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Aims Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk. Methods and results From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies. In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95–1.02) in group A, 0.98 (0.93–1.04) in group B, and 0.95 (0.89–1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07–1.23) in group A, 1.13 (1.05–1.22) in group B, and 1.12 (1.05–1.20) in group C. Conclusions We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals.

Supplemental material for The impact of risk factor trends on intracerebral hemorrhage incidence over the last two decades—The Tromsø Study by Maria Carlsson, Tom Wilsgaard, Stein Harald Johnsen, Liv-Hege Johnsen, Maja-Lisa Løchen, Inger Njølstad and Ellisiv Bøgeberg Mathiesen in International Journal of Stroke

OBJECTIVE: Carotid intima-media thickness (CIMT) is a marker of subclinical organ damage and predicts cardiovascular disease (CVD) events in the general population. It has also been associated with vascular risk in people with diabetes. However, the association of CIMT change in repeated examinations with subsequent CVD events is uncertain, and its use as a surrogate end point in clinical trials is controversial. We aimed at determining the relation of CIMT change to CVD events in people with diabetes. RESEARCH DESIGN AND METHODS: In a comprehensive meta-analysis of individual participant data, we collated data from 3,902 adults (age 33-92 years) with type 2 diabetes from 21 population-based cohorts. We calculated the hazard ratio (HR) per standard deviation (SD) difference in mean common carotid artery intima-media thickness (CCA-IMT) or in CCA-IMT progression, both calculated from two examinations on average 3.6 years apart, for each cohort, and combined the estimates with random-effects meta-analysis. RESULTS: Average mean CCA-IMT ranged from 0.72 to 0.97 mm across cohorts in people with diabetes. The HR of CVD events was 1.22 (95% CI 1.12-1.33) per SD difference in mean CCA-IMT, after adjustment for age, sex, and cardiometabolic risk factors. Average mean CCA-IMT progression in people with diabetes ranged between -0.09 and 0.04 mm/year. The HR per SD difference in mean CCA-IMT progression was 0.99 (0.91-1.08). CONCLUSIONS: Despite reproducing the association between CIMT level and vascular risk in subjects with diabetes, we did not find an association between CIMT change and vascular risk. These results do not support the use of CIMT progression as a surrogate end point in clinical trials in people with diabetes.

AIMS: Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk. METHODS AND RESULTS: From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies. In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95-1.02) in group A, 0.98 (0.93-1.04) in group B, and 0.95 (0.89-1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07-1.23) in group A, 1.13 (1.05-1.22) in group B, and 1.12 (1.05-1.20) in group C. CONCLUSIONS: We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals.

AIMS Averaged measurements, but not the progression based on multiple assessments of carotid intima-media thickness, (cIMT) are predictive of cardiovascular disease (CVD) events in individuals. Whether this is true for conventional risk factors is unclear. METHODS AND RESULTS An individual participant meta-analysis was used to associate the annualised progression of systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with future cardiovascular disease risk in 13 prospective cohort studies of the PROG-IMT collaboration (n = 34,072). Follow-up data included information on a combined cardiovascular disease endpoint of myocardial infarction, stroke, or vascular death. In secondary analyses, annualised progression was replaced with average. Log hazard ratios per standard deviation difference were pooled across studies by a random effects meta-analysis. In primary analysis, the annualised progression of total cholesterol was marginally related to a higher cardiovascular disease risk (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.00 to 1.07). The annualised progression of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol was not associated with future cardiovascular disease risk. In secondary analysis, average systolic blood pressure (HR 1.20 95% CI 1.11 to 1.29) and low-density lipoprotein cholesterol (HR 1.09, 95% CI 1.02 to 1.16) were related to a greater, while high-density lipoprotein cholesterol (HR 0.92, 95% CI 0.88 to 0.97) was related to a lower risk of future cardiovascular disease events. CONCLUSION Averaged measurements of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol displayed significant linear relationships with the risk of future cardiovascular disease events. However, there was no clear association between the annualised progression of these conventional risk factors in individuals with the risk of future clinical endpoints.

AIMS: Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk. METHODS AND RESULTS: From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies. In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95-1.02) in group A, 0.98 (0.93-1.04) in group B, and 0.95 (0.89-1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07-1.23) in group A, 1.13 (1.05-1.22) in group B, and 1.12 (1.05-1.20) in group C. CONCLUSIONS: We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals. The PROG-IMT project, which includes this publication, has been funded by the German Research Foundation (Deutsche Forschungsgemeinschaft, www.dfg.de) under the grants DFG Lo 1569/2-1 and DFG Lo 1569/2-3, received by MWL. The DFG had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Simon Thompson is supported by the British heart Foundation (CH/12/2/29428). Some of the contributing studies were funded by different parties, as listed in the acknowledgement section. Here, too, the funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Sí

