Association Between Barthel's Index Change and All-Cause Mortality Among COVID-19 Pneumonia Patients Aged Over 80 Years Old: A Retrospective Cohort Study.

Purpose: It has been shown that lower Barthel's index (BI) at admission is associated with a higher in-hospital mortality. There is a lack of evidence regarding the association between the change in BI during hospitalization and mortality after discharge. Our purpose was to determine whether the BI change during hospitalization is associated with all-cause mortality in older adults with COVID-19 pneumonia. Patients and Methods: We conducted a retrospective cohort study of 330 participants at Peking University Third Hospital during the COVID-19 pandemic period. In order to analyze the time to death data, a Kaplan-Meier survival curve was used. We used restricted cubic splines to analyze the association between BI change and all-cause mortality among COVID-19 pneumonia patients aged over 80 years old. Threshold effect analysis was used to assess the ability of BI change score to predict all-cause mortality. Results: Our study included 330 patients aged over 80 years with COVID-19 pneumonia. The Kaplan-Meier curve for mortality showed significantly worst survival with reduced BI among three groups (χ2= 6.896, P < 0.05). There was a non-linear association between the BI change and all-cause mortality (P for all over <0.001). The effect sizes on the left and right sides of the inflection point were 0.958 (HR: 0.958, 95% CI 0.932-0.958, P < 0.05) and 1.013 (HR: 1.013, 95% CI 0.967-1.062, P > 0.05), respectively. Conclusion: Reduced BI during hospitalization was associated with the highest mortality risk. It is crucial to monitor BI change among COVID-19 pneumonia patients aged over 80 years old.

Globular CTRP3 promotes mitochondrial biogenesis in cardiomyocytes through AMPK/PGC-1α pathway.

BACKGROUND: Mitochondrial biogenesis is crucial for the maintenance of mitochondrial function and cellular homeostasis. C1q/tumor necrosis factor-related protein-3 (CTRP3) is an adipokine that owns multiple functions on metabolic and cardiovascular diseases. However, whether CTRP3 affects mitochondrial biogenesis in cardiomyocytes remains unknown. METHODS: Neonatal rat ventricular myocytes were cultured and treated with globular CTRP3 (gCTRP3). The expression of mitochondrial biogenesis related genes was measured by real-time PCR and western blot analysis. Mitochondrial morphology was assessed by a transmission electron microscope. ATP content, oxygen consumption rate (OCR), and sirtuin1 activity were measured with commercial kits. RESULTS: gCTRP3 increased the expression of peroxisome proliferators activated receptor-γ co-activator-1α (PGC-1α), nuclear respiratory factor 1 (NRF-1), NRF-2, mitochondrial transcription factor A (TFAM), cytochrome B, and oxidative phosphorylation complexes III and V, and increased mitochondrial cristae components and OCR. Additionally, gCTRP3 enhanced mitochondrial DNA copy number and ATP content, while the induction was inhibited by knockdown of PGC-1α via small interfering RNA. gCTRP3 increased phosphorylation of AMP-activated protein kinase (AMPK), whereas adenine 9-ß-d-arabinofuranoside (AraA), an AMPK inhibitor, attenuated gCTRP3-mediated induction of NRF-1, TFAM, and complexes III and V. gCTRP3 increased both the expression and activity of sirtuin1, whereas inhibition of sirtuin1 by EX-527 attenuated gCTRP3-induced responses. Meanwhile, gCTRP3-mediated activation of sirtuin1 was attenuated by AraA. Moreover, gCTRP3 restored the reduction of sirtuin1, PGC-1α, NRF-1, complex III and ATP content induced by hypoxia-reoxygenation injury. CONCLUSION: CTRP3 promotes mitochondrial biogenesis in cardiomyocytes via AMPK/PGC-1α pathway. GENERAL SIGNIFICANCE: CTRP3 is an endogenous modulator for mitochondrial biogenesis, and may protect cardiomyocytes by ameliorating mitochondrial dysfunction.

Coronary flow velocity reserve is improved by PPAR-α agonist fenofibrate in patients with hypertriglyceridemia.

