Lymphocyte count was significantly associated with hyper-LDL cholesterolemia independently of high-sensitivity C-reactive protein in apparently healthy Japanese.

The aim of this study was to investigate the association between leukocyte subtype counts and hyper-LDL cholesterolemia, hypertriglyceridemia, and hypo-HDL cholesterolemia. Logistic regressions using hyper-LDL cholesterolemia, hypertriglyceridemia, and hypo-HDL cholesterolemia as a dependent variable and total leukocyte, basophil, eosinophil, neutrophil, lymphocyte, and monocyte counts as an independent variable were calculated adjusting for age, body mass index (BMI), high-sensitivity C-reactive protein (hs-CRP), smoking, drinking, and physical activity in apparently healthy Japanese men (1,803) and women (1,150). The odds ratio (OR) of hyper-LDL cholesterolemia for total leukocyte, eosinophil, and lymphocyte counts, the OR of hypertriglyceridemia for total leukocyte, eosinophil, neutrophil, and lymphocyte counts, and the OR of hypo-HDL cholesterolemia for total leukocyte, neutrophil, and lymphocyte counts were significant in men, and the OR of hyper-LDL cholesterolemia, for lymphocyte count, and the OR of hypo-HDL cholesterolemia for eosinophil count were significant in women. Lymphocyte count was significantly associated with hyper-LDL cholesterolemia independently of hs-CRP in apparently healthy Japanese.

A possible cross-sectional association of serum total bilirubin with coronary heart disease and stroke in a Japanese health screening population.

Bilirubin is a potent antioxidant, and serum total bilirubin (TB) is reported to be negatively associated with cardiovascular disease (CVD). There has been no report on the association between TB and CVD prevalence in Japanese. The aim of the study is to examine the association between TB and CVD prevalence in a Japanese health screening population. Prevalence of CVD was studied in 3,375 Japanese men and 2,069 Japanese women. Odds ratios (ORs) of each higher quintile of TB using the lowest quintile as the reference in men and of each higher tertile of TB using the lowest tertile as the reference in women were calculated for coronary heart disease (CHD) and stroke adjusting for age, liver function tests, smoking, physical activity, and alcohol consumption. The ORs [95% confidence intervals (CIs)] for CHD and stroke of the 2nd, 3rd, 4th, and 5th quintiles of TB were 0.63 (0.37-1.07) and 0.49 (0.24-1.00), 0.45 (0.22-0.90) and 0.65 (0.28-1.51), 0.69 (0.39-1.20) and 0.37 (0.15-0.87), and 0.61 (0.34-1.09) and 0.40 (0.18-0.92), respectively in men. The ORs (95% CIs) for CHD and stroke of the 2nd and 3rd tertiles of TB were 1.32 (0.49-3.54) and 0.35 (0.13-0.93), and 1.26 (0.44-3.62) and 0.34 (0.13-0.93), [corrected] respectively in women. Low TB was associated with the higher prevalence of CHD and stroke in men and with the higher prevalence of stroke in women among a Japanese health screening population.

Bilirubin is negatively associated with hemoglobin a(1c) independently of other cardiovascular risk factors in apparently healthy Japanese men and women.

BACKGROUND: Serum total bilirubin (TB) is a potent antioxidant and may be a negative risk factor of cardiovascular disease. In non-diabetic adults, hemoglobin A(1c) (HbA(1c)), but not fasting plasma glucose, is an independent risk factor of cardiovascular disease. METHODS AND RESULTS: Linear regression using TB as a dependent variable and cardiovascular risk factors, including HbA(1c), as independent variables, linear regression using HbA(1c) as a dependent variable and other cardiovascular risk factors, including TB, as independent variables, and logistic regression using the highest decile (≥ 5.4%) of HbA(1c) as a dependent variable and TB and other cardiovascular risk factors as independent variables were performed for 893 apparently healthy male smokers, 1,607 male nonsmokers, and 1,680 women. The standardized regression coefficient of HbA(1c) for TB and that of TB for HbA(1c) was -0.12 (P = 0.007) and -0.06 (P = 0.02), respectively, in the smokers, -0.20 (P < 0.0001) and -0.07 (P < 0.0001), respectively, in the nonsmokers, and -0.21 (P < 0.0001) and -0.14 (P < 0.0001), respectively, in the women. The odds ratio of 1 SD increment in TB for HbA(1c) ≥ 5.4% was not significant in the smokers, 0.67 (P = 0.002) in the nonsmokers, and 0.55 (P<0.0001) in the women. CONCLUSIONS: Bilirubin was negatively associated with HbA(1c) independently of other cardiovascular risk factors in apparently healthy Japanese men and women. The association was weak in male smokers.

