LncRNA CARMN inhibits abdominal aortic aneurysm formation and vascular smooth muscle cell phenotypic transformation by interacting with SRF.

Phenotypic transformation of vascular smooth muscle cells (VSMCs) plays a crucial role in abdominal aortic aneurysm (AAA) formation. CARMN, a highly conserved, VSMC-enriched long noncoding RNA (lncRNA), is integral in orchestrating various vascular pathologies by modulating the phenotypic dynamics of VSMCs. The influence of CARMN on AAA formation, particularly its mechanisms, remains enigmatic. Our research, employing single-cell and bulk RNA sequencing, has uncovered a significant suppression of CARMN in AAA specimens, which correlates strongly with the contractile function of VSMCs. This reduced expression of CARMN was consistent in both 7- and 14-day porcine pancreatic elastase (PPE)-induced mouse models of AAA and in human clinical cases. Functional analyses disclosed that the diminution of CARMN exacerbated PPE-precipitated AAA formation, whereas its augmentation conferred protection against such formation. Mechanistically, we found CARMN's capacity to bind with SRF, thereby amplifying its role in driving the transcription of VSMC marker genes. In addition, our findings indicate an enhancement in CAMRN transcription, facilitated by the binding of NRF2 to its promoter region. Our study indicated that CARMN plays a protective role in preventing AAA formation and restrains the phenotypic transformation of VSMC through its interaction with SRF. Additionally, we observed that the expression of CARMN is augmented by NRF2 binding to its promoter region. These findings suggest the potential of CARMN as a viable therapeutic target in the treatment of AAA.

Association between admission plasma 2-oxoglutarate levels and short-term outcomes in patients with acute heart failure: a prospective cohort study.

BACKGROUND: 2-oxoglutarate (2OG), an intermediate metabolite in the tricarboxylic acid cycle, has been found to associate with chronic heart failure (HF), but its effect on short-term adverse outcomes in patients with acute HF (AHF) is uncertain. METHODS: This prospective cohort study included 411 consecutive hospitalized patients with AHF. During hospitalization, fasting plasma samples were collected within the first 24 h of admission. Plasma 2OG levels were measured by hydrophilic interaction liquid chromatography-liquid chromatography tandem mass spectrometry (HILIC-LC/MS/MS). All participants were followed up for six months. Multiple logistic regression was used to determine the odds ratio (OR) and 95% confidence interval (CI) for primary outcomes. RESULTS: The AHF cohort consisted of HF with preserved ejection fraction (EF) (64.7%), mid-range EF (16.1%), and reduced EF (19.2%), the mean age was 65 (±13) years, and 65.2% were male. Participants were divided into two groups based on median 2OG levels (µg/ml): low group (< 6.0, n = 205) and high group (≥6.0, n = 206). There was a relatively modest correlation between 2OG and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels (r = 0.25; p < 0.001). After adjusting for age, sex, and body mass index, we found that the progression of the NYHA classification was associated with a gradual increase in plasma 2OG levels (p for trend< 0.001). After six months of follow-up, 76 (18.5%) events were identified. A high baseline 2OG level was positively associated with a short-term rehospitalization and all-cause mortality (OR: 2.2, 95% CI 1.3-3.7, p = 0.003), even after adjusting for NT-proBNP and estimated glomerular filtration rate (eGFR) (OR: 1.9, 95% CI 1.1-3.4, p = 0.032). After a similar multivariable adjustment, the OR was 1.4 (95% CI 1.1-1.7, p = 0.018) for a per-SD increase in 2OG level. CONCLUSIONS: High baseline 2OG levels are associated with adverse short-term outcomes in patients with AHF independent of NT-proBNP and eGFR. Hence plasma 2OG measurements may be helpful for risk stratification and treatment monitoring in AHF. TRIAL REGISTRATION: ChiCTR-ROC-17011240 . Registered 25 April 2017.

ß-blockers and risk of all-cause mortality in patients with chronic heart failure and atrial fibrillation-a meta-analysis.

