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Background and Aims: Psoas muscle parameters estimated from computed tomography images, as surrogates for sarcopenia, have been found to be associated with post-interventional outcomes after a wide range of cardiovascular procedures. The pre-interventional assessment in patients undergoing invasive treatment for peripheral arterial disease is increasingly often carried out with magnetic resonance imaging (MRI), and we therefore sought to investigate the predictive potential of MRI-derived psoas muscle area in this cohort., Methods: A total of 899 patients with available sufficient quality pre-interventional MRI conducted within 6 months prior to treatment undergoing open, endovascular, or hybrid revascularization procedures for claudication and/or limb-threatening ischemia at Tampere University hospital between 2010 and 2020 were retrospectively studied in this single-center cohort study. The follow-up lasted until 17 June 2021. Psoas muscle areas were measured from the magnetic resonance images at the L4 level, and the reliability of muscle parameter measurements was tested with intraclass correlation coefficient analysis. The average psoas muscle area values (mean of left and right psoas surface areas) were z-scored and analyzed separately for men and women., Results: The median follow-up time was 5.9 years (interquartile range (IQR) = 2.7-7.8), and the overall mortality count was 259 (28.8%) (29.5% n = 168/569 for men and 27.6% n = 91/330 for women). The intraclass correlation coefficient analysis showed excellent interrater reliability for psoas muscle measurements. The muscle surface areas were larger in men (mean = 7.58 cm 2 ) compared to women (mean = 5.27 cm 2 ) (p < 0.001). Higher psoas muscle area was associated with better survival in women (p = 0.003, hazard ratio (HR) = 0.71, 95% confidence interval (CI) = 0.6-0.9 per 1 SD), whereas in men, an independent association of the muscle parameter with mortality was not found., Conclusions: MRI-derived psoas muscle area may be a prognostic factor for clinical use., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Conventional measures of heart rate variability (HRV) have shown only modest associations with sudden cardiac death (SCD). Detrended fluctuation analysis (DFA), with novel methodological developments to evaluate the short-term scaling exponent, is a potentially superior method compared to conventional HRV tools., Objectives: In this study, the authors studied the analysis of the association between DFA and SCD., Methods: The investigators studied the predictive value of ultra-short-term heart rate fluctuations (1-minute electrocardiogram samples) with DFA at rest and during different stages of physical exertion for incident SCD among 2,794 participants undergoing clinical exercise testing in the prospective FINCAVAS (Finnish Cardiovascular Study). The novel key DFA measure, the short-scale scaling exponent computed with second-order detrending (DFA2 α 1 ), was the main exposure variable. SCDs were defined by American Heart Association/European Society of Cardiology criteria using death certificates with written accounts of the events., Results: During a median follow-up of 8.3 years (Q1-Q3: 6.4-10.5), 83 SCDs occurred. DFA2 α 1 measured at rest (but not in exercise) associated highly significantly with the risk of SCD, with 1-SD lower values associating with a 2.4-fold (Q1-Q3: 2.0-3.0) risk (P < 0.001). The results persisted when adjusting for other major risk factors for SCD, including age, cardiovascular morbidities, cardiorespiratory fitness, heart rate reduction, and left ventricular ejection fraction. Associations between conventional HRV parameters (measured at any stage of exercise or at rest) and SCD were substantially weaker and statistically nonsignificant after adjusting for other risk factors., Conclusions: Ultra-short-term DFA2 α 1 , when measured at rest, is a powerful and independent predictor of SCD. The association between DFA2 α 1 and SCD is modified by physical exertion., Competing Interests: Funding Support and Author Disclosures FINCAVAS has been financially supported by the Competitive Research Funding of Tampere University Hospital (grants 9M048 and 9N035); the Finnish Cultural Foundation; the Finnish Foundation for Cardiovascular Research (to T.L); the Emil Aaltonen Foundation; the Tampere Tuberculosis Foundation, EU Horizon 2020 (grants 755320 for TAXINOMISIS and 848146 for To Aition); and the Academy of Finland (grant 322098). Additional funding has been also granted by Business Finland, R2B Funding 2022-23 (to E.R). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Brain arteriovenous malformation (bAVM) might have a higher risk of rupture after partial embolization, and previous studies have shown that some metrics of vascular stability are related to bAVM rupture risk., Objective: To analyze vascular stability of bAVM in patients after partial embolization., Methods: Twenty-four patients who underwent partial embolization were classified into the short-term, medium-term, and long-term groups, according to the time interval between partial embolization and surgery. The control group consisted of 9 bAVM patients who underwent surgery alone. Hemodynamic changes after partial embolization were measured by angiogram. The inflammatory infiltrates and cell-cell junctions were evaluated by MMP-9 and VE-cadherin. At the protein level, the proliferative and apoptotic events of bAVMs were analyzed by immunohistochemical staining of VEGFA, eNOS, and caspase-3. Finally, neovascularity and apoptotic cells were assessed by CD31 staining and TUNEL staining., Results: Immediately after partial embolization, the blood flow velocity of most bAVMs increased. The quantity of MMP-9 in the medium-term group was the highest, and VE-cadherin in the medium-term group was the lowest. The expression levels of VEGFA, eNOS, and neovascularity were highest in the medium-term group. Similarly, the expression level of caspase-3 and the number of apoptotic cells were highest in the medium-term group., Conclusion: The biomarkers for bAVM vascular stability were most abnormal between 1 and 28 days after partial embolization., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Objective: The lateral supraorbital (LSO) approach is a minimally invasive craniotomy widely used in the surgical treatment of intracranial aneurysms (IAs). A protective bypass is considered a safety measure in high-risk and complex clipping procedures to maintain distal cerebral flow. However, the protective bypass has so far only been applied through a pterional or larger craniotomy. We aimed to describe the characteristics of the superficial temporal artery to middle cerebral artery (STA-MCA) bypass through the LSO craniotomy to treat complex IAs., Methods: We retrospectively identified six patients with complex IAs who underwent clipping and a protective STA-MCA bypass through the LSO approach between January 2016 and December 2020. The STA donor artery was harvested through the same curvilinear skin incision with a small extension, and it was anastomosed to the opercular segment of the MCA. Subsequently, aneurysm clipping followed standardized steps., Results: Anastomosis was successful in all patients. Despite requiring temporary occlusion of the parent artery, all aneurysms were successfully clipped without any neurological deterioration., Conclusions: A protective STA-MCA bypass is feasible through the LSO approach with certain technical modifications. This technique helps protect distal cerebral flow for safe clip placement in the treatment of complex IAs with the associated benefits of a less invasive craniotomy., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Results: In the meta-analysis, psoas muscle measurements were significantly associated with mortality among men ( p  < 0.05), with high heterogeneity in the associations across all cohorts. There was very little difference in the association between PMA and PMD and mortality (HR 0.83, 95% CI 0.69-0.99, p  = 0.002; HR 0.85, 95% CI 0.77-0.94, p  = 0.041 for one SD increase in PMA and PMD in the random effects model). Combining PMA and PMD into one composite variable by multiplying their values together showed the most robust association in terms of the magnitude of the effect size in men (HR, 0.77; 95% CI 0.73-0.87, p  < 0.001). Indexing PMA to body size did not result in any significant differences in this association. Among women, psoas muscle measurements were not associated with long-term mortality in this meta-analysis., Conclusions: Different psoas muscle measurements were significantly and very similarly associated with mortality among men but not among women. No single measurement stands out, although combining PMA and PMD seems to be a slightly stronger estimate in terms of effect size and should be considered in further studies.

Objective: To evaluate the safety and efficacy of the SeparGate™ balloon-guiding catheter (BGC) for blocking flow and delivering devices in neurointerventional surgery., Method: This prospective multicenter single-arm trial enrolled patients who received BGC adjuvant therapy to provide temporary blood flow arrest of the supra-aortic arch arteries and their branch vessels in interventional therapy. The primary endpoint was immediate procedural success rate in flow arrest, device delivery, and withdrawal. The efficacy endpoints were intraoperative product performance, including rigidity, smoothness, fracture resistance of the catheter wall, catheter push performance, compatibility and radiopaque display, integrity, adhesion thrombus after withdrawal and balloon rupture. The safety endpoints were adverse and serious adverse events associated with the test device and serious adverse events resulting in death or serious health deterioration., Result: A total of 129 patients were included; of them, 128 were analyzed in the full analysis set (FAS) and per protocol set (PPS). Immediate procedural success was achieved in 97.7% of patients with FAS and PPS. The lower bound of the 95% confidence interval was 94.6%, higher than the preset efficacy margin of 94%. Device-related adverse events occurred in 2 (1.6%) cases. One was mild adverse event of vasospasm, which resolved spontaneously. The other was serious adverse event of dissection aggravation, which was treated with stenting angioplasty. No device defects were observed., Conclusion: In neurointerventional surgery, the SeparGate™ BGC can be used to temporarily block the flow of the supra-aortic arch arteries and their branch vessels and guide the interventional device to the target vascular position., Competing Interests: The authors have no conflicts of interest to declare., (© 2022 Shanghai Journal of Interventional Radiology Press. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

