Divergent temporal trends in stroke incidence in younger versus older people: a systematic review, meta-analysis, and population based study

Problem

Stroke is the second leading cause of death worldwide. Stroke incidence has declined by 42% over the last four decades in high income countries. However, there have been recent reports that this trend has not been observed in younger age groups (<60 years). We aimed to confirm if stroke trends truly are diverging in younger vs. older populations, and to further explore trends in young stroke incidence by severity, gender, stroke sub-type, and study method.

Approach

We studied the temporal change of stroke incidence at age<55 years vs ≥55 years in a population based study in Oxfordshire, UK (1981-2017), stratified by severity (modified Rankin Score ≤2 vs ≥3). We incorporated the results with a systematic review using a comprehensive search of PubMed and Embase to October 2016 for published studies in high income settings, that reported stroke incidence over time (1970 onwards) in patients aged<60 years. Relative temporal change in incidence in younger vs older age groups (relative temporal rate ratio, RTTR) was calculated within each study and pooled between studies with inverse variance weighted random effects meta-analysis. Subgroup and sensitivity analysis were used to explore heterogeneity. Internal validity of included studies was assessed using a domain-based approach.

Findings

Of 16 636 abstracts screened, 37 studies reported stroke incidence trends at younger ages. Overall young stroke incidence was not following the decline seen at older ages; with a pooled age-difference in temporal trend (RTTR) of 1.59 (95% CI 1.41 to 1.78; 20 studies). The trend was consistent in population-based studies (1.70, 1.40-2.07) and for studies relying on administrative data alone (1.50, 1.29-1.75), in both male and female subgroups and most prominent for ischaemic stroke (1.62, 1.40-1.88), and after 2000 (1.49, 1.20-1.84). Explorative analysis in our population based study showed that the increase in incidence <55 years was driven by an increase in non-disabling stroke (2014-2017 vs1981-1986 IRR 2.00 (95%CI 1.23-3.26) while disabling or fatal stroke incidence did not increase at younger ages; IRR 0.88 (0.44-1.76).

Consequences

Our meta-analysis confirms that stroke incidence at younger ages has not seen the decline observed at older ages. The increasing incidence of stroke at younger ages in this study was driven by minor ischaemic events. It is reassuring that major and fatal stroke are not increasing, but it will be important to follow this carefully in the coming years. Overall trends reported in administrative based studies can mask or distort important and clinically meaningful results. Only high quality population based incidence studies allow for detailed analysis and explanation of stroke trends at the individual level. Changes in knowledge, attitudes, behaviors, risk factors, stroke investigation and ascertainment could be implicated in these divergent trends. The observation of increase in non-disabling stroke warrants further confirmation and future rates, alongside those of other diseases with shared risk factors, should be closely monitored.