BACKGROUND: Effects of ß-blockers on outcomes in patients with chronic heart failure (CHF) and atrial fibrillation (AF) is still in controversy. METHODS: Searching was conducted by using keywords "atrial fibrillation", and "heart failure" in PubMed, MEDLINE and Embase databases before November 30, 2017. Prospective studies [i.e. randomized control trials (RCTs), post-hoc analysis of RCTs, prospective cohort studies and registry studies] that studied the effect of ß-blockers and all-cause mortality in patients with CHF and AF were included. The analysis was stratified by study design. RESULTS: We identified 12 studies, including 6 post-hoc analysis of RCTs and 6 observational studies (including prospective registry studies and prospective cohort studies), which enrolled 38,133 patients with CHF and AF. Overall, ß-blockers treatment was associated with significant decrease in all-cause mortality [Risk Ratio (RR) =0.73; 95% Confidence Interval (CI) 0.65-0.82, P < 0.001]. When stratified by study design, ß-blockers treatment was associated with 34% reduction in patients with CHF and AF in observational study (RR = 0.66; 95% CI 0.58-0.76, P < 0. 001), but not in post-hoc analysis of RCT (RR = 0.87; 95% CI 0.74-1.02, P = 0.09). CONCLUSIONS: ß-blockers treatment was associated with significantly decrease the risk of all-cause mortality in patients with AF-CHF and it was only seen in observational study group, but not in subgroup analysis of RCT group. Further large RCTs are required to verify the effect of ß-blockers treatment on patients with CHF and AF. The main limitation of this study is the lack of individual data on patients in each study.

The top tertile of hematocrit change during hospitalization is associated with lower risk of mortality in acute heart failure patients.

BACKGROUND: Hemoconcentration has been proposed as surrogate for changes in volume status among patients hospitalized with acute heart failure (AHF) and is associated with a favorable outcome. However, there is a dearth of research assessing the clinical outcomes of hospitalized patients with hemoconcentration, hemodilution and unchanged volume status. METHODS: We enrolled 510 consecutive patients hospitalized for AHF from April 2011 to July 2015. Hematocrit (HCT) levels were measured at admission and either at discharge or on approximately the seventh day of admission. Patients were stratified by delta HCT tertitles into hemodilution (ΔHCT ≤ - 1.6%), no change (NC, -1.6% < ΔHCT ≤1.5%) and hemoconcentration (ΔHCT >1.5%) groups. The endpoint was all-cause death, with a median follow-up duration of 18.9 months. RESULTS: Hemoconcentration was associated with lower left ventricle ejection fraction, as compared with NC and hemodilution groups, while renal function at entry, New York Heart Association class IV, and in-hospital worsening renal function (WRF) were not significantly different across the three groups. After multivariable adjustment, hemoconcentration had a lower risk of mortality as compared with hemodilution [hazard ratio (HR) 0.39, 95% confidence interval (CI) 0.24-0.63, P < 0.001], or NC (HR 0.54, 95% CI 0.33-0.88, P = 0.015], while hemodilution and NC did not have significantly differ in mortality (HR 0.72, 95% CI 0.48-1.10, P = 0.130). CONCLUSIONS: In patients hospitalized with AHF, an increased HCT during hospitalization is associated with a lower risk of all-cause mortality than a decreased or unchanged HCT. Furthermore, all-cause mortality does not differ significantly between patients with unchanged and decreased HCT values.

Reappraisal and New Observations on Idiopathic Ventricular Arrhythmias Ablated From the Noncoronary Aortic Sinus.

