Hanne Ellekjær

Epidemiology of Stroke in Innherred, Norway, 1994 to 1996 Incidence and 30-Day Case-Fatality Rate

BACKGROUND AND PURPOSE In Norway, as well as other industrialized countries, mortality from stroke has declined over the past decades. Data on stroke morbidity are lacking. This study was conducted to determine the incidence, case fatality, and risk factors of stroke in a defined Norwegian population. METHODS During the period 1994 to 1996, a population-based stroke registry collected uniform information about all cases of first-ever and recurrent stroke occurring in people aged > or = 15 years in the region of Innherred in the central part of Norway (target population 70,000), where the prevalence of cardiovascular risk factors was screened in 1984 to 1986 and 1995 to 1997. RESULTS During the 2 years of registration (September 1, 1994, to August 31, 1996), 432 first-ever (72.8%) and 161 recurrent (27.2%) strokes were registered. The crude annual incidence rate was 3.12/1000 (2.85/1000 for males and 3.38/1000 for females). Adjusted to the European population, the annual incidence rate of first-ever stroke was 2.21/1000. The annual incidence rate of cerebral infarction was 2.32/1000, intracerebral hemorrhage 0.32/1000, subarachnoid hemorrhage 0.19/1000, and unspecified stroke 0.38/1000. The 30-day case-fatality rate was 10.9% for cerebral infarction, 37.8% for intracerebral hemorrhage, and 50.0% for unspecified stroke. Fourteen percent of the patients were found outside the hospital, and only 50% of the suspected stroke cases in the hospital (at admission or reviewed discharge diagnosis of ICD-9 codes 430 to 438) fitted the final inclusion criteria. CONCLUSIONS This first population-based stroke register in Norway revealed incidence rates of stroke similar to other Scandinavian countries, and comparison between other European countries did not indicate regional variations within Western Europe.

Physical Activity and Stroke Mortality in Women Ten-Year Follow-Up of the Nord-Trøndelag Health Survey, 1984–1986

BACKGROUND AND PURPOSE Few studies have reported a protective effect of physical activity on stroke in women, particularly among elderly women. This study was conducted to examine the association between different levels of leisure-time physical activity and stroke mortality in a large prospective study of middle-aged and elderly women. METHODS We conducted a 10-year mortality follow-up of women aged >/=50 years, free from stroke at baseline (n=14 101), who participated in the Nord-Trondelag Health Survey in Norway during 1984-1986. Main outcome measures were relative risk of stroke mortality according to increasing levels of physical activity, with the least active group used as reference. RESULTS In groups aged 50 to 69, 70 to 79, and 80 to 101 years, the relative risk of dying decreased with increasing physical activity, after adjustment for potentially confounding factors. In groups aged 50 to 69 and 70 to 79 years, the most active women had an adjusted relative risk of 0. 42 (95% CI, 0.24 to 0.75) and 0.56 (95% CI, 0.36 to 0.88), respectively. In the group aged 80 to 101 years, there was a consistent negative association with physical activity; the adjusted relative risk for the most active was 0.57 (95% CI, 0.30 to 1.09). CONCLUSIONS Physical activity was associated with reduced risk of death from stroke in middle-aged and elderly women. This association persisted after we excluded individuals with prevalent cardiovascular and cerebrovascular disease at baseline and women who died during the first 2 years of follow-up. These observations strengthen the evidence that physical activity should be part of a primary prevention strategy against stroke in women.

Microalbuminuria and All-Cause Mortality in Treated Hypertensive Individuals Does Sex Matter?: The Nord-Trøndelag Health Study (HUNT), Norway

