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It has been established that obstructive sleep apnea (OSA) is an independent risk factor for atherosclerosis. Chronic intermittent hypoxia (CIH) activates sympathoadrenal system and upregulates β3 adrenergic receptor (β3 AR). However, the effect of selective β3 AR agonist mirabegron in CIH-induced atherosclerosis remains unknown. We generated a CIH-induced atherosclerosis model through exposing ApoE−/− mice to CIH (8 h per day, cyclic inspiratory oxygen fraction 5–21%, 60-s cycle) for 6 weeks after 4-week high-fat dieting and investigated the effects of mirabegron, a selective β3 AR agonist, on CIH-induced atherosclerosis. The coronary endarterectomy (CE) specimens from coronary artery disease patients with OSA and without OSA were collected. The expression of β3 AR was significantly elevated in CIH-induced atherosclerosis model. Furthermore, treatment with mirabegron (10mg/kg per day by oral administration for 6 weeks) ameliorated atherosclerosis in ApoE−/− mice in CIH but not in normoxia. Mechanistically, mirabegron activated β3 AR and ameliorated intraplaque oxidative stress by suppressing p22phox expression and reactive oxygen species (ROS) level. In addition, in human CE specimens, β3 AR was also upregulated associated with increased p22phox expression and ROS level both in the lumen and in the plaque of coronary artery in OSA subjects. This study first demonstrated that mirabegron impeded the progression of CIH-induced atherosclerosis, at least in part, via β3 AR–mediated oxidative stress, suggesting a promising therapeutic strategy for protecting against atherosclerosis induced by CIH.

Background: Obstructive sleep apnea is an atherogenesis factor of which chronic intermittent hypoxia is a prominent feature. Chronic intermittent hypoxia (CIH) exposure can sufficiently activate the sympathetic system, which acts on the β3 adrenergic receptors of brown adipose tissue (BAT). However, the activity of BAT and its function in CIH-induced atherosclerosis have not been fully elucidated.Methods: This study involved ApoE−/− mice which were fed with a high-fat diet for 12 weeks and grouped into control and CIH group. During the last 8 weeks, mice in the CIH group were housed in cages to deliver CIH (12 h per day, cyclic inspiratory oxygen fraction 5–20.9%, 180 s cycle). Atherosclerotic plaques were evaluated by Oil Red O, hematoxylin and eosin, Masson staining, and immunohistochemistry. Afterward, we conducted immunohistochemistry, western blotting, and qRT-PCR of uncoupling protein 1 (UCP1) to investigate the activation of BAT. The level of serum total cholesterol (TC), triglyceride, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and free fatty acid (FFA) were measured. Finally, RNA-Sequencing was deployed to explore the differentially expressed genes (DEGs) and their enriched pathways between control and CIH groups.Results: Chronic intermittent hypoxia exposure promoted atherosclerotic plaque area with increasing CD68, α-SMA, and collagen in plaques. BAT activation was presented during CIH exposure with UCP1 up-regulated. Serum TC, triglyceride, LDL-c, and FFA were increased accompanied by BAT activation. HDL-c was decreased. Mechanistically, 43 lipolysis and lipid metabolism-associated mRNA showed different expression profiling between the groups. Calcium, MAPK, and adrenergic signaling pathway included the most gene number among the significantly enriched pathways.Conclusion: This study first demonstrated that BAT activation is involved in the progression of CIH-induced atherosclerosis, possibly by stimulating lipolysis.

The therapeutic effect of plasma exchange (PE) on hypertriglyceridemic acute pancreatitis (HTGAP) is unclear. Therefore, we aimed to explore this therapeutic effect.This study included 204 patients with HTGAP who underwent treatment at two provincial tertiary grade A hospitals in Fujian Province from October 2012 to May 2021. Patients were divided into a conventional group and a PE group. The Student's t-test and chi-square test were used for data analysis.Among 204 patients, 56 and 148 were included in the PE and conventional groups, respectively. After propensity score matching (PSM), the PE and conventional groups each had 42 patients. There was no significant difference in age; sex; pregnancy; comorbidities; laboratory findings; incidences of complications, and multiple organ dysfunction syndrome (MODS); organ support treatment; surgical rate; mortality; and hospital stay between the groups (p 0.05). The total expenses were significantly higher in the PE group than in the conventional group (p 0.05). There was no statistically significant difference in the times of PE; total volume of PE; incidences of complications, and MODS; organ support treatment; surgical rate; mortality; and hospital stay between the early PE and delayed PE groups (p 0.05). All patients in the PE group and conventional group with acute renal failure had significantly higher D-dimer levels than those without acute renal failure (p 0.05).Compared with conventional treatment, PE does not have a better therapeutic effect on HTGAP. The D-dimer level can predict whether patients with HTGAP will have acute renal failure.