BACKGROUND: The electrophysiological characteristics of idiopathic ventricular arrhythmias (VAs) from the noncoronary sinus (NCS) have not been fully described. OBJECTIVES: This study sought to investigate electrophysiological characteristics and catheter ablation in patients with idiopathic NCS-VA. METHODS: This study comprised 11 patients undergoing radiofrequency (RF) catheter ablation for idiopathic NCS-VA. Angiography was performed to confirm the origin in the aortic sinus before RF ablation. RESULTS: Clinical arrhythmias presented left bundle block/inferior axis morphology in all patients. QRS morphology of R' and R/s' pattern was dominantly found in lead III. Mapping in the right ventricle demonstrated the earliest ventricular activation (EVA) site at the His Bundle region, whereas mapping in the NCS demonstrated that the EVA preceded the activation at the His Bundle region by 12.1 ± 7.9 milliseconds. All VAs were successfully ablated in <2.5 seconds within the NCS with 1 RF application. The successful ablation site was at the nadir of NCS in 10 patients, and near the junction of NCS and the right coronary sinus in the remaining one. A discrete potential can be observed at the EVA site within the NCS in 10 patients (91%); however, an excellent pace mapping at the EVA site was obtained in only 2 patients. Junctional beats did not occur during RF application in all 11 patients. There were no complications or clinical recurrence during a mean follow-up of 26.0 ± 9.8 months. CONCLUSIONS: NCS-VA presents a peculiar electrocardiogram. A discrete potential can be mapped within the NCS during VA and sinus rhythm, and can be used in guiding ablation.

Comparative effects of Guanfu base A and Guanfu base G on HERG K+ channel.

BACKGROUND: Guanfu base A (GFA) and Guanfu base G (GFG) are chemicals isolated from Aconitum coreanum. The potassium channel encoded by the human ether-a-go-go related gene (HERG) plays an important role in repolarization of the cardiac action potential. The purpose of the present study was to investigate the effects of GFA and GFG on the HERG channel and its structure-function relationship. METHODS: The effects of GFA and GFG were investigated in human embryonic kidney 293 (HEK293) cells transiently transfected with HERG complementary DNA using a whole-cell patch clamp technique. RESULTS: GFA and GFG inhibited HERG channel current in concentration-, voltage-, and time-dependent manners. The IC50 for GFA and GFG was 1.64 mM and 17.9 µM, respectively. Both GFA and GFG shifted the activation curve in a negative direction and accelerated channel inactivation but showed no effect on the inactivation curve. Moreover, GFG also accelerated channel recovery from inactivation. CONCLUSIONS: Both GFA and GFG blocked HERG channel current. This effect was stronger after GFG treatment rather than GFA treatment. This blockade was dependent on open and inactivated channel states. These results indicate that GFA could be a rather promising antiarrhythmic drug without severe side effects, whereas GFG could cause QT prolongation and requires further research.

Active construction of southernmost Tibet revealed by deep seismic imaging.

Southernmost Tibet exhibits an anomalously twice the normal thickness of average continental crust. There is no available theory to explain and the driving mechanism remains uncertain. Here, we interpret a north-striking, 180 km-long deep seismic reflection profile traversing the southern Lhasa terrane (SLT) to the central Lhasa terrane (CLT). In addition to reflections showing subducting Indian crust, our results reveal lateral heterogeneity between the SLT and CLT, where north-dipping reflections beneath the CLT outline a tilted crystalline basement, while the non-reflective domain beneath the SLT represents homogeneous juvenile crust. Our integrated analysis leads to models calling upon episodic magmatism onto the southern margin of the basement to result in progressive construction of the SLT. We hypothesize that this crustal thickening via crustal-scale magma accretion contributed to surface uplift of the southern margin of the Tibetan plateau and leading to the development of the vast internal drainage system of Tibet.

Effect of Hypertension Duration and Blood Pressure Control During Early Adulthood on Cognitive Function in Middle Age.

BACKGROUND: Elevated blood pressure (BP) is a risk factor for cognitive impairment. OBJECTIVE: We aim to explore the association between the duration of hypertension in early adulthood, with cognitive function in midlife. Furthermore, we investigate whether this asssociation is altered among participants with controlled BP. METHODS: This prospective study included 2,718 adults aged 18-30 years without hypertension at baseline who participated in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Duration of hypertension was calculated based on repeat measurements of BP performed at 2, 5, 7, 10, 15, 20, and 25 years after baseline. Cognitive function was assessed at Year-25 using the Rey Auditory Verbal Learning Test (RAVLT), Digit Symbol Substitution Test (DSST), and Stroop test. RESULTS: After multivariable adjustment, a longer hypertension duration was associated with worse verbal memory (RAVLT, p trend = 0.002) but not with processing speed (DSST, p trend = 0.112) and executive function (Stroop test, p trend = 0.975). Among subgroups of participants with controlled (BP < 140/90 mmHg) and uncontrolled (SBP≥140 mmHg or DBP≥90 mmHg) BP at the time of cognitive assessment (i.e., Year-25 BP), longer duration of hypertension was associated with worse verbal memory. Similar results were observed in subgroups with controlled and uncontrolled average BP prior to cognitive assessment. CONCLUSION: Longer duration of hypertension during early adulthood is associated with worse verbal memory in midlife regardless of current or long-term BP control status. The potential risk of hypertension associated cognitive decline should not be overlooked in individuals with a long duration of hypertension, even if BP levels are controlled.

