WWP2 protects against sepsis-induced cardiac injury through inhibiting cardiomyocyte ferroptosis.

Background and Objectives: Cardiac injury plays a critical role in contributing to the mortality associated with sepsis, a condition marked by various forms of programmed cell deaths. Previous studies hinted at the WW domain-containing E3 ubiquitin protein ligase 2 (WWP2) involving in heart failure and endothelial injury. However, the precise implications of WWP2 in sepsis-induced cardiac injury, along with the underlying mechanisms, remain enigmatic. Methods: Sepsis induced cardiac injury were constructed by intraperitoneal injection of lipopolysaccharide. To discover the function of WWP2 during this process, we designed and performed loss/gain-of-function studies with cardiac-specific vectors and WWP2 knockout mice. Combination experiments were performed to investigate the relationship between WWP2 and downstream signaling in septic myocardium injury. Results: The protein level of WWP2 was downregulated in cardiomyocytes during sepsis. Cardiac-specific overexpression of WWP2 protected heart from sepsis induced mitochondrial oxidative stress, programmed cell death and cardiac injury, while knockdown or knockout of WWP2 exacerbated this process. The protective potency of WWP2 was predominantly linked to its ability to suppress cardiomyocyte ferroptosis rather than apoptosis. Mechanistically, our study revealed a direct interaction between WWP2 and acyl-CoA synthetase long-chain family member 4 (FACL4), through which WWP2 facilitated the ubiquitin-dependent degradation of FACL4. Notably, we observed a notable reduction in ferroptosis and cardiac injury within WWP2 knockout mice after FACL4 knockdown during sepsis. Conclusions: WWP2 assumes a critical role in safeguarding the heart against injury induced by sepsis via regulating FACL4 to inhibit LPS-induced cardiomyocytes ferroptosis.

E3 ubiquitin ligase WWP2 as a promising therapeutic target for diverse human diseases.

Mammalian E3 ubiquitin ligases have emerged in recent years as critical regulators of cellular homeostasis due to their roles in targeting substrate proteins for ubiquitination and triggering subsequent downstream signals. In this review, we describe the multiple roles of WWP2, an E3 ubiquitin ligase with unique and important functions in regulating a wide range of biological processes, including DNA repair, gene expression, signal transduction, and cell-fate decisions. As such, WWP2 has evolved to play a key role in normal physiology and diseases, such as tumorigenesis, skeletal development and diseases, immune regulation, cardiovascular disease, and others. We attempt to provide an overview of the biochemical, physiological, and pathophysiological roles of WWP2, as well as open questions for future research, particularly in the context of putative therapeutic opportunities.

Regulation of lipid metabolism by E3 ubiquitin ligases in lipid-associated metabolic diseases.

Previous studies have progressively elucidated the involvement of E3 ubiquitin (Ub) ligases in regulating lipid metabolism. Ubiquitination, facilitated by E3 Ub ligases, modifies critical enzymes in lipid metabolism, enabling them to respond to specific signals. In this review, we aim to present a comprehensive analysis of the role of E3 Ub ligases in lipid metabolism, which includes lipid synthesis and lipolysis, and their influence on cellular lipid homeostasis through the modulation of lipid uptake and efflux. Furthermore, it explores how the ubiquitination process governs the degradation or activation of pivotal enzymes, thereby regulating lipid metabolism at the transcriptional level. Perturbations in lipid metabolism have been implicated in various diseases, including hepatic lipid metabolism disorders, atherosclerosis, diabetes, and cancer. Therefore, this review focuses on the association between E3 Ub ligases and lipid metabolism in lipid-related diseases, highlighting enzymes critically involved in lipid synthesis and catabolism, transcriptional regulators, lipid uptake translocators, and transporters. Overall, this review aims to identify gaps in current knowledge, highlight areas requiring further research, offer potential targeted therapeutic approaches, and provide a comprehensive outlook on clinical conditions associated with lipid metabolic diseases.

Post-translational modifications in diabetic cardiomyopathy.

