Yasuhiko Wada

STUDY OBJECTIVES: To examine sex-specific associations between sleep duration and mortality from cardiovascular disease and other causes. DESIGN: Cohort study. SETTING: Community-based study. PARTICIPANTS: A total of 98,634 subjects (41,489 men and 57,145 women) aged 40 to 79 years from 1988 to 1990 and were followed until 2003. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: During a median follow-up of 14.3 years, there were 1964 deaths (men and women: 1038 and 926) from stroke, 881 (508 and 373) from coronary heart disease, 4287 (2297 and 1990) from cardiovascular disease, 5465 (3432 and 2033) from cancer, and 14,540 (8548 and 5992) from all causes. Compared with a sleep duration of 7 hours, sleep duration of 4 hours or less was associated with increased mortality from coronary heart disease for women and noncardiovascular disease/noncancer and all causes in both sexes. The respective multivariable hazard ratios were 2.32 (1.19-4.50) for coronary heart disease in women, 1.49 (1.02-2.18) and 1.47 (1.01-2.15) for noncardiovascular disease/noncancer, and 1.29 (1.02-1.64) and 1.28 (1.03-1.60) for all causes in men and women, respectively. Long sleep duration of 10 hours or longer was associated with 1.5- to 2-fold increased mortality from total and ischemic stroke, total cardiovascular disease, noncardiovascular disease/noncancer, and all causes for men and women, compared with 7 hours of sleep in both sexes. There was no association between sleep duration and cancer mortality in either sex. CONCLUSIONS: Both short and long sleep duration were associated with increased mortality from cardiovascular disease, noncardiovascular disease/noncancer, and all causes for both sexes, yielding a U-shaped relationship with total mortality with a nadir at 7 hours of sleep.

Hereditary hemorrhagic telangiectasia (HHT or Rendu-Osler-Weber syndrome) is an autosomal dominant disorder characterized by aberrant vascular development. We report here a genetic epidemiologic study in a county, A, in the Akita prefecture (population 1.2 million) located in northern Japan. Nine HHT patients who had been referred to tertiary-care hospitals were located in and near the study county. A total of 137 pedigree members were traced of which 81 were alive and 32 were affected by HHT. Complications associated with cerebral or pulmonary arteriovenous malformations were proven in six out of seven families. Linkage analysis in two large families revealed a weak yet suggestive linkage to the HHT1 locus (encoding endoglin; ENG). Three novel mutations were found in four families, all of which led to a frameshift: a G to C transversion at the splicing donor site of intron 3 (Inv3+1 G>C) in one family, one base pair insertion (A) at nucleotide 828 (exon 7) of the endoglin cDNA in two large families (c.828-829 ins A), and a four base pair deletion (AAAG) beginning with nucleotide 1120 (exon 8) of the endoglin cDNA (c.1120-1123 delAAAG) in one family. The insertion of A in exon 11 (c.1470-1471 insA) mutation found in one family has also been reported in a European family. No endoglin gene mutations were found in two families. The population prevalence of HHT in the county was estimated to be 1:8,000 approximately 1:5,000, roughly comparable with those reported in European and U.S. populations, which is contradictory to the traditional view that HHT is rare among Asians. We recommend that families with HHT be screened for gene mutations in order that high-risk individuals receive early diagnosis and treatment initiation that will substantially alter their clinical course and prognosis.