Background: Intracranial vertebrobasilar trunk large (≥10 mm) aneurysms (IVBTLAs) are rare and challenging to manage. In this study, we describe the natural prognosis and evaluate the safety and efficacy of endovascular treatment of IVBTLAs compared with conservative therapy., Methods: This prospective multicenter cohort study included patients with IVBTLAs, who chose either endovascular treatment (endovascular group) or conservative therapy (conservative group) after discussion with their doctors. The primary endpoint was the incidence of serious adverse events (SAEs) related to the target vessel, while secondary endpoints included target vessel-related mortality, major stroke, other serious adverse events, and aneurysm occlusion rate., Results: In total, 258 patients were referred to our two centers for the management of vertebrobasilar aneurysms, and 69 patients had IVBTLAs. Among them, 51 patients underwent endovascular treatment, and 18 patients received conservative therapy. The incidence of target vessel-related SAEs was 15.7% (8/51) in the endovascular group and 44.4% (8/18) in the conservative group ( P = 0.031). The target vessel-related mortality was 2.0% (1/51) in the endovascular group and 38.9% (7/18) in the conservative group ( P < 0.001). The cumulative survival rates in the endovascular group and conservative group within 1-year, 3-year, and 5-year were 98.0% vs. 83.3%, P = 0.020; 98.0% vs. 66.7%, P = 0.001; and 98.0% vs. 35.6%, P < 0.001, respectively. Multivariate analysis revealed conservative therapy, giant aneurysm, and ischemic onset as risks factor for SAEs., Conclusions: Compared with conservative treatment, endovascular treatment of the IVBTLAs may be associated with a lower incidence of SAEs, with higher 1-year, 3-year, and 5-year survival rates. Conservative therapy, giant aneurysm, and ischemic onset were associated with a high risk of SAEs., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2022 Qiaowei Wu et al.)

Background: Hemorrhagic transformation (HT) of acute ischemic stroke (AIS) is associated with poor outcome. Previous studies only reported the association of mean ischemic severity or total infarct volume with HT after endovascular therapy (EVT). We aimed to investigate the predictive value of preoperative apparent diffusion coefficient (ADC) map for HT by combinated ischemic severity and corresponding volume in AIS after successful recanalization with EVT., Methods: We retrospectively analyzed 119 consecutive cases of AIS with large vessel occlusion of anterior circulation within 24 hours after symptom onset and successful recanalization after EVT. All cases had baseline magnetic resonance imaging (MRI), follow-up computed tomography (CT), and magnetic resonance angiography (MRA) or computed tomography angiography (CTA). Volumes of ADC <0.6×10 -3 , 0.5×10 -3 , 0.4×10 -3 , and 0.3×10 -3 mm 2 /s, baseline characteristics and outcomes of patients with and without HT identified by European Collaborative Acute Stroke Study (ECASS) were compared. The optimal ADC and volume threshold for predicting HT were analyzed using receiver operating characteristic (ROC) curve, and multivariate logistic regression analysis were performed with clinical characteristics and volumes of optimal ADC threshold to determine risk factors for HT., Results: Among 119 patients, 42 patients had HT on follow-up CT, including 24 hemorrhagic infarct (HI) cases and 18 parenchymal hematoma (PH) cases. The optimal volumes were 6.46 mL with ADC <0.4×10 -3 mm 2 /s for predicting both HT and PH, with a larger area under curve (AUC) of 83.3% for HT than that for PH of 80%. In logistic regression analysis, intravenous tissue plasminogen activator (IV tPA) treatment, atrial fibrillation, and volume of ADC <0.4×10 -3 mm 2 /s were identified as independent predictors for HT and volume of ADC <0.4×10 -3 mm 2 /s had the highest odds ratio (OR) value., Conclusions: The combination of ischemic severity and corresponding volume in ADC map may predict HT after thrombectomy. In addition to the total infarct volume, volume with severe ischemia should be taken into consideration in preoperative patient selection., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-2255/coif). All authors report that this work was supported by the Key Research and Development Program of Henan Province (Scientific and Technological Project of Henan Province) (No. 202102310037), the Provincial and Ministerial Joint Project of Henan Provincial Medical Science and Technology (No. SBGJ2018063), and the Research and Popularization Project of Appropriate Intervention Techniques for High-risk Population of Stroke in China (No. GN-2018R0007). The authors have no other conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Background: Increased left ventricular mass (LVM) predicts cardiovascular events and mortality. The objective of this study was to determine whether early-life exposures to body mass index (BMI) and systolic blood pressure (SPB) affects the left ventricular structure in adulthood., Methods: We used longitudinal data from a 31-year follow-up to examine the associations between early-life (between ages 6-18) BMI and SPB on LVM in an adult population ( N  = 1864, aged 34-49). The burden of early-life BMI and SBP was defined as area under the curve., Results: After accounting for contemporary adult determinants of LVM, early-life BMI burden associated significantly with LVM (3.61 g/SD increase in early-life BMI; [1.94 - 5.28], p  < 0.001). Overweight in early-life (age- and sex-specific BMI values corresponding to adult BMI > 25 kg/m 2 ) associated with 4.7% (2.5-6.9%, p  < 0.0001) higher LVM regardless of BMI status in adulthood. Overweight in early-life combined with obesity in adulthood (BMI > 30kg/m 2 ) resulted in a 21% (17.3-32.9%, p  < 0.0001) increase in LVM. Higher early-life BMI was associated with a risk of developing eccentric hypertrophy. The burden of early-life SPB was not associated with adult LVM or left ventricular remodeling., Conclusions: High BMI in early-life confers a sustained effect on LVM and the risk for eccentric hypertrophy independently of adulthood risk factors. KEY MESSAGES Excess in BMI in early-life has an independent effect on LVM and the risk of developing eccentric hypertrophy regardless of overweight status in adulthood. Systolic blood pressure levels in early-life did not have an independent effect on LVM or LV remodeling. The clinical implication of this study is that primary prevention of obesity in early-life may prevent the development of high LVM and eccentric hypertrophy.

Objective: To evaluate whether cardiorespiratory fitness (CRF) and heart rate recovery (HRR) associate with the risk of sudden cardiac death (SCD) independently of left ventricular ejection fraction (LVEF)., Methods: The Finnish Cardiovascular Study is a prospective clinical study of patients referred to clinical exercise testing in 2001-2008 and follow-up until December 2013. Patients without pacemakers undergoing first maximal or submaximal exercise testing with cycle ergometer were included (n=3776). CRF in metabolic equivalents (METs) was estimated by achieving maximal work level. HRR was defined as the reduction in heart rate 1 min after maximal exertion. Adjudication of SCD was based on death certificates. LVEF was measured for clinical indications in 71.4% of the patients (n=2697)., Results: Population mean age was 55.7 years (SD 13.1; 61% men). 98 SCDs were recorded during a median follow-up of 9.1 years (6.9-10.7). Mean CRF and HRR were 7.7 (SD 2.9) METs and 25 (SD 12) beats/min/min. Both CRF and HRR were associated with the risk of SCD in the entire study population (HR CRF 0.47 (0.37-0.59), p<0.001 and HR HRR 0.57 (0.48-0.67), p<0.001 with HR estimates corresponding to one SD increase in the exposure variables) and with CRF, HRR and LVEF in the same model (HR CRF 0.60 (0.45-0.79), p<0.001, HR HRR 0.65 (0.51-0.82), p<0.001) or adjusting additionally for all significant risk factors for SCD (LVEF, sex, creatinine level, history of myocardial infarction and atrial fibrillation, corrected QT interval) (HR CRF 0.69 (0.52-0.93), p<0.01, HR HRR 0.74 (0.58-0.95) p=0.02)., Conclusions: CRF and HRR are significantly associated with the risk of SCD regardless of LVEF., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Investigation of the clinical potential of extensive phenotype data and machine learning (ML) in the prediction of mortality in acute coronary syndrome (ACS). Methods: The value of ML and extensive clinical data was analyzed in a retrospective registry study of 9066 consecutive ACS patients (January 2007 to October 2017). Main outcome was six-month mortality. Prediction models were developed using two ML methods, logistic regression and extreme gradient boosting (xgboost). The models were fitted in training set of patients treated in 2007-2014 and 2017 (81%, n  = 7344) and validated in a separate validation set of patients treated in 2015-2016 with full GRACE score data available for comparison of model accuracy (19%, n  = 1722). Results: Overall, six-month mortality was 7.3% ( n  = 660). Several variables were found to be significantly associated with six-month mortality by both ML methods. The xgboost scored the best performance: AUC 0.890 (0.864-0.916). The AUC values for logistic regression and GRACE score were 0.867(0.837-0.897) and 0.822 (0.785-0.859), respectively. The AUC value of xgboost was better when compared to logistic regression ( p  = .012) and GRACE score ( p  < .00001). Conclusions: The use of extensive phenotype data and novel machine learning improves prediction of mortality in ACS over traditional GRACE score. KEY MESSAGES The collection of extensive cardiovascular phenotype data from electronic health records as well as from data recorded by physicians can be used highly effectively in prediction of mortality after acute coronary syndrome. Supervised machine learning methods such as logistic regression and extreme gradient boosting using extensive phenotype data significantly outperform conventional risk assessment by the current golden standard GRACE score. Integration of electronic health records and the use of supervised machine learning methods can be easily applied in a single centre level to model the risk of mortality.

