Neuropathologic comorbidity and cognitive impairment in the Nun and Honolulu-Asia Aging Studies.

OBJECTIVE: To examine frequencies and relationships of 5 common neuropathologic abnormalities identified at autopsy with late-life cognitive impairment and dementia in 2 different autopsy panels. METHODS: The Nun Study (NS) and the Honolulu-Asia Aging Study (HAAS) are population-based investigations of brain aging that included repeated cognitive assessments and comprehensive brain autopsies. The neuropathologic abnormalities assessed were Alzheimer disease (AD) neuropathologic changes, neocortical Lewy bodies (LBs), hippocampal sclerosis, microinfarcts, and low brain weight. Associations with screening tests for cognitive impairment were examined. RESULTS: Neuropathologic abnormalities occurred at levels ranging from 9.7% to 43%, and were independently associated with cognitive impairment in both studies. Neocortical LBs and AD changes were more frequent among the predominantly Caucasian NS women, while microinfarcts were more common in the Japanese American HAAS men. Comorbidity was usual and very strongly associated with cognitive impairment. Apparent cognitive resilience (no cognitive impairment despite Braak stage V) was strongly associated with minimal or no comorbid abnormalities, with fewer neocortical AD lesions, and weakly with longer interval between final testing and autopsy. CONCLUSIONS: Total burden of comorbid neuropathologic abnormalities, rather than any single lesion type, was the most relevant determinant of cognitive impairment in both cohorts, often despite clinical diagnosis of only AD. These findings emphasize challenges to dementia pathogenesis and intervention research and to accurate diagnoses during life.

Associations of brain lesions at autopsy with polysomnography features before death.

OBJECTIVE: To determine how sleep-disordered breathing, nocturnal hypoxia, and changes in sleep architecture in the elderly may be related to the development of the neuropathologic correlates of dementia. METHODS: The Honolulu-Asia Aging Study is a prospective cohort study of Japanese American men in Honolulu, HI. We examined brain lesions at autopsy (Braak stage, neurofibrillary tangle and neuritic plaque counts, microinfarcts, generalized brain atrophy, lacunar infarcts, Lewy bodies [LBs], neuronal loss and gliosis in the locus ceruleus) in 167 participants who underwent polysomnography in 1999-2000 (mean age, 84 years) and died through 2010 (mean 6.4 years to death). Polysomnography measures included the apnea-hypopnea index, duration of apnea or hypopnea, duration of hypoxemia, minimum oxygen saturation (SpO2), duration of slow-wave sleep (SWS, non-REM stage N3), and arousals. RESULTS: Sleep duration with SpO2 <95% was associated with higher levels of microinfarcts (adjusted odds ratio [OR] 3.88, 95% confidence interval [CI] 1.10-13.76, comparing the highest to lowest quartiles of %sleep with SpO2 <95%). Greater SWS duration was associated with less generalized atrophy (adjusted OR 0.32, 95% CI 0.10-1.03, comparing highest to lowest quartiles of %sleep in SWS). LBs were less common with greater %sleep with SpO2 <95% (adjusted OR 0.17, 95% CI 0.04-0.78, comparing highest to lowest quartiles). Higher minimum SpO2 during REM sleep was associated with less gliosis and neuronal loss in the locus ceruleus. Cognitive scores declined less among men with greater SWS duration. CONCLUSIONS: The findings support a role for lower nocturnal oxygenation and SWS in the development of microinfarcts and brain atrophy, but not Alzheimer lesions or LBs.

Antihypertensive medication use and risk of cognitive impairment: the Honolulu-Asia Aging Study.

