Brain arterial remodeling contribution to nonembolic brain infarcts in patients with HIV.
Ontology highlight
ABSTRACT: Background
Cerebrovascular disease is a cause of morbidity in HIV-infected populations. The relationship among HIV infection, brain arterial remodeling, and stroke is unclear.Methods
Large brain arteries (n = 1,878 segments) from 284 brain donors with and without HIV were analyzed to obtain media and wall thickness and lumen-to-wall ratio, and to determine the presence of atherosclerosis and dolichoectasia (arterial remodeling extremes). Neuropathologic assessment was used to characterize brain infarcts. Multilevel models were used to assess for associations between arterial characteristics and HIV. Associations between arterial characteristics and brain infarcts were examined in HIV+ individuals only.Results
Adjusting for vascular risk factors, HIV infection was associated with thicker arterial walls and smaller lumen-to-wall ratios. Cerebral atherosclerosis accounted for one-quarter of the brain infarcts in HIV+ cases, and was more common with aging, diabetes, a lower CD4 nadir, and a higher antemortem CD4 count. In contrast, a higher lumen-to-wall ratio was the only arterial predictor of unexplained infarcts in HIV+ cases. Dolichoectasia was more common in HIV+ cases with smoking and media thinning, and with protracted HIV infection and a detectable antemortem viral load.Conclusions
HIV infection may predispose to inward remodeling compared to uninfected controls. However, among HIV+ cases with protracted immunosuppression, outward remodeling is the defining arterial phenotype. Half of all brain infarcts in this sample were attributed to the extremes of brain arterial remodeling: atherosclerosis and dolichoectasia. Understanding the mechanisms influencing arterial remodeling will be important in controlling cerebrovascular disease in the HIV-infected population.
SUBMITTER: Gutierrez J
PROVIDER: S-EPMC4603890 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Pathological arterial wall changes have been cited as potential mechanisms of cerebrovascular disease in the HIV population. We hypothesize that dilatation would be present in arterial walls of patients with HIV compared to controls. Fifty-one intracranial arteries, obtained from autopsies of five individuals with HIV infection and 13 without, were fixed, embedded, stained, and digitally photographed. Cross-sectional areas of intima, media, adventitia and lumen were measured by preset color thresholding. A measure of arterial remodeling was obtained by calculating the ratio between the lumen diameter and the thickness of the arterial wall. Higher numbers indicate arterial dilatation, while lower numbers indicate arterial narrowing. HIV-infected brain donors were more frequently black (80% vs. 15%, P = 0.02) compared with uninfected donors. Inter and intra-reader agreement measures were excellent. The continuous measure of vascular remodeling was significantly higher in the arteries from HIV donors (β = 2.8, P = 0.02). Adjustments for demographics and clinical covariates strengthen this association (β = 9.3, P = 0.01). We found an association of HIV infection with outward brain arterial remodeling. This association might be mediated by a thinner media layer. The reproduction of these results and the implications of this proposed pathophysiology merits further study.
| S-EPMC4388028 | biostudies-other
Project description:Mechanisms underlying brain arterial remodeling are uncertain. We tested the hypothesis that arterial size and location are important determinants of arterial characteristics. We collected large and penetrating brain arteries from cadavers with and without HIV. Morphometric characterization was obtained from digital images using color-based thresholding. The association of arterial size and location with lumen diameter, media and adventitia area, media proportion, a wall thickness, wall-to-lumen ratio and stenosis was obtained with multilevel mixed models and a P value ? 0.05 was considered significant. We included 336 brains, in which 2279 large arteries and 1488 penetrating arteries were identified. We found that arterial size was significantly associated with all arterial characteristics studied of large and penetrating arteries with exception of arterial stenosis in large arteries. After adjusting for size, an independent association was found between lumen diameters, media and adventitia thickness with artery locations. Arterial stenosis was also associated with artery location in both large and penetrating arteries. In summary, significant effects of size and/or location were found in arterial characteristics typically used to define arterial remodeling. Brain arterial remodeling characteristics differ across arterial sizes and location, and these differences should be controlled for in future studies of brain arterial remodeling.
