[AN ADULT CASE OF PERIODIC FEVER, APHTHOUS STOMATITIS, PHARYNGITIS, AND ADENITIS (PFAPA) SYNDROME DEVELOPED IN CHILDHOOD AND DIAGNOSED AFTER PROGRESS MORE THAN 30 YEARS].

We report an adult case of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome, who had a tonsillectomy at 10 years old and relapsed later. An early 40's-year-old man had been suffering from recurrent fever attack once in 1-2 months during childhood. He was accompanied by fever which was persist for several days, aphthous stomatitis, tongued tonsillitis with moss, pharyngitis, and submandibular lymphadenitis with tenderness. He was not doing well during fare-up. At the time of admission, CRP level was 12.5mg/dl and the remarkably increased expression of CD64 on neutrophils was found. Bacterial infections and collagen diseases were excluded by the several examinations. We suspected PFAPA syndrome, and treated with cimetidine, but cimetidine was not effective. At the time of flare up, administration of prednisolone was remarkably effective. We diagnosed PFAPA syndrome on the basis of clinical courses. Genetic analysis of responsible gene of familial Mediterranean fever, MEFV showed E148Q heterozygous mutation in exon 2.Since an adult case of PFAPA syndrome is likely to be made misunderstanding for infectious recurrent pharyngitis, it is important to note that we should consider PFAPA syndrome as a differential diagnosis when we meet with the adult patient of recurrent fever.

Long-term Impact of Cardiorespiratory Fitness on Type 2 Diabetes Incidence: A Cohort Study of Japanese Men.

BACKGROUND: We sought to examine the association between cardiorespiratory fitness (CRF) and incidence of type 2 diabetes considering the follow-up period in a cohort of Japanese men with a maximum follow-up period of 23 years. METHODS: This study enrolled 7,804 male workers free of diabetes in 1986. CRF was measured using a cycle ergometer, and maximal oxygen uptake was estimated. During 1986-2009, participants were followed for development of type 2 diabetes, which was diagnosed using fasting blood tests, self-administered questionnaires, or oral glucose tolerance tests after urinary tests from annual health checkups. Hazard ratios for the incidence of type 2 diabetes were estimated using Cox proportional hazards models. RESULTS: During the follow-up period, 1,047 men developed type 2 diabetes. In analyses by follow-up periods (1986-1993, 1994-2001, and 2002-2009), there was an inverse dose-response relationship between CRF and the development of type 2 diabetes for all three follow-up periods (P for trend 0.019, <0.001, and 0.001, respectively), and the association between CRF at baseline and the incidence of type 2 diabetes did not weaken with longer follow-up period. Compared with the lowest CRF group, hazard ratios of developing type 2 diabetes were 0.69 (95% confidence interval [CI], 0.49-0.97) for the highest CRF group in 1986-1993, 0.57 (95% CI, 0.42-0.79) for the highest CRF in 1994-2001, and 0.47 (95% CI, 0.30-0.74) for the highest CRF in 2002-2009. CONCLUSION: High CRF is associated with a lower risk of the incidence of type 2 diabetes over an extended period of >20 years among men.

Importance of Achieving a "Fit" Cardiorespiratory Fitness Level for Several Years on the Incidence of Type 2 Diabetes Mellitus: A Japanese Cohort Study.

BACKGROUND: The "Physical Activity Reference for Health Promotion 2013" provides "fit" reference values for cardiorespiratory fitness (CRF) for good health. The importance of achieving a fit CRF level for several years on the subsequent prevention of type 2 diabetes mellitus (T2DM) remains to be clarified. METHODS: This cohort study was conducted in 2,235 nondiabetic males aged 21 to 59 years, enrolled in April 1986 through March 1987. We calculated the ratio of the area under the curve (AUCratio) for actual measured values and the AUC for the reference values of CRF in each individual during an 8-year measurement period before the baseline. According to whether they met a fit CRF level or not, participants were categorized into groups based on the AUCratio (FitAUC or UnfitAUC) and initial CRF (Fitinitial or Unfitinitial), respectively. T2DM was evaluated on health checkups until March 2010. RESULTS: During the follow-up period, 400 men developed T2DM. After adjustment for confounders, as compared with those in the FitAUC group, the hazard ratio (HR) for those in the UnfitAUC group was 1.33 (95% confidence interval [CI], 1.06-1.65). A combined analysis with the categories of initial value and AUCratio showed that, compared with the Fitinitial and FitAUC group, the HRs of Fitinitial and UnfitAUC, Unfitinitial and FitAUC, and Unfitinitial and UnfitAUC groups were 1.41 (95% CI, 0.99-2.00), 1.18 (95% CI, 0.81-1.70), and 1.40 (95% CI, 1.08-1.83), respectively. CONCLUSION: Achievement of a fit CRF level established in the Japan physical activity guideline for several years was associated with lower subsequent risk of T2DM.

