Sex- and Age-Specific Associations Between Metabolic Syndrome and Future Functional Disability in the Japanese Older Population.

Whether the association between metabolic syndrome (MetS) and functional disability differs depending on sex or age remains unknown. To determine the association between MetS and functional disability in older people separately by sex and age groups. A total of 11 083 participants (4407 men and 6676 women) aged 65 years or over without functional disability were enrolled. MetS was defined according to the revised NCEP ATP III guidelines. Functional disability was defined by a new certification in the long-term care insurance in Japan. Cox proportional hazards models were used to assess the risk of functional disability with adjustment for possible confounding factors. Over the mean observation period of 10.5 years, 1282 men and 2162 women experienced functional disability. For those aged 65 to 74 years, HRs (95% CIs) for functional disability in the MetS group were 1.33 (1.07-1.66) in men and 1.15 (1.000-1.32) in women. For those aged 75 years or older, there was no significant association in men or women. In subjects with a severe care need level, there was a marginal significant association in men aged 65 to 74 years. Among the MetS components that independently increased the risk of functional disability were glucose intolerance and elevated blood pressure (men and women aged 65-74 years), obesity (women aged 65-74 years), and glucose intolerance (women aged 75 years or older). MetS contributed to an increase in a high risk of future functional disability among individuals aged 65 to 74 years. In this age group, improvement of lifestyle, health promotion and interventions for MetS from middle age may prevent future functional disability.

Rapid weight change as a predictor of disability among community-dwelling Japanese older adults.

AIM: To fill the knowledge gap regarding weight change and the onset of disability in community-dwelling Japanese older adults, we investigated the potential effects of rapid weight change on disability risk as defined by Japan's long-term care insurance (LTCI) system. METHODS: We analyzed data from a longitudinal study of 10 375 community-dwelling older Japanese adults (≥65 years) who were not LTCI needs certified at baseline and joined the study from 2002 to 2005. Weight change (percentage) was calculated by subtracting participants' weight in the previous year from that measured during a physical examination at study commencement. The five weight-change categories ranged from sizable weight loss (≤ -8.0%) to sizable weight gain (≥ +8.0%). Disability was defined according to LTCI certifications at follow-up. Hazard ratios (HRs) and 95% confidence intervals were calculated for new-onset disability using a Cox proportional hazards model that fitted the proportional subdistribution hazards regression model with weights for competing risks of death. RESULTS: During the mean 10.5-year follow-up, 2994 participants developed a disability. Sizable weight loss (HR [95% confidence intervals], 1.41 [1.17-1.71]) and weight loss (1.20 [1.05-1.36]) were significant predictors of disability onset. Sizable weight gain (1.45 [1.07-1.97]) corresponded to severe disability. Stratified analyses by lifestyle and initial body mass index categories revealed more pronounced associations between weight change and disability risk in the unhealthy lifestyle and below initial normal body mass index groups. CONCLUSIONS: Rapid and sizable weight gain could be additional criteria for disability risk in older adults. Geriatr Gerontol Int 2023; 23: 809-816.

Human Plasma Xanthine Oxidoreductase Activity in Cardiovascular Disease: Evidence from a Population-Based Study.

Xanthine oxidoreductase (XOR) and its products contribute to the development of chronic inflammation and oxidative stress. Excessive XOR activity is believed to promote inflammatory responses and atherosclerotic plaque formation, which are major cardiovascular risk factors. The mechanisms of XOR activity in the development and progression of cardiovascular disease (CVD), coupled with the complexity of the relationship between XOR activity and the biological effects of uric acid; reactive oxygen species; and nitric oxide, which are the major products of XOR activity, have long been debated, but have not yet been clearly elucidated. Recently, a system for measuring highly sensitive XOR activity in human plasma was established, and there has been progress in the research on the mechanisms of XOR activity. In addition, there are accumulating findings about the relationship between XOR activity and CVD. In this narrative review, we summarize existing knowledge regarding plasma XOR activity and its relationship with CVD and discuss future perspectives.

Association between the extent of house collapse and urine sodium-to-potassium ratio of victims affected by the 2011 Great East Japan Earthquake and Tsunami: a cross-sectional study.