| S-EPMC3928551 | biostudies-literature
Project description:Background?This study tests the hypothesis that increased elastolytic activity is associated differentially with dolichoectasia in individuals with and those without human immunodeficiency virus (HIV) infection.Methods?Large arteries from 84 autopsied brains from HIV-positive individuals and 78 autopsied brains from HIV-negative individuals were stained for metalloproteinase 2 (MMP-2), MMP-3, MMP-9, tissue inhibitor of metalloproteinases 1 (TIMP-1), TIMP-2, CD68, and caspase 3. Average pixel intensity was automatically obtained and categorized as high, moderate, or low. Dolichoectasia was defined as a lumen to wall ratio ?95th percentile.Results?High MMP-9 staining alone (P = .001) or coexistent with low TIMP-2 staining was associated with dolichoectasia only in HIV-negative individuals (P = <.001). In HIV-positive individuals, MMP-9 was associated with dolichoectasia only when coexpressed with caspase 3 (P = .01). Thinning of the media was associated with CD68 staining (P = <.001) in HIV-negative individuals, while caspase 3 was associated with a thinner media only in HIV-positive individuals (P = .01). Media thickness modified the association between lumen to wall ratio and MMP expression.Conclusions?A role for MMP/TIMP balance in dolichoectasia appears more prominent in HIV-negative individuals, while apoptosis, mediated by caspase 3, is the most important determinant of media thinning in HIV-infected individuals. Furthermore, apoptosis and media thickness appear to mediate the effects of MMP in the HIV-infected population.
| S-EPMC5079372 | biostudies-literature
Project description:BackgroundIncidentally discovered silent brain infarcts (id-SBIs) are an understudied condition with probable clinical significance, but it is not known how patients respond to or prioritize this condition. We sought to assess reporting of id-SBIs and how patients approach their diagnosis.MethodsPatients with id-SBIs were identified from sequential scans between 12/2015-5/2016, were referred by treating clinicians, or self-referred for the study. This study used qualitative semi-structured interviews. Purposeful sampling was used to achieve diversity in acuity, setting, and recruitment strategy. Interviews were audio-recorded and transcribed. A constant comparative method was used to develop a coding schema, find consensus, and iteratively explore emergent themes until thematic saturation was achieved.ResultsOnly 10 of 102 patients prospectively identified by neuroimaging were informed of the imaging findings. Twelve participants in total were interviewed. Among the study participants, the primary themes were cognitive, emotional, and behavioral responses to diagnostic, prognostic, and therapeutic uncertainty regarding id-SBIs. Clinicians described id-SBIs to participants as an ambiguous condition. Participants feared potential consequences of id-SBIs, including symptomatic stroke, dementia, and disability. Participants attempted to reduce uncertainty with strategies including equating id-SBIs with symptomatic stroke, self-education about stroke, and seeking second opinions.ConclusionParticipants considered id-SBIs to be a serious medical condition. Ambiguous counseling by clinicians on id-SBIs provoked or failed to attenuate fear, leading to participants adopting strategies aimed at reducing uncertainty.
| S-EPMC6462438 | biostudies-literature
Project description:ObjectiveTo determine the contribution of acute infarcts, evidenced by diffusion-weighted imaging positive (DWI+) lesions, to progression of white matter hyperintensities (WMH) and other cerebral small vessel disease (SVD) markers.MethodsWe performed monthly 3T magnetic resonance imaging (MRI) for 10 consecutive months in 54 elderly individuals with SVD. MRI included high-resolution multishell DWI, and 3-dimensional fluid-attenuated inversion recovery, T1, and susceptibility-weighted imaging. We determined DWI+ lesion evolution, WMH progression rate (ml/mo), and number of incident lacunes and microbleeds, and calculated for each marker the proportion of progression explained by DWI+ lesions.ResultsWe identified 39 DWI+ lesions on 21 of 472 DWI scans in 9 of 54 subjects. Of the 36 DWI+ lesions with follow-up MRI, 2 evolved into WMH, 4 evolved into a lacune (3 with cavity <3mm), 3 evolved into a microbleed, and 27 were not detectable on follow-up. WMH volume increased at a median rate of 0.027 ml/mo (interquartile range = 0.005-0.073), but was not significantly higher in subjects with DWI+ lesions compared to those without (p = 0.195). Of the 2 DWI+ lesions evolving into WMH on follow-up, one explained 23% of the total WMH volume increase in one subject, whereas the WMH regressed in the other subject. DWI+ lesions preceded 4 of 5 incident lacunes and 3 of 10 incident microbleeds.InterpretationDWI+ lesions explain only a small proportion of the total WMH progression. Hence, WMH progression seems to be mostly driven by factors other than acute infarcts. DWI+ lesions explain the majority of incident lacunes and small cavities, and almost one-third of incident microbleeds, confirming that WMH, lacunes, and microbleeds, although heterogeneous on MRI, can have a common initial appearance on MRI. ANN NEUROL 2019;86:582-592.
