Hypertensive disorders of pregnancy and the risk of dementia: a systematic review and meta-analysis of cohort studies.

This study aimed to investigate the association between hypertensive disorders of pregnancy (HDP) and subsequent risk of dementia using a systematic review and meta-analysis of cohort studies. We searched PubMed and Scopus for eligible studies that investigated the association between HDP and dementia risk. Using the random-effects model, pooled hazard ratio (HR) and 95% confidence interval (CI) of dementia risk in women with HDP were calculated. We applied the I2 statistic to measure heterogeneity across studies and the test for funnel plot asymmetry to evaluate publication bias. Six cohort studies were eligible: three from the United States, two from Sweden, and one from Denmark. When combined, HDP was associated with the risk of dementia: pooled HR (95% CI) = 1.31 (1.12, 1.53). The heterogeneity across studies was moderate (I2 = 47.3%, p-heterogeneity = 0.091), but no signs of publication bias were detected. The association of HDP with vascular dementia was stronger than that with Alzheimer's disease: pooled HRs (95% CIs) = 1.66 (1.13, 2.43) and 1.29 (0.97, 1.72), respectively. In conclusion, HDP was associated with a higher risk of dementia and this association was more prominent with vascular dementia.

Association between hypertension grades and cancer mortality among Japanese men and women.

PURPOSE: We aimed to examine the association between hypertension grades and the risk of total and site-specific cancer mortality among Japanese men and women. METHODS: In the Japan Collaborative Cohort Study, 27,332 participants aged 40-79 years were enrolled and followed up with their mortality until 2009. According to the measured blood pressure (BP) at baseline, we classified the participants into four BP categories based on 2018 European guidelines. The Cox proportional hazard models were used to calculate the multivariable hazard ratios (HRs) with 95% confidence intervals (CIs) of total and site-specific cancer mortality according to the hypertension category. RESULTS: During the 18.5 years of median follow-up, 1,927 cancer deaths were documented. Grade 1 (systolic blood pressure [SBP] 140-159 mmHg or diastolic blood pressure [DBP] 90-99 mmHg) and grade 2-3 hypertension (SBP ≥ 160 mmHg or DBP ≥ 100 mmHg) were associated with an increased risk of total cancer mortality; the multivariable HRs were 1.17 (1.04-1.32) for grade 1, and 1.27 (1.09-1.47) for grade 2-3 hypertension compared to optimal and normal BP (SBP < 130 mmHg and DBP < 85 mmHg). Linear and positive associations were observed between SBP and DBP 10 mmHg increment and the risk of total cancer mortality; HRs were 1.06 (1.03-1.08) for SBP and 1.07 (1.02-1.11) for DBP of 10 mmHg increment. The excess risk was primarily found for esophageal, liver, and pancreatic cancer; the respective multivariable HRs of grade 2-3 hypertension vs optimal and normal BP were 2.57 (1.10-6.04) for esophageal, 1.67 (1.01-2.77) for liver, and 1.95 (1.17-3.23) for pancreatic cancer. CONCLUSION: Hypertension was associated with the increased risk of total cancer mortality, primarily of esophageal, liver, and pancreatic cancer.

The association between the estimated glomerular filtration rate and cognitive impairment: the Suita Study.

This cross-sectional study investigated the association between the estimated glomerular filtration rate (eGFR), a measure of chronic kidney disease (CKD), and cognitive impairment. We used data from 6215 Japanese individuals registered in the Suita Study. Cognitive impairment was defined as a Mini-Mental State Examination (MMSE) score of ≤ 26. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) of cognitive impairment for eGFR 45-59.9 and < 45 mL/min/1.73 m2 (mild and moderate-to-severe eGFR reductions) compared to eGFR ≥ 60 mL/min/1.73 m2 (normal eGFR). The results showed that both mild and moderate-to-severe eGFR reductions were associated with cognitive impairment: ORs (95% CIs) = 1.49 (1.22-1.83) and 2.35 (1.69-3.26), respectively (p-trend < 0.001). Each increment of eGFR by 10 mL/min/1.73m2 was associated with 4.8% lower odds of cognitive impairment. In conclusion, eGFR reduction was associated with cognitive impairment. Managing CKD is essential for preventing cognitive impairment.