The increasing attention towards diabetic cardiomyopathy as a distinctive complication of diabetes mellitus has highlighted the need for standardized diagnostic criteria and targeted treatment approaches in clinical practice. Ongoing research is gradually unravelling the pathogenesis of diabetic cardiomyopathy, with a particular emphasis on investigating various post-translational modifications. These modifications dynamically regulate protein function in response to changes in the internal and external environment, and their disturbance of homeostasis holds significant relevance for the development of chronic ailments. This review provides a comprehensive overview of the common post-translational modifications involved in the initiation and progression of diabetic cardiomyopathy, including O-GlcNAcylation, phosphorylation, methylation, acetylation and ubiquitination. Additionally, the review discusses drug development strategies for targeting key post-translational modification targets, such as agonists, inhibitors and PROTAC (proteolysis targeting chimaera) technology that targets E3 ubiquitin ligases.

Advances in the study of exosomes in cardiovascular diseases.

BACKGROUND: Cardiovascular disease (CVD) has been the leading cause of death worldwide for many years. In recent years, exosomes have gained extensive attention in the cardiovascular system due to their excellent biocompatibility. Studies have extensively researched miRNAs in exosomes and found that they play critical roles in various physiological and pathological processes in the cardiovascular system. These processes include promoting or inhibiting inflammatory responses, promoting angiogenesis, participating in cell proliferation and migration, and promoting pathological progression such as fibrosis. AIM OF REVIEW: This systematic review examines the role of exosomes in various cardiovascular diseases such as atherosclerosis, myocardial infarction, ischemia-reperfusion injury, heart failure and cardiomyopathy. It also presents the latest treatment and prevention methods utilizing exosomes. The study aims to provide new insights and approaches for preventing and treating cardiovascular diseases by exploring the relationship between exosomes and these conditions. Furthermore, the review emphasizes the potential clinical use of exosomes as biomarkers for diagnosing cardiovascular diseases. KEY SCIENTIFIC CONCEPTS OF REVIEW: Exosomes are nanoscale vesicles surrounded by lipid bilayers that are secreted by most cells in the body. They are heterogeneous, varying in size and composition, with a diameter typically ranging from 40 to 160 nm. Exosomes serve as a means of information communication between cells, carrying various biologically active substances, including lipids, proteins, and small RNAs such as miRNAs and lncRNAs. As a result, they participate in both physiological and pathological processes within the body.

The role of glycolytic metabolic pathways in cardiovascular disease and potential therapeutic approaches.

Cardiovascular disease (CVD) is a major threat to human health, accounting for 46% of non-communicable disease deaths. Glycolysis is a conserved and rigorous biological process that breaks down glucose into pyruvate, and its primary function is to provide the body with the energy and intermediate products needed for life activities. The non-glycolytic actions of enzymes associated with the glycolytic pathway have long been found to be associated with the development of CVD, typically exemplified by metabolic remodeling in heart failure, which is a condition in which the heart exhibits a rapid adaptive response to hypoxic and hypoxic conditions, occurring early in the course of heart failure. It is mainly characterized by a decrease in oxidative phosphorylation and a rise in the glycolytic pathway, and the rise in glycolysis is considered a hallmark of metabolic remodeling. In addition to this, the glycolytic metabolic pathway is the main source of energy for cardiomyocytes during ischemia-reperfusion. Not only that, the auxiliary pathways of glycolysis, such as the polyol pathway, hexosamine pathway, and pentose phosphate pathway, are also closely related to CVD. Therefore, targeting glycolysis is very attractive for therapeutic intervention in CVD. However, the relationship between glycolytic pathway and CVD is very complex, and some preclinical studies have confirmed that targeting glycolysis does have a certain degree of efficacy, but its specific role in the development of CVD has yet to be explored. This article aims to summarize the current knowledge regarding the glycolytic pathway and its key enzymes (including hexokinase (HK), phosphoglucose isomerase (PGI), phosphofructokinase-1 (PFK1), aldolase (Aldolase), phosphoglycerate metatase (PGAM), enolase (ENO) pyruvate kinase (PKM) lactate dehydrogenase (LDH)) for their role in cardiovascular diseases (e.g., heart failure, myocardial infarction, atherosclerosis) and possible emerging therapeutic targets.

