Microalbuminuria and the Combination of MRI Markers of Cerebral Small Vessel Disease.

Kidney function has been related to the presence of individual markers of cerebral small vessel disease (CSVD), as lacunes, white matter hyperintensities (WMH) or microbleeds. We aimed at studying the relationship of kidney dysfunction with the combination of several markers of CSVD. Subjects are those included in the ISSYS cohort (Investigating Silent Strokes in hypertensives: a magnetic resonance imaging study). A scale ranging from 0 to 4 points was applied based on the presence (one point each) of lacunes, deep microbleeds, moderate to extensive basal ganglia enlarged perivascular spaces (EPVS), and periventricular or deep WMH. We determined the creatinine-based glomerular filtration rate and the urinary albumin-to-creatinine ratio (UACR) as markers of kidney function and studied their association with the scale of CSVD in univariate and ordinal logistic regression analyses. Among the 975 patients included, 28.2% presented one or more CSVD markers, being the most prevalent marker (either alone or in combination) basal ganglia EPVS. The UACR was elevated at increasing the scores of the CSVD scale and remained as independent predictor of the combination of markers (common OR per natural log unit increase in UACR: 1.23, 1.07-1.41) after controlling per age, gender, cardiovascular risk, antihypertensive treatment and hypertension duration. In contrast, no associations were found between the CSVD scores and the creatinine-based estimated glomerular filtration rate. A significant proportion of stroke-free hypertensives present at least one imaging marker of CSVD. UACR but not creatinine-based glomerular filtration rate is associated with the combination of markers of CSVD.

Vilar-Bergua A ，Riba-Llena I ，Ramos N ，Mundet X ，Espinel E ，López-Rueda A ，Ostos E ，Seron D ，Montaner J ，Delgado P ... -  《-》

Arterial Stiffness Is Associated With Basal Ganglia Enlarged Perivascular Spaces and Cerebral Small Vessel Disease Load.

We assessed whether the load of cerebral small vessel disease (cSVD) and its individual markers, including lacunes, white matter hyperintensities, microbleeds, and enlarged perivascular spaces (EPVS), are associated with arterial stiffness. We evaluated cSVD markers in a cohort of 782 hypertensive individuals without history of stroke or dementia. The load of the disease was calculated using an ordinal scale ranging from 0 to 4 (1 point was given for each of the 4 markers examined). The arterial stiffness was tested by measuring the carotid-femoral pulse wave velocity with an oscillometric automatic device. The mean age of the participants (49.6% women) was 62.7±5.4 years, and the mean systolic/diastolic blood pressure was 142.9/77.3 mm Hg (55.5% of the participants had poor blood pressure control). We found 7.2% cases with lacunes, 6.4% with microbleeds, 6.7% with extensive white matter hyperintensities, 24.5% with extensive basal ganglia EPVS, and 40.1% with extensive EPVS in the centrum semiovale. Regarding the cSVD load, 19.7% of the participants scored 1, 6.5% scored 2, and 1.4% scored ≥3. The median carotid-femoral pulse wave velocity was 10.5 m/s (interquartile range, 9.2-11.9) and was associated with lacunes (odds ratio per carotid-femoral pulse wave velocity SD increase, 1.51; 95% confidence interval, 1.13-2.03), extensive basal ganglia EPVS (odds ratio, 1.39; 95% confidence interval, 1.16-1.67), and cSVD load (common odds ratio, 1.42; 95% confidence interval, 1.19-1.68). We found that, in a cohort of hypertensive individuals, the arterial stiffness is associated with the total load of the cSVD, especially with lacunes and basal ganglia EPVS.

Riba-Llena I ，Jiménez-Balado J ，Castañé X ，Girona A ，López-Rueda A ，Mundet X ，Jarca CI ，Álvarez-Sabin J ，Montaner J ，Delgado P ... -  《-》

Kidney Dysfunction is Associated with a High Burden of Cerebral Small Vessel Disease in Primary Intracerebral Hemorrhage.

To investigate the association of kidney function with the total burden of Cerebral Small Vessel Disease (CSVD) in primary Intracerebral Hemorrhage (pICH). Cerebral magnetic resonance imagings of consecutively enrolled pICH patients were reviewed to assess for lacunes, White Matter Hyperintensity (WMH), Cerebral Microbleeds (CMBs) and Enlarged Perivascular Spaces (EPVS). Minor refinements to the CSVD score, namely modified CSVD score 1 and 2, were made by incorporating different weightings of CSVD markers. Kidney function was assessed using the estimated Glomerular Filtration Rate (eGFR). We used ordinal regression analysis to assess the association of kidney function with the CSVD score and modified scores. In the 108 patients included, the presence of lacunes, CMBs, MWH and basal ganglia EPVS>10 was 27.8%, 67.6%, 47.2% and 35.2%, respectively. In multivariable ordinal regression, a decreasing eGFR value was associated with an increased CSVD score [Odds Ratio (OR) 0.978, 95% Confidence Interval (CI) 0.962 to 0.995, P=0.013], modified CSVD score 1 (OR 0.973, 95% CI 0.957 to 0.990, P=0.002) and 2 (OR 0.969, 95% CI 0.953 to 0.986, P<0.001). The link between eGFR and the total burden of CSVD was significant in strictly deep pICH (P=0.011 for CSVD score; P=0.001 for modified score 1 and 2), but not strictly lobar pICH in subgroup analysis. Low eGFR is associated with a high burden of CSVD in patients with deep pICH, but not lobar pICH. Future studies are warranted to assess whether low eGFR is a potential therapeutic target for preventing the progress of CSVD burden for deep pICH.