OBJECTIVE: To determine the associations between classes of antihypertensive medication use and the risk of cognitive impairment among elderly hypertensive men. METHODS: The Honolulu-Asia Aging Study is a prospective, community-based cohort study of Japanese American men conducted in Honolulu, Hawaii. We examined 2,197 participants (mean age 77 years at cohort entry, 1991-1993, followed through September 2010) with hypertension and without dementia or cognitive impairment at baseline, who provided information on medication use. Cognitive function was assessed at 7 standardized examinations using the Cognitive Abilities Screening Instrument (CASI). Cognitive impairment was defined as a CASI score <74. RESULTS: A total of 854 men developed cognitive impairment (median follow-up, 5.8 years). ß-Blocker use as the sole antihypertensive drug at baseline was consistently associated with a lower risk of cognitive impairment (incidence rate ratio [IRR] 0.69; 95% confidence interval [CI] 0.50-0.94), as compared with men not taking any antihypertensive medications, adjusting for multiple potential confounders. The use of diuretics, calcium channel blockers, angiotensin-converting enzyme inhibitors, or vasodilators alone was not significantly associated with cognitive impairment. Results were similar excluding those with cardiovascular disease or <1 year of follow-up, and additionally adjusting for pulse pressure, heart rate, baseline and midlife systolic blood pressure, and midlife antihypertensive treatment (IRR 0.65; 95% CI 0.45-0.94). The association between ß-blocker use and cognitive impairment was stronger among men with diabetes, men aged >75 years, and those with pulse pressure ≥70 mm Hg. CONCLUSIONS: ß-blocker use is associated with a lower risk of developing cognitive impairment in elderly Japanese American men.

The Honolulu-Asia Aging Study: epidemiologic and neuropathologic research on cognitive impairment.

The Honolulu-Asia Aging Study (HAAS) is a longitudinal epidemiologic investigation of rates, risk factors, and neuropathologic abnormalities associated with cognitive decline and dementia in aged Japanese-American men. The project was established in 1991 and will be brought to closure in 2012. Age-specific rates of total dementia and the major specific types of dementia in HAAS participants are generally similar to those reported from other geographic, cultural, and ethnic populations. Risk factors for dementia in the HAAS include midlife hypertension and other factors previously shown to influence cardiovascular disease. The autopsy component of the project has yielded novel findings, the most illuminating of which is the demonstration of 5 important lesion types linked independently to cognitive impairment. While one of these--generalized atrophy--is strongly associated with both Alzheimer lesions and microinfarcts, it also occurs in the absence of these lesions and is independently correlated with dementia. Each lesion type is viewed as representing a distinct underlying pathogenic process. Their summed influences is an especially robust correlate of dementia in the months and years prior to death.

Lifestyle and the risk of dementia in Japanese-american men.

OBJECTIVES: To determine whether adhering to a healthy lifestyle in midlife may reduce the risk of dementia. DESIGN: Case-control study nested in a prospective cohort. SETTING: The Honolulu-Asia Aging Study, Oahu, Hawaii. PARTICIPANTS: Three thousand four hundred sixty-eight Japanese-American men (mean age 52 in 1965-1968) examined for dementia 25 years later. MEASUREMENTS: Men at low risk were defined as those with the following midlife characteristics: nonsmoking, body mass index (BMI) less than 25.0 kg/m(2) , physically active, and having a healthy diet (based on alcohol, dairy, meat, fish, fruits, vegetables, cereals, and ratio of monounsaturated to saturated fat). Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for developing overall dementia, Alzheimer's disease (AD), and vascular dementia (VaD), adjusting for potential confounders. RESULTS: Dementia was diagnosed in 6.4% of men (52.5% with AD, 35.0% with VaD). Examining the risk factors individually, BMI was most strongly associated with greater risk of overall dementia (OR = 1.87, 95% CI = 1.26-2.77; BMI > 25.0 vs <22.6 kg/m(2) ). All of the individual risk factors except diet score were significantly associated with VaD, whereas none were significantly associated with AD alone. Men with all four low-risk characteristics (7.2% of the cohort) had the lowest OR for overall dementia (OR = 0.36, 95% CI = 0.15-0.84). There were no significant associations between the combined low-risk characteristics and the risk of AD alone. CONCLUSION: Among Japanese-American men, having a healthy lifestyle in midlife is associated with a lower risk of dementia in late life.

Coffee intake in midlife and risk of dementia and its neuropathologic correlates.