Association between objectively measured physical activity and body mass index with low back pain: a large-scale cross-sectional study of Japanese men.

BACKGROUND: The relationship between the combination of physical activity (PA) and body mass index (BMI) with low back pain (LBP) is unclear. The present study offers a cross-sectional assessment of how combinations of PA and BMI are related to LBP in Japanese men. METHODS: Participants were 4022 Japanese men (mean age = 47) who underwent regular clinical examinations. PA was measured using a uniaxial accelerometer and divided into tertiles (PAhigh, PAmiddle, PAlow). A self-administered questionnaire was used to report on persistent LBP experience, drinking and smoking habits, and any existing lifestyle diseases. After covariance adjustment, a logistic regression model was used to assess how combinations of PA and BMI are related to persistent LBP. RESULTS: 428 of the participants had persistent LBP. A clear negative dose-response relationship was found between PA levels and persistent LBP (P for linearity = 0.012). Regarding BMI, odd ratios were shown to be higher in the overweight/obese category (BMI ≥ 25 kg/m2) than for the normal weight category (BMI < 25 kg/m2). When the PAhigh was taken as the reference in the normal weight category, odds ratios for PAlow and PAmiddle in the normal weight category were shown to be high. Moreover, in the overweight/obese category, odd ratios for every fitness level were also high as for the normal weight category. CONCLUSION: The present study showed that both PA and BMI are related to persistent LBP. Also, the prevalence of persistent LBP became higher when PAlow and high BMI are combined rather than the group of PAhigh and low BMI combination.

Obesity and low back pain: a retrospective cohort study of Japanese males.

[Purpose] This study evaluated whether obesity is a risk factor for low back pain, by using body fat percentage (%FAT) and body mass index (BMI) as indices of obesity among Japanese males. [Subjects and Methods] This study included 1,152 males (average age: 28.0 ± 4.6 years). BMI was calculated from subject's height and weight, and %FAT was estimated by the thickness of two parts of skin. Low back pain, drinking and smoking were surveyed using a self-administered questionnaire, and maximal oxygen uptake was measured by a submaximal exercise test using a cycle ergometer. [Results] A significant positive dose-response relationship was shown between %FAT and persistent low back pain prevalence. Similarly, a significant positive dose-response relationship was confirmed between BMI and persistent low back pain. [Conclusion] This study suggests that both high %FAT and BMI are risk factors for persistent low back pain.

A Naphthalimide-Based Cd(2+) Fluorescent Probe with Carbamoylmethyl Groups Working as Chelators and PET-Promoters under Neutral Conditions.

We have developed a novel naphthalimide-based Cd(2+) fluorescent probe (1), featuring almost no background response, high sensitivity and selectivity toward Cd(2+) through its high association constant [K=(2.10±0.423)×10(6) ], and a practical working pH range. Membrane-permeability was conferred on 1 by replacing the imide and amide substituents with n-butyl groups, and hence the derivative (4) has found practical utility on fluorescent imaging of Cd(2+) in HeLa cells. Comparison of fluorescent properties between various compounds derived from 1 has demonstrated that the carbamoylmethyl groups in 1 function not only as Cd(2+) chelators but also as promoters for photoinduced electron transfer (PET) by lowering the basicity of the two tertiary amino groups. As a result, 1 and 4 exhibited highly practical performance as Cd(2+) probes under neutral conditions.

Body Mass Index and Kidney Stones: A Cohort Study of Japanese Men.