Objective: Aortic sinus dilatation can lead to aortic valve regurgitation or even aortic dissection. Our objective was to examine the association between body surface area (BSA) measures from childhood to middle age and aortic sinus diameter in middle age. Understanding the relation of these two clarifies how aortic size is normally determined., Methods: Cardiovascular Risk in Young Finns Study is a longitudinal study with follow-up of over 31 years (1980-2011). The study comprises information of body composition from multiple time points of 1950 subjects with cardiac ultrasound measurements made in 2011. The association between BSA in different ages and aortic sinus diameter in middle age was analysed by linear regression modelling adjusted with age, sex and diastolic blood pressure. Missing BSA values were derived for each life year (ages 3-33 years) from subject-specific curves for body weight and height estimated from longitudinal measurements using mixed model regression splines., Results: BSA estimates in early 20s are most strongly associated with aortic sinus diameter in middle age. Top association was observed at age 23 years with one SD increase in estimated BSA corresponding to 1.04 mm (0.87-1.21 mm) increase in aortic diameter. Increase in body weight beyond early 20s does not associate with aortic sinus diameter, and the association between middle age BSA and aortic size is substantially weaker (0.74 mm increase (0.58-0.89 mm)). These results were confirmed in a subpopulation using only measured data., Conclusion: The association between aortic sinus diameter and BSA is stronger when considering BSA in young adulthood compared with BSA in middle age., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Previous data on the association of thyroid function with total mortality, cardiovascular disease (CVD) outcomes and sudden cardiac death (SCD) are conflicting or limited. We investigated associations of thyroid-stimulating hormone (TSH) with these outcomes in a nationwide population-based prospective cohort study., Methods: We examined 5211 participants representative of the Finnish population aged ≥30 years in 2000-2001 and followed them for a median of 13.2 years. Using Cox proportional hazards regression models adjusted for baseline age, gender, smoking, diabetes, systolic blood pressure and total and high-density lipoprotein cholesterol, we assessed the associations of continuous baseline TSH and TSH categories (low [<0.4 mU/L], reference range [0.4-3.4 mU/L] and high [>3.4 mU/L]) with incident total mortality, SCD, coronary heart disease events, stroke, CVD, major adverse cardiac events and atrial fibrillation., Results: High TSH at baseline was related to a greater risk of total mortality (HR 1.34, 95% CI 1.02-1.76) and SCD (HR 2.28, 95% CI 1.13-4.60) compared with TSH within the reference range. High TSH was not associated with the other outcomes (P ≥ .51), whereas low TSH was not associated with any of the outcomes (P ≥ .09). TSH at baseline over the full range did not have a linear relation with any of the outcomes (P ≥ .17). TSH showed a U-shaped association with total mortality after a restricted cubic spline transformation (P = .01)., Conclusions: Thyroid function abnormalities could be linked with higher risks of total mortality and SCD. Large-scale randomized studies are needed for evidence-based recommendations regarding treatment of mild thyroid failure., (© 2017 John Wiley & Sons Ltd.)

Objective: We aimed to characterize the occurrence of postoperative hematoma (POH) after neurosurgery overall and according to procedure type and describe the prevalence of possible confounders., Methods: Patient data between 2010 and 2012 at the Department of Neurosurgery in Helsinki University Hospital were retrospectively analyzed. A data search was performed according to the type of surgery including craniotomies; shunt procedures, spine surgery, and spinal cord stimulator implantation. We analyzed basic preoperative characteristics, as well as data about the initial intervention, perioperative period, revision operation and neurologic recovery (after craniotomy only)., Results: The overall incidence of POH requiring reoperation was 0.6% (n = 56/8783) to 0.6% (n = 26/4726) after craniotomy, 0% (n = 0/928) after shunting procedure, 1.1% (n = 30/2870) after spine surgery, and 0% (n = 0/259) after implantation of a spinal cord stimulator. Craniotomy types with higher POH incidence were decompressive craniectomy (7.9%, n = 7/89), cranioplasty (3.6%, n = 4/112), bypass surgery (1.7%, n = 1/60), and epidural hematoma evacuation (1.6%, n = 1/64). After spinal surgery, POH was observed in 1.1% of cervical and 2.1% of thoracolumbar operations, whereas 46.7% were multilevel procedures. 64.3% of patients with POH and 84.6% of patients undergoing craniotomy had postoperative hypertension (systolic blood pressure >160 mm Hg or lower if indicated). Poor outcome (Glasgow Outcome Scale score 1-3), whereas death at 6 months after craniotomy was detected in 40.9% and 21.7%. respectively, of patients with POH who underwent craniotomy., Conclusions: POH after neurosurgery was rare in this series but was associated with poor outcome. Identification of risk factors of bleeding, and avoiding them, if possible, might decrease the incidence of POH., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Posterior cerebral artery (PCA) aneurysms are rare and the majority are fusiform in shape. Proximal occlusion of PCA represents a treatment option for these lesions. However, this procedure carries a high risk of ischemic complications., Objective: To describe the technique of trapping a fusiform PCA aneurysm and revascularization of the distal PCA using a superficial temporal artery (STA) graft through the same microsurgical approach., Methods: From September 2012 to October 2014, we retrospectively identified 3 patients harboring a fusiform PCA aneurysm (P2 segment aneurysm) who underwent trapping of the aneurysm and reconstruction of the distal PCA through the same subtemporal approach. We analyzed immediate morbidity, surgical complications, and the patency of the bypass to determine the feasibility of this procedure., Results: All 3 patients underwent successful trapping of the fusiform PCA aneurysm and revascularization of the distal PCA. The origin of P3 segment or posterior temporal artery (PTA) served as recipient arteries. In all 3 cases, adequate blood flow was evident after performing the STA-P3/PTA bypass. None of the patients experienced a new permanent neurological deficit. At 1-year follow-up, the STA-PTA/PCA bypasses remained patent., Conclusion: The STA-P3/PTA bypass through the subtemporal approach is a feasible option to maintain blood flow in cases of PCA fusiform aneurysms requiring trapping of the P2 segment., (Copyright © 2017 by the Congress of Neurological Surgeons)

Background: Lateral approaches to treat anterior cranial fossa lesions have evolved since the first frontotemporal approach described by Dandy in 1918. We describe a less invasive approach to perform extradural anterior clinoidectomy through a lateral supraorbital (LSO) approach for anterior circulation aneurysms and anterolateral skull base lesions., Methods: The extended LSO approach involves performing a standard lateral supraorbital craniotomy followed by drilling of the sphenoid wing and lateral wall of the orbit through the frontal bony opening of the LSO approach, without any temporal extension of the craniotomy. This creates a frontopterio-orbital window exposing the periorbita; superior, medial, and anterior aspect of the temporal dura mater; and superior orbital fissure. After unroofing the superior orbital fissure, the meningo-orbital fold is cut, and the temporal dura mater is peeled from the lateral wall of the cavernous sinus to expose the anterior clinoid process allowing a standard opening of the optic canal and anterior clinoidectomy., Results: The extended LSO approach and extradural anterior clinoidectomy allowed access to 4 sphenoid wing/anterior clinoidal meningiomas, 5 anterior circulation aneurysms, 2 temporomesial lesions, and 1 orbital/cavernous sinus abscess. Postoperatively, 2 patients had transient hemiparesis, 2 patients had transient third nerve palsy, and 1 patient had minimal visual field deterioration. All patients had a modified Rankin Scale score ≤1 at 8-week follow-up., Conclusion: The extended LSO approach opens a new route (frontopterio-orbital window) to perform extradural anterior clinoidectomy safely and increases surgical exposure, angles, and operability of a less invasive keyhole craniotomy (LSO approach) to treat anterior cranial fossa lesions., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Cardiac troponin and N-terminal pro-brain natriuretic peptide (NT-proBNP) are known to associate with incident dementia. The purpose of our study was to examine whether high-sensitivity cardiac troponin I (hs-TnI) and NT-proBNP are associated with incident dementia and Alzheimer's disease (AD) independently of each other. Our study was a part of the national population-based health examination survey, FINRISK 1997, with a total sample of 7114 subjects, including 407 incident dementia cases and 319 AD cases during the follow-up time of 18 years. Using multivariate Cox regression analyses, we calculated the hazard ratios (HR) for hs-TnI and NT-proBNP. Analyses were adjusted for the previously known dementia/AD risk factors, including the apoE genotype. NT-proBNP was independently associated with incident dementia (HR 1.32, 95% CI 1.17-1.49) and AD (HR 1.30, 95% CI 1.13-1.5). Hs-TnI was also associated with incident dementia (HR 1.12, 95% CI 1.02-1.23), but not independent of NT-proBNP (HR 1.10, 95% CI 0.99-1.21). Hs-TnI was not associated with incident AD. The results remained similar in cause-specific Cox regression models and among subjects over 40 years of age. NT-proBNP and hs-TnI improved the reclassification of dementia risk in 10 years follow-up, and hs-TNI also in 18 years of follow-up. Neither hs-TnI nor NT-proBNP was able to outperform each other in risk reclassification of dementia. Both cardiovascular biomarkers, NT-proBNP and hs-TnI, were associated with incident dementia independently of traditional dementia risk factors including the apoE genotype. NT-proBNP was also associated with AD. Both markers offered a better dementia risk reclassification compared with traditional risk factors.

