Physiological Role of Serum Growth Differentiation Factor-15 (GDF-15) Level and Iron Metabolism in Community-Dwelling Older Adults.

Background Anemia is common in older adults and, together with heart failure and chronic kidney disease, forms a vicious cycle, whereas diseases such as chronic inflammation and cancer are associated with the anemia of chronic disease (ACD). Researchers have linked growth differentiation factor-15 (GDF-15) to a variety of conditions such as cardiovascular disease, inflammation, cancer, and kidney disease, and have reported hepcidin as a biomarker for iron regulation in ACD. Therefore, anemia, GDF-15, and hepcidin have significance in aging physiology. Hypothesis GDF-15 and hepcidin play important physiological roles in community-dwelling older adults. This study sought to explore the relationship between these biomarkers and anemia, inflammation, or other health outcomes. Methods This was a prospective study of 73 community-dwelling older adults (six men and 67 women, mean age of 76.3 years). Their serum iron level, percentage transferrin saturation (TSAT), high-sensitivity C-reactive protein (hs-CRP), and estimated glomerular filtration rate (eGFR) were measured. Enzyme-linked immunosorbent assays were used to assess their serum GDF-15, ferritin, and hepcidin levels. The participants' grip strength and walking speed were measured. The skeletal muscle mass index (SMI) of each participant was determined by bioelectrical impedance analysis. Results The GDF-15 level was significantly inversely correlated with serum iron, ferritin, and hepcidin levels; percentage TSAT; the eGFR; and gait speed. Serum hepcidin was positively correlated with levels of ferritin, albumin, and hemoglobin. Handgrip strength, SMI, and hs-CRP were not correlated with either GDF-15 or hepcidin levels. After adjusting for age, sex, and body mass index (BMI), multivariate analysis identified the log GDF-15 and serum iron level (log GDF-15: ß=-0.248, iron: ß=0.296) as significant factors determining hemoglobin levels, whose findings have significance due to novel results. Multivariate analysis identified eGFR and levels of hemoglobin and hepcidin as significant factors associated with log GDF-15 (eGFR: ß=-0.406, hemoglobin: ß=-0.269, hepcidin: ß=-0.235). Similarly, ferritin and albumin levels were identified as significant factors associated with hepcidin levels (ferritin: ß=0.590, Alb: ß=0.277). Conclusions Anemia in community-dwelling older adults was determined not only by increasing serum iron levels but also by decreasing GDF-15 levels. Also, the increasing GDF-15 level was determined by a decreasing hepcidin level as well as the presence of anemia and renal dysfunction, and the decreasing hepcidin level was determined by decreasing stored iron and decreasing albumin levels. Serum GDF-15 and hepcidin could potentially inform diagnostic or treatment strategies for anemia or age-related health conditions.

Pathophysiological roles of the serum acylcarnitine level and acylcarnitine/free carnitine ratio in patients with cardiovascular diseases.

Introduction: L-carnitine exerts protective effects, such as maintaining mitochondrial functions and decreasing reactive oxygen species, while acylcarnitine (AC) is linked to the development of heart failure and atherosclerosis. Hypothesis: Serum carnitines play important pathophysiological roles in cardiovascular diseases. Methods: Pre-operative biochemical data were obtained from 117 patients (71 men, average age 69.9 years) who underwent surgery for cardiovascular diseases. Measurements included pre-operative biochemical data including estimated glomerular filtration rate (eGFR), physical functions, skeletal muscle mass index (SMI) measured by bioelectrical impedance analysis, anterior thigh muscle thickness (MTh) measured by ultrasound, and routine echocardiography. Carnitine components were measured with the enzyme cycling method. Muscle wasting was diagnosed based on the Asian Working Group for Sarcopenia criteria. Results: Plasma brain natriuretic peptide (BNP) level was correlated with serum free carnitine (FC) and AC level, and the acylcarnitine/free carnitine ratio (AC/FC). AC/FC was elevated with stage of chronic kidney disease. In multivariate analysis, log (eGFR) and log (BNP) were extracted as independent factors to define log (serum AC) (eGFR: ß = 0.258, p = 0.008; BNP: ß = 0.273, p = 0.011), even if corrected for age, sex and body mass index. AC/FC was negatively correlated with hand-grip strength (r = -0.387, p = 0.006), SMI (r = -0.314, p = 0.012), and anterior thigh MTh (r = -0.340, p = 0.014) in men. Conclusions: A significant association between serum AC level and AC/FC, and chronic kidney disease and heart failure exists in patients with cardiovascular diseases who have undergone cardiovascular surgery. Skeletal muscle loss and muscle wasting are also linked to the elevation of serum AC level and AC/FC.

