Japanese Health Screening Population Research Articles

An observational cohort study of interstitial lung abnormalities (ILAs) in a large Japanese health screening population (Kumamoto ILA study in Japan: KILA-J)

BackgroundInterstitial lung abnormalities (ILAs) are subtle or mild parenchymal abnormalities observed in more than 5% of the lungs on computed tomography (CT) scans in patients in whom interstitial lung disease was not previously clinically suspected and is considered. ILA is considered to be partly undeveloped stages of idiopathic pulmonary fibrosis (IPF) or progressive pulmonary fibrosis (PPF). This study aims to clarify the frequency of subsequent IPF or PPF diagnosis, the natural course from the preclinical status of the diseases, and the course after commencing treatment.MethodsThis is an ongoing, prospective, multicentre observational cohort study of patients with ILA referred from general health screening facilities with more than 70,000 annual attendances. Up to 500 participants will be enrolled annually over 3 years, with 5-year assessments every six months. Treatment intervention including anti-fibrotic agents will be introduced in disease progression cases. The primary outcome is the frequency of subsequent IPF or PPF diagnoses. Additionally, secondary and further endpoints are associated with the efficacy of early therapeutic interventions in cases involving disease progression, including quantitative assessment by artificial intelligence.DiscussionThis is the first prospective, multicentre, observational study to clarify (i) the aetiological data of patients with ILA from the largest general health check-up population, (ii) the natural course of IPF or PPF from the asymptomatic stage, and (iii) the effects and outcomes of early therapeutic intervention including anti-fibrotic agents for progressive cases of ILA. The results of this study could significantly impact the clinical practice and treatment strategy for progressive fibrosing interstitial lung diseases.Trial registration numberUMIN000045149.

Low Vital Capacity Was Associated with Incident Diabetes in a Japanese Health Screening Population in Whom Obesity Was Not Prevalent.

There have been few studies regarding the relationship between respiratory function and incident diabetes in East Asian populations in whom obesity is not prevalent. This is a 6-year follow-up study in a Japanese health-screening population that included 1874 men and 1093 women. Using Cox regression models, hazard ratios (HRs) of incident diabetes for percent vital capacity (%VC) and forced expiratory volume in 1 second divided by forced vital capacity (FEV1/FVC) were calculated. Diabetes was defined as simultaneous fasting plasma glucose (FPG) ≥7.0 mmol/L and glycated hemoglobin (A1C) ≥6.5% or use of antidiabetic medications. During the 6-year follow-up period (mean of 4.8 years), 71 men (3.8%) and 18 women (1.7%) developed diabetes. The HRs (95% confidence intervals [CIs]) of incident diabetes for each 1 SD increase in %VC and the lowest tertile of %VC compared with the highest tertile were 0.81 (0.66 to 1.00) (p=0.045) and 1.78 (1.01 to 3.16) (p=0.048), respectively, adjusted for sex, age, body mass index, antihypertensive drug use and A1C levels. After further adjustment for log high-sensitivity C-reactive protein, the HRs (95% CI) of incident diabetes for each 1 SD increase in %VC and the lowest tertile of %VC were 0.82 (0.67 to 1.01) (p=0.063) and 1.69 (0.95 to 3.01) (p=0.073), respectively. The association between FEV1/FVC and incident diabetes was not significant. %VC, but not FEV1/FVC, was significantly associated with incident diabetes in a Japanese health-screening population in whom obesity was not prevalent.

Cross-Sectional and Longitudinal Associations between Serum Bilirubin and Prediabetes in a Health Screening Population.

Longitudinal associations between total bilirubin (TB) and prediabetes have not been reported. This study investigated cross-sectional and longitudinal associations between TB and prediabetes. Cross-sectional associations between TB and prediabetes were investigated in 3681 nondiabetic subjects. Longitudinal associations between TB and prediabetes over 6 years were investigated in 2149 subjects who were normoglycemic at baseline. Prediabetes was defined as fasting plasma glucose (FPG) levels of ≥5.6 mmol/L or glycated hemoglobin levels of ≥5.7% excluding diabetes. The prevalence of prediabetes was 25.4%, and the cumulative incidence of prediabetes during 6 years was 25.5% in a Japanese health screening population. Prevalent prediabetes was significantly associated with the quintiles of TB in nonsmoking men (trend, p<0.001) and women (trend, p=0.012), but not in smoking men (trend, p=0.689). Incident prediabetes was not significantly associated with the quintiles of TB, while it was positively associated with 1 standard deviation increase in TB in nonsmoking men (hazard ratio [95% confidence interval]; 1.21 [1.07 to 1.37], p=0.002). TB levels were significantly inversely associated with prevalent prediabetes in nonsmokers, but not in smokers, whereas an inverse association between TB levels and incident prediabetes seemed to be unlikely.

