Malnutrition is associated with sarcopenia, cachexia, and prognosis. We investigated the usefulness of phase angle (PhA) as a marker of sarcopenia, cachexia, and malnutrition in 412 hospitalized patients with cardiovascular disease. We analyzed body composition with bioelectrical impedance analysis, and nutritional status such as controlling nutritional status (CONUT) score. Both skeletal muscle mass index (SMI) and PhA correlated with age, grip strength and knee extension strength (p < 0.0001) in both sexes. The SMI value correlated with CONUT score, Hb, and Alb in males. Phase angle also correlated with CONUT score, Hb, and Alb in males, and more strongly associated with these nutritional aspects. In females, PhA was correlated with Hb and Alb (p < 0.001). In both sexes, sarcopenia incidence was 31.6% and 32.4%; PhA cut-off in patients with sarcopenia was 4.55° and 4.25°; and cachexia incidence was 11.5% and 14.1%, respectively. The PhA cut-off in males with cachexia was 4.15°. Multivariate regression analysis showed that grip strength and brain natriuretic peptide (BNP) were independent determinants of SMI, whereas grip strength, BNP, and Hb were independent determinants of PhA. Thus, PhA appears to be a useful marker for sarcopenia, malnutrition, and cachexia in hospitalized patients with cardiovascular disease.
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: β = −0.423, p < 0.001; Hb: β = −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.
Obstructive sleep apnea (OSA) is highly associated with cardiovascular diseases, but most patients remain undiagnosed. Cyclic variation of heart rate (CVHR) occurs during the night, and R-R interval (RRI) analysis using a Holter electrocardiogram has been reported to be useful in screening for OSA. We investigated the usefulness of RRI analysis to identify OSA using the wearable heart rate sensor WHS-1 and newly developed algorithm. WHS-1 and polysomnography simultaneously applied to 30 cases of OSA. By using the RRI averages calculated for each time series, tachycardia with CVHR was identified. The ratio of integrated RRIs determined by integrated RRIs during CVHR and over all sleep time were calculated by our newly developed method. The patient was diagnosed as OSA according to the predetermined criteria. It correlated with the apnea hypopnea index and 3% oxygen desaturation index. In the multivariate analysis, it was extracted as a factor defining the apnea hypopnea index (r = 0.663, p = 0.003) and 3% oxygen saturation index (r = 0.637, p = 0.008). Twenty-five patients could be identified as OSA. We developed the RRI analysis using the wearable heart rate sensor WHS-1 and a new algorithm, which may become an expeditious and cost-effective screening tool for identifying OSA.
Vascular endothelial dysfunction is part of the underlying pathophysiology of heart failure. However, there are no reports in which vascular endothelial function of both conduit arteries and microvasculature was assessed in patients with heart failure. This study was aimed to assess vascular endothelial function separately in heart failure with reduced (HFrEF) and preserved ejection fraction (HFpEF). We performed simultaneous measurement of both flow-mediated vasodilation for endothelial function of conduit arteries and reactive hyperemia-peripheral arterial tonometry for that of microvasculature in 88 consecutive patients with chronic heart failure. In 55 patients with ischemic heart disease as an underlying cause of heart failure, flow-mediated vasodilation value was comparable between the two groups of HFrEF (left ventricular ejection fraction < 50%, n = 31) and HFpEF (left ventricular ejection fraction ≥ 50%, n = 24). Reactive hyperemia index measured by reactive hyperemia peripheral arterial tonometry, however, was lower in HFrEF patients compared to HFpEF patients (P = 0.014). In contrast, among 33 patients with non-ischemic heart disease, the degree of flow-mediated vasodilation was lower in HFpEF patients (n = 18) compared with HFrEF patients (n = 15) (P = 0.009), while reactive hyperemia index was comparable between the two groups. The clinical and pathophysiological significance of endothelial function in heart failure differs between conduit artery and microvasculature, and these differences may contribute to the underlying pathophysiology of HFpEF and HFrEF, as well as in ischemic heart disease and non-ischemic heart disease.
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.
Introduction: Atrial fibrosis plays an important role in atrial remodeling and the development of atrial fibrillation (AF). Left atrium (LA) strain (LAS) measured by two-dimensional speckle tracking echocardiography (2DS) has been reported to be a useful method to predict the degree of atrial fibrosis. Hypothesis: To investigate whether LAS is an early marker of atrial fibrosis in cardiovascular surgery patients. Methods: Conventional echocardiography and 2DS method were performed in 131 patients (53 AF, 78 sinus rhythm (SR)) including cardiac valve disease (MR, AS, and CABG et al.). The mRNA and microRNA expression were analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR) in 59 cases in which LA tissues were removed from the appendage. Results: Left atrial reservoir strain (LASr) negatively correlated with left atrial volume index (LAVI), and E/e’ and positively correlated with LVEF, and left atrial conduit strain (LAScd). LASr was significantly lower, and LAVI was higher in AF group. The fibrosis-related (COL1A, COL3A1, TGFβ1) and peroxisome proliferator-activated receptor-α (PPARα)-related (PPARα, PGC1α, CPT1B) genes expression as a metabolic remodeling showed a positive association with atrial ANP mRNA expression level, reflecting atrial pressure and mechanical stretching. The expression level of COL1A and TGFβ1 mRNA was higher in AF group, compared with SR group. LASr, but not LAVI, negatively correlated with the expression of COL1A1, TGFβ1, and miR21. Multivariate regression analysis showed that LASr was an independent predictor of COL1A1, TGFβ1, or miR21 expression. The PPARα-related gene expression did not correlate with LASr, and LVEF in SR group, while they had a significant negative correlation with LVEF in AF patients. AF patients (LVEF<58%) had higher expression level of the PPARα-related genes, compared with those (LVEF≥58%). Conclusions: Low LASr exhibits increased atrial fibrosis, and LASr is extremely useful as an early marker for predicting atrial fibrosis and consequently AF in cardiovascular surgery patients. Furthermore, in progressed AF patients, overexpression of PPARα signaling may play a role in atrial degeneration eventually to leading to heart failure.
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