Cathepsin D Attenuates the Proliferation of Vascular Smooth Muscle Cells Induced by the AGE/RAGE Pathway by Suppressing the ERK Signal.

BACKGROUND: In this study, we aimed to clarify the role and mechanism by which Cathepsin D (CTSD) mediates the advanced glycation end products (AGEs)-induced proliferation of vascular smooth muscle cells (VSMCs). METHODS: We conducted a Western blotting assay and co-immunoprecipitation assay to detect the expression of target proteins and the interaction between different proteins. Cell Counting Kit-8 (CCK-8) assay and 5- ethynyl-2'-deoxyuridine (EdU) were used to evaluate the proliferation. RESULTS: AGEs significantly promoted phenotypic switching and proliferation of VSMCs in a concentration-dependent manner. This effect of AGEs was accompanied by inhibition of CTSD. Both the proliferation of VSMCs and inhibition of CTSD induced by AGEs could be attenuated by the specific inhibitor of the receptor for advanced glycation end products (RAGE), FPS-ZM1. Overexpression of CTSD significantly alleviated these effects of AGEs on VSMCs. The mechanism of CTSD action in VSMCs was also explored. Overexpression of CTSD reduced the activation of p-ERK caused by AGEs. By contrast, the knockdown of CTSD, elicited using a plasmid containing short hairpin RNA (shRNA) against CTSD, further increased the activation of p-ERK compared to AGEs alone. Additionally, co-immunoprecipitation studies revealed an endogenous interaction between CTSD, a protease, and p-ERK, its potential substrate. CONCLUSION: It has been demonstrated that CTSD downregulates the level of phosphorylated ERK by degrading its target, and this interaction plays a critical role in the proliferation of VSMCs induced by the AGE/RAGE axis. These results provide a novel insight into the prevention and treatment of vascular complications in diabetes.

α-myosin heavy chain lactylation maintains sarcomeric structure and function and alleviates the development of heart failure.

The sarcomeric interaction of α-myosin heavy chain (α-MHC) with Titin is vital for cardiac structure and contraction. However, the mechanism regulating this interaction in normal and failing hearts remains unknown. Lactate is a crucial energy substrate of the heart. Here, we identify that α-MHC undergoes lactylation on lysine 1897 to regulate the interaction of α-MHC with Titin. We observed a reduction of α-MHC K1897 lactylation in mice and patients with heart failure. Loss of K1897 lactylation in α-MHC K1897R knock-in mice reduces α-MHC-Titin interaction and leads to impaired cardiac structure and function. Furthermore, we identified that p300 and Sirtuin 1 act as the acyltransferase and delactylase of α-MHC, respectively. Decreasing lactate production by chemical or genetic manipulation reduces α-MHC lactylation, impairs α-MHC-Titin interaction and worsens heart failure. By contrast, upregulation of the lactate concentration by administering sodium lactate or inhibiting the pivotal lactate transporter in cardiomyocytes can promote α-MHC K1897 lactylation and α-MHC-Titin interaction, thereby alleviating heart failure. In conclusion, α-MHC lactylation is dynamically regulated and an important determinant of overall cardiac structure and function. Excessive lactate efflux and consumption by cardiomyocytes may decrease the intracellular lactate level, which is the main cause of reduced α-MHC K1897 lactylation during myocardial injury. Our study reveals that cardiac metabolism directly modulates the sarcomeric structure and function through lactate-dependent modification of α-MHC.

Central Aortic Blood Pressure Waveform Estimation with a Temporal Convolutional Network.

