Treating children's aggressive behavior problems using cognitive behavior therapy with virtual reality: A multicenter randomized controlled trial.

This multicenter randomized controlled trial investigated whether interactive virtual reality enhanced effectiveness of Cognitive Behavioral Therapy (CBT) to reduce children's aggressive behavior problems. Boys with aggressive behavior problems (N = 115; Mage = 10.58, SD = 1.48; 95.7% born in Netherlands) were randomized into three groups: CBT with virtual reality, CBT with roleplays, or care-as-usual. Bayesian analyses showed that CBT with virtual reality more likely reduced aggressive behavior compared to care-as-usual for six of seven outcomes (ds 0.19-0.95), and compared to CBT with roleplays for four outcomes (ds 0.14-0.68). Moreover, compared to roleplays, virtual reality more likely enhanced children's emotional engagement, practice immersion, and treatment appreciation. Thus, virtual reality may be a promising tool to enhance CBT effectiveness for children with aggressive behavior problems.

Detecting social information processing profiles of boys with aggressive behavior problems: An interactive virtual reality approach.

Children with aggressive behavior problems may aggress for different reasons, requiring tailored assessment and treatment. The aim of this study was to test whether it is possible to detect distinct social information processing (SIP) profiles among boys with aggressive behavior problems. We therefore conducted Latent Profile Analyses on boys' SIP patterns assessed in interactive virtual reality. Additionally, we examined the discriminant validity of these SIP profiles by comparing them on theoretically relevant child characteristics (i.e., temperament, executive functioning, aggressive belief systems, punishment insensitivity, sensation seeking). We presented boys (N = 181; ages 7-13) with a virtual classroom where they could play games with virtual peers. They reported on their SIP in four virtual reality scenarios, designed to assess reactive and proactive aggressive SIP. Results revealed four distinct SIP profiles: a general reactive SIP profile, a situation-specific reactive SIP profile, a mixed reactive-proactive SIP profile, and a nonaggressive SIP profile. Planned contrasts revealed that boys with these SIP profiles differed in temperament, aggressive belief systems, and punishment insensitivity, but not in executive functioning and sensation seeking. Overall, findings suggest that boys differ in the exact SIP patterns underlying their aggressive behavior, providing inroads to tailor interventions to children's individual needs.

Capturing mechanisms of change: Weekly covariation in anger regulation, hostile intent attribution, and children's aggression.

Interventions for children's aggression typically target assumed underlying mechanisms, such as anger regulation and hostile intent attribution. The expectation here is that targeting these mechanisms will result in within-person changes in aggression. However, evidence for these mechanisms is mostly based on between-person analyses. We, therefore, examined whether within-person changes in adaptive anger regulation and hostile intent attribution covaried with within-person changes in children's aggression. Children (N = 223; age 7-12; 46% boys) filled out four weekly report measures to assess adaptive anger regulation, hostile intent attribution, and aggression. The psychometric properties of these novel measures were adequate. Results of multi-level analyses revealed within-person effects: weekly changes in adaptive anger regulation and hostile intent attribution covaried with changes in children's aggression. This corresponded with between-person findings on the same data: children with lower levels of adaptive anger regulation and higher levels of hostile intent attribution reported more aggression than other children. These findings support the idea that targeting anger regulation and hostile intent attribution in interventions may lead to changes in individual children's aggression.

Association between Intraplaque Hemorrhage and Vascular Remodeling in Carotid Arteries: The Plaque at RISK (PARISK) Study.