While animal data suggest a protective effect of caffeine on cognition, studies in humans remain inconsistent. We examined associations of coffee and caffeine intake in midlife with risk of dementia, its neuropathologic correlates, and cognitive impairment among 3494 men in the Honolulu-Asia Aging Study (mean age 52 at cohort entry, 1965-1968) examined for dementia in 1991-1993, including 418 decedents (1992-2004) who underwent brain autopsy. Caffeine intake was determined according to self-reported coffee, tea, and cola consumption at baseline. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for overall dementia, Alzheimer's disease (AD), vascular dementia (VaD), cognitive impairment (Cognitive Abilities Screening Instrument score <74), and neuropathologic lesions at death (Alzheimer lesions, microvascular ischemic lesions, cortical Lewy bodies, hippocampal sclerosis, generalized atrophy), according to coffee and caffeine intake. Dementia was diagnosed in 226 men (including 118 AD, 80 VaD), and cognitive impairment in 347. There were no significant associations between coffee or caffeine intake and risk of cognitive impairment, overall dementia, AD, VaD, or moderate/high levels of the individual neuropathologic lesion types. However, men in the highest quartile of caffeine intake (>/=411.0 mg/d) [corrected] were less likely than men in the lowest quartile (

Measures of obesity and cardiovascular risk among men and women.

OBJECTIVES: This study examined associations between anthropometric measures (body mass index, waist circumference, waist-to-hip ratio, waist-to-height ratio [WHtR]) and risk of incident cardiovascular disease (CVD) (including nonfatal myocardial infarction, nonfatal ischemic stroke, and cardiovascular death). BACKGROUND: Controversy exists regarding the optimal approach to measure adiposity, and the utility of body mass index has been questioned. METHODS: Participants included 16,332 men in the Physicians' Health Study (mean age 61 years in 1991) and 32,700 women in the Women's Health Study (mean age 61 years in 1999). We used Cox proportional hazards models to determine relative risks and 95% confidence intervals (CIs) for developing CVD according to self-reported anthropometric indexes. RESULTS: A total of 1,505 CVD cases occurred in men and 414 occurred in women (median follow-up 14.2 and 5.5 years, respectively). Although WHtR demonstrated statistically the strongest associations with CVD and best model fit, CVD risk increased linearly and significantly with higher levels of all indexes. Adjusting for confounders, the relative risk for CVD was 0.58 (95% CI: 0.32 to 1.05) for men with the lowest WHtR (<0.45) and 2.36 (95% CI: 1.61 to 3.47) for the highest WHtR (>/=0.69; vs. WHtR 0.49 to <0.53). Among women, the relative risk was 0.65 (95% CI: 0.33 to 1.31) for those with the lowest WHtR (<0.42) and 2.33 (95% CI: 1.66 to 3.28) for the highest WHtR (>/=0.68; vs. WHtR 0.47 to <0.52). CONCLUSIONS: The WHtR demonstrated statistically the best model fit and strongest associations with CVD. However, compared with body mass index, differences in cardiovascular risk assessment using other indexes were small and likely not clinically consequential. Our findings emphasize that higher levels of adiposity, however measured, confer increased risk of CVD.

Blood pressure measures and risk of chronic kidney disease in men.

BACKGROUND: High blood pressure (BP) has been associated with a decrease in kidney function. However, it remains unclear which BP measure best predicts impaired kidney function. METHODS: We compared systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP) and mean arterial pressure (MAP) in predicting risk of chronic kidney disease (CKD). We prospectively followed 8093 male participants in the Physicians' Health Study, without a known history of kidney disease at baseline, who provided BP values on the baseline and 24-month questionnaires, and for whom we had creatinine measures after 14 years of follow-up. Reported BP was averaged from both questionnaires. The main outcome was CKD, defined as an estimated glomerular filtration rate <60 mL/min/1.73 m(2). We used multivariable-adjusted logistic regression to evaluate the association between BP measures and CKD and compared models using the likelihood ratio test. RESULTS: After 14 years of follow-up, 1039 men (12.8%) had CKD. An increase of 10 mmHg had corresponding multivariable-adjusted odds ratios (95% confidence intervals) of 1.11 (1.03-1.19) for SBP, 1.11 (1.00-1.23) for MAP, 1.14 (1.05-1.25) for PP and 1.05 (0.93-1.17) for DBP. SBP and PP were the strongest predictors of chronic kidney function, with equal predictive abilities. Combining BP measures did not add significantly to the prediction. CONCLUSIONS: Increases in SBP, PP and MAP were significantly associated with CKD. SBP may be the most clinically useful predictor of CKD, since no further calculations are required.

Antihypertensive adherence and drug class among Asian Pacific Americans.

