Relationship Among Falls, Fear of Falling, and Physical Activity Level in Patients on Hemodialysis.

OBJECTIVE: Patients on hemodialysis are highly susceptible to falls and fractures. Amplified apprehension regarding the fear of falling (FOF) constitutes a risk factor that restricts physical activity and escalates the probability of falls among the elderly population. This study aimed to elucidate the association between falls and FOF and physical activity in patients on hemodialysis. METHODS: A prospective cohort study was conducted across 9 centers. FOF was assessed using the Falls Efficacy Scale-International (FES-I). Physical activity was assessed using the Japanese version of the International Physical Activity Questionnaire short form. Subsequently, falls were monitored over a duration of 1 year. Logistic regression analysis was performed to evaluate the relationship between falls and FOF and physical activity. In addition, in the receiver operating characteristic analysis, the cutoff value of FES-I that predicts falls was determined using the Youden Index. A restricted cubic spline curve was utilized to analyze the nonlinear association between falls and the FES-I. RESULTS: A total of 253 patients on hemodialysis (70.0 [59.0-77.0] years old; 105 female [41.5%]) were included in the analysis. During the 1-year observation period, 90 (35.6%) patients experienced accidental falls. The median FES-I score was 36.0 (24.0-47.0) points, and patients with higher FES-I scores had more falls. Following adjusted logistic regression analysis, FES-I exhibited an independent association with falls (OR = 1.04; 95% CI = 1.01-1.06), but physical activity was not. The area under the receiver operating characteristic curve was 0.70 (95% CI = 0.64-0.77), and the FES-I threshold value for distinguishing fallers from non-fallers was determined as 37.5 points (sensitivity 65.6%, specificity 35.0%). A nonlinear relationship between falls and FES-I was observed. CONCLUSION: FOF was associated with the incidence of falls in patients on hemodialysis. IMPACT: The evaluation and implementation of interventions targeting the FOF may mitigate the risk of falls.

Protein intake and its relationship with frailty in chronic kidney disease.

INTRODUCTION: Patients with chronic kidney disease (CKD) are susceptible to frailty because of a range of nutrition-related factors. While protein restriction is commonly advised to preserve kidney function in patients with CKD, insufficient protein intake could potentially exacerbate frailty risk. This study aimed to elucidate the relationship between frailty and protein intake in patients with CKD. METHODS: This cross-sectional study enrolled patients with CKD stage 3-5. Frailty and prefrailty were assessed using the Japanese version of the Cardiovascular Health Study (J-CHS) criteria. To estimate dietary protein intake, Maroni's formula based on 24-h urine collection was used. The potential association between frailty/pre-frailty and protein intake was investigated using a logistic regression analysis. RESULTS: Ninety-seven individuals with CKD were included in the study, with a median age of 73.0 years (interquartile range: 67.0, 82.0). Among them, 34 were women (35.1%), and the estimated glomerular filtration rate (eGFR) was 36.3 mL/min/1.73 m2 (interquartile range: 26.9, 44.1). Frailty and pre-frailty were identified in 13.4% and 55.7% of participants, respectively. Comparing the groups, protein intake in the frailty/pre-frailty group (0.83 g/kgBW/day [0.72, 0.93]) was lower than that in the robust group (0.89 g/kgBW/day [0.84, 1.19], p = 0.002). Upon logistic regression analysis, protein intake exhibited an independent association with frailty/pre-frailty (odds ratio: 0.72, 95% confidence interval: 0.59-0.89, p = 0.003). CONCLUSION: Reduced protein intake in patients with CKD is associated with frailty and pre-frailty. It is advisable to ensure that patients with CKD who are at risk of frailty consume an adequate amount of protein.

Low muscle strength and physical function contribute to falls in hemodialysis patients, but not muscle mass.