Background—In hypertensive individuals, few prospective studies are available in which the association between microalbuminuria (MA) and all-cause mortality in the 2 sexes have been studied within the same population. Methods and Results—We conducted a 4.3-year follow-up of 2307 men and 3062 women (≥20 years old) with self-reported treated hypertension, all identified in the Nord-Trøndelag Health Study (HUNT), Norway, 1995 to 1997 (n=65 258). The main outcome measures were relative risk (RR) of all-cause mortality according to increasing albuminuria, defined at different levels of albumin-to-creatinine ratio (ACR). There was a consistent positive association between increasing ACR and all-cause mortality in men. The adjusted RR for ACR in the fourth quartile (≥1.70 mg/mmol) was 1.6 (95% CI, 1.0 to 2.6), compared with ACR in the first quartile (<0.55 mg/mmol). The corresponding RR in women was 1.5 (95% CI, 0.8 to 3.1). We found a positive association between mortality and increasing number of urine samples with ACR above different cutoff levels, especially in men. In 3 urine samples, the lowest ACR level associated with mortality in men was 0.86 mg/mmol, RR 1.6 (95% CI, 1.1 to 2.4). The sex differences persisted after exclusion of those who died during the first year of follow-up, those with hypertension not treated optimally, and those with known cardiovascular disease. Conclusions—The association between ACR and all-cause mortality was stronger in treated hypertensive men than in women. The persistent sex differences indicate that hypertensive women tolerate MA better than men and that MA in women should be interpreted differently than in men.

Functional Outcome After Common Poststroke Complications Occurring in the First 90 Days

Background and Purpose— The aim of this study was to explore the associations of common medical complications with functional outcome at 90 days post stroke. Methods— Patients with unselected acute stroke were included and observed for 16 predefined complications during the first week. Fifty percent (244 patients) were allocated to follow-up of 13 complications until 90 days and then assessed with the modified Rankin Scale 90. Common complications were defined as complications with frequencies of ≥5%. Ordinal logistic regression (worsened outcome), as well as binary logistic regression for severe dependency and death (modified Rankin Scale score>3) was performed. Results— Seven of the 13 complications occurred at a frequency ≥5%. Recurrent stroke and chest infection were found to have an odds ratio for worsened outcome of 7.45 (95% confidence interval, 2.83–20.96; P<0.0001) and 3.28 (95% confidence interval, 1.16–9.29; P=0.025), respectively. Infections other than chest infections and urinary tract infections had an odds ratio for worsened outcome of 1.59 (95% confidence interval, 1.12–2.24; P=0.009) and falls an odds ratio of 1.43 (95% confidence interval, 1.06 to 1.93; P=0.021). Myocardial infarction, urinary tract infections, and pain were not associated with a worsened outcome in terms of modified Rankin Scale 90. Conclusions— Recurrent stroke and chest infections were strongly associated with a worsened outcome. Other infections and falls were associated with less worsening. For myocardial infarction, urinary tract infections, and pain no association with functional outcome was found. Active strategies for prevention and early treatment of the first 2 complications seem advisable; patient monitoring as part of comprehensive stroke unit care should ensure timely identification and treatment of all complications.

Comparison of the validity of stroke diagnoses in a medical quality register and an administrative health register

Aims: Health registers are essential sources of data used in a wide range of stroke research, including epidemiological, clinical and healthcare studies. Regardless of the type of register, the data must be of high quality to be useful. In this study, we investigated and compared the correctness and completeness of the Norwegian Patient Register (an administrative health register) and the Norwegian Stroke Register (a medical quality register for acute stroke). Methods: We reviewed the medical records for 5192 admissions to hospital in 2012 and defined cases of stroke in the two registers as true positive, false positive, true negative or false negative. We calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value with 95% confidence intervals assuming a normal approximation of the binomial distribution. Results: The Norwegian Stroke Register was highly correct and relatively complete (sensitivity 88.1%, specificity 100% and PPV 98.6%). The Norwegian Patient Register was more complete, but less correct, when we included both the main and secondary diagnoses of stroke (sensitivity 96.8%, specificity 99.6% and PPV 79.7%); restricting the analyses to the main diagnoses of stroke resulted in less complete and more correct registrations (sensitivity 86.1%, specificity 99.9% and PPV 93.5%). Conclusions: The Norwegian Stroke Register and the Norwegian Patient Register are adequately complete and correct to serve as valuable sources of data for epidemiological, clinical and healthcare studies, as well as for administrative purposes.

