Background and ObjectivesScreening for unruptured intracranial aneurysms (UIAs) is effective for first-degree relatives(FDRs) of patients with aneurysmal subarachnoid hemorrhage (aSAH). Whether... Show moreBackground and ObjectivesScreening for unruptured intracranial aneurysms (UIAs) is effective for first-degree relatives(FDRs) of patients with aneurysmal subarachnoid hemorrhage (aSAH). Whether screening isalso effective for FDRs of patients with UIA is unknown. We determined the yield of screening insuch FDRs, assessed rupture risk and treatment decisions of aneurysms that were found, iden-tified potential high-risk subgroups, and studied the effects of screening on quality of life (QoL).MethodsIn this prospective cohort study, we included FDRs, aged 20–70 years, of patients with UIAwithout a family history of aSAH who visited the Neurology outpatient clinic in 1 of 3 partici-pating tertiary referral centers in the Netherlands. FDRs were screened for UIA with magneticresonance angiography between 2017 and 2021. We determined UIA prevalence and developed aprediction model for UIA risk at screening using multivariable logistic regression. QoL wasevaluated with questionnaires 6 times during the first year after screening and assessed with alinear mixed-effects model.ResultsWe detected 24 UIAs in 23 of 461 screened FDRs, resulting in a 5.0% prevalence (95% CI3.2–7.4). The median aneurysm size was 3 mm (interquartile range [IQR] 2–4 mm), and themedian 5-year rupture risk assessed with the PHASES score was 0.7% (IQR 0.4%–0.9%). AllUIAs received follow-up imaging, and none were treated preventively. After a median follow-up of24 months (IQR 13–38 months), no UIA had changed. Predicted UIA risk at screening rangedbetween 2.3% and 14.7% with the highest risk in FDRs who smoke and have excessive alcoholconsumption (c-statistic: 0.76; 95% CI 0.65–0.88). At all survey moments, health-related QoLand emotional functioning were comparable with those in a reference group from the generalpopulation. One FDR with a positive screening result expressed regret about screening.DiscussionBased on the current data, we do not advise screening FDRs of patients with UIA becauseall identified UIAs had a low rupture risk. We observed no negative effect of screening on QoL. Alonger follow-up should determine the risk of aneurysm growth requiring preventive treatment. Show less
BackgroundPatients with carotid artery occlusion (CAO) are vulnerable to cognitive impairment (CI). Anaemia is associated with CI in the general population. We hypothesized that lower haemoglobin... Show moreBackgroundPatients with carotid artery occlusion (CAO) are vulnerable to cognitive impairment (CI). Anaemia is associated with CI in the general population. We hypothesized that lower haemoglobin is associated with cognitive impairment (CI) in patients with CAO and that this association is accentuated by cerebral blood flow (CBF).Methods104 patients (mean age 66±8 years, 77% men) with complete CAO from the Heart-Brain Connection study were included. Anaemia was defined as haemoglobin < 12 g/dL for women and < 13 g/dL for men. Cognitive test results were standardized into z-scores (using a reference group) in four cognitive domains. Patients were classified as cognitively impaired when ≥ one domain was impaired. The association between lower haemoglobin and both cognitive domain z-scores and the presence of CI was assessed with adjusted (age, sex, education and ischaemic stroke) regression models. Total CBF (measured with phase contrast MRI) and the interaction term haemoglobin*CBF were additionally added to the analyses.ResultsAnaemia was present in 6 (6%) patients and was associated with CI (RR 2.54, 95% CI 1.36; 4.76). Lower haemoglobin was associated with the presence of CI (RR per minus 1 g/dL haemoglobin 1.15, 95% CI 1.02; 1.30). This association was strongest for the attention-psychomotor speed domain (RR for impaired attention-psychomotor speed functioning per minus 1 g/dL haemoglobin 1.27, 95% CI 1.09;1.47) and ß for attention-psychomotor speed z-scores per minus 1 g/dL haemoglobin -0.19, 95% CI -0.33; -0.05). Adjustment for CBF did not affect these results and we found no interaction between haemoglobin and CBF in relation to cognition.ConclusionLower haemoglobin concentrations are associated with CI in patients with complete CAO, particularly in the domain attention-psychomotor speed. CBF did not accentuate this association. If validated in longitudinal studies, haemoglobin might be a viable target to prevent cognitive deterioration in patients with CAO. Show less