CAN WE DIAGNOSE SARCOPENIA USING ANTERIOR FEMORAL MUSCLE THICKNESS IN PATIENTS WITH CARDIOVASCULAR DISEASE?

Objective: Making the diagnosis of sarcopenia is not always easy and this is especially true for those with cardiovascular disease. The purpose of this study is to investigate whether it is possible to diagnose sarcopenia by using ultrasound-guided measurements of anterior femoral muscle thickness. Methods: We investigated the utility of ultrasound-guided measurements of anterior femoral muscle thickness in 1075 hospitalized patients with cardiovascular disease (675 men). As a comparison, sarcopenia was assessed by skeletal muscle mass index using bioelectrical impedance analysis and the Asia Working Group for Sarcopenia criteria. Results: When the receiver operating characteristic curve using muscle thickness was examined, we found this could be used to make the diagnosis of sarcopenia (men: cutoff value 2.425 cm, area under the curve 0.796; women: cutoff value 1.995 cm, area under the curve 0.746). The prevalence of sarcopenia according to the criteria with skeletal muscle mass index was 34.2% in men and 51.8% in women, while its prevalence according to the cutoff value of muscle thickness was 29.2% in men and 36.7% in women. Conclusion: Ultrasound-guided measurement of the anterior femoral muscle thickness is a simple and useful method to help make the diagnosis of sarcopenia in patients with cardiovascular disease.

Clinical usefulness of phase angle as an indicator of muscle wasting and malnutrition in inpatients with cardiovascular diseases.

Background and Objectives: Extracellular water is increased in patients with edema, such as those with chronic heart failure, and it is difficult to assess skeletal muscle mass with the skeletal muscle mass index when extracellular water is high. We investigated the relationship between phase angle and physical function, nutritional indices, and sarcopenia in patients with cardiovascular diseases, including chronic heart failure. Methods and Study Design: In 590 patients with cardiovascular diseases (372 men), handgrip strength, gait speed, and anterior mid-thigh muscle thickness by ultrasound were measured, and the skeletal muscle mass index, phase angle, and the extracellular water: total body water ratio were measured with a bioelectrical impedance analyzer, and presence of sarcopenia was evaluated. Results: Phase angle, but not the skeletal muscle mass index, was correlated with serum albumin (r = 0.377, p < 0.001) and hemoglobin values in women. Multivariate regression analysis showed that at the extracellular water: total body water ratio below 0.4, both phase angle and skeletal muscle mass index were independent determinants of handgrip strength and log mid-thigh muscle thickness in men, after adjustment for age and presence of chronic heart failure. In contrast, for the ratio of 0.4 or greater, after adjustment for age and presence of chronic heart failure, phase angle was a stronger independent determinant of handgrip strength and log mid-thigh muscle thickness than the skeletal muscle mass index in men. Conclusions: Phase angle is a good marker of muscle wasting and malnutrition in patients with cardiovascular disease, including chronic heart failure.

Optimal uric acid reduction to improve vascular endothelial function in patients with chronic heart failure complicated by hyperuricemia.