Common Carotid Artery Stenosis Degree as a Predictor of Cardiovascular Disease in a General Population: The Suita Study.

BACKGROUND: The utility of screening for the degree of common carotid artery (CCA) stenosis as a predictor of cardiovascular disease (CVD) in a general population remains unclear. METHODS AND RESULTS: We studied 4775 Japanese men and women whose CCA was measured using bilateral carotid ultrasonography at baseline (April 1994-August 2001). We calculated the degree of stenosis as a percentage of the stenotic area of the lumen in the cross-section perpendicular to the long axis. The Cox proportional hazards model was used to calculate multivariable-adjusted hazard ratios (HRs) with 95% CIs for incident CVD and its subtypes according to the degree of CCA stenosis. During the median 14.2 years of follow-up, 385 incident CVD events (159 coronary heart disease and 226 stroke) were documented. The degree of CCA stenosis was associated with increased risks of incident CVD, coronary heart disease, and stroke, with multivariable-adjusted HRs (95% CIs) for <25%, 25%-49%, and ≥50% stenosis with plaque compared with no CCA plaque of 1.37 (1.07-1.76), 1.72 (1.23-2.40), and 2.49 (1.69-3.67), respectively. Adding the CCA stenosis degree to traditional CVD risk factors increased Harrell's C statistics (0.772 [95% CI, 0.751-0.794] to 0.778 [95% CI, 0.758-0.799]; P=0.04) and improved the 10-year risk prediction ability (integrated discrimination improvement, 0.0129 [95% CI, 0.0078-0.0179]; P<0.001; continuous net reclassification improvement, 0.1598 [95% CI, 0.0297-0.2881]; P=0.01). CONCLUSIONS: The degree of CCA stenosis may be used as a predictive marker for the development of CVD in the general population.

Development of new scores for atherosclerotic cardiovascular disease using specific medical examination items: the Suita Study.

BACKGROUND: We previously developed risk models predicting stroke, coronary heart disease (CHD), and cardiovascular disease (CVD) among Japanese people from the Suita Study. Yet, applying these models at the national level was challenging because some of the included risk factors differed from those collected in the Japanese governmental health check-ups, such as Tokutei-Kenshin. We, therefore, conducted this study to develop new risk models for stroke, CHD, and atherosclerotic CVD (ASCVD), based on data from the Suita Study. The new models used traditional cardiovascular risk factors similar to those in the Japanese governmental health check-ups. METHODS: We included 7,413 participants, aged 30-84 years, initially free from stroke and CHD. All participants received baseline health examinations, including a questionnaire assessing their lifestyle and medical history, medical examination, and blood and urine analysis. The risk factors of stroke, CHD, and ASCVD (cerebral infarction or CHD) were determined using the multivariable-adjusted Cox regression. The models' performance was assessed using the C-statistics for discrimination and the Hosmer-Lemeshow for calibration. We also developed three simple scores (zero to 100) that could predict the 10-year incidence of stroke, CHD, and ASCVD. RESULTS: Within 110,428 person-years (median follow-up = 16.6 years), 410 stroke events, 288 CHD events, and 527 ASCVD events were diagnosed. Age, smoking, hypertension, and diabetes were associated with stroke, CHD, and ASCVD risk. Men and those with decreased high-density lipoproteins or increased low-density lipoproteins showed a higher risk of CHD and ASCVD. Urinary proteins were associated with an increased risk of stroke and ASCVD. The C-statistic values of the risk models were >0.750 and the p-values of goodness-of-fit were >0.30. The 10-year incidence of stroke, CVD, and ASCVD events was 3.8%, 3.5%, and 5.7% for scores 45-54, 10.3%, 11.8%, and 19.6% for scores 65-74, and 27.7%, 23.5%, and 60.5% for scores ≥85, respectively. CONCLUSIONS: We developed new Suita risk models for stroke, CHD, and ASCVD using variables similar to those in the Japanese governmental health check-ups. We also developed new risk scores to predict incident stroke, CHD, and ASCVD within 10 years.