Data on associations of apolipoproteins A-I and B (apo A-I, apo B) and HDL cholesterol (HDL-C) with dementia and Alzheimer's disease (AD) are conflicting. Our aim was to examine, whether apo B, apoA-I, their ratio, or HDL-C are significant, independent predictors of incident dementia and AD in the general population free of dementia at baseline. We analyzed the results from two Finnish prospective population-based cohort studies in a total of 13,275 subjects aged 25 to 74 years with mainly Caucasian ethnicity. The follow-up time for both cohorts was 10 years. We used Cox proportional hazards regression to evaluate hazard ratios (HR) for incident dementia (including AD) (n = 220) and for AD (n = 154). Cumulative incidence function (CIF) analysis was also performed to adjust the results for competing risks of death. Adjusted for multiple dementia and AD risk factors, log-transformed apo A-I, log HDL-C, log apo B, and log apo B/A-I ratio were not associated with incident dementia or AD. HDL-C was inversely associated with AD risk when adjusted for competing risks but no other statistically significant associations were observed in the CIF analyses. Apo A-I, HDL-C, apo B, or apo B/A-I ratio were not associated with future dementia or AD. HDL-C was inversely associated with incident AD risk when adjusted for competing risks of death, but the finding is unlikely to be of clinical relevance. Our study does not support the use of these risk markers to predict incident dementia or AD., Competing Interests: The authors declare that they have no conflicts of interests.

Objective: Aneurysms of the posterior cerebral artery (PCA) are uncommon. Because of their low incidence, only 5 series with more than 30 patient cases have been reported. The treatment of PCA aneurysms is challenging because of the high frequency of fusiform aneurysms and closeness to important neuroanatomic structures., Methods: A total of 121 patients with 135 PCA aneurysms were reviewed. The clinical and radiologic data, treatment strategies, and 1-year outcomes were analyzed. Patients with giant aneurysms, associated aneurysms, and aneurysms on arteriovenous malformation-feeding PCAs were considered as complex cases. Outcomes were categorized into 3 groups: good (modified Rankin Scale [mRS], score 0-1), moderate (mRS score, 2-4), and poor (mRS score, 5-6)., Results: There were 52 ruptured (39%) and 83 unruptured (61%) PCA aneurysms in 121 patients, with the following distribution: P1 (n = 53), P1/2 (n = 39), P2 (n = 28), and P3 (n = 15). The incidence of fusiform PCA aneurysms was high (24%). Microsurgical treatment was applied to 63 aneurysms and endovascular treatment to 19 aneurysms; 55 aneurysms were treated conservatively. The following treatment results were achieved: for patients with unruptured PCA aneurysms, n = 19; 12 good outcomes, 63%; 6 moderate, 31%; 1 poor, 1%; for patients with ruptured PCA aneurysms, n = 27; 10 good, 37%; 9 moderate, 33%; 8 poor, 30%; and for patients with complex neurovascular diseases and PCA aneurysms, n = 96; 42 good, 43%; 40 moderate, 42%; 14 poor, 15%., Conclusions: Aneurysms of the PCA are infrequent and often associated with other vascular diseases. Microsurgery and endovascular treatment are effective for the occlusion of PCA aneurysms. The preservation or reconstruction of the parent vessel is crucial for favorable treatment outcomes., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The lateral supraorbital approach (LSO) provides access to a variety of pathologies including anterior and some posterior circulation aneurysms, sellar and suprasellar lesions, and anterior fossa tumors. Technical modifications of LSO improve the surgical exposure of the skull base., Methods: We retrospectively analyzed 73 consecutive patients treated by the senior author (Juha A. Hernesniemi), at the Department of Neurosurgery, Helsinki University Hospital in Helsinki, Finland from May 2013 to October 2013. This study cohort underwent a modified LSO to access anterior circulation aneurysms, sellar and suprasellar tumors, and anterior fossa tumors. The studied population comprised 30 men and 43 women, with a mean age at treatment of 54 years (9-83 years)., Results: LSO was successfully used to access anterior circulation aneurysms in 59 (81%) patients, 10 (14%) patients with anterior cranial fossa tumors, and 4 (5%) patients with suprasellar tumors. The skull base drilling provided a mean of 6.8 mm (1.7-22 mm) in increased exposure., Conclusion: LSO provides adequate access to vascular and neoplastic lesions of the anterior cranial fossa, by drilling approximately 6.8 mm (1.7-22 mm) of the lateral orbital wall and sphenoid wing. This enhances surgical exposure and trajectory. An additional trick while performing an LSO is to place a single or multiple stiches (orbitozygomatic stich) at the base of the dura once opened, eliminating the dead space between the dura and anterior skull base.

Asymmetric and symmetric dimethylarginines (ADMA and SDMA) impair nitric oxide bioavailability and have been implicated in the pathogenesis of atrial fibrillation (AF). Alanine-glyoxylate aminotransferase 2 (AGXT2) is the only enzyme capable of metabolizing both of the dimethylarginines. We hypothesized that two functional AGXT2 missense variants (rs37369, V140I; rs16899974, V498L) are associated with AF and its cardioembolic complications. Association analyses were conducted using 1,834 individulas with AF and 7,159 unaffected individuals from two coronary angiography cohorts and a cohort comprising patients undergoing clinical exercise testing. In coronary angiography patients without structural heart disease, the minor A allele of rs16899974 was associated with any AF (OR = 2.07, 95% CI 1.59-2.68), and with paroxysmal AF (OR = 1.98, 95% CI 1.44-2.74) and chronic AF (OR = 2.03, 95% CI 1.35-3.06) separately. We could not replicate the association with AF in the other two cohorts. However, the A allele of rs16899974 was nominally associated with ischemic stroke risk in the meta-analysis of WTCCC2 ischemic stroke cohorts (3,548 cases, 5,972 controls) and with earlier onset of first-ever ischemic stroke (360 cases) in the cohort of clinical exercise test patients. In conclusion, AGXT2 variations may be involved in the pathogenesis of AF and its age-related thromboembolic complications.

Background: The basilar bifurcation aneurysm (BBA) is still considered to be one of the most challenging aneurysms for micro- and endovascular surgery. Classic surgical approaches, such as subtemporal, lateral supraorbital (LSO), and modified presigmoid, are still reliable and effective., Objective: To analyze the clinical and radiological factors that affect the selection of these classic surgical approaches and their outcomes., Methods: A retrospective analysis was conducted on the clinical and radiological data from computed tomographic angiography of BBA that have been clipped in the Department of Neurosurgery of Helsinki University Central Hospital between 2004 and 2014. Statistical analyses were performed using parametric and nonparametric tests where values were considered significant below P = .05., Results: One hundred four patients with BBA underwent surgical clipping in our department between 2004 and 2014. Eight patients were excluded from the study because of incomplete preoperative radiological evaluations, leaving 96 patients for further analysis. Multiple aneurysm clipping, mean basilar bifurcation angle, and aneurysm neck distance from posterior clinoid process were shown to be factors that determine the surgical approach. Unfavorable outcome is strongly associated with poor Hunt-Hess grade on admission, distance from aneurysm neck (the posterior clinoid process), thrombosis, and dome size., Conclusion: Microsurgery for BBA clipping can be performed safely with simple surgical approaches: subtemporal and LSO. There are several factors determining the approach selected. Poor patient outcome in BBA was highly associated with poor preoperative clinical grade and large size of aneurysm dome.