This study aimed to evaluate the relationship between grayscale intravascular ultrasound-attenuated plaque (AP) and poststenting plaque prolapse (PP) as well as their influence on creatine kinase-myocardial band (CK-MB) elevation after drug-eluting stent (DES) implantation.The relationship between baseline AP and poststenting PP and their impacts on percutaneous coronary intervention (PCI) are not well known.A total of 141 single, native, de-novo coronary lesions in 141 patients with normal pre-PCI CK-MB levels who underwent intravascular ultrasound before and after DES implantation were studied.AP was found in 72 (51.1%) lesions and PP occurred in 43 (30.5%) lesions. Baseline AP was associated with greater plaque area, lesion eccentricity, and positive remodeling, and was associated with higher frequency of poststenting PP (47.2 vs. 13.0%, P0.001) as well as greater poststenting PP volume (2.2±1.3 vs. 1.9±1.1 mm, P=0.045). Elevated CK-MB levels were observed in 34 (24.1%) lesions and significantly more frequently in patients with baseline AP and poststenting PP than without both of these findings. Multivariate analysis indicated that AP with PP was the predictor of post-PCI CK-MB elevation.Baseline AP was associated with high-risk characteristics, higher frequency, and greater volume of poststenting PP accompanied by CK-MB elevation in patients with DES implantation.

There is no reliable way to identify the high-risk patients with intermediate coronary artery lesions (diameter stenosis 20%-70%) in early stage. Soluble CXC chemokine ligand 16 (CXCL16) is a newly discovered chemokine that can mediate inflammatory responses. It is released by proteolytic cleavage of its membrane-bound form, named scavenger receptor for phosphatidylserine and oxidized lipoprotein (SR-PSOX) that can promote the uptake of oxidized low-density lipoprotein cholesterol by macrophages. We have hypothesized that CXCL16 is an indicator of the prognosis of intermediate coronary artery lesions, and thus assessed the association between plasma CXCL16 concentrations and the 2-year prognosis in 616 patients with intermediate coronary artery lesions. The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, revascularization and angina pectoris requiring re-hospitalization. During the median follow-up time of 24 months, 69 events occurred. The plasma concentrations of CXCL16 (median 7712.88 pg/ml vs. 6792.43 pg/ml, P = 0.014) and high-sensitivity C-reactive protein (hs-CRP) (median 2.82 mg/L vs. 1.68 mg/L, P < 0.001) were higher in patients with events than patients without events. Cox hazard proportion analysis showed patients in upper CXCL16 quartile were more likely to suffer from adverse outcome than patients in lower quartile (RR = 1.271, P = 0.029, 95% CI: 1.025-1.577) after adjusting for sex, age, smoking, hypertension, diabetes, fat, dyslipidemia, hs-CRP, and medication use. In conclusion, plasma level of CXCL16 is an independent predictor of the prognosis of the patients with intermediate coronary lesions. Elevated plasma CXCL16 is associated with higher risk for these patients.

Percutaneous coronary intervention with drug-eluting stents (DES) may achieve midterm outcomes comparable to coronary artery bypass grafting (CABG) for unprotected left main coronary artery disease, but few real-world, long-term studies have been reported. In this study, 376 patients with unprotected left main coronary artery disease who underwent DES implantation (n = 131) or CABG (n = 245) were evaluated, and outcomes were compared using propensity analyses to adjust for baseline differences. Overall, 367 patients (98%) had complete clinical follow-up for a median of 4.0 years (interquartile range 3.2 to 4.7). Although the overall sample size was limited, there was a trend toward lower mortality with DES versus CABG in unadjusted (hazard ratio [HR] 0.50, 95% confidence interval [CI] 0.20 to 1.22, p = 0.13), multivariate-adjusted (HR 0.37, 95% CI 0.13 to 1.09, p = 0.07), and propensity score-adjusted (HR 0.34, 95% CI 0.12 to 1.03, p = 0.06) analyses. Treatment with DES was associated with a higher rate of target-vessel revascularization (TVR; 18% vs 9%, p = 0.02). However, ischemic TVR was not significantly different between the 2 groups (25% vs 39%, p = 0.15) in patients who received angiographic follow-up. No differences were detected in the occurrence of composite major adverse cardiac and cerebrovascular events between DES and CABG (27% vs 22%, p = 0.42). In conclusion, during 4-year follow-up, overall composite major adverse cardiac and cerebrovascular events were similar after DES and CABG treatment of unprotected left main coronary artery disease, with a trend toward lower mortality after percutaneous coronary intervention with DES. DES were associated with a higher rate of TVR compared to CABG, but ischemic TVR was not significantly different between the 2 groups.