Visit-to-Visit Fasting Glucose Variability in Young Adulthood and Nonalcoholic Fatty Liver Disease in Middle Age.

CONTEXT: Diabetes has a bidirectional association with nonalcoholic fatty liver disease (NAFLD) and increases the risk of cirrhosis and related complications. OBJECTIVE: To investigate the association between visit-to-visit fasting glucose (FG) variability in early adulthood and NAFLD in middle age. METHODS: This prospective cohort study included 2467 Black and White adults aged 18 to 30 years at baseline (1985-1986) who were followed over 25 years in the Coronary Artery Risk Development in Young Adults Study. FG variability measures included coefficient of variation about the mean FG (CV-FG), the SD of FG (SD-FG), and the average real variability of FG (ARV-FG) across 25 years (year 0, 7, 10, 15, 20, and 25 examinations). NAFLD was defined as liver attenuation ≤ 40 Hounsfield units on computed tomography scan at year 25 examination after excluding other causes of hepatic steatosis. RESULTS: Of the 2467 participants, 241 (9.8%) had NAFLD at year 25. In multivariate analysis, the odds ratio for NAFLD was 2.80 (95% CI, 1.69-4.64; P trend < 0.001) for the fourth quartile vs first quartile of CV-FG after adjusting for confounding variables, including mean FG. Similar results were observed for SD-FG and ARV-FG. CONCLUSION: Greater visit-to-visit FG variability in early adulthood was associated with higher risk of NAFLD in middle age independent of mean FG level. FG variability may help identify individuals at high risk for NAFLD.

Blood pressure trajectories in early adulthood and myocardial structure and function in later life.

AIMS: This study sought to investigate the association between blood pressure (BP) trajectories from early to middle adulthood and echocardiographic indices of structure and function in middle age. METHODS AND RESULTS: This prospective cohort study included 4717 black and white adults aged 18-30 years at baseline (1985-86) who were followed over 30 years in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Trajectories of systolic BP (SBP), diastolic BP (DBP), and pulse pressure (PP) from the Year 0 examination to Year 30 examination were identified using latent mixture modelling. Echocardiographic indices of myocardial structure, systolic function, and diastolic function were assessed at the Year 30 examination. Five distinct SBP trajectory groups were identified: low-stable [1110 participants (23.5%)], moderate-stable [2188 (46.4%)], high-stable [850 (18.0%)], moderate-increasing [416 (8.8%)], and high-increasing [153 (3.2%)]. After adjustment for clinical variables, a significant decreasing trend was observed from the high-increasing and moderate-increasing groups through to the low-stable group for left ventricular (LV) mass index [mean (SE): high-increasing, 112.3 (3.4); moderate-increasing, 99.3 (2.6); high-stable, 88.9 (2.5); moderate-stable, 86.1 (2.3); low-stable, 82.1 (2.4), P trend < 0.01], as well as LV end-diastolic dimension, left atrial volume index, and E/e', while an increasing trend was apparent for LV longitudinal strain, E/A ratio, and average e' velocities. Results were generally consistent for trajectories of DBP and PP. CONCLUSIONS: Higher BP trajectories from early to middle adulthood were associated with worse indices of myocardial modelling and LV systolic and diastolic function at middle age.

Triglyceride-Glucose Index and Homeostasis Model Assessment-Insulin Resistance in Young Adulthood and Risk of Incident Congestive Heart Failure in Midlife: The Coronary Artery Risk Development in Young Adults Study.

