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Aims: S100A8/A9 is expressed in activated monocytes/macrophages and assumed to be heavily involved in the pathogenesis of acute inflammation. Although several studies have asserted that S100A8/A9 has a proinflammatory function, the exact biological function of S100A8/A9 is yet to be described. We examined the anti-inflammatory effects of S100A8/A9 on experimental autoimmune myocarditis (EAM) in rats.Methods and Results: Experimental autoimmune myocarditis was induced in Lewis rats by immunization with porcine cardiac myosin. The recombinant (R-) S100A8/A9 was injected intraperitoneally into EAM rats. R-S100A8/A9 attenuated the severity of myocarditis, as evidenced by echocardiographic and histological findings. In addition, we found that not only the mRNA expression of proinflammatory cytokines [interleukin (IL)-1beta, IL-6, and tumour necrosis factor (TNF)-alpha] in the myocardium, but also their serum concentrations were suppressed in EAM rats treated with R-S100A8/A9. Nuclear factor-kappa B expression in inflammatory cells was also suppressed in the treated rats. To elucidate the mechanistic function of S100A8/A9 on proinflammatory cytokines in vivo, we used an ELISA on the supernatant of homogenized heart tissue treated with R-S100A8/A9. The findings revealed high-affinity binding of R-S100A8/A9 with IL-1beta, IL-6, and TNF-alpha in the myocardium, suggesting the trapping of proinflammatory cytokines by R-S100A8/A9.Conclusion: S100A8/A9 attenuates EAM through modulation of the proinflammatory cytokine network. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate association between magnetic resonance imaging (MRI) and histological findings of degenerated anterior cruciate ligament (ACL) in knee osteoarthritis (OA), and based on this result, to develop a new ACL degeneration grading system by MRI that corresponds to histological findings of degenerated ACL., Hypothesis: MRI signal intensity of the ACL could correspond to histological findings of collagen degeneration., Patients and Methods: A collection of 106 ACL specimens from 85 patients who underwent primary total knee arthroplasty was investigated for signal intensity of the ACL and muscle on axial Fat-saturated proton density-weighted MRI and MRI signal intensity ratio (ACL/muscle) was calculated. The correlation between ACL histological degeneration and MRI ACL/muscle signal intensity ratio was analyzed. The ACL was stratified into 3 grades based on signal intensity relative to muscle intensity (grade 1, low; grade 2, iso; and grade 3, high), and the extent to ACL degeneration in each MRI ACL degeneration grade was evaluated., Results: Collagen degeneration (53.5±24.0%) and myxoid change (25.2±18.8%) in degenerated ACL significantly correlated with MRI signal intensity ratio of the ACL/muscle (r=0.62, p<0.0001; r=0.67, p<0.0001). ACL were assigned to grade 1 (n=22 [20.8%]), grade 2 (n=56 [52.8%]), and grade 3 (n=28 [26.4%]). ACL collagen degeneration was 34.8±18.4% in grade 1, 49.3±21.7% in grade 2, and 76.6±12.0% in grade 3. ACL myxoid change was 10.0±11.3% in grade 1, 21.3±14.1% in grade 2, and 45.0±15.3% in grade 3., Discussion: The ACL/muscle signal intensity ratio on MRI correlated with the extent to ACL myxoid degeneration. The new MRI ACL degeneration grade is helpful to estimate the extent to ACL myxoid degeneration in knee OA., Level of Evidence: III; retrospective cohort study., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Purpose: This study aimed to retrospectively investigate (1) the reproducibility of gap measurements by manual stress using the Z-shaped retractor depending on the surgeon's experience with this maneuver and (2) the consistency of the gap distraction force produced by manual stress throughout the range of motion (ROM) in the robotic-assisted total knee arthroplasty (TKA). It was hypothesized that the joint gap produced by manual stress is not reproducible depending on the surgeon's experience, and the distraction force applied by manual stress throughout the ROM is not constant., Methods: Medial and lateral joint gaps were obtained throughout the ROM by manual stress or a tensioner by two surgeons with different levels of experience in robotic-assisted TKA. The association between the differences in gap measurement by the two surgeons and the preoperative radiographic parameters, including the hip-knee-ankle (HKA) angle and absolute and relative varus/valgus laxities were analyzed., Results: The experienced surgeon produced significantly greater gaps than the inexperienced surgeon from 0° to 100° flexion, with a mean difference of 0.35 ± 0.12 mm in the medial gap (p < 0.0001), and from 10° to 120° flexion with a mean difference of 0.57 ± 0.13 mm in the lateral gap (p < 0.0001). The tensioner produced a significantly greater medial gap from 70° to 110° flexion with a mean difference of 0.32 ± 0.01 mm in the medial gap (p < 0.0001) and from 0° to 110° flexion with a mean difference of 1.12 ± 0.26 mm in the lateral gap (p < 0.0001). The differences in gap distance by manual stress between experienced and inexperienced surgeons were moderately correlated with the HKA angle in the lateral gap (r = 0.40, p = 0.01). The gap differences due to manual stress and a tensioner showed moderate negative correlation with the HKA angle in the medial gap (r = - 0.50, p = 0.001) and weak negative correlation with the absolute valgus laxity in the lateral gap (r = - 0.35, p = 0.03)., Conclusions: The joint distraction force by manual stress may differ depending on the surgeon's experience and tended to be smaller in deep flexion; therefore, the flexion gap may be underestimated. Surgeons should determine implant positioning considering gap balance by manual stress, taking into account these characteristics of the manual stress maneuver., Level of Evidence: Level III, retrospective cohort study., (© 2022. The Author(s) under exclusive licence to European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

Objectives: The mechanism underlying neuropathic pain (NP) in osteoarthritis (OA) of the knee is not completely understood. This study aimed to investigate whether possible NP in patients with knee OA undergoing knee surgery is associated with specific radiological findings., Methods: This study included 197 patients who underwent knee surgery for symptomatic knee OA. Clinical evaluation was performed using the Central Sensitization Inventory (CSI), Western Ontario and McMaster Universities Arthritis Index (WOMAC), and PainDETECT questionnaire. Radiological evaluation was performed using the hip-knee-ankle (HKA) angle, posterior tibial slope (PTS), varus and valgus laxities, and magnetic resonance imaging OA Knee Score (MOAKS). Radiological findings were compared between patients with possible and unlikely NP. Logistic regression analysis was performed to identify the predictive factors for NP., Results: There were 163 and 34 patients with unlikely NP and with possible NP, respectively. The percentage of patients with CSI score ≥ 40 was significantly higher in the possible NP group than in the unlikely NP group (17.6% vs. 6.1%). Patients with possible NP had worse WOMAC scores than patients with unlikely NP. There were no significant positive associations between the possible NP and radiological findings in knee OA. Regression analysis showed no predictive factors for possible NP., Conclusions: Possible NP is not associated with specific radiological findings in knee OA. Patients with possible NP may mediate CS and experience more severe symptoms, including decreased knee function and lower quality of life, than patients with unlikely NP.