People who experience natural disasters have a high risk of developing cardiovascular diseases. We investigated the association between the extent of house collapse and urine sodium-to-potassium (UNa/K) ratio of 2011 Great East Japan Earthquake victims. We used the baseline survey data of the Tohoku Medical Megabank Project Community-Based Cohort Study of 29 542 individuals (aged 20-74 years) residing in the affected areas. The UNa/K ratio was calculated using spot urinary electrolyte values. Analysis of covariance was used to calculate the multivariate-adjusted geometric means of the UNa/K ratio in the following groups stratified according to the self-reported extent of house collapse: total collapse (TC), half collapse (HC), partial collapse (PC), and no damage (ND). Multivariable-adjusted odds ratios (ORs) for a high UNa/K ratio were calculated using logistic regression. The TC, HC, PC, and ND groups comprised 5 359 (18.1%), 3 576 (12.1%), 7 331 (24.8%), and 13 276 (44.9%) participants, respectively. The TC (3.33; 95% confidence interval [CI], 3.28-3.38), HC (3.37; 3.30-3.43), and PC (3.32; 3.28-3.37) groups had significantly higher multivariate-adjusted geometric means of the UNa/K ratio than the ND (3.24; 3.21-3.27) group. The multivariable-adjusted ORs (95% CIs) for a high UNa/K ratio in the TC, HC, and PC groups vs. the ND group were 1.07 (0.99-1.15), 1.20 (1.11-1.31), and 1.20 (1.12-1.28), respectively. Similar associations between house collapse and UNa/K ratio were observed for both sexes. We report that victims of a natural disaster tend to have a diet with high sodium-to-potassium ratio.

Association between Plasma Xanthine Oxidoreductase Activity and the Renal Function in a General Japanese Population: The Tohoku Medical Megabank Community-Based Cohort Study.

INTRODUCTION: Xanthine oxidoreductase (XOR) has been identified as a critical source of reactive oxygen species in various pathophysiological conditions, including hypertension, endothelial dysfunction, and atherosclerosis. This study investigated the association between XOR and renal function in a general Japanese population. METHODS: The Iwate Tohoku Medical Megabank Organization pooled individual participant data from a community-based cohort study in Iwate prefecture. Chronic kidney disease (CKD) was estimated using the estimated glomerular filtration rate of cystatin C (eGFRcys). Individuals with a history of hyperuricemia or severe renal dysfunction (eGFRcys <15 mL/min/1.73 m2 or undergoing dialysis) were excluded from the study. We performed a multinominal multivariate logistic analysis adjusted for age, blood pressure, uric acid, glycated hemoglobin A1c, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol to associate XOR activity and renal function. RESULTS: The present study included 4,248 participants (male/female: 1,373/2,875, age: 62.9 ± 11.7 years). When participants were divided according to XOR quartiles, blood pressure, body mass index, uric acid, low-density lipoprotein cholesterol, and glycated hemoglobin A1c were highest in the highest XOR quartile (all p < 0.001). The XOR activity was significantly higher in the subgroup with CKD stage G3 and G4 (G1 vs. G2 vs. G3-G4: 44.8 ± 40.5 vs. 52.0 ± 42.9 vs. 54.1 ± 43.9 pmol/h/mL, p = 0.02). The higher XOR activity was significantly associated with an increase of CKD stage: the odd ratios (95% confidence intervals) per 1 pmol/h/mL increase in XOR activity with CKD stage G1 as a reference were 1.37 (1.13-1.73) in G2 and 1.51 (1.30-1.84) in G3-G4. CONCLUSION: The present study concluded that high XOR activity was associated with the severity of CKD in a general Japanese population, suggesting that upregulated XOR activity may be involved in advanced renal dysfunction.

Renal thrombotic microangiopathy and nephrotic proteinuria induced by intravitreal injection of aflibercept for diabetic macular edema.