Algra, A.M.; Greving, J.P.; Wermer, M.J.H.; Walderveen, M.A.A. van; Schaaf, I.C. van der; Zwan, A. van der; ... ; Vergouwen, M.D.I. 2022
Background and Objectives In counseling patients with an unruptured intracranial aneurysm (UIA), quality of life (QoL) outcomes are important for informed decision making. We evaluated QoL outcomes... Show moreBackground and Objectives In counseling patients with an unruptured intracranial aneurysm (UIA), quality of life (QoL) outcomes are important for informed decision making. We evaluated QoL outcomes in patients with and without preventive aneurysm occlusion at multiple time points during the first year after UIA diagnosis and studied predictors of QoL outcomes. Methods We performed a prospective cohort study in patients aged >= 18 years with a newly diagnosed UIA in 2 tertiary referral centers in the Netherlands between 2017 and 2019. Patients were sent QoL questionnaires at 7 (aneurysm occlusion) or 5 (no occlusion) moments during the first year after diagnosis. We collected baseline data on patient and aneurysm characteristics, passive coping style (Utrecht Coping List), occlusion modality, and neurologic complications. We assessed health-related QoL (HRQoL) with the EuroQol 5 dimensions (EQ-5D), emotional functioning with the Hospital Anxiety and Depression Scale (HADS), and restrictions in daily activities with the Utrecht Scale for Evaluation of Rehabilitation-Participation (USER-P). We used a linear mixed-effects model to assess the course of QoL over time and to explore predictors of QoL outcomes. Results Of 153 eligible patients, 99 (65%) participated, of whom 30/99 (30%) underwent preventive occlusion. Patients undergoing occlusion reported higher baseline levels of passive coping, anxiety and depression, and restrictions than patients without occlusion. During recovery after occlusion, patients reported more restrictions compared with baseline (adjusted USER-P decrease 1 month post occlusion: -12.8 [95% CI -23.8 to -1.9]). HRQoL and emotional functioning gradually improved after occlusion (EQ-5D increase at 1 year: 8.6 [95% CI 0.1-17.0] and HADS decrease at 1 year: -5.4 [95% CI -9.4 to -1.5]). In patients without occlusion, the largest HRQoL improvement occurred directly after visiting the outpatient aneurysm clinic (EQ-5D increase: 9.2 [95% CI 5.5-12.8]). At 1 year, QoL outcomes were comparable in patients with and without occlusion. Factors associated with worse QoL outcomes were a passive coping style in all patients, complications in patients with occlusion, and higher rupture risks in patients without occlusion. Discussion After UIA diagnosis, QoL improves gradually after preventive occlusion and directly after counseling at the outpatient clinic in patients without occlusion, resulting in comparable 1-year QoL outcomes. A passive coping style is an important predictor of poor QoL outcomes in all patients with UIA. Show less
Background and Purpose: In previous studies, women had a higher risk of rupture of intracranial aneurysms than men, but female sex was not an independent risk factor. This may be explained by a... Show moreBackground and Purpose: In previous studies, women had a higher risk of rupture of intracranial aneurysms than men, but female sex was not an independent risk factor. This may be explained by a higher prevalence of patient- or aneurysm-related risk factors for rupture in women than in men or by insufficient power of previous studies. We assessed sex differences in rupture rate taking into account other patient- and aneurysm-related risk factors for aneurysmal rupture. Methods: We searched Embase and Pubmed for articles published until December 1, 2020. Cohorts with available individual patient data