Effect of Novel Stratified Lipid Risk by "LDL-Window" and Flow-Mediated Dilation on the Prognosis of Coronary Artery Disease Using the FMD-J Study A Data.

BACKGROUND: Elevated levels of triglyceride (TG) and non-high-density lipoprotein cholesterol (non-HDL-C) are regarded as a residual lipid risk in low-density lipoprotein cholesterol (LDL-C)-lowering therapy. This study investigated the association between lipid risk stratified by TG and non-HDL-C and the prognosis of patients with coronary artery disease (CAD), and the association between stratified lipid risk and flow-mediated dilatation (FMD) index.Methods and Results: The 624 CAD patients enrolled in flow-mediated dilation (FMD)-J study A were divided into 4 groups: low-risk group (n=413) with TG <150 mg/dL and non-HDL-C <170 mg/dL; hyper-TG group (n=180) with TG ≥150 mg/dL and non-HDL-C <170 mg/dL; hyper-non-HDL group (n=12) with TG <150 mg/dL and non-HDL-C ≥170 mg/dL; and high-risk group (n=19) with TG ≥150 mg/dL and non-HDL-C ≥170 mg/dL. Comparison of the groups showed the cumulative incidence of a 3-point major adverse cardiovascular event (MACE) was different and highest in the high-risk group in all the patients (P=0.009), and in patients with a FMD index ≥7.0% (P=0.021), but not in those with a FMD index <7.0%. Multivariable regression analysis showed that high lipid risk (P=0.019) and FMD <7.0% (P=0.040) were independently correlated with the incidence of a 3-point MACE. CONCLUSIONS: Novel stratification of lipid risk, simply using TG and non-HDL-C levels, combined with FMD measurement, is useful for predicting cardiovascular outcomes in patients with CAD.

Patient satisfaction and loyalty in Japanese primary care: a cross-sectional study.

BACKGROUND: This study aimed to explore associations between various elements of primary care, patient satisfaction, and loyalty. METHODS: This cross-sectional study used a modified version of the Primary Care Assessment Tool (PCAT), which was adapted for Japan. We distributed the PCAT questionnaire to patients aged 20 years or older at five rural primary care centres in Japan. We confirmed the validity and reliability of the measure for our study. Next, we examined which elements of primary care were related to patient satisfaction and loyalty using Spearman's correlation and structural equation modelling. RESULTS: Of 220 eligible patients, 206 participated in this study. We developed nine component scales: first contact (regular access), first contact (urgent access), longitudinality, coordination, comprehensiveness (variety of care), comprehensiveness (risk prevention), comprehensiveness (health promotion), family-centeredness, and community orientation. Longitudinality and first contact (urgent access) were related with patient satisfaction. Longitudinality, first contact (regular access), and family-centeredness were related to patient loyalty. In the structural equation modelling analysis, two variables were significantly related to loyalty, namely a combined variable including longitudinality and first contact (regular access), along with family-centeredness. CONCLUSIONS: While a patient satisfaction model could not be distilled from the data, longitudinality, first contact (urgent access), and family-centeredness were identified as important elements for the cultivation of patient loyalty. This implies that primary care providers need to develop a deep understanding of patients' contexts and concerns and pay attention to their level of access to cultivate greater patient loyalty.

Evaluation of Realistic Sensation Using Biological Reaction Measurements for Food Videos Presented by KMMD.

We have prototyped a KANSEI multimedia display (KMMD) that is able to release scent through the screen in order to realize collaboration between images and scents. Two types of "sukiyaki" food videos were presented to subjects using this device, and a method for objectively evaluating the realistic sensation of the food videos was examined using biological reaction measurements. The sukiyaki scent was added to one type of video to improve appetite. Viewers' saliva flow rate, line of sight, pupil diameter, autonomic nerve activity, and cerebral blood flow were measured at the same time, and changes in these measured values were analyzed. As a result, the scent was effective in improving the sensation, as if the food was present in front of the eyes and increasing the saliva flow rate. Additionally, in a realistic scene, it was found that the line of sight follows the performer's eating behavior as if the viewers themselves are eating. The sympathetic nervous system temporarily increases, mydriasis occurs, and the frontal lobe is activated. Furthermore, the possibility of objective evaluation of realistic sensations was demonstrated by the correlation between appetite, accompanied by salivary sensation, and the biological reaction measurement results.