Fatty Liver Index and the Risk of Atrial Fibrillation in a General Japanese Population　- The Suita Study.

BACKGROUND: Atrial fibrillation (AF) is the most diagnosed arrhythmia in clinical settings. The fatty liver index (FLI) is a marker of liver steatosis with potential cardiovascular implications. This study investigated whether FLI could predict the risk of AF.Methods and Results: We used data from the Suita Study, a Japanese population-based prospective cohort study. A total of 2,346 men and 3,543 women, aged 30-84 years, without prevalent AF were included and followed up. The diagnosis of AF was established during follow-up using electrocardiograms, hospital records, and death certificates. FLI was assessed during a baseline health checkup. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for incident AF per FLI quintile and log-transformed FLI. Within a median 14.5 years of follow-up, 142 men and 105 women developed AF. Compared with women in the third (middle) FLI quintile, women in the first (lowest), fourth, and fifth (highest) quintiles showed a higher risk of AF, with multivariable-adjusted HRs of 2.37 (95% CI 1.06-5.31), 2.60 (95% CI 1.30-5.17), and 2.04 (95% CI 1.00-4.18), respectively. No corresponding associations were observed in men. The change in log-transformed FLI was not associated with the risk of AF in either sex. CONCLUSIONS: A U-shaped association between FLI and AF risk was detected in Japanese women. FLI could be a screening tool to detect women at high risk of developing AF.

Crystal structure, microstructure, and mechanical properties of heat-treated oyster shells.

We investigated the crystal structure and mechanical properties of oyster shells subjected to heat treatment under increasing temperature conditions. The shell contained folia and chalky layers. The folia layer comprised two CaCO3 phases: 72.3% calcite and 27.7% aragonite. The lattice parameters of the calcite and aragonite present in the folia layer did not correspond to those of the synthesized sample. The anisotropic lattice expansion was observed in calcite and aragonite in the folia layer during heat-treatment. The chalky layer has also the anisotropic lattice expansion, but the expansion was disappeared at 573 K. The microhardness (HV value) of the folia layer decreased rapidly from 122 to 11 HV at temperatures 573-673 K owing to the phase transformation from aragonite to calcite in this temperature range. The microhardness of the chalky layer at RT was 125 HV, which decreased to 15 HV at 373 K. Crack propagation with increasing temperature was investigated using a micro-Vickers apparatus. In the folia layer, cracks were produced inside the prism, and they propagated along the lamellar structure. The cracks initiated and propagated along the organic biopolymer interlayers in a zigzag manner. No cracks were observed in the chalky layers of the heat-treated samples. The toughness of the chalky layer was superior to that of the folia layer. From our results, we can conclude that oyster shells comprise two types of materials with different mechanical properties.

Serum cholesterol levels and the risk of brain natriuretic peptide-diagnosed heart failure in postmenopausal women: a population-based prospective cohort study.