INTRODUCTION: Patients on hemodialysis (HD) have a higher incidence of fractures than the general population. Sarcopenia is frequently observed in patients on HD; however, the association of falls with sarcopenia and its diagnostic factors, including muscle mass, muscle strength, and physical function, are incompletely understood. METHODS: This prospective cohort study was conducted at a single center. Sarcopenia was assessed according to the 2019 Asian Working Group for Sarcopenia diagnostic criteria. Muscle mass was measured the bioelectrical impedance method. Grip strength was evaluated to assess muscle strength, while the Short Physical Performance Battery (SPPB) was used to assess physical function. Falls and their detailed information were surveyed every other week. RESULTS: This study analyzed 65 HD patients (median age, 74.5 [67.5-80.0] years; 33 women [49.2%]). Sarcopenia was diagnosed in 36 (55.4%) patients. During the 1-year observation period, 31 (47.7%) patients experienced accidental falls. The falls group had lower median grip strength than the non-falls group (14.7 [11.4-21.8] kg vs. 22.2 [17.9-27.6] kg; p < 0.001). The median SPPB score was also lower in the falls versus non-falls group (7.0 [5.0-11.0] vs. 11.0 [8.0-12.0]; p = 0.009). In adjusted multiple regression analysis, diagnostic factors, including grip strength (B = 0.96, p = 0.04, R2 = 0.19) and SPPB (B = 1.11, p = 0.006, R2 = 0.23), but not muscle mass, were independently associated with fall frequency. CONCLUSIONS: The frequency of falls in HD patients was related to muscle strength and physical function, but not muscle mass.

Dynamic and static balance functions in hemodialysis patients and non-dialysis dependent CKD patients.

INTRODUCTION: Chronic kidney disease (CKD) patients undergoing hemodialysis (HD) have a high risk of falls, whereas the impairment in balance function and their types in HD compared with non-dialysis dependent (ND) CKD have not been fully evaluated. METHODS: We conducted a cross-sectional study to assess the balance function in 91 ND-CKD and 65 HD patients. The participants underwent the timed up-and-go (TUG) test to assess dynamic balance and the length of the center of pressure (CoP) with open eyes or closed eyes to evaluate static balance. RESULTS: TUG, length of CoP with open eyes, and length of CoP with closed eyes were longer in HD patients compared with those with ND-CKD. Multiple regression analysis showed that dialysis treatment independently affected TUG and length of CoP with open eyes. CONCLUSION: The dynamic and static balance functions are impaired in HD patients compared with ND-CKD patients.

Rehabilitation Nutrition in Patients with Chronic Kidney Disease and Cachexia.

Rehabilitation nutrition is a proposed intervention strategy to improve nutritional status and physical function. However, rehabilitation nutrition in patients with cachexia and protein-energy wasting (PEW), which are the main nutrition-related problems in patients with chronic kidney disease (CKD), has not been fully clarified. Therefore, this review aimed to summarize the current evidence and interventions related to rehabilitation nutrition for cachexia and PEW in patients with CKD. CKD is a serious condition worldwide, with a significant impact on patient prognosis. In addition, CKD is easily complicated by nutrition-related problems such as cachexia and PEW owing to disease background- and treatment-related factors, which can further worsen the prognosis. Although nutritional management and exercise therapy are reportedly effective for cachexia and PEW, the effectiveness of combined nutrition and exercise interventions is less clear. In the future, rehabilitation nutrition addressing the nutritional problems associated with CKD will become more widespread as more scientific evidence accumulates. In clinical practice, early intervention in patients with CKD involving both nutrition and exercise after appropriate assessment may be necessary to improve patient outcomes.

Relationship between Nutrition-Related Problems and Falls in Hemodialysis Patients: A Narrative Review.

Falls are a social problem that increase healthcare costs. Hemodialysis (HD) patients need to avoid falling because fractures increase their risk of death. Nutritional problems such as frailty, sarcopenia, undernutrition, protein-energy wasting (PEW), and cachexia may increase the risk of falls and fractures in patients with HD. This review aimed to summarize the impact of frailty, sarcopenia, undernutrition, PEW, and cachexia on falls in HD patients. The reported global incidence of falls in HD patients is 0.85-1.60 falls per patient per year. HD patients fall frequently, but few reports have investigated the relationship between nutrition-related problems and falls. Several studies reported that frailty and undernutrition increase the risk of falls in HD patients. Nutritional therapy may help to prevent falls in HD patients. HD patients' falls are caused by nutritional problems such as iatrogenic and non-iatrogenic factors. Falls increase a person's fear of falling, reducing physical activity, which then causes muscle weakness and further decreased physical activity; this cycle can cause multiple falls. Further research is necessary to clarify the relationships between falls and sarcopenia, cachexia, and PEW. Routine clinical assessments of nutrition-related problems are crucial to prevent falls in HD patients.

Dysfunction in dynamic, but not static balance is associated with risk of accidental falls in hemodialysis patients: a prospective cohort study.