Background: The function of the anterior cruciate ligament (ACL) in osteoarthritis (OA) of the knee remains to be elucidated. The purpose of this study is to evaluate histological changes of the ACL in end-stage knee OA and to clarify the relationship between histological changes in the ACL and knee function., Hypothesis: The hypothesis in this study was that ACL degeneration in knee OA is associated with decreased knee function., Patients and Methods: Eighty-two ACL specimens from 65 patients who underwent primary total knee arthroplasty (TKA) were investigated. The correlation between histological changes of the ACL (myxoid changes, chondroid metaplasia, total collagen degeneration, microcyst formation, vascular proliferation, and inflammatory cell infiltration) and knee function (range of motion, anterior tibial translation test, knee extension muscle strength, one-leg standing time, and functional reach test) were investigated. Age, body mass index, joint space narrowing, osteophyte formation, lower extremity alignment, and knee medial/lateral instability were also evaluated., Results: Myxoid change in the ACLs was significantly negatively correlated with one-leg standing time. Chondroid metaplasia was not correlated with knee function. Collagen degeneration in the ACL was significantly negatively correlated with knee flexion angle and one-leg standing time. In addition, a negative correlation between microcyst formation and knee flexion angle was noted. Osteophyte formation, particularly lateral femoral intercondylar osteophytes, was correlated with myxoid changes. The other parameters did not correlate with ACL histological changes., Discussion: Myxoid changes in the ACL were shown to correlate with knee function. The osteophyte score, particularly as related to lateral femoral intercondylar osteophytes, correlated with the severity of myxoid changes in the ACL in knee OA. Precise ACL evaluation should be included in the indications for ACL-retaining surgeries because ACL degeneration may be related to decreased knee function after surgery., Level of Evidence: IV, Diagnostic case series., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background: The purpose of this study was to investigate axial load resistance of the tibia depending on the thickness of tibial tuberosity osteotomy in medial open-wedge distal tuberosity proximal tibial osteotomy (OWDTO). The hypothesis is that a thin tibial tuberosity osteotomy shows high axial load resistance of the tibia., Methods: The OWDTO model was constructed from imitation bones of the tibia. Distal tibial tuberosity osteotomy was performed with thicknesses of 7, 14, and 21 mm (n = 5 for each group). Cyclic axial-load fatigue tests were performed to investigate the strain at five measurement points on the OWDTO model. An axial-load failure test was also performed to investigate the maximum strain for failure., Results: The 7-mm OWDTO model showed a significantly lower stain range than the 14-mm model at the middle part of the lateral hinge (P = 0.0263, mean difference: -852.6 με), posterior part (P = 0.0465, mean difference: -1040.0 με), posterior tibial cortex (P < 0.0001, mean difference: -583.4 με), and plate (P = 0.0029, mean difference: -121.6 με). There were no significant differences in the strain at the tibial tuberosity between the groups. The axial load for complete failure was significantly higher in the 7-mm model than in the 21-mm model (P = 0.0010, mean difference: 2577.0 N). The failure points were at the lateral hinges., Conclusions: Thinner distal tibial tuberosity osteotomy is more resistant to axial load and may be recommended for the prevention of tibial and lateral hinge fractures after OWDTO., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: In kinematically aligned total knee arthroplasty (TKA), it is necessary to infer the pre-arthritic constitutional medial proximal tibial angle (MPTA) in advanced osteoarthritis (OA) of the knee with bone loss. The aim of this study was to investigate whether MPTA at the posterior tibial plateau represents the pre-arthritic constitutional MPTA in anterior cruciate ligament (ACL)-intact, advanced OA knees. It was hypothesized that MPTA at the posterior tibial plateau represents the pre-arthritic constitutional MPTA of ACL-intact, advanced knee OA., Methods: One hundred varus, anterior cruciate ligament (ACL)-intact, advanced OA knees were analysed. The hip-knee-ankle (HKA) angle and MPTA were assessed on computed radiography (CR) and MPTAs at the anterior, middle, and posterior part of the tibial plateau were assessed on computed tomography (CT) images. The association between these parameters was also analysed., Results: CR images showed an HKA angle of 172.4 ± 4.1° and MPTA of 84.3 ± 2.5°. CT images showed different MPTAs in the three regions, ranging from 83.9 ± 2.4° to 85.9 ± 2.8°. The middle MPTA was the lowest at 83.9 ± 2.4°. HKA angle correlated with the middle MPTA (r = 0.3355, 95% confidence interval [CI] 0.1489-0.4991, p = 0.0006) and ΔMPTA (Middle-Posterior) (r = 0.5128, 95% CI 0.3518-0.6443, p < 0.0001)., Conclusion: The MPTA at the posterior tibial plateau represents the pre-arthritic constitutional MPTA in ACL-intact, advanced OA knees., Level of Evidence: III, retrospective cohort study., (© 2022. The Author(s) under exclusive licence to European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

Objectives: Cerebral microbleeds (CMBs), which can be detected by gradient-echo T2*-weighted magnetic resonance imaging (MRI), represent small chronic brain hemorrhages caused by structural abnormalities in cerebral small vessels. CMBs are known to be a potential predictor of future stroke, and are associated with age, various cardiovascular risk factors, cognitive impairment, and the use of antithrombotic drugs. Patients with coronary artery disease (CAD) are at potentially high risk of CMBs due to the presence of coexistent conditions. However, little is known about CMBs in patients with CAD. We aimed to identify the factors associated with the presence of CMBs among patients with CAD., Methods: We evaluated 356 consecutive patients [mean age, 72 ± 10 years; men = 276 (78%)] with angiographically proven CAD who underwent T2*-weighted brain MRI. The brain MRI was assessed by researchers blinded to the patients' clinical details., Results: CMBs were found in 128 (36%) patients. Among 356 patients, 119 (33%) had previously undergone percutaneous coronary intervention (PCI), and 26 (7%) coronary artery bypass grafting (CABG). There was no significant relationship between CMBs and sex, hypertension, dyslipidemia, diabetes mellitus, anticoagulation therapy, antiplatelet therapy, or prior PCI. CMBs were significantly associated with advanced age, previous CABG, eGFR, non-HDL cholesterol, carotid artery disease, long-term antiplatelet therapy, and long-term dual antiplatelet therapy (DAPT) using univariate logistic regression analysis. The multivariate logistic regression analysis showed that long-term antiplatelet therapy (odds ratio, 1.73; 95% CI, 1.06 - 2.84; P = 0.03) or long-term DAPT (odds ratio, 2.92; 95% CI, 1.39 - 6.17; P = 0.004) was significantly associated with CMBs after adjustment for confounding variables., Conclusions: CMBs were frequently observed in patients with CAD and were significantly associated with long-term antiplatelet therapy, especially long-term DAPT., Competing Interests: Conflict of Interest The authors have no conflicts of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The spleen is associated with inflammation, and the size of the spleen is affected by hemodynamic congestion and sympathetic stimulation. However, the association between splenic size and prognosis in patients with heart failure remains unknown. Between January 2015 and March 2017, we analyzed 125 patients with acute decompensated heart failure who were assessed by computed tomography (CT) on the day of admission. The spleen was measured by 3-dimensional CT and then the patients were assigned to groups according to their median splenic volume indexes (SpVi; splenic volume/body surface area). We then compared their baseline characteristics and rates of readmission for heart failure after one year. The median SpVi was 63.7 (interquartile range: 44.7-95.3) cm 3 /m 2 . Age did not significantly differ between the groups. Patients with a high SpVi had more significantly enlarged left atria and left ventricles. Multiple regression analysis identified significant positive correlations between SpVi and posterior wall thickness as well as left ventricular mass index. Kaplan-Meier analysis revealed lower event-free rates in the patients with a high, than a low SpVi (P = 0.041, log-rank test). After adjustment for potential cofounding factors, SpVi was independently associated with readmission for heart failure (Hazard ratio, 2.25; 95% confidence interval, 1.01-5.02; P = 0.047). In conclusion, increased splenic volume is independently associated with readmission for heart failure among patients with acute decompensated heart failure.

