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.
Angiography derived fractional flow reserve (angio-FFR) has been proposed. This study aimed to assess its diagnostic performance with cadmium-zinc-telluride single emission computed tomography ...(CZT-SPECT) as reference.
Patients underwent CZT-SPECT within 3 months of coronary angiography were included. Angio-FFR computation was performed using computational fluid dynamics. Percent diameter (%DS) and area stenosis (%AS) were measured by quantitative coronary angiography. Myocardial ischemia was defined as a summed difference score ≥ 2 in a vascular territory. Angio-FFR ≤ 0.80 was considered abnormal. 282 coronary arteries in 131 patients were analyzed. Overall accuracy of angio-FFR to detect ischemia on CZT-SPECT was 90.43%, with a sensitivity of 62.50% and a specificity of 98.62%. The diagnostic performance (= area under ROC = AUC) of angio-FFR AUC = 0.91, 95% confidence intervals (CI) 0.86–0.95 was similar as those of %DS (AUC = 0.88, 95% CI 0.84–0.93, p = 0.326) and %AS (AUC = 0.88, 95% CI 0.84–0.93 p = 0.241) by 3D-QCA, but significantly higher than those of %DS (AUC = 0.59, 95% CI 0.51–0.67, p < 0.001) and %AS (AUC = 0.59, 95% CI 0.51–0.67, p < 0.001) by 2D-QCA. However, in vessels with 50–70% stenoses, AUC of angio-FFR was significantly higher than those of %DS (0.80 vs. 0.47, p < 0.001) and %AS (0.80 vs. 0.46, p < 0.001) by 3D-QCA and %DS (0.80 vs. 0.66, p = 0.036) and %AS (0.80 vs. 0.66, p = 0.034) by 2D-QCA.
Angio-FFR had a high accuracy in predicting myocardial ischemia assessed by CZT-SPECT, which is similar as 3D-QCA but significantly higher than 2D-QCA. While in intermediate lesions, angio-FFR is better than 3D-QCA and 2D-QCA in assessing myocardial ischemia.
Background
Chronic kidney disease is a global health problem that is closely related to the aging population. Although plasma glucose levels have been shown to be related to renal dysfunction, risk ...factors for renal functional impairment in the geriatric population are unknown. The authors therefore aimed to investigate the determinants of renal functional impairment in an elderly population.
Methods
From June 2014 to August 2015, 912 participants (aged > 65 years) were recruited. Renal function was assessed at baseline; follow-up was conducted in 2016. Within the framework of comprehensive cardiovascular examinations, all conventional cardiovascular risk factors, fasting plasma glucose (FPG), and renal function were assessed. Renal function was evaluated by the estimated glomerular filtration rate (e-GFR) using a modified Modification of Diet in Renal Disease formula. Rapid decline in e-GFR was defined as an e-GFR slope > 5 mL/min per 1.73 m
2
per year.
Results
We observed that FPG levels were significantly higher in participants with (6.15 ± 2.76 mmol/L) than in those without (5.56 ± 1.61 mmol/L) a rapid decline in e-GFR (
p
= 0.02). The average decline in e-GFR was 0.149 mL/min/1.73m
2
per year in this elderly population, and the increasing risk of having rapid decline in e-GFR was 0.44-fold each year. In the full adjustment model, decline in e-GFR (
p
= 0.02) and rapid decline in e-GFR (OR1.33, 95% CI 1.03–1.72) were significantly associated with FPG, independent of other conventional cardiovascular risk factors. Using the same models, decline in e-GFR (
p
= 0.04) and rapid decline in e-GFR (OR 1.57, 95% CI 1.05–2.35) were also significantly associated with FPG in diabetic population, but they were not in non-diabetic population.
Conclusions
In community-dwelling elderly Chinese, the average decline in e-GFR was 0.149 mL/min/1.73m
2
per year. FPG control is important for delaying renal functional impairment in elderly population.
