Influence of blood pressure variations during hemodialysis on the prognosis of dialysis patients.

The prognosis of dialysis patients is poorer than that of the general population. The relationship between dialysis patients' blood pressure (BP) and mortality is controversial. We investigated the relationships between mortality and (i) pre-dialysis BP and (ii) BP variation during hemodialysis in maintenance dialysis patients.We retroactively analyzed the cases of the 284 patients on hemodialysis (mean age 68 ± 13 years old) who had been regularly followed at Kokura Daiichi Hospital, Japan in 2018. We assessed the relationship between the patients' BP components and risk of mortality over a 40-month follow-up.The patients' average systolic/diastolic BP values before dialysis in 2018 were 145 ± 18/77 ± 11, and those after dialysis were 129 ± 17/71 ± 10 mmHg. The prevalence of intradialytic hypotension was 46.8%. During an average follow-up of 35 months, 72 patients died, including from infectious diseases (n = 41), cardiovascular diseases (n = 9), malignancies (n = 5), and others (n = 17). The mortality rate was 32.7% in the pre-dialysis SBP < 140 mmHg group, 20.6% in the 140-159 mmHg group, and 22.2% in ≥ 160 mmHg group. In a multivariable-adjusted analysis, the hazard ratio for mortality in the pre-dialysis SBP < 140 mmHg group with intradialytic hypotension was significantly higher than that in the 140-159 mmHg group.In dialysis patients, pre-dialysis SBP < 140 mmHg and intradialytic hypotension posed a significantly higher risk for mortality. Our findings suggest that not only lower pre-dialysis BP, but also intradialytic hypotension is associated with poor prognosis in dialysis patients.

Swallowing dysfunction and the onset of fever in older residents with special care needs: a thirteen-month longitudinal prospective study.

A decline in swallowing function is frequently observed among older residents in nursing homes. We investigated whether swallowing dysfunction was related to the onset of fever in such individuals. Older residents aged ≥ 65 years from three nursing homes were included in this prospective study conducted from July 2017 to May 2019. The follow-up period was 13 months. The outcome was fever incidence in relation to the swallowing dysfunction. Baseline data on the activities of daily living, cognitive function, swallowing function, respiratory function, tongue pressure, and comorbidity conditions were collected. Dates on which the axillary temperature measured ay of participants was > 37.5 °C during the follow-up period were also recorded. For the statistical analyses, swallowing function assessed by the modified water swallow test (MWST) score was used to divide the participants into three groups: scores ≤ 3, 4, and 5. A total of 52 participants [median age, 89.5 years (67-104)] were enrolled. Kaplan-Meier analysis showed that the average periods until onset of fever in participants with MWST scores of ≤ 3, 4, and 5 were 8.0 (6.0-11.0), 10.0 (7.0-12.0), and 12.0 (10.0-13.0) months, respectively. Cox's proportional hazards regression model revealed that participants with an MWST score ≤ 3 were at a higher risk of fever than those with an MWST score of 5 (hazard ratio 11.5, 95% confidence interval 1.5-63.4, adjusted for possible confounders. The swallowing dysfunction correlated with the risk of fever in older residents of nursing homes.

Relationship between salt intake and sleep disordered breathing in dialysis patients.

BACKGROUND: The prevalence of sleep disordered breathing is high in patients with end-stage renal disease. Salt intake is related to the severity of obstructive sleep apnea in patients with resistant hypertension and hyperaldosteronism. We investigated the relationship between salt intake and sleep disordered breathing in patients on maintenance hemodialysis. PATIENTS AND METHODS: We studied 128 dialysis outpatients (mean age 63 ± 11 years) who were followed at Kokura Daiichi Hospital. We estimated each patient's salt intake using an InBody S10 body composition analyzer and measured the 3% oxygen desaturation index (ODI) during sleep using a Pulsewatch: PMP-200 GplusX. RESULTS: The average estimated salt intake was 8.0 ± 2.6 g/day, and the median value of that was 7.5 g/day. Blood pressure (BP) before and after dialysis were 140 ± 18/78 ± 11 and 127 ± 13/72 ± 8 mmHg, respectively. The geometric average number of 3% ODI was 7.1, and sleep disordered breathing was detected in 30% of all subjects. The patients with ≥ 7.5 g/day salt intake were younger and more frequently male and had higher body mass index (BMI) and BP before dialysis compared to those with salt intakes < 7.5 g/day. Patients with ≥ 7.5 g/day salt intake had a significantly higher geometric average number of 3% ODI; however, this relationship became weaker after adjusting for BMI. The same relationship was obtained for the prevalence of sleep disordered breathing. CONCLUSION: The prevalence of sleep disordered breathing in patients on maintenance hemodialysis was high, and the sleep disordered breathing was associated with salt intake and BMI.

