-25 μm. Results: PBR did not differ between lacunar stroke patients and healthy controls (2.10 ± 0.25 vs. 2.08 ± 0.24 μm, p = 0.8). However, lacunar stroke patients with white matter lesions had an increased PBR compared with both healthy controls (2.35 ± 0.23 vs. 2.08 ± 0.24 μm, p = 0.03) and patients without white matter lesions (2.04 ± 0.22 μm, p = 0.004). Conclusions: White matter lesions are associated with an increase in the red blood cell permeable part of the sublingual microvascular glycocalyx in lacunar stroke patients. This implicates compromised glycocalyx barrier properties, which is consistent with impaired endothelial function in lacunar stroke patients with white matter lesions.

Microvascular dysfunction (MVD) is considered a crucial pathway in the development and progression of cardiometabolic and renal disease and is associated with increased cardiovascular mortality. MVD often coexists with or even precedes macrovascular disease, possibly due to shared mechanisms of vascular damage, such as inflammatory processes and oxidative stress. One of the first events in MVD is endothelial dysfunction. With the use of different physiologic or pharmacologic stimuli, endothelium-dependent (micro)vascular reactivity can be studied. This reactivity depends on the balance between various mediators, including nitric oxide, endothelin, and prostanoids, among others. The measurement of microvascular (endothelial) function is important to understand the pathophysiologic mechanisms that contribute to MVD and the role of MVD in the development and progression of cardiometabolic/renal disease. Here, we review a selection of direct, noninvasive techniques for measuring human microcirculation, with a focus on methods, interpretation, and limitations from the perspective of chronic cardiometabolic and renal disease.

In the entire study population, albuminuria was independently associated with lower information processing speed, whereas eGFR was not associated with cognitive performance. However, both were more strongly and extensively associated with cognitive performance in older individuals.

BackgroundChronic kidney disease, which is defined as having a reduced kidney function (estimated glomerular filtration rate (eGFR)) and/or signs of kidney damage (albuminuria), is highly prevalent in Western society and is associated with adverse health outcomes, such as cardiovascular disease. This warrants a search for risk factors of lower eGFR and higher albuminuria. Physical activity and sedentary behavior may be such risk factors.ObjectiveTo examine associations of physical activity (total, high, low), sedentary time and sedentary behavior patterns (breaks, prolonged bouts, average bout duration) with eGFR and albuminuria.MethodsWe examined these associations in 2,258 participants of the Maastricht Study (average age 60.1±8.1 years; 51.3% men), who wore an accelerometer 24h/day on 7 consecutive days. Associations with continuous eGFR and categories of urinary albumin excretion (UAE; <15 [reference category], 15-<30, ≥30 mg/24h) were evaluated with linear regression analyses and multinomial logistic regression analyses, respectively.ResultsAfter adjustment for potential confounders, each extra hour of total physical activity was associated with a more favorable kidney function (betaeGFR = 2.30 (95%CI = 1.46; 3.14)), whereas each extra hour of sedentary behavior was associated with a more adverse kidney function (betaeGFR = -0.71 (-1.08; -0.35)). Also, compared to individuals with the lowest levels of total physical activity, individuals with the highest levels had less kidney damage (OR15-<30mg/24h = 0.63 (0.41; 0.96), OR≥30mg/24h = 0.84 (0.53; 1.35). An extra hour of sedentary behavior was associated with more kidney damage (OR15-<30 mg/24h = 1.11 (1.01; 1.22), OR≥30 mg/24h = 1.10 (0.99; 1.22)). Further, a highly sedentary pattern was associated with a more adverse kidney function, but no association was seen with kidney damage.ConclusionsPhysical activity and sedentary behavior were associated with kidney function and kidney damage. Additionally, sedentary behavior patterns were associated with kidney function. Causal studies are required to examine whether this indeed implicates that prevention strategies should focus not only on increasing physical activity, but on reducing sedentary behavior as well.