Background: The disadvantages of a contralateral approach (CA) include deep and narrow surgical corridors and inconsistent ability to achieve proximal control of the supraclinoid internal carotid artery (ICA). However, a CA remains as a microsurgical option for selected ICA-ophthalmic (opht) segment aneurysms., Objective: To describe transient cardiac arrest induced by adenosine as an alternative tool to obtain proximal vascular control and soften the aneurysm sac in selected patients while performing a CA., Methods: From January 1998 to December 2013, we retrospectively identified 30 patients with ICA-opht segment aneurysms treated through a CA. Of those, 8 patients received an intravenous bolus of adenosine to induce transient cardiac arrest for softening of the aneurysm sac. We reviewed preoperative clinical status, characteristics of the contralateral aneurysm, adenosine doses, asystole time, recovery of normal circulation, outcome, and complications., Results: No preoperative cardiac or pulmonary pathologies were found in the study population. All contralateral ICA-opht segment aneurysms were unruptured, small, and saccular in shape. Transient cardiac arrest was induced because it was impossible to apply a temporary clip on the parent contralateral supraclinoid ICA. The median dose of adenosine was 22.5 mg (range, 5-50 mg) and the asystole time ranged from 20 to 40 seconds. All patients (n = 8) had good postoperative outcomes. No brain infarction or cardiac complications appeared postoperatively., Conclusions: In selected patients, transient cardiac arrest induced by adenosine during a contralateral approach allows a brief flow arrest and softening of the aneurysm for safer exposure and clipping., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Bilateral aneurysms located between the 2 middle cerebral artery (MCA) bifurcations may be approachable through a single unilateral approach., Objective: To identify anatomic parameters based on imaging that would favor a contralateral approach., Methods: From January 1998 to December 2013, we retrospectively identified 173 patients with bilateral intracranial aneurysms. Fifty-one patients had bilateral MCA aneurysms. A total of 38 patients underwent a single craniotomy with a contralateral microsurgical approach (group 1 or contralateral group) and 13 patients underwent bilateral craniotomies (group 2 or bilateral group). For both groups, we analyzed aneurysm characteristics, morphology, size, projections, and distance to the contralateral corridor, as well as surgical time, outcome, and postoperative complications., Results: All aneurysms approached contralaterally were unruptured and without wall calcifications. Of the contralaterally approached aneurysms, 97% were smaller than 14 mm. The median length of the contralateral A1 was 13.2 mm (range: 6-19.8 mm) and the median length of the contralateral M1 was 14.2 mm (range: 4.6-21 mm). The contralateral group had a good postoperative outcome (modified Rankin Scale 0-3) in 80% of ruptured cases and 86% of unruptured cases. The median surgical time was 120 minutes (range: 75-255 minutes), 43% shorter than the bilateral group., Conclusion: The contralateral approach for bilateral MCA aneurysms in selected patients is feasible in experienced hands, with acceptable morbidity and mortality. The contralateral approach requires a meticulous preoperative analysis of the characteristics of the aneurysms to be clipped and of the anatomic constraints of the microsurgical operative corridor., Abbreviations: A1, anterior cerebral artery proximal segmentbMCA, bilateral middle cerebral arteryCTA, computed tomographic angiographyHH, Hunt-Hess scaleIA, intracranial aneurysmsICA, internal carotid arteryICAbif, internal carotid artery bifurcationMCA, middle cerebral arteryM1, middle cerebral artery proximal segmentmRS, modified Rankin ScaleSAH, subarachnoid hemorrhage.

Aims: Genome-wide association studies (GWAS) have identified many variants associating with an increased risk of coronary artery disease (CAD). We studied the possible association between these variants and the risk of sudden cardiac death (SCD)., Methods and Results: A weighted genetic risk score (GRSCAD) was formed from variants most strongly associating with CAD identified by the CARDIoGRAMplusC4D Consortium explaining 10.6% of the heritability of CAD [153 single-nucleotide polymorphisms with r(2) < 0.2]. The association between GRSCAD and the occurrence of SCD was studied in three independent autopsy series of consecutive cases combining altogether 1035 autopsies with 306 SCDs due to CAD (SCDCAD). The results were replicated in a prospective follow-up study of 2321 patients (mean follow-up time of 6.2 years with 48 incident SCDs of which 39 due to CAD) undergoing clinical exercise test at baseline. In a meta-analysis of the autopsy series, GRSCAD associated significantly with the risk of SCDCAD with age, body mass index, and sex adjusted odds ratio (OR) of 1.042 (1.023-1.061, P = 9.1 × 10(-6)) for one allele increase in GRSCAD. The same association was seen in both sexes. GRSCAD predicted significantly the risk of SCDCAD also in a prospective study setting (Cox regression analysis adjusted with all relevant clinical data): hazard ratio 1.049 (1.010-1.090, P = 0.014). In meta-analysis of all cohorts (adjusting further for other genetic markers related to traditional risk factors and QT-interval), the association was highly significant [OR 1.045 (1.028-1.063), P = 1.7 × 10(-7)]., Conclusion: Genetic risk estimate for CAD may also be used to predict SCD., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Objective: Emerging evidence suggests high prevalence of abdominal aortic aneurysm (AAA) among patients with coronary disease. Accurate characterization of the association between coronary disease and AAA and of the actual prevalence of AAA among patients with angiography-verified coronary artery disease (CAD) is needed to evaluate the possible benefits of systematic screening for AAA., Methods: We searched for studies that reported the association between AAA and CAD or coronary heart disease (CHD; wider phenotype definition) in the general population (randomized controlled trials, prospective population cohorts) and those that reported the prevalence of AAA among patients with angiography-verified CAD through PubMed, Embase, and reference lists for the period between 1980 and 2014. Random-effects models were applied because of the high heterogeneity between included studies., Results: Among the general population, 23 studies reported the association between CHD and the occurrence of subclinical AAA (positive ultrasound screening; meta-analyzed odds ratio of 2.38 with 95% confidence interval [CI] of 1.78-3.19; P = 4.1 × 10(-9)). According to four prospective studies, CHD is a strong predictor of future AAA events (fatal and nonfatal; meta-analyzed hazard ratio of 3.49 with 95% CI of 2.56-4.76; P = 2.4 × 10(-15)). Altogether, 10 studies reported the prevalence of AAA among patients with angiography-verified CAD or undergoing coronary artery bypass grafting. Among men, meta-analyzed prevalence was 9.5% (95% CI, 7.6%-11.7%). Among men undergoing coronary artery bypass grafting or with three-vessel disease, the prevalence was 11.4% (95% CI, 9.1%-13.9%). Among women, the prevalence was low (0.35%)., Conclusions: The risk of subclinical AAA and future AAA events is high among patients with coronary disease. Screening for AAA among CAD patients by cardiologists would be easy and inexpensive, with possible benefits to survival and risk evaluation., (Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Contralateral aneurysm clipping can be applied to bilateral intracranial aneurysms of the anterior circulation and to selected aneurysms on the medial wall of the internal carotid artery (ICA)., Objective: To identify anatomic and radiological parameters that would favor a contralateral microsurgical approach to ICA-ophthalmic segment (ICA-opht) aneurysms., Methods: For the period January 1957 to December 2012, we retrospectively analyzed 268 patients with ICA-opht aneurysms treated in our institution. Of these patients, 30 underwent a contralateral approach; 15 patients (50%) had multiple intracranial aneurysms, and 15 patients had a single aneurysm on the contralateral side of the craniotomy., Results: Thirty saccular aneurysms located on the contralateral ICA were treated. Six aneurysms (20%) were present in patients with a subarachnoid hemorrhage due to associated aneurysms, whereas 24 aneurysms (80%) had no history of bleeding. Contralateral aneurysms were smaller than 14 mm and showed no wall irregularities, calcifications, or secondary pouches. Projections of the aneurysms were superomedial (n = 23, 77%), medial (n = 4, 13%), and superior (n = 3, 10%). The median prechiasmatic distance was 5.7 mm (range, 3.4-8.7 mm), the median interoptic distance was 10.5 mm (range, 7.6-15.9 mm), and the median distance between both ICAs was 14.7 mm (range, 10.4-21.4 mm)., Conclusion: The contralateral approach for ICA-opht aneurysms remains a treatment option for intracranial aneurysms. Its feasibility depends on specific anatomic parameters related to the aneurysm itself and to the prechiasmatic distance, interoptic distance, and relationship of the ICA with the anterior clinoid process.

Objective: Aneurysms of the posterior cerebral artery (PCA) are rare, and therefore the individual and institutional experience of their microsurgical management is usually limited. In the present article, we describe our experience with the subtemporal approach to aneurysms arising from the PCA., Methods: We reviewed 34 patients diagnosed with 37 PCA aneurysms, all microsurgically managed using the subtemporal approach between 1980 and 2012 at 2 Finnish neurosurgical centers (Helsinki and Kuopio). The following procedures were applied using the subtemporal approach: neck clipping (n = 24); proximal occlusion (n = 7); trapping (n = 2); wrapping (n = 1); aneurysmoraphy (n = 1); bypass bridging/trapping (n = 1); and a complex excimer laser-assisted nonocclusive anastomosis procedure (n = 1)., Results: Of these 34 patients, 16 presented with acute subarachnoid hemorrhage as a result of PCA aneurysm rupture, and 11 of the 16 had good outcome (modified Rankin scale 0-2) at 3 months The remaining 18 patients were treated microsurgically for incidentally diagnosed unruptured aneurysms, and 14 of the 18 had a good outcome. The most common serious complication in this series was an ipsilateral PCA infarction (12/34; 35%), mostly after proximal occlusion (n = 7) and/or trapping (n = 2)., Conclusions: The subtemporal approach is a suitable approach to aneurysms of the segments P1, P1-P2 junction, and P2, as well as the anterior P3 segment of the PCA. Using the subtemporal approach, the cerebrospinal fluid is released before retraction is necessary to prevent temporal lobe injury. The subtemporal approach can provide enough space for revascularization procedures. The most encountered complications were not related to the subtemporal approach but to the specific nature of PCA aneurysms., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aims: The aim was to carry out a systematic screening of interactions between the traditional risk factors and to evaluate which interactions are truly relevant for estimation of cardiovascular disease (CVD) risk., Methods: Cox regression was used in a meta-analysis of five independent, population-based health examination surveys (the National FINRISK Study). End-points were 10-year incidence of coronary heart disease (CHD), ischemic stroke (IS), and CVD in a population free of cardiovascular disease (n = 35,460)., Results: In addition to expected age interactions, systolic blood pressure was found to be a markedly stronger risk factor for CVD (and for CHD) among subjects with normal BMI (BMI < 25: HR 1.42 [1.30-1.55] for one SD increase in systolic blood pressure) when compared to obese subjects (BMI > 30: HR 1.10 [1.01-1.19]) (P < 0.001 for interaction) and among subjects with highest high-density lipoprotein (HDL) (33% tertile: HR 1.43 [1.29-1.58]) when compared to subjects with low HDL (lowest 33% tertile: HR 1.20 [1.13-1.28]) (P < 0.001 for interaction). Interactions improved risk prediction of CVD (cross-validated continuous net reclassification improvement [NRI] 49.4% with 95% CI 44.7%-54.1%, P < 0.0001 and clinical NRI 4.7%, with 95% CI 2.8%-6.5%, P < 0.0001). The C-statistic improved from 0.8438 to 0.8455 (P = 0.010). No significant interaction was associated with the risk of IS., Conclusions: There are significant effect modifications between major risk factors, and accounting for them leads to significantly more accurate estimation of cardiovascular risk.