Tongue cleaning maintains respiratory function in older individuals: A 1-year randomised controlled trial.

OBJECTIVE: The aim of this 1-year longitudinal randomised controlled trial was to evaluate the effectiveness of tongue cleaning on the maintenance of respiratory function in older adults requiring care. METHODS: The participants included 24 residents of two nursing homes in Kitakyushu, Japan. The participants were randomised to receive tongue cleaning with routine oral care (intervention group, n = 12), or routine oral care alone (control group, n = 12). Among the participants, three in the intervention group and four in the control group had cerebrovascular disease history, four in the intervention group and four in the control group had a history of cardiac disease, and five in the intervention group and four in the control group were without medical history. Respiratory function was assessed on the basis of the peak expiratory flow rate (PEFR). Tongue pressure, swallowing function, oral health status, activities of daily living and nutritional status were also measured at baseline and at the end of the 1-year follow-up period. RESULTS: The number of analysed participants in each group was 12. In the control group, the PEFR (1.6 [0.4-4.2] L s-1 vs 1.4 [0.4-3.2] L s-1 , P = .034) and tongue pressure (16.4 [1.7-35.2] kPa vs 8.0 [1.4-38.6] kPa, P = .032) significantly declined after 1-year. However, the PEFR (1.5 [0.8-2.9] L s-1 vs 1.6 [0.7-4.2] L s-1 , P = .366) and tongue pressure (18.1 [4.2-37.1] kPa vs 16.1 [5.2-41] kPa, P = .307) were maintained in the intervention group. The change in the PEFR was significantly greater in the intervention group compared with the control group (0.130 [-0.45-1.70] L s-1 vs -1.70 [-10.00-10.00] L s-1 , P = .028). CONCLUSION: Our findings suggest that tongue cleaning may help maintain tongue and respiratory function in older adults requiring care.

The relationship between masticatory performance and intakes of foods and nutrients in Japanese male workers: A cross-sectional study.

BACKGROUND: Although many studies have been conducted on the relationship between masticatory performance and nutrient ingestion in the elderly, few large-scale studies have been carried out using relatively young individuals. OBJECTIVES: The objective of this study was to clarify the association between the masticatory performance evaluated by the gummy-jelly test, not by visual examination, and nutrient ingestion state based on the brief self-administered diet history questionnaire (BDHQ). METHODS: This was a cross-sectional survey of 540 male workers. Somatometry, blood pressure measurement, blood test and medical interview were performed as a periodic health check-up. In the dental check-up, an oral examination, gummy-jelly test (glucosensor) and survey of ingested food and nutrients using BDHQ were performed. The participants were classified into two groups with low and normal values of masticatory performance. Participants with a score on the gummy-jelly test below 150 mg/dL or 150 mg/dL or higher were included in the low and normal groups, respectively. RESULTS: Two hundred and forty-eight participants (45.8%) had low masticatory performance, and 292 (53.2%) had normal masticatory performance. The intakes of some minerals and vitamins, such as calcium, vitamin D, vitamin B2 , small fish with bones and non-oily fish, were significantly lower in the low masticatory group than in the normal group. In contrast, the intake of sugar for coffee and tea and that of chicken were significantly higher in the low masticatory group than in the normal group. CONCLUSION: This study suggested that low masticatory performance can affect nutrient intake, which may cause non-communicable diseases.

Reduced Estimated GFR and Cardiac Remodeling: A Population-Based Autopsy Study.

