Risk factors for intracerebral hemorrhage by five specific bleeding sites: Japan Public Health Center-based Prospective Study.

BACKGROUND: Evaluating the risk factors for intracerebral hemorrhage is indispensable for primary prevention. However, the pathogenesis varies depending on the bleeding site, and few prospective studies have explored risk factors in detail for each site. PARTICIPANTS AND METHODS: The Japan Public Health Center-based Prospective Study is a prospective study comprising a population-based sample of Japanese adults in 1990 (Cohort I) and in 1993 (Cohort II). A total of 34,137 participants (11,907 men and 22,230 women) were enrolled in this study and followed up until 2009 for Cohort I and until 2012 for Cohort II. The association between risk factors (age, sex, blood pressure, serum cholesterol, triglycerides, blood glucose, body mass index, smoking, and drinking status) and intracerebral hemorrhage by its bleeding site (lobes, putamen, thalamus, cerebellum, and brainstem) was assessed using Cox proportional hazards analysis. RESULTS: During a median 20-year follow-up, 571 intracerebral hemorrhage events occurred. Hypertension was associated with an increased risk of total intracerebral hemorrhage, but not lobar hemorrhage. The multivariable hazard ratio (95% confidence intervals) was 2.09 (1.75-2.50) for total intracerebral hemorrhage. In contrast, a low serum total cholesterol level was associated only with lobar hemorrhage (1.73 (1.01-2.96)). Heavy drinking was associated with the risk of total and putamen hemorrhage, and obesity was associated with the risk of putamen hemorrhage. DISCUSSION AND CONCLUSION: The present study identified different risk factors depending on the bleeding site of intracerebral hemorrhage.

Equol Nonproducing Status as an Independent Risk Factor for Acute Cardioembolic Stroke and Poor Functional Outcome.

Background/Objectives: Equol has protective effects against coronary artery disease and dementia by strongly binding to estrogen receptor beta, whereas the intake of soy isoflavone alone does not always confer such protective effects. Equol production is completely dependent on the existence of equol-producing gut microbiota. The effects of equol-producing status on the cerebrovascular diseases remain unclear. The current study was aimed to investigate the association of equol-producing status with the development of stroke and its neurological prognosis. Methods: Frequencies of equol producers were compared between healthy subjects (HS) registered in the Suita Study and patients with acute stroke admitted to our stroke center from September 2019 to October 2021 in a retrospective cohort study. Results: The proportion of HSs and patients with ischemic stroke who were equol producers did not significantly differ (50/103 [48.5%] vs. 60/140 [42.9%], p = 0.38). However, cardioembolic stroke was significantly associated with low a prevalence of equol producers (adjusted odds ratio [aOR] 0.46, 95% confidence interval [CI] 0.21-0.99, p = 0.05). A higher left atrial volume index was observed in equol nonproducers (46.3 ± 23.8 vs. 36.0 ± 11.6 mL/m2, p = 0.06). The equol nonproducers had a significantly higher prevalence of atrial fibrillation than the equol producers (27.5% vs. 13.3%, p = 0.04). Furthermore, the equol producers exhibited a significantly favorable functional outcome upon discharge (aOR 2.84, 95% CI 1.20-6.75, p = 0.02). Conclusions: Equol is a promising candidate for interventions aiming to reduce the risk of CES and atrial dysfunction, such as atrial fibrillation and improve neurological prognosis after ischemic stroke.

The association between serum cholesterol levels and mild-to-moderate cognitive impairment in the Suita Study and evidence from other epidemiological studies.

BACKGROUND: Serum cholesterols are well-documented markers of cardiovascular diseases; however, their association with cognitive well-being is uncertain. This study investigated the association between serum cholesterol levels and mild-to-moderate cognitive impairment. METHODS: Epidemiological evidence on the role of total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), non-HDL-C, and low-density lipoprotein cholesterol (LDL-C) in cognitive impairment was highlighted. Then, data from 6216 Japanese individuals, aged ≥50 years, from the Suita Study were analyzed. Mini-Mental State Examination (MMSE) scores <27 and < 24 were used to define cognitive impairment. Logistic regression was used to calculate the odds ratios (ORs) and 95 % confidence intervals (95 % CIs) for cognitive impairment. RESULTS: Epidemiological studies investigating the association between serum cholesterol and cognitive impairment have shown conflicting findings: elevated risk with certain lipid components in some studies and no association in others. In the Suita Study, HDL-C < 40 mg/dL was associated with cognitive impairment: ORs (95 % CIs) = 1.36 (1.08, 1.72) for MMSE <27 and 1.61 (1.00, 2.60) for MMSE <24. Non-HDL-C ≥ 200 mg/dL was also associated with cognitive impairment: ORs (95 % CIs) = 1.53 (1.02, 2.31) for MMSE <27 and 1.80 (1.16, 2.79) for MMSE <24. No such associations were detected with TC. CONCLUSION: While epidemiological evidence remains inconsistent, the Suita Study showed that decreased HDL-C and increased non-HDL-C, but not increased TC, were associated with mild-to-moderate cognitive impairment. Management of serum cholesterol levels should be considered to prevent cognitive impairment.