A novel temporal convolutional network (TCN) model is utilized to reconstruct the central aortic blood pressure (aBP) waveform from the radial blood pressure waveform. The method does not need manual feature extraction as traditional transfer function approaches. The data acquired by the SphygmoCor CVMS device in 1,032 participants as a measured database and a public database of 4,374 virtual healthy subjects were used to compare the accuracy and computational cost of the TCN model with the published convolutional neural network and bi-directional long short-term memory (CNN-BiLSTM) model. The TCN model was compared with CNN-BiLSTM in the root mean square error (RMSE). The TCN model generally outperformed the existing CNN-BiLSTM model in terms of accuracy and computational cost. For the measured and public databases, the RMSE of the waveform using the TCN model was 0.55 ± 0.40 mmHg and 0.84 ± 0.29 mmHg, respectively. The training time of the TCN model was 9.63 min and 25.51 min for the entire training set; the average test time was around 1.79 ms and 8.58 ms per test pulse signal from the measured and public databases, respectively. The TCN model is accurate and fast for processing long input signals, and provides a novel method for measuring the aBP waveform. This method may contribute to the early monitoring and prevention of cardiovascular disease.

Effectiveness of a non-physician community health-care provider-led intensive blood pressure intervention versus usual care on cardiovascular disease (CRHCP): an open-label, blinded-endpoint, cluster-randomised trial.

BACKGROUND: Effectiveness of a non-physician community health-care provider-led intensive blood pressure intervention on cardiovascular disease has not been established. We aimed to test the effectiveness of such an intervention compared with usual care on risk of cardiovascular disease and all-cause death among individuals with hypertension. METHODS: In this open-label, blinded-endpoint, cluster-randomised trial, we recruited individuals aged at least 40 years with an untreated systolic blood pressure of at least 140 mm Hg or a diastolic blood pressure of at least 90 mm Hg (≥130 mm Hg and ≥80 mm Hg for those at high risk for cardiovascular disease or if currently taking antihypertensive medication). We randomly assigned (1:1) 326 villages to a non-physician community health-care provider-led intervention or usual care, stratified by provinces, counties, and townships. In the intervention group, trained non-physician community health-care providers initiated and titrated antihypertensive medications according to a simple stepped-care protocol to achieve a systolic blood pressure goal of less than 130 mm Hg and diastolic blood pressure goal of less than 80 mm Hg with supervision from primary care physicians. They also delivered discounted or free antihypertensive medications and health coaching for patients. The primary effectiveness outcome was a composite outcome of myocardial infarction, stroke, heart failure requiring hospitalisation, and cardiovascular disease death during the 36-month follow-up in the study participants. Safety was assessed every 6 months. This trial is registered with ClinicalTrials.gov, NCT03527719. FINDINGS: Between May 8 and Nov 28, 2018, we enrolled 163 villages per group with 33 995 participants. Over 36 months, the net group difference in systolic blood pressure reduction was -23·1 mm Hg (95% CI -24·4 to -21·9; p<0·0001) and in diastolic blood pressure reduction, it was -9·9 mm Hg (-10·6 to -9·3; p<0·0001). Fewer patients in the intervention group than the usual care group had a primary outcome (1·62% vs 2·40% per year; hazard ratio [HR] 0·67, 95% CI 0·61-0·73; p<0·0001). Secondary outcomes were also reduced in the intervention group: myocardial infarction (HR 0·77, 95% CI 0·60-0·98; p=0·037), stroke (0·66, 0·60-0·73; p<0·0001), heart failure (0·58, 0·42-0·81; p=0·0016), cardiovascular disease death (0·70, 0·58-0·83; p<0·0001), and all-cause death (0·85, 0·76-0·95; p=0·0037). The risk reduction of the primary outcome was consistent across subgroups of age, sex, education, antihypertensive medication use, and baseline cardiovascular disease risk. Hypotension was higher in the intervention than in the usual care group (1·75% vs 0·89%; p<0·0001). INTERPRETATION: The non-physician community health-care provider-led intensive blood pressure intervention is effective in reducing cardiovascular disease and death. FUNDING: The Ministry of Science and Technology of China and the Science and Technology Program of Liaoning Province, China.

Personalized aortic pressure waveform estimation from brachial pressure waveform using an adaptive transfer function.