OBJECTIVE: Hormonal changes during menopause can disturb serum cholesterol which is closely associated with cardiovascular disease. This study investigated the prospective association between serum cholesterol and heart failure (HF) risk in postmenopausal women. METHODS: We analyzed data from 1,307 Japanese women, aged 55 to 94 years. All women had no history of HF, and their baseline brain natriuretic peptide (BNP) levels were less than 100 pg/mL. During the follow-ups conducted every 2 years, HF was diagnosed among women who developed BNP of 100 pg/mL or greater. Cox proportional hazard models were applied to calculate hazard ratios and 95% CI of HF for women per their baseline total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (HDL-C) levels. The Cox regression models were adjusted for age, body mass index, smoking, alcohol drinking, hypertension, diabetes, cardiac murmurs, arrhythmia, stroke or ischemic heart disease, chronic kidney disease, and lipid-lowering agent use. RESULTS: Within an 8-year median follow-up, 153 participants developed HF. In the multivariable-adjusted model, women with total cholesterol of 240 mg/dL or greater (compared with 160-199 mg/dL) and HDL-C of 100 mg/dL or greater (compared with 50-59 mg/dL) showed an increased risk of HF: hazard ratios (95% CI) = 1.70 (1.04-2.77) and 2.70 (1.10-6.64), respectively. The results remained significant after further adjusting for baseline BNP. No associations were observed with low-density lipoprotein cholesterol. CONCLUSIONS: Total cholesterol of 240 mg/dL or greater and HDL-C of 100 mg/dL or greater were positively associated with the risk of HF in postmenopausal Japanese women.

Alcohol consumption and the risk of heart failure: the Suita Study and meta-analysis of prospective cohort studies.

BACKGROUND: Alcohol consumption is a modifiable lifestyle, but its role in heart failure (HF) development is controversial. Herein, we investigated the prospective association between alcohol consumption and HF risk. METHODS: A total of 2,712 participants (1,149 men and 1,563 women) from the Suita Study were followed up every two years. Cox regression was applied to calculate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of HF risk for heavy drinking (≥46 g/day in men or ≥23 g/day in women) and never drinking compared to light drinking (<23 g/day in men or <11.5 g/day in women). Then, we combined the results of the Suita Study with those from other eligible prospective cohort studies in a meta-analysis using the random-effects model. RESULTS: In the Suita Study, within a median follow-up period of 8 years, 319 HF cases (162 in men and 157 in women) were detected. In men, but not women, never and heavy drinking carried a higher risk of HF than light drinking: HRs (95% CIs) = 1.65 (1.00, 2.73) and 2.14 (1.26, 3.66), respectively. Alike, the meta-analysis showed a higher risk of HF among heavy drinkers: HR (95% CI) = 1.37 (1.15, 1.62) and abstainers: HR (95% CI) = 1.18 (1.02, 1.37). CONCLUSION: We indicated a J-shaped association between alcohol consumption and HF risk among Japanese men. The results of the meta-analysis came in line with the Suita Study. Heavy-drinking men should be targeted for lifestyle modification interventions.

Childhood secondhand smoke exposure and respiratory disease mortality among never-smokers: the Japan collaborative cohort study for evaluation of cancer risk.

BACKGROUND: The main source of secondhand smoke (SHS) exposure during childhood occurs at home due to close family members who smoke. This study examined the association between childhood SHS exposure and the risk of respiratory disease mortality among non-smoking adults. METHODS: Data from 44 233 never-smoking Japanese men and women aged 40-79 years who participated in the JACC study between 1988 and 1990 were analyzed. The Cox proportional hazards model was used to calculate hazard ratios and 95% confidence intervals of respiratory disease mortality according to the number of smoking family members during childhood. Subdistribution HRs (SHRs) were calculated as a competing risk analysis. RESULTS: A total of 735 deaths from respiratory diseases were documented in a median follow-up of 19.2 years. Living with three or more smoking family members during childhood was associated with a higher risk of respiratory disease mortality in adulthood among women; multivariable SHR compared with participants with no family member smokers during childhood was 1.60 (1.01-2.54) for participants with three or more family members who smoked during their childhood. CONCLUSIONS: SHS exposure from three or more family members during childhood was associated with an increased risk of respiratory disease-related mortality in adulthood.

Television Viewing Time and All-cause and Cardiovascular Disease Mortality Among Japanese Adults with and without a History of Stroke or Myocardial Infarction.