The association between antenatal coffee consumption and preeclampsia: a systematic review and meta-analysis.

BACKGROUND: A growing body of evidence has documented unfavorable maternal outcomes attributed to excessive antenatal coffee consumption. Preeclampsia is one of the most common hypertensive disorders of pregnancy with several adverse maternal and neonatal outcomes. However, the association between antenatal coffee consumption and preeclampsia remains debatable. Herein, we performed a systematic review and meta-analysis of available evidence to investigate this association. METHODS: After systematically reviewing PubMed and Scopus for eligible studies published until October 2023, we pooled the odds ratios (ORs) and their 95% confidence intervals (CIs) of preeclampsia for women who reported the highest versus the lowest frequencies of antenatal coffee consumption. We used the I2 statistic to measure heterogeneity across studies and the funnel plot asymmetry to assess publication bias. RESULTS: This meta-analysis included seven retrospective studies (six case-control studies and one cross-sectional study) investigating 904 women with preeclampsia and 6,257 women without it. Combined, the highest frequencies of antenatal coffee consumption were associated with higher odds of preeclampsia: (pooled OR = 1.39, 95% CI: 1.03, 1.86), with a moderate heterogeneity across studies (I2 = 40.34% and p-value for heterogeneity = 0.122) and no publication bias (z = 0.610 and p-value for publication bias = 0.542). However, excluding the cross-sectional study, which contributed to 24.3% of the meta-analysis weight, left the association statistically non-significant: (pooled OR = 1.33, 95% CI: 0.91, 1.95; I2 = 44.59%). The association became even weaker after limiting the analysis to studies that excluded women with chronic hypertension: (pooled OR = 1.21, 95% CI: 0.77, 1.89; I2 = 41.64%) or after excluding studies with low quality: (pooled OR = 1.24, 95% CI: 0.70, 2.19; I2 = 65.79%). CONCLUSION: The association between antenatal coffee consumption and preeclampsia remains inconclusive. Future prospective cohort studies are needed to better investigate this association.

Lifetime Risk of Incident Coronary Heart Disease, Stroke, and Cardiovascular Disease: The Japan Public Health Center-Based Prospective Study.

AIM: The constellation of cardiovascular disease (CVD) risk factors greatly impacts the lifetime risk (LTR) of incident CVD, but the LTR has not been thoroughly evaluated in the Japanese population. METHODS: We conducted a prospective study involving a total of 25,896 individuals 40-69 years old without a history of CVD in 1995 (Cohort I) and 1993-1994 (Cohort II) in Japan. CVD risk factors (blood pressure, non-high-density lipoprotein [HDL] cholesterol levels, smoking status, and glucose concentrations) were used to stratify them by risk. The sex-specific LTR of incident coronary heart disease, stroke, atherosclerotic CVD, and total CVD were estimated for participants 45 years old in the 4 risk categories with the cumulative incidence rate, adjusting for the competing risk of death. RESULTS: We found apparent differences in the LTR of total CVD according to the risk stratification. Individuals with ≥ 2 of the risk factors of blood pressure ≥ 140/90 mmHg or treated, non-HDL cholesterol level ≥ 170 mg/dL or treated, current smoker, and diabetes had substantially higher adjusted LTRs of CVD than those in other groups, with a LTR of 26.5% (95% confidence interval, 24.0%-29.0%) for men and 15.3% (13.1%-17.5%) for women at 45 years. The LTR of incident stroke was the highest among CVDs, and the presence of hypertension and diabetes mellitus strongly influenced the LTR of total CVD. CONCLUSION: The impact of risk accumulation on LTR of CVD was greater in men, and 1 in 4 men with ≥ 2 major risk factors at 45 years of age developed CVD in their lifetime.

