It has been reported that the triglyceride-glucose (TyG) index may serve as a simple and credible surrogate marker of insulin resistance (IR). However, its association with macrovascular and ...microvascular damage is unclear. Accordingly, the objective of the present study is to investigate the association of macrovascular and microvascular damage with the TyG index.
A total of 2830 elderly participants from the Northern Shanghai Study (NSS) were enrolled. The TyG index was calculated as lnfasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2. Parameters of vascular damage, including carotid-femoral pulse wave velocity (cf-PWV), brachial-ankle pulse wave velocity (ba-PWV), ankle-brachial index (ABI), carotid intima-media thickness (CMT), carotid plaque, estimated glomerular filtration rate (eGFR) and the urine albumin-to-creatinine ratio (UACR), were measured and calculated.
In univariate logistic regression, an increased TyG index was associated with a higher risk of cf-PWV > 10 m/s, ba-PWV > 1800 cm/s, ABI < 0.9, microalbuminuria (MAU) and chronic kidney disease (CKD). In multivariable logistic regression, there was a significant increase in the risk of cf-PWV > 10 m/s (OR = 1.86, 95% confidence interval 95% CI 1.37-2.53, P
< 0.001), ba-PWV > 1800 cm/s (OR = 1.39, 95% CI 1.05-1.84, P
= 0.02), MAU (OR = 1.61, 95% CI 1.22-2.13, P
< 0.001) and CKD (OR = 1.67, 95% CI 1.10-1.50, P
= 0.02) after adjustment for age, sex, BMI, waist circumference, smoking habit, hypertension, family history of premature CVD, diabetes, HDL-C, LDL-C, insulin therapy and statin therapy. However, no significant relationship was observed between the TyG index and lower extremity atherosclerosis, carotid hypertrophy or carotid plaque.
An elevated TyG index was significantly associated with a higher risk of arterial stiffness and nephric microvascular damage. This conclusion lends support to the clinical significance of the TyG index for the assessment of vascular damage.
The application of multiparametric magnetic resonance imaging (mpMRI) for diagnosis of prostate cancer has been recommended by the European Association of Urology (EAU), National Comprehensive Cancer ...Network (NCCN), and European Society of Urogenital Radiology (ESUR) guidelines. The purpose of this study is to systematically review the literature on assessing the accuracy of mpMRI in patients with suspicion of prostate cancer.
We searched Embase, Pubmed and Cochrane online databases from January 12,000 to October 272,018 to extract articles exploring the possibilities that the pre-biopsy mpMRI can enhance the diagnosis accuracy of prostate cancer. The numbers of true- and false-negative results and true- and false-positive ones were extracted to calculate the corresponding sensitivity and specificity of mpMRI. Study quality was assessed using QUADAS-2 tool. Random effects meta-analysis and a hierarchical summary receiver operating characteristic (HSROC) plot were performed for further study.
After searching, we acquired 3741 articles for reference, of which 29 studies with 8503 participants were eligible for inclusion. MpMRI maintained impressive diagnostic value, the area under the HSROC curve was 0.87 (95%CI,0.84-0.90). The sensitivity and specificity for mpMRI were 0.87 95%CI, 0.81-0.91 and 0.68 95%CI,0.56-0.79 respectively. The positive likelihood ratio was 2.73 95%CI 1.90-3.90; negative likelihood ratio was 0.19 95% CI 0.14,-0.27. The risk of publication bias was negligible with P = 0.96.
Results of the meta-analysis suggest that mpMRI is a sensitive tool to diagnose prostate cancer. However, because of the high heterogeneity existing among the included studies, further studies are needed to apply the results of this meta-analysis in clinic.