BACKGROUND: Vascular endothelial growth factor inhibitors (VEGFIs) are used to treat malignant neoplasms and ocular diseases by inhibiting angiogenesis. Systemic use of VEGFIs has various side effects, including hypertension, proteinuria, and thrombotic microangiopathy, but adverse events due to intravitreal injection of VEGFIs have not been fully clarified. Although age-related macular degeneration was initially the most common target of intravitreal injection of VEGFIs, it has also been applied sporadically for diabetic macular edema in recent years. Proteinuria following intravitreal injection of VEGFIs would be reversible. In patients with diabetes mellitus (DM), however, it would be difficult to determine whether kidney damage arises from the clinical course of DM or from intravitreal injection of VEGFIs for diabetic macular edema. CASE PRESENTATION: A 55-year-old woman with a 20-year history of type 2 DM began intravitreal injection of VEGFI (aflibercept, 2 mg every 4 weeks) for treatment of diabetic macular edema 2 years previously. She presented with leg edema, hypertension, and nephrotic-range proteinuria 14 months after the first injection. Histological examination of renal biopsy specimens revealed diabetic nephropathy with renal thrombotic microangiopathy probably associated with intravitreal injection of VEGFI. The patient's nephrotic syndrome completely improved at 6 months after simply discontinuing aflibercept. CONCLUSIONS: This is a precious report of pathologically investigated renal thrombotic microangiopathy leading to nephrotic syndrome due to intravitreal injection of aflibercept for diabetic macular edema in a patient with type 2 DM. Renal function and proteinuria should be monitored in diabetic patients who receive intravitreal injection of a VEGFI. If kidney damage develops independent of the clinical course of DM during intravitreal injection of a VEGFI, renal biopsy should be performed and intravitreal VEGFI injection discontinued.

Association between Milk Intake and Incident Stroke among Japanese Community Dwellers: The Iwate-KENCO Study.

We aimed to evaluate the association between the milk consumption and incident stroke in a Japanese population, where milk consumption is lower than that of Western countries. In total, 14,121 participants (4253 men and 9868 women) aged 40-69 years, free from cardiovascular diseases (CVD) were prospectively followed for 10.7 years. Participants were categorized into four groups according to the milk intake frequency obtained from a brief-type self-administered diet questionnaire. The adjusted HRs of total stroke, ischemic stroke and haemorrhagic stroke associated with milk intake frequency were calculated using the Cox proportional hazards model. During the follow-up, 478 stroke cases were detected (208 men and 270 women). Compared to women with a milk intake of <2 cups/week, those with an intake of 7 to <12 cups/week had a significantly low risk of ischemic stroke in a model adjusting CVD risk factors; the HR (95% CI) was 0.53 (0.32-0.88). No significant associations were found in men. This study suggested that milk intake of 7 to <12 cups/week decreased the risk of ischemic stroke in Japanese women. Milk intake of about 1 to <2 cups/day may be effective in the primary prevention of ischemic stroke in a population with low milk intake.

Utility of urinary albumin excretion as an index for stratifying the residual cardiovascular risk in patients undergoing antihypertensive agents treatment.

BACKGROUND: Patients treated with antihypertensive medication, even those with well controlled blood pressure (BP), are at higher risk for the development of atherosclerotic cardiovascular disease (ASCVD) in comparison to nonhypertensive individuals with optimal risk levels. We hypothesized that this residual risk could be stratified based on urinary albumin excretion (UAE). METHODS: A total of 13 082 middle-aged and older individuals with SBP/DBP of less than 160/100 mmHg and urinary albumin-to-creatinine ratios (UACRs) of less than 300 mg/g, and who were free from ASCVD events, were followed to investigate the incidence of ASCVD. The baseline BP was classified into four categories: normal BP (BP1), high normal BP (BP2), elevated BP (BP3), and grade 1 hypertension (BP4) based on the 2019 Japanese Society of Hypertension guidelines. RESULTS: After an average 10.6 ±â€Š2.6 years of follow-up, the multivariable hazard ratio for the development of ASCVD (n = 994) was already increased in medicated hypertensive patients with BP1 in comparison with untreated individuals with BP1; however, among medicated hypertensive patients, this risk was separated between the UAE groups, which were classified according to the median UACR (male, 15.4 mg/g; female, 19.0 mg/g). In medicated hypertensive patients with any category of BP1-BP3, the adjusted risk of the development of ASCVD in those with lower and higher UACRs was comparable to that observed in untreated individuals in the BP1 and BP4 categories, respectively. CONCLUSION: In medicated patients with well controlled hypertension, UAE is useful for stratifying the residual risk of developing ASCVD in comparison to nonhypertensive individuals with optimal risk levels.

Low educational level increases functional disability risk subsequent to heart failure in Japan: On behalf of the Iwate KENCO study group.