RATIONALE & OBJECTIVE: Evidence suggests that cardiac remodeling, including left ventricular hypertrophy and myocardial fibrosis, develops with progression of kidney disease. Few studies have examined cardiac pathology across a range of estimated glomerular filtration rates (eGFRs), which was the objective of this investigation. STUDY DESIGN: Population-based cross-sectional study of deceased patients undergoing autopsy. SETTING & PARTICIPANTS: 334 of 694 consecutive deceased patients undergoing autopsy with available cardiac tissue, with a prior health examination within 6 years and without a prior diagnosis of heart disease. EXPOSURE: eGFR. OUTCOMES: The thickness of the left ventricular wall, sizes of cardiac cells, and percentages of fibrosis, estimated from pathology examination of autopsy samples. ANALYTICAL APPROACH: Generalized estimating equations. RESULTS: Lower eGFRs were associated with greater left ventricular wall thickness. Deceased patients with eGFRs≥60, 45 to 59, 30 to 44, and <30mL/min/1.73m2 had left ventricular wall thicknesses of 9.1, 9.5, 9.8, and 10.3mm, respectively (P for trend<0.05). Lower eGFRs were also significantly associated with greater mean values of cardiac cell size in the left ventricular wall after adjusting for confounders: 15.3, 16.1, 16.4, and 17.4µm for eGFRs≥60, 45 to 59, 30 to 44, and <30mL/min/1.73m2 (P for trend<0.01). Patients with lower eGFRs had significantly higher multivariable-adjusted geometric mean values for fibrosis percentage in the left ventricular wall: 3.22%, 4.33%, 3.83%, and 6.14% for eGFRs≥60, 45 to 59, 30 to 44, and <30mL/min/1.73m2 (P for trend<0.001). The negative association of eGFR with multivariable-adjusted mean values of cardiac cell width was stronger among patients with than those without anemia. LIMITATIONS: Cross-sectional study with a high proportion of elderly patients, no available information for severity or duration of hypertension and other cardiovascular risk factors, no information for medication use. CONCLUSIONS: These findings suggest that reduced eGFR is associated with cardiac hypertrophy and fibrosis of the left ventricle, cardiac cell enlargement, and cardiac fibrosis.

Day-to-Day Blood Pressure Variability and Risk of Dementia in a General Japanese Elderly Population: The Hisayama Study.

BACKGROUND: Several observational studies have reported that higher visit-to-visit blood pressure variability is a risk factor for cognitive impairment and dementia. However, no studies have investigated the association of day-to-day blood pressure variability assessed by home blood pressure measurement with the development of dementia. METHODS: A total of 1674 community-dwelling Japanese elderly without dementia, ≥60 years of age, were followed up for 5 years (2007-2012). Home blood pressure was measured 3 times every morning for a median of 28 days. Day-to-day systolic (SBP) and diastolic blood pressure variabilities, calculated as coefficients of variation (CoV) of home SBP and diastolic blood pressure, were categorized into quartiles. The hazard ratios and their 95% confidence intervals of the CoV levels of home blood pressure on the development of all-cause dementia, vascular dementia (VaD), and Alzheimer disease (AD) were computed with a Cox proportional hazards model. RESULTS: During the follow-up, 194 subjects developed all-cause dementia; of these, 47 had VaD and 134 had AD. The age- and sex-adjusted incidences of all-cause dementia, VaD, and AD increased significantly with increasing CoV levels of home SBP (all P for trend <0.05). These associations remained unchanged after adjustment for potential confounding factors, including home SBP. Compared with subjects in the first quartile of CoV levels of home SBP, the risks of the development of all-cause dementia, VaD, and AD were significantly higher in those in the fourth quartile (hazard ratio=2.27, 95% confidence interval=1.45-3.55, P<0.001 for all-cause dementia; hazard ratio=2.79, 95% confidence interval=1.04-7.51, P=0.03 for VaD; hazard ratio=2.22, 95% confidence interval=1.31-3.75, P<0.001 for AD). Similar associations were observed for CoV levels of home diastolic blood pressure. Meanwhile, home SBP levels were significantly associated with the risk of VaD but not with the risks of all-cause dementia and AD. There was no interaction between home SBP levels and CoV levels of home SBP on the risk of each subtype of dementia. CONCLUSIONS: Our findings suggest that increased day-to-day blood pressure variability is, independently of average home blood pressure, a significant risk factor for the development of all-cause dementia, VaD, and AD in the general elderly Japanese population.

Morning and Evening Blood Pressures Are Associated With Intima-Media Thickness in a General Population　- The Hisayama Study.