Target of Triglycerides as Residual Risk for Cardiovascular Events in Patients With Coronary Artery Disease　- Post Hoc Analysis of the FMD-J Study A.

BACKGROUND: Circulating triglyceride (TG) levels are a current focus as a residual risk for cardiovascular (CV) events. We evaluated the relationship between circulating TG levels and future CV events in patients with coronary artery disease (CAD) who were treated with conventional therapy. Methods and Results: We analyzed data for 652 patients who were enrolled in the FMD-J Study A. We investigated the associations between serum TG levels and first major CV events (death from CV cause, nonfatal acute coronary syndrome (ACS), nonfatal stroke, and CAD) for a 3-year follow-up period. Patients were divided into 4 groups based on serum TG level: low-normal (<100 mg/dL), high-normal (100-149 mg/dL), borderline hypertriglyceridemia (150-199 mg/dL), and moderate hypertriglyceridemia (≥200 mg/dL). During a median follow-up period of 46.6 months, 14 patients died (9 from CV causes), 16 had nonfatal ACS, 6 had nonfatal stroke, and 54 had CAD. The Kaplan-Meier curves for first major CV event among the 4 groups were significantly different (P=0.04). After adjustment for various confounders, serum TG level ≥100 mg/dL were significantly associated with an increased risk of first major CV events compared with serum TG level <100 mg/dL. CONCLUSIONS: Serum TG level may be a surrogate marker for predicting CV events in patients with CAD.

Development of the Japanese version of the general practice assessment questionnaire: measurement of patient experience and testing of data quality.

BACKGROUND: Physicians' interpersonal performance is critical in medical practice, especially primary care practice. The General Practice Assessment Questionnaire (GPAQ) was developed in the United Kingdom to evaluate the quality of primary care from the viewpoint of patients. This questionnaire highlights the evaluation of interpersonal skills and interactions between physicians and patients. Though several other tools also exist to evaluate primary care quality, the GPAQ has several distinctive evaluation items, covering receptionists, access to primary care, and enablement (patients' understanding of self-care and of their own health after consultation). Our purpose was to develop and validate a Japanese version of the GPAQ. METHODS: This cross-sectional study tested the validity and reliability of the Japanese version of the questionnaire. We translated the original GPAQ into Japanese and assessed its reliability and validity among patients aged ≥20 years at five rural primary care centres located in Shimane and Okayama prefectures, Japan. We also examined its internal reliability using Cronbach's alpha coefficient and construct validity-including item-scale correlations, item-other scale correlations, and inter-scale correlations. Moreover, we examined correlations between each score and overall satisfaction using Spearman's correlation coefficient for criterion-related validity. RESULTS: The translated version of the GPAQ was administered, and we received 252 responses (mean age: 68 ± 12.3 years, male: 42.9%); all data were analysed. The translated questionnaire showed good reliability and validity, with Cronbach's alphas ranging from 0.79-0.92 for all scales, and satisfactory item-scale, item-other scale, and inter-scale correlations. Correlations with overall satisfaction were strong (Spearman's correlation coefficients: 0.31-0.38) for all scales except 'continuity of care'. CONCLUSIONS: The Japanese version of the GPAQ was acceptable, reliable, and valid. This could be a useful instrument to evaluate key areas of primary care performance in Japan, particularly physicians' communication skills. Further work is required to evaluate its utility in urban areas.

Association Between Waist-to-Height Ratio and Endothelial Dysfunction in Patients With Morbidity　- A Report From the FMD-J Study.