Objective: This study aimed to assess the association between triglyceride-glucose (TyG) index/homeostasis model assessment-insulin resistance (HOMA-IR) within young adults and congestive heart failure (CHF), and to explore whether TyG index can replace HOMA-IR as a surrogate marker for IR in predicting the risk of CHF. Methods: A total of 4,992 participants between the ages of 18 and 30 years were enrolled from the Coronary Artery Risk Development in Young Adults (CARDIA) investigation [from 1985 to 1986 (year 0)]. A Cox proportional hazard regression analysis was conducted for assessing correlations between baseline TyG index/HOMA-IR and CHF events, together with the receiver operating characteristic (ROC) curve employed for scrutinizing TyG index/HOMA-IR and the risk of CHF. Results: During the 31-year follow-up period, 64 (1.3%) of the 4,992 participants developed CHF. In multivariable Cox proportional hazards models, adjusted for confounding factors for CHF, an increased risk of CHF was associated with a per-unit increase in the TyG index [hazard ratio (HR) 2.8; 95% confidence interval (CI), 1.7-4.7] and HOMA-IR (HR 1.2; 95% CI, 1.1-1.3). A Kaplan-Meier curve analysis showed that participants in the TyG index and HOMA-IR index Q4 group had a higher risk of CHF than those in the Q1 group. The area under curve (AUC) for the TyG index and HOMA-IR consisted of 0.67 (95% CI, 0.6-0.742) and 0.675 (95% CI, 0.604-0.746), respectively. There were no significant differences between the TyG index and HOMA-IR for AUC (p = 0.986). Conclusion: The higher TyG index and HOMA-IR are independent risk factors for CHF. The TyG index can replace HOMA-IR in young adulthood as a surrogate marker for IR to predict the risk of CHF.

Growth of CeO2 nanocubes showing size-dependent optical and oxygen evolution reaction behaviors.

CeO2 nanocubes with average sizes of 9, 13, and 18 nm have been synthesized by preparing a slightly basic aqueous mixture of Ce(NO3)3, Na2SO4, and NH4OH and heating the solution to 100 to 150 °C in 4 or 9 h. The nanocubes possess high crystalline quality. Their band gaps decrease gradually beyond the quantum confinement regime from 3.57 eV to 3.45 eV with increasing particle sizes. The 9 nm CeO2 nanocubes have the most positive valence band energy and correspondingly they exhibit the best electrochemical oxygen evolution reaction activity. Since band gaps of semiconductor nanocrystals can be tuned substantially through particle size control to yield different band energies, this fact can be utilized to enhance the electrochemical and photocatalytic properties.

p53 SUMOylation Mediates AOPP-Induced Endothelial Senescence and Apoptosis Evasion.

The aging of endothelial cells plays a critical role in the development of age-related vascular disease. We established a model of endothelial premature senescence by application of Advanced oxidation protein products (AOPPs) modified bovine serum albumin (AOPP-BSA) in human umbilical vein endothelial cells (HUVECs). This cellular senescence was accompanied with endothelial barrier dysfunction and angiogenesis impairment. It was further revealed that these senescent HUVECs underwent apoptosis evasion and the receptor for advanced glycation endproducts (RAGE) played a role in these processes. The AOPP-induced senescence was regulated by the state of autophagy in HUVECs. We further proved that AOPP-BSA attenuated the autophagy of HUVECs, led to p53 SUMOylation at K386, resulting in endothelial senescence. We also established the animal model of vascular senescence by using ApoE-/- mice fed with high-fat diet plus daily injection of AOPP-BSA to verify the role of p53 SUMOylation in vascular senescence. Combined with intraperitoneal injection of rapamycin, the effect of autophagy on AOPP-induced p53 SUMOylation was also confirmed in vivo. Our data indicates that p53 SUMOylation at K386 plays an important role in AOPP-induced endothelial senescence and apoptosis evasion, suggesting that p53 K386 SUMOylation may serve as a potential therapeutic target in protecting against vascular senescence.

One-year change in resting heart rate and subsequent risk of hypertension in healthy Chinese adults.