OBJECTIVE: Research on adherence has emphasized the need to consider patient ethnicity when developing adherence plans. The objective of this study is to identify predictors of adherence for specific groups, particularly Asian Americans and Pacific Islanders. METHODS: We examined the factors, including drug class, associated with antihypertensive adherence for 28,395 adults in Hawaii (July 1999-June 2003) using health plan administrative data. The population included Japanese (n=13,836), Filipino (n=3,812), Chinese (n=2,280), Korean (n=450), part-Hawaiian (n=3,746) and white (n=3,920) patients. Members with antihypertensive medication in their possession >or=80% of the time were considered adherent. Multivariable logistic regression models were used to identify factors associated with adherence. RESULTS: Overall adherence rates were less than 65% among all racial/ethnic groups. After adjustment for patient age, gender, morbidity level, health plan type, isle of residence, comorbidities and year of treatment, Japanese were more likely than whites to adhere to antihypertensive therapy [OR=1.21 (1.14-1.29)], whereas Filipino [OR=0.69 (0.64-0.74)], Korean [OR=0.79 (0.67-0.93)] and Hawaiian [OR=0.84 (0.78-0.91)] patients were less likely to adhere. These results were consistent across therapeutic class. Other patient factors associated with lower adherence included younger age, higher morbidity and history of heart disease. Patient factors were also significantly related to adherence, including gender and seeing a sub-specialist. Seeing a physician of the same ethnicity did not appear to improve adherence. CONCLUSIONS: Our findings of substantial disparities among Asian Pacific American subgroups highlight the need to examine subgroups separately. Future qualitative research is needed to determine appropriate interventions, particularly for Filipino, Korean and Hawaiian patients.

Development of a risk score for colorectal cancer in men.

BACKGROUND: Colorectal cancer is a common and preventable disease for which screening rates remain unacceptably low. METHODS: We developed a risk scoring system for the development of colorectal cancer among participants in the Physician's Health Study, a prospective cohort of 21,581 US male physicians who were all free of cancer. Predictors of colorectal cancer were self-reported and identified from the baseline questionnaire. Logistic regression was used to determine the independent predictors of incident colorectal cancer over the follow-up period. Risk scores were created from the sum of the odds ratios of the final predictors and used to divide the cohort into categories of increasing relative risk. RESULTS: During 20 years of follow-up, 381 cases of colon cancer and 104 cases of rectal cancer developed in the cohort. Age, alcohol use, smoking status, and body mass index were independent significant predictors of colorectal cancer. The point scores were used to define 10 risk groups. Those in the highest risk group (9-10 points) had an odds ratio of 15.29 (6.19-37.81) for colorectal cancer compared with those with the lowest risk. We further stratified scores into 3 risk classes. Compared with those at the lowest relative risk, the odds ratio for colorectal cancer was 3.07 (2.46-3.83) in the intermediate risk group and 5.75 (4.44-7.44) in the highest risk group. CONCLUSIONS: We developed a simple scoring system for colorectal cancer that identifies men at increased relative risk on the basis of age and modifiable factors. This tool should be validated in other populations.

A prospective study of body mass index and the risk of developing hypertension in men.

BACKGROUND: Although obesity is known to increase the risk of hypertension, few studies have prospectively evaluated body mass index (BMI) across the range of normal weight and overweight as a primary risk factor. METHODS: In this prospective cohort, we evaluated the association between BMI and risk of incident hypertension. We studied 13,563 initially healthy, nonhypertensive men who participated in the Physicians' Health Study. We calculated BMI from self-reported weight and height and defined hypertension as self-reported systolic blood pressure (BP) > or = 140 mm Hg, diastolic BP > or = 90 mm Hg, or new antihypertensive medication use. RESULTS: After a median 14.5 years, 4920 participants developed hypertension. Higher baseline BMI, even within the "normal" range, was consistently associated with increased risk of hypertension. Compared to participants in the lowest BMI quintile (<22.4 kg/m(2)), the relative risks (95% confidence interval) of developing hypertension for men with a BMI of 22.4 to 23.6, 23.7 to 24.7, 24.8 to 26.4, and >26.4 kg/m(2) were 1.20 (1.09-1.32), 1.31 (1.19-1.44), 1.56 (1.42-1.72), and 1.85 (1.69-2.03), respectively (P for trend, <.0001). Further adjustment for diabetes, high cholesterol, and baseline BP did not substantially alter these results. We found similar associations using other BMI categories and after excluding men with smoking history, those who developed hypertension in the first 2 years, and those with diabetes, obesity, or high cholesterol at baseline. CONCLUSIONS: In this large cohort, we found a strong gradient between higher BMI and increased risk of hypertension, even among men within the "normal" and mildly "overweight" BMI range. Approaches to reduce the risk of developing hypertension may include prevention of overweight and obesity.

