Kaula- ja aivovaltimodissektoitumien riskitekijät ja taudinkuva

Cervicocerebral artery dissection (CeAD) is one of the leading causes of ischemic stroke in the young and middle-aged adults. The pathophysiology of CeAD is poorly understood. CeAD patients probably have a constitutional, partly genetic weakness of the vessel wall, which predisposes to tears in the connective tissue within the vascular wall in occurrence of environmental triggers of the disease, such as acute infection, migraine, or minor trauma. For this thesis project, we collected a register of all consecutive CeAD patients treated at the Helsinki University Central Hospital, Finland, between 1994 and 2008. In the first part of the thesis, we studied 103 patients with intracranial artery dissections (IAD). IADs could be divided into 2 distinct groups: i) non-aneurysmatic IADs presenting without subarachnoid hemorrhage that are associated with favorable outcomes and safe anticoagulant therapy, and ii) aneurysmatic IADs, characterized by subarachnoid hemorrhage and poorer prognosis. Secondly, we evaluated characteristics, prognostic factors and vascular risk factors in 301 CeAD patients. We found association of CeAD with male sex, and possible association with smoking and migraine, especially migraine with aura. Stroke severity and recent infection were associated with poorer outcome. The three other publications for the thesis were part of the CADISP project (Cervical Artery Dissection and Ischemic Stroke Patients), an international consortium focusing on research on CeAD. For the clinical part of CADISP, 983 patients with CeAD, 658 patients with ischemic stroke due to causes other than dissection, and 1170 healthy control subjects were included in 8 countries and 18 centers. In the CADISP cohort, vascular risk factors were less frequent in CeAD patients compared with young patients with a non-CeAD ischemic stroke. In comparison with healthy controls, hypercholesterolemia, obesity, and overweight were less frequent in CeAD patients, whereas CeAD patients had more hypertension. This suggests that hypertension may be a risk factor for CeAD. Finally, migraine was more common in CeAD patients with stroke than in patients with ischemic stroke due to a cause other than CeAD. We detected no excess of ischemic strokes, specific arterial distribution or other clinical or prognostic features characteristic to migraineous CeAD patients compared to those without migraine.Kaula- ja aivovaltimodissektoituma on yleisimpiä aivoinfarktin aiheuttajia nuorilla ja keski-ikäisillä potilailla. Taudin patofysiologia tunnetaan puutteellisesti. Potilailla ajatellaan olevan altistava valtimoseinämän sidekudoksen rakenteellinen heikkous, mahdollisesti geneettisistä syistä. Heikko seinämä on alttiimpi repeämälle, jonka laukaisee jokin tilapäinen tekijä kuten akuutti tulehdustauti, vähäpätöinen vamma tai migreeni. Väitöskirjan kaksi ensimmäistä osatyötä perustuu Helsingin ja Uudenmaan sairaanhoitopiirin alueella vuosien 1994-2008 välisenä aikana hoidetuista kaula- ja aivovaltimodissektoitumapotilaista kerättyyn rekisteriin. Ensimmäisessä osatyössä oli mukana 103 kallonsisäisen dissektoituman sairastanutta potilasta. Nämä dissektoitumat jakaantuivat kahteen eri ryhmään: i) ei-aneurysmaattisiin kallonsisäisiin dissektoitumiin, jotka eivät johtaneet lukinkalvonalaiseen vuotoon, joiden ennuste oli hyvä, ja joiden hoidossa verenohennuslääkkeet olivat turvallisia. ii) Lukinkalvonalaiseen vuotoon johtaneisiin dissektoitumiin, joilla oli huono ennuste. Toisessa osatyössä käsiteltiin kaula- ja aivovaltimodissektoitumapotilaiden taudinkuvaa, ennustetekijöitä ja riskitekijöitä 301 suomalaisen potilaan aineistossa. Enemmistö potilaista oli miehiä, ja dissektoitumapotilailla tupakointi ja migreeni, erityisesti aurallinen migreeni, olivat yleisiä. Vakava aivoinfarkti ja viimeaikaiset tulehdustaudit liittyivät huonompaan ennusteeseen. Kolme muuta osatyötä ovat osa CADISP-projektia (Cervical Artery Dissection and Ischemic Stroke Patients). Tämän kansainvälisen kaulavaltimodissektoitumien tutkimukseen keskittyvän hankkeen tavoitteet ovat selvittää taudin geneettisiä ja muita riskitekijöitä, sen hoitoa ja ennustetekijöitä. CADISP-hankkeen kliiniseen osaan osallistui 8 maasta 18 keskuksesta 983 kaulavaltimodissektoitumapotilasta, 658 aivoinfarktiverrokkia joilla infarkti johtui muusta syystä kuin dissektoitumasta, ja 1170 tervettä henkilöä. CADISP-aineistossa sydän- ja verisuonitautien riskitekijöitä oli kaulavaltimodissektoitumapotilailla vähemmän kuin aivoinfarktin muusta syystä sairastaneilla verrokeilla. Terveisiin verrokkeihin nähden dissektoitumapotilailla oli harvemmin kohonneita kolesteroliarvoja ja ylipainoa, mutta useammin korkea verenpaine. Hypertensio saattaakin olla kaulavaltimodissektoituman riskitekijä. Viidennessä osatyössä todettiin migreenin olevan yleisempää aivoinfarktin saaneilla kaulavaltimodissektoitumapotilailla kuin muusta syystä aivoinfarktin saaneilla verrokeilla. Migreeniä sairastavat kaulavaltimodissektoitumapotilaat eivät eronneet migreeniä sairastamattomista aivoinfarktien yleisyyden, dissektoituneen valtimon, taudinkuvan tai ennusteen suhteen