Changes in body weight are significantly associated with changes in fasting plasma glucose and HDL cholesterol in Japanese men without abdominal obesity (waist circumference < 85 cm).

The aims are to examine whether changes in body weight (dBW) are associated with changes in cardiovascular risk factors in Japanese men without abdominal obesity (waist circumference (WC) < 85 cm) and which anthropometric index, dBW or changes in WC (dWC), is more strongly associated with changes in cardiovascular risk factors in men without abdominal obesity. It is a retrospective study in 692 Japanese men without abdominal obesity who took annual health screening tests consecutively over one year. Standardized linear regression coefficients (SRCs) of dBW and dWC were calculated for changes in systolic blood pressure (dSBP), diastolic blood pressure (dDBP), fasting plasma glucose (dFPG), triglycerides (dTG), HDL cholesterol (dHDL), and high-sensitivity C-reactive protein (dCRP). The SRCs of dBW for dFPG and dHDL were significant in all men and in men with each risk factor corresponding to the component of metabolic syndrome (MetS). The SRCs of dWC for dTG and dCRP were significant in all men but not in men with each risk factor corresponding to the MetS component. In conclusions, dBW were significantly associated with dFPG and dHDL in Japanese men without abdominal obesity. Therefore, abdominal obesity should not be considered as a necessary component of MetS in Japanese men. dBW may be more useful than dWC as a marker of changes in cardiovascular risk factors in lifestyle intervention programs.

Comparison among body mass index (BMI), waist circumference (WC), and percent body fat (%BF) as anthropometric markers for the clustering of metabolic risk factors in Japanese.

OBJECTIVE: To compare body mass index (BMI), waist circumference (WC), and percent body fat (%BF) as markers for the clustering of metabolic risk factors in Japanese. METHODS: Age-adjusted correlation coefficients (Rs) were calculated between the three anthropometric markers of obesity and metabolic risk factors in 2,444 men and 1,442 women among Japanese. Areas under receiver operating characteristic curves (AUCs) of BMI, WC, and %BF were calculated for diagnosing the clustering of 1 or more, 2 or more, 3 or more, and 4 risk factors among increased blood pressure, impaired fasting glucose, increased triglycerides, and decreased HDL cholesterol and for the clustering of 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, and 6 risk factors among the upper four risk factors as well as increased high-sensitivity C-reactive protein and increased LDL cholesterol. RESULTS: The Rs were not significantly different among BMI, WC, and %BF except for the difference between the R of BMI (0.217) and that of %BF (0.283) with LDL cholesterol in men (p=0.014). The AUCs of BMI, WC, and %BF for diagnosing any of the risk factor clustering patterns defined above were not significantly different in both men and women. CONCLUSION: The AUCs for diagnosing the clustering of metabolic risk factors were not significantly different among BMI, WC, and %BF.

Body mass index is more strongly associated with hypertension than waist circumference in apparently healthy Japanese men and women.