INTRODUCTION: Vascular remodeling is a compensatory enlargement of the vessel wall in response to atherosclerotic plaque growth. We aimed to investigate the association between intraplaque hemorrhage (IPH), vascular remodeling, and luminal dimensions in recently symptomatic patients with mild to moderate carotid artery stenosis in which the differences in plaque size were taken into account. MATERIALS AND METHODS: We assessed vessel dimensions on MRI of the symptomatic carotid artery in 164 patients from the Plaque At RISK study. This study included patients with recent ischemic neurological event and ipsilateral carotid artery stenosis <70%. The cross section with the largest wall area (WA) in the internal carotid artery (ICA) was selected for analysis. On this cross section, the following parameters were determined: WA, total vessel area (TVA), and lumen area (LA). Vascular remodeling was quantified as the remodeling ratio (RR) and was calculated as TVA at this position divided by the TVA in an unaffected distal portion of the ipsilateral ICA. Adjustment for WA was performed to correct for plaque size. RESULTS: Plaques with IPH had a larger WA (0.56 vs. 0.46 cm2; p < 0.001), a smaller LA (0.17 vs. 0.22 cm2; p = 0.03), and a higher RR (2.0 vs. 1.9; p = 0.03) than plaques without IPH. After adjustment for WA, plaques containing IPH had a smaller LA (B = -0.052, p = 0.01) than plaques without IPH, but the RR was not different. CONCLUSION: After correcting for plaque size, plaques containing IPH had a smaller LA than plaques without IPH. However, RR was not different.

Interactive virtual reality assessment of aggressive social information processing in boys with behaviour problems: A pilot study.

Children's aggressive behaviour is partly determined by how they process social information (e.g., making hostile interpretations or aiming to seek revenge). Such aggressive social information processing (SIP) may be most evident if children are emotionally engaged in actual social interactions. Current methods to assess aggressive SIP, however, often ask children to reflect on hypothetical vignettes. This pilot study therefore examined a new method that actually involves children in emotionally engaging social interactions: interactive virtual reality (VR). We developed a virtual classroom where children could play games with virtual peers. A sample of boys (N = 32; ages 8-13) from regular and special education reported on their SIP in distinct VR contexts (i.e., neutral, instrumental gain and provocation). They also completed a standard vignette-based assessment of SIP. Results demonstrated good convergent validity of interactive VR assessment of SIP, as indicated by significant moderate to large correlations of VR-assessed SIP with vignette-assessed SIP for all SIP variables except anger. Interactive VR showed improved measurement sensitivity (i.e., larger variances in SIP compared to vignettes) for aggressive responding, but not for other SIP variables. Discriminant validity (i.e., distinct SIP patterns across contexts) of interactive VR was supported for provocation contexts, but not for instrumental gain contexts. Last, children were more enthusiastic about the VR assessment compared to the vignette-based assessment. These findings suggest that interactive VR may be a promising tool, allowing for the assessment of children's aggressive SIP in standardized yet emotionally engaging social interactions.

Does Parent-Child Discussion of Peer Provocations Reduce Young Children's Hostile Attributional Bias?

Two studies investigated whether parent-child discussion of peer provocations reduces young children's hostile attributional bias. Study 1 (N = 109, age 4-7)-an observational study-showed that parent-child discussion of nonhostile attributions (when reading a picture book) predicted reductions in children's hostile attributional bias from pre- to postdiscussion. Study 2 (N = 160, age 4-6)-an experimental study-showed that stimulating parents to discuss either nonhostile attributions or normative beliefs (vs. a control condition) reduced children's hostile attributional bias in response to hypothetical vignettes, but not in response to a staged peer provocation. These findings suggest that by framing social situations, parents may help their children perceive less hostility in their social worlds.

Psychological processes in young bullies versus bully-victims.