Although an association of serum uric acid levels with endothelial function has been shown in various clinical settings, the optimal treatment target that would benefit vascular endothelial function has not been established. We, therefore, conducted a post hoc analysis of the Excited-UA study to identify an optimal target. Patients (N = 133) with chronic heart failure and comorbid hyperuricemia who enrolled in the Excited-UA study were divided into three tertiles based on their serum uric acid level 24 weeks after initiating xanthine oxidase inhibitor treatment with topiroxostat or allopurinol (i.e., groups with low, moderate, and high uric acid levels). Flow-mediated dilation (FMD) and reactive hyperemia index (RHI) values measured by reactive hyperemia peripheral arterial tonometry (RH-PAT) were compared among groups. The change from baseline in the FMD value 24 weeks after treatment was comparable among the three groups. In contrast, the change from baseline in the RHI was significantly different among the three groups (-0.153 ± 0.073, 0.141 ± 0.081 and -0.103 ± 0.104 in the low, moderate, and high uric acid level groups, respectively, P = 0.032). After adjustment for age, body mass index, and concomitant use of diuretics, which differed among the three groups, the change in the RHI in the moderate uric acid level group tended to be higher than that in the high uric acid level group (P = 0.057) and was significantly higher than that in the low uric acid level group (P = 0.020). These results indicate that targeting excessively low uric acid levels by treatment with xanthine oxidase inhibitors might be less beneficial for improving microvascular endothelial function in patients with chronic heart failure. Comparisons of the changes from baseline in vascular endothelial function parameters at 24 weeks among the 3 groups of low, moderae and high uric acid levels achieved with xanthine oxidase inhibitors. After adjustment for confounding factors, such as age, body mass index and concomitant diuretic use, which showed differences among the 3 groups, the change in RHI in the moderate uric acid level group tended to be higher than that in the high uric acid level group and was significantly higher than that in the low uric acid level group.

Association between serum GDF-15, myostatin, and sarcopenia in cardiovascular surgery patients.

Background: Myostatin is a negative regulator of skeletal muscle mass. On the other hand, growth differentiation factor (GDF)-15 is associated with lower muscle strength and muscle mass. We investigated the relationship between serum GDF-15, myostatin, and sarcopenia in patients receiving cardiovascular surgery through a ROC curve and a multivariate regression analysis. Methods: Skeletal muscle mass index (SMI) by bioelectrical impedance analysis, hand-grip strength, knee extension strength, and walking speed were measured. Preoperative serum GDF-15 and myostatin levels were determined by ELISA. The sarcopenia index could be expressed as: -0.0042 × [myostatin] + 0.0007 × [GDF-15] + 0.0890 × age + 1.4030 × sex - 0.2679 × body mass index (BMI) - 2.1186. A ROC curve was plotted to identify the optimal cutoff level of the sarcopenia index to detect sarcopenia. Results: 120 patients receiving cardiovascular surgery were included in the study. SMI, hand-grip strength, knee extension strength, and walking speed inversely correlated with GDF-15, but positively correlated with myostatin. In the multivariate stepwise regression analysis, SMI was a determinant of myostatin, and both GDF-15 and myostatin were determinants of SMI and muscle thickness, even after adjustment for age, sex, and BMI. A ROC curve showed that the sarcopenia index was a determinant of sarcopenia (cutoff value -1.0634, area under the curve 0.901, sensitivity 96.9%, specificity 70.9%). Conclusion: GDF-15 and myostatin are associated with skeletal muscle volume in patients receiving cardiovascular surgery, but these associations are different. The sarcopenia index calculated from GDF-15 and myostatin levels may be a biomarker of sarcopenia.

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.

Relationship between the serum GDF-15 concentration and muscle function in female patients receiving aortic valve replacement (TAVR, SAVR): Comparison with healthy elderly female subjects.