BACKGROUND: The association of morning and evening home blood pressures (HBPs) with carotid atherosclerosis has been uncertain in general populations, so we aimed to investigate it in a general Japanese population.Methods and Results:We performed a cross-sectional survey of 2,856 community-dwelling individuals aged ≥40 years to examine the association of morning and evening HBPs with carotid mean intima-media thickness (IMT). The age- and sex-adjusted geometric averages of carotid mean IMT increased significantly with increasing morning HBP (optimal: 0.67 mm; normal: 0.69 mm; high normal: 0.72 mm; grade 1 hypertension: 0.74 mm; and grade 2+3 hypertension: 0.76 mm) and with increasing evening HBP (0.68 mm, 0.71 mm, 0.73 mm, 0.76 mm, and 0.78 mm, respectively) (both P for trend <0.001). These associations remained significant even after adjusting for potential confounding factors. Likewise, both isolated morning hypertension (morning HBP ≥135/85 mmHg and evening HBP <135/85 mmHg) and isolated evening hypertension (evening HBP ≥135/85 mmHg and morning HBP <135/85 mmHg) as well as sustained hypertension (both morning and evening HBP ≥135/85 mmHg) were significantly associated with thicker mean IMT. CONCLUSIONS: Our findings suggested that both morning and evening HBPs were significantly associated with carotid atherosclerosis in this general Japanese population.

The long-term association between physical activity and risk of dementia in the community: the Hisayama Study.

We investigated the long-term influence of physical activity on the risk of dementia in an elderly Japanese population. A total of 803 community-dwelling elderly Japanese individuals without dementia aged ≥65 years were followed prospectively for 17 years. Physically active status was defined as engaging in exercise at least one or more times per week during leisure time, and participants were divided into an active group and an inactive group by the presence or absence of such physical activity. The risk estimates of physical activity on the development of all-cause dementia and its subtypes were computed using a Cox proportional hazards model. During the follow-up, 291 participants developed all-cause dementia. Of these, 165 had Alzheimer's disease (AD), 93 had vascular dementia (VaD), and 47 had other dementia. Compared with the inactive group, the active group showed significantly lower crude incidence of AD (21.8 vs. 14.2 per 1000 person-years, p = 0.01), but no significant differences were observed for all-cause dementia (35.6 vs. 30.5, p = 0.17), VaD (11.3 vs. 9.8, p = 049), and other dementia (4.6 vs. 7.1, p = 0.15). After adjusting for potential confounders, the relationship between physical activity and risk of AD remained significant (adjusted hazard ratio 0.59, 95% confidence interval 0.41-0.84, p = 0.003). Our findings suggest that physical activity reduces the long-term risk of dementia, especially AD, in the general Japanese population.

Combination of Helicobacter pylori Antibody and Serum Pepsinogen as a Good Predictive Tool of Gastric Cancer Incidence: 20-Year Prospective Data From the Hisayama Study.

BACKGROUND: There is little information regarding whether the combination of Helicobacter pylori (H. pylori) antibody and serum pepsinogen (sPG), which is a marker of the degree of atrophic gastritis, has a discriminatory ability for detecting incident gastric cancer. We examined this issue in a long-term prospective cohort study of a Japanese population. METHODS: A total of 2446 Japanese community-dwelling individuals aged ≥40 years were stratified into four groups according to baseline H. pylori serological status and sPG: Group A (H. pylori[-], sPG[-]), Group B (H. pylori[+], sPG[-]), Group C (H. pylori[+], sPG[+]), and Group D (H. pylori[-], sPG[+]), and participants were followed up prospectively for 20 years. RESULTS: During the follow-up, 123 subjects developed gastric cancer. Compared with that in Group A, the cumulative incidence of gastric cancer was significantly increased in Groups B, C, and D, whereas no significant difference was found between Groups C and D. The multivariable-adjusted risk of gastric cancer was significantly increased in Group B (hazard ratio [HR], 4.08; 95% confidence interval [CI], 1.62-10.28) and in Groups C and D combined (HR 11.1; 95% CI, 4.45-27.46). When the multivariable model with H. pylori antibody was changed into that with the combination of H. pylori antibody and sPG, the C statistics for developing gastric cancer increased significantly (0.773 vs 0.732, P = 0.005), and the continuous net reclassification improvement value was 0.591 (P < 0.001). CONCLUSIONS: Our findings suggest that the combination of H. pylori antibody and sPG is a useful tool for predicting the development of gastric cancer.

Association of hemoglobin A1c and glycated albumin with carotid atherosclerosis in community-dwelling Japanese subjects: the Hisayama Study.