BACKGROUND AND OBJECTIVE: The aortic pressure waveform (APW) provides reliable information for the diagnosis of cardiovascular disease. APW is often measured using a generalized transfer function (GTF) applied to the peripheral pressure waveform acquired noninvasively, to avoid the significant risks of invasive APW acquisition. However, the GTF ignores various physiological conditions, which affects the accuracy of the estimated APW. To solve this problem, this study utilized an adaptive transfer function (ATF) combined with a tube-load model to achieve personalized and accurate estimation of APW from the brachial pressure waveform (BPW). METHODS: The proposed method was validated using APWs and BPWs from 34 patients. The ATF was defined using a tube-load model in which pulse transit time and reflection coefficients were determined from, respectively, the diastolic-exponential-pressure-decay of the APW and a piece-wise constant approximation. The root-mean-square-error of overall morphology, mean absolute errors of common hemodynamic indices (systolic blood pressure, diastolic blood pressure and pulse pressure) were used to evaluate the ATF. RESULTS: The proposed ATF performed better in estimating diastolic blood pressure and pulse pressure (1.63 versus 1.94 mmHg, and 2.37 versus 3.10 mmHg, respectively, both P < 0.10), and produced similar errors in overall morphology and systolic blood pressure (3.91 versus 4.24 mmHg, and 2.83 versus 2.91 mmHg, respectively, both P > 0.10) compared to GTF. CONCLUSION: Unlike the GTF which uses fixed parameters trained on existing clinical datasets, the proposed method can achieve personalized estimation of APW. Hence, it provides accurate pulsatile hemodynamic measures for the evaluation of cardiovascular function.

Interventricular Septum Thickness for the Prediction of Coronary Heart Disease and Myocardial Infarction in Hypertension Population: A Prospective Study.

The aim of the present study was to evaluate the prognostic value of interventricular septum thickness (IVSd) on the incidence of cardiovascular diseases. Based on the general population in Northeast China, 10,349 participants were successfully followed up for echocardiography over a median follow-up time of 4.66 years, among which 4801 were hypertensive. Coronary heart disease (CHD) and myocardial infarction (MI) incidence were followed up. Cox proportional hazards models were used to estimate the association of the baseline IVSd with adverse outcomes. IVS hypertrophy increased incident rates of CHD and MI compared with normal IVSd in the overall population and in the female sex-stratification group. In males, IVS hypertrophy had parallel increase rates of CHD (all p < 0.05). Kaplan−Meier analysis showed that IVS hypertrophy could predict CHD and MI incidence and CHD-free and MI-free survival. Multivariable Cox analysis revealed that IVS hypertrophy was correlated with CHD incidence (HR = 1.155, 95% CI = 1.155−2.861, p = 0.01) and MI incidence (HR = 2.410, 95% CI = 1.303−4.458, p = 0.005). In women, IVS hypertrophy was independently associated with CHD and MI incidence (all p < 0.05). Our prospective cohort study illustrated that IVS hypertrophy detected by echocardiography has a prognostic significance for CHD and MI. Therefore, the early detection of IVSd should be conducted to avoid adverse outcomes in further clinical practice.

Is waist-to-height ratio the best predictive indicator of cardiovascular disease incidence in hypertensive adults? A cohort study.

BACKGROUND: Cardiovascular disease (CVD) brings high mortality and economic burden to patients, especially in rural areas. Simple, low-cost abdominal adiposity measures may help identify individuals with increased CVD risk. It is unclear that which obesity indices is the best to predict CVD in hypertensive people. METHODS: Northeast China Rural Cardiovascular Health Study (NCRCHS) is a prospective cohort study in a general population in Northeast China. The study examined the cardiovascular health from 2013 to 2015, and follow-up captured the CVD incidence in 2018. Baseline waist-to-height ratio (WHtR), waist circumference (WC), waist-to-hip (WHR)and body mass index (BMI) were calculated and analyzed in relation to the CVD incidence. RESULTS: A total of 4244 hypertensive adults without pre-existing CVD at baseline were included in this analysis (age 35-92 years; 2108 men). Over a median follow-up of 4.66 years, a total of 290 CVD cases (6.83%) were documented during the follow-up. Baseline WHtR showed a significant positive association with CVD incidence, even after adjusting for age, sex, diabetes, drinking, smoking, SBP, DBP, Triglyceride, HDL-C, LDL-C, and TC (Hazard Ratios per SD of WHtR ranging from 1.03 to 1.31, p = 0.017). Reclassification and discrimination analyses indicated WHtR addition could improve the conventional model for predicting adverse outcomes within 4 years. Moreover, WHtR predicted the CVD incidence better than other obesity indices (BMI, WC, WHR). CONCLUSION: These findings support a positive association between WHtR and CVD incidence in CVD-free hypertensive adults. WHtR can be used to predict CVD incidence in hypertensive adults.