BACKGROUND: Changes in baseline resting heart rate (RHR) appear to predict new-onset hypertension (NOH). However, RHR is a dynamic anthropometric parameter; thus, the association between changes in RHR and NOH requires further investigation. METHODS: We studied 10 403 participants who were initially normotensive and who had at least one routine health examination at baseline and 1 year later during 2011-2016. We compared the RHR between the baseline and 1-year follow-up. We defined hypertension as SBP ≥140 mmHg or DBP ≥90 mmHg. Participants were divided into three groups: RHR decreased, RHR unchanged [from 0 to 10 beats per minute (bpm)], and RHR increased ≥10 bpm. Cox regression analysis was performed to calculate relative risk with 95% confidence intervals (CIs) for the association between NOH and RHR change. RESULTS: During a mean follow-up period of 2.42 years, 1173 (11.28%) participants developed hypertension. After adjusting for age, sex, SBP, DBP, RHR and other confounders obtained at baseline, and compared with participants with unchanged RHR, participants with decreased RHR had a 17% decreased risk of NOH (adjusted hazard ratio: 0.83, 95% CI 0.73-0.95), whereas subjects with RHR that increased ≥10 bpm had a 23% increased risk of NOH (adjusted hazard ratio: 1.23, 95% CI 1.04-1.46). CONCLUSION: A 1-year increase in RHR for initially normotensive subjects is an independent risk factor for subsequent hypertension.

Comparative effects of intensive ganglionated plexus ablation in treating paroxysmal atrial fibrillation and vasovagal syncope.

BACKGROUND: Ganglionated plexus (GP) ablation is used to treat atrial fibrillation (AF) and vasovagal syncope (VVS). However, the comparative effects of GP ablation in treating paroxysmal atrial fibrillation (PAF) and VVS have not been well studied. OBJECTIVE: The purpose of this study was to investigate the effects of intensive GP ablation on PAF and VVS. METHODS: PAF and VVS patients were enrolled in this study. Pulmonary vein isolation (PVI) was performed in the PAF group, and additional ablation was performed at GP sites. Anatomic ablation of left atrial GPs was performed in the VVS group. The primary endpoint was freedom from AF or other sustained atrial tachycardia and syncope recurrence. RESULTS: A total of 195 patients were enrolled: 146 patients with PAF, including eight patients with combined VVS (PAF group), and 49 patients with VVS (VVS group). Vasovagal response (VR) was achieved in 78 (53.4%) patients in the PAF group and 48 patients (98.0%) in the VVS group (P < .05). During the 17.8 ± 10.5 (range, 3-42) month follow-up, 126 (86.3%) patients were free of AF in the PAF group, and 45 (91.8%) patients in the VVS group had no syncope recurrence and significantly improved symptoms. CONCLUSIONS: Anatomically guided intensive GP ablation showed efficient clinical outcomes for both groups of patients. Compared with PAF patients, VVS patients had more VR during ablation in the left atrium. Furthermore, VR during ablation indicated a better prognosis in PAF patients.

Personalized Fluoroscopic Angles in Watchman™ Left Atrial Appendage Closure Landing Zone Assessment: A Three-Dimensional Printed Simulation Study.