AIMS: We examined the association between television (TV) viewing time and all-cause and cardiovascular disease (CVD) mortality among Japanese adults with and without a history of stroke or myocardial infarction (MI). METHODS: In the Japan Collaborative Cohort Study, 76,572 participants (851 stroke survivors, 1,883 MI survivors, and 73,838 persons without a history of stroke or MI), aged 40-79 years at baseline (1988-1990), completed a lifestyle, diet, and medical history questionnaire, and were followed up regarding mortality until 2009. The Cox proportional hazard model was used to calculate the multivariable-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of all-cause and CVD mortality. RESULTS: During the 19.3-year median follow-up period, 17,387 deaths were documented. TV viewing time was positively associated with all-cause and CVD mortality regardless of stroke or MI history. The multivariable-adjusted HRs of all-cause mortality with 95% CIs for TV viewing time of 3-4.9 h, 5-6.9 h, and ≥ 7 h were 1.18 (0.95-1.48), 1.12 (0.86-1.45), and 1.61 (1.12-2.32) for stroke survivors; 0.97 (0.81-1.17), 1.40 (1.12-1.76), and 1.44 (1.02-2.03) for MI survivors; and 1.00 (0.96-1.03), 1.07 (1.01-1.12), and 1.22 (1.11-1.34) for persons without a history of stroke or MI, respectively, compared with ＜3 h. CONCLUSIONS: Prolonged TV viewing time was associated with higher risks of all-cause and CVD mortality in stroke or MI survivors and in persons without a history of them. It may be recommended to reduce sedentary time for stroke or MI survivors, independent of the level of physical activity.

Prevalence of family history of cancer in the NC-CCAPH consortium of Japan.

The objective of this study was to identify the prevalence of family history of cancer using cohorts participating in the Japanese National Center Cohort Collaborative for Advancing Population Health (NC-CCAPH). We pooled data from seven eligible cohorts of the Collaborative with available data on family history of cancer. Prevalence of family history of cancer and corresponding 95% confidence intervals are presented for all cancers and selected site-specific cancers for the total population and stratified by sex, age, and birth cohort. Prevalence of family history of cancer increased with age ranging from 10.51% in the 15 to 39 year age category to 47.11% in 70-year-olds. Overall prevalence increased in birth cohorts from ≤ 1929 until 1960 and decreased for the next two decades. Gastric cancer (11.97%) was the most common site recorded for family members, followed by colorectal and lung (5.75%), prostate (4.37%), breast (3.43%) and liver (3.05%) cancer. Women consistently had a higher prevalence of family history of cancer (34.32%) versus men (28.75%). Almost one in three participants had a family history of cancer in this Japanese consortium study highlighting the importance of early and targeted cancer screening services.

Blood pressure per the 2017 ACC/AHA and 2018 ESC/ESH guidelines and heart failure risk: the Suita Study.

Hypertension is a significant risk factor for heart failure (HF). Since hypertension definition varies across guidelines, identifying blood pressure (BP) categories that should be targeted to prevent HF is required. We, therefore, investigated the association between hypertension per the 2017 American College of Cardiology/American Heart Association (ACC/AHA) and 2018 European Society of Cardiology/European Society of Hypertension (ESC/ESH) guidelines and HF risk. This prospective cohort study included randomly selected 2809 urban Japanese people from the Suita Study. Cox regression was used to assess HF risk, in the form of hazard ratios (HRs) and 95% confidence intervals (95% CIs), for different BP categories in both guidelines, compared to a reference category defined as systolic BP (SBP) <120 mmHg and diastolic BP (DBP) <80 mmHg. Within 8 years of median follow-up, 339 HF cases were detected. Per the 2017 ACC/AHA guidelines, hypertension I and II and isolated systolic hypertension were associated with increased HF risk: HRs (95% CIs) = 1.81 (1.33-2.47), 1.68 (1.24-2.27), and 1.64 (1.13-2.39), respectively. Per the 2018 ESC/ESH guidelines, high-normal BP, hypertension I, II, and III, and isolated systolic hypertension were associated with increased HF risk: HRs (95% CIs) = 1.88 (1.35-2.62), 1.57 (1.13-2.16), 2.10 (1.34-3.29), 2.57 (1.15-5.77), and 1.51 (1.04-2.19), respectively. In conclusion, hypertension and isolated systolic hypertension per the 2017 ACC/AHA and 2018 ESC/ESH guidelines and high-normal BP per the 2018 ESC/ESH guidelines are risk factors for HF.