Trends in use of warfarin and direct oral anticoagulants in atrial fibrillation in Norway, 2010 to 2015

PurposeSince 2011, several direct oral anticoagulants (DOACs; dabigatran, rivaroxaban, apixaban) have been introduced as alternatives to warfarin for stroke prophylaxis in atrial fibrillation. We wanted to investigate changes in utilization of oral anticoagulants for atrial fibrillation in Norway following the introduction of DOACs.MethodsUsing nationwide registries, we identified all adults with pharmacy dispensings for warfarin or DOACs between January 2010 and December 2015 in Norway, and used ambulatory reimbursement codes to identify atrial fibrillation as indication. We defined incident use by a 1-year washout period. We describe trends in prevalent and incident use of warfarin and DOACs between 2010 and 2015, as well as patterns of treatment switching for incident users.ResultsOne hundred twenty-nine thousand two hundred eighty-five patients filled at least one prescription for an oral anticoagulant for atrial fibrillation; the yearly number of incident users increased from 262 to 421 per 100,000 person-years; and the yearly share of incident users who initiated a DOAC increased to 82%. Half the prevalent users were on a DOAC by 2015. Within a year of drug initiation, 6, 12, 16 and 20% of incident users of apixaban, rivaroxaban, warfarin and dabigatran, respectively, switched oral anticoagulant.ConclusionsUse of DOACs for anticoagulation in atrial fibrillation became more prevalent between 2010 and 2015 in Norway, at the expense of warfarin.

Mechanisms, predictors and clinical impact of early neurological deterioration: the protocol of the Trondheim early neurological deterioration study

Background10-40% of patients with acute ischemic stroke (AIS) suffer an early neurological deterioration (END), which may influence their long term prognosis. Multiple definitions of END exist, even in recently published papers. In the search for causes, various biochemical, clinical, and imaging markers have been found to be associated to END after AIS in some but not in other studies.The primary aim of this study is to assess the contribution of END to functional level at 3 months post stroke measured by modified Rankin Scale (mRS). Secondary aims are to identify factors and mechanisms associated with END and to define the prevalence, degree and timing of END in relation to stroke onset, and to compare Scandinavian Stroke Scale (SSS) and National Institute of Health Stroke Scale (NIHSS) based END-definitions.We hypothesized that END detected by changes in NIHSS and SSS (according to previously published criteria) at a threshold of 2 points indicate worsened prognosis, and that SSS is not inferior to NIHSS in predicting such a change. We further hypothesized that clinical deterioration has several causes, including impaired physiological homeostasis, vascular pathology, local effects and reactions secondary to the ischemic lesion, along with biochemical disturbances.MethodsSingle-centre prospective observational study.Participants: Previously at home-dwelling patients admitted to our stroke unit within 24 hours after ictus of AIS are included into the study, and followed for 3 months. They are managed according to current procedures and national guidelines. A total of 368 patients are included by the end of the enrolment period (December 31st 2013), and the material will be opened for analysis by June 30th 2014.Frequent neurological assessments, continuous monitoring, and repeated imaging and blood samples are performed in all patients in order to test the hypotheses.DiscussionStrengths and weaknesses of our approach, along with reasons for the methods chosen in this study are discussed.

Validation of self-reported and hospital-diagnosed atrial fibrillation: the HUNT-study

Background Self-reported atrial fibrillation (AF) and diagnoses from hospital registers are often used to identify persons with AF. The objective of this study was to validate self-reported AF and hospital discharge diagnoses of AF among participants in a population-based study. Materials and methods Among 50,805 persons who participated in the third survey of the HUNT Study (HUNT3), 16,247 participants from three municipalities were included. Individuals who reported cardiovascular disease, renal disease, or hypertension in the main questionnaire received a cardiovascular-specific questionnaire. An affirmative answer to a question on physician-diagnosed AF in this second questionnaire defined self-reported AF diagnoses in the study. In addition, AF diagnoses were retrieved from hospital and primary care (PC) registers. All AF diagnoses were verified by review of hospital and PC medical records. Results A total of 502 HUNT3 participants had a diagnosis of AF verified in hospital or PC records. Of these, 249 reported their AF diagnosis in the HUNT3 questionnaires and 370 had an AF diagnosis in hospital discharge registers before participation in HUNT3. The sensitivity of self-reported AF in HUNT3 was 49.6%, specificity 99.2%, positive predictive value (PPV) 66.2%, and negative predictive value (NPV) 98.4%. The sensitivity of a hospital discharge diagnosis of AF was 73.7%, specificity 99.7%, PPV 88.5%, and NPV 99.2%. Conclusion Use of questionnaires alone to identify cases of AF has low sensitivity. Extraction of diagnoses from health care registers enhances the sensitivity substantially and should be applied when estimates of incidence and prevalence of AF are studied.