Gut microbiota dysbiosis has been considered to be an important risk factor that contributes to coronary artery disease (CAD), but limited evidence exists about the involvement of gut microbiota in ...the disease. Our study aimed to characterize the dysbiosis signatures of gut microbiota in coronary artery disease. The gut microbiota represented in stool samples were collected from 70 patients with coronary artery disease and 98 healthy controls. 16S rRNA sequencing was applied, and bioinformatics methods were used to decipher taxon signatures and function alteration, as well as the microbial network and diagnostic model of gut microbiota in coronary artery disease. Gut microbiota showed decreased diversity and richness in patients with coronary artery disease. The composition of the microbial community changed; Escherichia-Shigella false discovery rate (FDR = 7.5*10
and Enterococcus (FDR = 2.08*10
) were significant enriched, while Faecalibacterium (FDR = 6.19*10
), Subdoligranulum (FDR = 1.63*10
), Roseburia (FDR = 1.95*10
), and Eubacterium rectale (FDR = 2.35*10
) were significant depleted in the CAD group. Consistent with the taxon changes, functions such as amino acid metabolism, phosphotransferase system, propanoate metabolism, lipopolysaccharide biosynthesis, and protein and tryptophan metabolism were found to be enhanced in CAD patients. The microbial network revealed that Faecalibacterium and Escherichia-Shigella were the microbiotas that dominated in the healthy control and CAD groups, respectively. The microbial diagnostic model based on random forest also showed probability in identifying those who suffered from CAD. Our study successfully identifies the dysbiosis signature, dysfunctions, and comprehensive networks of gut microbiota in CAD patients. Thus, modulation targeting the gut microbiota may be a novel strategy for CAD treatment.
Background
Carotid‐femoral pulse‐wave velocity (cf‐PWV) and brachial‐ankle PWV (ba‐PWV) are the 2 most frequently applied PWV measurements. However, little is known about the comparison of ...hypertensive target organ damage (TOD) with cf‐PWV and ba‐PWV.
Methods and Results
A total of 1599 community‐dwelling elderly subjects (age >65 years) in northern Shanghai were recruited from June 2014 to August 2015. Both cf‐PWV and ba‐PWV were measured using SphygmoCor and VP1000 systems, respectively. Within the framework of comprehensive cardiovascular examinations, risk factors were assessed, and asymptomatic TOD, including left ventricular mass index, peak transmitral pulsed Doppler velocity/early diastolic tissue Doppler velocity (E/Ea), carotid intima‐media thickness, arterial plaque, creatinine clearance rate, and urinary albumin‐creatinine ratio were all evaluated. Both PWVs were significantly associated with male sex, age, waist/hip circumference, fasting plasma glucose, and systolic blood pressure, and ba‐PWV was also significantly related to body mass index. Both PWVs were significantly correlated with most TOD. When cf‐PWV and ba‐PWV were both or separately put into the stepwise linear regression model together with cardiovascular risk factors and treatment, only cf‐PWV, but not ba‐PWV, was significantly associated with carotid intima‐media thickness and creatinine clearance rate (P<0.05). When cf‐PWV and ba‐PWV were both or separately put into the same full‐mode model after adjustment for confounders, only cf‐PWV, but not ba‐PWV, showed significant association with carotid intima‐media thickness and creatinine clearance rate (P<0.05). Similar results were observed in logistic regression analysis.
Conclusions
Taken together, in the community‐dwelling elderly Chinese, cf‐PWV seems to be more closely associated with hypertensive TOD, especially vascular and renal TOD, as compared with ba‐PWV.
Clinical Trial Registration
URL: http://www.clinicaltrials.gov. Unique identifier: NCT02368938.
Abstract
Aims
Conventional fractional flow reserve (FFR) is measured invasively using a coronary guidewire equipped with a pressure sensor. A non-invasive derived FFR would eliminate risk of coronary ...injury, minimize technical limitations, and potentially increase adoption. We aimed to evaluate the diagnostic performance of a computational pressure-flow dynamics derived FFR (caFFR), applied to coronary angiography, compared to invasive FFR.
Methods and results
The FLASH FFR study was a prospective, multicentre, single-arm study conducted at six centres in China. Eligible patients had native coronary artery target lesions with visually estimated diameter stenosis of 30–90% and diagnosis of stable or unstable angina pectoris. Using computational pressure-fluid dynamics, in conjunction with thrombolysis in myocardial infarction (TIMI) frame count, applied to coronary angiography, caFFR was measured online in real-time and compared blind to conventional invasive FFR by an independent core laboratory. The primary endpoint was the agreement between caFFR and FFR, with a pre-specified performance goal of 84%. Between June and December 2018, matched caFFR and FFR measurements were performed in 328 coronary arteries. Total operational time for caFFR was 4.54 ± 1.48 min. caFFR was highly correlated to FFR (R = 0.89, P = 0.76) with a mean bias of −0.002 ± 0.049 (95% limits of agreement −0.098 to 0.093). The diagnostic performance of caFFR vs. FFR was diagnostic accuracy 95.7%, sensitivity 90.4%, specificity 98.6%, positive predictive value 97.2%, negative predictive value 95.0%, and area under the receiver operating characteristic curve of 0.979.