Trial registration
NSS, NCT02368938
Background. Catheter ablation combined with left atrial appendage closure (LAAC) was reported as a feasible strategy for atrial fibrillation (AF) patients with high risk of stroke or ...contraindications of oral anticoagulants. We aimed to observe the short-term safety and efficacy of combining cryoballoon ablation (CBA) with LAAC in paroxysmal (PAF) patients. Method and Results. From Jan 2016 to Dec 2017, 304 patients diagnosed with nonvalvular, drug-refractory PAF were included, who underwent either CBA alone (n = 262) or combined procedure (n = 42). Instant pulmonary vein isolation (PVI) with CBA was achieved in all patients, while successful LAAC achieved in 41 (97.6%) of combined procedure patients. 1-year freedom of AF rate was lower in combined procedure group (84.7% vs 70.7%, p=0.04), with unadjusted hazard ratio (HR = 1.97) and 95% confidence interval (CI) 1.03–3.77. However, the multivariate COX model revealed left atrial diameter (p=0.002, HR = 1.10, and 95% CI 1.04, 1.17), rather than procedure type (p=0.51, HR = 1.34, and 95% CI 0.57, 3.17), was the predictor for freedom of AF. Only 2 patients in the CBA group had stroke, contributing to the nonsignificant higher stroke incidence (p=1.00). Transoesophageal echochardiography (TEE) achieved in 35 patients (83.3%) showed complete occlusion with no obvious residual flow (>3 mm), Device-related thrombosis, or pericardial perfusion. All-cause mortality, rehospitalization, and complication rates were similar. Conclusion. Combining CBA with LAAC in a single procedure is a feasible strategy for PAF patients, with comparable short-term safety and efficacy to CBA alone.
Left atrial appendage morphology has been proved to be an important predictor of left atrial thrombus (LAT) and left atrial spontaneous echo contrast (LASEC) and stroke in patients with non-valvular ...atrial fibrillation (NVAF). However, the relation between left atrial appendage (LAA) lobes and LAT or LASEC is still unknown. The aim of this study is to investigate the correlation between the number of left atrial appendage lobes and LAT/LASEC in patients with NVAF.
This monocentric cross-sectional study enrolled 472 consecutive patients with non-valvular atrial fibrillation, who had transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) prior to cardioversion or left atrial appendage closure (LAAC) from July 2009 to August 2015 in department of cardiology of Shanghai Tenth People's Hospital. Patients who had significant mitral or aortic valve disease, previous cardiac valvular surgery and other complicated cardiac diseases were excluded. Individuals were divided into two groups:the LAT/LASEC group (16.95%), which comprised patients with LAT or LASEC, as confirmed by TEE; and a negative control group (83.05%).Baseline overall group characterization with demographic, clinical, laboratory data and echocardiographic parameters, alongside with information on medication was obtained for all patients. Subgroup analysis with line chart was applied for exploring the association between LAA lobes and LAT/LAESC. Receptor-operating curves (ROC) were used to test the value of LA anteroposterior diameter detected by different echocardiography methods predicting LAT or LASEC. Multivariable logistic regression analysis was used to investigate independent predictors of LAT/LASEC.
Among 472 patients, 23 (4.87%) had LA/LAA thrombus and 57 (12.1%) had LA spontaneous echo contrast. Compared to the negative group, patients in LAT/LASEC group had higher CHA
DS
-VASc score (3.79 ± 1.75 vs 2.65 ± 1.76, p < 0.001), larger LAD (measured by TTE, 48.1 ± 7.7 vs 44.6 ± 6.5, P < 0.001; measured by TEE, 52.2 ± 6.2 vs 46.7 ± 7.1, P < 0.001), lower left upper pulmonary venous flow velocity (LUPVFV) (0.54 ± 0.17 m/s vs 0.67 ± 0.26 m/s, CI 95% 0.05-0.22, P = 0.003), more left atrial appendage lobes (1.67 ± 0.77 vs 1.25 ± 0.50, p < 0.001). There was a good discriminative capacity for LAD detected by TTE (area under the curve (AUC), 0.67, CI 95% 0.61-0.73, p < 0.001) and LAD detected by TEE (AUC, 0.73, CI 95% 0.67-0.79, p < 0.001). The subgroup analysis based on gender and different LAA lobes yielded similar results (male group: p < 0.001;female group: p = 0.004) that the number of LAA lobes were significantly associated with LA thrombus or SEC. In multivariable logistic regression analysis, both the number of LAA lobes (odds ratio: 2.37; CI 95% 1.37-4.09; p = 0.002) and the persistent AF (odds ratio: 3.57; CI 95% 1.68-7.57; p = 0.001) provided independent and incremental predictive value beyond CHA
DS
-VASc score.