Stroke in Norway

In Norway, as in several other countries, a decreasing mortality from stroke has occurred during recent decades. The aim of this article is to discuss the decreasing stroke mortality that could be explained by either reduced incidence or case-fatality or both based on epidemiological data and information about the current stroke service. The mortality statistics from the Norwegian Cause of Death Register shows a steady decline since the 1960s (Fig. 1) (1). In age groups below 65 years the decline started even earlier. Agestandardized stroke mortality for all age groups combined was 74 and 59 per 100 000 per year in men and women, respectively, 2001–2005; compared with 207 and 204, respectively, in 1961– 1965, a decrease of 65–70%. Even from 2000 to 2005 stroke mortality decreased by 23–24%. The numbers of deaths from stroke decreased from 5220 in 1996 to 3688 in 2005 (2). Based on data from the Innherred Stroke Registry 1994– 1996, the stroke incidence was estimated to three per thousand in age group 151, giving a number of 11 000 first-ever strokes and 3500 recurrent stroke in Norway annually (Fig. 2) (3). Trend studies from other Nordic countries show conflicting results with both increasing and decreasing incidence (4). Change in time trends may reflect risk factor modification, but methodological problems must also be taken into consideration. Data from the Norwegian Patient Register shows that the number of hospitalized stroke patients increased from 11 000 to 12 000 a year during the period 2000–2005 (5). It is not known, whether the increase reflects a higher stroke morbidity in the population or is due to increasing hospitalisation rate, changing coding practice or better detection rate. A change in the prevalence of traditional risk factors might be reflected in the incidence of stroke. Large population-based Norwegian health surveys have shown a decline in blood pressure since the 1960s (4, 6). A decrease in the prevalence of daily smoking has also been observed, from 50% in men and 30% in women aged 16–74 years in 1973 to 24% in both genders in 2006 (7). Treatment with antihypertensive and antithrombotic drugs has increased considerably since the 1970s (8). In the population-based study from Innherred in Norway, the overall 30-day case-fatality for first-ever stroke was 19%,

Does moderate drinking increase the risk of atrial fibrillation? The norwegian HUNT (Nord-Trøndelag Health) study

Background Compelling evidence suggests that excessive alcohol consumption increases the risk of atrial fibrillation (AF), but the effect of light‐moderate alcohol consumption is less certain. We investigated the association between alcohol consumption within recommended limits and AF risk in a light‐drinking population. Methods and Results Among 47 002 participants with information on alcohol consumption in a population‐based cohort study in Norway, conducted from October 2006 to June 2008, 1697 validated AF diagnoses were registered during the 8 years of follow‐up. We used Cox proportional hazard models with fractional polynomials to analyze the association between alcohol intake and AF. Population attributable risk for drinking within the recommended limit (ie, at most 1 drink per day for women and 2 drinks per day for men without risky drinking) compared with nondrinking was also calculated. The average alcohol intake was 3.8±4.8 g/d. The adjusted hazard ratio for AF was 1.38 (95% confidence interval, 1.06–1.80) when we compared participants consuming >7 drinks per week with abstainers. When we modeled the quantity of alcohol intake as a continuous variable, the risk increased in a curvilinear manner. It was higher with heavier alcohol intake, but there was virtually no association at <1 drink per day for women and <2 drinks per day for men in the absence of risky drinking. The population attributable risk among nonrisky drinkers was 0.07% (95% confidence interval, −0.01% to 0.13%). Conclusions Although alcohol consumption was associated with a curvilinearly increasing risk of AF in general, the attributable risk of alcohol consumption within recommended limits among participants without binge or problem drinking was negligible in this population.