BACKGROUND: Waist circumference (WC), waist-to-height ratio (WHtR) and body mass index (BMI) are known as easy anthropometric markers of abnormal obesity and screening tools for predicting cardiovascular outcomes, but which indices are best is unclear. We therefore investigated the superiority and association between each index and low flow-mediated dilatation (FMD) as a surrogate marker for cardiovascular outcomes in patients with morbidity in a large Japanese prospective cohort.Methods and Results:A total of 1,645 Japanese patients who had coronary artery disease and hypertension or diabetes mellitus were enrolled, and 1,087 of them were analyzed. The high-WHtR group (≥0.5) showed greater morbidity and increased inflammation in association with atherosclerosis compared with the low-WHtR group. High WHtR and advanced age were identified as predictors of low FMD (odds ratio (OR) 1.39, 95% confidence interval (CI) 1.02-1.88, P=0.037 and OR 1.55, 95% CI 1.19-2.01, P=0.001, respectively). However, WC was not associated with that risk in either sex (male: OR 1.37, 95% CI 0.97-1.93, P=0.076; female: OR 1.08, 95% CI 0.68-1.73, P=0.74), and no association was evident between high BMI and low FMD (OR 0.92, 95% CI 0.71-1.19, P=0.54). CONCLUSIONS: WHtR offers a superior predictor of decreased FMD than other anthropometric indices, and progression of arteriosclerosis might be detected more sensitively. Further study is needed to investigate the relationship between cardiovascular mortality and WHtR.

Awareness of salt restriction is not reflected in the actual salt intake in Japanese hypertensive patients.

OBJECTIVES: The Japanese guidelines for hypertension management recommend reducing salt intake to <6 g/day for hypertensive patients. However, it is not currently known whether hypertensive patients' awareness of the recommended reduced salt diet correlates with their actual intake. Therefore, the purpose of this study was to investigate the relationship between actual salt intake of Japanese hypertensive patients and their awareness of the recommended guidelines for reduced dietary salt intake. METHODS: In total, 236 outpatients (146 males and 90 females) with a mean age 69.7 ± 12.5 years were included in this study. Daily dietary salt intake was estimated using sodium and creatinine concentrations detected in spot urine samples. The patients filled out a questionnaire regarding their awareness of recommended salt restriction for hypertension management. The questionnaire distinguished the patients' awareness of recommended salt restriction in four levels (low, moderate, high and very high). RESULTS: The mean estimated salt intake was 9.72 ± 2.43 g/day. Patients' awareness regarding salt intake in all levels provided in the questionnaire did not correlate with actual salt intake (p = 0.731). CONCLUSION: Our results demonstrated that Japanese hypertensive outpatients consumed higher levels of salt than the target value recommended by Japanese guidelines. There was no correlation between actual salt intake and patients' awareness of the recommended reduction in salt. These results suggest that monitoring salt intake and informing patients of their actual salt intake are necessary for effective hypertension management.

Close relationship between serum hyaluronan levels and vascular function in patients with type 2 diabetes.

OBJECTIVE: To clarify the relationship between serum hyaluronan levels and vascular function in type 2 diabetic patients. METHODS: A cross-sectional cohort study. RESULTS: In multivariate regression analysis, endothelium-dependent flow-mediated dilation was associated with age and duration of diabetes, but not with serum hyaluronan level, while endothelium-independent nitroglycerine-mediated dilation (NMD) was only associated with serum hyaluronan level (standardized estimate = -0.401, p = 0.003). NMD in the lowest tertile of hyaluronan level was significantly higher than the other tertiles (15.9% versus 12.5% and 10.4%, p = 0.047 and p = 0.002, respectively). CONCLUSIONS: Serum hyaluronan level may be useful as a surrogate marker for early changes in the vascular function, which often occurs in patients with diabetes mellitus.

A case of ascending aortic dissection and rupture caused by giant cell arteritis.

Giant cell arteritis (GCA) is an autoimmune disease characterized by granulomatous inflammation in the wall of medium-sized and large-sized arteries, and it usually occurs in patients over 50 years of age.(1)) Symptoms are nonspecific, and include fatigue, fever, and headache.(2)) It is occasionally combined with aortic complications, and ruptures resulting in death. These complications occur as late events, usually several years after diagnosis and often after other symptoms have subsided.(3)) Physicians should therefore be alert for complications of the large arteries in GCA. Here we present a case of GCA combined with ascending aortic dissection and rupture 3 weeks after diagnosis.

Simulation and application assessment of the efficacy of fosthiazate-loaded microcapsules against root-knot nematode.

