Background Chronic kidney disease (CKD) is associated with increased risk of coronary heart disease. However, information regarding the histopathologic characteristics of coronary atherosclerosis in ...individuals with CKD is scarce. This study investigated the relationship between CKD and severity of coronary atherosclerosis in population-based autopsy samples. Study Design Cross-sectional study. Setting & Participants 126 individuals randomly selected from 844 consecutive population-based autopsy samples. Predictor Estimated glomerular filtration rate (eGFR) calculated using the 6-variable Modification of Diet in Renal Disease (MDRD) Study equation. Outcomes Severity of atherosclerosis in 3 main coronary arteries, including atherosclerotic lesion types defined using the American Heart Association classification; stenosis rates; and coronary calcified lesions. Measurements The relationship between CKD and severity of coronary atherosclerosis was evaluated using generalized estimating equation methods. Results Frequencies of advanced atherosclerotic lesions increased gradually as eGFR decreased (33.6%, 41.7%, 52.3%, and 52.8% for eGFRs ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2 , respectively; P for trend = 0.006). This relationship was substantially unchanged even after adjustment for potential confounding factors (ORs, 1.40 95% CI, 0.76-2.55, 2.02 95% CI, 0.99-4.15, and 3.02 95% CI, 1.22-7.49 for eGFRs of 45-59, 30-44, and <30 mL/min/1.73 m2 , respectively). Frequencies of calcified lesions of coronary arteries also increased gradually with lower eGFRs ( P for trend = 0.02). Hypertension and diabetes were associated with increased risk of advanced coronary atherosclerosis and calcification of coronary arteries in individuals with decreased eGFR. Limitations Cross-sectional study, absence of data for proteinuria, and extremely high proportion of aged people. Conclusions The autopsy findings presented here suggest that CKD is associated significantly with severity of coronary atherosclerosis. Patients with CKD should be considered a high-risk population for advanced coronary atherosclerosis.
Little is known about the association between dairy intake and risk of functional disability in the elderly.
We examined the influence of dairy intake on the development of declining functional ...capacity and activities of daily living (ADL) in a prospective cohort study of an elderly population.
A total of 859 community-dwelling Japanese residents, aged ≥65 y without functional disability, were followed up for 7 y. Functional capacity impairment was defined as a Tokyo Metropolitan Institute of Gerontology Index of Competence score of ≤12, and ADL disability was defined as a Barthel Index score of ≤95. Dairy intake was evaluated using a 150-item semiquantitative food frequency questionnaire, grouped into quartiles. The RR of dairy intake on incident functional disability was computed using a Poisson regression model.
The multivariable-adjusted RR of impaired functional capacity decreased significantly with increasing dairy intake levels (RR 95% CI: quartile 1, 1.00 reference; quartile 2, 0.85 0.71, 1.02; quartile 3, 0.81 0.68, 0.98; and quartile 4, 0.74 0.61, 0.90; P-trend=0.001). Regarding the three subscales of functional capacity, the inverse association between dairy intake and risk for impairment of intellectual activity and social role remained significant (P-trend=0.0009 and 0.02, respectively), but such an association was not observed for instrumental ADL. The multivariable-adjusted risk of ADL disability also decreased weakly but significantly with elevating dairy intake (P-trend=0.04). A similar association was seen for severity of functional disability (P-trend=0.002). However, the magnitude of these associations was attenuated after further adjustment for protein intake.
Our findings suggest that higher dairy intake is associated with a lower risk of functional disability and its progression in the elderly, probably via an increase in protein intake.
Abstract Regulated upon Activation, Normal T-cell Expressed, and Secreted (RANTES) is a well-known pro-inflammatory chemokine and its role in ischemic stroke remains controversial. We examined the ...significance of RANTES in ischemic stroke and aimed to elucidate the direct effect of RANTES on neurons. Plasma concentrations of major C-C chemokines, including RANTES, and neurotrophic factors were examined in 171 ischemic stroke patients and age- and gender- matched healthy subjects. Plasma concentrations of RANTES at day 0 after onset were significantly elevated in stroke patients, compared with controls, and were highly correlated with those of BDNF, EGF, and VEGF. In a mouse middle cerebral artery occlusion model (MCAO), plasma RANTES was significantly elevated and the expression of RANTES was markedly upregulated in neurons particularly in peri-infarct areas. The expression of CCR3 and CCR5, receptors for RANTES, was also induced in neurons, while another receptor, CCR1, was observed in vascular cells, in peri-infarct areas after MCAO. We examined the effects of RANTES on differentiated PC12 cells, a model of neuronal cells. Treatment with RANTES induced the activation of Akt and Erk1/2, and attenuated the cleavage of caspase-3 in the cells. RANTES increased the expression of BDNF, EGF, and VEGF in the cells. Moreover, RANTES maintained the number of cells under serum free conditions. The RANTES-mediated upregulation of neurotrophic factors and cell survival were significantly attenuated by the inhibition of Akt or Erk1/2. Taken together, RANTES is an interesting chemokine that is produced from neurons after ischemic stroke and has the potential to protect neurons directly or indirectly through the production of neurotrophic factors in peri-infarct areas.
