Cerebrovascular disease is Japan's fourth leading cause of death, following malignant neoplasm, heart disease, and senility. The statistics from the Ministry of Health, Labor and Welfare in Japan¹ in 2020 show that there were 56,864 deaths (45.1 mortality rate per 100,000 population) due to cerebral infarction, which was higher than 31,997 deaths due to intracerebral hemorrhage and 11,416 deaths due to subarachnoid hemorrhage, although recombinant tissue plasminogen activator (rt-PA) therapy and/or thrombectomy is gaining more attention for acute ischemic stroke. The reduction of the mortality rate of cerebral infarction remains among the critical issues for a super-aging society like Japan.

Virchow's triad is a concept originally based on venous thrombus formation and has been known as a mechanism of thrombus formation. In arterial thrombus formation, the weighting of each factor is considered to be different from venous thrombus formation, but dehydration is a common causal factor of thrombosis and embolism. Dehydration causes an increase in protein concentration in the blood, resulting in blood stasis. On the other hand, human beings live under the influence of various weather changes, and can become ill under certain weather conditions, such as being prone to heatstroke under high temperature and humidity. In addition, in an anticyclone belt type, one of the atmospheric pressure distribution patterns (APDPs) in Japan, fine weather and dry air continue for several days or more, so there is a high possibility that we will easily become dehydrated if we neglect to replenish water. Therefore, we consider that there may be a link between weather changes and the Virchow's triad including the concept of dehydration. Some recent papers have highlighted a possible causal relationship between the onset of ischemic stroke and weather conditions (1, 2). Hence, this study aimed to elucidate the onset mechanism of cerebral infarction from a meteorological approach and to consider preventive methods against cerebral infarction. We focused on the APDPs peculiar to Japan in meteorology.

Management of comorbidities such as hypertension, diabetes, dyslipidemia, smoking, drinking, heart disease, and obesity is critical to prevent the development of ischemic stroke. It is known that there are differences in risk factors for each subtype of cerebral infarction. It has been reported that cardiogenic embolism was found to have a higher mean age compared with other categories (6). Hypertension is already known to be the most frequently identified risk factor in all subtypes of ischemic stroke. The Takashima Stroke Registry did not find any significant difference in the prevalence of hypertension across ischemic stroke subtypes (7). Diabetes mellitus has been reported to be more closely associated with small-vessel disease than other subtypes (8). Hypercholesterolemia is a recognized risk factor for stroke due to large-artery atherosclerosis (9). A study examining cerebral infarction by subtypes in Japanese subjects showed that there was a correlation between serum total cholesterol levels and the risk of developing cerebral infarction in large-artery occlusive infarction, but the relationship was weak in other subtypes (10). It is known that BMI may be associated with diabetes mellitus and dyslipidemia, and patients with cardiogenic embolism are often rushed to hospital by ambulance transportation because it is more sudden and serious than cerebral thrombosis. It has been reported that smoking did not show association with any particular subtype (6). In this study, the clinical characteristics of Groups A and B were consistent with these previously reported clinical characteristics of cerebral embolism and cerebral thrombosis except for smoking. The reason for “except for smoking” may be considered to be that there was a large difference in the smoking rate between Reference 6 (7.2%) and our study (48.6%).

Diseases linked to weather changes are collectively called “meteoropathy.” Meteoropathy includes migraines, arthralgia, and asthma, alongside life-threatening myocardial infarction and stroke. In Rome, Italy, climate significantly affects the risk of primary percutaneous coronary intervention for acute myocardial infarction in the current era, with a complex interplay based on the season. Higher risk is expected with lower minimum atmospheric pressure in the preceding days, lower rainfall in winter, greater changes in atmospheric pressure in spring, and higher temperatures in summer (11). Some evidence implies that weather and seasonal variations could affect stroke incidence and outcome. However, in Riyadh, Saudi Arabia, a study observed no impact of weather or seasonal variations on stroke incidence, hospital course, or outcomes (12). Weather conditions often have adverse effects on human health, but this varies by country and region; hence, investigation of the clinical data and weather data in each country and region is necessary.

Japan is an island nation with a temperate climate and has four distinct seasons (spring, summer, autumn, and winter) and characteristic APDPs. An APDP changes the direction of the wind and the flow of the air, also causing the change of the temperature and humidity. In other words, an APDP largely determines wind direction, temperature, humidity, etc., and creates typical weather conditions for each season. There are some characteristic APDPs for each season and the turn of the season, and they are demonstrated on weather charts, which are always reported along with temperature, humidity, wind speed, and wind direction in daily weather forecasts according to data provided by the Japan Meteorological Agency. The Japanese Meteorological Business Law stipulates that forecasts of phenomena must be made by certified and accredited meteorologists, who passed an examination with an average pass rate of 5.5% conducted by the designated examination institution and have been registered by the Director-General of the Japan Meteorological Agency. Then, the first author qualified as a certified and accredited meteorologist of Japan (No. 4282).