INTRODUCTION: Fenofibrate, an agonist of peroxisome proliferator-activated receptor-α (PPAR-α), has a vascular protective effect. AIMS: We investigated the effect of the PPAR-α agonist on coronary artery endothelial function in patients with hypertriglyceridemia. METHODS: Fifty-eight patients with hypertriglyceridemia were divided into two groups: control (no treatment; n = 23) and fenofibrate treatment (n = 35), 200 mg/d, for 6 months. The patients had undergone rest and adenosine treatment to induce hyperemia for quantification of coronary flow velocity reserve (CFVR) by noninvasive Doppler echocardiography before treatment and at 6-month follow-up. Pulse wave velocity (PWV) was measured before treatment and at 6-month follow-up. RESULTS: CFVR was significantly improved with fenofibrate treatment as compared with baseline level and control group (3.14 ± 0.36 vs. 2.80 ± 0.58 and 2.79 ± 0.65, P < 0.01 and 0.05, respectively), with no difference between baseline levels and untreated controls. In addition, at 6 months, plasma level of homocysteine was significantly increased with fenofibrate treatment as compared with at baseline and control group (median 18.13 [range 14.46-22.02]µmol/L vs. 14.09 [12.01-18.81] and 13.34 [9.69-17.06]µmol/L, P < 0.001 and 0.01, respectively). Furthermore, at 6 months, PWV was significantly decreased with fenofibrate treatment as compared with control group (1446 ± 136 cm/s vs. 1570 ± 203 cm/s, P < 0.05). CONCLUSIONS: Treatment with PPAR-α agonist fenofibrate significantly improved CFVR and arterial stiffness in patients with hypertriglyceridemia. This endothelial protective effect may be reduced in part by the side effect of increasing homocysteine.

[Correlation of large artery stiffness and coronary flow velocity reserve].

OBJECTIVE: Coronary flow velocity reserve (CFVR) is an important indicator of coronary endothelial functions and microcirculation. Pulse wave velocity (PWV) reflects the degree of aortic sclerosis and it is an independent predictor of cardiovascular events. The present study was designed to evaluate the correlation of large artery stiffness and CFVR. METHODS: A total of 101 consecutive subjects were enrolled to measure the brachial-ankle pulse wave velocity (baPWV). According to the presence or absence of higher baPWV (> 1400 cm/s), they were divided into 2 groups. Transthoracic echocardiography was employed to measure coronary flow velocity in coronary left anterior descending (LAD). Then after an intravenous infusion of adenosine triphosphate, the velocity of blood flow was measured when the vessel was in maximal dilation. The ratio of flow velocity of those in maximal dilation to those at rest was CFVR. RESULTS: The subjects with a higher baPWV (> 1400 cm/s) were markedly elder and had higher risks of hypertension and diabetes. Thus age, hypertension and diabetes contributed to arteriosclerosis. More importantly, the subjects with a higher baPWV (> 1400 cm/s) had a much lower level of CFVR (2.66 ± 0.74 vs 2.95 ± 0.76; P < 0.01) than those with a lower baPWV (< 1400 cm/s). Furthermore correlation analysis showed that CFVR and baPWV levels were significantly negatively correlated (r = -0.35, P < 0.01). CONCLUSIONS: A negative correlation exists between artery stiffness and coronary flow velocity reserve. The increased vascular stiffness may impair coronary endothelial function, cause the dysfunction of coronary microcirculation and raise the risks of cardiovascular events.

PPAR-α Agonist Fenofibrate Upregulates Tetrahydrobiopterin Level through Increasing the Expression of Guanosine 5'-Triphosphate Cyclohydrolase-I in Human Umbilical Vein Endothelial Cells.

Tetrahydrobiopterin (BH4) is an essential cofactor for endothelial nitric oxide (NO) synthase. Guanosine 5'-triphosphate cyclohydrolase-I (GTPCH-I) is a key limiting enzyme for BH4 synthesis. In the present in vitro study, we investigated whether peroxisome proliferator-activated receptor α (PPAR-α) agonist fenofibrate could recouple eNOS by reversing low-expression of intracellular BH4 in endothelial cells and discussed the potential mechanisms. After human umbilical vein endothelial cells (HUVECs) were treated with lipopolysaccharide (LPS) for 24 hours, the levels of cellular eNOS, BH4 and cell supernatant NO were significantly reduced compared to control group. And the fluorescence intensity of intracellular ROS was significantly increased. But pretreated with fenofibrate (10 umol/L) for 2 hours before cells were induced by LPS, the levels of eNOS, NO, and BH4 were significantly raised compared to LPS treatment alone. ROS production was markedly reduced in fenofibrate group than LPS group. In addition, our results showed that the level of intracellular GTPCH-I detected by western blot was increased in a concentration-dependent manner after being treated with fenofibrate. These results suggested that fenofibrate might help protect endothelial function and against atherosclerosis by increasing level of BH4 and decreasing production of ROS through upregulating the level of intracellular GTPCH-I.