BACKGROUND: Patients with chronic kidney disease undergoing hemodialysis (HD) have a high incidence of falls. Impairment of balance function is a risk factor for falls in the general elderly, and no report examining the association between balance dysfunction and fall incidence in HD patients exists. METHODS: This prospective cohort study was conducted at a single center. The timed-up-and-go test (TUG) as a dynamic balance function was performed and length of the center of pressure (CoP) as a static balance function was measured before and after the HD session at baseline. Data of the number and detailed information of accidental falls for 1 year were collected. Multiple regression analyses were performed to assess the relationships between the number of falls and balance function. RESULTS: Forty-three patients undergoing HD were enrolled in the study. During 1 year of observation, 24 (55.8%) patients experienced accidental falls. TUG time was longer, and CoP was shorter in the post-HD session than in the pre-HD session. Adjusted multiple regression analyses showed that the number of accidental falls was independently associated with TUG time in the pre-HD session (B 0.267, p < 0.001, R2 0.413) and that in the post-HD session (B 0.257, p < 0.001, R2 0.530), but not with CoP. CONCLUSIONS: Dynamic balance was associated with fall incidence in maintenance HD patients. The evaluation and intervention of dynamic balance function might reduce the risk of falls in HD patients. TRIAL REGISTRATION: This study was carried out with the approval of the Niigata Rinko Hospital Ethics Committee (approval number 2005-92) (Registered on December 11, 2019) and registered in The University Hospital Medical Information Network (registration number 000040618 ).

Comparison of muscle strength between hemodialysis patients and non-dialysis patients with chronic kidney disease.

[Purpose] Muscle weakness in patients with chronic kidney disease is associated with several disease-related factors, and this study aimed to examine whether hemodialysis is one of risk factors for muscle weakness in patients with chronic kidney disease. [Participants and Methods] We conducted a cross-sectional study with 74 non-dialysis and 84 hemodialysis patients. Muscle strength evaluations were performed by measuring isometric knee extensor muscle strength and grip strength. Each evaluation item was compared between the hemodialysis and non-dialysis groups, and multiple regression analysis was performed to determine the factors associated with muscle strength. In addition, the correlation between lower-extremity muscle strength and grip strength was examined in each group. [Results] Isometric knee extensor muscle strength was significantly lower in the hemodialysis group than in the non-dialysis group. Grip strength was also significantly lower in the hemodialysis group than in the non-dialysis group. Hemodialysis was determined to be an independent risk factor associated with lower limb muscle strength as well as grip strength. The positive correlation between isometric knee extensor muscle strength and grip strength was almost the same in the groups. [Conclusion] Hemodialysis treatment was an independent risk factor for muscle weakness. Regular monitoring of grip strength may facilitate better management with physical therapy in hemodialysis patients.

The Association between time spent in performing physical activity and physical function in outpatients with type 2 diabetes who may have diabetic neuropathy.

AIMS: To determine the relationship between physical activity time and physical function according to the Japanese Clinical Practice Guideline for Diabetes, which recommended 150 min of activity for outpatients with type 2 diabetes who may have diabetic neuropathy. METHODS: We examined a cross-sectional study with 79 outpatients with Type 2 diabetes participated. A short version, Japanese language edition of the International Physical Activity Questionnaire (IPAQ) was used to evaluate physical activity. Isometric knee extensor strength, grip strength, maximum 10-m walking speed, the Michigan Neuropathy Screening Instrument score, and the Short Physical Performance Battery (SPPB). Each evaluation item was compared between time spent performing physical activity ≥150 min group and <150 min group, and multiple regression analysis was performed to determine the factors associated with time spent performing physical activity. Further, the correlation between time spent performing physical activity and isometric knee extensor strength was examined. RESULTS: The ≥150 min group had significantly higher isometric knee extensor strength than the <150 min group. In addition, the ≥150 min group had significantly faster maximum 10-m walking speed and sit-to-stand time than the <150 min group. Isometric knee extensor strength was determined to be an independent factor associated with the IPAQ score. A positive correlation was found between the IPAQ score and isometric knee extensor strength. CONCLUSIONS: Among the patients with type 2 diabetes who may have diabetic neuropathy, those who performed physical activity for ≥150 min per week were suggested to have higher physical function than those with <150 min of activity.

Neointimal coverage after second generation drug-eluting stent implantation has a relationship with pre-existing atherosclerotic lesion characteristics.