OBJECTIVES: The risk factors that contribute to future functional disability after heart failure (HF) are poorly understood. The aim of this study was to determine potential risk factors to future functional disability after HF in the general older adult population in Japan. METHODS: The subjects who were community-dwelling older adults aged 65 or older without a history of cardiovascular diseases and functional disability were followed in this prospective study for 11 years. Two case groups were determined from the 4,644 subjects: no long-term care insurance (LTCI) after HF (n = 52) and LTCI after HF (n = 44). We selected the controls by randomly matching each case of HF with three of the remaining 4,548 subjects who were event-free during the period: those with no LTCI and no HF with age +/-1 years and of the same sex, control for the no LTCI after HF group (n = 156), and control for the LTCI after HF group (n = 132). HF was diagnosed according to the Framingham diagnostic criteria. Individuals with a functional disability were those who had been newly certified by the LTCI during the observation period. Objective data including blood samples and several socioeconomic items in the baseline survey were assessed using a self-reported questionnaire. RESULTS: Significantly associated risk factors were lower educational levels (odds ratio (OR) [95% confidence interval (CI)]: 3.72 [1.63-8.48]) in the LTCI after HF group and hypertension (2.20 [1.10-4.43]) in no LTCI after HF group. Regular alcohol consumption and unmarried status were marginally significantly associated with LTCI after HF (OR [95% CI]; drinker = 2.69 [0.95-7.66]; P = 0.063; unmarried status = 2.54 [0.91-7.15]; P = 0.076). CONCLUSION: Preventive measures must be taken to protect older adults with unfavorable social factors from disability after HF via a multidisciplinary approach.

Plasma Xanthine Oxidoreductase Activity Is Associated with a High Risk of Cardiovascular Disease in a General Japanese Population.

The purpose of this study was to investigate the association between xanthine oxidoreductase (XOR) activity and a high risk of cardiovascular disease (CVD) in a general Japanese population. The Iwate Tohoku Medical Megabank Organization pooled individual participant data from a general population-based cohort study in Iwate prefecture. The cardiovascular risk was calculated using the Framingham Risk Score (FRS). A total of 1605 of the 1631 participants (98.4%) had detectable XOR activity. Multiple regression analysis demonstrated that XOR activity was independently associated with body mass index (ß = 0.26, p < 0.001), diabetes (ß = 0.09, p < 0.001), dyslipidemia (ß = 0.08, p = 0.001), and uric acid (ß = 0.13, p < 0.001). Multivariate analysis showed that the highest quartile of XOR activity was associated with a high risk for CVD (FRS ≥ 15) after adjustment for baseline characteristics (OR 2.93, 95% CI 1.16-7.40). The area under the receiver operating characteristic curves of the FRS with XOR activity was 0.81 (p = 0.008). XOR activity is associated with a high risk for CVD, suggesting that high XOR activity may indicate cardiovascular risk in a general Japanese population.

Five-year blood pressure trajectories of survivors of the tsunami following the Great East Japan Earthquake in Iwate.

Whether tsunami survivors who suffered substantial damage experienced increases in blood pressure (BP) immediately after the disaster and in the medium to long term is unclear. We divided tsunami survivors into groups, those who relocated (substantial damage) and those who did not (little damage) and compared the BP trajectories between the groups over the first 5 years after the disaster. Of the 42,831 residents, 3914 were assessed from 2010 to 2015. Subgroup analysis was performed among the 2037 subjects with no information on antihypertensive medications between 2010 and 2015 (no antihypertensive medication group). The BP trajectories in the relocation and no relocation groups were compared using linear mixed models. The multivariate-adjusted mean systolic BP (SBP) values for all subjects significantly decreased after the disaster in both the group who relocated (2010: 130.6 mmHg, 2015: 124.8 mmHg) and the group who did not relocate (2010: 130.7 mmHg, 2015: 126.7 mmHg). The interaction between relocation and time points on SBP was significant (P = 0.017). In the no antihypertensive medication group, the SBP values in the subgroup who relocated were significantly lower in the second, third, and fifth years after the disaster than those in the subgroup who did not relocate. It was concluded that the SBP values of survivors of the tsunami caused by Great East Japan Earthquake decreased in the medium to long term after the disaster, and the group who relocated had a larger decrease in SBP than the group who did not relocate.