Risk factors for venous thromboembolism in Japan: a hospital-based case-control study.

BACKGROUND: Previous studies suggest that Asians may be less likely to develop venous thromboembolism (VTE) than Caucasians. While inherited thrombophilias occur infrequently among Asians, the distribution of other VTE risk factors in these populations remains unclear. OBJECTIVE: To identify VTE risk factors in a Japanese population. PATIENTS AND METHODS: We evaluated 131,060 patients admitted to Okinawa Chubu Hospital in Japan (January 1987-December 1999). Patients with VTE were identified through discharge diagnoses using the hospital database. Medical records were reviewed for information on demographics, potential VTE risk factors, and diagnostic modalities. Controls were randomly selected from the same database, matched 1:1 to cases on age, sex, year of hospital admission, and nearest medical record number We used conditional logistic regression to examine potential VTE risk factors. RESULTS: We identified 141 cases of newly diagnosed VTE (128 with deep vein thrombosis, 41 with pulmonary embolism). In multivariable analyses adjusting for all measured potential risk factors, statistically significant VTE risk factors included lower extremity paralysis [odds ratio (OR), 3.07; 95% CI, 1.01-9.33], immobilization >7 days (OR, 4.96; 95% CI, 2.26-10.9), diagnosis of an acquired hypercoagulable state (OR, 19.1; 95% CI, 1.75-209.2), body mass index > or = 25.0 kg/nm2 (OR, 2.35; 95% CI, 1.13-4.89), and prior VTE (OR, 22.37; 95% CI, 2.35-213.4). CONCLUSION: The VTE risk factors identified in this Japanese population are similar to those previously described among Caucasians. Further study is needed to define how the distribution of VTE risk factors in Asian populations may influence appropriate preventive strategies.

Ethnic disparities in breast cancer management among Asian Americans and Pacific Islanders.

BACKGROUND: Little is known about breast cancer management among Asian Americans and Pacific Islanders (AAPI). METHODS: We performed a retrospective analysis of 2030 women (935 Japanese, 144 Chinese, 235 Filipino, 293 Hawaiian, and 423 white; mean age +/- SD, 59 +/- 13 years) with a diagnosis of early breast cancer (stages I, II, and IIIA) in Hawaii from 1995 to 2001. We linked data from the Surveillance, Epidemiology, and End Results program's Hawaii Tumor Registry to administrative health care claims. We evaluated (1) breast-conserving surgery (BCS); (2) radiotherapy after BCS; and (3) chemotherapy for node-positive disease. We used logistic regression to examine the association between AAPI ethnicity and treatment, adjusting for age, year, rural residence, tumor size, grade, nodal status, receptor status, prior cancer, comorbidity index, health plan type, and income. RESULTS: Overall, 60.3% of women had stage I disease, 36.8% had stage II, and 2.9% had stage IIIA. Only 55.6% received BCS, and 85.1% of these women also received radiation. Of those with nodal involvement (n = 521), 82.7% received chemotherapy. Japanese and Filipino women were significantly less likely than white women to undergo BCS (for Japanese: adjusted odds ratio, 0.62; 95% confidence interval, 0.48-0.80; for Filipinos: adjusted odds ratio, 0.47; 95% confidence interval, 0.33-0.66). Filipinos tended to be less likely than white women to receive radiation after BCS (adjusted odds ratio, 0.80; 95% confidence interval, 0.42-1.49). AAPI women were as likely as white women to receive adjuvant chemotherapy for nodal spread. CONCLUSIONS: We found disparities in the management of early-stage breast cancer among AAPI women, particularly among Japanese and Filipinos. Further study is needed to determine the reasons for the observed disparities and to understand their effect on health outcomes.

Patient ethnicity and use of venous thromboembolism prophylaxis.