Machine Learning Approaches for Stroke Risk Prediction: Findings from the Suita Study.

Stroke constitutes a significant public health concern due to its impact on mortality and morbidity. This study investigates the utility of machine learning algorithms in predicting stroke and identifying key risk factors using data from the Suita study, comprising 7389 participants and 53 variables. Initially, unsupervised k-prototype clustering categorized participants into risk clusters, while five supervised models including Logistic Regression (LR), Random Forest (RF), Support Vector Machine (SVM), Extreme Gradient Boosting (XGBoost), and Light Gradient Boosted Machine (LightGBM) were employed to predict stroke outcomes. Stroke incidence disparities among identified risk clusters using the unsupervised k-prototype clustering method are substantial, according to the findings. Supervised learning, particularly RF, was a preferable option because of the higher levels of performance metrics. The Shapley Additive Explanations (SHAP) method identified age, systolic blood pressure, hypertension, estimated glomerular filtration rate, metabolic syndrome, and blood glucose level as key predictors of stroke, aligning with findings from the unsupervised clustering approach in high-risk groups. Additionally, previously unidentified risk factors such as elbow joint thickness, fructosamine, hemoglobin, and calcium level demonstrate potential for stroke prediction. In conclusion, machine learning facilitated accurate stroke risk predictions and highlighted potential biomarkers, offering a data-driven framework for risk assessment and biomarker discovery.

The association between stair climbing and modifiable cardiovascular disease risk factors: the Suita Study.

BACKGROUND: Stair climbing is a readily available form of physical activity with potential cardiovascular benefits. This study aimed to investigate the association between stair climbing and numerous modifiable cardiovascular disease (CVD) risk factors. METHODS: In this cross-sectional study, we used data from 7282 Japanese people (30-84 years) residing in Suita City, Osaka. CVD risk factors and stair climbing frequency were assessed during the Suita Study health examination. Logistic regressions were used to calculate the odds ratios (ORs) and 95% confidence intervals (95% CIs) for CVD risk factors across stair climbing frequencies. RESULTS: After adjustment for age, sex, lifestyle, and medical conditions, stair climbing >60% of the time, compared to <20% of the time, was inversely associated with obesity, smoking, physical inactivity, and stress: ORs (95% CIs) = 0.63 (0.53, 0.75), 0.81 (0.69, 0.96), 0.48 (0.41, 0.55), and 0.67 (0.58, 0.78), respectively (p-trends < 0.05). CONCLUSION: Stair climbing was inversely associated with obesity, smoking, physical inactivity, and stress; suggesting a potential role for cardiovascular disease prevention.

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.

Fatty Liver Index as a proxy for non-alcoholic fatty liver disease and the risk of stroke and coronary heart disease: The Suita Study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in developed countries, but its role in predicting cardiovascular disease (CVD) needs further investigation. Herein, we studied the association between NAFLD and the risk of CVD, stroke, and coronary heart disease (CHD) among Japanese people. METHODS: This prospective cohort study analyzed data from 2,517 men and 3,958 women, aged 30-84 years, who were registered in the Suita Study. NAFLD was defined as Fatty Liver Index (FLI) ≥ 60. Cox proportional hazard models were applied to calculate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of incident CVD, stroke, and CHD events by baseline FLI. The results were adjusted for age, smoking, alcohol consumption, hypertension, diabetes, lipid profile, chronic kidney disease, and cardiac murmur or valvular diseases. RESULTS: Within 16.6 years of median follow-up, 590 participants developed CVD (346 stroke events and 244 CHD events). Women with NAFLD (FLI ≥ 60) showed a higher risk of CVD and stroke: HRs (95% CIs) = 1.69 (1.16, 2.46) and 2.06 (1.31, 3.24), respectively. Besides, women in the fourth and fifth (highest) FLI quintiles showed a higher risk of CVD and stroke than those in the third (middle) quintile: HRs (95% CIs) = 1.60 (1.08, 2.36) and 1.67 (1.13, 2.45) for CVD and 1.73 (1.07, 2.79) and 1.90 (1.18, 3.05) for stroke, respectively. No corresponding associations were detected in men. NAFLD was not associated with CHD risk in either sex. CONCLUSIONS: NAFLD, diagnosed by FLI, was associated with a higher risk of CVD and stroke in Japanese women. From a preventive perspective, women with NAFLD should be targeted for CVD screenings and interventions.

