Soluble ST2 for predicting heart failure, atrial fibrillation and death in patients with coronary heart disease with or without renal insufficiency.

Background: This study aimed to investigate the relationship between baseline soluble suppression of tumorigenesis-2 (sST2) concentration and the outcomes of heart failure (HF), atrial fibrillation (AF) or death in patients with coronary heart disease (CHD) with or without renal insufficiency (RI). Methods: Between March 2011 and December 2015, 3454 patients with CHD from the Chinese PLA General Hospital were enrolled in this cohort study. The patients were followed up until October 2021. AF, HF, and death events were recorded. Associations between baseline sST2 concentrations and clinical outcomes were assessed using Kaplan-Meier (K-M) curves, and Cox regression and generalised additive models. Subgroup analysis were carried out between RI and non-RI groups. Results: Among the patients with CHD (61.5 ± 11.8 years; 78.6 % men), 415 (12.02 %) had RI. During a median follow-up of 8.37 years, HF and AF were reported in 216 (6.25 %) and 174 (5.04 %) patients, respectively, and 297 (8.60 %) died. The K-M curves indicated that patients in the higher quartiles of sST2 concentrations were correlated with a poor survival rate of HF, AF, or death (all Ps < 0.001). Generalised additive model (GAM) demonstrated a nonlinear positive association between sST2 concentration and the risk of HF, AF, and death in CHD patients. The cut-off value of sST2 for predicting HF, AF and death were 32.1, 25.4 and 28.6 ng/mL, respectively. CHD patients with sST2 higher than the cut-off value had higher risks of HF (HR: 3.02, 95%CI: 2.24-4.05), AF (HR: 2.86; 95%CI: 2.10-3.90), and death (HR:2.11, 95%CI: 1.67-2.67). Furthermore, in patients with RI (12.02 %, n = 415), the prognostic value of sST2 over the cut-off value for HF and death remained unchanged (HR: 3.21 and 2.35; P < 0.05). In patients with CHD with or without RI, sST2 improved the area under the curve (AUC) of traditional risk models for predicting clinical endpoint events. Conclusions: The biomarker sST2 may be useful for predicting HF, AF, and death in patients with CHD. The predicted value was not affected by renal function.

Antiviral effectiveness and survival correlation of azvudine and nirmatrelvir/ritonavir in elderly severe patients with COVID-19: a retrospective real-world study.

Background: Azvudine and nirmatrelvir/ritonavir are approved to treat mild-to-moderate coronavirus disease 2019 (COVID-19) in adults with a high risk for progression to severe infection. We sought to compare the antiviral effectiveness and clinical outcomes of elderly severe patients with COVID-19 receiving these two antiviral agents. Methods: In this observational study, we identified 249 elderly patients with severe COVID-19 infection who were admitted to the Second Medical Center of the People's Liberation Army General Hospital from December 2022 to January 2023, including 128 azvudine recipients, 66 nirmatrelvir/ritonavir recipients and 55 patients not received antiviral treatments. We compared the cycle threshold (Ct) value dynamic change of all three groups. The primary outcome was a composite outcome of disease progression, including all-cause death, intensive care unit admission, and initiation of invasive mechanical ventilation. The outcomes of all enrolled patients were followed up from the electronic medical record system. Kaplan-Meier and Cox risk proportional regression analyses were used to compare the clinical outcomes of all three groups. To more directly compare the effectiveness of the two antiviral drugs, we performed propensity-score matching between the two antiviral groups and compared antiviral efficacy and clinical outcomes in the matched population. Findings: Among 249 patients (mean age, 91.41 years), 77 patients died during the follow-up period. When compared to patients who did not receive any antivirals, neither nirmatrelvir/ritonavir nor azvudine demonstrated a survival benefit. The Cox analysis of the all-cause death of the three groups showed that the risk of death was 0.730 (0.423-1.262) in the azvudine group 0.802 (0.435-1.480) and in the nirmatrelvir/ritonavir group compared with the non-antiviral group. After propensity score matching, we included 58 azvudine recipients and 58 nirmatrelvir/ritonavir recipients. The fitted curve of the Ct value after matching illustrated that the rate of viral decline in the early stage of nirmatrelvir/ritonavir treatment seems to surpass that of azvudine, but there was no statistical significance. Azvudine was seemly associated with a lower risk of composite outcomes (HR:1.676, 95% CI:0.805-3.488) and short-term all-cause death (HR: 1.291, 95%CI: 0.546-3.051). Interpretation: Patients who received azvudine have a similar antiviral effectiveness and survival curve trend compared to nirmatrelvir/ritonavir. In this limited series, antiviral treatment was not associated with a significant clinical benefit. This lack of clinical benefit might be attributed to potential bias. Funding: This study was supported by the "National Key R&D Program of China" (Funding No. 2020YFC2008900) and the National Defense Science and Technology Innovation Special Zone Project (223-CXCY-N101-07-18-01).