Obesity is associated with hypertension. However, it is controversial which obesity index, body mass index (BMI) or waist circumference (WC), is more strongly associated with hypertension. We compared the cross-sectional associations of BMI and WC with hypertension. Logistic regressions using hypertension as a dependent variable and age, BMI, WC, fasting plasma glucose, triglycerides, high-density lipoprotein cholesterol, smoking status, drinking status, and physical activity as independent variables were performed using data from apparently healthy 1,803 Japanese men aged 49.9 ± 9.0 and 1,150 women aged 49.5 ± 9.0 excluding subjects with a history of cardiovascular disease, or with antidiabetic, antihypertensive and/or antihyperlipidemic medications. The odds ratio [95% confidence interval] of 1 kg/m² increase in BMI and that of 1 cm increase in WC for diagnosing hypertension were 1.23 [1.11-1.36] (p < 0.0001) and 0.99 [0.95-1.02] (p = 0.4) in men and 1.35 [1.16-1.58] (p < 0.0001) and 0.97 [0.91-1.03] (p = 0.4) in women, respectively. Thus, BMI, but not WC, was independently associated with hypertension in apparently healthy Japanese men and women.

Reproducibility of high-sensitivity C-reactive protein as an inflammatory component of metabolic syndrome in Japanese.

BACKGROUND: Cutoff points for high-sensitivity C-reactive protein (hs-CRP) as a component of metabolic syndrome (MetS) in Japanese have been proposed as 0.40-0.45 mg/L for men and 0.25-0.35 mg/L for women. However, there are some concerns about the reproducibility of hs-CRP. METHODS AND RESULTS: Reproducibility of hs-CRP as a component of MetS was examined using receiver-operating characteristic (ROC) curves for diagnosing MetS in 1,274 men and 673 women whose serum levels of hs-CRP were measured twice at annual health screening tests. The Spearman's correlation coefficient between baseline hs-CRP and hs-CRP at the next year's test was 0.68 in men and 0.71 in women. The area under the ROC curves of baseline hs-CRP, hs-CRP at the next year's test, and the mean of the 2 hs-CRP tests for diagnosing baseline MetS were 0.71, 0.71, and 0.72, respectively, in men and 0.75, 0.74, and 0.74, respectively, in women. Optimal cutoff points of baseline hs-CRP, hs-CRP at the next year's test, and the mean of 2 tests for diagnosing baseline MetS were all 0.40 mg/L in men and 0.35 mg/L in women. CONCLUSIONS: The serum level of hs-CRP was stable enough for use as a measure of the inflammatory component of MetS, and the optimal cutoff point of hs-CRP was 0.40 mg/L for men and 0.35 mg/L for women in a Japanese health-screening population.

Low-density lipoprotein (LDL) cholesterol is cross-sectionally associated with preclinical chronic kidney disease (CKD) in Japanese men.

BACKGROUND: Low-density lipoprotein (LDL) cholesterol and chronic kidney disease (CKD) are both well-known risk factors for cardiovascular disease. However, few studies have examined the associations between LDL cholesterol and CKD. METHODS: In the present study, we investigated the associations between LDL cholesterol and CKD using medical check-up data from 2,449 Japanese men and 1,448 Japanese women. Metabolic syndrome (MetS) was defined according to the revised National Cholesterol Education Program (NCEP) criteria for Japanese people. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2) and/or proteinuria. RESULTS: Blood levels of LDL cholesterol were higher in CKD subjects than in non-CKD subjects only in men and the frequency of antihyperlipidemic medication and MetS was higher in CKD subjects than in non-CKD subjects, regardless of gender. The frequency of CKD was significantly higher in male subjects with the highest quartile of LDL cholesterol than in those with the lowest quartile of LDL cholesterol. LDL cholesterol levels were significantly higher in subjects with eGFR corresponding to CKD stages 2 and 3 than in those with eGFR corresponding to CKD stage 1 both in men and women. LDL cholesterol was independently associated with CKD, eGFR <60 mL/min/1.73 m(2), and proteinuria in Japanese men, but not in women. CONCLUSION: LDL cholesterol is cross-sectionally associated with preclinical CKD in Japanese men.

Comparison between high-sensitivity C-reactive protein (hs-CRP) and white blood cell count (WBC) as an inflammatory component of metabolic syndrome in Japanese.