The relationship between preexisting atherosclerotic lesion characteristics and neointimal thickness after second-generation drug-eluting stent (DES) placement is still unknown. Thus, we evaluated that relationship using optical coherence tomography (OCT).A single-center, retrospective, observational study was conducted. Patients with stable angina or asymptomatic myocardial ischemia who received percutaneous coronary intervention for a de novo lesion using a second-generation DES under frequency domain OCT guidance and underwent follow-up coronary angiography (CAG) and OCT between December 2010 and December 2015 were included. The relationship between the neointimal thickness on the stent strut and the plaque characteristics was retrospectively evaluated using OCT immediately after stent implantation and at the time of follow-up CAG.We analyzed 3459 struts from 20 stents in 15 patients. The mean follow-up period was 264 days. In the follow-up study, no angiographic in-stent restenosis was found. Of the 3459 struts, 3315 (95.8%) were covered with neointima. The median neointimal thicknesses of the stent struts on calcified, fibrous, and lipid-rich lesions were 20 µm (interquartile range [IQR], 10-50 µm), 70 µm (40-140 µm; P < .001), and 90 µm (50-170 µm; P < .001), respectively. These differences were observed regardless of the type of second-generation DES used.Most of the stent struts were covered with neointima. The neointimal thickness after the second-generation DES implantation had a close relationship with the preexisting atherosclerotic lesion characteristics. In this study, we found differences in arterial healing processes due to underlying plaque; therefore, evaluating the lesion characteristics by OCT may predict the risk for future restenosis and thrombosis.

Neopterin and Cardiovascular Events Following Coronary Stent Implantation in Patients with Stable Angina Pectoris.

AIM: Neopterin is an activation marker for monocytes/macrophages. We prospectively investigated the predictive value of plasma neopterin levels on 2-year and long-term cardiovascular events in patients with stable angina pectoris (SAP) undergoing coronary stent implantation. METHODS: We studied 123 consecutive patients with SAP who underwent primary coronary stenting (44 patients with bare metal stent: BMS group and 79 with drug-eluting stent: DES group). Plasma neopterin levels were measured on admission using HPLC. Moreover, one frozen coronary artery specimen after DES and three frozen coronary specimens after BMS were obtained by autopsy or endarterectomy, followed by immunohistochemical staining for neopterin. RESULTS: Plasma neopterin levels were significantly higher in patients with cardiovascular events than in those without them (P＜0.001). In subgroup analyses, higher levels of plasma neopterin in patients with cardiovascular events (P＜0.001) and a positive correlation between neopterin levels and late lumen loss after stenting (P =0.008) were observed in the BMS group but not in the DES group (P=0.53 and P=0.17, respectively). In long-term cardiovascular events, multivariate Cox regression analysis identified the significance of the high-neopterin group as independent determinants of cardiovascular events (hazard ratio, 2.225; 95% CI, 1.283-3.857; P =0.004). Immunohistochemical staining showed abundant neopterin-positive macrophages in the neointima after BMS implantation but no neopterin-positive macrophages in the neointima after DES implantation. CONCLUSION: These findings suggest that neopterin is associated with cardiovascular events after coronary stent implantation in patients with SAP. However, there might be a strong association between neopterin and cardiovascular events after BMS but not after DES in these patients.

Enhanced expression of natriuretic peptide receptor A and B in neutrophils of culprit lesions in patients with acute myocardial infarction.

Natriuretic peptides and their specific receptors have been suggested to have regulatory effects on smooth muscle cell (SMC) growth and inflammatory cell reactions. However, the roles of natriuretic peptide receptor A (NPR­A) and B (NPR­B) in unstable plaques remain to be studied in detail. Frozen sections from 82 coronary artery segments were used. These segments were obtained at autopsy from 13 patients with acute myocardial infarction (AMI; 7 ruptured and 6 eroded plaques) and from 30 patients with non­cardiovascular diseases. Antibodies against SMCs, endothelial cells, macrophages, neutrophils, NPR­A, NPR­B and neutral endopeptidase (NEP) were used. Neutrophil infiltration was identified in all lesions with plaque rupture or erosion. Double immunostaining identified that the majority of NPR­A­ or NPR­B­positive cells were neutrophils in ruptured and eroded plaques. Using morphometric analysis, no significant difference was observed in the percentage of NPR­A­ and NPR­B­positive cells between ruptured and eroded plaques, while the number of NEP­positive neutrophils in ruptured plaques was significantly higher compared with eroded plaques (P<0.0001). These results of the distinct presence of NPR­A­ and NPR­B­positive cells in unstable plaques underlying AMI suggested that natriuretic peptides serve a role in regulating plaque instability in humans.