Conclusions
Using wire-based FFR as the reference, caFFR has high accuracy, sensitivity, and specificity. caFFR could eliminate the need of a pressure wire, technical error and potentially increase adoption of physiological assessment of coronary artery stenosis severity.
Clinical Trial Registration
URL: http://www.chictr.org.cn Unique Identifier: ChiCTR1800019522.
Cardiac hypertrophy is a common pathophysiological process in various cardiovascular diseases, which still has no effective therapies. Irisin is a novel myokine mainly secreted by skeletal muscle and ...is believed to be involved in the regulation of energy metabolism. In the present study, we found that irisin expression was elevated in hypertrophic murine hearts and serum. Moreover, angiotension II-induced cardiomyocyte hypertrophy was attenuated after irisin administration and aggravated after irisin knockdown
Next, we generated transverse aortic constriction (TAC)-induced cardiac hypertrophy murine model and found that cardiac hypertrophy and fibrosis were significantly attenuated with improved cardiac function assessed by echocardiography after irisin treatment. Mechanistically, we demonstrated that FNDC5 was cleaved into irisin, at least partially, in a disintegrin and metalloproteinase (ADAM) family-dependent manner. ADAM10 was the candidate enzyme responsible for the cleavage. Further, we found irisin treatment activated AMPK and subsequently inhibited activation of mTOR. AMPK inhibition ablated the protective role of irisin administration. In conclusion, we find irisin is secreted in an ADAM family-dependent manner, and irisin treatment improves cardiac function and attenuates pressure overload-induced cardiac hypertrophy and fibrosis mainly through regulating AMPK-mTOR signaling.
Several studies have assessed the effect of angiotensin II receptor blockers (ARBs) on peripheral endothelial dysfunction as measured by flow-mediated vasodilatation (FMD), a widely-used indicator ...for endothelial function. We conducted a meta-analysis to investigate the effect in comparison to placebo or no treatment and other antihypertensives.
MEDLINE, Cochrane library and EMBASE were searched to September 2013 for randomized controlled trials (RCTs) that assessed the effect of ARBs versus placebo or no treatment and other antihypertensives (angiotensin-converting enzyme inhibitors (ACEIs), calcium channel blockers (CCBs), β-blockers, diuretics) by forearm FMD. Furthermore, we also use meta-regression to analyze the relationship between the endothelial function and the duration of ARBs treatments.
In 11 trials including 590 patients, ARBs (n = 315) significantly improved FMD (1.36%, 95% confidence internal CI:1.28 to 1.44) versus placebo or no treatment (n = 275). In 16 trials that included 1028 patients, ARBs (n = 486) had a significant effect (0.59%, 95% CI: 0.25 to 0.94) on FMD when compared with other antihypertensives (n = 542). In 8 trials, ARBs (n = 174) had no significant effect (-0.14%, 95% CI: -0.32 to 0.03) compared with ACEI (n = 173). Compared with others, the benefits of ARBs, respectively, were 1.67% (95% CI: 0.65 to 0.93) in 7 trials with CCBs, 0.79% (95% CI: 0.42 to 1.01) with β-blockers in 3 trials and 0.9% (95% CI: 0.77 to 1.03) with diuretics in 3 trials. Importantly, we found ARBs were less effective in a long time span (95% CI: -1.990 to -0.622) than the first 6 months (95% CI: -0.484 to 0.360).
This study shows that ARBs improve peripheral endothelial function and are superior to CCBs, β-blockers and diuretics. However, the effect couldn't be maintained for a long time. In addition, there was no significant difference between ARBs and ACEI.
DNA methylation plays an important role in chronic diseases such as atherosclerosis, yet the mechanisms are poorly understood. The objective of our study is to indicate the regulatory mechanisms of ...DNA methylation in vascular smooth muscle cells (VSMCs) and its roles in atherosclerosis.