Abstract
Context and Objective
We investigated the associations of hemoglobin A1c (HbA1c), glycated albumin (GA), GA/HbA1c ratio, and 1,5-anhydroglucitol (1,5-AG) with the development of Alzheimer’s ...disease (AD).
Design and Participants
A total of 1187 community-dwelling Japanese subjects aged ≥65 years without dementia were followed up for an average of 4.8 years.
Results
The age- and sex-adjusted incidence of AD increased significantly with higher quartiles of GA/HbA1c ratio, and a similar tendency was seen for GA, whereas no such association was observed for HbA1c and 1,5-AG. After adjusting for potential confounding factors, positive association of GA/HbA1c ratio with the risk of AD remained significant: the multivariable-adjusted hazard ratio (HR) was significantly higher in the third HR = 2.11, 95% confidence interval (CI) = 1.16 to 3.82 and fourth (HR = 2.01, 95% CI = 1.09 to 3.68) quartile than in the first quartile. Among subjects with normal glucose tolerance, those with high GA/HbA1c ratio had a higher risk of AD than those with low GA/HbA1c ratio (HR = 1.82, 95% CI = 1.05 to 3.16), and a similar tendency was found in those with glucose intolerance (HR = 1.73, 95% CI = 0.96 to 3.13). No such associations were observed for HbA1c, GA, and 1,5-AG, regardless of glucose tolerance status.
Conclusions
Our findings suggest that elevated GA/HbA1c ratio—but not HbA1c, GA, or 1,5-AG level—is significantly associated with the risk of AD in subjects both with and without glucose intolerance. GA/HbA1c ratio may be a useful biomarker for predicting incident AD.
We studied alternative measures of hyperglycemia in community-based population and found that higher glycated albumin to HbA1c ratio levels were closely associated with risk of Alzheimer’s disease.
Aim: It is not clear whether elevated serum non-high-density lipoprotein cholesterol (non-HDL-C) levels are a risk factor for cardiovascular disease (CVD) in subjects with chronic kidney disease ...(CKD) in the general population.Methods: A total of 2,630 community-dwelling Japanese subjects (1,107 men and 1,523 women) without history of CVD and aged ≥40 years were prospectively followed up for an average of 19 years, and the association between serum non-HDL-C levels and the incidence of type-specific CVD was estimated using a Cox proportional hazards model. CKD was defined as estimated glomerular filtration rate ＜60 mL/min/1.73 m2 or proteinuria (≥1＋ on dipstick).Results: At baseline, 357 subjects had CKD. During the follow up, 186 coronary heart disease (CHD) and 277 stroke events occurred. The age- and sex-adjusted incidence of CHD was significantly higher in subjects with higher non-HDL-C levels, both in those with and without CKD. In the CKD group, the risk of CHD was significantly higher in those with non-HDL-C levels of 150– 189 mg/dL adjusted hazard ratio (HR), 2.23; 95% confidence interval (CI), 1.04–4.77 and those with levels ≥190 mg/dL (adjusted HR, 3.20; 95% CI, 1.46–7.03) than in those with levels ＜150 mg/dL. In the non-CKD group, the risk of CHD was significantly higher only in those with nonHDL-C levels ≥190 mg/dL (adjusted HR, 2.12; 95% CI, 1.33–3.38). However, no such association was observed for the risk of stroke.Conclusions: Our findings suggest that higher serum non-HDL-C levels are associated with greater risk of CHD in subjects with and without CKD and that this association is greater in subjects with CKD than in those without CKD.
Chronic kidney disease and cardiovascular disease in a general Japanese population: The Hisayama Study.
Chronic kidney disease has been shown to be an independent risk factor for cardiovascular ...disease in high-risk populations. However, this relationship is inconclusive in community-based populations.
To clarify this issue, we followed 2634 community-dwelling individuals without cardiovascular disease, aged 40 years or older, for 12 years and examined the relationship between chronic kidney disease and the incidence of cardiovascular disease.
During the follow-up period, 99 subjects (56 men and 43 women) experienced coronary heart disease, 137 subjects (60 men and 77 women) ischemic stroke, and 60 subjects (26 men and 34 women) hemorrhagic stroke. In men, the age-adjusted incidence of coronary heart disease was significantly higher in subjects with chronic kidney disease than in those without it (6.2 vs. 2.9 per 1000 person-years) (P < 0.05), but such a relationship was not observed with ischemic stroke. In contrast, in women, the age-adjusted incidence of ischemic stroke was significantly higher in subjects with chronic kidney disease than in those without it (3.4 vs. 2.5) (P < 0.05), while that of coronary heart disease was not. Chronic kidney disease was not found to be associated with the incidence of hemorrhagic stroke. In multivariate analysis, even after adjustments for traditional and nontraditional cardiovascular disease risk factors, chronic kidney disease was found to be an independent risk factor for the occurrence of coronary heart disease in men hazard ratio (HR), 2.26; 95% CI, 1.06-4.79, and for the occurrence of ischemic stroke in women (HR, 1.91; 95% CI, 1.15-3.15).