Physical function was related to mortality in patients with chronic kidney disease and dialysis.

Previous studies have shown that exercise improves aerobic capacity, muscular functioning, cardiovascular function, walking capacity, and health-related quality of life (QOL) in patients with chronic kidney disease (CKD) and dialysis. Recently, additional studies have shown that higher physical activity contributes to survival and decreased mortality as well as physical function and QOL in patients with CKD and dialysis. Herein, we review the evidence that physical function and physical activity play an important role in mortality for patients with CKD and dialysis. During November 2016, Medline and Web of Science databases were searched for published English medical reports (without a time limit) using the terms "CKD" or "dialysis" and "mortality" in conjunction with "exercise capacity," "muscle strength," "activities of daily living (ADL)," "physical activity," and "exercise." Numerous studies suggest that higher exercise capacity, muscle strength, ADL, and physical activity contribute to lower mortality in patients with CKD and dialysis. Physical function is associated with mortality in patients with CKD and dialysis. Increasing physical function may decrease the mortality rate of patients with CKD and dialysis. Physicians and medical staff should recognize the importance of physical function in CKD and dialysis. In addition, exercise is associated with reduced mortality among patients with CKD and dialysis.

Typical coronary appearance of dilated cardiomyopathy versus left ventricular concentric hypertrophy: coronary volumes measured by multislice computed tomography.

Several coronary angiographic studies have reported that enlarged and tortuous epicardial coronary arteries are characteristic of patients with left ventricular concentric hypertrophy (LVCH). Recently, we showed that small volumes opacified by contrast medium can be accurately measured by 64-multislice computed tomography (MSCT) and that there is a direct relationship between the coronary artery volume and left ventricular (LV) mass. However, the relationship of coronary artery volume with LV mass in patients with dilated cardiomyopathy (DCM) is unknown. The present study was designed to investigate this issue. Thirteen patients with DCM and 18 patients with LVCH who underwent MSCT angiography were included in this analysis. The coronary arteries were segmented on a workstation, and the appropriate window settings obtained from the results of the phantom experiments were applied to the volume-rendered images to calculate the total coronary artery volume (right and left coronary arteries). The absolute coronary lengths and volumes in patients with LVCH and DCM were greater than those in controls. The coronary artery volumes adjusted for LV mass in patients with DCM were found to be smaller than those in patients with LVCH or in controls, and these values did not differ between patients with LVCH and controls (DCM 4.1 ± 0.9, LVCH 5.4 ± 1.4, controls 5.5 ± 2.3 ml/100 g of LV mass, P < 0.005; DCM vs LVCH, P < 0.01; and DCM vs control, P < 0.0005). This study showed that the increase in the coronary artery volume in patients with LVCH matched the increase in LV mass, but a decreased coronary volume with regard to LV mass was characteristic of patients with DCM.

The clinical value of apex beat and electrocardiography for the detection of left ventricular hypertrophy from the standpoint of the distance factors from the heart to the chest wall: a multislice CT study.

The aim of this study was to investigate the clinical value of the apex beat and two ECG voltage criteria in the detection of left ventricular hypertrophy (LVH) while considering two distances, from the heart to the inner chest wall and to the chest surface, measured by using multislice CT (MSCT). The study population consisted of 151 patients clinically judged as requiring MSCT angiography. The apex beat was palpated with patients in the supine. Sokolow-Lyon voltage and Cornell voltage to detect LVH were determined. The pattern of sustained or double apical impulse and Cornell voltage had higher specificity as an indicator of LVH than Sokolow-Lyon voltage. Furthermore, the distance to the inner chest wall was negatively correlated with left ventricular end-diastolic volume and mass. Contrarily, the distance to the chest surface was correlated with the body mass index. Multivariate analyses revealed that the pattern of sustained or double apical impulse showed a stronger association with the distance to the inner chest wall than to the chest surface, but Sokolow-Lyon voltage was associated with the distance to the chest surface. Among the screening tests for excluding patients with LVH, Cornell voltage or the apex beat would be better than Sokolow-Lyon voltage because these are less dependent on body size and have higher specificity.

Utility of myocardial fractional flow reserve for prediction of restenosis following sirolimus-eluting stent implantation.