The effect of age on the relationship between body mass index and risks of incident stroke subtypes: The JPHC study.

OBJECTIVE: The associations between body mass index (BMI) and stroke subtypes, particularly intracerebral hemorrhage, have not been consistent. Such inconsistencies may be due to differences in the age at which BMI was obtained. We examined the possible age modifications in the association between BMI and stroke risk. MATERIALS AND METHODS: We followed 88,754 participants, aged 40-69 years at baseline (1990-1994), of the Japan Public Health Center-based prospective (JPHC) study for stroke incidence. BMI was obtained using self-reported body weight and height, which were categorized using the following cut-off points: 18.5, 21, 23, 25, 27.5, and 30 kg/m2. Time-dependent Cox proportional hazards models that updated BMI and covariates using 5- and 10-year questionnaire responses were used to estimate hazard ratios and 95 % confidence intervals. The analyses were stratified by age group (40-59 and ≥60 years) and the age of the individuals was updated. RESULTS: During the median follow-up period of 19 years, we documented 4,690 strokes, including 2,781 ischemic strokes and 1,358 intracerebral hemorrhages. After adjusting for sex, age, smoking, alcohol consumption, leisure-time physical activity, history of hypertension, dyslipidemia, and diabetes mellitus, we observed a positive linear association between BMI and ischemic stroke (linear trend, p < 0.001) in both age groups (interaction p>0.05). In contrast, a curvilinear association between BMI and intracerebral hemorrhage was observed in both the middle (curvilinear trend, p=0.017) and the older group (curvilinear trend, p=0.098) (interaction p>0.05). CONCLUSION: BMI and stroke associations did not vary significantly with age, although the association may differ according to subtype.

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.

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.

Stair climbing and the incidence of atherosclerotic cardiovascular disease: a population-based prospective cohort study.

BACKGROUND: Stair climbing is a readily available form of physical activity with potential cardioprotective merits. Herein, we investigated the association between stair climbing and atherosclerotic cardiovascular disease (ASCVD) incidence among Japanese people. METHODS: This prospective cohort study used data from 7,282 participants, aged 30-84 years, registered in the Suita Study and free from stroke and ischemic heart disease (IHD). Standard approaches were used to detect incident ASCVD events, including cerebral infarction and IHD, during follow-up. Stair climbing was assessed using a baseline questionnaire. We applied the Cox regression to calculate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of incident ASCVD for climbing stairs in 20-39%, 40-59%, and ≥60% compared to <20% of the time. We adjusted the regression models for age, sex, body mass index, smoking, alcohol consumption, physical activity, hypertension, diabetes, atrial fibrillation, lipid profile, chronic kidney disease, and history of cardiac murmur or valvular diseases. RESULTS: A total of 536 new ASCVD events were detected within a median follow-up period of 16.6 years. In the age- and sex-adjusted model, stair climbing 20-39%, 40-59%, and ≥60% of the time was associated with lower ASCVD incidence: HRs (95% CIs) = 0.72 (0.56, 0.92), 0.86 (0.68, 1.08), and 0.78 (0.61, 0.99), respectively (p-trend = 0.020). The corresponding associations were attenuated after adjusting for lifestyle and clinical factors: HRs (95% CIs) = 0.74 (0.58, 0.95), 0.90 (0.71, 1.13), and 0.89 (0.69, 1.13), respectively (p-trend = 0.152). CONCLUSION: Frequent stair climbing was associated with lower ASCVD incidence; however, this association was partly explained by lifestyle and clinical factors of participants.

Life satisfaction and the risk of atherosclerotic cardiovascular disease in the general Japanese population: the Suita Study.