Our findings suggest that chronic kidney disease is an independent risk factor for the occurrence of cardiovascular disease in the general Japanese population.
This study examined the relationship between stimulated salivary flow rate and oral health status in an adult population. Multinomial multivariate logistic regression analysis was used to examine the ...associations of salivary flow rate with dental caries status and periodontal status at the individual level among 2,110 Japanese adults with ≥10 teeth. Then, a spline model was used to examine the nonlinear relationship between salivary flow rate and teeth with dental caries or periodontal disease in multilevel analysis. Odds ratios were calculated for a 1.0-mL/min reduction in salivary flow rate at a point. After adjusting for confounding variables, participants with a flow rate ≤3.5 mL/min had significantly higher odds ratios for high caries status, and participants with a flow rate ≤1.4 mL/min had a higher odds ratio for broad periodontal disease, than did those with a flow rate >3.5 mL/min. In spline models, the odds ratio for teeth with dental caries or periodontal disease increased with reduced saliva secretion. The present findings suggest that decreased saliva secretion affects both dental caries and general periodontal health status.
Accurate estimation of the glomerular filtration rate (GFR) is crucial for the detection of chronic kidney disease (CKD). In clinical practice, GFR is estimated from serum creatinine using the ...Modification of Diet in Renal Disease (MDRD) study equation or the Cockcroft-Gault (CG) equation instead of the time-consuming method of measured clearance for exogenous markers such as inulin. In the present study, the equations originally developed for a Caucasian population were tested in Japanese CKD patients, and modified with the Japanese coefficient determined by the data.
The abbreviated MDRD study and CG equations were tested in 248 Japanese CKD patients and compared with measured inulin clearance (Cin) and estimated GFR (eGFR). The Japanese coefficient was determined by minimizing the sum of squared errors between eGFR and Cin. Serum creatinine values of the enzyme method in the present study were calibrated to values of the noncompensated Jaffé method by adding 0.207 mg/dl, because the original MDRD study equation was determined by the data for serum creatinine values measured by the noncompensated Jaffé method. The abbreviated MDRD study equation modified with the Japanese coefficient was validated in another set of 269 CKD patients.
There was a significant discrepancy between measured Cin and eGFR by the 1.0xMDRD or CG equations. The MDRD study equation modified with the Japanese coefficient (0.881xMDRD) determined for Japanese CKD patients yielded lower mean difference and higher accuracy for GFR estimation. In particular, in Cin 30-59 ml/min per 1.73 m(2), the mean difference was significantly smaller with the 0.881xMDRD equation than that with the 1.0xMDRD study equation (1.9 vs 7.9 ml/min per 1.73 m(2); P < 0.01), and the accuracy was significantly higher, with 60% vs 39% of the points deviating within 15%, and 97% vs 87% of points within 50%, respectively (both P < 0.01). Validation with the different data set showed the correlation between eGFR and Cin was better with the 0.881xMDRD equation than with the 1.0xMDRD study equation. In Cin less than 60 ml/min per 1.73 m(2), the accuracy was significantly higher, with 85% vs 69% of the points deviating within 50% (P < 0.01), respectively. The mean difference was also significantly smaller (P < 0.01). However, GFR values calculated by the 0.881xMDRD equation were still underestimated in the range of Cin over 60 ml/min per 1.73 m(2).
Although the Japanese coefficient improves the accuracy of GFR estimation of the original MDRD study equation, a new equation is needed for more accurate estimation of GFR in Japanese patients with CKD stages 3 and 4.
Epidemiological and clinical studies have investigated the influence of hypertension on chronic kidney disease (CKD), but limited data are available for the associations of white-coat hypertension ...(WCHT), masked hypertension (MHT) and sustained hypertension (SHT) with kidney dysfunction in general populations. We examined the associations of these types of hypertension with CKD (albuminuria and reduction in estimated glomerular filtration rate (eGFR)) in a cross-sectional survey of 2974 community-dwelling Japanese aged ⩾40 years. The types of hypertension were defined based on combined measurements of clinic and home blood pressures. Albuminuria was determined as urinary albumin-creatinine ratio (UACR) levels ⩾30.0 mg g
. The eGFR was calculated using the Japanese equation. The age- and sex-adjusted geometric mean of the UACR values was significantly higher in the subjects with WCHT (20.2 mg g
), MHT (19.6 mg g
) and SHT (31.6 mg g
) than in those with normotension (NT) (12.5 mg g
) (all P<0.001). Compared with NT, all types of hypertension were significantly associated with an increased likelihood of albuminuria (the age- and sex-adjusted prevalence of albuminuria; NT 14.1%, WCHT 26.3%, MHT 26.4% and SHT 43.3%; all P<0.001). These associations remained significant even after adjustment for other risk factors. However, the age- and sex-adjusted mean of eGFR and the prevalence of low eGFR (<60 ml min
per 1.73 m
) did not differ between NT and the three hypertension types. The associations of the types of hypertension with the likelihood of CKD were similar to those for albuminuria. Our findings suggest that WCHT, MHT and SHT are associated with albuminuria in the general Japanese population.
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