Drug-eluting stents reduce restenosis due to neointimal growth suppression. Considering long-term outcomes, it is both difficult and important to predict drug-eluting stent restenosis. Thus, this study was designed to examine the utility of myocardial fractional flow reserve (FFR) as a predictor of sirolimus-eluting stent (SES) restenosis. Thirty-three patients (35 lesions) were enrolled. Upon completion of SES implantation, FFR was obtained under hyperemia. At 8 months of follow-up, coronary angiography revealed that five lesions had restenosis. Percent diameter stenosis (restenosis 68.7 ± 12.8% vs. non-restenosis 68.7 ± 12.4%, p = 0.78) and lesion length (restenosis 15.8 ± 9.4 mm vs. non-restenosis 14.4 ± 9.2 mm, p = 0.60) were similar. At post-intervention, percent diameter stenosis (restenosis 16.4 ± 6.1% vs. non-restenosis 14.0 ± 7.4%, p = 0.48) and minimum stent area (restenosis 6.01 ± 1.08 mm2 vs. non-restenosis 6.27 ± 1.85 mm2, p = 0.92) were also equivalent. However, proximal edge lumen area was smaller (restenosis 4.24 ± 1.40 mm2 vs. non-restenosis 7.73 ± 2.64 mm2, p = 0.004) and FFR was lower in the restenosis group (restenosis 0.81 ± 0.12 vs. non-restenosis 0.92 ± 0.06, p = 0.029). SES patients with restenosis had a lower FFR post stent deployment, suggesting the decreased FFR may be a useful predictor for SES restenosis.

Absence of left ventricular concentric hypertrophy: a prerequisite for zero coronary calcium score.

The identification and intervention of factors associated with a coronary artery calcification (CAC) score of zero, suggesting the absence of significant coronary artery disease (CAD) with high probability, would be meaningful in the clinical setting. Thus far, the relationship between CAC and left ventricular (LV) hypertrophy has not been documented. We identified factors associated with a CAC score of zero and evaluated the relationship between this score and LV concentric hypertrophy in 309 consecutive patients with suspected CAD who were clinically indicated to undergo multislice computed tomography angiography for coronary artery evaluation. The quantitative CAC score was calculated according to Agatston's method. The total coronary calcium score (TCS) was defined as the sum of the scores for each lesion. Four absolute TCS categories were considered: zero, mild (0-100), moderate (100-400), and severe (>400). LV hypertrophy was classified into concentric (LV mass index >104 g/m(2) in women or >116 g/m(2) in men; LV end-diastolic volume index ≤109.2 mL/m(2)) and eccentric (LV end-diastolic volume index >109.2 mL/m(2)) patterns. In the zero-TCS group, the frequency of LV concentric hypertrophy was extremely low (zero 6%, mild 17%, moderate 26%, severe 19%). Multivariate analysis revealed that age, hypercholesterolemia, diabetes mellitus, LV concentric hypertrophy, and LV mass index, but not hypertension, were the independent factors associated with a CAC score of zero. The present study demonstrated that the absence of LV concentric hypertrophy was a prerequisite for a CAC score of zero. That is, the presence of LV concentric hypertrophy, which indicated more severe underlying hypertension, long duration, or poor control of blood pressure, implicates the presence of CAC.

Neopterin and atherosclerotic plaque instability in coronary and carotid arteries.

Inflammation plays a key role in atherosclerosis and plaque vulnerability, and monocyte/macrophage activation contributes to these processes. Neopterin, a by-product of the guanosine triphosphate pathway, is produced by activated macrophages on stimulation with interferon-γ released from T lymphocytes, and is an activation marker for monocytes/macrophages. Coronary angiographic studies have shown a relationship between increased circulating levels of neopterin and the presence of complex coronary lesions in patients with unstable angina pectoris (UAP). Furthermore, in an immunohistochemical study performed using coronary atherectomy specimens, a significantly higher prevalence of neopterin-positive macrophages was found in culprit lesions in patients with UAP than in those with stable angina pectoris (SAP). We recently clarified that the presence of complex carotid plaques detected by carotid ultrasound was related to increased circulating levels of neopterin, and immunohistochemical localization of neopterin was observed in complex carotid lesions obtained from carotid endarterectomy in patients with SAP. These findings suggest that neopterin is an important biomarker of plaque instability in both coronary and carotid atherosclerotic lesions.