Some children who bully others are also victimized themselves ("bully-victims") whereas others are not victimized themselves ("bullies"). These subgroups have been shown to differ in their social functioning as early as in kindergarten. What is less clear are the motives that underlie the bullying behavior of young bullies and bully-victims. The present study examined whether bullies have proactive motives for aggression and anticipate to feel happy after victimizing others, whereas bully-victims have reactive motives for aggression, poor theory of mind skills, and attribute hostile intent to others. This "distinct processes hypothesis" was contrasted with the "shared processes hypothesis," predicting that bullies and bully-victims do not differ on these psychological processes. Children (n = 283, age 4-9) were classified as bully, bully-victim, or noninvolved using peer-nominations. Theory of mind, hostile intent attributions, and happy victimizer emotions were assessed using standard vignettes and false-belief tasks; reactive and proactive motives were assessed using teacher-reports. We tested our hypotheses using Bayesian model selection, enabling us to directly compare the distinct processes model (predicting that bullies and bully-victims deviate from noninvolved children on different psychological processes) against the shared processes model (predicting that bullies and bully-victims deviate from noninvolved children on all psychological processes alike). Overall, the shared processes model received more support than the distinct processes model. These results suggest that in early childhood, bullies and bully-victims have shared, rather than distinct psychological processes underlying their bullying behavior.

High Spatial Inhomogeneity in the Intima-Media Thickness of the Common Carotid Artery is Associated with a Larger Degree of Stenosis in the Internal Carotid Artery: The PARISK Study.

Purpose Inhomogeneity of arterial wall thickness may be indicative of distal plaques. This study investigates the intra-subject association between relative spatial intima-media thickness (IMT) inhomogeneity of the common carotid artery (CCA) and the degree of stenosis of plaques in the internal carotid artery (ICA). Materials and Methods We included 240 patients with a recent ischemic stroke or transient ischemic attack and mild-to-moderate stenosis in the ipsilateral ICA. IMT inhomogeneity was extracted from B-mode ultrasound recordings. The degree of ICA stenosis was assessed on CT angiography according to the European Carotid Surgery Trial method. Patients were divided into groups with a low (≤ 2 %) and a high (> 2 %) IMT inhomogeneity scaled with respect to the local end-diastolic diameter. Results 182 patients had suitable CT and ultrasound measurements. Relative CCA-IMT inhomogeneity was similar for the symptomatic and asymptomatic side (difference: 0.02 %, p = 0.85). High relative IMT inhomogeneity was associated with a larger IMT (difference: 235 µm, p < 0.001) and larger degree of ICA stenosis (difference: 5 %, p = 0.023) which remained significant (p = 0.016) after adjustment for common risk factors. Conclusion Regardless of common risk factors, high relative CCA-IMT inhomogeneity is associated with a greater degree of ICA stenosis and is therefore indicative of atherosclerotic disease. The predictive value of CCA-IMT inhomogeneity for plaque progression and recurrence of cerebrovascular symptoms will be determined in the follow-up phase of PARISK.

Heritability and Genome-Wide Association Analyses of Intracranial Carotid Artery Calcification: The Rotterdam Study.

BACKGROUND AND PURPOSE: Intracranial carotid artery calcification (ICAC) is one of the most important risk factors for stroke. Although several environmental risk factors for ICAC have been identified, its genetic background remains unclear. METHODS: Between 2003 and 2006, 2034 participants from the prospective population-based Rotterdam study (mean age: 69.6±6.8 years; 51.7% female) underwent computed tomography to quantify vascular calcification in the intracranial internal carotid artery. Blood samples were drawn for genotyping. Genotypes of the participants were imputed to the 1000 Genomes reference panel to generate genetic relationship matrices for the estimation of the heritability of ICAC volume. Adjustments were made for age and sex. Subsequently, genome-wide association analyses were performed to identify specific variants. RESULTS: The age- and sex-adjusted heritability (h(2)) of ICAC was 47% [standard error (SE): 19%; P=0.009]. Genome-wide association analyses identified a variant on chromosome 9p21.3 (rs1537372; N=2034; P=4.75×10(-9)) and 1 variant on chromosome 11p11.2 (rs11038042, N=2034; P=3.27×10(-8)) that were significantly associated with ICAC volume. Rs1537372 replicated in an independent sample of 716 stroke patients (Pcombined=1.38×10(-10)). CONCLUSIONS: ICAC volume is a heritable trait, which is partly explained by common genetic variation. We identified specific genetic variants associated with ICAC, which given the importance of ICAC in stroke risk, needs replication in larger-scale studies to further elucidate its genetic basis.