Background: Memory disorders and Alzheimer's disease (AD) share the same risk factors with cardiovascular diseases., Objective: We tested whether elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) levels would predict any incident dementia or AD., Methods: The association between NT-proBNP and the risk of dementia was evaluated in a total of 7,158 subjects without previous memory disorders in a prospective study with a median follow-up of 13.8 years., Results: A total of 220 new dementia cases occurred, of which 149 were AD. Baseline logNT-proBNP levels were associated significantly with the risk of dementia in the entire study population (HR 1.32, 95%CI 1.17-1.56, p = 0.001) per 1SD difference, adjusted for multiple cardiovascular risk factors. Integrated discrimination improvement (IDI) and continuous net-reclassification improvement (continuous NRI) were improved in the study population over 40 years of age: continuous NRI was 17.5% (95%CI 4.4-30.6%, p = 0.009) and IDI was 0.005 (95%CI 0.001-0.010, p = 0.021). Regarding AD, the HR for 1SD logNT-proBNP change was 1.23 (95%CI 1.01-1.49, p = 0.040) in the entire study population, but no IDI or continuous NRI improvement was seen., Conclusion: NT-proBNP is also an independent risk marker for dementia, and patient discrimination regarding dementia risk could be improved by using it.

Background: Better diagnostic tools to identify rupture-prone saccular intracranial aneurysms (sIA) are needed. Inflammation and luminal thrombus associate with degeneration and rupture of the sIA wall. Iron-uptake has been detected in the inflammatory cells of the sIA wall and thrombus is the likely source of this iron. We investigated ex vivo the use of magnetic resonance imaging (MRI) to detect iron accumulation and luminal thrombus in giant sIAs., Methods: Giant sIAs (n = 3) were acquired from microsurgical operations, fixed with formalin, embedded in agar and imaged at 4.7T. Samples were sectioned maintaining the orientation of the axial plane of MRI scans, and stained (hematoxylin-eosin and Prussian blue)., Results: All three giant sIAs showed a degenerated hypocellular wall with both mural and adventitial iron accumulation and displayed different degrees of luminal thrombus formation and thrombus organization. Signal intensity varied within the same sIA wall and associated with iron accumulation in all tested sequences. Wall areas with iron accumulation had significantly lower signal to noise ratio (SNR) compared with areas without iron accumulation (P = 0.002). Fresh and organizing thrombus differed in their MRI presentation and differed in signal intensity of the aneurysm wall (P = 0.027)., Conclusion: MRI can detect ex vivo the accumulation of iron in giant sIA wall, as well as fresh and organizing luminal thrombus. These features have been previously associated with fragile, rupture-prone aneurysm wall. Further studies of iron accumulation as a marker of rupture-prone aneurysm wall are needed.

Background and Purpose: Patients with genetic background for high circulating oxidized low-density lipoprotein (oxLDL) levels might be at an increased risk of cerebrovascular disease (CVD)., Methods: The association of oxLDL-variant rs676210 with CVD events was studied in patients undergoing coronary angiography (study A; N = 2913 [271 cases]). We sought to replicate the results in a large genome-wide association study meta-analysis of ischaemic stroke (study B; N = 3548 cases, 5972 controls)., Results: In study A, the prevalence of hypertension, diabetes and >50% carotid stenosis as well as the levels of LDL cholesterol differed significantly between cases and controls. In a logistic regression model adjusted for the significant covariates, rs676210 associated with CVD events (p = 0.030; odds ratio = 1.29 [95% confidence interval 1.03‒1.63] for risk allele G). In study B, rs676210 did not associate with the history of ischaemic stroke., Conclusions: The oxLDL levels increasing variant rs676210 associates with CVD events in patients undergoing coronary angiography., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Aims: The purpose of this study was to identify novel genetic variants influencing circulating asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) levels and to evaluate whether they have a prognostic value on cardiovascular mortality., Methods and Results: We conducted a genome-wide association study on the methylarginine traits and investigated the predictive value of the new discovered variants on mortality. Our meta-analyses replicated the previously known locus for ADMA levels in DDAH1 (rs997251; P = 1.4 × 10(-40)), identified two non-synomyous polymorphisms for SDMA levels in AGXT2 (rs37369; P = 1.4 × 10(-40) and rs16899974; P = 1.5 × 10(-38)) and one in SLC25A45 (rs34400381; P = 2.5 × 10(-10)). We also fine-mapped the AGXT2 locus for further independent association signals. The two non-synonymous AGXT2 variants independently associated with SDMA levels were also significantly related with short-term heart rate variability (HRV) indices in young adults. The major allele (C) of the novel non-synonymous rs16899974 (V498L) variant associated with decreased SDMA levels and an increase in the ratio between the low- and high-frequency spectral components of HRV (P = 0.00047). Furthermore, the SDMA decreasing allele (G) of the non-synomyous SLC25A45 (R285C) variant was associated with a lower resting mean heart rate during the HRV measurements (P = 0.0046), but not with the HRV indices. None of the studied genome-wide significant variants had any major effect on cardiovascular or total mortality in patients referred for coronary angiography., Conclusions: AGXT2 has an important role in SDMA metabolism in humans. AGXT2 may additionally have an unanticipated role in the autonomic nervous system regulation of cardiac function.

Background: Oxidized low-density lipoprotein may be a key factor in the development of atherosclerosis. We performed a genome-wide association study on oxidized low-density lipoprotein and tested the impact of associated single-nucleotide polymorphisms (SNPs) on the risk factors of atherosclerosis and cardiovascular events., Methods and Results: A discovery genome-wide association study was performed on a population of young healthy white individuals (N=2080), and the SNPs associated with a P<5×10(-8) were replicated in 2 independent samples (A: N=2912; B: N=1326). Associations with cardiovascular endpoints were also assessed with 2 additional clinical cohorts (C: N=1118; and D: N=808). We found 328 SNPs associated with oxidized low-density lipoprotein. The genetic variant rs676210 (Pro2739Leu) in apolipoprotein B was the proxy SNP behind all associations (P=4.3×10(-136), effect size=13.2 U/L per allele). This association was replicated in the 2 independent samples (A and B, P=2.5×10(-47) and 1.1×10(-11), effect sizes=10.3 U/L and 7.8 U/L, respectively). In the meta-analyses of cohorts A, C, and D (excluding cohort B without angiographic data), the top SNP did not associate significantly with the age of onset of angiographically verified coronary artery disease (hazard ratio=1.00 [0.94-1.06] per allele), 3-vessel coronary artery disease (hazard ratio=1.03 [0.94-1.13]), or myocardial infarction (hazard ratio=1.04 [0.96-1.12])., Conclusions: This novel genetic marker is an important factor regulating oxidized low-density lipoprotein levels but not a major genetic factor for the studied cardiovascular endpoints.

Background: Genome-wide association studies (GWASs) have identified a large number of variants (SNPs) associating with an increased risk of coronary artery disease (CAD). Recently, the CARDIoGRAM consortium published a GWAS based on the largest study population so far. They successfully replicated twelve already known associations and discovered thirteen new SNPs associating with CAD. We examined whether the genetic profiling of these variants improves prediction of subclinical atherosclerosis--i.e., carotid intima-media thickness (CIMT) and carotid artery elasticity (CAE)--beyond classical risk factors., Subjects and Methods: We genotyped 24 variants found in a population of European ancestry and measured CIMT and CAE in 2001 and 2007 from 2,081, and 2,015 subjects (aged 30-45 years in 2007) respectively, participating in the Cardiovascular Risk in Young Finns Study (YFS). The Bogalusa Heart Study (BHS; n = 1179) was used as a replication cohort (mean age of 37.5). For additional replication, a sub-sample of 5 SNPs was genotyped for 1,291 individuals aged 46-76 years participating in the Health 2000 population survey. We tested the impact of genetic risk score (GRS(24SNP/CAD)) calculated as a weighted (by allelic odds ratios for CAD) sum of CAD risk alleles from the studied 24 variants on CIMT, CAE, the incidence of carotid atherosclerosis and the progression of CIMT and CAE during a 6-year follow-up., Results: CIMT or CAE did not significantly associate with GRS(24SNP/CAD) before or after adjusting for classical CAD risk factors (p>0.05 for all) in YFS or in the BHS. CIMT and CAE associated with only one SNP each in the YFS. The findings were not replicated in the replication cohorts. In the meta-analysis CIMT or CAE did not associate with any of the SNPs., Conclusion: Genetic profiling, by using known CAD risk variants, should not improve risk stratification for subclinical atherosclerosis beyond conventional risk factors among healthy young adults.