Background Atrial fibrillation causes ischemic stroke when thrombi dislodge from a cardiac outpouching, the left atrial appendage (LAA), and embolize to the brain. LAA occlusion with the Watchman™ device (Boston Scientific Corporation, MA, USA), which prevents stroke, requires accurate LAA measurements for device sizing. We explore whether standard fluoroscopic LAA measurements improve when obtained at CT-derived viewing angles personalized to LAA anatomy while concurrently referring to three-dimensional (3D) CT. Methods Left atrial 3D reconstructions created from contrast CT (n=28) were analysed to identify personalized viewing angles wherein LAA dimensions (LAA maximum landing zone diameter and LAA length) were best observed. The 3D-CT reconstructions were then 3D printed with stands. Fluoroscopy of anatomically oriented models in the catheter lab simulated LAA angiography. Fluoroscopic images were acquired at standard (caudal 20˚/right anterior oblique 30˚) and personalized viewing angles. Repeated measurements of LAA dimensions were taken from CT (Control), fluoroscopy at standard angles (Standard), personalized angles (Blinded), and personalized angles while concurrently referring to 3D CT (Referred). Results Control measurements correlated and agreed better with Referred and Blinded measurements than with Standard measurements (diameter correlation and agreement: Control/Standard r=.554, limits of agreement [LOAs]=6.83/-5.91; Control/Blinded r=.641, LOA =5.67/-5.54; Control/Referred r=.741, LOA=4.69/-4.14; length correlation and agreement: Control/Standard rs=.829, LOA=9.61/-3.02; Control/Blinded rs=0.789, LOA=7.13/-4.94; Control/Referred rs=.907, LOA=4.84/-4.13). Personalized angles resulted in hypothetical device size predictions more consistent with Control (device size correlation: Control/Standard rs=.698, Control/Blinded rs=.731, Control/Referred rs=.893, P<0.001). False ineligibility rates were Standard=6/28, Blinded=6/28, and Referred=2/28. Conclusion This simulation suggests that personalized fluoroscopic viewing angles with in-procedural reference to 3D CT may improve the accuracy of LAA maximum landing zone diameter and length measurements at the Watchman landing zone. This improvement may result in more consistent device size selection and procedural eligibility assessment. Further clinical research on these interventions is merited.

Clustering of risk factors and the risk of new-onset hypertension defined by the 2017 ACC/AHA Hypertension Guideline.

The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) lowered the diagnostic criteria for hypertension. We aimed to explore whether clustering of multiple risk factors are associated with the risk of new-onset hypertension defined by the 2017 ACC/AHA Hypertension Guideline. Subjects who attended ≥2 annual health examinations without baseline hypertension and cardiovascular disease were included. Hypertension was defined according to the 2017 ACC/AHA Hypertension Guideline. Seven predefined risk factors, including age, resting heart rate, overweight or obesity, dyslipidemia, hyperuricemia, impaired glucose regulation, and a poor estimated glomerular filtration rate, were analyzed. A composite, individual-level, cumulative score incorporating these seven risk factors (no = 0 point; yes = 1 point; total range of 0-7 points) was calculated. The association between the cumulative score and the risk of hypertension was analyzed using a Cox regression model. A total of 4424 (21.6%) of 20,190 subjects included had new-onset hypertension during a follow-up duration of 3.6 years. Compared with subjects with 0 points, the adjusted hazard ratios (95% confidence intervals) for the development of hypertension for those with 1, 2, 3, and ≥4 points were 1.21 (1.07-1.38), 1.34 (1.19-1.52), 1.44 (1.26-1.63), and 1.64 (1.44-1.87), respectively (P < 0.001), after adjustment for sex and baseline blood pressure. Age, resting heart rate, overweight/obesity, dyslipidemia, hyperuricemia, impaired glucose regulation, and a poor estimated glomerular filtration rate are associated with an increased risk of future hypertension. When these factors are combined, there is an accumulated increase in risk.

Association of Urine Albumin/Creatinine Ratio below 30 mg/g and Left Ventricular Hypertrophy in Patients with Type 2 Diabetes.

Several studies show that even a level of urine albumin/creatinine ratio (UACR) within the normal range (below 30 mg/g) increases the risk of cardiovascular diseases. We speculate that mildly increased UACR is related to left ventricular hypertrophy (LVH) in patients with type 2 diabetes mellitus (T2DM). In this retrospective study, 317 patients with diabetes with normal UACR, of whom 62 had LVH, were included. The associations between UACR and laboratory indicators, as well as LVH, were examined using multivariate linear regression and logistic regression, respectively. The diagnostic efficiency and the optimal cutoff point of UACR for LVH were evaluated using the area under the receiver operating characteristic curve (AUC) and Youden index. Our results showed that patients with LVH had significantly higher UACR than those without LVH (P < 0.001). The prevalence of LVH presented an upward trend with the elevation of UACR. UACR was independently and positively associated with hemoglobin A1c (P < 0.001). UACR can differentiate LVH (AUC = 0.682, 95% CI (0.602-0.760), P < 0.001). The optimal cutoff point determined with the Youden index was UACR = 10.2 mg/g. When categorized by this cutoff point, the odds ratio (OR) for LVH in patients in the higher UACR group (10.2-30 mg/g) was 3.104 (95% CI: 1.557-6.188, P=0.001) compared with patients in the lower UACR group (<10.2 mg/g). When UACR was analyzed as a continuous variable, every double of increased UACR, the OR for LVH was 1.511 (95% CI: 1.047-2.180, P=0.028). Overall, UACR below 30 mg/g is associated with LVH in patients with T2DM. The optimal cutoff value of UACR for identifying LVH in diabetes is 10 mg/g.