Thrombus formation is mediated by the four stages (initiation, amplification, propagation, and stabilization) of the blood coagulation cascade, centered on the key enzyme thrombin generation. AF changes this fine-tuned coagulation system and induces a pro-thrombotic state by the mechanisms outlined in Virchow's triad of blood stasis, hypercoagulability, and endothelial dysfunction, significantly increasing the risk of stroke (13). Dehydration is frequent among stroke subjects and is linked to poor outcomes (14). Ischemic stroke development may be caused by hypoperfusion, renal impairment, and hypercoagulability associated with dehydration status (15–17). Additionally, a recent study indicated that blood urea nitrogen/creatinine > 15 combined with urine specific gravity > 1.010 as a marker of dehydration status was an independent risk factor for long-term poor prognosis of thrombolyzed patients with acute ischemic stroke, implying that rapidly correcting dehydration may be among the therapy strategy in the thrombolyzed patients with acute ischemic stroke (18).

Because of differences in APDPs, weather factors such as temperature, humidity, and wind direction, as well as atmospheric pressure, inevitably change. Hence, the homeostasis of human beings living in such an unstable environment is often upset by dynamic weather changes, and arterial or intra-atrial thrombus may suddenly occur, causing ischemic stroke. In our prior research (1), we categorized the hospitalized severe cases of cerebral infarction that received rt-PA therapy for the first time into embolic and thrombotic infarction and examined the APDP at the onset day. The study demonstrated that the other high-pressure type except for the anticyclone belt type and the migratory anticyclone type was significantly more common in the thrombotic group than in the embolic group, consistent with this study. High-pressure atmospheric conditions, as suggested by the results, might be involved in thrombus formation. The duration of the other high-pressure type is relatively shorter than the migratory anticyclone type and the anticyclone belt type, so short-time pressure fluctuations may be linked to the formation of arterial thrombi.

Some recent papers have reported that prolonged living at higher altitudes, where atmospheric pressure and oxygen concentration decreased, reduced the risk of developing ischemic stroke or dying from it and increased irrigation due to angiogenesis and increased vascular perfusion might be the reason behind improved survival profiles among those living between 2,000 and 3,500 m (19, 20). Based on these reports, it can be also considered that an increase in atmospheric pressure might conversely increase the risk of cerebral infarction, which is very interesting and consistent with the present results.

Alternatively, the anticyclone belt type was significantly more common in Group A than in Group B in this study. This interesting result is the first report in the world. The anticyclone belt type defines a situation where a migratory anticyclone that has passed near Japan intensifies over the east ocean, and two or more high-pressure areas are connected to the east and west to form a belt that covers the vicinity of Japan. It often appears in spring and autumn, and on the Toyama Bay coast in Japan, land–sea breeze circulation is driven and mirages are observed on consecutive days from the coast of Uozu City. Notably, the occurrence of mirages might be associated with atmospheric currents from the southwest and an increase in temperature (21). In the anticyclone belt type, dry and sunny weather lasts for a few days to a week, triggering dehydration and increased blood viscosity in humans. It was also reported that the anticyclone belt type had the second-highest incidence of two or more myocardial infarction patients per day in Hiroshima City (22). This specific weather change in the anticyclone belt type might be a reason why embolic infarction occurred more frequently than thrombotic infarction although there may be differences in the mechanisms of occurrence between cerebral infarction and myocardial infarction. Cerebral embolism often results from dehydration (23) and blood stagnation in the left atrial, specifically in AF patients, and conversely, cerebral thrombosis is caused mainly by arteriosclerosis plus dehydration. Prevention of dehydration is considered to be a significant method for preventing the onset of cerebral infarction, since dehydration is one of the causes of cerebral embolism or cerebral thrombosis.

Even if the APDP is the same, the weather conditions are not always the same among the Hokkaido region, the Kanto region, and the Kyusyu region. Since this is a research study based on clinical data at one facility in Tokyo, Kanto region, the interpretation of this result may not be applicable to all regions in Japan. Similarly, it is unclear whether the results of this survey apply to other countries around the world, as this survey is only about the APDP in Japan and its surroundings. In this study, we first focused on the APDP so as not to see the forest for the trees, but in the future, we will focus on weather factors such as temperature, atmospheric pressure, and humidity, and their changes. Future research is warranted.

Cerebral embolism and cerebral thrombosis exhibited significant differences in APDPs on the day of onset. In the case of cerebral thrombosis, the other high-pressure type was significantly more frequent, and in the case of cerebral embolism, the anticyclone belt type was significantly more frequent. The onset of cerebral infarction may be affected by differences in APDPs. Since dehydration is among the causes of cerebral embolism or cerebral thrombosis, dehydration particularly in the other high-pressure type or in the anticyclone belt type in Tokyo, Japan, should be prevented. Further research should focus on the other meteorological factors.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by the Ethics Review Board of Fussa Hospital, Tokyo, Japan. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.

AF: study design, collection and analysis of data, and drafting the manuscript. HK, TF, and AH: revision of the manuscript for important intellectual content. All authors contributed to the article and approved the submitted version.