Background: B-type natriuretic peptide (BNP) has been widely used for the diagnosis of heart failure, its severity, and prognosis. However, little is known about factors related to disproportionately low BNP levels even during acute heart failure conditions., Methods and Results: Among 424 patients hospitalized for acute heart failure, we categorized the patients into the HFpEF (LVEF > 50%) or HFrEF (LVEF ≤ 50%) group and subdivided them into disproportionately low BNP (LB) group and high BNP (HB) group using a cut-off BNP level of 200 pg/mL at admission. The proportion of patients with LB was higher in the HFpEF group (22.2%) than in the HFrEF group (10.9%, p = 0.002). Patients with LB had a high BMI, lower blood pressure, and history of previous cardiovascular surgery in the HFpEF group, while patients in the HFrEF group had a high BMI and smaller left ventricular end-diastolic volume index. Furthermore, presence of LB in the HFrEF group was related to good prognosis, but LB in the HFpEF group was an indicator of poor prognosis as HB group., Conclusions: The factors associated with LB were different between the HFpEF and HFrEF groups. LB was related to good prognosis in HFrEF, but not in HFpEF., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Elevated liver fibrosis markers are associated with worse prognosis in acute heart failure (AHF). The aspartate aminotransferase to alanine aminotransferase ratio (AAR) is one such fibrosis marker, and low ALT is a surrogate marker of malnutrition. Here, we evaluated the association between AAR and nutritional status and prognosis in patients with AHF. Consecutive 774 patients who were admitted due to AHF were divided into 3 groups according to AAR at discharge: first tertile, AAR<1.16 (n = 262); second tertile, 1.16≤AAR<1.70 (n = 257); and third tertile, AAR≥1.70 (n = 255). Nutritional indices and a composite of all-cause death or HF rehospitalization were compared in the 3 tertiles. Patients in the third AAR tertile were older and had lower body mass index than patients in other AAR tertiles. A higher AAR was associated with worse nutritional indices (i.e., controlling nutritional status score, geriatric nutritional risk index, and prognostic nutritional index). Clinical outcome rates significantly increased along AAR tertiles (first tertile, 28%; second tertile, 43%; third tertile, 58%, p < 0.001). Cox proportional hazards models including potential prognostic factors revealed high AAR was an independent prognostic factor of AHF. In conclusion, AAR at discharge may be associated with nutritional status and worse clinical outcomes in patients with AHF., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relations that could have appeared to influence the work reported in this study., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Malnutrition and systemic inflammation are associated with poor outcomes in patients with heart failure. Recent studies have reported that the advanced lung cancer inflammation index (ALI), derived from the body mass index (BMI), serum albumin level, and neutrophil-to-lymphocyte ratio (NLR), is associated with poor prognosis in several types of cancers. Each marker is also known to prognostic factor of heart failure. Therefore, we hypothesized that ALI may be useful for determining the prognosis of patients with acute decompensated heart failure (ADHF). We reviewed survival in 381 consecutive patients (age, 73.1 ± 11.4 years, 59% men) who were hospitalized for ADHF and discharged. ALI at discharge, calculated as BMI × albumin level/NLR, was used to divide the patients into tertiles (ALI < 23.88, 23.88 ≤ ALI < 42.43, and ALI ≥ 42.43). The patients were also stratified into six groups according to the ALI tertiles and median concentration (177 pg/mL) of brain natriuretic peptide (BNP). The primary endpoint comprised all-cause mortality and readmission because of heart failure. The median follow-up duration was 363 days (interquartile range: 147-721 days), and 166 patients (44%) experienced the primary endpoint. Kaplan-Meier analysis showed that the event rate decreased progressively from the first to the third ALI tertile (52%, 48%, and 31%, respectively; p = 0.0013). In a multivariate Cox proportional hazards model, the first tertile was an independent prognostic factor for the primary endpoint (third vs. first tertile: hazard ratio, 0.57; 95% confidence interval, 0.34-0.95; p = 0.031). The hazard ratio for the primary endpoint for the patients with high BNP and first tertile ALI relative to the patients with low BNP and third tertile ALI was 5.3 (95% confidence interval, 2.9-9.5; p < 0.001). ALI at discharge, a novel and simple index of nutrition and inflammation, may be useful for risk stratification and predicting the prognosis of patients with ADHF.