were included in our meta-analysis. We compared rupture rates of women versus men using a Cox proportional hazard regression model adjusted for the PHASES score (Population, Hypertension, Age, Size of Aneurysm, Earlier Subarachnoid Hemorrhage From Another Aneurysm, Site of Aneurysm), smoking, and a positive family history of aneurysmal subarachnoid hemorrhage. Results: We pooled individual patient data from 9 cohorts totaling 9940 patients (6555 women, 66%) with 12 193 unruptured intracranial aneurysms, and 24 357 person-years follow-up. Rupture occurred in 163 women (rupture rate 1.04%/person-years [95% CI, 0.89-1.21]) and 63 men (rupture rate 0.74%/person-years [95% CI, 0.58-0.94]). Women were older (61.9 versus 59.5 years), were less often smokers (20% versus 44%), more often had internal carotid artery aneurysms (24% versus 17%), and larger sized aneurysms (>= 7 mm, 24% versus 23%) than men. The unadjusted women-to-men hazard ratio was 1.43 (95% CI, 1.07-1.93) and the adjusted women/men ratio was 1.39 (95% CI, 1.02-1.90). Conclusions: Women have a higher risk of aneurysmal rupture than men and this sex difference is not explained by differences in patient- and aneurysm-related risk factors for aneurysmal rupture. Future studies should focus on the factors explaining the higher risk of aneurysmal rupture in women. Show less
Background and Objectives We combined individual patient data (IPD) from prospective cohorts of patients with unruptured intracranial aneurysms (UIAs) to assess to what extent patients with... Show moreBackground and Objectives We combined individual patient data (IPD) from prospective cohorts of patients with unruptured intracranial aneurysms (UIAs) to assess to what extent patients with familial UIA have a higher rupture risk than those with sporadic UIA. Methods For this IPD meta-analysis, we performed an Embase and PubMed search for studies published up to December 1, 2020. We included studies that (1) had a prospective study design; (2) included 50 or more patients with UIA; (3) studied the natural course of UIA and risk factors for aneurysm rupture including family history for aneurysmal subarachnoid haemorrhage and UIA; and (4) had aneurysm rupture as an outcome. Cohorts with available IPD were included. All studies included patients with newly diagnosed UIA visiting one of the study centers. The primary outcome was aneurysmal rupture. Patients with polycystic kidney disease and moyamoya disease were excluded. We compared rupture rates of familial vs sporadic UIA using a Cox proportional hazard regression model adjusted for PHASES score and smoking. We performed 2 analyses: (1) only studies defining first-degree relatives as parents, children, and siblings and (2) all studies, including those in which first-degree relatives are defined as only parents and children, but not siblings. Results We pooled IPD from 8 cohorts with a low and moderate risk of bias. First-degree relatives were defined as parents, siblings, and children in 6 cohorts (29% Dutch, 55% Finnish, 15% Japanese), totaling 2,297 patients (17% familial, 399 patients) with 3,089 UIAs and 7,301 person-years follow-up. Rupture occurred in 10 familial cases (rupture rate: 0.89%/person-year; 95% confidence interval [CI] 0.45-1.59) and 41 sporadic cases (0.66%/person-year; 95% CI 0.48-0.89); adjusted hazard ratio (HR) for familial cases 2.56 (95% CI 1.18-5.56). After adding the 2 cohorts excluding siblings as first-degree relatives, resulting in 9,511 patients, the adjusted HR was 1.44 (95% CI 0.86-2.40). Discussion The risk of rupture of UIA is 2.5 times higher, with a range from a 1.2 to 5 times higher risk, in familial than in sporadic UIA. When assessing the risk of rupture in UIA, family history should be taken into account. Show less