BACKGROUND: It is not clear which glucose measure is more useful in the assessment of atherosclerosis. We investigated the associations of hemoglobin A1c (HbA1c), glycated albumin (GA), 1,5-anhydroglucitol (1,5-AG), fasting plasma glucose (FPG), and 2-hour postload glucose (PG) with carotid intima-media thickness (IMT) in community-dwelling Japanese subjects. METHODS: A total of 2702 subjects aged 40-79 years underwent a 75-g oral glucose tolerance test and measurements of HbA1c, GA, 1,5-AG, and carotid IMT by ultrasonography in 2007-2008. Carotid wall thickening was defined as a maximum IMT of >1.0 mm. The crude and multivariable-adjusted linear and logistic regression models were used to analyze cross-sectional associations between levels of glycemic measures and carotid IMT. RESULTS: The crude average of the maximum IMT increased significantly with rising quartiles of HbA1c, GA, FPG, and 2-hour PG levels in subjects with and without glucose intolerance (GI), while no clear association was observed for 1,5-AG. After adjustment for other confounding factors, positive trends for HbA1c, GA, and FPG (all p for trend < 0.05), but not 2-hour PG (p = 0.07) remained robust in subjects with GI, but no such associations were found in those without GI. When estimating multivariable-adjusted ß values for the associations of 1 SD change in glycemic measures with the maximum IMT in subjects with GI, the magnitude of the influence of HbA1c (ß = 0.021), GA (ß = 0.024), and FPG (ß = 0.024) was larger than that of 2-hour PG (ß = 0.014) and 1,5-AG (ß = 0.003). The multivariable-adjusted odds ratios for the presence of carotid wall thickening increased significantly with elevating HbA1c, GA, and FPG levels only in subjects with GI (all p for trend < 0.001). Among subjects with GI, the area under the receiver operating characteristic curve significantly increased by adding HbA1c (p = 0.04) or GA (p = 0.04), but not 1,5-AG, FPG, or 2-hour PG, to the model including other cardiovascular risk factors. CONCLUSIONS: In community-dwelling Japanese subjects with GI, elevated HbA1c, GA, and FPG levels were significantly associated with increased carotid IMT, and HbA1c and GA provided superior discrimination for carotid wall thickening compared to 1,5-AG, FPG, and 2-hour PG, suggesting that HbA1c and GA are useful for assessing carotid atherosclerosis.

Effect of losartan on serum uric acid in hypertension treated with a diuretic: the COMFORT study.

It has been shown that losartan, an angiotensin II receptor blocker (ARB), reduces serum uric acid levels. However, the effects of losartan on serum uric acid levels in the patients treated with a thiazide diuretic have not been fully elucidated. We have investigated the effects of losartan compared with other ARBs on blood variables and blood pressure control in hypertensive patients treated with a thiazide diuretic using data from the COMFORT study. The present analysis included a total of 118 hypertensive subjects on combination treatment with ARBs except for losartan and a diuretic who were randomly assigned to a daily regimen of a combination pill (losartan 50 mg/hydrochlorothiazide 12.5 mg) or to continuation of two pills, an ARB except for losartan and a diuretic. Blood pressures were evaluated at 1, 3, and 6 months after randomization and changes in blood variables including serum uric acid were evaluated during 6 months treatment period. Mean follow-up blood pressure levels were not different between the combination pill (losartan treatment) group and the control (ARBs except for losartan) group. On the other hand, serum uric acid significantly decreased in the combination pill group compared with the control group (-0.44 versus + 0.10 mg/dl; p = 0.01), although hematocrit, serum creatinine, sodium and potassium were not different between the groups. These results suggest that the treatment regimen switched from a combination therapy of ARBs except for losartan and a diuretic to a combination pill (losartan/ hydrochlorothiazide) decreases serum uric acid without affecting blood pressure control.

Secular trends in cardiovascular disease and its risk factors in Japanese: half-century data from the Hisayama Study (1961-2009).

BACKGROUND: Changes in lifestyle and advances in medical technology during the past half century are likely to have affected the incidence and mortality of cardiovascular disease and the prevalence of its risk factors in Japan. METHODS AND RESULTS: We established 5 cohorts consisting of residents aged ≥40 years in a Japanese community, in 1961 (n=1618), 1974 (n=2038), 1983 (n=2459), 1993 (n=1983), and 2002 (n=3108), and followed up each cohort for 7 years. The age-adjusted incidence of stroke decreased greatly, by 51% in men and by 43% in women, from the 1960s to the 1970s, but this decreasing trend slowed from the 1970s to the 2000s. Among the stroke subtypes, ischemic stroke in both sexes and intracerebral hemorrhage in men showed a similar pattern. Stroke mortality decreased as a result of the decline in incidence and a significant improvement in survival rate. Although the incidence of acute myocardial infarction did not change in either sex, disease mortality declined slightly in women. From the 1960s to the 2000s, blood pressure control among hypertensive individuals improved significantly and the smoking rate decreased, but the prevalence of glucose intolerance, hypercholesterolemia, and obesity increased steeply. CONCLUSIONS: Our findings suggest that in Japanese, the decreasing trends in the incidence of ischemic stroke have recently slowed down, and there has been no clear change in the incidence of acute myocardial infarction, probably because the benefits of hypertension control and smoking cessation have been negated by increasing metabolic risk factors.