The number of LAA lobes is an independent risk factor and has a moderate predictive value for LAT/LASEC among NVAF patients in China.
While specific patterns of circulating dendritic cells (DCs) and monocytes are associated with the incidence of coronary artery disease, the characterization of circulating DC and monocyte subsets in ...patients with different stages of atherosclerosis remains unclear.
Forty-eight patients with unstable angina pectoris (UAP) diagnosed by angiography were enrolled. Likewise, 31 patients with ST-segment elevation myocardial infarction (STEMI) were enrolled and confirmed with the presence of thrombosis by angiography. Plaque features of 48 UAP patients were evaluated at the culprit lesions by OCT. Circulating myeloid DCs (mDCs), plasmacytoid DCs (pDCs) and monocyte subsets were analyzed using flow cytometry.
The proportions and absolute counts of mDC2s, which specifically express CD141 and possess the ability to activate CD8+ T lymphocytes, significantly decreased in patients with UAP and STEMI when compared with controls (0.08 × 10
± 0.05 × 104/ml and 0.08 × 10
± 0.06 × 104/ml vs. 0.11 × 10
± 0.06 × 104/ml, p = 0.027). On the other hand, patients with UAP and STEMI had significantly higher proportions and counts of Mon2 subsets. In the OCT subgroup, patients with thin-cap fibroatheroma (TCFA) had higher proportions and absolute number of Mon2 (11.96% ± 4.27% vs. 9.42% ± 4.05%, p = 0.034; 5.17 × 104/ml ± 1.92 × 104/ml vs. 3.53 × 104/ml ± 2.65 × 104/ml, p = 0.045) than those without TCFA. However, there was no remarkable difference in mDC2s between patients with and without TCFA.
Circulating Mon2 appears to be a promising marker for the severity of atherosclerotic plaque.
Translocase of inner membrane 50 (TIM50) is a member of the translocase of inner membrane (TIM) complex in the mitochondria. Previous research has demonstrated the role of TIM50 in the regulation of ...oxidative stress and cardiac morphology. However, the role of TIM50 in pathological cardiac hypertrophy remains unknown.
In the present study we found that the expression of TIM50 was downregulated in hypertrophic hearts. Using genetic loss-of-function animal models, we demonstrated that TIM50 deficiency increased heart and cardiomyocyte size with more severe cardiac fibrosis compared with wild-type littermates. Moreover, we generated cardiomyocyte-specific TIM50 transgenic mice in which the hypertrophic and fibrotic phenotypes were all alleviated. Next, we tested reactive oxygen species generation and the activities of the antioxidant enzymes superoxide dismutase and catalase, and also respiratory chain complexes I, II, and IV, finding that all the activities were regulated by TIM50. Meanwhile, expression of the ASK1-JNK/P38 axis was increased in TIM50-deficient mice, and TIM50 overexpression decreased the activity of the ASK1-JNK/P38 axis. Finally, we treated mice with the antioxidant N-acetyl cysteine to reduce oxidative stress. After N-acetyl cysteine treatment, the deteriorative hypertrophic and fibrotic phenotypes caused by TIM50 deficiency were all remarkably reversed.
These data indicated that TIM50 could attenuate pathological cardiac hypertrophy primarily by reducing oxidative stress. TIM50 could be a promising target for the prevention and therapy of cardiac hypertrophy and heart failure.