Background: In management decisions on saccular unruptured intracranial aneurysms (UIAs) the risk of rupture is an important factor. The PHASES score, introduced in 2014, provides absolute 5-year... Show moreBackground: In management decisions on saccular unruptured intracranial aneurysms (UIAs) the risk of rupture is an important factor. The PHASES score, introduced in 2014, provides absolute 5-year risks of rupture based on six easily retrievable patient and aneurysm characteristics. We assessed whether management decisions on UIAs changed after implementation of the PHASES score. Patient and methods: We included all patients with UIAs who were referred to two Dutch tertiary referral centers for aneurysm care in the Netherlands (University Medical Center Utrecht (UMCU) and Leiden University Medical Center (LUMC)) between 2011 and 2017. Analyses were done on an aneurysm level. We calculated the overall proportion of UIAs with a decision to treat before and after PHASES implementation and studied the influence of age and center on post-implementation management changes. Results: We included 623 patients with 803 UIAs. The proportion of UIAs with a decision to treat was 123/360 (34.2%) before and 117/443 (26.4%) after PHASES implementation (absolute risk difference:-7.8%; 95% CI: -14.1 to-1.4). The decision to treat was made at a higher median PHASES score after implementation (7 points (IQR 5;10) pre-versus 8 points (IQR 5;10) post-implementation; p = 0.14). The reduced proportion with a treatment decision after implementation was most pronounced in patients <50 years (-22.3%; 95% CI:-39.2 to -3.4) and was restricted to treatment decisions made at the UMCU (-10.6%; 95% CI:-18.5 to-2.5). Discussion and conclusions: Management of UIAs changed following implementation of the PHASES score, but the impact of PHASES implementation on treatment decisions differed across age subgroups and centers. Show less
Background: Emerging evidence shows sex differences in manifestations of vascular brain injury in memory clinic patients. We hypothesize that this is explained by sex differences in cardiovascular... Show moreBackground: Emerging evidence shows sex differences in manifestations of vascular brain injury in memory clinic patients. We hypothesize that this is explained by sex differences in cardiovascular function.Objective: To assess the relation between sex and manifestations of vascular brain injury in patients with cognitive complaints, in interaction with cardiovascular function.Methods: 160 outpatient clinic patients (68.8 +/- 8.5 years, 38% female) with cognitive complaints and vascular brain injury from the Heart-Brain Connection study underwent a standardized work-up, including heart-brain MRI. We calculated sex differences in vascular brain injury (lacunar infarcts, non-lacunar infarcts, white matter hyperintensities [WMHs], and microbleeds) and cardiovascular function (arterial stiffness, cardiac index, left ventricular [LV] mass index, LV mass-to-volume ratio and cerebral blood flow). In separate regression models, we analyzed the interaction effect between sex and cardiovascular function markers on manifestations of vascular brain injury with interaction terms (sex*cardiovascular function marker).Results: Males had more infarcts, whereas females tended to have larger WMH-volumes. Males had higher LV mass indexes and LV mass-to-volume ratios and lower CBF values compared to females. Yet, we found no interaction effect between sex and individual cardiovascular function markers in relation to the different manifestations of vascular brain injury (p-values interaction terms > 0.05).Conclusion: Manifestations of vascular brain injury in patients with cognitive complaints differed by sex. There was no interaction between sex and cardiovascular function, warranting further studies to explain the observed sex differences in injury patterns. Show less
Amier, R.P.; Marcks, N.; Hooghiemstra, A.M.; Nijveldt, R.; Buchem, M.A. van; Roos, A. de; ... ; Heart-Brain Connection Consortium 2021