A village doctor-led multifaceted intervention for blood pressure control in rural China: an open, cluster randomised trial.

BACKGROUND: The prevalence of uncontrolled hypertension is high and increasing in low-income and middle-income countries. We tested the effectiveness of a multifaceted intervention for blood pressure control in rural China led by village doctors (community health workers on the front line of primary health care). METHODS: In this open, cluster randomised trial (China Rural Hypertension Control Project), 326 villages that had a regular village doctor and participated in the China New Rural Cooperative Medical Scheme were randomly assigned (1:1) to either village doctor-led multifaceted intervention or enhanced usual care (control), with stratification by provinces, counties, and townships. We recruited individuals aged 40 years or older with an untreated blood pressure of 140/90 mm Hg or higher (≥130/80 mm Hg among those with a history of cardiovascular disease, diabetes, or chronic kidney disease) or a treated blood pressure of 130/80 mm Hg or higher. In the intervention group, trained village doctors initiated and titrated antihypertensive medications according to a standard protocol with supervision from primary care physicians. Village doctors also conducted health coaching on home blood pressure monitoring, lifestyle changes, and medication adherence. The primary outcome (reported here) was the proportion of patients with a blood pressure of less than 130/80 mm Hg at 18 months. The analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT03527719, and is ongoing. FINDINGS: Between May 8 and November 28, 2018, we enrolled 33 995 individuals from 163 intervention and 163 control villages. At 18 months, 8865 (57·0%) of 15 414 patients in the intervention group and 2895 (19·9%) of 14 500 patients in the control group had a blood pressure of less than 130/80 mm Hg, with a group difference of 37·0% (95% CI 34·9 to 39·1%; p<0·0001). Mean systolic blood pressure decreased by -26·3 mm Hg (95% CI -27·1 to -25·4) from baseline to 18 months in the intervention group and by -11·8 mm Hg (-12·6 to -11·0) in the control group, with a group difference of -14·5 mm Hg (95% CI -15·7 to -13·3 mm Hg; p<0·0001). Mean diastolic blood pressure decreased by -14·6 mm Hg (-15·1 to -14·2) from baseline to 18 months in the intervention group and by -7·5 mm Hg (-7·9 to -7·2) in the control group, with a group difference of -7·1 mm Hg (-7·7 to -6·5 mm Hg; p<0·0001). No treatment-related serious adverse events were reported in either group. INTERPRETATION: Compared with enhanced usual care, village doctor-led intervention resulted in statistically significant improvements in blood pressure control among rural residents in China. This feasible, effective, and sustainable implementation strategy could be scaled up in rural China and other low-income and middle-income countries for hypertension control. FUNDING: Ministry of Science and Technology of China.

Research progress of Nedd4L in cardiovascular diseases.

Post-translational modifications (PTMs) are a covalent processing process of proteins after translation. Proteins are capable of playing their roles only after being modified, so as to maintain the normal physiological function of cells. As a key modification of protein post-translational modification, ubiquitination is an essential element, which forms an enzyme-linked reaction through ubiquitin-activating enzyme, ubiquitin binding enzyme, and ubiquitin ligase, aiming to regulate the expression level and function of cellular proteins. Nedd4 family is the largest group of ubiquitin ligases, including 9 members, such as Nedd4-1, Nedd4L (Nedd4-2), WWP1, WWP2, ITCH, etc. They could bind to substrate proteins through their WW domain and play a dominant role in the ubiquitination process, and then participate in various pathophysiological processes of cardiovascular diseases (such as hypertension, myocardial hypertrophy, heart failure, etc.). At present, the role of Nedd4L in the cardiovascular field is not fully understood. This review aims to summarize the progress and mechanism of Nedd4L in cardiovascular diseases, and provide potential perspective for the clinical treatment or prevention of related cardiovascular diseases by targeting Nedd4L.

