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.

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.

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.

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.

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.

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.

New 2019 JSH guidelines and the risk of incident cardiovascular disease: The Suita Study.

Hypertension is the most critical risk factor for cardiovascular disease (CVD). Since the definition of hypertension varies across guidelines, identifying blood pressure (BP) categories that should be targeted to prevent CVD is needed. Herein, we investigated the association between BP per the 2019 Japanese Society of Hypertension (JSH) guidelines and the risk of CVD, stroke, and coronary heart disease (CHD) using data from 7,643 participants (30-84 years) registered in the Suita Study. Within 113,838 person-years (16.6 median years of follow-up), 690 participants developed CVD (411 cases of stroke and 279 cases of CHD). Compared to normal BP (Systolic BP (SBP) < 120 and diastolic BP (DBP) < 80 mmHg), elevated BP (SBP 130-139 and/or DBP 80-89 mmHg) and hypertension (SBP ≥ 140 and/or DBP ≥ 90 mmHg) were associated with a higher risk of CVD, stroke, and CHD. High-normal BP (SBP 120-129 and DBP < 80 mmHg) was associated with a higher risk of CVD and CHD. In conclusion, CVD preventive interventions should begin at lower BP levels than those applied in the 2019 JSH guidelines.

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.

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.

Serum uric acid levels and the risk of diabetes mellitus in premenopausal and postmenopausal women: the Suita study.

OBJECTIVE: The association between serum uric acid levels and the risk of diabetes mellitus in women stratified by menopausal status is not well-established. Therefore, we investigated this association among a cohort of Japanese urban women. METHODS: We conducted a prospective cohort study on 3,304 women (1,252 premenopausal and 2,052 postmenopausal), aged 30 to 79 years, with no prior cardiovascular disease or diabetes mellitus, and enrolled from a general urban population. Cox proportional hazard model was used to calculate hazard ratios and 95% confidence intervals (CIs) for incident diabetes mellitus according to serum uric acid quartiles. RESULTS: During 13.8 years of median follow-up, 219 incident diabetes mellitus cases were diagnosed. The incidence rate per 1,000 person-years was 3.42 in premenopausal women and 6.19 in postmenopausal women. After adjustment for potential risk factors, the multivariable hazard ratios (95% CIs) of the highest versus lowest serum uric acid quartiles were 1.56 (0.77-3.16) in premenopausal women, 2.00 (1.19-3.34) in postmenopausal women, and 1.81 (1.21-2.73) in all women. The interaction based on menopausal status was not significant ( P = 0.872). The corresponding population attributable fractions (95% CIs) were 13.3% (-8.9% to 31.1%), 19.1% (5.3%-30.9%), and 17.0% (5.6%-27.0%), respectively. CONCLUSIONS: Serum uric acid levels were positively associated with the risk of diabetes mellitus in postmenopausal women, but not in premenopausal women. However, the lack of an association in premenopausal women may have been due to limited power, so further research is required to confirm this menopausal status-specific association.

Liver enzymes, alcohol consumption and the risk of diabetes: the Suita study.

AIM: We aimed to investigate the combined impact of liver enzymes and alcohol consumption on the diabetes risk. METHODS: Data on 5972 non-diabetic participants aged 30-79 years from the Suita study were analyzed. Diabetes incidence was surveyed every 2 years. Current daily alcohol consumption was defined as light drinking (< 23.0 g ethanol/day in men and < 11.5 g in women), moderate drinking (23.0-45.9 g and 11.5-22.9 g), and heavy drinking (≥ 46.0 g and ≥ 23.0 g). The nondrinkers category included both never-drinkers and former drinkers. RESULTS: During the median follow-up of 13 years, 597 incident diabetes cases were diagnosed. Higher levels of γ-glutamyltransferase (GGT), alanine aminotransferase (GPT), and aspartate aminotransferase (GOT) were associated with an increased diabetes risk, and current light drinkers had a lower risk of diabetes than nondrinkers. No sex differences were observed in these associations. Compared to nondrinkers having the lowest quartiles of liver enzymes, nondrinkers and current moderate/heavy drinkers having the highest quartiles had an increased risk of diabetes. However, no association was observed for current light drinkers having the highest quartiles of liver enzymes; the multivariable hazard ratios (95% CIs) in current light drinkers with the highest quartile of liver enzymes were 1.27 (0.68-2.37) for GGT, 1.05 (0.59-1.89) for GPT, and 0.76 (0.40-1.47) for GOT, respectively. CONCLUSION: High liver enzymes were associated with an increased diabetes risk. No increased diabetes risk was observed in current light drinkers, even in these who had high levels of liver enzymes.