Poor self-rated health predicts the incidence of functional disability in elderly community dwellers in Japan: a prospective cohort study.

BACKGROUND: Although previous large population studies showed elderly with poor self-rated health (SRH) to be at a high risk of functional disability in Western countries, there have been few studies in which the association between SRH and functional disability was investigated in Japanese community dwellers. The association between SRH and functional disability, defined as certification of the long-term care insurance (LTCI) system, in Japanese elderly community dwellers was examined in this study. METHODS: A total of 10,690 individuals (39.5% men, mean age of 71.4 years) who were 65 years of age or more who did not have a history of cardiovascular disease or LTCI certification were followed in this prospective study for 10.5 years. SRH was classified into four categories: good, rather good, neither good nor poor, and poor. A Cox proportional-hazards model was used to determine the hazard ratios (HRs) for the incidence of functional disability among the SRH groups for each sex. RESULTS: The number of individuals with functional disability was 3377. Men who rated poor for SRH scored significantly higher for functional disability (HR [95% confidence interval]: poor = 1.74 [1.42, 2.14]) while women who rated rather good, neither good nor poor, and poor scored significantly higher for functional disability (rather good =1.12 [1.00, 1.25], neither good nor poor = 1.29 [1.13, 1.48], poor = 1.92 [1.65, 2.24]: p for trend < 0.001 in both sexes). CONCLUSION: Self-rated health, therefore, might be a useful predictor of functional disability in elderly people.

Additional prognostic value of electrocardiographic left ventricular hypertrophy in traditional cardiovascular risk assessments in chronic kidney disease.

BACKGROUND: Left ventricular hypertrophy (LVH) is a common predictor of the cardiovascular prognosis in chronic kidney disease (CKD). However, whether or not electrocardiography-derived LVH (ECG-LVH) has prognostic value in patients with various degrees of CKD and improves the cardiovascular risk stratification based on traditional risk factors remains unclear. METHODS: A total of 7206 participants at least 40 years of age who were free from cardiovascular events in a general population were followed for the incidence of cardiovascular events. CKD was confirmed by either the presence of a reduced estimated glomerular filtration rate (eGFR) (<60 ml/min per 1.73 m) or albuminuria, defined as a urinary albumin-to-creatinine ratio (UACR) of at least 30 mg/g Cr. RESULTS: A total of 1886 (26.2%) had CKD, of which 1471 (78.0%) had a preserved eGFR (CKD stage 1-2). After an average 11.3 years of follow-up, the adjusted hazard ratio for the incidence of cardiovascular events significantly increased for ECG-LVH according to the Sokolow--Lyon voltage, Cornell voltage, or Cornell voltage product among participants with CKD (hazard ratio 1.47, P = 0.002), in contrast to those without CKD (hazard ratio 1.15, P = 0.210). The inclusion of any ECG-LVH parameters improved the accuracy of reclassification in any risk prediction model based on the eGFR, UACR, or Framingham 10-year risk score in the CKD participants (net reclassification improvement = 0.13-0.32, all P values <0.040). CONCLUSION: In patients with CKD stage 1-5, ECG-LVH is useful for predicting the risk of future cardiovascular events and adds prognostic information to traditional cardiovascular risk assessments.

The Value of a Cystatin C-based Estimated Glomerular Filtration Rate for Cardiovascular Assessment in a General Japanese Population: Results From the Iwate Tohoku Medical Megabank Project.

BACKGROUND: Epidemiological studies have shown that high circulating cystatin C is associated with a risk of cardiovascular disease (CVD) independent of creatinine-based renal function measurements. The present study investigated the comparison between the cystatin C-based estimated glomerular filtration rate (GFRcys) and creatinine-based GFR (GFRcr) to determine whether these measurements are associated with CV biomarkers and elevated CVD risk in a general Japanese population. METHODS: The Iwate Tohoku Medical Megabank Organization pooled individual participant data from a general population-based cohort study in Iwate prefecture (n = 29,375). Chronic kidney disease (CKD) was estimated using the GFRcys, GFRcr and the urine albumin-to-creatinine ratio (UACR). RESULTS: The prevalence of CKD in the participants was found to be higher based on the GFRcr than the GFRcys. Multiple variable analyses after adjusting for baseline characteristics showed that high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were associated with the GFRcys. The area under the receiver operating characteristic (AUROC) curve for identifying individuals with a high Suita score was higher for the GFRcys (AUROC = 0.68) than it was for the GFRcr (AUROC = 0.64, P < 0.001). The GFRcys provided reclassification improvement for the CVD risk prediction model by the GFRcr (net reclassification improvement = 0.341; integrated discrimination improvement = 0.018, respectively, P < 0.001). CONCLUSIONS: The GFRcys is more closely associated with CV biomarkers, including hs-cTnT and NT-proBNP levels, and a high Suita score than the GFRcr, and it provides additional value in the assessment of CVD risk using GFRcr.