Thresholds of various glycemic measures for diagnosing diabetes based on prevalence of retinopathy in community-dwelling Japanese subjects: the Hisayama Study.

BACKGROUND: There has been controversy over the diagnostic thresholds of hemoglobin A1c (HbA1c) for diabetes. In addition, no study has examined the thresholds of glycated albumin (GA) and 1,5-anhydroglucitol (1,5-AG) for diagnosing diabetes using the presence of diabetic retinopathy (DR). We examined the optimal thresholds of various glycemic measures for diagnosing diabetes based on the prevalence of DR in community-dwelling Japanese subjects. METHODS: A total of 2,681 subjects aged 40-79 years underwent a 75-g oral glucose tolerance test, measurement of HbA1c, GA, and 1,5-AG, and an ophthalmic examination in 2007-2008. The associations of glycemic measures with DR status were examined cross-sectionally. DR was assessed by an examination of the fundus photograph of each eye and graded according to the International Clinical Diabetic Retinopathy Disease Severity Scale. We divided the values of glycemic measures into ten groups on the basis of deciles. The receiver operating characteristic (ROC) curve analysis was performed to determine the optimal threshold of each glycemic measure for detecting the presence of DR. RESULTS: Of the subjects, 52 had DR. The prevalence of DR increased steeply above the ninth decile for fasting plasma glucose (FPG) (6.2-6.8 mmol/l), for 2-hour postload glucose (PG) (9.2-12.4 mmol/l), for HbA1c (5.9-6.2% [41-44 mmol/mol]), and for GA (16.2-17.5%), and below the second decile for 1,5-AG (9.6-13.5 µg/mL). The ROC curve analysis showed that the optimal thresholds for DR were 6.5 mmol/l for FPG, 11.5 mmol/l for 2-hour PG, 6.1% (43 mmol/mol) for HbA1c, 17.0% for GA, and 12.1 µg/mL for 1,5-AG. The area under the ROC curve (AUC) for 2-hour PG (0.947) was significantly larger than that for FPG (0.908), GA (0.906), and 1,5-AG (0.881), and was marginally significantly higher than that for HbA1c (0.919). The AUCs for FPG, HbA1c, GA, and 1,5-AG were not significantly different. CONCLUSIONS: Our findings suggest that the FPG and HbA1c thresholds for diagnosing diabetes in the Japanese population are lower than the current diagnostic criterion, while the 2-hour PG threshold is comparable with the diagnostic criterion. 2-hour PG had the highest discriminative ability, whereas FPG, HbA1c, GA, and 1,5-AG were similar in their ability.

Trends in the incidence and survival of intracerebral hemorrhage by its location in a Japanese community.

BACKGROUND: No previous population-based studies have examined secular trends in the incidence of intracerebral hemorrhage (ICH) by its location. METHODS AND RESULTS: We established 3 cohorts consisting of residents of Hisayama, Japan, aged ≥40 years without a history of stroke or myocardial infarction in 1961 (the first cohort, n=1,618), in 1974 (the second cohort, n=2,038), and in 1988 (the third cohort, n=2,637). Each cohort was followed for 13 years. The age- and sex-adjusted incidence of ICH significantly declined from the first to the second cohort and showed no further change in the third cohort. With regard to the ICH location, the incidence of putaminal hemorrhage decreased steadily, mainly in subjects aged 60-69 years, whereas the incidence of thalamic hemorrhage increased, especially in those aged ≥70 years. Both hypertension and alcohol intake were strong risk factors for ICH in the first cohort, but their influence declined with time. Blood pressure levels in hypertensive subjects decreased significantly, and the proportion of current drinkers decreased slightly over the study period. CONCLUSIONS: Our findings suggest that the ICH incidence steeply declined from the 1960s to the 1970s in Japan as a result of the reduced influence of hypertension and alcohol intake, but that this decline has leveled off since then, probably because of the increased incidence of thalamic hemorrhage in the elderly in recent years.