Objective: To investigate whether chromosome 10q11.21 influences common carotid intima-media thickness (IMT) and atherosclerosis and whether it is associated with stromal cell-derived factor-1α (SDF-1α) plasma levels., Methods and Results: Variation on chromosome 10q11.21 has been consistently associated with coronary artery disease. The genetic variant lies upstream of the gene encoding SDF-1α. We genotyped 3 population cohorts (Bruneck [age range, 45 to 94 years; 50.0% men; n=738], Health2000 [age range, 46 to 76 years; 55.4% men; n=1237], and essential hypertension in families collected in the region of Oxford [HTO] [age range, 19 to 88 years; 47.9% men; n=770]) for single-nucleotide polymorphism rs501120 at the 10q11.21 locus and conducted a meta-analysis in these cohorts to ascertain a relationship between the polymorphism and carotid IMT. The analysis showed that individuals with the T/T genotype had a significantly higher carotid IMT than individuals with the C/T or C/C genotype (pooled weighted mean difference, 23 μm [95% CI, 9 to 37 μm], P=0.0014 under a fixed-effects model; and 23 μm [95% CI, 6 to 41 μm], P=0.009 under a random-effects model). In the Bruneck cohort, in which data for carotid atherosclerosis and plasma SDF-1α levels were available, we observed an association of the T/T genotype with a higher burden of atherosclerosis and increased susceptibility to the development of atherosclerosis during a 5-year follow-up (multivariable odds ratio, 1.73 [95% CI, 1.18 to 2.52]; P=0.005 for the recessive model) and an association between the T/T genotype and lower SDF-1α levels (2.62 ng/mL for T/T versus 2.74 ng/mL for C/C or C/T; P=0.023)., Conclusions: The coronary heart disease-related variant at the 10q11.21 locus is associated with carotid IMT and atherosclerosis.

Background: Interleukin 18(IL-18) is a pro-atherosclerotic cytokine. Elevated IL-18 levels and the genetic variation of the IL-18 have been previously linked with acute coronary events and cardiovascular mortality among patients with coronary artery disease (CAD). We studied the possible association between the IL-18 gene polymorphism and cardiovascular mortality during follow-up among Finnish patients who had undergone a clinical exercise stress test, in addition to the possible effect on the expression of angiography-verified CAD., Materials and Methods: A total of 2152 patients of the Finnish Cardiovascular Study (cohort study) were followed up for 6·3years and cardiovascular mortality was recorded. Angiography was performed on 461 patients. Genotyping of five common single nucleotide polymorphisms (SNPs) of the IL-18 gene was performed using the 5'nuclease assay for allelic discrimination with the ABI Prism 7900HT Sequence Detection System., Results: Among the study population, IL-18 gene polymorphism did not associate with cardiovascular mortality. According to adjusted binary regression analysis, the male carriers of one major haplotype (the only ones carrying the t allele of the +127 C/t SNP) had a lower occurrence rate for significant CAD defined as > 50% stenosis in at least one of the main branches of the coronary arteries (OR 0·495, 95% CI 0·862-0·284, P=0·041). No associations were observed among women. The sex-by-genotype interaction was significant (P=0·033)., Conclusions: The IL-18 gene was not found to associate significantly with mortality. Among patients who had coronary angiography, one major haplotype of the IL-18 gene has a gender-dependent different impact on the expression of CAD., (© 2010 The Authors. European Journal of Clinical Investigation © 2010 Stichting European Society for Clinical Investigation Journal Foundation.)

Purpose: To characterize the effect of ultrasmall superparamagnetic iron oxides (USPIOs) on magnetic resonance imaging (MRI) signal at 4.7 T, and to find the highest sensitivity pulse sequence for high-resolution USPIO MRI., Materials and Methods: A novel phantom was constructed for optimization of sequence parameters for neuroradiological MR applications, and a wide range of dilutions of the USPIO ferumoxtran-10 was imaged using T(2)/T(1)-, T(1)-, T(2)-, T* (2)-, and PD-weighted sequences. The effect of varying sequence parameters was investigated using phantom measurements and simulations., Results: The relaxivities r(1), r(2), and r*(2) of ferumoxtran-10 at 4.7 T (21°C) were 5.1, 82.2, and 148.4 mmol(-1) L s(-1), respectively. Gradient echo sequences produced superior susceptibility artifacts at high concentrations; susceptibility artifacts were seen down to a concentration of 137 nmol Fe/mL. A concentration of 17.5 μmol Fe/mL caused a signal void independently of sequence and parameters, and at concentrations ≤273 nmol Fe/mL no signal void was caused. Signal enhancement on T(1)-weighted imaging was seen only at concentrations 137-547 nmol Fe/mL. For the same effective echo time T(2)-weighted rapid acquisition with relaxation enhancement (RARE) yielded significantly higher contrast-to-noise ratio with RARE factor 16 than with RARE factor 8., Conclusion: At nanomolar concentrations of USPIO, steady-state free precession offers an alternative to T(2)- and T*(2)-weighted sequences. Optimum parameters depend highly on USPIO concentration., (© 2010 Wiley-Liss, Inc.)

The authors report the successful removal of Onyx HD-500 from an aneurysm sac by means of ultrasonic aspiration. This 46-year-old woman presented with progressive spasms of her left arm and leg due to mass effect and compression on the right cerebral peduncle 5 years after endovascular treatment of an unruptured giant posterior communicating artery aneurysm with Onyx HD-500. No filling of the aneurysm was detected on angiography. The patient underwent a right pterional craniotomy and the aneurysm was opened to remove the Onyx mass. However, contrary to expectations, the aneurysm was still patent, filling with blood between the Onyx mass and the aneurysm wall. Under temporary clipping of the carotid artery, the Onyx mass within the aneurysm was removed in a piecemeal fashion using an ultrasonic aspirator and the aneurysm was then successfully clipped. The patient experienced significant improvement of the spasm after surgery. Angiography showed complete occlusion of the posterior communicating artery aneurysm. It is rarely necessary to remove embolization material such as Onyx HD-500, and little is known about the most appropriate surgical technique. This case report demonstrates that removal can be safely accomplished by means of ultrasonic aspiration.

The relative contribution of genetic risk factors to the progression of subclinical atherosclerosis is poorly understood. It is likely that multiple variants are implicated in the development of atherosclerosis, but the subtle genotypic and phenotypic differences are beyond the reach of the conventional case-control designs and the statistical significance testing procedures being used in most association studies. Our objective here was to investigate whether an alternative approach--in which common disorders are treated as quantitative phenotypes that are continuously distributed over a population--can reveal predictive insights into the early atherosclerosis, as assessed using ultrasound imaging-based quantitative measurement of carotid artery intima-media thickness (IMT). Using our population-based follow-up study of atherosclerosis precursors as a basis for sampling subjects with gradually increasing IMT levels, we searched for such subsets of genetic variants and their interactions that are the most predictive of the various risk classes, rather than using exclusively those variants meeting a stringent level of statistical significance. The area under the receiver operating characteristic curve (AUC) was used to evaluate the predictive value of the variants, and cross-validation was used to assess how well the predictive models will generalize to other subsets of subjects. By means of our predictive modeling framework with machine learning-based SNP selection, we could improve the prediction of the extreme classes of atherosclerosis risk and progression over a 6-year period (average AUC 0.844 and 0.761), compared to that of using conventional cardiovascular risk factors alone (average AUC 0.741 and 0.629), or when combined with the statistically significant variants (average AUC 0.762 and 0.651). The predictive accuracy remained relatively high in an independent validation set of subjects (average decrease of 0.043). These results demonstrate that the modeling framework can utilize the "gray zone" of genetic variation in the classification of subjects with different degrees of risk of developing atherosclerosis., Competing Interests: The authors have declared that no competing interests exist.

Background and Aim: Interleukin-18 (IL-18) is a pro-atherosclerotic cytokine. We wanted to evaluate whether IL-18 gene polymorphism associates independently of risk factors, with early subclinical markers of atherosclerosis (intima-media thickness (IMT), coronary artery compliance (CAC), and flow-mediated dilatation (FMD)) in a population of young healthy Caucasian adults., Methods: This study was based on the on-going Cardiovascular Risk in Young Finns Study consisting of 2260 young adults, mean age being 31.7 (range 24-39 years) (1247 women and 1013 men)., Results: Five studied tagSNPs formed six major haplotypes, which accounted for 99.9% of all variation of the IL-18 gene. According to adjusted analysis of variance, the IL-18 gene polymorphism did not associate with subclinical atherosclerosis in the whole study population. However, one major haplotype associated differently among men and women with IMT (P = 0.011). Male carriers of a major CCTgT haplotype (n = 441) seemed to have a lower IMT when compared to the non-carriers (-0.016 mm, 95% confidence interval (CI) -0.028 to -0.004, P = 0.014). Among women no significant associations were observed., Conclusions: Among all study subjects, the polymorphism of the IL-18 gene is not associated with subclinical markers of atherosclerosis. However, among men one major IL-18 haplotype seemed to associate with substantially lower IMT values.