Use of Antiplatelet Agents Is Associated With Intraplaque Hemorrhage on Carotid Magnetic Resonance Imaging: The Plaque at Risk Study.

BACKGROUND AND PURPOSE: Intraplaque hemorrhage (IPH), visualized by magnetic resonance imaging, has shown to be associated with the risk of stroke in patients with carotid artery stenosis. The mechanisms of IPH development are poorly understood. In this study, we investigated the association between clinical patient characteristics and carotid IPH on high-resolution magnetic resonance imaging. METHODS: Patients participate in the Plaque at Risk (PARISK) study. This prospective, multicenter cohort study included patients with recent amaurosis fugax, hemispheric transient ischemic attack, or nondisabling stroke in the internal carotid artery territory and an ipsilateral carotid stenosis of <70%, who were not scheduled for carotid revascularization procedure. One hundred patients, recruited between 2010 and 2012, underwent a 3-T high-resolution carotid magnetic resonance imaging. We documented clinical patient characteristics and performed multivariable logistic regression analysis to investigate their association with IPH. RESULTS: IPH was observed in 45 patients (45%) in 1 or both carotid arteries. Male sex and the use of antiplatelet agents before the index event were associated with IPH in univariable analysis. In a multivariable analysis, only previous use of antiplatelet agents was significantly associated with IPH (odds ratio, 2.71; 95% confidence interval, 1.12-6.61). Risk factors of atherosclerotic arterial disease, including a history of symptomatic arterial diseases, were not associated with IPH. CONCLUSIONS: In this cohort of 100 patients with recently symptomatic carotid stenosis, the previous use of antiplatelet agents is associated with carotid IPH on magnetic resonance imaging. Antiplatelet therapy may increase the risk of IPH, but our findings need to be confirmed in larger patient cohorts. The implications for risk stratification remain to be determined.

Plaque components in symptomatic moderately stenosed carotid arteries related to cerebral infarcts: the plaque at RISK study.

BACKGROUND AND PURPOSE: Carotid plaque composition is a major determinant of cerebrovascular events. In the present analysis, we evaluated the relationship between intraplaque hemorrhage (IPH) and a thin/ruptured fibrous cap (TRFC) in moderately stenosed carotid arteries and cerebral infarcts on MRI in the ipsilateral hemisphere. METHODS: A total of 101 patients with a symptomatic 30% to 69% carotid artery stenosis underwent MRI of the carotid arteries and the brain, within a median time of 45 days from onset of symptoms. The presence of ipsilateral infarcts in patients with and without IPH and TRFC was evaluated. RESULTS: IPH was seen in 40 of 101 plaques. TRFC was seen in 49 of 86 plaques (postcontrast series were not obtained in 15 patients). In total, 51 infarcts in the flow territory of the symptomatic carotid artery were found in 47 patients. Twenty nine of these infarcts, found in 24 patients, were cortical infarcts. No significant relationship was found between IPH or TRFC and the presence of ipsilateral infarcts. CONCLUSIONS: MRI detected IPH and TRFC are not related to the presence of old and recent cortical and subcortical infarcts ipsilateral to a symptomatic carotid artery stenosis of 30% to 69%. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01208025.

Association between arterial calcifications and nonlacunar and lacunar ischemic strokes.