BACKGROUND: Perceived mental stress has been associated with risk of coronary heart disease (CHD) in white men, but no prospective data are available for other ethnic groups. METHODS AND RESULTS: From 1988 to 1990, a total of 73 424 Japanese (30 180 men and 43 244 women), aged 40 to 79 years, without a history of stroke, CHD, or cancer completed a lifestyle questionnaire including perception of mental stress under the Japan Collaborative Cohort Study for Evaluation of Cancer Risk Sponsored by Monbusho (JACC Study). Systematic surveillance was completed until the end of 1997, with a 580 378 person-year follow-up, and the underlying causes of death were determined according to the International Classification of Diseases, 10th revision. For women, there were 316 with total stroke, 113 with CHD, and 643 with total cardiovascular disease (CVD); for men, there were 341, 168, and 778, respectively. Women who reported high stress had a 2-fold higher age-adjusted risk of mortality from total stroke and CHD and 1.5-fold higher risk of total CVD compared with those who reported low stress. Further adjustment for known cardiovascular risk factors and selected psychological variables did not alter the associations materially. The multivariate relative risk for women who perceived high stress versus low stress was 2.24 (95% CI 1.52 to 3.31, P<0.001) for total stroke, 2.28 (95% CI 1.17 to 4.43, P=0.02) for CHD, and 1.64 (95% CI 1.25 to 2.16, P<0.001) for total CVD. For men, these relations were generally weaker but suggestive of myocardial infarction. CONCLUSIONS: Perceived mental stress was associated with increased mortality from stroke for women and with CHD for men and women.

Recent studies have suggested that vitamin D is an important determinant of prostate cancer risk and inherited polymorphisms in the 3'-untranslated region (3'UTR) of the vitamin D receptor (VDR) gene are associated with the risk and progression of prostate cancer. This study was conducted to explore the association of VDR gene polymorphisms with prostate cancer risk in Japanese men who are considered to be much less influenced by environmental risk factors for prostate cancer. We studied 222 prostate cancer patients, 209 benign prostatic hyperplasia (BPH) patients, 128 male controls who were over 60 years old and without any evidence of prostate cancer or BPH, and 198 female controls. A PCR-RFLP method was used to determine three VDR gene polymorphisms in the 3'UTR characterized by restriction enzymes BsmI, ApaI and TaqI. In the BsmI polymorphism, heterozygosity or homozygosity for the absence of the BsmI restriction site was associated with one-third the risk of prostate cancer (P < 0.0001; odds ratio, 3.31; 95% confidence interval, 2.05-5.32) and with one-half the risk of BPH (P < 0.005; odds ratio, 2.07; 95% confidence interval, 1.33-3.22) compared with the male controls. The TaqI and ApaI polymorphisms did not show any significant association with either prostate cancer or BPH. The results indicate that the BsmI polymorphism in the VDR gene plays a significant role in protection against prostate cancer and BPH. Because of the racial difference in the strength of the linkage disequilibrium between the three polymorphisms, additional studies are required to apply the present results to other racial-ethnic groups.

To examine the association of plant-based food intakes with CVD and total mortality among Japanese. In the Japan Collaborative Cohort Study for Evaluation of Cancer Risk, 25 206 men and 34 279 women aged 40-79 years, whose fruit, vegetable and bean intakes were assessed by questionnaire at baseline in 1988-90, were followed for 13 years. Deaths from total stroke, stroke subtypes, CHD and total CVD, according to the International Classification for Diseases 10th Revision, were registered. During 756 054 person-years of follow-up, there were 559 deaths from total stroke, 258 from CHD, 1207 from total CVD and 4514 from total mortality for men, and for women, 494, 194, 1036 and 3092, respectively. Fruit intake was inversely associated with mortality from total stroke (the multivariable hazard ratio (HR (95 % CI)) in the highest v. lowest quartiles = 0.67 (0.55, 0.81)), total CVD (HR = 0.75 (0.66, 0.85)) and total mortality (HR = 0.86 (0.80, 0.92)). Vegetable intake was inversely associated with total CVD (HR = 0.88 (0.78, 0.99)). Bean intake was inversely associated with other CVD (HR = 0.79 (0.64, 0.98)), total CVD (HR = 0.84 (0.74, 0.95)) and total mortality (HR = 0.90 (0.84, 0.96)). Further adjustment for other plant-based foods did not alter the association of fruit intake with mortality from total stroke, total CVD and total mortality, but attenuated the associations of vegetables and beans with mortality risk. In conclusion, intakes of plant-based foods, particularly fruit intake, were associated with reduced mortality from CVD and all causes among Japanese men and women.