Background: Left atrial spontaneous echo contrast (LASEC) is common in patients with atrial fibrillation (AF), although scarce information exists on LASEC occurring in nonvalvular AF patients who have low thromboembolic risk scores. We therefore examined prevalence and determinants of LASEC under low CHADS 2 or CHA 2 DS 2 -VASc scores in these patients., Methods: Among 713 patients who underwent transesophageal echocardiography, 349 with a CHADS 2 score < 2 (CHADS 2 group) (93 women, mean age 65 years) and 221 with a CHA 2 DS 2 -VASc score < 2 (CHA 2 DS 2 -VASc group) (39 women, mean age 62 years) were separately examined for clinical and echocardiographic findings., Results: LASEC was found in 77 patients of CHADS 2 group (22%) and in 41 of CHA 2 DS 2 -VASc group (19%). Multivariate logistic regression analysis, adjusted for several parameters including non-paroxysmal AF, LA enlargement (LA diameter ≥ 50 mm), left ventricular (LV) hypertrophy, and an elevated B-type natriuretic peptide (BNP) (BNP ≥200 pg/mL) revealed that for CHADS 2 group, non-paroxysmal AF (Odds ratio 5.65, 95%CI 3.08-10.5, P < 0.001), BNP elevation (Odds ratio 3.42, 95%CI 1.29-9.06, P = 0.013), and LV hypertrophy (Odds ratio 2.26, 95%CI 1.19-4.28, P = 0.013) were significant independent determinants of LASEC, and that for CHA 2 DS 2 -VASc group, non-paroxysmal AF (Odds ratio 3.38, 95%CI 1.51-7.54, P = 0.003) and LV hypertrophy (Odds ratio 2.53, 95%CI 1.13-5.70, P = 0.025) were significant independent determinants of LASEC., Conclusions: LASEC was present in a considerable proportion of patients with nonvalvular AF under low thromboembolic risk scores. Information on AF chronicity, BNP, and LV hypertrophy might help identify patients at risk for thromboembolism, although large-scale studies are necessary to confirm our observations.

Background: Tissue Doppler imaging (TDI)-derived atrial electromechanical delay (AEMD) has been reported to be useful for detecting paroxysmal atrial fibrillation (PAF). However, its usefulness remains unknown when analyzed along with patients seemingly at high-risk for AF as controls. From this standpoint, we investigated whether AEMD would be of use for identifying patients with PAF., Methods: We retrospectively analyzed TDI recordings to obtain AEMD in 63 PAF patients. Thirty-three patients with multiple cardiovascular risk factors (MRFs) but without history of AF and 50 healthy individuals served as disease and healthy controls, respectively. AEMD was defined as the time-interval between the electrocardiogram P-wave and the beginning of the spectral TDI-derived A' for the septal (septal EMD) and lateral (lateral EMD) sides of the mitral annulus., Results: There was no significant difference in the left atrial volume index between PAF patients and disease controls (28 ± 9 mL/m 2 vs. 27 ± 5 mL/m 2 ). PAF patients had longer AEMD, particularly for the lateral EMD (75 ± 23 ms), compared with disease (62 ± 22 ms, P = 0.009) and healthy (54 ± 24 ms, P < 0.001) controls. Multivariate logistic regression analysis revealed that the lateral EMD (OR 1.25, 95%CI 1.03-1.52, P = 0.023), along with the left atrial volume index (OR 2.25, 95%CI 1.44-3.51, P < 0.001), was one of the significant independent associates of identifying PAF patients., Conclusions: This cross-sectional study indicates that even analyzed together with MRFs patients, AEMD remains useful for identifying patients at risk for AF. Our results need to be confirmed by a large-scale prospective study.

The fibrosis-4 index (FIB-4 index) is a marker of liver fibrosis. It has been reported that the FIB-4 index in compensated phase is associated with estimated right-sided filling pressure and poor prognosis in patients with heart failure. However, the relationship with invasively obtained right-sided cardiac pressures has been unclear. Hemodynamic status was evaluated by right heart catheterization in 189 heart failure patients who were in a clinically compensated phase between January 2015 and September 2017. Patients were assigned to two groups based on a median FIB-4 index of 2.15, then hemodynamic parameters and event rates were compared. Endpoint was defined as a composite of all-cause death, readmission for heart failure, or left ventricular-assist device implantation. Then, we also investigated correlations between the FIB-4 index and clinical factors, including hemodynamic parameters. Patients with a high FIB-4 index were significantly older (76 [IQR, 63-80] vs. 65 [IQR, 56-74] years, P < 0.001) and had higher right atrial pressure (RAP; 7 [IQR, 5-11] vs. 4 [IQR, 1-6] mmHg, P < 0.001) and pulmonary capillary wedge pressure (16 [IQR, 12-22] vs. 12 [IQR, 8-19] mmHg, P = 0.011) than those with a low FIB-4 index. The FIB-4 index correlated more strongly with parameters of right-sided than left-sided HF (RAP, R = 0.41, P < 0.001; inferior vena cava diameter, R = 0.44, P < 0.001; pulmonary capillary wedge pressure, R = 0.15, P = 0.038; brain natriuretic peptide, R = 0.14, P = 0.29). Multiple regression analysis showed that the FIB-4 index independently correlated with RAP. In conclusion, the FIB-4 index can non-invasively reflect right-sided filling pressure, which might explain why it is associated with a poor prognosis, among patients with heart failure.

Gradient-echo T2-star (T2*)-weighted magnetic resonance imaging (MRI) is a sensitive method to detect cerebral microbleeds (CMBs). The presence of CMBs was reported to be a marker of future cardiovascular mortality and is associated with various cardiovascular risk factors, use of antithrombotic drugs, and cognitive dysfunction. However, the relationship between cardiac function and CMBs remains unclear. We investigated the association between cardiac function and presence of CMBs in patients with cardiovascular diseases. This single-center retrospective study included a total of 424 participants (mean age 70 ± 12 years; men 286 (67%); mean left ventricular ejection fraction (LVEF) 61% ± 12%] who underwent echocardiography and brain T2*-weighted MRI within 1 month without neurologic abnormality. CMBs were found in 118 (28%) patients. There was no significant relationship between CMBs and anticoagulant or antiplatelet therapy. LVEF was significantly lower in patients with CMBs than in those without CMBs (59% ± 13% vs. 62% ± 11%, P < 0.05). On multivariate logistic analysis, lower LVEF [odds ratio (OR) 0.98, 95% confidence interval (CI) 0.96-1.00; P < 0.05] and age (OR 1.02, 95% CI 1.00-1.05; P < 0.05) were significantly associated with CMBs. The presence of CMBs was frequently observed in the patients with cardiovascular disease and was significantly associated with age and LVEF.

The prevalence and extent of immunoglobulin G4 (IgG4)-positive cell infiltration were investigated in 282 surgical samples of aortic wall and aortic valve. Tissue infiltration of IgG4-positive cells was observed in 24 (17.3%) of 139 aortic valve samples and 46 (32%) of 143 aortic wall samples, and the condition of IgG4-positive cell infiltration > 30/hpf together with IgG4/CD138 ratio > 40% was observed in 2 (1.4%) of aortic valve samples and 14 (9.8%) of aortic wall samples. Among 275 patients, preoperative serum IgG4 level was available in 48 patients (50 samples), and it was > 135 mg/dL in only one patient. Of these 48 patients with serum IgG4 measurement, 29 patients had aortic valve stenosis and 12 had aortic aneurysm. Compared with 23 aortic stenosis patients without tissue infiltration of IgG4-positive cells in the aortic valve, six patients with IgG4-positive cell infiltration had a more prevalent smoking history (26% versus 83%) and borderline significantly higher serum IgG4 (median, 24.5 mg/dL versus 55.5 mg/dL), although either preoperative peak pressure gradient between left ventriculum and aorta or aortic valve area did not differ significantly between groups. Compared with six aortic aneurysm patients without tissue infiltration of IgG4-positive cells in the aortic wall, six patients with IgG4-positive cell infiltration had borderline significantly higher serum IgG4 (median, 28.9 mg/dL versus 68.2 mg/dL). The current study showed that tissue IgG4-positive infiltration is not a rare occurrence in the aortic stenosis and aortic aneurysm. Clinical significance of tissue IgG4-postive cell infiltration in these patients requires further investigation.