Coffee and Green Tea Consumption and Cardiovascular Disease Mortality Among People With and Without Hypertension.

Background This study was conducted to examine the impacts of coffee and green tea consumption on cardiovascular disease (CVD) mortality among people with severe hypertension. Methods and Results In the JACC (Japan Collaborative Cohort Study for Evaluation of Cancer Risk), 18 609 participants (6574 men and 12 035 women) aged 40 to 79 years at baseline who completed a lifestyle, diet, and medical history questionnaire, and health examinations, were followed up until 2009. We classified the participants into four blood pressure (BP) categories: optimal and normal BP, high-normal BP, grade 1 hypertension, and grade 2-3 hypertension. A Cox proportional hazard model was used to calculate the multivariable hazard ratios with 95% CIs of CVD mortality. During the 18.9 years of median follow-up, a total of 842 CVD deaths were documented. Coffee consumption was associated with an increased risk of CVD mortality among people with grade 2-3 hypertension; the multivariable hazard ratios (95% CI) of CVD mortality were 0.98 (0.67-1.43) for <1 cup/day, 0.74 (0.37-1.46) for 1 cup/day, and 2.05 (1.17-3.59) for ≥2 cups/day, compared with non-coffee drinkers. Such associations were not found among people with optimal and normal, high-normal BP, and grade 1 hypertension. Green tea consumption was not associated with an increased risk of CVD across any BP categories. Conclusions Heavy coffee consumption was associated with an increased risk of CVD mortality among people with severe hypertension, but not people without hypertension and with grade 1 hypertension. In contrast, green tea consumption was not associated with an increased risk of CVD mortality across all categories of BP.

Association of Physical Activity with Aortic Disease in Japanese Men and Women: The Japan Collaborative Cohort Study.

AIMS: Evidence of the effects of physical activity on mortality from aortic diseases, especially in Asian populations, remains limited. This study aimed to examine these effects using data from a large long-term cohort study of Japanese men and women. METHODS: Between 1988 and 1990, 32,083 men and 43,454 women in Japan, aged 40-79 years with no history of coronary heart disease, stroke, aortic diseases, or cancer, filled in questionnaires on time spent walking and participating in sports and were followed up until 2009. Multivariable hazard ratios (HRs) with 95% confidence intervals (CIs) of aortic disease mortality and its types (aortic aneurysm and dissection) according to the time spent walking and participating in sports were calculated after adjusting for potential confounding factors using the Cox proportional hazards model. RESULTS: During a median follow-up of 19.1 years, a total of 173 deaths from aortic disease (91 cases of aortic dissection and 82 of aortic aneurysm) were documented. Sports participation time was inversely associated with the risk of death from aortic aneurysm: the multivariable HRs (95% CIs) were 0.68 (0.40-1.16) for ＜1 h/week, 0.50 (0.19-1.35) for 3-4 h/week, and 0.31 (0.10-0.93) for ≥ 5 h/week (p for trend=0.23) compared with 1-2 h/week. The time spent walking was not associated with death from aortic aneurysm, dissection, and total aortic diseases. CONCLUSIONS: Greater time spent in sports participation was associated with a reduced risk of mortality from aortic aneurism in the Japanese population. Further studies are needed to investigate the relationship between physical activity and aortic dissection.

Secondhand Smoke Exposure in Childhood and Mortality from Coronary Heart Disease in Adulthood: the Japan Collaborative Cohort Study for Evaluation of Cancer Risk.