Serum Spermidine in Relation to Risk of Stroke: A Multilevel Study.

The relationship between serum spermidine levels and future cardiovascular disease risk has not yet been well elucidated in the general population based on community studies. Using a nested case-control study, we estimated the association between serum spermidine level and future stroke. New stroke cases had higher baseline levels of spermidine than controls [182.8 (141.8-231.5) vs. 152.0 (124.3-193.0), P < 0.001]. After multivariable adjustment, individuals with spermidine ≥ 205.9 nmol/L (T3) higher risks of stroke (HR 5.02, 95% CI 1.58-16.02) with the lowest quartile (< 136.9 nmol/L) as reference. The association between serum spermidine levels and risk of stroke seemed to be consistent and was reproducible in our cross-sectional studies. In addition, comparisons of the areas under receiver operator characteristics curves confirmed that a model including spermidine had better discrimination than without (0.755 vs. 0.715, P = 0.04). Here we report a close relationship exists between serum spermidine levels and risk of stroke.

Noninvasive estimation of aortic pressure waveform based on simplified Kalman filter and dual peripheral artery pressure waveforms.

BACKGROUND AND OBJECTIVE: Aortic pressure (Pa) is important for the diagnosis of cardiovascular disease. However, its direct measurement is invasive, not risk-free, and relatively costly. In this paper, a new simplified Kalman filter (SKF) algorithm is employed for the reconstruction of the Pa waveform using dual peripheral artery pressure waveforms. METHODS: Pa waveforms obtained in a previous study were collected from 25 patients. Simultaneously, radial and femoral pressure waveforms were generated from two simulation experiments, using transfer functions. In the first, the transfer function is a known finite impulse response; and in the second, it is derived from a tube-load model. To analyze the performance of the proposed SKF algorithm, variable amounts of noise were added to the observed output signal, to give a range of signal-to-noise ratios (SNRs). Additionally, central aortic, brachial and femoral pressure waveforms were simultaneously collected from 2 Sprague-Dawley rats and the measured and reconstructed Pa waveforms were compared. RESULTS: The proposed SKF algorithm outperforms canonical correlation analysis (CCA), which is the current state-of-the-art blind system identification method for the non-invasive estimation of central aortic blood pressure. It is also shown that the proposed SKF algorithm is more noise-tolerant than the CCA algorithm over a wide range of SNRs. CONCLUSION: The simulations and animal experiments illustrate that the proposed SKF algorithm is accurate and stable in the face of low SNRs. Improved methods for estimating central blood pressure as a measure of cardiac load adds to their value as a prognostic and diagnostic tool.

Effect of different alcohol consumption levels on the left atrial size: A cross-sectional study in rural China.

OBJECTIVE: Previous studies have investigated the relationship between alcohol and ventricular structure; however, few studies have evaluated the relation between alcohol consumption and the atrium size. In this study, we aimed to test the association between alcohol consumption and left atrium (LA) size in the general population. METHODS: A population-based sample of 10,211 subjects aged ≥35 years and free from hypertension at baseline were followed from January 2012 to August 2013. Left atrial enlargement (LAE) was defined as the ratio of LA diameter to body surface area exceeding 2.4 cm/m2 in both the sexes. Independent factors for LAE were estimated by multiple logistic regression analyses. RESULTS: The study included 10,211 participants (4,751 men and 5,460 women). Left atrial diameter/body surface area (LAD/BSA) was higher in the moderate and heavy alcohol consumption groups than in the non-drinker group (non-drinker, 20.5±0.03 cm/m2; moderate, 20.8±0.09 cm/m2; and heavy, 20.6±0.06 cm/m2; p<0.001). Both the groups of moderate and heavy drinkers had a higher incidence of LAE than the non-drinker group (6.9% of non-drinkers, 9.9% of moderate drinkers, and 8.4% of heavy drinkers; p<0.001). After adjusting for related risk factors, multiple logistic regression analyses showed that moderate drinkers had an approximately 1.4-fold higher risk of LAE [odds ratio (OR): 1.387, 95% confidence interval (CI) 1.056-1.822, p=0.019] compared with the non-drinkers, and the heavy drinkers had an approximately 1.2-fold higher risk of LAE (OR: 1.229, 95% CI: 1.002-1.508, p=0.047) compared with that of the non-drinkers. CONCLUSION: Both heavy and moderate drinkers had increased odds for LAE compared with participants with no alcohol consumption in the general population.