BACKGROUND: This article aims to investigate the changes of plasma cystatin C concentration (PcyC), and to evaluate the relationship between PcyC and acute coronary syndrome. METHODS: A total of 126 consecutive patients with coronary artery disease (CAD) were enrolled in this study, consisting of 34 patients with stable angina pectoris (SAP), 56 patients with unstable angina pectoris (UAP), 36 patients with acute myocardial infarction (AMI), and 34 healthy subjects as controls. Plasma cystatin C, high sensitivity C‐reactive protein (hs‐CRP), total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein cholesterol (HDL‐C), triglycerides (TG), and uric acid (UA) in all subjects were determined. All patients were followed up for 6 months and adverse cardiovascular events were recorded. RESULTS: Plasma cystatin C was elevated in CAD. Cystatin C levels were significantly higher in UAP patients than those in SAP patients and controls (2013.83 ± 633.85 ng/mL vs 1348.41 ± 369.62 ng/mL and 1509.99 ± 408.65 ng/mL, P < 0.05), but were much lower than those in AMI patients (2013.83 ± 633.85 ng/mL vs 2873.55 ± 1149.48 ng/mL, P < 0.05). Patients with AMI also exhibited significantly higher cystatin C levels than SAP patients and the control group (2873.55 ± 1149.48 ng/mL vs 1348.41 ± 369.62 ng/mL and 1509.99 ± 408.65 ng/mL, P < 0.01). Much higher hs‐CRP concentrations were found in UAP patients (1.58 ± 2.81 mg/L, P < 0.05) and AMI patients (20.68 ± 18.98 mg/L, P < 0.01). Cystatin C was positively and significantly correlated with age, hs‐CRP, white blood cells (WBC), creatinine, and UA (r > 0, P < 0.05), whereas a significantly negative correlation was observed with HDL‐C (r = − 0.227, P < 0.05). These coefficients were clearly high for creatinine (r = + 0.612) and WBC (r = + 0.459). During the 6 month follow‐up, 26 patients were found with adverse cardiovascular events and had significantly higher cystatin C levels than the 22 control patients at admission (2356.73 ± 897.64 ng/mL vs 1469.51 ± 574.83 ng/mL, P < 0.01). CONCLUSIONS: Cystatin C plays an important role in the development of CAD and PcyC is a strong predictor for risk of cardiovascular events. Copyright © 2009 Wiley Periodicals, Inc.

Our aim in this study was to investigate the changes of serum high-sensitive C-reactive protein (hs-CRP) and uric acid (UA), and evaluate the synergistic effect of amlodipine and atorvastatin on blood pressure and left ventricular remodeling in hypertensive patients with primary hypercholesterolemia. One hundred and twenty-six hypertensive patients with hypercholesterolemia were randomized into amlodipine group (10 mg/day, group A, n = 65) and amlodipine (10 mg/day) plus atorvastatin group (20 mg/day, group B, n = 61), treated for 4 months continuously. Serum concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, hs-CRP, and UA were determined, and blood pressure of both groups was examined before and after treatment. Left ventricular posterior wall thickness and interventricular spectum thickness were measured by echocardiography, and left ventricular mass index (LVMI) was calculated. After 4-months of treatment with atorvastatin, serum concentrations of total cholesterol, low-density lipoprotein cholesterol, triglycerides, hs-CRP, and UA were significantly decreased in group B (P < 0.05, P < 0.01), while serum concentrations of high-density lipoprotein cholesterol was elevated (P < 0.05). Meanwhile, systolic blood pressure and diastolic blood pressure were reduced in both groups (P < 0.05), and blood pressure in group B was markedly lower than that in group A after treatment (P < 0.05). Compared with that before treatment, LVMI in both groups decreased (P < 0.05), to a significantly lower degree in group B than in group A (P < 0.05). Atorvastatin can decrease serum concentrations of hs-CRP and UA. The amlodipine-atorvastatin combination markedly reduces blood pressure and reverses left ventricular hypertrophy more than amlodipine monotherapy. The positive effect suggests that in hypertensive and hypercholesterolemic patients, the combination of amlodipine and atorvastatin could be the treatment of choice.