Purpose: Sarcopenia is closely associated with postoperative prognosis in patients undergoing cardiovascular surgery. Growth differentiation factor (GDF)-15 is involved in the pathogenesis of cardiovascular disease. We examined the relationship between the serum GDF-15 concentration and muscle function in patients receiving aortic valve replacement and healthy elderly subjects. Methods: Forty-three female patients undergoing aortic valve surgery (79.9 ± 6.4 years; transcatheter aortic valve replacement [TAVR] n = 19, conventional surgical aortic valve replacement [SAVR] n = 24) and 64 healthy elderly female subjects (75.9 ± 6.1 years) were included. Walking speed, grip strength, and skeletal muscle mass index (SMI) by a multifrequency bioelectrical impedance analyzer were measured to determine the presence of sarcopenia. Preoperative serum GDF-15 concentration was measured by enzyme-linked immunosorbent assay. Results: The GDF-15 level was higher in patients receiving aortic valve replacement than in healthy elderly subjects (aortic valve replacement: 1624 ± 1186 pg/mL vs. healthy: 955 ± 368 pg/mL, p < 0.001). Multivariate linear regression analysis showed that the serum GDF-15 level determined grip strength independently of the high-sensitivity C-reactive protein level and eGFR, even after adjusting for age (ß = -0.318, p = 0.025). Sarcopenia was found in 12.5% of healthy elderly subjects, 83.3% of patients with TAVR, and 64.3% of patients with SAVR. The GDF-15 concentration that defined sarcopenia was 1109 pg/mL in subjects including patients receiving aortic valve replacement. Conclusions: The preoperative serum GDF-15 concentration, which was higher in female patients receiving aortic valve replacement than in healthy elderly subjects, may be a serum marker of sarcopenia.

Benefit of veno-arterial extracorporeal membrane oxygenation combined with Impella (ECpella) therapy in acute coronary syndrome with cardiogenic shock.

BACKGROUND: Patients with acute coronary syndrome complicated with cardiogenic shock (ACS-CS) frequently require mechanical circulatory support. In addition to veno-arterial extracorporeal membrane oxygenation (VA-ECMO), use of the Impella® (ECpella) (Abiomed Inc., Danvers, MA, USA) heart pump may improve the prognosis of such patients. In this study, we compared the efficacy of VA-ECMO plus intra-aortic balloon pumping (ECMO-IABP) with that of the ECpella for add-on circulatory support of VA-ECMO. METHODS: Clinical outcomes of 64 patients with ACS-CS treated with ECMO-IABP (n = 41) or ECpella (n = 23) between January 2013 and April 2021 were retrospectively analyzed. The primary outcomes were 30-day and 365-day mortality. In addition, patients resuscitated after cardiopulmonary arrest (CPA) were evaluated separately. RESULTS: The ECpella group showed significantly lower mid-term mortality than the ECMO-IABP group [30-day mortality (39.1% vs 56.1%, respectively; p = 0.193) and 365-day mortality (43.5% vs 75.6%, respectively; p = 0.010)], with significantly higher rates of new hemodialysis and bleeding at the vascular access site. Also, among the limited number of patients resuscitated from CPA, mortality was significantly lower in the ECpella group than the ECMO-IABP group [30-day mortality (28.6% vs 65.4%, respectively; p = 0.026) and 365-day mortality (28.6% vs 84.6%, respectively; p < 0.001)]. Among the resuscitated patients, ECMO weaning period and the incidence of neurological complications were related to 30-day mortality; The incidence of neurological complications was related to 365-day mortality. The use of ECpella was strongly associated with both 30-day and 365-day survival. CONCLUSIONS: The ECpella heart pump may provide a survival advantage over ECMO-IABP in patients with ACS-CS.

Repeated In-Stent Restenosis Despite Aggressive Lipid Loweringby PCSK-9 Inhibitor Treatment: A Case Report.

A 76-year-old woman with unstable angina underwent coronary stent implantation. At the same time, rosuvastatin therapy was started. However, she experienced repeated in-stent restenosis (ISR). Treatment with a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor along with rosuvastatin (5 mg/day) reduced plasma low-density lipoprotein cholesterol to 10 mg/dL, but failed to prevent further ISR. Eventually, an increase in the rosuvastatin dose to the permitted maximum of 20 mg/day succeeded in preventing further in-stent restenosis. Rather than using PCSK9 inhibitors, intensive statin treatment, using the maximum dose of statins, should be prioritized for the secondary prevention of coronary artery disease.