BACKGROUND: Although microencapsulation technology is an effective pesticide formulation method, the correlation between the release properties of microcapsules and pesticide concentrations in soil and their efficacy has not been thoroughly investigated. Here, the effects of the release properties of the nematicide Fosthiazate (FTZ) from microcapsules on their efficacy against the nematode Meloidogyne incognita were examined using experimental and mathematical approaches. RESULTS: Gradual release of FTZ from both polyurea microcapsules (PU-MC) and melamine-formaldehyde microcapsules (MF-MC) was observed over 30 days in the release test, and each release curve was completely distinct. In the biological test, the efficacy of both microcapsules against M. incognita 42 days after the application was 8-15% higher than that of the non-encapsulated FTZ at a concentration of 2.0 mg FTZ kg-1 soil. Soil degradation experiments suggested that the microcapsules worked effectively to protect the FTZ from degradation, which resulted in higher efficacy at a later stage. A simulation study to predict the concentration of FTZ outside the microcapsule found that the timing of supplying FTZ was important and suggested that the mixture of non-encapsulated FTZ (non-MC) and MF-MC showed enhanced efficiency for the entire cultivation period in the biological test; the efficacy against nematodes was also confirmed by the measurement of nematode density using the Bearman funnel method. CONCLUSION: The release properties of FTZ from microcapsules are critical for their effective application against M. incognita, and the established simulation study is a useful step in designing suitable release properties under complex soil conditions. © 2024 Society of Chemical Industry.

Accelerometer-measured physical activity and posture among older adults in assisted-living residences.

Objective: Few studies have detailed the physical activity and postural patterns (e.g. lying or sitting) in older adults with declining activities of daily living (ADL). Therefore, we aimed to address this issue by quantifying physical activity using an accelerometer and measuring time spent in various postures among older adults in assisted-living residences. Methods: We quantified physical activity using an accelerometer (ActivPAL) and measured time spent in various postures in 35 older adults (mean age: 89.1 years) with chronic conditions residing in two assisted-living residences in Japan. ActivPAL was attached to the thigh and trunk of patients to distinguish between sitting and lying postures. Results: Participants had a mean count of 6.2 comorbidities, and they were divided into three groups (fully independent, requiring minimal assistance and requiring care) based on their activities of daily living capacity using the Barthel Index. Residents aged ⩾90 years walked a mean of 1109.1 steps and spent 167.3 min upright per day. Fully independent participants walked a mean of 3587.6 steps daily; those requiring minimal assistance walked 1681.0 steps daily; and those requiring care walked 428.9 steps daily. Conclusions: Our findings indicated that step count, number of sit-to-stand transitions, stepping time, and upright time decreased significantly as activities of daily living capacity decreased. Comorbidity type and number of comorbidities were not related to their lying time except for depression status. Lying time was associated with depression status.

Role of Small Dense Low-density Lipoprotein Cholesterol in Cardiovascular Events in Patients with Coronary Artery Disease and Type 2 Diabetes Mellitus Receiving Statin Treatment.

AIM: There is little information on the relationships of serum small dense low-density lipoprotein cholesterol (sdLDL-C) levels and serum triglyceride (TG) levels with cardiovascular events in patients with coronary artery disease (CAD) and type 2 diabetes mellitus (DM) who are receiving statins. The aim of this study was to evaluate the relationships of serum TG levels and sdLDL-C levels as residual risks for cardiovascular events in patients with CAD and type 2 DM who were being treated with statins. METHODS: The subjects were divided into four groups based on TG levels and sdLDL-C levels: sdLDL-C of ＜40.0 mg/dL and TG of ＜150 mg/dL, sdLDL-C of ≥ 40.0 mg/dL and TG of ＜150 mg/dL, sdLDL-C of ＜40.0 mg/dL and TG of ≥ 150 mg/dL, and sdLDL-C of ≥ 40.0 mg/dL and TG of ≥ 150 mg/dL. During a median follow-up period of 1419 days, cardiovascular events occurred in 34 patients. RESULTS: The incidences of cardiovascular events were significantly higher in patients with sdLDL-C of ≥ 40.0 mg/dL and TG of ＜150 mg/dL and in patients with sdLDL-C of ≥ 40.0 mg/dL and TG of ≥ 150 mg/dL, but not in patients with sdLDL-C of ＜40.0 mg/dL and TG of ≥ 150 mg/dL, than in patients with sdLDL-C of ＜40.0 mg/dL and TG of ＜150 mg/dL. CONCLUSIONS: Under the condition of treatment with statins, patients with CAD and type 2 DM who had sdLDL-C levels of ≥ 40.0 mg/dL had a high risk for cardiovascular events even though serum TG levels were controlled at ＜150 mg/dL.

