Trends in Stroke Incidence in High-Income Countries in the 21st Century

Population-Based Study and Systematic Review

Linxin Li, DPhil; Catherine A. Scott, BMBCh; Peter M. Rothwell, FMedSci

Disclosures

Stroke. 2020;51(5):1372-1380. 

In This Article

Methods

Requests for access to data from the OXVASC (Oxford Vascular Study) will be considered by the corresponding author.

Study Population

OXVASC is an ongoing prospective population-based study of the incidence and outcome of all acute vascular events in a mixed rural/urban population. The study population comprises all 92 728 individuals, irrespective of age, registered with ≈100 general practitioners in 9 general practices in Oxfordshire, United Kingdom. Ascertainment of acute vascular events started on April 1, 2002, and is ongoing. This analysis reports all first-ever incident strokes during the first 15 years (2002–2017).

The detailed study methodology and case definitions have been published before (Methods in the Data Supplement), and multiple overlapping methods of hot and cold pursuit were used to achieve near complete and consistent ascertainment of all individuals with stroke.[19,20] To ensure consistency, one senior stroke neurologist (P.M.R.) has prospectively reviewed all cases over the 15 years. Stroke was defined as an event with appropriate symptoms lasting >24 hours.

Stroke incidence in OXVASC was also compared with that in OCSP (Oxfordshire Community Stroke Project), which was a high-quality, population-based study of all first-ever strokes in 1981 to 1986 in the same general practice population. The methodology of OCSP has also been published before (Methods in the Data Supplement),[21] and the case diagnosis, assessment, and follow-up were similar to those in OXVASC. In particular, to ensure consistency of clinical diagnosis between OCSP and OXVASC, summaries of all potential cases in the first 2 years of OXVASC were reviewed by the principal investigator of OCSP to ensure that the application of definitions of strokes was comparable between the 2 studies.[19]

In both OCSP and OXVASC, patients were ascertained and assessed face-to-face by study physicians as soon as possible after the initial presentation in hospital, an emergency clinic, or at home. If a patient died before assessment, we obtained an eyewitness account of the clinical event and reviewed any relevant clinical records. In OCSP, brain computed tomography or autopsy was the first-line imaging modality, and 12% of the cases did not have brain imaging or autopsy. In OXVASC, patients routinely had brain imaging (computed tomography or magnetic resonance), vascular imaging (carotid Doppler or computed tomography angiography/magnetic resonance angiography or digital subtraction angiography), 12-lead electrocardiography, and standard blood tests. Echocardiography, 24-hour ECG (Holter), and 5-day ambulatory ECG monitoring were done when clinically indicated. Less than 5% of the cases in OXVASC did not have any brain imaging or autopsy.

All patients were followed up face-to-face at 1, 6, 12, 60, and 120 months by a study nurse or physician to determine their functional status (modified Rankin Scale [mRS]).[22] Disabling or fatal stroke is defined as a new disability (mRS score, >2) or death or progression of disability (1 score increase in mRS) in those with premorbid disability (premorbid mRS score, >2) using the 1-month mRS. For patients who had moved out of the study area, follow-up was performed by telephone or email. All patients were flagged for the Office for National Statistics mortality data, and all deaths during follow-up were recorded with causes.

Systematic Review

We followed the PRISMA guideline and identified all stroke incidence and prevalence studies referenced in previous published reviews and hand-searched PUBMED and EMBASE for any follow-up or secondary studies using the author and study names from the primary studies. We also performed a further search of PUBMED (1950 to December 2017) and EMBASE (1974 to December 2017) using the following search terms without restrictions: "exp STROKE/" or "first ever stroke*.ti,ab." and "incidence/" or "registries/." The abstracts of all articles identified from initial searches were reviewed by 2 authors (L.L. and C.A.S.), and both authors reviewed the full text of all eligible studies. In cases of disagreement about the eligibility of studies or data extraction, consensus was reached through joint reassessment.

Studies were included in the main analysis if they fulfilled the following criteria: (1) published incidence studies satisfying the quality criteria of ideal population-based study;[23,24] (2) conducted in high-income countries;[10] (3) reported stroke incidence, incidence rate ratio (IRR) or raw numbers sufficient to calculate incidence, or change in incidence at ≥2 time periods; (4) reported stroke incidence between 1990 (±5 years) and 2017, with the latest time period after 2010; and (5) English language. Studies that fulfilled criterias 1 to 3 and reported the latest time point between year 2000 and 2010 were also included in subgroup analyses. Population-based studies confined to only one pathological stroke subtype were excluded. Where there was >1 publication on a cohort of patients, data on incidence rate (IR) were taken from the most recent publication or the publication with the most complete raw numbers. Updated data from OXVASC were also included.

Information was extracted from each report on the population studied, study period (duration), observed person-years, and the total number of incident stroke cases. Where possible, we also documented the reported numbers of incident stroke cases by sex, stroke subtype (ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage), and stroke severity (disabling/fatal versus nondisabling). Where available, crude and standardized IRs with CIs, as well as raw numbers (numerator, n, and denominator, N), were extracted for each time period reported. Where IR, n, or N were not reported, when possible, these were calculated based on reported IRR.

Statistical Analyses

For Oxfordshire and other included studies, age-specific crude IRs (per 100 000 population/year) were calculated with CIs estimated assuming a Poisson distribution. For studies that reported stroke incidence in different age groups, sexes, ethnicities, or stroke subgroups, where raw numbers were not available, we used inverse-variance weighted fixed-effects meta-analysis to generate summary IRs.

All crude IRs were standardized to the European population using the direct method.[25] Standardized relative IRRs were then calculated for the chosen 2 periods within each study using Poisson regression models adjusting for the age structure of the 2 populations. IRRs from individual studies were then pooled with inverse-variance weighted random-effects meta-analysis to generate a pooled IRR with 95% CIs. We estimated the percentage of variability across studies attributable to heterogeneity beyond chance using the I2 statistic.

In the main analysis, pooled estimates for temporal trends of stroke incidence between 1990s and 2010s were calculated. We also performed subgroup analyses stratified by stroke subtypes (ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage), sex, stroke severity (disabling/fatal versus nondisabling), and study periods (1990–2000 versus after year 2000). Sensitivity analyses were also performed in relation to study duration.

Finally, to estimate the number of incident stroke patients on a national basis in the United Kingdom from 2015 up to 2045, we used the age-specific incidence during 2014 to 2017 in OXVASC for standardization to the projected UK population.[26] Two different scenarios for changes in age-specific incidence were used: stable rates over time or maintaining the current 6% decrease every 5 years. Moreover, we calculated how much the incidence would have to decrease every 5 years to maintain a stable number of incident stroke patients in the United Kingdom in 2045 compared with 2015.

All analyses were performed using SPSS, version 22.

Standard Protocol Approvals, Registrations, and Patient Consents

Written informed consent or assent from relatives was obtained in all participants. OXVASC was approved by the local research ethics committee (OREC A: 05/Q1604/70).

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