OBJECTIVE: To compare two systemic inflammatory markers, high-sensitivity C-reactive protein (hs-CRP) and white blood cell count (WBC), as a component of metabolic syndrome (MetS). METHODS: Data of hs-CRP and WBC from 2,185 Japanese men and 1,383 Japanese women were examined using receiver operating characteristic (ROC) curve for diagnosing MetS and Spearman's correlation coefficients. RESULTS: The area under ROC curve (AUC) of hs-CRP was 0.71 in men and 0.74 in women. The AUC of WBC was 0.65 in men and 0.69 in women. The optimal cutoff point (sensitivity; specificity) of hs-CRP was 0.40 mg/L (0.69; 0.65) in men and 0.35 mg/L (0.67; 0.72) in women. The optimal cutoff point (sensitivity; specificity) of WBC was 5,600/L(-6) (0.61; 0.61) in men and 5,000/L(-6) (0.65; 0.63) in women. Correlations between obesity parameters, blood pressure, and liver function tests were stronger with hs-CRP than with WBC. But, no correlation between MetS-related risk factors was stronger with WBC than with hs-CRP. CONCLUSION: Hs-CRP is superior to WBC as an inflammatory component of MetS in Japanese. However, WBC may be useful when hs-CRP is not available because WBC is routinely measured in clinical practice.

Uric acid is positively associated with metabolic syndrome but negatively associated with diabetes in Japanese men.

BACKGROUND: The relationships between uric acid and metabolic syndrome (MetS) and diabetes, as well as the gender differences in these relationships are controversial. METHODS: Medical check-up data from 2,449 Japanese men and 1,448 Japanese women were examined. The prevalence of MetS and diabetes was calculated by the quartiles of serum levels of uric acid. Correlation coefficients between uric acid and MetS-related risk factors were calculated and compared between men and women. RESULTS: The prevalence of MetS in the 3rd quartile (Q3) of uric acid was significantly higher than that in the 1st (lowest) quartile (Q1) and the prevalence of MetS in the 4th quartile (Q4) was significantly higher than that in Q1, the 2nd quartile (Q2), and Q3 in men. The prevalence of MetS in Q4 was significantly higher than that in Q1, Q2, and Q3 in women. The prevalence of diabetes in Q3 was significantly lower than that in Q1 and the prevalence of diabetes in Q4 was significantly lower than that in Q1 and Q2 in men. The prevalence of diabetes was not significantly different among the quartiles of uric acid in women. The age-adjusted correlation coefficient between uric acid and fasting glucose was not significant in men. CONCLUSION: Uric acid is positively associated with metabolic syndrome but negatively associated with diabetes in Japanese men.

LDL cholesterol is more strongly associated with metabolic syndrome in Japanese women than in men.

OBJECTIVE: LDL cholesterol is not usually considered as a component of metabolic syndrome (MetS) but rather it is associated with MetS components. METHODS: Data from 2,449 men and 1,448 women were examined using receiver operating characteristic (ROC) curve for diagnosing MetS and correlation coefficients. RESULTS: Blood levels of LDL cholesterol increased more steeply in women than in men as the number of MetS components increased. The area under ROC curve (AUC) and its 95% confidence interval (CI) of LDL cholesterol for diagnosing MetS were 0.57 and 0.53-0.60 in men and 0.66 and 0.61-0.71 in women. The optimal cut-off point (sensitivity; specificity) of LDL cholesterol was 127 mg/dL (0.50; 0.60) in men and 125 mg/dL (0.64; 0.61) in women. Correlations between LDL cholesterol and systolic blood pressure, diastolic blood pressure, gamma glutamyltransferase, and hemoglobin A1c were stronger in women than in men even after adjustment for age. The correlation between LDL cholesterol and blood pressure was significant in women, but not in men, even after adjusting for age. CONCLUSION: LDL cholesterol was more strongly associated with MetS in Japanese women than in men. The correlation between LDL cholesterol and blood pressure was significant in women, but not in men.

Prevalence of metabolic syndrome increases with the increase in blood levels of gamma glutamyltransferase and alanine aminotransferase in Japanese men and women.