Artificial Intelligence-Assisted Left Ventricular Diastolic Function Assessment and Grading: Multiview Versus Single View.

BACKGROUND: Clinical assessment and grading of left ventricular diastolic function (LVDF) requires quantification of multiple echocardiographic parameters interpreted according to established guidelines, which depends on experienced clinicians and is time consuming. The aim of this study was to develop an artificial intelligence (AI)-assisted system to facilitate the clinical assessment of LVDF. METHODS: In total, 1,304 studies (33,404 images) were used to develop a view classification model to select six specific views required for LVDF assessment. A total of 2,238 studies (16,794 two-dimensional [2D] images and 2,198 Doppler images) to develop 2D and Doppler segmentation models, respectively, to quantify key metrics of diastolic function. We used 2,150 studies with definite LVDF labels determined by two experts to train single-view classification models by AI interpretation of strain metrics or video. The accuracy and efficiency of these models were tested in an external data set of 388 prospective studies. RESULTS: The view classification model identified views required for LVDF assessment with good sensitivity (>0.9), and view segmentation models successfully outlined key regions of these views with intersection over union > 0.8 in the internal validation data set. In the external test data set of 388 cases, AI quantification of 2D and Doppler images showed narrow limits of agreement compared with the two experts (e.g., left ventricular ejection fraction, -12.02% to 9.17%; E/e' ratio, -3.04 to 2.67). These metrics were used to detect LV diastolic dysfunction (DD) and grade DD with accuracy of 0.9 and 0.92, respectively. Concerning the single-view method, the overall accuracy of DD detection was 0.83 and 0.75 by strain-based and video-based models, and the accuracy of DD grading was 0.85 and 0.8, respectively. These models could achieve diagnosis and grading of LVDD in a few seconds, greatly saving time and labor. CONCLUSION: AI models successfully achieved LVDF assessment and grading that compared favorably with human experts reading according to guideline-based algorithms. Moreover, when Doppler variables were missing, AI models could provide assessment by interpreting 2D strain metrics or videos from a single view. These models have the potential to save labor and cost and to facilitate work flow of clinical LVDF assessment.

Joint association of hyperuricemia and chronic kidney disease with mortality in patients with chronic heart failure.