Mobilization of progenitor cells and vessel healing after implantation of SYNERGY in acute coronary syndrome.

This study was aimed to compare the vascular healing process of a SYNERGY stent with that of a PROMUS PREMIER stent in patients with acute coronary syndrome (ACS). In 71 patients with ACS, undergoing coronary stent implantation using the SYNERGY stent (n = 52) or PROMUS PREMIER stent (n = 19), we measured circulating CD34+/CD133+/CD45null cells and CD34+/KDR+ cells and observed vascular healing at the stented sites using optical coherence tomography (OCT) and coronary angioscopy. On the day 7, circulating CD34+/CD133+/CD45null cells increased in SYNERGY group (P < 0.0001), while it did not change in PROMUS group. The CD34+/KDR+ cells also increased in SYNERGY group (P < 0.0001) but less significantly in the PROMUS group (P < 0.05). The OCT-based neointimal thickness (P < 0.0005) and neointimal coverage rate (P < 0.05) at 12 months were greater in SYNERGY group, compared with PROMUS group. The coronary angioscopy-based neointimal coverage grade at 12 months was also greater in SYNERGY group (P < 0.001). In overall patients, the change in CD34+/KDR+ cells on the day 7 correlated with the OCT-based neointimal thickness at 12 months (R = 0.288, P < 0.05). SYNERGY stent seems to have potential advantages over PROMUS PREMIER stent for ACS patients in terms of vascular healing process at the stented sites.

Preoperative Serum GDF-15, Endothelin-1 Levels, and Intraoperative Factors as Short-Term Operative Risks for Patients Undergoing Cardiovascular Surgery.

OBJECTIVES: The Society of Thoracic Surgeons (STS) risk score is widely used for the risk assessment of cardiac surgery. Serum biomarkers such as growth differentiation factor-15 (GDF-15) and endothelin-1 (ET-1) are also used to evaluate risk. We investigated the relationships between preoperative serum GDF-15, ET-1 levels, and intraoperative factors and short-term operative risks including acute kidney injury (AKI) for patients undergoing cardiovascular surgery. METHODS: In total, 145 patients were included in this study (92 males and 53 females, age 68.4 ± 13.2 years). The preoperative STS score was determined, and the serum GDF-15 and ET-1 levels were measured by ELISA. These were related to postoperative risks, including AKI, defined according to the Acute Kidney Injury Network (AKIN) classification criteria. RESULTS: AKI developed in 23% of patients. The GDF-15 and ET-1 levels correlated with the STS score. The STS score and GDF-15 and ET-1 levels all correlated with preoperative eGFR, Alb, Hb, and BNP levels; perioperative data (urine output); ICU stay period; and postoperative admission days. Patients with AKI had longer circulatory pulmonary bypass (CPB) time, and male patients with AKI had higher ET-1 levels than those without AKI. In multivariable logistic regression analysis, the preoperative ET-1 level and CPB time were the independent determinants of AKI, even adjusted by age, sex, and BMI. The preoperative GDF-15 level, CPB time, and RCC transfusion were independent determinants of 30-day mortality plus morbidity. CONCLUSION: Preoperative GDF-15 and ET-1 levels as well as intraoperative factors such as CPB time may be helpful to identify short-term operative risks for patients undergoing cardiovascular surgery.

Vascular Endothelial Dysfunction and Autonomic Nervous Hyperactivity among Premenopausal Women with Cold-Sensitivity Constitution (Hiesho).