BACKGROUND: Gamma glutamyltransferase (GGT) or alanine aminotransferase (ALT) is reported to be an independent risk factor of diabetes and cardiovascular disease and proposed as a component of metabolic syndrome (MS). However, there are few studies examining the direct association between MS and GGT or ALT in Japanese men and women. METHODS: Direct associations between GGT or ALT and MS defined by revised NCEP criteria for Japanese and between GGT or ALT and Japanese MS (JMS) defined by the Examination Committee for the Criteria of Metabolic Syndrome were examined using medical check-up data from 1,880 men and 1,079 women. RESULTS: The prevalence of MS and JMS was significantly higher in subjects with the highest quartile of GGT or ALT than the subjects with the lowest quartile of GGT or ALT (p<0.0001 in men and p<0.0001 for MS and p<0.001 for JMS in women). The optimal cutoff points of GGT and ALT for diagnosing MS or JMS were 42 U/L or 41 U/L, respectively for GGT and both 25 U/L for ALT in men and 21 U/L or 23 U/L, respectively for GGT and 20 U/L or 25 U/L, respectively for ALT in women. CONCLUSION: The prevalence of MS and JMS increases with the increase in blood levels of GGT or ALT even through the normal range of GGT or ALT in Japanese men and women.

Low vital capacity is associated with diabetes despite inverse relationships with metabolic risk factors in lean Japanese men.

BACKGROUND: There is no study examining the relationships between vital capacity and diabetes or metabolic risk factors in lean subjects. METHODS: Cross-sectional relationships between % vital capacity (%VC) and diabetes and metabolic risk factors were examined in Japanese subjects using medical check-up data from 2,079 men and 1,215 women. Subjects were divided into lean (BMI <23 kg/m(2)) and obese (BMI >or=23 kg/m(2)) groups and then subdivided into lower %VC (or=96%) subgroups by gender. Metabolic risk factors and prevalence of diabetes and MS were compared between the subjects in each group, and then excluding current smokers and between subjects with the lowest quartile of %VC and those with the highest quartile of %VC in the lean men group. Spearman's correlation coefficients between %VC and metabolic risk factors were calculated separately in obese subjects and in lean subjects by gender. RESULTS: The prevalence of diabetes, but not metabolic syndrome, was significantly higher in subjects with the lower %VC than in those with the higher %VC in the lean men despite the fact that age, obesity parameters, systolic and diastolic blood pressures were significantly lower in subjects with the lower %VC than in those with the higher %VC and triglycerides, high-density lipoprotein cholesterol, high-sensitivity C-reactive protein, white blood cell count, and heart rate were not significantly different between the two groups. CONCLUSION: Low vital capacity was significantly associated with diabetes in lean Japanese men despite inverse relationships with metabolic risk factors.

A cross-sectional relationship between vital capacity and metabolic syndrome and between vital capacity and diabetes in a sample Japanese population.

OBJECTIVES: A lower vital capacity (VC) has been reported to be an independent predictor of diabetes in Western countries. The aim of this study was to examine the relationships between VC and diabetes and between VC and metabolic syndrome (MS) in Japanese individuals. METHODS: Stepwise multiple linear regressions with fasting glucose as a dependent variable and age, metabolic risk factors, and percentage vital capacity (%VC) as independent variables were performed using data obtained from 1651 men and 957 women. Area under the receiver operating characteristic curve (AUC) of -%VC for diagnosing diabetes, MS, and Japanese MS (JMS) were calculated, and stepwise logistic regressions using diabetes, MS, and JMS as dependent variables were performed. RESULTS: Percentage vital capacity was independently associated with fasting glucose in men, but not in women. The AUC of -%VC for diagnosing diabetes, MS, and JMS were 0.647, 0.606, and 0.598, respectively (all p < 0.0001) in men and 0.639 (p = 0.065), 0.513 (p = 0.732), and 0.668 (p = 0.01), respectively, in women. Age, waist circumference (WC), and %VC in men and WC and %VC in women were independently associated with diabetes. Age and %VC in men and only age in women were independently associated with MS, and age and %VC in both men and women were independently associated with JMS. CONCLUSIONS: Among a representative Japanese population, a lower VC was significantly associated with diabetes and MS in men, but the relationships were not conclusive in women.