BACKGROUND: In Japan, the incidence of kidney stones has increased markedly in recent decades. Major causes of kidney stones remain unclear, and limited data are available on the relationship between overweight/obesity and the incidence of kidney stones. We therefore evaluated body mass index (BMI) and the incidence of kidney stones in Japanese men. METHODS: Of the workers at a gas company, 5984 males aged 20-40 years underwent a medical examination in 1985 (baseline). This study includes 4074 of the men, who were free of kidney stones at baseline and underwent a second medical examination performed between April 2004 and March 2005. BMI was calculated from measured height and weight in 1985, and men were categorized into tertiles. The development of kidney stones during follow-up was based on self-reports from questionnaires at the second medical examination. RESULTS: The average duration of follow-up was 19 years, with 258 participants developing kidney stones during this period. Using the lowest BMI (1st tertile) group as a reference, the hazard ratios (95% confidence intervals [CIs]) for the 2nd and 3rd BMI tertiles were: 1.26 (95% CI, 0.92-1.73) and 1.44 (95% CI, 1.06-1.96), respectively (P for trend = 0.019). After additionally adjusting for potential confounders, such as age, systolic blood pressure, cardiorespiratory fitness, cigarette smoking, and alcohol consumption, the hazard ratios were 1.28 (95% CI, 0.93-1.76) and 1.41 (95% CI, 1.02-1.97), respectively (P for trend = 0.041). CONCLUSIONS: These results suggest that increased BMI is a risk factor for kidney stones in Japanese men.

Dynapenic Obesity and Prevalence of Type 2 Diabetes in Middle-Aged Japanese Men.

BACKGROUND: The independent and combined associations of muscle strength and obesity on the prevalence of type 2 diabetes in Japanese men remain unclear. METHODS: Hand grip strength was cross-sectionally evaluated between 2011 and 2013 to assess muscle strength in 5039 male workers aged 40 to 64 years. Weight and height were measured, and overweight/obesity was defined as a body mass index ≥25 kg/m(2). The prevalence of type 2 diabetes, defined as fasting plasma glucose ≥126 mg/dL and/or hemoglobin A1c ≥6.5% and/or self-reported physician-diagnosed diabetes, was evaluated. Odds ratios (OR) and 95% confidence intervals (95% CI) for the prevalence of type 2 diabetes were obtained using a logistic regression model. RESULTS: In total, 611 participants had type 2 diabetes, and 1763 participants were overweight/obese. After adjustment for covariates, we found an inverse association between muscle strength and the prevalence of type 2 diabetes (P for trend <0.01). In addition, when the analyses were stratified by obesity status, the multivariable-adjusted OR per 2-standard-deviation increase in muscle strength was 0.64 (95% CI, 0.49-0.83) in the overweight/obese group, compared to a weaker relationship in the normal-weight group (OR 0.79 per 2-standard-deviation increase; 95% CI, 0.60-1.06). CONCLUSIONS: Dynapenia, an age-related decrease in muscle strength, is associated with increased prevalence of type 2 diabetes, and this relationship is stronger in overweight/obese middle-aged Japanese men than in normal-weight men.

Reference values for cardiorespiratory fitness and incidence of type 2 diabetes.

BACKGROUND: In "Physical Activity Reference for Health Promotion 2013" the Japan Ministry of Health, Labour and Welfare publication gives reference values for cardiorespiratory fitness (CRF) required for good health. We examined the associations between the CRF reference values and incidence of type 2 diabetes. METHODS: This prospective cohort study enrolled 4633 nondiabetic Japanese men aged 20 to 39 years at baseline. CRF was measured using the cycle ergometer test, and maximal oxygen uptake was estimated. On the basis of the CRF reference value, participants were classified into 2 groups: those with values less than the reference value (under-RV) and those with values equal to or greater than reference value (over-RV). Hazard ratios (HRs) and 95% CIs for incident type 2 diabetes were estimated using a Cox proportional hazards model. RESULTS: A total of 266 participants developed type 2 diabetes during the 14 years of follow-up. As compared with the under-RV group, the over-RV group had a significantly lower multivariable-adjusted HR for type 2 diabetes (HR 0.67; 95% CI, 0.51-0.89). In receiver operating characteristic analysis, the optimal CRF cut-off value for predicting incident type 2 diabetes was 10.8 metabolic equivalents (sensitivity, 0.64; specificity, 0.64), which was close to the CRF reference value of 11.0 metabolic equivalents. CONCLUSIONS: The reference CRF value appears to be reasonably valid for prevention of type 2 diabetes, especially among Japanese men younger than 40 years. Development of type 2 diabetes can be prevented by maintaining a CRF level above the reference value.

Cardiorespiratory fitness, body mass index, and cancer mortality: a cohort study of Japanese men.