Immunoglobulin G4 (IgG4)-related disease, that is characterized by the elevation of circulating IgG4 level and the tissue-infiltration of IgG4-positive plasma cells, can target the cardiovascular tissue, although the diagnosis of IgG4-related cardiovascular lesion is not easy owing to the substantial risk for the tissue sampling. We herein examined the serum IgG4 levels among cardiac patients. In patients who were admitted to the cardiology department (n=477) and those who underwent computed tomography coronary artery angiography (n=401), elevated serum IgG4 level (≥135 mg/dL) was found 23 (4.8%) and 17 (4.2%), respectively. However, among those with elevated serum IgG4, only two patients could be clinicopathologically diagnosed with IgG4-related disease. Cardiovascular organ involvement may aggravate the prognosis of IgG4-related disease which in general not life-threatening. Considering that the non-negligible prevalence of high IgG4 level among cardiac patients who were not diagnosed with IgG4-related disease, however, physicians should not count too much on the serum IgG4 levels for the diagnosis of IgG4-related cardiovascular lesions, especially when histopathologic findings are not available, or when other-tissue involvement of IgG4-related disease is not apparent. (This is a translation of J Jpn Coll Angiol 2017; 57: 91-98.).

Patients with chronic kidney disease (CKD) experiencing atrial arrhythmia are hypothesized to have elevated CHADS 2 and CHA 2 DS 2 -VASc scores, thereby predisposed to left atrial (LA) thrombus formation and subsequent thromboembolism. We examined possible association of LA thrombogenic milieu (TM) with CKD in patients with nonvalvular atrial fibrillation. A total of 581 patients (181 women; mean age, 67 years) who underwent transesophageal echocardiography were examined. Patients were divided into 4 groups based on the estimated glomerular filtration rate (eGFR) (ml/min/1.73 m 2 ): eGFR ≥90 (n = 29), 60≤ eGFR <90 (n = 329), 30≤ eGFR <60 (n = 209), and eGFR <30 (n = 14). TM was defined as the presence of LA thrombus, dense spontaneous echo contrast, or LA appendage velocity ≤25 cm/s. Of 581 patients, 147 (25%) had TM. The prevalence of TM increased with decreasing eGFR (4%, 18%, 36%, and 86% for each group, p <0.001). Similar trends were observed for some of the clinical and echocardiographic variables including CHA 2 DS 2 -VASc score and LA size. Multivariate logistic regression analysis revealed that every 10 ml/min/1.73 m 2 decrement in eGFR was a significant independent correlate of TM (odds ratio 0.80, p = 0.005), along with nonparoxysmal atrial fibrillation (AF) (odds ratio 0.45, p = 0.004), higher CHA 2 DS 2 -VASc score (odds ratio 1.24, p = 0.012), every 5 ml/m 2 increment in LA volume index (odds ratio 1.57, p <0.001), and every 10% decrement in left ventricular ejection fraction (odds ratio 0.51, p <0.001). In conclusion, CKD may be a significant risk factor for LA thrombus formation in patients with nonvalvular atrial fibrillation., (Copyright © 2018. Published by Elsevier Inc.)

BACKGROUND Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis of unknown cause accompanied by prominent eosinophilia. Intracardiac thrombosis is one of the major cardiac complications in EGPA that may cause thromboembolism. CASE REPORT A 46-year-old male presenting with intermittent chest pain and numbness of the lower extremities was admitted to our center. His case was complicated by multiple brain infarcts and endocardial thrombosis in the left ventricle. A condition of restrictive cardiomyopathy was also found. After a thorough workup, he was diagnosed with antineutrophil cytoplasmic antibody (ANCA) positive EGPA. Interestingly, the thrombus was accompanied by a pressure gradient producing mid-ventricular obstruction. The patient improved reasonably with immunosuppression and anticoagulation treatment, in addition to heart failure treatment, and had a concomitant regression of the thrombus and reduction of the pressure gradient. CONCLUSIONS For an EGPA patient complicated by intraventricular obstruction caused by endocardial thrombosis, which could accelerate the release of the thrombus into the systemic circulation resulting in a life-threating condition, timely and aggressive measures against cardioembolic complications should be considered.

A 74-year-old man was admitted for preoperative screening of aortic stenosis. Five months before this admission, he was found to have elevated serum immunoglobulin G4 (IgG4; 2,010 mg/dL). Computed tomography (CT) showed a soft tissue mass surrounding the abdominal aorta, suggestive of IgG4-related periaortitis. CT coronary angiography showed perivascular thickening of the right coronary artery, and subsequent coronary angiography showed a multi-vessel disease. The patient underwent aortic valve replacement and coronary bypass surgery. Immunohistochemical analysis showed IgG4-positive plasmacytic infiltration in specimens from the aortic valve, epicardium, and aortic adventitia, suggestive of the possible role of IgG4-related immune inflammation for the pathogenesis.

Background: Fibroblast growth factor 23 (FGF23) induces cardiac remodeling. We investigated the changes in serum FGF23 levels in patients diagnosed with acute myocardial infarction (AMI).Methods and Results:A total of 44 patients diagnosed with AMI were included in the current study. All patients underwent emergency percutaneous coronary intervention (PCI). The median of peak creatine kinase (CK) and CKMB values was 1,816 U/L and 159 U/L, respectively. Serum levels of FGF23, calcium, and inorganic phosphate (iP) were measured before PCI, and on days 1, 3, 5, 7 after PCI. Serum FGF23 levels showed a slight, but significant decrease on days 1 and 3 after PCI, and a 1.5- and 2.0-fold increase on days 5 and 7, respectively, after PCI. As compared with propensity score-matched patients without AMI, serum FGF23 was significantly lower among the current cohort of AMI patients. In 22 subjects who underwent a follow-up echocardiographic examination at 6 months after the onset of AMI, the log-transformed relative increase in FGF23 on day 7 significantly and negatively correlated with changes between LVEF on admission and that at 6 months afterward., Conclusions: After a slight decrease on days 1 and 3 after admission, serum FGF23 increased significantly on days 5 and 7. The underlying mechanism and potential clinical importance of these observations require further investigation.

