Stroke is the second leading cause of global deaths and disability-adjusted life years lost worldwide; although Japan had the highest stroke mortality in 1965, it has decreased rapidly, decreasing by approximately 80% in the past four decades, while the age-adjusted stroke mortality rate has also decreased worldwide in the past two decades [1-3]. Of all strokes, subarachnoid hemorrhage (SAH) is unique in that it develops in younger age groups, and the functional prognosis tends to be worse compared with ischemic stroke and intracerebral hemorrhage [4,5]. Despite advances in diagnostic and treatment strategies, and the gradual improvement of the fatality rate, SAH still exacts high economic and social costs [4,5]. It is well known that Finland and Japan have high incidence rates of SAH compared to the rest of the world [5]. This study aimed to evaluate the incidence rate of SAH in Japan using data from a large-scale, population-based stroke registry in Shiga Prefecture, Japan, between 2011 and 2015.

The design and information regarding the Shiga Stroke and Heart Attack Registry (SSHR) has previously been described [6]. In summary, it is an ongoing population-based registry that covers approximately 1.4 million residents of Shiga Prefecture in Japan and all cases of acute stroke that occur within that population. SSHR uses central-local coordination and monitoring, combined with remote data collection and quality control systems to create an integrated surveillance system that involves the registration of cases among a network of all acute-care hospitals with neurology and neurosurgery facilities in Shiga Prefecture. All stroke cases from January 1, 2011, to December 31, 2015, were included, and a total of 1,056 first-ever patients with SAH who were residents of Shiga Prefecture were included in the final analyses. The determination of stroke, patients’ variables, and statistical analyses are shown in the Supplementary Methods [7,8]. The age- and sex-standardized incidence rates were also calculated using the direct method with the population of the 2015 Japanese vital statistics as a reference [8].

The SSHR has been approved by the Institutional Review Board of Shiga University of Medical Science (Reference number: 23-186-1) and is in accordance with the Declaration of Helsinki and the ethical standards of the responsible committee on human experimentation. Written informed consent of participants was waived due to the nature of this study.

Table 1 shows the annual distribution of patients with SAH. A total of 1,056 patients had first-ever SAH. Women were affected approximately twice as often as men for the 5-year period. The baseline characteristics of 1,056 patients are presented in Table 2. The mean age (±standard deviation) at the time of hemorrhage was 66±15 years. Regardless of sex, the worst grade (World Federation of Neurosurgical Societies [WFNS] grade=V) was observed most frequently (36.7%), followed by the mildest grade (WFNS grade=I) (28.1%). More than 80% of the patients were transported to the hospital by ambulance and hypertension was found in 55.7% of all patients. Current smokers accounted for 49.0% of men and 16.9% of women; current drinkers accounted for 54.6% of men and 12.8% of women, and 30.8% of all patients died in the acute stage. Table 3 shows the distribution of the patients according to sex and 10-year age band and the age- and sex-standardized incidence rates according to Japan Vital Statistics 2015. Patients with SAH were most often identified in the 70s age group (22.7%), followed by the 60s age group (22.6%). The age- and sex-standardized SAH incidence rate, with the population of the 2015 Japanese vital statistics as a reference, was 10.4 per 100,000 person-years (95% confidence interval [CI], 10.2 to 10.7) in men and 22.4 per 100,000 person-years (95% CI, 22.0 ro 22.8) in women.

To the best of our knowledge, these data provide an initial estimate of the overall impact of SAH and the incidence data derived from the Japanese prefectural complete enumeration registry in the 2010s for several years, where the burden of stroke has been generally higher than that of coronary heart disease [1]. The strength of this study is that a comprehensive case ascertainment protocol was used to identify non-fatal or non-hospitalized stroke cases. Determining this in a relatively large multicenter database sheds light on important aspects of patient care and can guide future research and funding. Recently, a meta-analysis showed that while worldwide SAH incidence has decreased by 40% between 1980 and 2010, SAH incidence has conversely increased by 59.1% over the last three decades in Japan [9]. In this study, the age- and sex-adjusted SAH incidence was 16.6 per 100,000 person-years (95% CI, 16.4 to 16.8), and these figures remained high compared with other countries, but were lower compared with previous Japanese registry studies; however, there are large differences in population distribution, climate, and the prevalence of risk factors between regions in Japan [8,9]. As mentioned in the meta-analysis, compared with men aged 45 to 54 years from the same region, Japanese women aged >75 years had a higher risk ratio than European women aged >75 years, and there were 362 patients (50.1%) among women aged >70 years in this study [9]. Hypothetically, this could be a consequence of the distinctly higher share of people aged ≥65 years within the total population in Japan compared with other countries; addressing the threat posed by the declining birthrate and aging population is an urgent priority for Japan, and is a challenge that has never been faced before in the world [10]. It must also be noted that most of the figures compared in the meta-analysis were obtained from hospital-based studies. Taken together, these factors suggest that further cooperation between regions and countries is desirable to encourage the establishment of nationwide registry systems, such as the nationwide Hospital Discharge Register and Causes of Death Register in Finland [11].

There are some limitations to this study. First, the present findings cannot be generalized to other Japanese regions, given the geographic and climatic disparities throughout the country. Second, there was no information on patients with stroke admitted to hospitals outside of Shiga Prefecture, which may have led to underestimating the SAH incidence rate.

In conclusion, the findings of this study underline that Japan has one of the highest SAH incidence rates in the world. The SAH incidence rate in Japan appears to be decreasing but remains high compared with that in other countries.