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Increased Cerebral Small Vessel Disease Burden With Renal Dysfunction and Albuminuria in Patients Taking Antithrombotic Agents: The Bleeding With Antithrombotic Therapy 2.

ABSTRACT: Background The aim of this study was to determine the associations of cerebral small vessel disease (SVD) burden with renal dysfunction and albuminuria in patients taking oral antithrombotic agents. Methods and Results Patients who newly started or continued taking oral antiplatelets or anticoagulants were enrolled in a prospective, multicenter, observational study. Obligatorily acquired multimodal magnetic resonance imaging at registration with prespecified imaging conditions was assessed for cerebral microbleeds, white matter hyperintensities, enlarged basal ganglia perivascular spaces, or lacunes, and an ordinal SVD score was calculated (range, 0-4). Multivariable adjusting covariates were age, sex, hypertension, diabetes, dyslipidemia, current smoking, drinking, and estimated glomerular filtration rate (eGFR). Of 5324 patients (1762 women; median age, 73 years), 4797 (90.1%) patients were taking oral antithrombotic agents for secondary stroke prevention. Cerebral microbleeds were present in 32.7%, confluent white matter hyperintensities in 51.8%, extensive basal ganglia perivascular spaces in 38.9%, and lacunes in 59.4%. Median SVD score was 2. Compared with eGFR category G1 (eGFR ≥90 mL/min per 1.73 m²), adjusted odds ratios for SVD score increment were 1.63 (95% CI, 1.11-2.39) at category G4 (eGFR 15-<30 mL/min per 1.73 m²) and 2.05 (95% CI, 1.33-3.16) at G5 (eGFR <15 mL/min per 1.73 m²). Corresponding odds ratios relative to urinary albumin-to-creatinine ratio (ACR) category A1 (ACR <30 mg/g) were 1.29 (95% CI, 1.12-1.49) for category A2 (ACR 30-<300 mg/g) and 1.37 (95% CI, 1.05-1.77) for A3 (ACR ≥300 mg/g). When combined eGFR and ACR categories were assessed, risks for SVD score increment generally increased as eGFR decreased and ACR increased. Conclusions Both reduced eGFR and albuminuria were independently associated with increased cerebral SVD burden in patients requiring oral antithrombotic medication mainly for secondary stroke prevention. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01581502; URL: https://www.umin.ac.jp/ctr; Unique identifier: UMIN000023669.

SUBMITTER: Tanaka K

PROVIDER: S-EPMC9075282 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background & aimsThe safety of different antithrombotic strategies for patients with 1 or more indication for antithrombotic drugs has not been determined. We investigated the risk and time frame for gastrointestinal bleeding (GIB) in patients prescribed different antithrombotic regimens. We proposed that risk would increase over time and with combination regimens, especially among elderly patients.MethodsWe performed a retrospective analysis of nationwide claims data from privately insured and Medicare Advantage enrollees who received anticoagulant and/or antiplatelet agents from October 1, 2010, through May 31, 2017. Patients were stratified by their prescriptions (anticoagulant alone, antiplatelet alone, or a combination) and by their primary diagnosis (atrial fibrillation, ischemic heart disease, or venous thromboembolism). The 1-year GIB risk was estimated using parametric time-to-event survival models and expressed as annualized risk and number needed to harm (NNH).ResultsOur final analysis included 311,211 patients (mean ages, 67 years for monotherapy and 69.8 years for combination antithrombotic therapy). There was no significant difference in the proportion of patients with bleeding after anticoagulant or antiplatelet monotherapy (∼3.5%/year). Combination antithrombotic therapy increased GIB risk compared with anticoagulant (NNH, 29) or antiplatelet (NNH, 31) monotherapy, regardless of the patients' diagnosis or time point analyzed. Advancing age was associated with increasing 1-year probability of GIB. Patients prescribed combination therapy were at the greatest risk for GIB, especially after the age of 75 years (GIB occurred in 10%-17.5% of patients/y).ConclusionsIn an analysis of nationwide insurance and Medicare claims data, we found GIB to occur in a higher proportion of patients prescribed combinations of anticoagulant and antiplatelet agents compared with monotherapy. Among all drug exposure categories and cardiovascular conditions, the risk of GIB increased with age, especially among patients older than 75 years.