A nomogram integrating non-ECG factors with ECG to screen left ventricular hypertrophy among hypertensive patients from northern China.

OBJECTIVE: We aimed to establish and validate a user-friendly and clinically practical nomogram for estimating the probability of echocardiographic left ventricular hypertrophy (echo-LVH) indexed to BSA among hypertensive patients from northern China. METHODS: A total of 4954 hypertensive patients were recruited from a population-based cohort study from January 2012 to August 2013. The dataset was randomly split into two sets: training (n = 3303) and validation (n = 1651). Three nomograms were initially constructed. That is the Cornell product nomogram, the non-ECG nomogram, and the integrated nomogram which integrated non-ECG risk factors and Cornell-voltage duration product. The least absolute shrinkage and selection operator strategies were employed to screen for non-ECG features. The performance of the nomograms was evaluated using discrimination, calibration, and decision curve analysis (DCA). The net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were also calculated. RESULTS: The AUCs, NRIs, IDIs, and DCA curves of the nomograms demonstrated that the integrated nomogram performed best among all three nomograms. The integrated nomogram incorporated age, sex, educational level, hypertension duration, SBP, DBP, eGFR, sleep duration, tea consumption, and the Cornell-voltage duration product. The AUC was 0.758 and had a good calibration (Hosmer-Lemeshow test, P = 0.73). Internal validation showed an acceptable AUC of 0.735 and good calibration was preserved (Hosmer-Lemeshow test, P = 0.19). The integrated nomogram was clinically beneficial across a range of thresholds of 10-50%. CONCLUSION: The integrated nomogram is a convenient and reliable tool that enables early identification of hypertensive patients at high odds of LVH and can assist clinicians in their decision-making.

Simultaneous adaption of the gain and phase of a generalized transfer function for aortic pressure waveform estimation.

GOAL: This paper proposes and validates a completely adaptive transfer function (CATF) based on an autoregressive exogenous (ARX) model which adjusts the gain and phase of a generalized transfer function (GTF) simultaneously to estimate the aortic pressure waveform from a brachial pressure waveform. METHODS: Invasive aortic and brachial pressure waveforms were recorded from 34 subjects for the validation of the proposed method. Individual transfer functions (ITFs) were trained based on the pressure waveforms using an ARX model. The GTF was derived by averaging the ITFs. CATF was then obtained by adjusting both the gain and phase of the GTF using regression formulas calculated from the ITFs and brachial hemodynamic parameters. Meanwhile the quantitative contributions of the adaption of gain and phase of the GTF were investigated respectively. The root-mean-square-error of the total waveform and absolute errors of common hemodynamic indices including systolic and diastolic blood pressures (SBP and DBP, respectively), pulse pressure (PP) and augmentation index were used to evaluate the performance of the proposed method in the data divided into low, middle and high PP amplification groups. RESULTS: The CATF achieved lower errors for DBP and PP in the low PP amplification group (1.79 versus 2.10 mmHg and 5.08 versus 6.23 mmHg, respectively, both P < 0.05) and PP in the middle amplification group (1.43 versus 1.92 mmHg, P < 0.05) compared with the GTF. SIGNIFICANCE: The proposed method provides a step towards the development of an improved and clinically useful non-invasive approach for estimating the aortic pressure waveform from a peripheral pressure waveform.