Several studies have shown that subjects with higher serum bilirubin may have a lower risk of cardiovascular disorders. We herein investigated whether serum bilirubin concentration is associated with lower extremity ischemia among cardiology patients. In total, 935 patients without a history of angioplasty or bypass surgery of the lower limb arteries and who had bilateral ankle-brachial index measurements were included in the study. Peripheral arterial disease (PAD) was defined to be present when ABI of either or both sides was <0.9. Overall, the serum total bilirubin concentration ranged between 0.1 and 2.7mg/dL (normal range, 0.1-1.0mg/dL). Across the bilirubin tertiles, age did not differ significantly. On the other hand, male patients (median 0.6mg/dL, interquartile range (IQR) 0.4-0.7mg/dL) had significantly higher bilirubin levels than female patients (median 0.5mg/dL, IQR 0.4-0.7mg/dL, P=0.014). Logistic regression analysis showed that, as compared with the lowest bilirubin tertile (0.1-0.4mg/dL), the highest tertile (0.7-2.7mg/dL) was significantly negatively associated with prevalent PAD after adjusting for sex, age, eGFR, white blood cell count, inorganic phosphate, HbA1C, total and HDL cholesterol, triglycerides, current smoking, diabetic medication, and statin use. This association remained significant when only those with serum bilirubin in the normal range were included in the analysis. Among cardiology patients, serum bilirubin concentration was significantly negatively associated with prevalence of PAD. The underlying mechanism and therapeutic indications should be investigated in further investigations., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Serum levels of the soluble urokinase-type plasminogen activator receptor (suPAR) reflect immune and inflammatory activation, and are shown to be associated with cardiovascular outcomes. We herein investigated the potential association between suPAR and left ventricular diastolic dysfunction among patients with preserved left ventricular ejection fraction (LVEF) and sinus rhythm. Among 291 patients who had sinus rhythm and an LVEF of ≥50% enrolled in the study, 26 (8.9%) were considered to have diastolic dysfunction. Patients with diastolic dysfunction had lower estimated glomerular filtration rate (eGFR), and higher systolic blood pressure (BPs), BNP, C-reactive protein, and suPAR than those without diastolic dysfunction. As compared with the first suPAR quartile, the fourth suPAR quartile was significantly associated with both diastolic dysfunction with an odds ratio of 8.95 [95% confidence interval (CI), 1.04-77.0, P < 0.05] after adjusting for sex, age, BPs log(eGFR), CRP, and diuretic use. On the other hand, receiver-operating characteristic curve (ROC) analysis showed that addition of log(suPAR) to the combination of age, sex, and log(eGFR), CRP, and diuretic use did not significantly improve the prediction of diastolic dysfunction. Among cardiac patients with preserved LVEF, serum suPAR was associated with diastolic dysfunction independent of confounding factors by logistic regression analysis. However, according to the ROC analysis, the utility of suPAR as a biomarker for diastolic dysfunction may be limited from a clinical point of view.

Background: Circulating soluble urokinase-type plasminogen activator receptor (suPAR), which can reflect immune activation and low-grade inflammation, may be a novel biomarker of cardiovascular disease., Methods: We investigated the potential association between suPAR and the prevalence of atrial fibrillation (AF) by analyzing patients with either sinus rhythm, paroxysmal atrial fibrillation (PAF), or non-paroxysmal atrial fibrillation (NPAF), which indicates either permanent or persistent AF., Results: Among 426 patients enrolled (mean age 71.4±9.2 years; 110 (25.8%) female), 310, 62, and 54 were diagnosed with sinus rhythm, PAF, and NPAF, respectively. NPAF was >10-fold more prevalent in the highest suPAR quartile (>3534 pg/mL; 32 (30.2%) of 106 patients) than in the lowest suPAR quartile (<1802 pg/mL; 3 (2.8%) of 107 patients). Logistic regression analysis showed that, as compared with the lowest suPAR quartile, the highest suPAR quartile was associated with NPAF with an odds ratio of 6.48 (95% confidence interval, 1.71-24.5) after adjustment for sex, age, log(eGFR), C-reactive protein, and systolic blood pressure. In multivariate receiver operating characteristic analysis to predict NPAF, the area under the curve (AUC) for the combination of age, sex, log(eGFR), and C-reactive protein was 0.777 (standard error [SE], 0.036); the addition of log(suPAR) slightly improved the prediction (AUC, 0.812; SE, 0.034, P=0.084)., Conclusions: Serum suPAR was associated with AF, particularly NPAF, as demonstrated by multivariate logistic regression analysis. Whether suPAR promotes or maintains AF should be investigated in further studies.

Background and Purpose: Xanthine oxidoreductase (XOR), which catalyzes purine catabolism, has two interconvertible forms, xanthine dehydrogenase and xanthine oxidase, the latter of which produces superoxide during uric acid (UA) synthesis. An association between plasma XOR activity and cardiovascular and renal outcomes has been previously suggested. We investigated the potential association between cardiac parameters and plasma XOR activity among cardiology patients., Methods and Results: Plasma XOR activity was measured by [13C2,15N2]xanthine coupled with liquid chromatography/triplequadrupole mass spectrometry. Among 270 patients who were not taking UA-lowering drugs, XOR activity was associated with body mass index (BMI), alanine aminotransferase (ALT), HbA1c and renal function. Although XOR activity was not associated with serum UA overall, patients with chronic kidney disease (CKD), those with higher XOR activity had higher serum UA among patients without CKD. Compared with patients with the lowest XOR activity quartile, those with higher three XOR activity quartiles more frequently had left ventricular hypertrophy. In addition, plasma XOR activity showed a U-shaped association with low left ventricular ejection fraction (LVEF) and increased plasma B-type natriuretic peptide (BNP) levels, and these associations were independent of age, gender, BMI, ALT, HbA1C, serum UA, and CKD stages., Conclusions: Among cardiac patients, left ventricular hypertrophy, low LVEF, and increased BNP were significantly associated with plasma XOR activity independent of various confounding factors. Whether pharmaceutical modification of plasma XOR activity might inhibit cardiac remodeling and improve cardiovascular outcome should be investigated in future studies.

Mean serum uric acid (SUA) levels are higher in men than women. In addition, recent studies have suggested that the SUA threshold at which the cardiovascular risk might increase may vary between women and men. In the current retrospective study, by analyzing the data from 219 female and 519 male patients who were free from uric acid-lowering medication, we investigated whether SUA is associated with left ventricular mass index (LVMI), left ventricular ejection fraction (LVEF), and plasma levels of B-type natriuretic peptide (BNP) independent of confounding factors, such as serum calcium, inorganic phosphate, and fibroblast growth factor 23 (FGF23), in a gender-specific manner.In multivariate stepwise linear regression analysis in which age, blood pressure, eGFR, corrected calcium, inorganic phosphate, and FGF23 were entered as potential covariates, SUA was selected as a factor significantly associated with LVEF, LVMI, and plasma levels of BNP in both genders. On the other hand, however, after adding diuretic use as a potential covariate, the association between SUA and LVEF lost statistical significance in both genders, and that between SUA and BNP lost significance among female patients. These findings suggest that diuretic use is a non-negligible confounder in understanding the observed association between SUA and cardiac dysfunction and heart failure.In summary, SUA is associated with left ventricular hypertrophy independent of confounding factors including FGF23 and diuretic use in female and male patients. Whether lowering SUA can influence the progression of cardiac remodeling awaits further investigation.