The cold-sensitivity constitution (CSC), termed "Hiesho" in Japanese, is a woman-specific cold sense of peripheral sites. The etiology of and criteria for CSC are not yet well established. We defined CSC as temperature gradient > 6˚C between body surface and core, and investigated the autonomic nervous activity by measuring heart rate variability and the vascular endothelial function by determining reactive hyperemia index (RHI) in 43 healthy premenopausal women, aged 18-47 years. Twenty five women had CSC during both the follicular and luteal phases of their menstrual cycles (sustained-CSC group), 8 women did not show CSC during both phases (non-CSC group), and the remaining 10 women showed CSC in either menstrual phase (occasional CSC). To identify the pathophysiological bases of CSC, we compared the sympathetic nervous activity and vascular endothelial function between sustained-CSC and non-CSC. We thus found that sympathetic nervous activity was higher among the sustained-CSC group (p = 0.042) during the follicular phase, compared with the non-CSC group, while the RHI was similar in both groups. Furthermore, the sympathetic nervous activity was similar between the sustained-CSC women aged ≥ 40 years (n = 10) and those aged < 40 years (n = 15) during either menstrual phase, whereas the RHI of the women aged < 40 years was lower during the follicular phase (p = 0.045), compared with the women aged ≥ 40 years. In conclusion, CSC is associated with sympathetic nervous hyperactivity in premenopausal women, and vascular endothelial dysfunction is also involved in CSC among younger women.

Insufficient recovery of fractional flow reserve even after optimal implantation of drug-eluting stents: 3-year outcomes from the FUJI study.

BACKGROUND: Adequate improvement in fractional flow reserve (FFR) is not necessarily achieved in some cases of drug-eluting stent (DES) implantation, even when imaging confirms successful placement. We hypothesized that post-stent FFR may be associated with advanced diffuse atherosclerotic condition. We explored the relationships between FFR values after DES implantation (post-stent FFR). METHODS: A total of 218 patients were included in this prospective, multicenter study and were divided into two groups: adequate FFR group (post-stent FFR >0.80, n=176) and inadequate FFR group (post-stent FFR ≤0.80, n=42). The primary endpoint was a major adverse cardiovascular event (MACE) including cardiac death, non-fatal myocardial infarction (MI), unplanned coronary revascularization, and hospitalization for heart failure. The secondary endpoints were event rate of all-cause death, non-fatal MI, unplanned coronary revascularization, non-fatal stroke, and hospitalization for heart failure. RESULTS: During follow-up of 31.4±8.7 months, 34 patients (16%) had cardiovascular events. Inadequate FFR group was significantly associated with higher risk of MACE (hazard ratio: 3.86; 95% confidence interval: 1.17-12.76, p=0.026; log-rank p=0.027). In particular, the incidence of unplanned coronary revascularization on non-target lesions was significantly higher in the inadequate FFR group (log-rank p=0.031). CONCLUSIONS: Post-stent FFR ≤0.80 was associated with a high incidence of non-target lesion revascularization and could be a surrogate marker for advanced atherosclerotic condition in the vessels of the entire coronary artery.

Time-restricted feeding prevents high-fat and high-cholesterol diet-induced obesity but fails to ameliorate atherosclerosis in apolipoprotein E-knockout mice.

One of the leading risk factors for atherosclerosis is obesity, which is commonly caused by a nutrient-rich Western-style diet, sedentary behaviors, and shift work. Time-restricted (TR) feeding and intermittent fasting are both known to prevent overweight and adiposity, improve glucose tolerance, and decrease plasma cholesterol in high-fat diet-induced obese mice. Here we examined the overall effects of TR feeding of a Western diet (fat, 40.5 Kcal%; cholesterol, 0.21 g%) using 8-week-old Apoe-/- mice. Mice were assigned into three groups: (1) an ad libitum (AL) group fed an AL Western diet, (2) a TR group with restricted access to a Western diet (15 h/day, 12:00 to 3:00 Zeitgeber time [ZT]); and (3) an Ex/TR group fed a TR Western diet and subjected to physical exercise at 12:00 ZT. Mice in the AL group gained body weight rapidly during the 14-week observation period. With TR feeding, excessive weight gain, liver adiposity, visceral fat, and brown adipose tissue volume were effectively suppressed. Although TR feeding failed to decrease Oil Red O-stained aortic plaques in Apoe-/- mice, physical exercise significantly decreased them. Neither TR feeding with exercise nor that without exercise decreased the mean area under the curve of the plasma cholesterol level or the fasting plasma glucose. Collectively, TR feeding of a Western diet prevented the development of obesity but failed to ameliorate atherosclerosis in Apoe-/- mice.