The prevalence of metabolic syndrome and diabetes increases through the quartiles of white blood cell count in Japanese men and women.

OBJECTIVE: Low-grade systemic inflammation is proposed as a component of metabolic syndrome (MS) and is reported as a predictor of diabetes. We studied the association between white blood cell count (WBC) and MS and diabetes in Japanese men and women. METHODS: Cross-sectional associations between WBC and metabolic syndrome (MS) defined by revised NCEP criteria for Japanese, Japanese MS (JMS) defined by the Examination Committee for Criteria of Metabolic Syndrome, and diabetes were examined using medical check-up data from 1,880 men and 1,079 women. RESULTS: The prevalence of MS, JMS, and diabetes was 6.4%, 5.5%, and 4.3%,13.2%, 11.5%, and 5.5%, 15.1%, 13.8%, and 5.1%, and 24.3%, 21.3%, and 8.5%, respectively through the quartiles of WBC in men (p<0.0001, <0.0001, and <0.01, respectively in comparison between the lowest quartile of WBC and the highest quartile of WBC) and 2.2%, 0.4%, and 0.4%, 4.5%, 0.7%, and 1.1%, 9.3%, 1.9%, and 1.5%, and 12.3%, 4.8%, and 3.3%, respectively through the quartiles of WBC in women (p<0.0001, <0.01, and <0.05, respectively in comparison between the lowest quartile of WBC and the highest quartile of WBC). CONCLUSION: The prevalence of MS, JMS, and diabetes increases through the quartiles of WBC in Japanese men and women. Thus, WBC may be useful as a marker of cardiovascular disease risk.

Significance of heart rate in the prevalence of metabolic syndrome and its related risk factors in Japanese.

BACKGROUND: Autonomic dysfunction is thought to be an important mechanism of metabolic syndrome (MetS), but there has not been a study on the direct association between MetS and heart rate (HR) in Japanese. METHODS AND RESULTS: The association between MetS and HR was examined using medical check-up data from 1,880 men and 1,079 women. HR was significantly higher in MetS subjects than in non-MetS subjects in both men and women (P<0.0001 in men, P<0.001 in women). The prevalence of MetS increased linearly through the quartiles of HR in both men and women. HR was significantly correlated with MetS-related risk factors other than uric acid in men and other than uric acid, body mass index, waist circumference, and high-density lipoprotein cholesterol in women. CONCLUSIONS: The prevalence of MetS increased linearly with the increase in HR among Japanese men and women, and HR was significantly correlated with MetS-related risk factors.

Very low levels of high-sensitivity C-reactive protein are not bimodally distributed but are significantly related to other metabolic risk factors in Japanese.

BACKGROUND: High-sensitivity C-reactive protein (hs-CRP) is an independent risk factor of diabetes and cardiovascular disease and it is proposed as a component of metabolic syndrome. Blood levels of hs-CRP are reported to be much lower in Japanese than in Westerners and bimodally distributed in Japanese. METHODS: Very low levels of hs-CRP were examined using medical check-up data of 1,360 Japanese men and 821 women whose plasma levels of high-sensitivity C-reactive protein (hs-CRP) were below 10 mg/L. RESULTS: The distribution of hs-CRP levels were skewed but not bimodal in both men and women and very low levels of hs-CRP were significantly related to waist circumference, systolic blood pressure, diastolic blood pressure, fasting glucose, triglycerides, and low-density lipoprotein cholesterol in both men and women. The area under receiver operating characteristic curve of hs-CRP for diagnosing metabolic syndrome and Spearman's correlation coefficients between hs-CRP and components of metabolic syndrome were comparable to those of components of metabolic syndrome in both men and women. CONCLUSION: Very low levels of hs-CRP were not bimodally distributed but were significantly related to metabolic risk factors in Japanese.