AIMS: We examined whether secondhand smoke exposure in childhood affects the risk of coronary heart disease (CHD) in adulthood. METHODS: In the Japan Collaborative Cohort Study, we analyzed data on 71,459 participants aged 40-79 years, with no history of CHD, stroke, or cancer at baseline (1988-1990) and who completed a lifestyle questionnaire including the number of smoking family members in childhood (0, 1, 2, and 3+ members) and followed them up until the end of 2009. The Cox proportional hazards model was used to calculate the multivariable hazard ratios (HRs) with 95% confidence intervals (CIs) of CHD mortality according to the number of smoking family members in childhood. RESULTS: During the median 18.9 years' follow-up, 955 CHD deaths were reported. There was a dose-response relationship between the number of smoking family members at home and CHD mortality among middle-aged individuals (40-59 years); the multivariable HRs (95% CIs) were 1.08 (0.76-1.54) for 1, 1.35 (0.87-2.08) for 2, and 2.49 (1.24-5.00) for 3+ smoking family members compared with 0 members (p for trend=0.03). The association for 3+ smoking family members among the middle-aged group was more evident in men than in women (the multivariable HRs [95% CIs] were 2.97 [1.34-6.58] and 1.65 [0.36-7.52], respectively) and more evident in non-current smokers than in current smokers (the multivariable HRs [95% CIs] were 4.24 [1.57-11.45] and 1.93 [0.72-5.15], respectively). CONCLUSIONS: Secondhand smoke exposure in childhood was associated with an increased risk of CHD mortality in adulthood, primarily in middle-aged men and non-current smokers.

Body Mass Index and Mortality from Nonrheumatic Aortic Valve Disease among Japanese Men and Women.

AIM: We aimed to examine the impact of overweight and obesity on mortality from nonrheumatic aortic valve disease. METHODS: In the Japan Collaborative Cohort Study, we analyzed data of 98,378 participants aged 40-79 years, with no history of coronary heart disease, stroke, or cancer at baseline (1988-1990) and who completed a lifestyle questionnaire including height and body weight; they were followed for mortality until the end of 2009. The Cox proportional hazards model was used to calculate the multivariable hazard ratios (HRs) with 95% confidence intervals (CIs) of nonrheumatic aortic valve disease mortality according to body mass index (BMI) after adjusting for potential confounding factors. RESULTS: During the median 19.2 years follow-up, 60 deaths from nonrheumatic aortic valve disease were reported. BMI was positively associated with the risk of mortality from nonrheumatic aortic valve disease; the multivariable HRs (95% CIs) were 0.90 (0.40-2.06) for persons with BMI ＜21 kg/m2, 1.71 (0.81-3.58) for BMI 23-24.9 kg/m2, 1.65 (0.69-3.94) for BMI 25-26.9 kg/m2, and 2.83 (1.20-6.65) for BMI ≥ 27 kg/m2 (p for trend=0.006), compared with persons with BMI 21-22.9 kg/m2. Similar associations were observed between men and women (p for interaction=0.56). Excluding those who died during the first ten years of follow-up or a competing risk analysis with other causes of death as competing risk events did not change the association materially. CONCLUSIONS: Overweight and obesity may be independent risk factors for nonrheumatic aortic valve disease mortality in Asian populations.

Sleep Duration and Daytime Napping and Risk of Type 2 Diabetes Among Japanese Men and Women: The Japan Collaborative Cohort Study for Evaluation of Cancer Risk.