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is a major cause of morbidity and mortality. Life satisfaction is a measure of mental health with a potential cardioprotective role. This study aimed to investigate the association between life satisfaction and ASCVD risk in the general Japanese population. METHOD: We used data from 6,877 people (30-84 years) registered in the Suita Study, a Japanese population-based prospective cohort study. All participants were free from stroke and coronary heart disease (CHD) at baseline. Then, participants were followed up for incident ASCVD, including cerebral infarction and CHD. Cox proportional hazards models were used to calculate the hazard ratio (HR) and 95% confidence interval (95% CI) of incident ASCVD according to life satisfaction. RESULTS: Within 102,545 person-years (median follow-up = 16.6 years), 482 incident ASCVD events were identified. In the age- and sex-adjusted model, being very satisfied, rather satisfied, or not sure, compared to being dissatisfied with life, showed a lower risk of ASCVD: HR (95% CI) = 0.55 (0.41, 0.74), 0.67 (0.50, 0.89), and 0.57 (0.36, 0.88), respectively (p-trend < 0.001). The associations remained consistent after adjusting for stress and unfortunate events: HR (95% CI) = 0.57 (0.42, 0.77), 0.68 (0.50, 0.91), and 0.54 (0.35, 0.84), respectively (p-trend < 0.001). The results did not vary between cerebral infarction and CHD: HR (95% CI) for being very satisfied with life = 0.58 (0.37, 0.91) and 0.55 (0.36, 0.84), respectively. CONCLUSION: Life satisfaction was inversely associated with the risk of ASCVD in the investigated general Japanese population.

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.

Liver enzymes and the risk of stroke among the general Japanese population: a prospective cohort study.

BACKGROUND: Stroke is a major cause of morbidity and mortality. Liver enzymes, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transpeptidase (GGT), are markers of liver diseases with potential cardiovascular implications. OBJECTIVE: This study aimed to investigate the prospective association between liver enzymes and stroke risk. METHODS: We analyzed data from 3,379 men and 4,007 women without cardiovascular disease and registered in the Suita Study; a Japanese population-based prospective cohort study. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) of stroke risk were estimated per quintiles of ALT, AST, and GGT in men and women. RESULTS: Within a median follow-up period of 16.7 years, 438 incident stroke events were diagnosed. In men, compared to the second quintiles, the fifth (highest) quintiles of liver enzymes showed increased stroke risks: HRs (95% CIs) = 2.07 (1.35, 3.18) in ALT, 1.66 (1.10, 2.53) in AST, and 1.76 (1.11, 2.81) in GGT. The associations did not change with cerebral infarction risk: HRs (95% CIs) = 2.09 (1.24, 3.50) in ALT, 1.84 (1.11, 3.06) in AST, and 1.74 (1.00, 3.04) in GGT, respectively. The lowest ALT, AST, and GGT quintiles tended to show increased stroke and cerebral infarction risks, yet these associations were statistically insignificant. No such associations were shown in women. CONCLUSION: Elevated ALT, AST, and GGT levels were associated with increased stroke and cerebral infarction risks among Japanese men.

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.

Risk and population attributable fraction of stroke subtypes in Japan.

BACKGROUND: Associations of major risk factors for stroke with total and each type of stroke as well as subtypes of ischemic stroke and their population attributable fractions had not been examined comprehensively. METHODS: Participants of the Japan Public Health Center-based prospective (JPHC) Study Cohort II without histories of cardiovascular disease and cancer (n=14,797) were followed from 1993 through 2012. Associations of current smoking, hypertension, diabetes, overweight (body mass index ≥ 25 kg/m2), non-high-density lipoprotein cholesterol (non-HDLC) categories, low HDLC (< 40 mg/dL), urine protein, and history of arrhythmia were examined in a mutually-adjusted Cox regression model that included age and sex. Population attributable fraction (PAF) was estimated using the hazard ratios and the prevalence of risk factors among cases. RESULTS: Subjects with hypertension were 1.63 to 1.84 times more likely to develop any type of stroke. Diabetes, low HDLC, current smoking, overweight, urine protein, and arrhythmia were associated with risk of overall and ischemic stroke. Hypertension and urine protein were associated with risk of intracerebral hemorrhage while current smoking, hypertension, and low non-HDLC were associated with subarachnoid hemorrhage. Hypertension alone accounted for more than a quarter of stroke incidence, followed by current smoking and diabetes. High non-HDLC, current smoking, low HDLC, and overweight contributed mostly to large-artery occlusive stroke. Arrhythmia explained 13.2% of embolic stroke. Combined PAFs of all the modifiable risk factors for total, ischemic and large-artery occlusive strokes were 36.7 and 44.5% and 61.5%, respectively. CONCLUSION: Although there are differences according to the subtypes, hypertension could be regarded as the most crucial target for preventing strokes in Japan.