Aims: The interleukin 18 (IL-18) gene has a single nucleotide promoter region (-137) G-to-C polymorphism (rs187238) which leads to attenuated transcriptional activity of the gene and to lower production of pro-atherogenic IL-18. The C allele of this polymorphism is associated with a lower risk of sudden cardiac death (SCD). We examined the process by which this polymorphism alters the risk of SCD and coronary artery disease (CAD) by analysing the interactions between this polymorphism and environmental factors., Methods and Results: TaqMan 5' nuclease assay was used to genotype the study population of the Helsinki Sudden Death Study, comprising medicolegal autopsies of 700 men. According to adjusted logistic regression analysis, there was a significant interaction between IL-18 genotype and hypertension impacting on the risk of SCD due to coronary heart disease (CHD) (P = 0.011) and the severity of autopsy-verified CAD (P = 0.026). Among GG homozygotes, hypertension was a major risk factor for SCD due to CHD [adjusted odds ratio (OR) 3.75 with 95% CI 1.78-7.91, P < 0.001] and hypertension also associated with larger coronary atherosclerotic plaque areas (P = 0.002) and the occurrence of complicated plaques (adjusted OR 8.38 with 95% CI 2.39-29.33, P < 0.001). Among C allele carriers, hypertension was not a significant risk factor for CHD-related SCD or CAD and did not associate with the development of coronary atherosclerotic plaques. According to gene expression analysis of atherosclerotic tissue samples obtained from live patients, hypertension also interacted significantly with IL-18 genotype affecting the expression of IL-18 (P = 0.030) mRNA and interferon-gamma mRNA (P = 0.004)., Conclusion: Hypertension interacts with IL-18 gene promoter -137 G/C polymorphism, affecting the risk of SCD and the development of coronary atherosclerosis.

Background: Neck remnants and aneurysm recurrences are marked limitations of endovascular treatment of cerebral artery aneurysms. We compared the evolution of neck remnants of experimental arterial rat aneurysms after treatment with either platinum- or PGLA-coated coils., Methods: We created 20 standard-size aneurysms in the abdominal aortas of male Wistar rats. Aneurysms were embolized with either PGLA-coated coils or platinum coils, with care taken to leave a neck remnant. Neck remnant size and shape was closely monitored to detect progressive enlargement or occlusion. Using a 4.7 T MR scanner, we acquired high-resolution MR images 6 times during the 4-week follow-up. For quantitative measurements, we used a high-resolution 3D-TOF angiography sequence. Results were verified by endoscopy and histology., Results: Aneurysms treated with PGLA coils showed, on average, a 12.9% reduction of neck remnant size (P = .044) and significant disappearance of dog ears, the blood-filled spaces between coils and aneurysm wall. The aneurysms treated with platinum coils lacked these changes. In endoscopy, neointima was found to cover both PGLA and platinum coils but was more often incomplete or translucent in the platinum group. In histology, thrombus organization and inflammatory cell infiltration were higher with PGLA., Conclusion: Use of PGLA-coated coils was followed by a moderate progressive reduction of the neck remnant size and a better angiographic outcome, seen as disappearance of dog ears during follow-up. The rat model proved to be suitable for comparison of different coil types.

Objective: Fenestration of the lamina terminalis (LT) is an alternative means of cerebrospinal fluid (CSF) drainage during acute or emergency surgery of ruptured intracranial aneurysms in patients with high-grade subarachnoid hemorrhage. External ventricular drainage allows drainage of CSF and also measurement of intracranial pressure after the surgery. Catheterization of the third ventricle via the fenestrated LT after clipping the aneurysm is an alternative to conventional ventriculostomies. This method has been used by the senior author (JAH) since 2001. The authors describe their experience with this technique, which can be used safely in selected cases of high-grade subarachnoid hemorrhage., Methods: Seventy-eight patients with aneurysmal subarachnoid hemorrhage underwent third ventriculostomy via the LT between March 2001 and December 2005. Clinical and radiological data of these consecutive patients were retrospectively reviewed., Results: There were no procedure-related complications. Eight patients (10%) later required a conventional ventriculostomy, 7 because of catheter occlusion and 1 because of catheter displacement. In 7 patients (9%), a positive CSF culture was found., Conclusion: Ventriculostomy via the fenestrated LT performed during aneurysm surgery is a practical way for later CSF removal and intracranial pressure monitoring. The catheter can be applied via the same craniotomy without the need for an additional intervention. No procedure-related complications were observed in the present series. This technique can be suggested as a safe alternative to a classical ventriculostomy.

Objective: The prognosis of giant aneurysms remains poor despite recent advances in microneurosurgery. Thick-walled and partially calcified giant aneurysms with an atheromatic base are difficult to clip safely. Special techniques allowing reshaping of the base and ensuring the stability of clips are often needed. We present our experience with direct clipping of thick-walled giant aneurysms with the aid of the DeBakey cardiovascular clamp (Aesculap, Tuttlingen, Germany)., Methods: Eighty-two patients with a giant aneurysm (>/=25 mm) were treated actively at the Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland, between 1997 and 2007. The vascular clamp technique was used in 8 of 50 patients in whom direct clipping was performed. The remaining patients were treated with bypass and trapping, trapping only, proximal occlusion, coiling, or explorative surgery., Results: The vascular clamp (DeBakey in 5 cases, Crile forceps [Medicon Medizin-Technik, Tuttlingen, Germany] in 2 cases, and Halsted-Mosquito forceps [Medicon Medizin-Technik, Tuttlingen, Germany] in 1 case) was used in 7 saccular middle cerebral artery aneurysms and 1 fusiform basilar bifurcation aneurysm. Two patients had postoperative infarctions, 1 attributable to occlusion of perforators by a clip and the other caused by clips sliding down the calcified base, occluding a major branch. Six patients had no neurological sequelae, 1 patient had transient upper limb paresis, and the patient with the occluded major branch died., Conclusion: The DeBakey vascular clamp is helpful in assisting direct clipping of thick-walled giant aneurysms with a partially calcified atheromatic base. Some practical features of this instrument require further refinement.

Objective: Previously, we scanned all 23,000 human genes for differential expression between normal and atherosclerotic tissues and found the involvement of ADAM8., Methods: We investigated the expression of ADAM8 mRNA and protein level in human atherosclerotic tissues and non-atherosclerotic internal thoracic arteries as well as the association of ADAM8 2662 T/G single nucleotide polymorphism (SNP) with the extent of coronary atherosclerosis and with the risk of fatal myocardial infarction., Results: ADAM8 mRNA was up-regulated in carotid, aortic, and femoral atherosclerotic plaques (n=24) when compared with non-atherosclerotic arteries. ADAM8 protein expression was increased in advanced atherosclerotic plaques as compared to control vessels wherein it was localized to macrophages and smooth muscle cells The G allele carriers of the ADAM8 2662 T/G SNP had significantly larger areas of fibrotic, calcified, and complicated plaques in coronary arteries (P=0.027, P=0.011, and P=0.011, respectively) and significantly higher occurrence of myocardial infarction (MI) (P=0.004) and fatal pre-hospital MI (P=0.003) than did the TT homozygotes., Conclusion: ADAM8 is a promising candidate to be involved in atherosclerosis, and its 2662 T/G allelic variant significantly associates with advanced atherosclerotic lesion areas and MI.

Objective and Importance: Colloid cysts of the third ventricle are rare benign tumors of endodermal origin accounting for 1% of all intracranial tumors. Interestingly, a few familial cases have been reported previously. We present the first case of dizygotic twins with a symptomatic colloid cyst of the third ventricle., Clinical Presentation: A 10-year-old boy was admitted to a local hospital in 1993 because of severe progressive headache. Computed tomographic and magnetic resonance imaging scans revealed acute obstructive hydrocephalus attributable to a third ventricular colloid cyst, which was removed after emergent ventricular drainage. Fourteen years later, a nonidentical twin brother complained of continuous headache with nausea and vomiting. A magnetic resonance imaging scan showed obstructive hydrocephalus and a third ventricle colloid cyst, which was removed by use of the transcallosal approach., Intervention: Both twins underwent complete removal of the cyst by the interhemispheric transcallosal approach without postoperative complications., Conclusion: On the basis of a literature review, 2 cases of colloid cysts of the third ventricle in monozygotic twins and a few familial cases have been reported. Our case is the first in dizygotic twin brothers. These findings suggest that the prevalence of colloid cyst may be higher in twins than in the general population. We believe that the presence of this lesion in a twin necessitates magnetic resonance imaging of the other twin, and a clinical follow-up would be recommended in all other first-degree relatives.