Association between high-sensitivity cardiac troponin T and future cardiovascular incidence in a general Japanese population: results from the Tohoku medical megabank project.

Purpose: Elevation of high-sensitivity cardiac troponin T (hs-cTnT) is associated with an increased risk of cardiovascular disease (CVD). This study determined whether hs-cTnT was detectable with N-terminal pro-b-type natriuretic peptide (NT-proBNP) and related to CV risk factors in a general Japanese population. Materials and methods: The Tohoku Medical Megabank Organization pooled individual participant data for a population-based cohort study in the Iwate prefecture (n = 30,193, age = 60.2 ± 11.5 year). Results: Hs-cTnT levels were higher in participants with hypertension, diabetes mellitus than in participants without these conditions (all ps < 0.001). Logistic regression analysis demonstrated that NT-proBNP was strongly associated with elevation of hs-cTnT (OR = 3.35, 95% CI = 2.90-3.89, p < 0.001). The receiver operating characteristic curve analysis showed that hs-cTnT was one of useful biomarker for the differentiation of high risk for CVD (the Suita score ≥ 56) from a general population. Logistic regression analysis demonstrated hs-cTnT levels were related to the CVD high risk group (OR = 2.67, 95% CI = 2.28-3.14, p < 0.001). Conclusions: Hs-cTnT levels are associated with elevation of NT-proBNP and high Suita score, which suggests that elevated hs-cTnT is related to subclinical myocardial damage and indicates CV risk.

Prognostic Value of Electrocardiographic Left Ventricular Hypertrophy on Cardiovascular Risk in a Non-Hypertensive Community-Based Population.

BACKGROUND: The appearance of left ventricular hypertrophy on 12-lead electrocardiography (ECG-LVH) has been clarified to be associated with the risk of incidence of cardiovascular events (CVEs) in hypertensive individuals and the general population, but not enough in non-hypertensive individuals. METHODS: A total of 4,927 non-hypertensive individuals ≥40 years of age who were free of CVE in the general population were followed for the incidence of CVE. ECG-LVH was defined according to criteria of the Sokolow-Lyon (SL) voltage, Cornell voltage (CV), or Cornell voltage product (CP). RESULTS: During the average 9.8 ± 2.0 years of follow-up, 267 individuals (5.4%) had their first CVE. The hazard ratio (HR) for the incidence of CVE after full adjustment by potential confounders significantly increased in the individuals with ECG-LVH by any criteria of the SL voltage, CV, and CP (HR = 1.77, P < 0.001) compared to those with no ECG-LVH. This association was also significant in individuals without any of obesity, dyslipidemia, and diabetes mellitus or those with systolic blood pressure (BP) <120 mm Hg and diastolic BP <80 mm Hg. Furthermore, ECG-LVH by each criteria provided the reclassification improvement for the CVE risk prediction model by the Framingham 10-year risk score (the net reclassification improvement = 0.17-0.22, each P value < 0.010). CONCLUSIONS: In the absence of hypertension, ECG-LVH parameters are associated with the increased risk of developed CVEs independent of the established risk factors and provide the additional prognostic value in an assessment of the CVE risk using the traditional risk factors.

Burden of high blood pressure as a contributing factor to stroke in the Japanese community-based diabetic population.

