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.

Health Statuses of People in Poverty Receiving Public Assistance in Japan: A Scoping Review.

Background: Promoting health and well-being is essential to ensure dignified lives of the entire population, including those living in poverty. Guaranteeing the human right to health is a critical responsibility of social security policies. To address emerging issues associated with poverty, the Japanese government has implemented a welfare program known as public assistance-seikatsu-hogo. However, financial welfare programs may not fully mitigate health risks due to the complex impact of poverty on health. Although a global systematic review of the health status of public and social assistance recipients has been conducted, it did not include any studies from Japan. Furthermore, evidence for the development of health support strategies for Japanese recipients remains scarce. This scoping review aims to identify the current situation and potential issues concerning the health of recipients. Methods: PubMed was searched for articles published before November 2023. Of the 357 articles identified, 56 were included. Among those included, 35 used the individual status of receiving public assistance as an exposure variable, 13 considered public assistance recipients as the study population, and 8 used the prefectural proportion of the population receiving public assistance as an environmental predictor. Results: We found that public assistance recipients tend to have more disadvantageous health and well-being statuses than the general population, as reported in the global systematic review. Health inequalities were also observed among recipients based on their sociodemographic characteristics. In Japan, public assistance recipients face several health risks and are at a disadvantage compared with the general population. Conclusions: The distribution of risks is heterogeneous among recipients, despite the minimum income protection and financial benefits in health and long-term care use. Further studies to identify the effects of public assistance policy on the health of the impoverished population, evidence-based discussions, and reform of social security policies are warranted.

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.

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.

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.

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.

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.

Factors associated with prolonged duration of viral clearance in non-severe SARS-CoV-2 patients in Osaka, Japan.

BACKGROUND: We investigated factors associated with prolonged viral clearance of SARS-CoV-2 among non-severe adult patients in Osaka, Japan. A total of 706 laboratory-confirmed COVID-19 patients were enrolled in this longitudinal observational study between 29 January 2020 and 31 May 2020, across 62 hospitals and three non-hospital recuperation facilities. METHODS: Logistic regression analysis was performed to investigate the factors associated with prolonged (29 days: upper 25% in duration) viral clearance of SARS-CoV-2. Linear regression analysis was conducted to assess these factors 14 days after symptom onset. RESULTS: The median duration of viral clearance was 22 days from symptom onset. After adjustment for sex, age, symptoms, comorbidity, and location of recuperation, comorbidities were associated with prolonged duration: (OR, 1.77 [95% CI, 1.11-2.82]) for one, (OR, 2.47 [95% CI, 1.32-4.61]) for two or more comorbidities. Viral clearance 14 days after symptom onset was 3 days longer for one comorbidity and 4 days longer for two or more comorbidities compared to clearance when there was no comorbidity. CONCLUSION: The presence of comorbidity was a robust factor associated with a longer duration of viral clearance, extending by 3 to 4 days compared to patients with no comorbidity.

The characteristics and clinical course of patients with COVID-19 who received invasive mechanical ventilation in Osaka, Japan.

OBJECTIVE: To describe the detailed clinical course of patients with coronavirus disease 2019 (COVID-19) who received invasive mechanical ventilation. METHODS: We conducted a case series of patients with COVID-19 who received invasive mechanical ventilation in Osaka, Japan, between January 29 and May 28, 2020. We describe the patient characteristics and clinical course from onset. Additionally, we fitted logistic regression models to investigate the associations between patient characteristics and the 30-day mortality rate. RESULTS: A total of 125 patients who received invasive mechanical ventilation (median age [interquartile range], 68 [57-73] years; male, 77.6%) were enrolled. Overall, the 30-day mortality was 24.0%, and the median (interquartile range) length of ICU stay and length of invasive mechanical ventilation use were 16 (12-29) days and 13 (9-26) days, respectively. From clinical onset, 121 patients (96.8%) were intubated within 14 days. In multivariable logistic regression analysis, age of 65 years or older (odds ratio, 3.56; 95% confidence interval, 1.21-10.49; P = 0.02) and male sex (odds ratio, 3.75; 95% confidence interval, 1.00-11.24, P = 0.04) were significantly associated with a higher 30-day mortality rate. CONCLUSIONS: In this case series of patients with COVID-19 who received invasive mechanical ventilation in Japan, the 30-day mortality rate was 24.0%, and age 65 years or older and male sex were associated with higher 30-day mortality rate.

Influence of Hemoglobin Level on Muscle and Physical Functions, Activities of Daily Living, and Quality of Life in Patients With Hematological Malignancies.

PURPOSE: Patients with hematological malignancies often present with reduced muscle and physical functions, which are caused by the disease or related treatment. Moreover, patients with hematological malignancies rapidly develop low hemoglobin levels, and this may affect muscle and physical functions. This study aimed to identify the influence of hemoglobin levels on muscle and physical functions in patients with hematological malignancies. METHODS: Using a cross-sectional study design, this study included 60 patients with hematological malignancies (mean age = 68.0 ± 10.2 years, women 56.7%) who were hospitalized for chemotherapy- and radiotherapy-related side effects and underwent examination for skeletal muscle mass (SMM), muscle strength, physical function, activities of daily living (ADLs), psychological status, and quality-of-life (QOL), including physical symptoms. Participants were divided into 3 groups according to tertiles of hemoglobin levels: low (n = 19), middle (n = 20), and high (n = 21). Evaluation items were compared among the 3 groups. RESULTS: There was no significant difference among the 3 groups in terms of SMM. The low hemoglobin group showed significantly higher values of fatigue and dyspnea and lower values of muscle strength, ADLs, and QOL than the high hemoglobin group. CONCLUSIONS: Hemoglobin levels did not affect SMM; however, muscle weakness, decrease in physical function, physical symptoms such as fatigue and dyspnea, and decline in ADLs and QOL were observed in patients with low hemoglobin levels.