| S-EPMC6771732 | biostudies-literature
Project description:ImportanceCerebral vascular territories are of key clinical importance in patients with stroke, but available maps are highly variable and based on prior studies with small sample sizes.ObjectiveTo update and improve the state of knowledge on the supratentorial vascular supply to the brain by using the natural experiment of large artery infarcts and to map out the variable anatomy of the anterior, middle, and posterior cerebral artery (ACA, MCA, and PCA) territories.Design, setting, and participantsIn this cross-sectional study, digital maps of supratentorial infarcts were generated using diffusion-weighted magnetic resonance imaging (MRI) of 1160 patients with acute (<1-week) stroke recruited (May 2011 to February 2013) consecutively from 11 Korean stroke centers. All had supratentorial infarction associated with significant stenosis or occlusion of 1 of 3 large supratentorial cerebral arteries but with patent intracranial or extracranial carotid arteries. Data were analyzed between February 2016 and August 2017.Main outcomes and measuresThe 3 vascular territories were mapped individually by affected vessel, generating 3 data sets for which infarct frequency is defined for each voxel in the data set. By mapping these 3 vascular territories collectively, we generated data sets showing the Certainty Index (CI) to reflect the likelihood of a voxel being a member of a specific vascular territory, calculated as either ACA, MCA, or PCA infarct frequency divided by total infarct frequency in that voxel.ResultsOf the 1160 patients (mean [SD] age, 67.0 [13.3] years old), 623 were men (53.7%). When the cutoff CI was set as 90%, the volume of the MCA territory (approximately 54% of the supratentorial parenchymal brain volume) was about 4-fold bigger than the volumes of the ACA and PCA territories (each approximately 13%). Quantitative studies showed that the medial frontal gyrus, superior frontal gyrus, and anterior cingulate were involved mostly in ACA infarcts, whereas the middle frontal gyrus and caudate were involved mostly by MCA infarcts. The PCA infarct territory was smaller and narrower than traditionally shown. Border-zone maps could be defined by using either relative infarct frequencies or CI differences.Conclusions and relevanceWe have generated statistically rigorous maps to delineate territorial border zones and lines. The new topographic brain atlas can be used in clinical care and in research to objectively define the supratentorial arterial territories and their borders.
| S-EPMC6439879 | biostudies-literature
Project description:Cardiovascular disease is increased in patients with human immunodeficiency virus (HIV), but the specific mechanisms are unknown.To assess arterial wall inflammation in HIV, using 18fluorine-2-deoxy-D-glucose positron emission tomography (18F-FDG-PET), in relationship to traditional and nontraditional risk markers, including soluble CD163 (sCD163), a marker of monocyte and macrophage activation.A cross-sectional study of 81 participants investigated between November 2009 and July 2011 at the Massachusetts General Hospital. Twenty-seven participants with HIV without known cardiac disease underwent cardiac 18F-FDG-PET for assessment of arterial wall inflammation and coronary computed tomography scanning for coronary artery calcium. The HIV group was compared with 2 separate non-HIV control groups. One control group (n = 27) was matched to the HIV group for age, sex, and Framingham risk score (FRS) and had no known atherosclerotic disease (non-HIV FRS-matched controls). The second control group (n = 27) was matched on sex and selected based on the presence of known atherosclerotic disease (non-HIV atherosclerotic controls).Arterial inflammation was prospectively determined as the ratio of FDG uptake in the arterial wall of the ascending aorta to venous background as the target-to-background ratio (TBR).Participants with HIV demonstrated well-controlled HIV disease (mean [SD] CD4 cell count, 641 [288] cells/?L; median [interquartile range] HIV-RNA level, <48 [<48 to <48] copies/mL). All were receiving antiretroviral therapy (mean [SD] duration, 12.3 [4.3] years). The mean FRS was low in both HIV and non-HIV FRS-matched control participants (6.4; 95% CI, 4.8-8.0 vs 6.6; 95% CI, 4.9-8.2; P = .87). Arterial inflammation in the aorta (aortic TBR) was higher in the HIV group vs the non-HIV FRS-matched control group (2.23; 95% CI, 2.07-2.40 vs 1.89; 95% CI, 1.80-1.97; P < .001), but was similar compared with the non-HIV atherosclerotic control group (2.23; 95% CI, 2.07-2.40 vs 2.13; 95% CI, 2.03-2.23; P = .29). Aortic TBR remained significantly higher in the HIV group vs the non-HIV FRS-matched control group after adjusting for traditional cardiovascular risk factors (P = .002) and in stratified analyses among participants with undetectable viral load, zero calcium, FRS of less than 10, a low-density lipoprotein cholesterol level of less than 100 mg/dL (<2.59 mmol/L), no statin use, and no smoking (all P ? .01). Aortic TBR was associated with sCD163 level (P = .04) but not with C-reactive protein (P = .65) or D-dimer (P = .08) among patients with HIV.Participants infected with HIV vs noninfected control participants with similar cardiac risk factors had signs of increased arterial inflammation, which was associated with a circulating marker of monocyte and macrophage activation.