Serum 1,25-dihydroxyvitamin d and the development of kidney dysfunction in a Japanese community.

BACKGROUND: Recent evidence indicates that vitamin D deficiency is associated with an increased risk of renal impairment, but studies addressing the influence of vitamin D deficiency on the development of chronic kidney disease (CKD) in the general Asian population have been few. METHODS AND RESULTS: A total of 2,417 community-dwelling individuals without CKD stage 3-5 aged ≥40 years were followed for 5 years (mean age, 60 years; women, 59.1%). The cumulative incidence of CKD stage 3-5, defined as estimated glomerular filtration rate (eGFR) <60ml·min(-1)·1.73m(-2), and the rate of decline in eGFR according to quartile of serum 1,25-dihydroxyvitamin D (1,25(OH)2D), were estimated. During follow-up, 378 subjects experienced CKD stage 3-5. The age- and sex-adjusted incidence of CKD stage 3-5 increased significantly with decreasing serum 1,25(OH)2D (P for trend <0.001). Compared with the highest quartile, the multivariate-adjusted odds ratio for the development of CKD stage 3-5 was 1.90 in the lowest quartile and 1.74 in the second lowest quartile, after adjusting for confounding factors. Additionally, lower serum 1,25(OH)2D was significantly associated with a greater change in eGFR (-0.10ml·min(-1)·1.73m(-2)·year(-1) per 10-pg/ml decrement in serum 1,25(OH)2D). CONCLUSIONS: Lower serum 1,25(OH)2D is a significant risk factor for the development of CKD stage 3-5 in the general Asian population.

Decreased serum creatinine to cystatin C ratio is associated with low tongue pressure.

AIM: Tongue strength plays an important role in the process of food intake, and low tongue pressure has been associated with aspiration pneumonia, cognitive decline, and mortality. However, special equipment for tongue pressure measurement is uncommon in general practice. Recently, the serum creatinine-to-cystatin C (Cr/CysC) ratio has been validated as a marker of muscle volume mass. Thus, we aimed to investigate the association of the serum Cr/CysC ratio with tongue pressure in a cross-sectional study. METHODS: This single-center, cross-sectional study enrolled 73 participants (mean age, 71.7 years; men, 49.3%) who regularly attended the hospital for treatment of chronic disease. A tongue pressure of <30 kPa was defined as low tongue pressure. We evaluated the relationships between the serum Cr/CysC ratio and tongue pressure using multiple regression analysis. RESULTS: The serum Cr/CysC ratio was correlated with tongue pressure (R2 = 0.25, P < 0.0001). In multiple regression analyses adjusted for confounders including age, sex, body mass index, and serum albumin, the association remained significant (P = 0.0001). In logistic analyses, the multivariable-adjusted odds ratios of the Cr/CysC ratio for tertiles 1 and 2 compared with tertile 3 for low tongue pressure were 7.81 (95% confidence interval, 1.45-51.73) and 2.71 (95% confidence interval, 0.60-13.19), respectively. CONCLUSIONS: We demonstrated that a decreased serum Cr/CysC ratio was associated with a higher risk of low tongue pressure. Our findings suggest that this simple serum surrogate marker may be a first step toward an intervention for oral function by general practitioners. Geriatr Gerontol Int 2024; 24: 102-108.

White-coat and masked hypertension are associated with carotid atherosclerosis in a general population: the Hisayama study.