OBJECTIVES This study sought to investigate the extent of hypertensive exposure as assessed by cardiovascular magnetic resonance imaging (MRI) in relation to cerebral small vessel disease (CSVD)... Show moreOBJECTIVES This study sought to investigate the extent of hypertensive exposure as assessed by cardiovascular magnetic resonance imaging (MRI) in relation to cerebral small vessel disease (CSVD) and cognitive impairment, with the aim of understanding the role of hypertension in the early stages of deteriorating brain health.BACKGROUND Preserving brain health into advanced age is one of the great challenges of modern medicine. Hypertension is thought to induce vascular brain injury through exposure of the cerebral microcirculation to increased pressure/pulsatility. Cardiovascular MRI provides markers of (subclinical) hypertensive exposure, such as aortic stiffness by puke wave velocity (PWV), left ventricular (LV) mass index (LVMi), and concentricity by mass-to-volume ratio.METHODS A total of 559 participants from the Heart-Brain Connection Study (431 patients with manifest cardiovascular disease and 128 control participants), age 67.8 +/- 8.8 years, underwent 3.0-T heart-brain MRI and extensive neuropsychological testing. Aortic PWV, LVMi, and LV mass-to-volume ratio were evaluated in relation to presence of CSVD and cognitive impairment. Effect modification by patient group was investigated by interaction terms; results are reported pooled or stratified accordingly.RESULTS Aortic PWV (odds ratio [OR]: 1.17; 95% confidence interval [CI]: 1.05 to 1.30 in patient groups only), LVMi (in carotid occlusive disease, OR: 5.69; 95% CI: 1.63 to 19.87; in other groups, OR: 1.30; 95% CI: 1.05 to 1.62]) and LV mass-to-volume ratio (OR: 1.81; 95% CI: 1.46 to 2.24) were associated with CSVD. Aortic PWV (OR: 1.07; 95% CI: 1.02 to 1.13) and LV mass-to-volume ratio (OR: 1.27; 95% CI: 1.07 to 1.51) were also associated with cognitive impairment. Relations were independent of sociodemographic and cardiac index and mostly persisted after correction for systolic blood pressure or medical history of hypertension. Causal mediation analysis showed significant mediation by presence of CSVD in the relation between hypertensive exposure markers and cognitive impairment.CONCLUSIONS The extent of hypertensive exposure is associated with CSVD and cognitive impairment beyond clinical brood pressure or medical history. The mediating role of CSVD suggests that hypertension may lead to cognitive impairment through the occurrence of CSVD. (C) 2021 Published by Elsevier on behalf of the American College of Cardiology Foundation. Show less
Purpose The aim of this study was to evaluate whether the addition of brain CT imaging data to a model incorporating clinical risk factors improves prediction of ischemic stroke recurrence over 5... Show morePurpose The aim of this study was to evaluate whether the addition of brain CT imaging data to a model incorporating clinical risk factors improves prediction of ischemic stroke recurrence over 5 years of follow-up. Methods A total of 638 patients with ischemic stroke from three centers were selected from the Dutch acute stroke study (DUST). CT-derived candidate predictors included findings on non-contrast CT, CT perfusion, and CT angiography. Five-year follow-up data were extracted from medical records. We developed a multivariable Cox regression model containing clinical predictors and an extended model including CT-derived predictors by applying backward elimination. We calculated net reclassification improvement and integrated discrimination improvement indices. Discrimination was evaluated with the optimism-corrected c-statistic and calibration with a calibration plot. Results During 5 years of follow-up, 56 patients (9%) had a recurrence. The c-statistic of the clinical model, which contained male sex, history of hyperlipidemia, and history of stroke or transient ischemic attack, was 0.61. Compared with the clinical model, the extended model, which contained previous cerebral infarcts on non-contrast CT and Alberta Stroke Program Early CT score greater than 7 on mean transit time maps derived from CT perfusion, had higher discriminative performance (c-statistic 0.65,P= 0.01). Inclusion of these CT variables led to a significant improvement in reclassification measures, by using the net reclassification improvement and integrated discrimination improvement indices. Conclusion Data from CT imaging significantly improved the discriminatory performance and reclassification in predicting ischemic stroke recurrence beyond a model incorporating clinical risk factors only. Show less