| S-EPMC3724172 | biostudies-literature
Project description:Preliminary studies suggest that intracranial arteries are capable of accommodating plaque formation by remodeling. We sought to study the ability and extent of intracranial arteries to remodel using 3-dimensional high-resolution black blood magnetic resonance imaging and investigate its relation to ischemic events.Forty-two patients with cerebrovascular ischemic events underwent 3-dimensional time-of-flight magnetic resonance angiography and contrast-enhanced black blood magnetic resonance imaging examinations at 3 T for intracranial atherosclerotic disease. Each plaque was classified by location (eg, posterior versus anterior circulation) and its likelihood to have caused a stroke identified on magnetic resonance imaging (culprit, indeterminate, or nonculprit). Lumen area, outer wall area, and wall area were measured at the lesion and reference sites. Plaque burden was calculated as wall area divided by outer wall area. The arterial remodeling ratio (RR) was calculated as outer wall area at the lesion site divided by outer wall area at the reference site after adjusting for vessel tapering. Arterial remodeling was categorized as positive if RR>1.05, intermediate if 0.95?RR?1.05, and negative if RR<0.95.One hundred and thirty-seven plaques were identified in 42 patients (37% [50] posterior and 63% [87] anterior). Compared with anterior circulation plaques, posterior circulation plaques had a larger plaque burden (77.7±15.7 versus 69.0±14.0; P=0.008), higher RR (1.14±0.38 versus 0.95±0.32; P=0.002), and more often exhibited positive remodeling (54.0% versus29.9%; P=0.011). Positive remodeling was marginally associated with downstream stroke presence when adjusted for plaque burden (odds ratio 1.34, 95% confidence interval: 0.99-1.81).Intracranial arteries remodel in response to plaque formation, and posterior circulation arteries have a greater capacity for positive remodeling and, consequently, may more likely elude angiographic detection. Arterial remodeling may provide insight into stroke risk.
| S-EPMC4729583 | biostudies-literature
Project description:Purpose: Silent brain infarcts (SBI) are frequently detected in patients with atrial fibrillation (AF), but it is unknown whether SBI are linked to autonomic dysfunction. We aimed to explore the association of autonomic dysfunction with SBI in AF patients. Methods: 1,358 AF patients without prior stroke or TIA underwent brain MRI and 5-min resting ECG. We divided our cohort into AF patients who presented in sinus rhythm (SR-group, n = 816) or AF (AF-group, n = 542). HRV triangular index (HRVI), standard deviation of normal-to-normal intervals, mean heart rate, root mean square root of successive differences of normal-to-normal intervals, 5-min total power and power in the low frequency, high frequency and very low frequency range were calculated. Primary outcome was presence of SBI in the SR group, defined as large non-cortical or cortical infarcts. Secondary outcomes were SBI volumes and topography. Results: Mean age was 72 ± 9 years, 27% were female. SBI were detected in 10.5% of the SR group and in 19.9% of the AF group (p < 0.001). HRVI <15 was the only HRV parameter associated with the presence of SBI after adjustment for clinical covariates in the SR group [odds ratio (OR) 1.67; 95% confidence interval (CI): 1.03-2.70; p = 0.037]. HRVI <15 was associated with larger brain infarct volumes [β (95% CI) -0.47 (-0.84; -0.09), p = 0.016] in the SR group and was more frequently observed in patients with right- than left-hemispheric SBI (p = 0.017). Conclusion: Impaired HRVI is associated with SBI in AF patients. AF patients with autonomic dysfunction might undergo systematic brain MRI screening to initiate intensified medical treatment. Clinical Trials Gov Identifier: NCT02105844.
| S-EPMC8175975 | biostudies-literature
Project description:Arterial stiffness is evaluated with the measurement of pulse wave velocity (PWV), while overhydration (OH) and nutritional status are evaluated with bioimpedance spectroscopy (BIS). In this study, we investigated the effect of a single dialysis session on arterial stiffness, hydration status, and laboratory parameters. The observational, cross-sectional, cohort study included 71?HD patients with mean age 64?±?16?yrs. A Complior device was used to perform PWV measurements. The patients were examined immediately before and 15?min after a mid-week hemodialysis session. Body fluids and nutritional status were studied using a Body Composition Monitor (BCM), Fresenius Medical Care. Clinical and laboratory data were also analyzed. Multivariate regression analysis of PWV before HD showed that an OH increase of 1?L relate to a PWV parameter rise before HD of 0.523?m/s. Multivariate regression analysis of PWV after HD showed that a rise of central SBP after HD of 10?mmHg relate to a PWV increase after HD of 0.707?m/s. Our data indicate that hydration status and blood pressure may be major determinants of PWV in HD patients.
| S-EPMC6014471 | biostudies-literature