Serum Peroxisome Proliferator-activated Receptor Gamma Coactivator-1α Related to Myocardial Energy Expenditure in Patients With Chronic Heart Failure.

BACKGROUND: Peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) plays key roles in controlling cardiac metabolism and function. Myocardial energy expenditure (MEE) can reflect myocardial energy metabolism and cardiac function. Whether the variation of PGC-1α can influence MEE levels in chronic heart failure (CHF) is unclear. Therefore, we investigated the relationship between PGC-1α and MEE. MATERIAL AND METHODS: We studied 219 patients with CHF and 66 healthy controls. MEE was measured according to echocardiographic parameters. Serum PGC-1α, N-terminal pro-B-type natriuretic peptide and other parameters were detected. Patients with CHF were divided into different groups according to the left ventricular ejection fraction (LVEF) and the tertile range of MEE. RESULTS: Serum PGC-1α was lower in the MEE 2 and 3 groups compared with controls (both P < 0.05). Patients in the MEE 2 (1.73 ± 0.83 versus 2.16 ± 0.82 ng/mL, P = 0.001) and 3 groups (1.65 ± 0.73 versus 2.16 ± 0.82 ng/mL, P < 0.001) possessed lower levels of PGC-1α than those in the MEE 1 group. Compared with high LVEF, patients with low LVEF had higher MEE (median, 167 versus 73 cal/minute, P < 0.05) and lower PGC-1α (1.71 ± 0.65 versus 1.95 ± 0.91 ng/mL, P = 0.032). Multivariate logistic regression analysis showed that MEE (OR = 0.517, 95% CI = 0.267-0.998, P = 0.049) and creatinine (OR = 2.704, 95% CI = 1.144-6.391, P = 0.023) were independently associated with increased PGC-1α. CONCLUSIONS: Serum PGC-1α was related to MEE and LVEF in patients with CHF and can reflect the degree of MEE and the systolic function of the left ventricle.

Identification of differentially expressed circular RNAs during TGF-ß1-induced endothelial-to-mesenchymal transition in rat coronary artery endothelial cells.

OBJECTIVE: Although differentially expressed circRNAs have been proposed to be closely associated with epithelial-mesenchymal transition (EMT), the roles of circRNAs remain unclear in endothelial-to-mesenchymal transition (EndMT), which is a subcategory of EMT. Herein, we characterized the expression and potential function of circRNAs during TGF-ß1-induced EndMT in rat coronary artery endothelial cells (CAEC). METHODS: High-throughput RNA sequencing was performed for unbiasedly profiling the expression of circRNAs. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analysis were performed using online forecasting databases. Real-time quantitative polymerase chain reaction (RT-qPCR) was used for confirming the circRNA expression obtained from the sequencing data. RESULTS: Among the candidated circRNAs, 102 circRNAs were differentially expressed, among which 66 circRNAs and 36 circRNAs were up-regulated and down-regulated, respectively, in TGF-ß1-treated rat CAEC. GO analysis findings revealed that numerous differentially expressed circRNAs were closely associated with the biological process. KEGG signaling pathway analysis suggested that the abnormal expression of circRNAs had been implicated in regulating the dynamics endothelial cell junctions. Furthermore, we also found that three EndMT-related circRNAs, chr5:90817794|90827570, chr8:71336875|71337745, and chr6:22033342|22038870, were significantly up-regulated in TGF-ß1-treated rat CAEC. CONCLUSION: The findings of this study reveal a comprehensive expression and potential functions of differentially expressed circRNAs during TGF-ß1-induced EndMT. These findings provide mechanistic insights into the role of circRNAs in EndMT-related cardiovascular diseases (CVDs).