WSO - April 2023 - 463

Kõrv et al.
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standard " for studying the epidemiology of stroke,14 such
studies reporting the trends in stroke incidence in younger
ages are rare.
The epidemiology of stroke has been repeatedly studied in
Tartu, Estonia. Three comprehensive stroke registries were
created in 1970-1973,15 in 1991-1993,16 and 2001-2003.17
Most recently, in 2013-2017,18 an epidemiological study was
performed in young adults of the same population.
Aims
The aim of this study was to analyze the trends in first-ever
stroke incidence in 15- to 54-year-old residents of Tartu,
Estonia, from 1991 to 2017 by comparing data from previous
population-based registries.
Methods
Study population
Tartu is the second-largest town in Estonia and houses the
only University Hospital in the country. All strokes from
South Estonia are hospitalized to the comprehensive
stroke center of the Tartu University Hospital. The mean
population of Tartu in 1991 to 1993 (first period) was
110,631
inhabitants,
in
2001-2003
(second
period)
101,122 inhabitants and in 2013-2017 (third period)
97,600 inhabitants.19
Case ascertainment
All previously conducted studies have used prospective
population-based design with multiple overlapping data
sources. The methodology used has been previously published
more extensively elsewhere18,20,21 and is described
in more detail in Supplementary material 1. The design
has been similar throughout all periods using " hot pursuit "
procedures to ascertain cases hospitalized to the
Tartu University Hospital's department of neurology combined
with " cold pursuit " to ensure completeness and
validity.
The first two periods used identical case ascertainment
procedures, with the only difference being the incomplete
availability of imaging techniques in 1991-1993. During
the third study period, we used additional novel digital
solutions for " cold pursuit " of cases: death certificates from
the Estonian Cause of Death Registry and the Estonian
Electronic Health Record (e-Health Record).22
All medical documents of the retrieved cases were
reviewed and verified by the study team.
Stroke was diagnosed based on clinical evaluation
according to the World Health Organization (WHO) definition
criteria23 and was classified into subtypes as AIS,
intracerebral hemorrhage (ICH) or subarachnoid hemorrhage
(SAH).
Statistical analysis
Incidence rates per 100,000 person-years were calculated
using population data from Statistics Estonia for relevant
age- and sex-groups. For the first study period in 1991 to
1993 mean population of Tartu was used, for the second and
third study period the population sizes of Tartu were received
from 2000 and 2011 censuses, respectively.19 Incidence
rates were standardized to the 197624 European standard
population using five-year age groups. Incidence rates
between sexes and between study periods were compared
using rate ratio (RR). Confidence intervals (CIs) to RR were
calculated using Poisson regression. CIs to the standardized
RR have been estimated by the modified F-interval method.
Trends have been calculated and presented as annual percentage
change in incidence rates and are assumed to be
constant between study periods. Comparisons were made
first versus second, second versus third, and first versus
third study period.
The mean age at onset in different study periods was
compared using the Kruskal-Wallis test. Pairwise comparisons
were made with Wilcoxon rank sum tests, and p values
were adjusted for multiple comparisons using the Holm-
Bonferroni method. Variance has been represented using
standard deviation (SD).
Statistical analysis was performed with Stata 14.2
(StataCorp, College Station, TX, USA).
Ethics approval
Ethics approval was obtained from the Research Ethics
Committee of the University of Tartu (281/M-11), the
Estonian Council on Bioethics (1.1-12/619), and the
Estonian Data Protection Inspectorate (2.2.-1/17/46).
Informed consent was obtained from patients included prospectively;
from patients included retrospectively, informed
consent was not required.
Results
There were altogether 259 first-ever strokes in 15- to
54-year-old residents of Tartu during the study period. The
proportion of strokes in females increased through the
study years from 38.3% during the first to 43.6% during the
third period. The mean age at onset decreased during the
study years being 46.6 (SD: 8.3) during the first, 45.1 (SD:
7.8) during the second and 44.3 (SD: 8.5) during the third
period (p = 0.037). There were no changes in the mean age
of first-ever stroke in men; however, in women, the mean
age decreased from 46.9 (SD: 7.3) to 42.6 (SD: 8.9) 1991
through 2017 (p = 0.022).
The overall incidence rates of first-ever stroke decreased
significantly as can be observed from Table 1. The change
happened mostly in men between the first two study periods.
For example, compared to the 1991 to 1993 study
International Journal of Stroke, 18(4)
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