BACKGROUND: The aim of this study is to investigate the independent and joint effects of cardiorespiratory fitness (CRF) and body mass index (BMI) on cancer mortality in a low body mass index population. METHODS: We evaluated CRF and BMI in relation to cancer mortality in 8760 Japanese men. The median BMI was 22.6 kg/m2 (IQR: 21.0-24.3). The mean follow-up period was more than 20 years. Hazard ratios and 95% CI were obtained using a Cox proportional hazards model while adjusting for several confounding factors. RESULTS: Using the 2nd tertile of BMI (21.6-23.6 kg/m2) as reference, hazard ratios and 95% CI for the lowest tertile of BMI (18.5-21.5) were 1.26 (0.87-1.81), and 0.92 (0.64-1.34) for the highest tertile (23.7-37.4). Using the lowest tertile of CRF as reference, hazard ratios and 95% CIs for 2nd and highest tertiles of CRF were 0.78 (0.55-1.10) and 0.59 (0.40-0.88). We further calculated hazard ratios according to groups of men cross-tabulated by tertiles of CRF and BMI. Among men in the second tertile of BMI, those belonging to the lowest CRF tertile had a 53% lower risk of cancer mortality compared to those in the lowest CRF tertile (hazard ratio: 0.47, 95% CI: 0.23-0.97). Among those in the highest BMI tertile, the corresponding hazard ratio was 0.54 (0.25-1.17). CONCLUSION: These results suggest that high CRF is associated with lower cancer mortality in a Japanese population of men with low average BMI.

Impact of salvage chemotherapy after immune checkpoint inhibitor for recurrent or metastatic head and neck cancer.

BACKGROUND: It is unclear witch regimen is optimal as salvage chemotherapy (SCT) after immune checkpoint inhibitor (ICI) monotherapy for recurrent or metastatic head and neck cancer (RM-HNC). METHODS: This study enrolled 109 patients. Overall survival (OS) and progression-free survival 2 (PFS2) were compared between patients stratified by SCT regimen. RESULTS: Of the 109 patients, 55 underwent SCT after the failure of ICI monotherapy. The OS of these 55 patients was longer than that of patients who did not undergo SCT. The OS and PFS2 were similar between patients treated with paclitaxel (PTX) and cetuximab (Cmab) combination and those treated with PTX monotherapy. The occurrence of irAEs did not impact PFS2 nor OS. CONCLUSIONS: SCT can improve the survival outcomes of patients with RM-HNC. In addition to PTX and Cmab, PTX monotherapy is also considered an effective SCT regimen. SCT is effective regardless of the presence or absence of irAEs.

Impact of tumor burden on survival in patients with recurrent or metastatic head and neck cancer treated with immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) have become the standard treatment for recurrent or metastatic head and neck cancer (RM-HNC). However, many patients fail to benefit from the treatment. Previous studies have revealed that tumor burden predicts the efficacy of ICIs, but this association remains unclear for RM-HNC. We retrospectively analyzed 94 patients with RM-HNC treated with ICI monotherapy. We estimated the tumor burden using the baseline number of metastatic lesions (BNML) and the baseline sum of the longest diameters of the target lesions (BSLD), and evaluated the association between BNML, BSLD, and standardized uptake value (SUV) and clinical outcomes. The median progression-free survival (PFS) was 7.1 and 3.1 months in the low-BNML and high-BNML groups, respectively (p = 0.010). The median PFS was 9.1 and 3.5 months in the low-BSLD and high-BSLD groups, respectively (p = 0.004). Moreover, patients with high SUVmax levels had worse overall survival (OS) and PFS. BNML, BSLD, and SUVmax are useful prognostic factors in patients with RM-HNC treated with ICIs. Imaging examinations before ICI treatment are recommended to predict the efficacy of ICIs. If the tumor burden is high, cytotoxic anticancer agents may be administered concomitantly with or prior to ICI monotherapy.

Synthesis of fused and linked bicyclic nitrogen heterocycles by palladium-catalyzed domino cyclization of propargyl bromides.

The palladium(0)-catalyzed direct construction of bicyclic heterocycles is described. Treatment of propargyl bromides that have nucleophilic functional groups connected by two or three carbon atoms with catalytic [Pd(PPh(3))(4)] affords bis-cyclization products in good yields. The desired bicyclic heterocycles can be obtained selectively when using substrates with appropriate nucleophilic groups. We also describe the reaction of a 2-alkynylazetidine derivative with a catalytic amount of [Pd(PPh(3))(4)] under base-free conditions, which affords the same fused heterocycles as the corresponding propargyl bromides.