Background: The diagnosis of Immunoglobulin G4 (IgG4)-related disease (IgG4-RD), in general, depends on serum IgG4 concentrations and histopathological findings; therefore, diagnosis of IgG4-RD in cardiovascular organs/tissues is often difficult owing to the risk of tissue sampling., Methods: Prevalence of IgG4-positive lymphoplasmacytic infiltration in 103 consecutive cardiovascular surgical samples from 98 patients with various cardiovascular diseases was analyzed immunohistochemically., Results: The diagnoses of the enrolled patients included aortic aneurysm (abdominal, n = 8; thoracic, n = 9); aortic dissection (n = 20); aortic stenosis (n = 24), aortic regurgitation (n = 10), and mitral stenosis/regurgitation (n = 17). In total, 10 (9.7%) of the 103 specimens showed IgG4-positive cell infiltration with various intensities; five of these were aortic valve specimens from aortic stenosis, and IgG4-positive cell infiltration was present at >10 /HPF in three of them. In one aortic wall sample from an abdominal aortic aneurysm, various histopathological features of IgG4-RD, such as IgG4-positive cell infiltration, obliterating phlebitis, and storiform fibrosis, were observed., Conclusions: IgG4-positive cell infiltration was observed in 9.7% of the surgical cardiovascular specimens, mainly in the aortic valve from aortic stenosis and in the aortic wall from aortic aneurysm. Whether IgG4-positive cell infiltration has pathophysiological importance in the development or progression of cardiovascular diseases should be investigated in future studies.

Background: Few data have existed on myocardial postsystolic shortening (PSS) accounting for left ventricular (LV) diastolic dysfunction in systemic hypertension. We examined this relationship, along with clinical and other cardiac parameters, in asymptomatic patients with hypertension., Methods: We analyzed 104 patients on pharmacological treatment for hypertension who had no signs or symptoms of heart failure for conventional and speckle tracking echocardiography. The sum of the postsystolic index for multiple LV segments (total PSI) and global longitudinal strain (GLS) was computed and used as measures for global PSS and myocardial systolic function, respectively. The tissue Doppler e' and the speckle tracking-derived global strain rate during early diastole (e'sr) were obtained as indicators of LV relaxation. The circumferential end-systolic stress was also determined noninvasively and substituted for a measure of myocardial afterload., Results: Main variables that correlated with the e' and e'sr were shown to be age, LV mass index, left atrial volume index, GLS, and the total PSI. Multivariate analysis including gender, circumferential end-systolic stress, and the use of calcium channel blockers as possible covariates revealed that age (β = -0.29, P = 0.002), total PSI (β = -0.26, P = 0.008), and LV mass index (β = -0.25, P = 0.017) were significant independent determinants of e' and that age (β = -0.34, P < 0.001) and GLS (β = -0.28, P = 0.006) were of e'sr., Conclusions: Our findings indicate that while depending on the degree of GLS, PSS may affect diastolic relaxation in patients with asymptomatic, but treated, hypertensive patients., (© 2015, Wiley Periodicals, Inc.)

Elevated eosinophil count was shown to be associated with the development of cholesterol embolization syndrome, a potentially life-threatening condition, after catheter-based procedures. We investigated the association between stages of chronic kidney disease (CKD) and the absolute eosinophil count (AEC) among cardiac patients. CKD stages were determined solely on the estimated glomerular filtration rate or requirement for hemodialysis. Eosinophilia is defined as an eosinophil count exceeding 500/μL. A total of 1022 patients were enrolled in the current study, and eosinophil counts (/μL) in the first through fourth eosinophil count quartiles were <88, 88 to 154, 155 to <238, and 238 ≤, respectively, and 29 patients (2.8 %) had eosinophilia. Correlation coefficient between the AEC and age was -0.188 (P = 0.001) in women and -0.042 (n.s.) in men (by Spearman's correlation test). Patients with higher CKD stages had a higher prevalence of the highest AEC quartile or eosinophilia. Logistic regression analysis using severe renal dysfunction (i.e., CKD stage 4 or 5) as the dependent variable, the highest AEC quartile had a significant positive association with an odds ratio of 1.99 (95 % confidence interval, 1.20-3.31, P < 0.01) after adjustment for sex, age, systolic blood pressure, and total white blood cell count. Similarly, after adjustment for the same variables, eosinophilia was associated with severe renal dysfunction with an odds ratio of 2.60 (95 % confidence interval, 1.08-6.26, P < 0.05). Eosinophil count was positively associated with higher CKD stages among cardiology patients, some fraction of which might be related to subclinical cholesterol embolization.

Besides regulating calcium-phosphate metabolism, fibroblast growth factor-23 (FGF23) and Klotho have been proposed to have other roles in heart and vasculature. For example, FGF23 has been associated with cardiac hypertrophy and reduced left ventricular ejection fraction among patients with chronic kidney disease and cardiovascular disorders. The purpose of the study was to investigate whether serum FGF23 and α-Klotho concentrations are associated with cardiac diastolic dysfunction and related parameters among cardiac patients with preserved left ventricular ejection fraction. The current study enrolled 269 patients (69 women, 200 men) who were admitted to our cardiology department between October 2012 and January 2014 and had a left ventricular ejection fraction of >50%. Cardiac diastolic function was assessed by blood flow and tissue Doppler velocities, plasma B-type natriuretic peptide (BNP) concentration, and cardiac hypertrophy. After adjusting for sex, and age, logistic regression analysis showed that log(α-Klotho), but not log(FGF23), was significantly associated with diastolic dysfunction. After further adjustment for renal function, blood hemoglobin, and serum albumin levels, the negative association between log(α-Klotho) and diastolic dysfunction retained statistical significance with an odds ratio of 0.50 (95% confidence interval 0.31-0.81, P = 0.005, per 1 standard deviation). Among patients with preserved LVEF, serum α-Klotho concentrations were negatively associated with diastolic dysfunction. Whether modulation of serum levels α-Klotho will ameliorate cardiac diastolic function among patients with this disorder awaits further investigation.