OBJECTIVE: Patients at highest risk for developing venous thromboembolism include those undergoing major orthopedic surgery. However, physicians vary in their strategies to prevent venous thromboembolism. We evaluated whether the use of venous thromboembolism prophylaxis after orthopedic surgery is related to patient ethnicity. DESIGN: Retrospective cohort study, 1998-2002. SETTING: Tertiary care, university-affiliated hospital in Hawaii. STUDY PARTICIPANTS: 1811 adults (1085 women; 743 Asians; 206 Pacific Islanders; mean age 70.6 +/- 14.7 years) who underwent hip replacement, hip fracture surgery, or total knee replacement. MAIN OUTCOME MEASURES: Use of venous thromboembolism prophylaxis as recommended by the American College of Chest Physicians. Multivariable logistic regression was used to identify factors associated with prophylaxis use. RESULTS: Overall, 49.4% of patients received venous thromboembolism prophylaxis. After adjustment for patient age, sex, thromboembolism and bleeding risk factors, type of surgery, and anesthesia, Japanese patients were less likely to receive prophylaxis [odds ratio (OR) = 0.7; 95% confidence interval (CI) = 0.5-0.9; P = 0.01], whereas other ethnic groups were treated similarly to whites. Relative to patients undergoing hip replacement, those with hip fracture surgery were less likely (OR = 0.4; 95% CI = 0.3-0.5; P < 0.01), and those receiving total knee replacement more likely (OR = 4.5; 95% CI = 3.6-5.7; P < 0.01) to receive appropriate prophylaxis. CONCLUSION: Despite consensus recommendations, venous thromboembolism prophylaxis use among high-risk patients remains low. Japanese patients and those undergoing hip fracture surgery are at particular risk for not receiving appropriate prophylaxis in our population. Further research is needed to clarify the reasons for our findings and to determine if this variation is associated with increased risk of thromboembolic complications.

Association between body mass index and CKD in apparently healthy men.

BACKGROUND: Overweight and obesity are well-established risk factors for cardiovascular disease and decline in kidney function in individuals with existing chronic kidney disease (CKD). Conversely, their association with the development of CKD is less clear. METHODS: We evaluated the association between body mass index (BMI) and risk for CKD in a cohort of 11,104 initially healthy men who participated in the Physicians' Health Study and provided a blood sample after 14 years. BMI was calculated from self-reported weight and height. We estimated glomerular filtration rate (GFR) by using the abbreviated equation from the Modification of Diet in Renal Disease Study and defined CKD as GFR less than 60 mL/min/1.73 m2 (<1 mL/s/1.73 m2). RESULTS: After an average 14-year follow-up, 1,377 participants (12.4%) had a GFR less than 60 mL/min/1.73 m2 (<1 mL/s/1.73 m2). Higher baseline BMI was associated consistently with increased risk for CKD. Compared with participants in the lowest BMI quintile (<22.7 kg/m2), those in the highest quintile (>26.6 kg/m2) had an odds ratio (OR) of 1.45 (95% confidence interval [CI], 1.19 to 1.76; P trend <0.001) after adjusting for potential confounders. We found similar associations by using different categories of BMI. Compared with men who remained within a +/-5% range of their baseline BMI, those who reported a BMI increase greater than 10% had a significant increase in risk for CKD (OR, 1.27; 95% CI, 1.06 to 1.53). CONCLUSION: In this large cohort of initially healthy men, BMI was associated significantly with increased risk for CKD after 14 years. Strategies to decrease CKD risk might include prevention of overweight and obesity.

Prevalence of venous thromboembolism at a teaching hospital in Okinawa, Japan.

Limited data suggest that Asian Americans may have a lower risk of venous thromboembolism (VTE) than Caucasians. However, the actual prevalence of VTE among Asians remains controversial, and has not been described in Japan. We studied all 131,060 patients hospitalized at a single medical centre in Japan (January 1987 - December 1999). Patients with VTE were identified through discharge diagnoses. Hospital records were reviewed for information on patient demographics, risk factors, and diagnostic modalities. VTE occurred in 0.11% of admissions (n=141, 95%CI 0.09-0.13%). Mean age (+/-SD) was 64+/-17 years, 70% were women, 91% had deep vein thrombosis, and 29% pulmonary embolism. Among hospitalized patients 50-69 years old, VTE was significantly more common among women than men (0.31% vs. 0.08%; OR 3.88; 95%CI 1.45-6.31). We found a low prevalence of VTE in Japan compared to that reported in the US. Future studies are needed to clarify the reasons for our findings.