High-sensitivity C-reactive protein, but not white blood cell count, independently predicted incident diabetes in a Japanese health screening population.

To compare high-sensitivity C-reactive protein (hs-CRP) and white blood cell count (WBC) as a predictor of incident diabetes in a population where obesity is not prevalent. This is a retrospective 6-year follow-up study in a Japanese health screening population including 1874 men and 1094 women. Using Cox regression methods, hazard ratios (HRs) of incident diabetes for hs-CRP and WBC adjusting for fasting plasma glucose (FPG), hemoglobin A1c (HbA1c) and other confounders were calculated, and using areas under receiver operating characteristic curve (AUCs), diabetes-predicting abilities of hs-CRP and WBC were compared. Diabetes was defined as FPG ≥ 126 mg/dL and HbA1c ≥ 6.5 % or use of antidiabetic medication. During the 6-year follow-up period (mean ± SD, 4.8 ± 1.7 years), 71 men (3.8 %) and 19 women (1.7 %) developed incident diabetes. The fully adjusted HRs [95 % confidence intervals (CIs)] of incident diabetes for each 1 SD increase in log hs-CRP and WBC were 1.20 (0.92-1.56) (p = 0.174) and 1.01 (0.78-1.30) (p = 0.946), respectively. The fully adjusted HRs (95 % CIs) of incident diabetes for the highest tertile of hs-CRP and WBC compared with the lowest tertile were 2.57 (1.05-6.27) (p = 0.039) and 1.20 (0.53-2.70) (p = 0.665), respectively. The AUCs (95 % CIs) of hs-CRP and WBC for the discrimination of incident diabetes were 0.73 (0.68-0.77) and 0.67 (0.62-0.72), respectively. Hs-CRP, but not WBC, was independently associated with incident diabetes in a Japanese health screening population where obesity is not prevalent.

Albumin may prevent hypertension by inhibiting renin angiotensin aldosterone system

Decreased serum albumin concentrations predicted hypertension in a Japanese health screening population comprised of 1385 normotensive men and 855 normotensive women without cardiovascular disease at baseline (1). Compared with the lowest quartile of serum albumin (Q1) (3.0–4.1g/dL), the multivariable adjusted hazard ratios (95% confidence intervals; p values) of hypertension for the second (Q2) (4.2–4.3g/dL), third (Q3) (4.4g/dL) and fourth (Q4) (4.5–5.0g/dL) quartiles of serum albumin were 0.765 (0.574–1.018; p=0.066), 0.628 (0.440–0.895; p=0.010) and 0.520 (0.364–0.742; p<0.001), respectively (Table 1).

Comparison Among Body Mass Index, Waist Circumference, Waist-to-height Ratio, and Percent Body Fat as Predictors of Incident Diabetes in a Japanese Health Screening Population

Comparison Among Body Mass Index, Waist Circumference, Waist-to-height Ratio, and Percent Body Fat as Predictors of Incident Diabetes in a Japanese Health Screening Population

Low vital capacity was found to be associated with incident diabetes in health screening population of Japanese women.

There have been no previous studies regarding the relationship between the respiratory function and incident diabetes in East Asian women in whom obesity is not prevalent. Using Cox regression models, hazard ratios (HRs) for incident diabetes for each one SD increase in the percent vital capacity (%VC), a parameter of restrictive pulmonary dysfunction, forced expiratory volume in one second over forced vital capacity (FEV1/FVC), a parameter of obstructive pulmonary dysfunction, and log high-sensitivity C-reactive protein (hs-CRP) were calculated in 1,704 men and 1,016 women among a Japanese health screening population. Over the four-year study period (mean of 3.4 years), 54 men (3.2%) and 19 women (1.9%) developed diabetes. The HRs [95% confidence intervals (CIs); p values] for incident diabetes for each one SD increase in %VC and log hs-CRP were 0.81 (0.61-1.06; 0.127) and 1.29 (0.97-1.73; 0.085), respectively in men, and 0.55 (0.35-0.88) 0.012 and 2.50 (1.37-4.57; 0.003), respectively in women adjusted for age, fasting glucose and body mass index. The FEV1/FVC was not found to be significantly associated with incident diabetes in any regression models. The Spearman's correlation coefficients between %VC and hs-CRP was -0.11 (p<0.001) in men and -0.08 (p=0.007) in women. The HRs (95% CIs; p values) for each one SD increase in %VC and hs-CRP were 0.86 (0.65-1.13; 0.278) and 1.26 (0.94-1.70; 0.125), respectively in men, and 0.56 (0.34-0.94; 0.028) and 2.95 (1.49-5.81; 0.002), respectively in women, further adjusted for each other, systolic blood pressure, triglycerides and HDL cholesterol. A low %VC was found to be associated with incident diabetes, independent of hs-CRP in women among a Japanese health screening population.

