University of Minnesota

Shiga University Studies

Year Begun: 1980
Location: Shiga, Japan
Principal Investigator: Ueshima, Hirotsugu

Epidemiological research in cardiovascular disease at the Shiga University of Medical Science is led by Hirotsugu Ueshima, and includes associate Tomonori Okamura, Yoshikuni Kita, and Takashi Kadowaki. They have formed a collaborative unit with Yasuyuki Nakamura from Kyoto Women’s University, and Akira Okayama, director of the National Cardiovascular Center.

The department of Health Science at Shiga University represents one of the bases for an international collaborative research effort, the first of which was the INTERSALT study that began in the 1980s. At that time, Ueshima was working at the Department of Preventive Cardiology at the National Cardiovascular Center and coordinated the three Japanese groups that participated in the study. Following on from the INTERSALT study, Ueshima’s group became involved in INTERMAP, an epidemiological investigation initiated in the 1990s to examine the correlation between multiple nutrients and patterns of blood pressure worldwide. Jeremiah Stamler of the United States leads the research, which includes Paul Elliot from England, Hugo Kesteloot from Belgium, and Beifan Zhou from China. Ueshima is the coordinator of the four Japanese groups involved. (Photo 1)

The INTERSALT and INTERMAP studies, through highly standardized methodology, confirmed that the average of 12 g of salt the Japanese consume per day was considerably higher than in the United States or England. Recent publications from the INTERMAP study suggest an inverse relationship between an individual’s vegetable protein intake and blood pressure level.

Previously the only multi-national epidemiologic investigation into the study of coronary artery disease was by Noboru Kimura, professor of the Department of Internal Medicine at Kurume University School of Medicine, and the Seven Countries Study led by Ancel Keys. Another multi-national epidemiologic investigation has been undertaken by Ueshima looking into subclinical coronary atherosclerosis in Japanese and American men, a collaborative effort involving Lewis Kuller and Akira. Sekikawa, from the University of Pittsburgh, David Curb, from Pacific Health Institute in Hawaii, and Chol Shin, from Korea University Medical Center. The research so far showed that although American and Japanese men aged in their 40’s now have similar blood cholesterol levels, when examined under electron-beam CT, Japanese have a lower prevalence of coronary artery calcium. Research is now being focused on finding out why this occurs, and the team is collaborating with clinicians at the Clinical Medicine at Shiga University of Medical Science. The study involves randomly sampling the people of Kusatsu, and looking into their genetics and unknown risk factors.

The group is also involved in coordinating domestic research. The NIPPON DATA 80/90 study, long term cohort studies that comprise random samples of Japanese numbering 10,000 and 8,000 with 24 years and 15 years follow-up respectively, conducted by many researchers in Japan (Tomonori Okamura, Akira Okamura, Takehito Hayakawa and others). It is still in progress today.

With the Japan Arteriosclerosis Prevention Fund, Ueshima has recruited 32 Japanese research groups to launch the Japan Arteriosclerosis Longitudinal Study, and in collaboration with Yasuo Ohashi from the University of Tokyo, they have a study population of 100,000. The research united epidemiological groups in Japan, among which there is great anticipation on finding out more about the etiology of coronary artery atherosclerosis.

There are also collaborative efforts for interventional studies. With Akira Okayama, from the National Cardiovascular Center, they are conducting a randomized controlled trial with 2,000 participants. The study aims are to improve control of hypertension, high blood cholesterol, smoking and lifestyles. The knowledge acquired from this trial is in publication so people can achieve better lifestyle practices. They are also conducting an interventional study with 7,000 participants from 12 businesses on various risk factors led by Hirotsugu Ueshima, Akira Okayama and Taichiro Tanaka. 

From 1989, Yoshikuni Kita has been a key leader in developing a cardiovascular disease registry. Records are kept of cerebrovascular and cardiovascular disease occurrence from 50,000 people that live in Shiga prefecture’s Takashima. The structure of the registry is the same as that of MONICA, making it possible to compare data internationally. It is particularly valuable as a complete region’s morbidity rate of cerebrovascular and cardiovascular disease. (H.Ueshima)


[1] Sekikawa A, et al.: Much lower prevalence of coronary calcium detected by electron-beam computed tomography among men aged 40-49 in Japan than in the US, despite a less favorable profile of major risk factors. Int J Epidemiol 34:173-9, 2005

[2] Ueshima H, et al.: Cigarette smoking as a risk factor for stroke death in Japan: NIPPON DATA80. Stroke 35:1836-41, 2004

[3] Elliott P, Stamler J, et al.: Association between protein intake and blood pressure: the INTERMAP Study. Arch Intern Med 166:79-87, 2006