BACKGROUND AND PURPOSE: On the basis of combined measurements of clinic blood pressure (CBP) and home blood pressure (HBP), blood pressure status can be divided into normotension, white-coat hypertension (WCHT), masked hypertension (MHT), and sustained hypertension (SHT). Despite the clear impact of MHT and SHT on clinical and subclinical arterial disease, uncertainty about the influence of WCHT remains. The objective of this study was to investigate the associations of WCHT, MHT, and SHT with carotid atherosclerosis in a general population. METHODS: This is a cross-sectional survey of 2915 community-dwelling Japanese aged ≥ 40 years. Normotension was defined as CBP<140/90 and HBP<135/85 mm Hg; WCHT, CBP ≥ 140/90 and HBP<135/85 mm Hg; MHT, CBP<140/90 and HBP ≥ 135/85 mm Hg; and SHT, CBP ≥ 140/90 and HBP ≥ 135/85 mm Hg. Mean intima-media thickness of carotid arteries was measured using a computer-automated system, and carotid stenosis was defined as diameter stenosis ≥ 30%. RESULTS: There were 1374 subjects (47.1%) with normotension, 200 (6.9%) with WCHT, 639 (21.9%) with MHT, and 702 (24.1%) with SHT. The geometric average of mean intima-media thickness was significantly higher among subjects with WCHT (0.73 mm), MHT (0.77 mm), and SHT (0.77 mm) than those with normotension (0.67 mm; all P<0.001 versus normotension). Compared with normotension, all types of hypertension were also associated with increased likelihood of carotid stenosis (age- and sex-adjusted odds ratio, 2.36 [95% confidence interval, 1.27-4.37] for WCHT, 1.95 [1.25-3.03] for MHT, and 3.02 [2.01-4.54] for SHT). These associations remained significant even after adjustment for other cardiovascular risk factors. CONCLUSIONS: WCHT, as well as MHT, and SHT were associated with carotid atherosclerosis in a general Japanese population.

Clinical significance of plasma VEGF value in ischemic stroke - research for biomarkers in ischemic stroke (REBIOS) study.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a well-known molecule mediating neuronal survival and angiogenesis. However, its clinical significance in ischemic stroke is still controversial. The goal of this study was to examine the temporal profile of plasma VEGF value and its clinical significance in ischemic stroke with taking its subtypes into consideration. METHODS: We prospectively enrolled 171 patients with ischemic stroke and age- and gender-matched healthy subjects. The stroke patients were divided into 4 subtypes: atherothrombotic infarction (ATBI, n = 34), lacunar infarction (LAC, n = 45), cardioembolic infarction (CE, n = 49) and other types (OT, n = 43). Plasma VEGF values were measured as a part of multiplex immunoassay (Human MAP v1.6) and we obtained clinical information at 5 time points (days 0, 3, 7, 14 and 90) after the stroke onset. RESULTS: Plasma VEGF values were significantly higher in all stroke subtypes but OT than those in the controls throughout 90 days after stroke onset. There was no significant difference in the average VEGF values among ATBI, LAC, and CE. VEGF values were positively associated with neurological severity in CE patients, while a negative association was found in ATBI patients. After adjustment for possible confounding factors, plasma VEGF value was an independent predictor of poor functional outcome in CE patients. CONCLUSIONS: Although plasma VEGF value increases immediately after the stroke onset equally in all stroke subtypes, its significance in functional outcome may be different among the stroke subtypes.

Angiopoietin-like protein 2 is associated with chronic kidney disease in a general Japanese population: the Hisayama Study.

BACKGROUND: Angiopoietin-like protein 2 (Angptl2) is an adipokine that promotes inflammation and endothelial dysfunction of the vessels. The aim of this study was to investigate the relationship between serum Angptl2 level and chronic kidney disease (CKD). METHODS AND RESULTS: A total of 3,169 community-dwelling subjects aged ≥40 years were divided into quintiles by Angptl2 level. CKD was defined as the presence of albuminuria (urine albumin-creatinine ratio ≥30.0mg/g) or decreased estimated glomerular filtration rate (eGFR <60ml·min(-1)·1.73m(-2)). The odds ratio (OR) for the presence of CKD was calculated using a logistic regression model. The overall prevalence of CKD was 37.5%. The age- and sex-adjusted ORs for the presence of CKD increased with higher serum Angptl2 level. This trend remained significant after adjusting for known cardiovascular risk factors (<2.01ng/ml: OR, 1.00 (reference); 2.01-2.48ng/ml: OR, 1.67, 95% confidence interval [CI]: 1.24-2.24; 2.49-2.99ng/ml: OR, 1.70, 95% CI: 1.27-2.28; 3.00-3.65ng/ml: OR, 1.78, 95% CI: 1.32-2.39; ≥3.66ng/ml: OR, 1.79, 95% CI: 1.32-2.43; P-value for trend=0.001). Multivariate-adjusted ORs for the presence of albuminuria increased significantly with elevated serum Angptl2 (P-value for trend=0.004), while there was no evidence of a significant relationship between serum Angptl2 level and decreased eGFR (P-value for trend=0.08). CONCLUSIONS: Elevated serum Angptl2 is associated with the likelihood of CKD in the general population.