Human mesenchymal stem cell transplantation changes proinflammatory gene expression through a nuclear factor-κB-dependent pathway in a rat focal cerebral ischemic model.

Previous studies have demonstrated the immunomodulatory functions of mesenchymal stem cells (MSCs) in cerebral ischemic rats. However, the underlying mechanisms are unclear. The purpose of this study is to investigate the effects of MSC transplantation on transcriptional regulations of proinflammatory genes in cerebral ischemia. Transient ischemia was induced by middle cerebral artery occlusion (MCAO) in adult male Sprague-Dawley rats. After 24 hr, vehicle (PBS) or a human MSC line (B10) was transplanted intravenously. The neurological deficits, infarct volume, cellular accumulations, and gene expression changes were monitored by means of behavior tests, MRI, immunohistochemistry, Western blotting, laser capture microdissection, and real-time PCR. In the core area of the B10 transplantation group, the number of ED1-positive macrophage/microglia was decreased compared with the PBS group. In the core, nuclear factor-κB (NF-κB) was decreased, although CCAAT/enhancer-binding protein ß was not changed; both were expressed mainly in ED1-positive macrophage/microglia. Likewise, mRNAs of NF-κB-dependent genes including interleukin-1ß, MCP-1, and inducible nitric oxide synthase were decreased in ED1-positive and Iba-1-positive macrophage/microglia in the B10 transplantation group. Moreover, upstream receptors of the NF-κB pathway, including CD40 and Toll-like receptor 2 (TLR2), were decreased. Immunofluorescence results showed that, in the B10 transplantation group, the percentages of NF-κB-positive, CD40-positive, and TLR2-positive cells were decreased in ED1-positive macrophage/microglia. Furthermore, NF-κB-positive cells in the CD40- or TLR2-expressing cell population were decreased in the B10 transplantation group. This study demonstrates that B10 transplantation inhibits NF-κB activation, possibly through inhibition of CD40 and TLR2, which might be responsible for the inhibition of proinflammatory gene expression in macrophage/microglia in the infarct lesion.

[Assessment of the vulnerable elders survey as a predictive test for elderly patients with advanced or metastatic gastric cancer treated with combined S-1 and docetaxel therapy].

Ten patients aged 75 years or more with advanced or metastatic gastric cancer were prescribed S-1 plus docetaxel (DOC) combination therapy. None of the patients showed complete response, but 2 showed partial response and 4 showed stable disease. Grade 3 or 4 toxicities occurred in 3 patients. Three patients with performance status (PS) 1 achieved partial response or stable disease and were free of Grade 3 or 4 toxicities, whereas the response and occurrence of adverse events in 7 patients with PS 2 varied widely. In these patients, an investigation of the relationship between response to treatment and the Vulnerable Elders Survey (VES-13) score showed that VES-13 scores were higher in the non-response group than in the other patients and in patients who experienced adverse events than in those who did not. These findings suggest that VES-13 could be a useful screening tool for predicting response and the occurrence of adverse events in elderly patients undergoing combined S-1 plus DOC therapy for advanced or metastatic gastric cancer.

Relationship between Diabetes Mellitus and Serum Lathosterol and Campesterol Levels: The CACHE Study DM Analysis.

AIM: Risk of cardiovascular disease is increased in patients with diabetes mellitus (DM). Cholesterol metabolism (hepatic synthesis and intestinal absorption) is known to be associated with cardiovascular risk. Next, we examined the association of DM with cholesterol absorption/synthesis. METHODS: The CACHE Consortium, which is comprised of 13 research groups in Japan possessing data of lathosterol (Latho, synthesis marker) and campesterol (Campe, absorption marker) measured by gas chromatography, compiled the clinical data using the REDCap system. Among the 3597 records, data from 2944 individuals were used for several analyses including this study. RESULTS: This study analyzed data from eligible 2182 individuals including 830 patients with DM; 42.2% were female, median age was 59 years, and median HbA1c of patients with DM was 7.0%. There was no difference in Latho between DM and non-DM individuals. Campe and Campe/Latho ratio were significantly lower in DM individuals than in non-DM individuals. When the associations of glycemic control markers with these markers were analyzed with multivariable-adjusted regression model using restricted cubic splines, Campe and Campe/Latho ratio showed inverse associations with glucose levels and HbA1c. However, Latho showed an inverted U-shaped association with plasma glucose, whereas Latho showed a U-shaped association with HbA1c. These associations remained even after excluding statin and/or ezetimibe users. CONCLUSION: We demonstrated that DM and hyperglycemia were independent factors for lower cholesterol absorption marker levels regardless of statin/ezetimibe use.