Frequency of achieving a 'fit' cardiorespiratory fitness level and hypertension: a cohort study.

OBJECTIVES: Although maintaining cardiorespiratory fitness is encouraged to reduce the risk of hypertension, the level at, and length of time for which, individuals need to maintain fitness remains unclear. We examined the association between the frequency of achieving the recommended fitness levels of the 'Physical Activity Reference for Health Promotion 2013' and the risk of hypertension among Japanese men. METHODS: This cohort study was conducted in 6653 men without hypertension enrolled in 1986. Whether the participants' fitness level was equal to or exceeded the reference value (fit) or not (unfit) was determined. The frequency of achieving the recommended fitness level was calculated by counting the number of times the fitness level was achieved in 1980 through 1986. Incident hypertension was defined as the first visit with a SBP/DBP of at least 140/90 mmHg or self-reported antihypertensive medication use and was evaluated during annual health examinations from 1986 until 2009. RESULTS: During the follow-up period, 3630 men developed hypertension. The multivariable-adjusted hazard ratios (95% confidence interval) for incident hypertension comparing men with fit versus unfit at baseline was 0.79 (0.74-0.85). Moreover, the frequency of achieving the recommended fitness level was inversely associated with the incidence of hypertension. The risk of hypertension was lower among those who achieved three or more of the recommended levels (0.72 for three times to 0.62 for seven times). CONCLUSION: Achieving the fitness level recommended in the Japanese guideline three or more times during a 6-year period can be beneficial for the risk reduction of hypertension.

Polyamines stabilize left-handed Z-DNA: using X-ray crystallographic analysis, we have found a new type of polyamine (PA) that stabilizes left-handed Z-DNA.

There are many great reports of polyamine stabilization of the Z-DNA by bridge conformation between neighboring, symmetry-related Z-DNA in the packing of crystals. However, polyamine binding to the minor groove of Z-DNA and stabilizing the Z-DNA structure has been rarely reported. We proved that the synthesized polyamines bind to the minor groove of Z-DNA and stabilize the conformation under various conditions, by X-ray crystallographic study. These polyamines consist of a polyamine nano wire structure. The modes of the polyamine interaction were changed under different conditions. It is the first example that the crystals consisted of metal free structure. This finding provides a basis for clarifying B-Z transition mechanics.

Direct construction of bicyclic heterocycles by palladium-catalyzed domino cyclization of propargyl bromides.

The palladium-catalyzed domino cyclization of propargyl bromides having two nucleophilic functional groups is described. Treatment of 1,7-diamino-5-bromohept-3-yne derivatives with catalytic Pd(PPh3)4 in the presence of NaH in MeOH gives the 2,7-diazabicyclo[4.3.0]non-5-enes in good yields. Interestingly, the regioselectivity of the reaction is completely controlled by the relative reactivity of the amine functional groups, irrespective of the position of the nucleophiles. The malonate derivative also undergoes domino cyclization to produce a hexahydroindole derivative.

The Association of Fit-Fat Index with Incident Diabetes in Japanese Men: A Prospective Cohort Study.

Type 2 diabetes is increasing globally and in Asia. The purpose of this study was to examine the association of a fit-fat index (FFI) with diabetes incidence among Japanese men. In total 5,014 men aged 18-64 years old, who had an annual health check up with no history of major chronic disease at baseline from 2002 to 2009 were observed. CRF was estimated via cycle ergometry. Overall, 7.6% of the men developed diabetes. The mean follow-up period was 5.3 years. Hazard ratios, 95% confidence intervals and P trend for diabetes incidence were obtained using the Cox proportional hazards model while adjusting for confounding variables. High FFI demonstrated lower risk 0.54 (0.36-0.82) compared to low BMI 0.63 (0.44-0.90), low WHtR 0.64 (0.41-1.02), and High CRF 0.72 (0.51-1.03). FFI showed a marginally stronger dose response relationship across quartiles (P (trend) =0.001) compared to BMI (P (trend) =0.002), WHtR (P (trend) =0.055), and CRF (P (trend) =0.005). Overall, both fitness and fatness play independent roles in determining diabetes incidence in Japanese men. FFI may be a more advantageous physical fitness measure because it can account for changes in fitness and/or fatness.

Combined association of cardiorespiratory fitness and family history of hypertension on the incidence of hypertension: a long-term cohort study of Japanese males.