Migraine, Stroke, and Cervical Arterial Dissection Shared Genetics for a Triad of Brain Disorders With Vascular Involvement

Background and Objectives Migraine, stroke, and cervical artery dissection (CeAD) represent a triad of cerebrovascular disorders with pairwise comorbid relationships and vascular involvement. Larger samples and recent advances in methodology invite systematic exploration of their shared genetics. Methods Genetic analyses leveraged summary statistics from genome-wide association studies of the largest available samples of each disorder, including subtypes of stroke (ischemic stroke, large artery stroke, small vessel stroke, and cardioembolic stroke) and migraine (with aura and without aura). For each pair of disorders, genetic correlation was assessed both on a genome-wide basis and within independent segments across the genome including known specific loci for each disorder. A cross-trait meta-analysis was used to identify novel candidate loci. Finally, potential causality of migraine susceptibility on stroke and CeAD was assessed by Mendelian randomization. Results Among all pairs of disorders, genome-wide genetic correlation was observed only between CeAD and migraine, particularly MO. Local genetic correlations were more extensive between migraine and CeAD than those between migraine and stroke or CeAD and stroke and revealed evidence for novel CeAD associations at rs6693567 (ADAMTSL4/ECM1), rs11187838 (PLCE1), and rs7940646 (MRVI1) while strengthening prior subthreshold evidence at rs9486725 (FHLS) and rs650724 (LRP1). At known migraine loci, novel associations with stroke had concordant risk alleles for small vessel stroke at rs191602009 (CARP) and for cardioembolic stroke at rs55884259 (NKX2-5). Known migraine loci also revealed novel associations but with opposite risk alleles for all stroke, ischemic stroke, and small vessel stroke at rs55928386 (HTRA1), for large artery stroke at rs11172113 (LRP1), and for all stroke and ischemic stroke at rs1535791 and rs4942561 (both LRCH1), respectively. rs182923402 (near PTCH1) was a novel concordant locus for migraine and cardioembolic stroke. Mendelian randomization supported potential causal influences of migraine on CeAD (odds ratio [95% confidence interval] per doubling migraine prevalence = 1.69 [1.24-2.3], p = 0.0009) with concordant risk, but with opposite risk on large artery stroke (0.86 [0.76-0.96], p = 0.0067). Discussion The findings emphasize shared genetic risk between migraine and CeAD while identifying loci with likely vascular function in migraine and shared but opposite genetic risk between migraine and stroke subtypes, and a central role of LRP1 in all 3 cerebrovascular disorders.Peer reviewe

TTR kuvastaa varfariinihoidon laatua

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TTR kuvastaa varfariinihoidon laatua

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Helsinki experience on nonvitamin K oral anticoagulants for treating cervical artery dissection