Hjerte- og karsykdom er ledende årsak til død og sykelighet på verdensbasis. I Norge er det årlig ca. 13 000 hjerteinfarkt og 12 000 hjerneslag. Til tross for at den forebyggende og akuttmedisinske behandlingen er betydelig forbedret i løpet av de siste 30 år, forventes en fortsatt økning i hjerte- og karsykdommer på verdensbasis. De tradisjonelle risikofaktorene (alder, kjønn, blodtrykk, kolesterol, diabetes og røyking) har begrenset evne til å forutsi hvilke individer som har økt risiko for hjerte- og karsykdom. Det er derfor viktig å identifisere nye markører som er assosiert med økt risiko for sykdom for å kunne tilby personer med økt risiko en bedre tilpasset forebyggende behandling. Aterosklerose er bakenforliggende årsak til de fleste kliniske hendelser og er en sykdomsprosess som fører til avleiring (plakk) av fett, kalk og betennelsesceller i arterier. Aterosklerotiske plakk som sprekker kan føre til at det dannes blodpropper som tetter til pulsårer og hemmer blodtilførselen til viktige organer som hjerte og hjerne. Grad av aterosklerose kan måles med ultralyd av halskar. Mye tyder på at plakk som øker i størrelse utgjør en høyere risiko for hjerte- og karsykdom enn aterosklerose som forblir stabil over tid. Målet med denne studien var å undersøke sammenhengen mellom betennelsesmarkøren C-reaktivt protein (CRP) og andre markører i blod med utvikling av aterosklerose, samt kliniske hendelser som hjerteinfarkt og hjerneslag. Tromsøundersøkelsen er en pågående helseundersøkelse av befolkningen i Tromsø hvor deltakerne har blitt invitert til gjentatte undersøkelser. Denne avhandlingen bygger på repeterte målinger av tradisjonelle risikofaktorer, blodprøver samt ultralyd av halskar hos deltakerne i perioden 1994-2008. I tillegg er det registrert kliniske hendelser som hjerteinfarkt og hjerneslag til og med 2013. Dette har gitt oss en unik mulighet til å undersøke sammenhengen mellom markører i blodet og utviklingen av aterosklerose i halskar, samt kliniske hendelser. Vi fant at nivå av CRP i blodet var assosiert med tilstedeværelse av plakk i halskar og totalt plakkareal i tverrsnittsundersøkelse. Sammenhengen var sterkest hos menn. CRP kunne ikke forutsi fremtidig utvikling av plakk eller økning av plakkstørrelse i analyser justert for tradisjonelle risikofaktorer. Både CRP i blod og plakkstørrelse i halskar var assosiert med høyere risiko for fremtidig hjerteinfarkt og hjerneslag. De som hadde både forhøyet CRP og store plakk hadde den høyeste risiko for hjerteinfarkt og hjerneinfarkt. Ultralydundersøkelse av halskar og nivå av CRP i blodet ga tilleggseffekt utover tradisjonelle risikofaktorer når det gjaldt å identifisere individer med økt risiko for hjerte- og karsykdom. Nivå av betennelsesmarkøren interleukin-6 var forbundet med plakkvekst seks år senere. Dette tyder på at interleukin-6 kan være en nyttig markør for å identifisere pasienter med ustabile plakk.

Tema og formål Tid er hjerne. Målet med denne oppgaven var å kartlegge hvordan den prehospitale og intrahospitale tidsbruken i behandlingskjeden av hjerneslagpasienter har endret seg i perioden 2012 – 2015, og videre om dette har påvirket utkomme hos pasientgruppen. Materiale og metode Oppgaven inneholder pasientdata for alle hjerneslagpasienter innlagt UNN Tromsø i perioden 01.04.2012 – 31.12.2015 og som har møtt kriteriene for å bli registrert i Norsk Hjerneslagregister (n = 1157). Dataene er hentet fra NHR og AMIS, samt DIPS. Resultater Av studiepopulasjonens 1157 pasienter mottok 152 pasienter trombolysebehandling. Samlet gjennomsnittlig tidsbruk fra symptomdebut til innleggelse var 99,9 minutter (95% CI 89,2 – 110,1) uten statistisk signifikant forskjell mellom innleggelsesår. I 2012 var gjennomsnittlig door-to-needle time 82,7 minutter (95% CI 72,4 – 93,1), i 2015 var den redusert til 43,6 minutter (95% CI 31,6 – 55,6), en statistisk signifikant forbedring. Det ble ikke funnet forskjell i overlevelse eller funksjonsnivå ved 3 måneders oppfølging i trombolysegruppen. Diskusjon Det har skjedd en signifikant reduksjon i tidsbruken på sykehusene, men ikke prehospitalt. Dette kan skyldes økt fokus blant helsearbeiderne og bedre rutiner på helseinstitusjonene/sykehuset, mens det fortsatt ikke er like allment kjent i befolkning hvor viktig tiden er for hjernen. Større internasjonale forskningrapporter har vist klare sammenhenger mellom kortere symptomdebut til behandlingstid og økt overlevelse og funksjonsnivå. Konklusjon Den intrahospitale tidsbruken har hatt en statistisk signifikant reduksjon i undersøkelsesperioden, men analysene viser ikke en signifikant påvirkning på overlevelse eller funksjonsnivå 3 måneder etter utskrivelse mellom studiepopulasjonen.

In 2009 stroke care in the University Hospital of Northern Norway was reorganized. Until that year the hospital provided stroke care in two separate locations: patients 75 years and older were treated in the Geriatric Unit of the Medical Department while those younger were treated in the Neurological Department. Waiting times in the emergency unit were long, especially for the older patients. With the objective of reducing waiting times and offering equal service to all patients, reorganization by merging the two stroke units into one acute stroke unit was carried out. Lean methodology was applied in this process. This thesis presents and evaluates the effect of the reorganization. A medical record review of patients admitted before and after the reorganization was performed. The main findings were reductions in waiting time for CT scans and for first doctor’s visit for the geriatric patients. Furthermore, the proportion of patients receiving thrombolytic therapy increased. No major differences could be found concerning duration of hospitalization or discharge location. Thus, some of the objectives for the reorganization were achieved, while others were not.