In ApoE
mice fed a Western diet, DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine, significantly attenuated atherosclerotic lesions (20.1±2.2% versus 30.8±7.5%; P=0.016) and suppressed DNA methyltransferase activity and concomitantly decreased global 5-methylcytosine content in atherosclerotic lesions of ApoE
mice. Using a carotid ligation model, we found that 5-aza-2'-deoxycytidine also dramatically inhibited neointimal formation (intimal area: 2.25±0.14×10
versus 4.07±0.22×10
μm
; P<0.01). Abnormal methylation status at the promoter of ten-eleven translocation 2, one of the key demethylation enzymes in mammals, was ameliorated after 5-aza-2'-deoxycytidine treatment, which in turn caused an increase in global DNA hydroxymethylation and 5-hydroxymethylcytosine enrichment at the promoter of Myocardin. In vitro, 5-aza-2'-deoxycytidine treatment or DNA methyltransferase 1 knockdown decreased global 5-methylcytosine content and restored Myocardin expression in VSMCs induced by platelet-derived growth factor, thus preventing excessive VSMCs dedifferentiation, proliferation, and migration. Furthermore, DNA methyltransferase 1 binds to ten-eleven translocation 2 promoter and is required for ten-eleven translocation 2 methylation in VSMCs.
The inhibitory effects of DNA demethylation on global 5-methylcytosine content and ten-eleven translocation 2 hypermethylation in atherosclerotic aorta can recover 5-hydroxymethylcytosine enrichment at the Myocardin promoter and prevent VSMC dedifferentiation and vascular remodeling.
Heart failure (HF) is the single largest cause for increased hospitalization after fine particulate matter (PM2.5) exposure. Patients with left HF often progress to right ventricular (RV) failure ...even with optimal medical care. An increase of PM2.5 of 10 μg per cubic meter was associated with a 76% increase in the risk of death from cardiovascular disease in 4 years' period. However, the role and mechanism of PM2.5 in HF progression are not known. Here we investigated the role of PM2.5 exposure in mice with existing HF mice produced by transverse aortic constriction (TAC). TAC-induced HF caused lung inflammation, vascular remodeling and RV hypertrophy. We found increased PM2.5 profoundly exacerbated lung oxidative stress in mice with existing left HF. To our surprise, PM2.5 exposure had no effect on LV hypertrophy and function, but profoundly exacerbated lung inflammation, vascular remodeling, and RV hypertrophy in mice with existing left HF. These striking findings demonstrate that PM2.5 and/or air pollution is a critical factor for overall HF progression by regulating lung oxidative stress, inflammation and remodeling as well as RV hypertrophy. Improving air quality may save HF patients from a dismal fate.
The proliferation, migration and dedifferentiation of vascular smooth muscle cells (VSMCs) exert crucial roles in atherosclerosis (AS) progression. The aim of our study was to explore the influences ...of circular RNA 0004872 (circ_0004872) in platelet-derived growth factor-BB (PDGF-BB)-induced AS cell model and investigate the underlying mechanisms. Real-time quantitative polymerase chain reaction (RT-qPCR) was implemented for the expression detection of circ_0004872, mitogen-activated protein kinase 1 (MAPK1) messenger RNA (mRNA), microRNA-513a-5p (miR-513a-5p) and thioredoxin interacting protein (TXNIP). Cell proliferation was analyzed via Cell Counting Kit 8 (CCK8) assay. Cell migration was assessed via wound healing assay and transwell migration assay. Western blot assay was used to measure the expression of alpha smooth muscle actin (α-SMA), osteopontin (OPN), calponin and TXNIP. Dual-luciferase reporter assay and RNA-pull down assay were used for confirmation of interaction between miR-513a-5p and circ_0004872 or TXNIP. Circ_0004872 expression was elevated in PDGF-BB-induced human aortic vascular smooth muscle cells (HA-VSMCs) and carotid plaque tissues. Circ_0004872 silencing alleviated PDGF-BB-induced proliferation, migration and dedifferentiation in HA-VSMCs. MiR-513a-5p bound to circ_0004872, and circ_0004872 knockdown-induced effects in PDGF-BB-treated HA-VSMCs were largely attenuated by the silencing of miR-513a-5p. MiR-513a-5p bound to the 3′ untranslated region (3′UTR) of TXNIP, and miR-513a-5p overexpression-mediated effects were counteracted by the transfection of pcDNA-TXNIP in PDGF-BB-induced HA-VSMCs. TXNIP was modulated by circ_0004872/miR-513a-5p signaling cascade in HA-VSMCs. Circ_0004872 accelerated PDGF-BB-induced proliferation, migration and dedifferentiation in HA-VSMCs through enhancing TXNIP level via sponging miR-513a-5p.
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