BACKGROUND AND PURPOSE: Nonlacunar cerebral infarcts are presumed to be caused by thromboembolism from the heart or extracranial arteries, whereas lacunar infarcts are thought to be caused by small vessel disease. We investigated to what extent arterial calcifications differ between nonlacunar and lacunar ischemic strokes. METHODS: We studied 820 consecutive patients with transient ischemic attack or ischemic stroke in the anterior circulation who underwent multidetector computed tomography angiography and had no rare cause of stroke. The presence of likely cardioembolic pathogenesis was determined according to the Trial of Org 10172 in Acute Stroke Treatment criteria. The remaining 708 patients were categorized as nonlacunar or lacunar strokes, either transient ischemic attacks or strokes, based on clinical symptoms corrected by brain imaging results. We measured volume of calcifications in the aortic arch, symptomatic extracranial and intracranial carotid artery using multidetector computed tomography angiography. The difference in calcifications between nonlacunar and lacunar strokes was assessed with a multivariable logistic regression analysis. We adjusted for degree of symptomatic carotid artery stenosis and cardiovascular risk factors. RESULTS: We found an independent association between volume of aortic arch calcifications and nonlacunar ischemic strokes (adjusted odds ratio [95% confidence interval], 1.11 [1.02-1.21]). No independent associations between extracranial and intracranial carotid artery calcifications and nonlacunar strokes were present. CONCLUSIONS: The only difference we found between nonlacunar and lacunar strokes was a higher calcification volume in the aortic arch in nonlacunar strokes. Our findings only partially confirm the notion of distinct etiologies and suggest that the potential role of other plaque components, plaque morphology, and aortic arch calcifications in ischemic stroke subtypes awaits further evaluation.

Intraplaque hemorrhage, fibrous cap status, and microembolic signals in symptomatic patients with mild to moderate carotid artery stenosis: the Plaque at RISK study.

BACKGROUND AND PURPOSE: In patients with mild to moderate symptomatic carotid artery stenosis, intraplaque hemorrhage (IPH) and a thin/ruptured fibrous cap (FC) as evaluated with MRI, and the presence of microembolic signals (MESs) as detected with transcranial Doppler, are associated with an increased risk of a (recurrent) stroke. The objective of the present study is to determine whether the prevalence of MES differs in patients with and without IPH and thin/ruptured FC, and patients with only a thin/ruptured FC without IPH. METHODS: In this multicenter, diagnostic cohort study, patients with recent transient ischemic attack or minor stroke in the carotid territory and an ipsilateral mild to moderate carotid artery plaque were included. IPH and FC status were dichotomously scored. Analysis of transcranial Doppler data was done blinded for the MRI results. Differences between groups were analyzed with Fisher exact test. RESULTS: A total of 113 patients were included. Transcranial Doppler measurements were feasible in 105 patients (average recording time, 219 minutes). A total of 26 MESs were detected in 8 of 105 patients. In 44 of 105 plaques IPH was present. In 92 of 105 plaques FC status was assessable, 36 of these had a thin/ruptured FC. No significant difference in the prevalence of MES between patients with and without IPH (P=0.46) or with thick versus thin/ruptured FC (P=0.48) was found. CONCLUSIONS: In patients with a symptomatic mild to moderate carotid artery stenosis, IPH and FC status are not associated with MES. This suggests that MRI and transcranial Doppler provide different information on plaque vulnerability. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01709045.

One research question, two meta-analyses, three conclusions: Commentary on "A systematic review with meta-analysis of Cognitive Bias Modification interventions for anger and aggression".

Recently two independent meta-analyses on the efficacy of Cognitive Bias Modification of Interpretation (CBM-I) to reduce aggressive behavior came to different conclusions: Ciesinski et al. (2023) concluded that "CBM demonstrates efficacy for the treatment of aggressive behavior" (Abstract), whereas our research team concluded that "findings show limited support for the efficacy of CBM-I to reduce aggressive behavior" (AlMoghrabi et al., 2023, Discussion). How can similar meta-analyses reach such different conclusions? In this commentary, we raise awareness concerning how 1) seemingly identical research questions can be based on meaningfully different definitions of the intervention and outcomes; 2) intervention efficacy conclusions can depend on outcome assessment type; and 3) the interpretation of underpowered moderator analyses should not depend on statistical significance. We end our commentary with a third, more nuanced conclusion that can reconcile the two disparate conclusions: that current CBM-I is an effective experimental manipulation to modify interpretation biases, but not an effective stand-alone treatment to reduce aggressive behavior.

"I'm not here to push you:" raising adolescents' treatment engagement via autonomy support.