Diabetes mellitus is characterized by alterations in blood glucose (BG) metabolism, and glycated hemoglobin (HbA1c) has been widely used as a marker of the BG concentration. Diabetes often coexists with high blood pressure (BP). High BP and hyperglycemia are well-known risk factors of stroke. We examined the extent to which the increased risk of stroke in diabetic individuals is attributable to BP and BG using prospectively collected data from the Japanese general population. During an average 8.3 ± 2.2 years of follow-up, out 1606 diabetic individuals aged ≥40 years who were free of cardiovascular disease, 119 participants (7.4%) developed stroke. In multivariable analysis, a significant difference in the risk of incident stroke was noted among the BP categories, including normotension (BP1), prehypertension (BP2), and hypertension (BP3; P for trend = 0.001). By contrast, no difference was noted among the BG categories, including HbA1c levels <7.0% (HB1), 7.0-7.9% (HB2), and ≥8.0% (HB3; P for trend = 0.430). Compared with the category that included both BP1 and HB1, the population-attributable fraction (PAF) for stroke incidence was 52.0% from the BP2 and BP3 categories and 24.1% from the HB2 and HB3 categories, and the increased incidence from the HB2 and HB3 categories was mostly caused from coexistent BP2 and BP3 categories. In conclusion, in the Japanese community-based diabetic population, concomitant BP elevation largely contributes to the increased incidence of stroke and links BG elevation, as indicated by HbA1c, to the increased risk of stroke.

The urine albumin-creatinine ratio is a predictor for incident long-term care in a general population.

BACKGROUND: Several types of cardiovascular diseases (CVDs) impair the physical and mental status. The purpose of this study was to assess the predictive ability of several cardiovascular biomarkers for identifying the incidence of disability as future recipients of public long-term care (LTC) service. METHODS: The subjects of this study were community-dwelling elderly individuals ≥ 65 years of age without a history of CVD (n = 5,755; mean age, 71 years). The endpoint of this study was official certification as a recipient of LTC. The cohort was divided into quartiles (Qs) based on the levels of three CVD biomarkers: the urinary albumin-creatinine ratio (UACR), plasma B-type natriuretic peptide concentration (BNP), and serum high-sensitivity C-reactive protein concentration (hsCRP). A time-dependent Cox proportional hazard model was used to determine the multi-adjusted relative hazard ratios (HRs) for incident LTC among the quartiles of each biomarker. RESULTS: During the follow-up (mean 5.6 years), 710 subjects were authorized as recipients of LTC. The HR was only significantly increased in the higher Qs of UACR (Q3, p < 0.01; Q4, p < 0.001). However, other biomarkers were not significantly associated with the endpoint. The risk predictive performance for the incidence of LTC as evaluated by an essential model (i.e. age- and sex-adjusted) was significantly improved by incorporating the UACR (net reclassification improvement = 0.084, p < 0.01; integrated discrimination improvement = 0.0018, p < 0.01). CONCLUSIONS: These results suggest that an increased UACR is useful for predicting physical and cognitive dysfunction in an elderly general population.

Ability of B-Type Natriuretic Peptide Testing to Predict Cardioembolic Stroke in the General Population　- Comparisons With C-Reactive Protein and Urinary Albumin.

BACKGROUND: The ability of cardiovascular biomarkers to predict the incidence of stroke subtypes remains ill-defined in the general population.Methods and Results:The blood levels of B-type natriuretic peptide (BNP) and high-sensitivity C-reactive protein (hs-CRP) and urinary albumin corrected by urinary creatinine (UACR) were determined in a general population (n=13,575). The ability to predict the incidence of ischemic stroke subtypes (lacunar, atherothrombotic, cardioembolic) for each biomarker was assessed based on the area under the receiver-operating characteristic curve (AUC-ROC) and using Cox proportional hazard modeling. The predictive abilities of UACR and hs-CRP for any subtype of ischemic event were found to be suboptimal. However, the ability of BNP to predict the incidence of cardioembolic stroke was excellent (AUC-ROC=0.81). When BNP was added to established stroke risk factors, the ability to predict cardioembolic stroke in terms of the AUC-ROC significantly improved (4-year follow-up, P=0.018; 8-year follow-up, P=0.009). Furthermore, when BNP was added to the JPHC score, the ability to predict cardioembolic stroke was significantly improved (net reclassification improvement=0.968, P<0.0001: integrated discrimination improvement=0.039, P<0.05). CONCLUSIONS: In the general population, plasma BNP was an excellent biomarker for predicting the incidence of cardioembolic stroke when used alone or in combination with established stroke risk factors.