Serum Values of Cholesterol Absorption and Synthesis Biomarkers in Japanese Healthy Subjects: The CACHE Study HEALTHY Analysis.

AIM: Blood cholesterol absorption and synthesis biomarkers predict cardiovascular risk. This study aimed to determine the values of serum non-cholesterol sterol markers [lathosterol (Latho), campesterol (Campe), and sitosterol (Sito)] in healthy individuals and factors affecting these markers. METHODS: The CACHE Consortium compiled clinical data, including serum Latho (cholesterol synthesis marker), and Campe and Sito (cholesterol absorption markers), by a gas chromatography method in 2944 individuals. Healthy subjects were selected by excluding those with prior cardiovascular disease, diabetes mellitus, hypertension, chronic kidney disease, familial hypercholesterolemia, sitosterolemia, current smokers, those with low (＜17 kg/m2) or high (≥ 30 kg/m2) body mass index (BMI), and those with treatment for dyslipidemia or hyperuricemia. Nonlinear regression stratified by sex was used to examine the associations of cholesterol metabolism markers with age, BMI, and serum lipid levels. RESULTS: Of 479 individuals selected, 59.4% were female; the median age was 48 years in females and 50 years in males. The three markers showed positively skewed distributions, and sex differences were present. Age was associated positively with Latho, inversely with Campe, but not significantly with Sito. BMI was associated positively with Latho, but not significantly with Campe or Sito. High-density lipoprotein cholesterol (HDL-C) was positively associated with Campe and Sito, but not significantly with Latho. Non-HDL-C was positively associated with the three markers. CONCLUSION: Our study results in the healthy subjects help to interpret the non-cholesterol sterol markers for cardiovascular risk assessment in patients with cardiovascular risk factors.

Reduced reactive hyperemia of the brachial artery in diabetic patients assessed by repeated measurements: The FMD-J B study.

Type 2 diabetes mellitus (T2DM) is a major cause of microvascular dysfunction. However, its effect on blood flow patterns during ischemic demand has not been adequately elucidated. In this study, we investigated the hypothesis that microvascular dysfunction in patients with T2DM manifests as brachial reactive hyperemia (BRH), defined as the ratio of peak blood flow velocities in a brachial artery before and after forearm cuff occlusion. The study enrolled 943 subjects (men, n = 152 [T2DM] and n = 371 [non-T2DM]; women, n = 107 [T2DM] and n = 313 [non-T2DM], respectively) with no history of cardiovascular disease. Semiautomatic measurements were obtained three times at 1.5-year intervals to confirm the reproducibility of factors involved in BRH for each sex. An age-adjusted mixed model demonstrated attenuated BRH in the presence of T2DM in both men (p = 0.022) and women (p = 0.031) throughout the study period. Post hoc analysis showed that the estimated BRH was significantly attenuated in patients with T2DM regardless of sex, except at baseline in women. In multivariate regression analysis, T2DM was a negative predictor of BRH at every measurement in men. For women, BRH was more strongly associated with alcohol consumption. Repeated measurements analysis revealed that T2DM was associated with attenuated postocclusion reactive hyperemia.

Association between Familial Hypercholesterolemia and Serum Levels of Cholesterol Synthesis and Absorption Markers: The CACHE Study FH Analysis.