More than 45% of adolescents with aggressive behavior problems drop out of treatment prematurely. Building on insights from self-determination theory, we examined in three studies whether clinicians can raise adolescents' treatment engagement by supporting their autonomy. In an interview study (Study 1), clinicians (N = 16; 43.8% female; ages 30-57) spontaneously described 12 times more autonomy-supportive than controlling strategies to engage adolescents. In a preregistered experiment (Study 2), clinicians (N = 68; 88.2% female; ages 23-65) were confronted with videos of adolescents displaying resistance. We manipulated the DSM diagnosis of adolescents to indicate either aggressive behavior problems or other problems. We found that, regardless of diagnosis, clinicians used both autonomy-supportive strategies (57.7% of responses) and controlling strategies (39.3%), suggesting that applying autonomy support can be challenging with any adolescent displaying resistance. In an experimental study (Study 3), adolescents (N = 252; 50.0% female; ages 12-17) reported higher therapeutic alliance (d = 0.95, 95% CI [0.80, 1.10]) and treatment engagement (d = 0.77, 95% CI [0.63, 0.91]) after listening to audio-recorded autonomy-supportive versus controlling responses from clinicians, regardless of whether these adolescents had aggressive behavior problems. Overall, this research suggests that clinicians can raise adolescents' treatment engagement through autonomy support.

Interactive Virtual Reality versus Vignette-Based Assessment of Children's Aggressive Social Information Processing.

This study examined whether interactive Virtual Reality (VR) provides a more ecologically valid assessment of children's aggressive social information processing (SIP) and aggressive responses than a standard vignette-based assessment. We developed a virtual classroom where children could meet and play games with virtual peers. Participants were boys (N = 184; ages 7-13) from regular education and special education for children with disruptive behavior problems. They reported on their SIP in four scenarios (i.e., two instrumental gain and two provocation scenarios) presented through both interactive VR and vignettes. Teachers reported on children's real-life aggressive behavior and reactive and proactive motives for aggression. Results demonstrated that children found the interactive VR assessment more emotionally engaging and immersive than the vignette-based assessment. Moreover, compared to vignettes, the interactive VR assessment evoked higher levels of aggressive SIP and responses in provocation scenarios only. Results supported the enhanced predictive validity of the interactive VR assessment of children's aggressive SIP and responses, which predicted children's real-life aggression above and beyond the vignette-based assessment with 2 to 12% additional explained variance. Similar results were found for children's real-life reactive and proactive motives for aggression, with 3 to 12% additional variance explained by interactive VR above and beyond vignettes. Interactive VR did not, however, evoke larger individual differences (i.e., variances) in children's aggressive SIP and responses than vignettes. Together, these findings suggest that interactive VR provides a more ecologically valid method to assess children's aggressive SIP and responses than hypothetical vignettes.

Do Distinct Groups of Reactively and Proactively Aggressive Children Exist? A Confirmatory Latent Profile Approach.

The present study examined whether there are distinct groups of children with reactive versus proactive motives for their aggressive behavior. We extended previous research by using a person-based analytical approach on data from a questionnaire assessing children's motives independently from the severity of their aggression. Two competing hypotheses were tested. The both subtypes hypothesis holds that both reactive and proactive subtypes exist, as well as a mixed subtype. The reactive only hypothesis holds that only reactive and mixed subtypes exist. Hypotheses were tested on existing data from a community sample of children displaying aggression (Study 1: n = 228, ages 10-13, 54% boys), and two clinical samples of children with aggressive behavior problems (Study 2: n = 115, ages 8-13, 100% boys; Study 3: n = 123, ages 6-8, 78% boys). Teachers reported on children's reactive and proactive motives. We selected measures available from peers, parents, teachers, and children themselves to compare the supported subtypes on variables that previous literature suggests uniquely correlate with reactive versus proactive aggression. Confirmatory latent profile analyses revealed that the both subtypes hypothesis best fit the data of all three samples. Most children were classified as reactive (55.7-61.8% across samples), with smaller percentages classified as proactive (10.4-24.1%) and mixed (18.0-33.9%). However, these subtypes only differed in expected directions on 7 out of 34 measures. Overall, results support the existence of both reactive and proactive subtypes of aggressive children, but the distinctiveness of these subtypes in terms of social-emotional characteristics warrants further study.