Xu M ，Zhang S ，Liu J ，Luo H ，Wu S ，Cheng Y ，Liu M ... -  《-》

Kidney function changes and their relation with the progression of cerebral small vessel disease and cognitive decline.

We aimed to study whether worsening in markers of kidney function parallels the progression in cerebral small vessel disease (cSVD) and cognitive decline. Data from the ISSYS (Investigating Silent Strokes in Hypertensives Study), a longitudinal population-based study in hypertensives aged 50-70 and dementia and stroke-free at baseline. At both visits, patients underwent a brain MRI, a cognitive diagnosis (normal aging or mild cognitive impairment, [MCI]) and urine and blood sampling collection. We assessed the incidence of infarcts and cerebral microbleeds, and the progression of white matter hyperintensities at periventricular (PVH) and deep areas. We determined changes in albumin-creatinine ratio and estimated glomerular filtration rate (eGFR). These changes were dichotomized into microalbuminuria at follow-up -either in subjects with or without baseline microalbuminuria- and significant decline in eGFR -lowest quintile of eGFR change (-10.57 mL/min/1.73m2)-. 360 patients were followed-up for 4 years. 80 (23%) patients presented microalbuminuria at follow-up and 68 (20.1%) experienced a significant eGFR decline. Considering cSVD change, we found a relationship between microalbuminuria at follow-up and progression in PVH (β = 0.31, P-value = .01). Regarding cognitive decline, presence of microalbuminuria at follow-up related to a steeper decrease in memory function (β = -0.36, P-value<.01). Moreover, patients with significant decline in eGFR were at higher risk of incident MCI (OR = 3.54, P-value = .02). These associations were independent of progression of cSVD. The worsening in markers of kidney function paralleled the decrease in cognition and the progression of cSVD, and this may be explained by common shared underlying risk factors.

Jiménez-Balado J ，Riba-Llena I ，Pizarro J ，Palasí A ，Penalba A ，Ramírez C ，Maisterra O ，Espinel E ，Ramos N ，Pujadas F ，Serón D ，Delgado P ... -  《-》

Chronic Kidney Disease in Patients With Lacunar Stroke: Association With Enlarged Perivascular Spaces and Total Magnetic Resonance Imaging Burden of Cerebral Small Vessel Disease.

The relationship between chronic kidney disease and cerebral small vessel disease (cSVD), especially enlarged perivascular spaces (EPVS), has not been fully understood. This study aimed to investigate the association of chronic kidney disease and EPVS, as well as the total burden of cSVD on magnetic resonance imaging, expressed by the simultaneous presence of multiple markers of cSVD, among patients with first-ever lacunar stroke. Four hundred and thirteen consecutive patients were prospectively enrolled. Centrum semiovale and basal ganglia EPVS on T2-weighted magnetic resonance imaging, as well as other imaging markers of cSVD, including lacune, white matter lesions, and cerebral microbleeds, were rated using validated scales. Chronic kidney disease was defined as either reduced estimated glomerular filtration rate or the presence of proteinuria. After adjustments for potential confounders by logistic regression, proteinuria and impaired estimated glomerular filtration rate were correlated with the severity of EPVS in both centrum semiovale (odds ratio [OR] 2.59; 95% confidence interval [CI] 1.19-5.64 and OR 2.37; 95% CI 1.19-4.73) and basal ganglia (OR 5.12; 95% CI 2.70-12.10 and OR 4.17; 95% CI 2.08-8.37). A similar association was also found between proteinuria and low estimated glomerular filtration rate levels and the comprehensive cSVD burden (OR 2.13; 95% CI 1.10-4.14 and OR 5.59; 95% CI 2.58-12.08). Proteinuria and impaired estimated glomerular filtration rate are associated with increasing EPVS severity and, furthermore, accumulated magnetic resonance imaging burden of cSVD in patients with first-ever acute lacunar stroke.

Xiao L ，Lan W ，Sun W ，Dai Q ，Xiong Y ，Li L ，Zhou Y ，Zheng P ，Fan W ，Ma N ，Guo Z ，Chen X ，Xie X ，Xu L ，Zhu W ，Xu G ，Liu X ... -  《-》