Serum uric acid is an independent predictor of metabolic syndrome in a Japanese health screening population

Serum levels of uric acid (UA) are associated with metabolic syndrome (MetS). However, no study has been aimed to investigate whether baseline UA is a predictor of MetS in a Japanese population. The multivariable adjusted hazard ratios (HRs) of MetS through 3 years were calculated for each 1 SD increase in baseline UA, for the higher quartiles of baseline UA compared with the lowest quartile, and for baseline hyperuricemia defined as ≥7.0 mg/dl for men and ≥6.0 mg/dl for women in apparently healthy 1,606 men aged 51.7 ± 9.4 years and 953 women aged 51.6 ± 9.4 years who visited a medical check-up center in Japan. The HRs (95 % confidence interval; p value) were 1.282 (1.097-1.499; 0.002) in men and 1.354 (1.041-1.762; 0.024) in women for 1 SD increase in baseline UA, 2.206 (1.344-3.620; 0.002) in men and 3.110 (1.121-8.627; 0.029) in women for the highest quartile of baseline UA compared with the lowest quartile, and 1.900 (1.376-2.622; <0.001) in men and 2.088 (1.040-4.190; 0.038) in women for baseline hyperuricemia adjusting for the pre-existing components of MetS, age, smoking, drinking, physical activity, use of antihypertensive, antihyperlipidemic, and antidiabetic medications and histories of coronary heart disease and stroke. However, no significant association was found between longitudinal changes in UA and incident MetS. Baseline UA is an independent predictor of MetS in a Japanese health screening population.

High-sensitivity C-reactive protein and white blood cell count equally predict development of the metabolic syndrome in a Japanese health screening population

To compare high-sensitivity C-reactive protein (hs-CRP) and white blood cell count (WBC) as a predictor of metabolic syndrome (MetS). Hazard ratios (HRs) adjusted for age, smoking, and other confounding covariates and areas under receiver operating characteristic curve (AUCs) of hs-CRP and WBC for developing MetS were calculated in 1,463 men and 920 women from a Japanese health screening population who were free from MetS, diabetes, histories of coronary heart disease, and stroke at baseline and followed through 3 years. The adjusted HRs (95% confidence interval-CI; p value) of MetS for each 1 SD increases in log hs-CRP, and log WBC were 1.345 (1.166-1.553; <0.001) and 1.406 (1.188-1.664; <0.001), respectively, in men and 1.388 (1.110-1.736; 0.004) and 1.358 (1.072-1.721; 0.011), respectively, in women. However, the HRs became nonsignificant after further adjusted for the components of MetS. The AUCs (95% CI; p value) of hs-CRP and WBC for predicting MetS were 0.616 (0.573-0.660; <0.001) and 0.613 (0.566-0.659; <0.001), respectively, in men and 0.636 (0.573-0.698; <0.001) and 0.606 (0.538-0.673; 0.003), respectively, in women. Hs-CRP and WBC equally predict development of MetS, but both are poor predictors of MetS in a Japanese health screening population where obesity is not prevailing.

Low-density Lipoprotein Cholesterol is a Predictor of Metabolic Syndrome in a Japanese Health Screening Population