Project description:ObjectiveWe investigated the contribution of small vessel disease (SVD) to anticoagulant-associated intracerebral haemorrhage (ICH).MethodsClinical Relevance of Microbleeds in Stroke-2 comprised two independent multicentre observation studies: first, a cross-sectional study of patients with ICH; and second, a prospective study of patients taking anticoagulants for atrial fibrillation (AF) after cerebral ischaemia. In patients with ICH, we compared SVD markers on CT and MRI according to prior anticoagulant therapy. In patients with AF and cerebral ischaemia treated with anticoagulants, we compared the rates of ICH and ischaemic stroke according to SVD burden score during 2 years follow-up.ResultsWe included 1030 patients with ICH (421 on anticoagulants), and 1447 patients with AF and cerebral ischaemia. Medium-to-high severity SVD was more prevalent in patients with anticoagulant-associated ICH (CT 56.1%, MRI 78.7%) than in those without prior anticoagulant therapy (CT 43.5%, p<0.001; MRI 64.5%, p=0.072). Leukoaraiosis and atrophy were more frequent and severe in ICH associated with prior anticoagulation. In the cerebral ischaemia cohort (779 with SVD), during 3366 patient-years of follow-up the rate of ICH was 0.56%/year (IQR 0.27-1.03) in patients with SVD, and 0.06%/year (IQR 0.00-0.35) in those without (p=0.001); ICH was independently associated with severity of SVD (HR 5.0, 95% CI 1.9 to 12.2,p=0.001), and was predicted by models including SVD (c-index 0.75, 95% CI 0.63 to 0.85).ConclusionsMedium-to-high severity SVD is associated with ICH occurring on anticoagulants, and independently predicts ICH in patients with AF taking anticoagulants; its absence identifies patients at low risk of ICH. Findings from these two complementary studies suggest that SVD is a contributory factor in ICH in patients taking anticoagulants and suggest that anticoagulation alone should no longer be regarded as a sufficient 'cause' of ICH.Trial registrationNCT02513316.

Project description:BackgroundAs the retinal microvasculature shares similarities with the cerebral microvasculature, numerous studies have shown that retinal vascular is associated with cognitive decline. In addition, several population-based studies have confirmed the association between retinal vascular and cerebral small vessel disease (CSVD) burden. However, the association of retinal vascular with CSVD burden as well as cognitive function has not been explored simultaneously. This study investigated the relations of retinal microvascular parameters (RMPs) with CSVD burden and cognitive function.MethodsWe conducted a cross-sectional study of participants in the KaiLuan study. Data were collected from subjects aged ≥18 years old who could complete retinal photography and brain magnetic resonance imaging (MRI) between December 2020 to October 2021 in the Kailuan community of Tangshan. RMPs were evaluated using a deep learning system. The cognitive function was measured using the Montreal Cognitive Assessment (MoCA). We conducted logistic regression models, and mediation analysis to evaluate the associations of RMPs with CSVD burden and cognitive decline.ResultsOf the 905 subjects (mean age: 55.42±12.02 years, 54.5% female), 488 (53.9%) were classified with cognitive decline. The fractal dimension (FD) [odds ratio (OR), 0.098, 95% confidence interval (CI): 0.015-0.639, P=0.015] and global vein width (OR: 1.010, 95% CI: 1.005-1.015, P<0.001) were independent risk factors for cognitive decline after adjustment for potential confounding factors. The global artery width was significantly associated with severe CSVD burden (OR: 0.985, 95% CI: 0.974-0.997, P=0.013). The global vein width was sightly associated with severe CSVD burden (OR: 1.005, 95% CI: 1.000-1.010, P=0.050) after adjusting for potential confounders. The multivariable-adjusted odds ratios (95% CI) in highest tertile versus lowest tertile of global vein width were 1.290 (0.901-1.847) for cognitive decline and 1.546 (1.004-2.290) for severe CSVD burden, respectively. Moreover, CSVD burden played a partial mediating role in the association between global vein width and cognitive function (mediating effect 6.59%).ConclusionsRMPs are associated with cognitive decline and the development of CSVD. A proportion of the association between global vein width and cognitive decline may be attributed to the presence of CSVD burden.

Project description:This study aims to investigate the disrupted topological organization of gray matter (GM) structural networks in cerebral small vessel disease (CSVD) patients with cerebral microbleeds (CMBs). Subject-wise structural networks were constructed from GM volumetric features of 49 CSVD patients with CMBs (CSVD-c), 121 CSVD patients without CMBs (CSVD-n), and 74 healthy controls. The study used graph theory to analyze the global and regional properties of the network and their correlation with cognitive performance. We found that both the control and CSVD groups exhibited efficient small-world organization in GM networks. However, compared to controls, CSVD-c and CSVD-n patients exhibited increased global and local efficiency (Eglob/Eloc) and decreased shortest path lengths (Lp), indicating increased global integration and local specialization in structural networks. Although there was no significant global topology change, partially reorganized hub distributions were found between CSVD-c and CSVD-n patients. Importantly, regional topology in nonhub regions was significantly altered between CSVD-c and CSVD-n patients, including the bilateral anterior cingulate gyrus, left superior parietal gyrus, dorsolateral superior frontal gyrus, and right MTG, which are involved in the default mode network (DMN) and sensorimotor functional modules. Intriguingly, the global metrics (Eglob, Eloc, and Lp) were significantly correlated with MoCA, AVLT, and SCWT scores in the control group but not in the CSVD-c and CSVD-n groups. In contrast, the global metrics were significantly correlated with the SDMT score in the CSVD-s and CSVD-n groups but not in the control group. Patients with CSVD show a disrupted balance between local specialization and global integration in their GM structural networks. The altered regional topology between CSVD-c and CSVD-n patients may be due to different etiological contributions, which may offer a novel understanding of the neurobiological processes involved in CSVD with CMBs.

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Increased Cerebral Small Vessel Disease Burden With Renal Dysfunction and Albuminuria in Patients Taking Antithrombotic Agents: The Bleeding With Antithrombotic Therapy 2.

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