AIM: Serum levels of cholesterol absorption and synthesis markers are known to be associated with cardiovascular risk. Familial hypercholesterolemia (FH) is a well-known inherited disorder presenting elevated low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) levels and premature coronary disease. In this study, we aim to examine the differences in terms of serum markers of cholesterol metabolism between FH and non-FH individuals and to examine their associations with serum lipid levels. METHODS: In this study, we utilized data on serum markers of cholesterol metabolism, namely, lathosterol (Latho, synthesis marker), campesterol (Campe, absorption marker), and sitosterol (Sito, absorption marker) measured by gas chromatography of the CACHE consortium, which comprised of 13 research groups in Japan. Clinical data were compiled using REDCap system. Among the 2944 individuals in the CACHE population, we selected individuals without lipid-lowering medications and hemodialysis patients for this CACHE study FH analysis. Multivariable adjustment was performed to assess the associations. RESULTS: In this study, we analyzed data from 51 FH patients and 1924 non-FH individuals. After adjustment for possible confounders, the FH group was shown to have significantly higher Campe and Sito concentrations and insignificantly higher Latho concentrations than the non-FH group. These marker concentrations showed nonlinear associations with TC in the FH group. Campe/Latho and Sito/Latho ratios were significantly higher in the FH group than in the non-FH group. CONCLUSION: FH group had significantly elevated serum Campe and Sito concentrations and insignificantly elevated Latho concentrations; thus, intestinal cholesterol absorption relative to hepatic cholesterol synthesis was suggested to be elevated in patients with FH. Serum Latho, Campe, and Sito concentrations showed nonlinear associations with TC in the FH group.

Association of Serum Levels of Cholesterol Absorption and Synthesis Markers with the Presence of Cardiovascular Disease: The CACHE Study CVD Analysis.

AIM: Serum levels of cholesterol absorption and synthesis markers have been associated with cardiovascular risk in the United States and European countries. In this study, we examined the relevance of these biomarkers and the presence of cardiovascular disease (CVD) in Japanese individuals. METHODS: The CACHE consortium, comprising of 13 research groups in Japan possessing data on campesterol, an absorption marker, and lathosterol, a synthesis marker measured by gas chromatography, compiled the clinical data using the REDCap system. RESULTS: Among the 2,944 individuals in the CACHE population, those with missing campesterol or lathosterol data were excluded. This cross-sectional study was able to analyze data from 2,895 individuals, including 339 coronary artery disease (CAD) patients, 108 cerebrovascular disease (CeVD) patients, and 88 peripheral artery disease (PAD) patients. The median age was 57 years, 43% were female, and the median low-density lipoprotein cholesterol and triglyceride levels were 118 mg/dL and 98 mg/dL, respectively. We assessed the associations of campesterol, lathosterol, and the ratio of campesterol to lathosterol (Campe/Latho ratio) with the odds of CVD using multivariable-adjusted nonlinear regression models. The prevalence of CVD, especially CAD, showed positive, inverse, and positive associations with campesterol, lathosterol, and the Campe/Latho ratio, respectively. These associations remained significant even after excluding individuals using statins and/or ezetimibe. The associations of the cholesterol biomarkers with PAD were determined weaker than those with CAD. Contrarily, no significant association was noted between cholesterol metabolism biomarkers and CeVD. CONCLUSION: This study showed that both high cholesterol absorption and low cholesterol synthesis biomarker levels were associated with high odds of CVD, especially CAD.

A multicenter study design to assess the clinical usefulness of semi-automatic measurement of flow-mediated vasodilatation of the brachial artery.

Flow-mediated vasodilatation of the brachial artery (FMD) is a marker which is related to endothelial nitric oxide bioavailability. Commercially available ultrasound machines equipped with online computer-assisted semi-automatic analysis software to measure FMD have recently become available in Japan. These devices enable more convenient examination, enhanced reproducibility of FMD measurement, and a shortened examination time. Using such devices, in the present multicenter prospective study we propose to: 1) establish standardized FMD values and determine the annual rates of FMD change in healthy subjects; 2) confirm the predictive value of FMD for future cardiovascular events in Japanese subjects; 3) evaluate the potential usefulness of a multimarker strategy, including measurements of FMD, pulse-wave velocity (PWV), ankle-brachial pressure index, biochemical markers, and proteomic biomarkers obtained by mass spectroscopic analysis to assess the prognosis of subjects with coronary artery disease; and 4) clarify the usefulness of FMD measurement to predict the rate of progression of carotid atherosclerosis, arterial stiffness and microalbuminuria in subjects with hypertension or diabetes mellitus. In total, we estimate that approximately 4000 Japanese subjects in 3 different study groups will eventually be enrolled in this prospective observational investigation. We anticipate that the present study will provide important evidence for the usefulness of FMD measurement in the risk stratification for cardiovascular disease.