Both increased serum levels of low-density lipoprotein cholesterol (LDLC) and metabolic syndrome (MetS) are associated with obesity and have been established to be risk factors of cardiovascular disease. However, studies on the relationship between LDLC and MetS have been limited. Cross-sectional (n=3,871) and longitudinal (n=2,558) associations between LDLC and MetS were examined in a Japanese health screening population. The odds ratio (OR) [95% confidence interval (CI)] of coexisting MetS for each one SD increase in the LDLC level was 1.25 [1.12-1.40] (p<0.001) adjusted for body mass index (BMI) and other confounding covariates and 1.12 [0.97-1.28] (p=0.119) adjusted for numerical values of the components of MetS and other confounding covariates. The similarly adjusted ORs [95% CIs] for the highest quartile of LDLC (Q4) compared with the lowest quartile (Q1) were 1.76 [1.22-2.54] (p=0.002) and 1.46 (0.93-2.30) (p=0.101), respectively. The hazard ratio (HR) [95% CI] for developing MetS for each one SD increase in the LDLC level was 1.24 [1.10-1.40] (p<0.001) adjusted for BMI and other confounding covariates and 1.19 [1.05-1.34] (p=0.006) adjusted for the pre-existing dichotomous five components of MetS and other confounding covariates. The similarly adjusted HRs [95% CIs] for developing MetS for Q4 compared with Q1 were 1.71 [1.17-2.51] (p=0.006) and 1.61 [1.08-2.40] (p=0.020), respectively. The LDLC level is associated with coexisting MetS and functions as a predictor of the development of MetS, independent of BMI or the pre-existing components of MetS, in a Japanese health screening population.

Metabolic Syndrome is a Poor Predictor of Diabetes in a Japanese Health Screening Population

Although metabolic syndrome (MS) is considered to be a predictor of diabetes and cardiovascular disease, its value for predicting diabetes beyond the levels of fasting glucose (FG) and hemoglobin A1c (HbA1c) remains questionable. In this study, we evaluated the usefulness of MS and Japanese MS (JMS) as predictors of diabetes. This study is a longitudinal study using data for 2,034 subjects who visited our Medical Check-up Center in both 2008 and 2011 and were free from diabetes at baseline. The odds ratios (ORs) of developing diabetes in 2011 for MS and JMS were calculated after being adjusted for FG, age, sex and antihypertensive and antihyperlipidemic medication use, then further adjusted for HbA1c. The optimal cutoff points for FG, HbA1c and body mass index (BMI) to discriminate the development of diabetes and their sensitivities/specificities were obtained from receiver operating characteristic curves. These sensitivities/specificities were compared with the sensitivities/specificities of MS and JMS. The ORs (95% confidence intervals (CIs)) of developing diabetes for MS and JMS were 1.36 (0.57-3.23) (p=0.484) and 3.23 (1.25-8.36) (p=0.016), respectively, after being adjusted for FG and 1.06 (0.39-2.86) (p=0.915) and 2.34 (0.79-6.95) (p=0.126), respectively, after being further adjusted for HbA1c. The sensitivities/specificities of FG, HbA1c, BMI, MS and JMS were 0.625/0.897, 0.828/0/919, 0.625/0.734, 0.375/0.911, and 0.375/0.941, respectively. MS and JMS were found to be poor predictors of diabetes in a Japanese health screening population.

Decreased Serum Albumin Predicts Hypertension in a Japanese Health Screening Population

The serum albumin level has been reported to be positively associated with blood pressure in some cross-sectional studies. However, the longitudinal relationships between the serum albumin level and incident hypertension have been poorly studied. The incidence of hypertension was calculated for each quartile of serum albumin in 1,385 normotensive men and 855 normotensive women without cardiovascular disease at baseline who revisited for four years thereafter. The hazard ratios (HRs) of incident hypertension were calculated for each one SD increase in the serum albumin level and for the higher quartiles of serum albumin compared with the lowest quartile adjusted for smoking, alcohol drinking, body mass index, proteinuria, estimated glomerular filtration rate, uric acid, fasting glucose, log triglycerides, log high-sensitivity C-reactive protein, white blood cell count, hemoglobin, and systolic blood pressure. During four years of follow-up (mean; 3.1 years), 242 men (17.5%) and 89 women (10.4%) developed hypertension. The incidence of hypertension significantly decreased through the quartiles of albumin (p for trend=0.012). The HR (95% confidence interval (CI); p value) of hypertension for each one SD increase in the serum albumin level was 0.779 (0.696-0.872; <0.001). Compared with the lowest quartile of serum albumin, the HRs (95% CIs; p values) of hypertension for the second, third and fourth quartiles were 0.765 (0.574-1.018; 0.066), 0.628 (0.440-0.895; 0.010) and 0.520 (0.364-0.742; <0.001), respectively. A decreased serum albumin level was found to be a significant predictor of hypertension in a Japanese health screening population.

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

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

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.

Reproducibility of High-Sensitivity C-Reactive Protein as an Inflammatory Component of Metabolic Syndrome in Japanese

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. 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. 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.