BackgroundCervical artery dissection (CeAD) patients with or without stroke are frequently treated with either antiplatelet agents or vitamin K antagonists (VKAs), but few data are reported on the use of nonvitamin K oral anticoagulants (NOACs). MethodsBetween November 2011 and January 2014, we recorded data from patients with a stroke due to vertebral (VAD) or internal carotid artery dissection (ICAD). Patients using oral anticoagulants were included in the study and were divided into two treatment groups: patients using NOACs and those using VKAs. Excellent outcome was defined on modified Rankin Scale (mRS) 1 at 6months. ResultsOf 68 stroke patients (67% male; median age 45 [39-53]), six (8.8%; two with VAD and four with ICAD) were treated with NOACs: three with direct thrombin inhibitor dabigatran and three with direct factor Xa inhibitor rivaroxaban. National Institutes of Health Stroke Scale score at baseline was 4 (3-7) in the NOAC versus 2 (1-7) in the VKA groups. Complete recanalization at 6months was seen in most patients in the NOAC (n=5; 83%) and VKA (n=34; 55%) groups. All the patients using NOACs had mRS 1 at 6months and none had an intracerebral hemorrhage (ICH). In the VKA group most patients (n=48; 77%) had mRS 1, one patient (1.7%) had an ICH and one died. ConclusionsIn this small, consecutive single-center patient sample treating ischemic stroke patients with CeAD with NOACs did not bring up safety concerns and resulted in similar, good outcomes compared to patients using VKAs.Peer reviewe

HDL enhances oxidation of LDL in vitro in both men and women

Background Oxidative modification of low-density lipoprotein (LDL) is a key event in the oxidation hypothesis of atherogenesis. Some in vitro experiments have previously suggested that high-density lipoprotein (HDL) co-incubated with LDL prevents Cu2+-induced oxidation of LDL, while some other studies have observed an opposite effect. To comprehensively clarify the role of HDL in this context, we isolated LDL, HDL2 and HDL3 from sera of 61 free-living individuals (33 women and 28 men). Results When the isolated LDL was subjected to Cu2+-induced oxidation, both HDL2 and HDL3 particles increased the rate of appearance and the final concentration of conjugated dienes similarly in both genders. Oxidation rate was positively associated with polyunsaturated fatty acid content of the lipoproteins in that it was positively related to the content of linoleate and negatively related to oleate. More saturated fats thus protected the lipoproteins from damage. Conclusion We conclude that in vitro HDL does not protect LDL from oxidation, but is in fact oxidized fastest of all lipoproteins due to its fatty acid composition, which is oxidation promoting.BioMed Central Open acces

Antiplatelets versus Anticoagulants for the Treatment of Cervical Artery Dissection: Bayesian Meta-Analysis

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Valtava-hanke : Diabetesrekisterin pääraportti

Tässä raportissa kuvataan STM:n Toivo-ohjelman Valtava-hankkeen projektin "Diabetesrekisterin tietoallaspilotti" toteutusta ja tuloksia. Projekti toteutettiin vuosina 2020-2021 yhteistyössä Valtava-hankkeen Kelan projektin "Potilastiedon arkisto tietoaltaaseen (PTA)" sekä THL:n laaturekisterien kehittämisen projektin kanssa

Nuoren aivoinfarktipotilaan erityispiirteet

English summaryPeer reviewe

University education and cervical artery dissection

We investigated whether university education is more likely in cervical artery dissection (CeAD)-patients than in age- and sex-matched patients with ischemic stroke (IS) due to other causes (non-CeAD-IS-patients). Patients from the Cervical Artery Dissection and Ischemic Stroke Patients study with documented self-reported profession before onset of IS due to CeAD (n = 715) or non-CeAD causes (n = 631) were analyzed. In the reported profession, the absence or presence of university education was assessed. Professions could be rated as academic or non-academic in 518 CeAD and 456 non-CeAD patients. Clinical outcome at 3 months was defined as excellent if modified Rankin Scale was 0-1. University education was more frequent in CeAD-patients (100 of 518, 19.3%) than in non-CeAD-IS-patients (61 of 456, 13.4%, p = 0.008). CeAD-patients with and without university education differed significantly with regard to smoking (39 vs. 57%, p = 0.001) and excellent outcome (80 vs. 66%, p = 0.004). In logistic regression analysis, university education was associated with excellent outcome in CeAD-patients (OR 2.44, 95% CI 1.37-5.38) independent of other outcome predictors such as age (OR 0.97, 95% CI 0.84-0.99), NIHSS (OR 0.80, 95% CI 0.76-0.84) and local signs (OR 2.77, 95% CI 1.37-5.57). We observed a higher rate of university education in patients with CeAD compared with non-CeAD patients in our study population. University education was associated with favorable outcome in CeAD-patients. The mechanism behind this association remains unclear.Peer reviewe