BACKGROUND: Little is known about the impacts of sleep duration and daytime napping on the risk of type 2 diabetes mellitus (T2DM). METHODS: In this study, 20,318 participants (7,597 men, 12,721 women) aged 40-79 years without a history of T2DM, stroke, coronary heart disease, or cancer at baseline (1988-1990), completed the baseline survey and the 5-year follow-up questionnaires, which included average sleep duration, napping habits, and self-reports of physician-diagnosed diabetes. The multivariable odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a logistic regression model. RESULTS: During the 5-year follow-up, 531 new cases of T2DM (266 men and 265 women) were documented. Sleep duration ≥10 hours was associated with higher risk of T2DM compared to sleep duration of 7 hours (OR 1.99; 95% CI, 1.28-3.08). The excess risk was observed for both sexes and primarily found among the non-overweight; the multivariable ORs of sleeping ≥10 hours compared to 7 hours were 2.05 (95% CI, 1.26-3.35) for the non-overweight (BMI <25 kg/m2) and 1.38 (95% CI, 0.49-3.83) for the overweight (BMI ≥25 kg/m2). The respective ORs of nappers versus non-nappers were 1.30 (95% CI, 1.03-1.63) and 0.92 (95% CI, 0.65-1.29). Among the non-overweight, nappers who slept ≥10 hours had the highest risk of T2DM (OR 2.84; 95% CI, 1.57-5.14), non-nappers who slept ≥10 hours (OR 2.27; 95% CI, 1.27-4.06), and nappers who slept <10 hours (OR 1.30; 95% CI, 1.03-1.64), compared with non-nappers who slept <10 hours. CONCLUSION: Long sleep duration was associated with the risk of T2DM in both sexes, which was confined to the non-overweight.

Playing a musical instrument and the risk of dementia among older adults: a systematic review and meta-analysis of prospective cohort studies.

BACKGROUND: Engaging in leisure activities was suggested to protect older adults from dementia. However, the association between playing a musical instrument and the risk of dementia is not well-established. This study aimed to investigate this association in older adults using a systematic review and meta-analysis of prospective cohort studies. METHODS: Pooled hazard ratio (HR) and 95% confidence interval (CI) of having dementia for older adults playing a musical instrument were calculated using the random-effects model. We performed the I2 statistic to detect heterogeneity across studies and the test for funnel plot asymmetry to assess publication bias. The risk of bias assessment was conducted using the modified Newcastle-Ottawa Scale. RESULTS: A total of three prospective cohort studies were found eligible: two from the U.S. and one from Japan. Playing a musical instrument, in the meta-analysis, was significantly associated with a decreased risk of dementia (HR = 0.64; 95% CI: 0.41, 0.98) among older adults. No signs of significant heterogeneity across studies (I2 = 23.3% and p-heterogeneity = 0.27) or publication bias (z= -1.3 and p-publication bias = 0.18) were identified. CONCLUSION: Playing a musical instrument was associated with a decreased risk of dementia among older adults. Older adults should be encouraged to engage in leisure activities, especially playing musical instruments.

Association Between White Blood Cell Count and Atrial Fibrillation Risk　- A Population-Based Prospective Cohort Study.

BACKGROUND: The incidence and prevalence of atrial fibrillation (AF) are increasing. The white blood cell (WBC) count is an indicator of systemic inflammation and is related to increased cardiovascular disease risk. Using data from the Suita Study, we investigated the association between WBC count and AF risk in the general Japanese population.Methods and Results: This prospective cohort study included 6,884 people, aged 30-84 years, with no baseline AF. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for AF incidence by WBC count quintile. Within a median follow-up period of 14.6 years, 312 AF cases were diagnosed. Compared with the lowest WBC count quintile, the highest quintile was associated with an increased AF risk (HR 1.57; 95% CI 1.07-2.29). The association was more pronounced among women than men (HR 2.16 [95% CI 1.10-4.26] and 1.55 [95% CI 0.99-2.44], respectively; P interaction=0.07), and among current than non-smokers (HR 4.66 [95% CI 1.89-11.50] and 1.61 [95% CI 1.01-2.57], respectively; P interaction=0.20). For each 1.0×109-cells/L increment in WBC count, AF risk increased by 9% in men (9% in non-smokers, 10% in current smokers) and 20% in women (13% in non-smokers, 32% in current smokers). CONCLUSIONS: A higher WBC count was positively associated with an elevated AF risk in the general Japanese population, especially in women who smoked.