Background: Acute cholecystitis sometimes displays symptoms and electrocardiographic changes mimicking cardiovascular problems. It may also coexist with cardiovascular disorders. We analyzed the clinical characteristic of the cardiac patients who were diagnosed with acute cholecystitis during hospitalization in the cardiology department., Methods: Using the department database, we identified 16 patients who were diagnosed with acute cholecystitis during the hospitalization in the cardiology department between June 2010 and June 2014., Results: Five patients who were initially suspected to have cardiac problems (acute coronary syndrome, four patients; Adams-Stokes syndrome, one patient) owing to their symptoms were subsequently diagnosed with acute cholecystitis. Two of these patients showed electrocardiographic changes mimicking myocardial ischemia, and three tested positive for a biomarker (heart-type fatty acid binding protein) of acute myocardial injury. The 11 remaining cardiac patients were diagnosed with acute cholecystitis during their hospitalization or at the time of admission. Prolonged fasting and/or staying in an intensive care unit (ICU) may have contributed to their condition. Among these 11 patients, aortic dissection was the most prevalent underlying cardiac condition, affecting 5 patients., Conclusions: Although it is a rare condition, acute cholecystitis may coexist with or be misdiagnosed as a cardiovascular disorder. This possibility should not be overlooked in cardiac patients because a delay in treatment may result in critical complications.

Background: Subjects with high fibroblast growth factor 21(FGF21) and 23 (FGF23), endocrine hormones that regulate insulin sensitivity and phosphate metabolism, respectively, are reported to have a higher risk for adverse cardiovascular outcome. Therefore, the relationship of FGF21, FGF23, and α-Klotho (co-receptor for FGF23 signaling) with mean platelet volume (MPV) and platelet distribution width (PDW), two platelet volume indices that reflect platelet activity, was investigated., Methods: Data from 156 patients admitted to the cardiology department were analyzed. MPV and PDW were measured by an automatic blood counter, and serum FGF21, FGF23, and α-Klotho concentrations were measured by an enzyme-linked immunoassay., Results: Log(FGF21) was significantly correlated with serum triglycerides but did not differ according to the use of non-use of antidiabetic or lipid-lowering drugs. MPV and PDW were significantly correlated (R=0.475, p<0.001). MPV was significantly correlated with log(FGF21) (R=-0.167, p<0.05) and log(FGF23) (R=0.351, p<0.001) but not with log(α-Klotho). Linear regression analysis showed a negative and positive association of log(FGF21) and log(FGF23), respectively, with MPV that was independent of possible confounders including sex, age, renal function, and antithrombotic drug use. In addition, log(FGF23) was found to have a significant independent positive association with PDW., Conclusions: Among cardiac patients, FGF21 had a negative association with MPV, whereas FGF23 had a positive association. Future studies of serum FGF23/FGF21 concentrations and the incidence of thromboembolic disorders are warranted.

Serum uric acid (SUA) is associated with the severity and prognosis of systolic heart failure. We investigated the potential association between SUA and cardiac diastolic dysfunction among total of 744 cardiac patients (202 women and 542 men) who had preserved left ventricular ejection fraction. Presence of diastolic dysfunction was assessed by echocardiographic data, plasma B-type natriuretic peptide concentration, and left ventricular hypertrophy. Univariate analysis showed that the prevalence of diastolic dysfunction increased with increasing SUA value in women, but not in men. When sex-nonspecific SUA quartiles were used, multivariate logistic regression analysis, among female patients who were not taking uric acid lowering medication, showed that the third (SUA, 5.7-6.4 mg) and the fourth (SUA, ≥6.5 mg/dl) SUA quartiles were associated with diastolic dysfunction with an odds ratio of 3.25 (P < 0.05) and 8.06 (P < 0.001), respectively, when compared with the first SUA quartile (≤4.7 mg/dl). When sex-specific SUA quartiles were used among these population, multivariate logistic regression analysis showed that the fourth SUA quartile (≥5.7 mg/dl) was associated with diastolic dysfunction with an odds ratio of 5.34 (P < 0.05) when compared with the first SUA quartile (≤4.1 mg/dl). By contrast, the relationship between SUA and diastolic dysfunction was not significant in men, irrespective of which of the sex-nonspecific or sex-specific SUA quartiles were used. These data indicated that among cardiac patients with preserved ejection fraction, SUA was significantly associated with diastolic dysfunction in women but not in men., (Copyright © 2015 the American Physiological Society.)

Background: Mean platelet volume (MPV) and platelet distribution width (PDW) are indices that reflect platelet activity. We investigated the association between these platelet indices and left ventricular hypertrophy and cardiac function., Methods: We analyzed the data of 1241 patients who were admitted to the Cardiology Department., Results: Both MPV and PDW were selected as independent factors associated with left ventricular systolic and diastolic dysfunction, and left ventricular hypertrophy. The highest tertile of MPV and PDW was associated with left ventricular systolic dysfunction (left ventricular ejection fraction of <50 %) with an odds ratio of 1.53 and 2.03, respectively, when the respective lowest tertile was used as reference. The highest PDW tertile was associated with left ventricular hypertrophy with an odds ratio of 1.56 (95 % CI, 1.13-2.15) and with dysfunction with an odds ratio of 3.34 (95 % CI, 1.54-7.25)., Conclusions: Indices of platelet activation (MPV and/or PDW) were independently associated positively with left ventricular hypertrophy and left ventricular systolic and diastolic dysfunction. Whether these platelet indices represent useful markers for identifying individuals at higher risk for thromboembolic disease and organ damage among cardiac patients awaits further investigation.

Background: Atrial fibrillation (AF) occurs more frequently among patients with renal dysfunction. We investigated the possible association between prevalence of AF and serum fibroblast growth factor 23 (FGF23), which has been shown to be increased in subjects with renal dysfunction., Methods and Results: Among the total enrollment of 851 cardiac patients, 188 patients had AF (paroxysmal AF, 95; non-paroxysmal AF, 93). Prevalence of AF for FGF23 octile had a U-shaped relationship with the lowest prevalence at the fifth octile. On logistic regression analysis, when the third FGF23 quartile was used as the reference, the first and fourth FGF23 quartiles were associated with prevalence of AF with an odds ratio (OR) of 3.34 (95% confidence interval [CI]: 1.89-5.88) and 2.58 (95% CI: 1.45-4.58), respectively, after adjusting for confounding factors including estimated glomerular filtration rate (eGFR). Among the subgroup of 416 patients for whom serum parathyroid hormone and 25-hydroxy vitamin D data were available, OR of the first and the fourth FGF23 quartile were calculated to be 3.52 and 2.97, respectively, when further adjusted for these two variables in the statistical model., Conclusions: Serum FGF23 had a U-shaped relationship with prevalence of AF among Japanese cardiac patients, which was independent of other calcium/phosphate metabolism-related parameters and eGFR. Pathophysiology underlying the observed link, if at all, awaits further investigation.