Diesel particulate extract (DPE), which is a significant constituent of airborne particle pollution, has a strong association with the development of cancer and respiratory diseases. Fulvic acid ...(FA), a plentiful organic macromolecule found in water, has the capability to modify particle surface charge and adsorption capacity when combined with minerals. Nevertheless, there is a scarcity of data regarding the influence of their interaction on DPE toxicity. To examine the impact of environmental factor on the toxic effects of DPE, we used the Caenorhabditis elegans (C. elegans) model to investigate the reproductive toxicity of DPE and FA on insulin signaling pathway. C. elegans were subjected to a semi-fluid medium (NGG) containing different concentrations of DPE or DPE + FA in order to assess germline apoptosis and the expression of important genes in the insulin signaling pathway. Through several mutant strains, we found that daf-2, age-1, pdk-1, akt-1 and daf-16 were involved in DPE-induced apoptosis. Furthermore, and the expression levels of these genes significantly altered. The ratio of daf-16 translocation to nucleation, as well as the amount of reactive oxygen species (ROS), exhibited a dose-response relationship, however, the presence of FA could altered these effects. The results revealed that the insulin signaling pathway plays a vital role in mediating the harmful effects caused by DPE, whereas environmental factors have a substantial impact on its toxicity. Moreover, it was noted that semi-fluid medium could effectively replicate three-dimensional exposure circumstances closely resembling those observed in actual situations.
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•The semi-fluid NGG has more advantages and sensitivity for evaluating the toxicity of DPE.•Diesel particulate extract modulates the apoptosis of germ cells via the insulin signaling pathway.•Under the presence of environmental factor fulvic acid, the damage caused by DPE is significantly weakened.
A La(OTf)3‐catalyzed domino method has been developed to synthesize the cis‐1,4‐benzoxazine derivatives from 2‐furylcarbinols 1 and o‐aminophenol derivatives, by a Piancatelli/C–N coupling/Michael ...addition process. A wide array of substrates could be used to give the desired products in good yields. Since this method involves simple reaction conditions and short reaction times, and has a broad substrate scope, it is particularly attractive for the efficient development of libraries of biologically relevant 1,4‐benzoxazine derivatives. Furthermore, a similar strategy was also successfully applied to form 1,2,3,4‐tetrahydroquinoxaline derivatives from 1 and N‐substituted o‐diaminobenzenes.
A La(OTf)3‐catalyzed domino method has been developed to synthesize the cis‐1,4‐benzoxazine derivatives by a Piancatelli/C–N coupling/Michael addition process. A similar strategy was used to form 1,2,3,4‐tetrahydroquinoxaline derivatives from 1 and N‐substituted o‐diaminobenzenes. This method should be valuable for the construction of heterocycles with biological and medicinal activities.
BK polyomavirus (BKV) is widespread among humans, asymptomatically infecting children and then persisting in renal tissue. The transcriptional control region (TCR) of the BKV genome is variable among ...clinical isolates. Thus, archetypal TCRs with a common basic configuration generally occur in BKV isolates from the urine of immunocompromised patients, but rearranged TCRs that possibly arise from the archetypal configuration have also been detected in clinical specimens. To examine the hypothesis that archetypal strains represent wild-type strains circulating in the human population (the archetype hypothesis), we analysed 145 complete viral genomes amplified directly from the urine of non-immunocompromised individuals worldwide. These genomes included 82, three, two and 58 sequences classified as belonging to subtypes I, II, III and IV, respectively. Rearranged TCRs with long duplications or deletions were detected from two subtype I and two subtype IV genomes, but not from the other 141 genomes (thus, the TCRs of these genomes were judged to be archetypal). The variations in the archetypal TCRs were nucleotide substitutions and single-nucleotide deletions, most of which were unique to particular subtypes or subgroups. We confirmed that the four complete BKV genomes with rearranged TCRs did not form a unique lineage on a phylogenetic tree. Collectively, the findings demonstrate that the archetypal TCR configuration has been conserved during the evolution of BKV, providing support for the archetype hypothesis. Additionally, we suggest that 'archetype' should be used as a conceptual term that denotes a prototypical structure that can generate various rearranged TCRs during viral growth in vivo and in vitro.
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