Family history of hypertension (FH) is a nonmodifiable risk factor for hypertension. However, cardiorespiratory fitness (CRF) is a modifiable risk factor and might be important for preventing hypertension in both people with and without FH. The purpose of this study was to investigate the combined association of CRF and FH on the incidence of hypertension in normotensive male Japanese workers. A total of 6890 workers were included in this study. CRF was determined using a submaximal exercise test. A self-reported questionnaire was used to determine FH. Six groups were established, combining the two groups with and without FH (Yes, No) and the three CRF groups (Low, Moderate, High). The incidence of hypertension, defined as systolic blood pressure of ≥140 mmHg or diastolic blood pressure of ≥90 mmHg, or self-reported physician-diagnosed hypertension was evaluated. During the observation period of 101,212 man-years (median 17 years, minimum 1 year, maximum 23 years), 2210 workers developed hypertension. There were 3860 participants who had FH (56%). Compared with the Yes-Low CRF group, the HRs (95% CI) for hypertension were 66% lower in the No-High CRF group (0.34 [0.28-0.40]), 47% lower in the No-Low CRF group (0.53 [0.46-0.61]), and 24% lower in the Yes-High CRF group (0.76 [0.67-0.86]). FH and CRF did not show a significant interaction (p for interaction = 0.181). The combination of FH and CRF showed a clear association with the risk of incident hypertension, and moderate to high levels of CRF might be equally beneficial for preventing hypertension for both people with and without FH.

Objectively Measured Physical Activity and Low Back Pain in Japanese Men.

BACKGROUND: There are several studies on the relationship between low back pain and physical activity. However, the results of these studies vary, and the relationship between them remains unclear. Therefore, we conducted a cross-sectional study to evaluate the association between objectively measured physical activity and low back pain in Japanese men. METHODS: The study included 4022 Japanese men [average age: 47 (10) y]. Daily amount of moderate to vigorous physical activity and step counts were measured using an accelerometer. Low back pain, drinking and smoking, and lifestyle-related diseases were surveyed using a self-administered questionnaire. A logistic regression model was used to evaluate the relationship between physical activity and step counts with persistent low back pain after adjusting for confounders. RESULTS: Persistent low back pain was reported in 428 participants. The multivariable-adjusted odds ratios of presenting persistent low back pain across quartiles of amount of moderate to vigorous physical activity were 1.00 (reference); 0.93 (95% confidence interval, 0.70-1.22); 0.97 (95% confidence interval, 0.74-1.28); and 0.67 (95% confidence interval, 0.50-0.90); P for linearity = .012. CONCLUSION: We found a significant inverse relationship between objectively measured physical activity and persistent low back pain.

Relationship between Cardiorespiratory Fitness and Non-High-Density Lipoprotein Cholesterol: A Cohort Study.

AIM: Recent studies have suggested that non-high-density lipoprotein cholesterol (non-HDL-C) may be a good marker of coronary heart disease and cardiovascular disease risk. Therefore, we investigated the relationship between cardiorespiratory fitness (CRF) and non-HDL-C. METHODS: We evaluated CRF and the incidence of high level of non-HDL-C in 4,067 Japanese men without dyslipidemia. The participants were given a submaximal exercise test, a medical examination, and questionnaires on their health habits in 1986. A cycle ergometer was used to measure the CRF and maximal oxygen uptake was estimated. The incidence of a high level of non-HDL -C (≥170 mg/dL) from 1986 to 2006 was ascertained based on the fasting blood levels. A high level of non-HDL-C was found in 1,482 participants during the follow-up. Cox proportional hazard models were used to obtain the hazard ratios (HRs) and 95% confidence intervals (CIs) for the incidence of a high level of non-HDL-C. RESULTS: Following age adjustment, and using the lowest CRF group (quartile Ⅰ) as reference, the HRs and 95% CIs for quartiles II through IV were: 1.00 (95% CI: 0.87-1.15), 0.87 (95% CI: 0.76-1.00), and 0.70 (95% CI: 0.60-0.81), respectively (P for trend ＜0.001). After additional adjustment for body mass index, systolic blood pressure, smoking, alcohol intake, and family history of dyslipidemia, the HRs and 95% CIs were: 1.05 (95% CI: 0.92-1.21), 0.94 (95% CI: 0.81-1.08), and 0.79 (95% CI: 0.67-0.92), respectively (P for trend=0.001). CONCLUSIONS: These results suggest that there is an inverse relationship between CRF levels and the incidence of a high level of non-HDL-C in Japanese men.