Using virtual reality to treat aggressive behavior problems in children: A feasibility study.

Evidence-based cognitive behavioral therapies (CBTs) for children with aggressive behavior problems have only modest effects. Research is needed into new methods to enhance CBT effectiveness. The aims of the present study were to (1) examine whether interactive virtual reality is a feasible treatment method for children with aggressive behavior problems; (2) investigate children's appreciation of the method; and (3) explore whether children's aggression decreased during the ten-session treatment. Six boys (8-12 years) participated at two clinical centers in the Netherlands. Newly developed weekly reports were collected on treatment feasibility (therapist-report), treatment appreciation (child report), and children's aggression (child/parent report). Results supported treatment feasibility: therapists delivered on average 98% of the session content, provided more than the recommended practice time in virtual reality, experienced few technical issues, and were satisfied with their treatment delivery. Children highly appreciated the treatment. Parents reported decreases in children's aggression over the treatment period (i.e., between week 1 and week 10), but children did not. The promising findings of this feasibility study warrant randomized controlled trials to determine whether interactive virtual reality enhances CBT effectiveness for children with aggressive behavior problems.

Lipoprotein(a) levels and atherosclerotic plaque characteristics in the carotid artery: The Plaque at RISK (PARISK) study.

BACKGROUND AND AIMS: Lipoprotein(a) is an independent risk factor for cardiovascular disease and recurrent ischemic stroke. Lipoprotein(a) levels are known to be associated with carotid artery stenosis, but the relation of lipoprotein(a) levels to carotid atherosclerotic plaque composition and morphology is less known. We hypothesize that higher lipoprotein(a) levels and lipoprotein(a)-related SNPs are associated with a more vulnerable carotid plaque and that this effect is sex-specific. METHODS: In 182 patients of the Plaque At RISK study we determined lipoprotein(a) concentrations, apo(a) KIV-2 repeats and LPA SNPs. Imaging characteristics of carotid atherosclerosis were determined by MDCTA (n = 161) and/or MRI (n = 171). Regressions analyses were used to investigate sex-stratified associations between lipoprotein(a) levels, apo(a) KIV-2 repeats, and LPA SNPs and imaging characteristics. RESULTS: Lipoprotein(a) was associated with presence of lipid-rich necrotic core (LRNC) (aOR = 1.07, 95% CI: 1.00; 1.15), thin-or-ruptured fibrous cap (TRFC) (aOR = 1.07, 95% CI: 1.01; 1.14), and degree of stenosis (ß = 0.44, 95% CI: 0.00; 0.88). In women, lipoprotein(a) was associated with presence of intraplaque hemorrhage (IPH) (aOR = 1.25, 95% CI: 1.06; 1.61). In men, lipoprotein(a) was associated with degree of stenosis (ß = 0.58, 95% CI: 0.04; 1.12). Rs10455872 was significantly associated with increased calcification volume (ß = 1.07, 95% CI: 0.25; 1.89) and absence of plaque ulceration (aOR = 0.25, 95% CI: 0.04; 0.93). T3888P was associated with absence of LRNC (aOR = 0.36, 95% CI: 0.16; 0.78) and smaller maximum vessel wall area (ß = -10.24, 95%CI: -19.03; -1.44). CONCLUSIONS: In patients with symptomatic carotid artery stenosis, increased lipoprotein(a) levels were associated with degree of stenosis, and IPH, LRNC, and TRFC, known as vulnerable plaque characteristics, in the carotid artery. T3888P was associated with lower LRNC prevalence and smaller maximum vessel wall area. Further research in larger study populations is needed to confirm these results.