Effects of switching from clopidogrel to prasugrel at the chronic phase after coronary stenting on antiplatelet action and vascular endothelial function: Switch-Pras study.

Compared to clopidogrel, prasugrel has a lower incidence of ischemic events following percutaneous coronary intervention (PCI) because of an early reduction during the acute phase in P2Y12 reaction units (PRU). The objective of this study was to compare the antiplatelet effect and vascular endothelial function of both drugs during the chronic phase after PCI. Patients who had undergone PCI and were confirmed to have no restenosis by follow-up coronary angiography under dual anti-platelet therapy with clopidogrel (75 mg/day) and aspirin (100 mg/day) were randomized to either continue clopidogrel or switch to prasugrel (3.75 mg/day). At baseline, prior to randomization we determined the CYP2C19 genotype. At the baseline and 24 weeks after randomization, the P2Y12 reactivity unit (PRU) was measured using the VerifyNow™ P2Y12 assay. Endothelial function was evaluated by flow-mediated vasodilation (FMD) and reactive hyperemia peripheral arterial tonometry (RH-PAT), while and circulating CD34+/CD133+/CD45low progenitor cells were measured by flow cytometric analysis. Serum high-sensitivity C-reactive protein (hsCRP) level was also measured. The PRU was reduced significantly in the prasugrel group (P = 0.0008), especially in patients who were intermediate or poor metabolizers based on the CYP2C19 genotype (P < 0.0001). This reduction was not observed in the clopidogrel group. The number of CD34+/CD133+/CD45low cells increased in the clopidogrel group (P = 0.008), but not in the prasugrel group. The hsCRP, FMD and reactive hyperemia index measured by RH-PAT did not change in either group. Prasugrel is potentially better than clopidogrel for preventing thrombotic events, although clopidogrel may have an advantage over prasugrel in terms of preventing atherosclerotic events. Proper use of thienopyridine drugs based on the CYP2C19 genotype has promising clinical potential.

Association of serum growth differentiation factor-15 with eGFR and hemoglobin in healthy older females.

PURPOSE: Anemia and sarcopenia associated with renal dysfunction caused by cytokine imbalance can contribute to decreased quality of life for older individuals. Growth differentiation factor-15 (GDF-15) is associated with renal dysfunction, although whether it is related to anemia or sarcopenia is unclear. In this study we examined the association of GDF-15 with renal function, hemoglobin and sarcopenia in healthy community-dwelling older females in Japan. METHODS: A total of 66 healthy older community-dwelling females (age: 75.8 ± 6.2 years) were enrolled for this study. Skeletal muscle mass index was determined by bioelectrical impedance analysis. Hand-grip strength and walking speed were also assessed. Serum GDF-15 concentration was determined by enzyme-linked immunosorbent assay and both hemoglobin (Hb) level and estimated glomerular filtration rate (eGFR) were measured. RESULTS: Serum GDF-15 levels positively correlated with age but negatively correlated with eGFR and walking speed. In multiple regression analysis, eGFR and hemoglobin (Hb) were independent variables to predict serum GDF-15 levels, even after adjusting for age and body mass index (eGFR: ß = -0.423, p < 0.001; Hb: ß = -0.363, p = 0.004). Serum GDF-15 level was an independent variable to predict eGFR and Hb. CONCLUSIONS: Both Hb and eGFR are predictors for serum GDF-15 concentration in healthy older females. In these community-dwelling older females, renal dysfunction via GDF-15 may be accompanied by anemia, but not sarcopenia.