Background: The joint association of hyperuricemia and chronic kidney disease (CKD) with mortality in patients with chronic heart failure (CHF) is not conclusive. Methods: This retrospective cohort study was conducted in Chinese People's Liberation Army General Hospital, Beijing, China. We included 9,367 patients with CHF, who were hospitalized between January 2011 and June 2019. The definitions of hyperuricemia and CKD were based on laboratory test, medication use, and medical record. We categorized patients with CHF into 4 groups according to the absence (-) or presence (+) of hyperuricemia and CKD. The primary outcomes included in-hospital mortality and long-term mortality. We used multivariate logistic regression and Cox proportional hazards regression to estimate the mortality risk according to the hyperuricemia/CKD groups. Results: We identified 275 cases of in-hospital mortality and 2,883 cases of long-term mortality in a mean follow-up of 4.81 years. After adjusting for potential confounders, we found that compared with the hyperuricemia-/CKD- group, the risks of in-hospital mortality were higher in the hyperuricemia+/CKD- group (odds ratio [OR], 95% confidence interval [CI]: 1.58 [1.01-2.46]), hyperuricemia-/CKD+ group (OR, 95% CI: 1.67 [1.10-2.55]), and hyperuricemia+/CKD+ group (OR, 95% CI: 2.12 [1.46-3.08]). Similar results were also found in long-term mortality analysis. Compared with the hyperuricemia-/CKD- group, the adjusted hazard ratios and 95% CI for long-term mortality were 1.25 (1.11-1.41) for hyperuricemia+/CKD- group, 1.37 (1.22-1.53) for hyperuricemia-/CKD+ group, and 1.59 (1.43-1.76) for hyperuricemia+/CKD+ group. The results remained robust in the sensitivity analysis. Conclusions: Hyperuricemia and CKD, both individually and cumulatively, are associated with increased mortality risk in patients with CHF. These results highlighted the importance of the combined control of hyperuricemia and CKD in the management of heart failure.

Pipersentan: A De Novo Synthetic Endothelin Receptor Antagonist that Inhibits Monocrotaline- and Hypoxia-Induced Pulmonary Hypertension.

Background: Although major advances have been made in the pathogenesis and management of pulmonary arterial hypertension (PAH), the endothelin system is still considered to play a vital role in the pathology of PAH due to its vasoconstrictive action. Endothelin receptor antagonists (ERAs), either as monotherapy or in combination with other drugs, have attracted much attention in the treatment of this lethal disease, and research is continuing. Methods: A novel ERA, pipersentan 5-(1,3-Benzodioxol-5-yl)-6-[2-(5-bromopyrimidin-2-yl)oxyethoxy]-N-(2-methoxyethylsulfamoyl)pyrimidin-4-amine, was recently synthesized and the physicochemical characterizations and the pharmacology both in vitro and in vivo were studied. Results: This orally administered ERA can both competitively and selectively inhibit the binding of endothelin-1 (ET-1) to its receptors with good physicochemical characteristics. Pipersentan efficaciously antagonized the effects of ET-1 on pulmonary artery smooth muscle cell proliferation, migration and calcium mobilization and effectively improved right ventricular hypertrophy and pulmonary arterial pressure in both monocrotaline- and hypoxia-induced pulmonary hypertension (PH) rat models. Conclusions: This profile identifies pipersentan as a new agent for treating ET-1 system activation-related PH.

Establishment of a diagnostic model of coronary heart disease in elderly patients with diabetes mellitus based on machine learning algorithms.

OBJECTIVE: To establish a prediction model of coronary heart disease (CHD) in elderly patients with diabetes mellitus (DM) based on machine learning (ML) algorithms. METHODS: Based on the Medical Big Data Research Centre of Chinese PLA General Hospital in Beijing, China, we identified a cohort of elderly inpatients (≥ 60 years), including 10,533 patients with DM complicated with CHD and 12,634 patients with DM without CHD, from January 2008 to December 2017. We collected demographic characteristics and clinical data. After selecting the important features, we established five ML models, including extreme gradient boosting (XGBoost), random forest (RF), decision tree (DT), adaptive boosting (Adaboost) and logistic regression (LR). We compared the receiver operating characteristic curves, area under the curve (AUC) and other relevant parameters of different models and determined the optimal classification model. The model was then applied to 7447 elderly patients with DM admitted from January 2018 to December 2019 to further validate the performance of the model. RESULTS: Fifteen features were selected and included in the ML model. The classification precision in the test set of the XGBoost, RF, DT, Adaboost and LR models was 0.778, 0.789, 0.753, 0.750 and 0.689, respectively; and the AUCs of the subjects were 0.851, 0.845, 0.823, 0.833 and 0.731, respectively. Applying the XGBoost model with optimal performance to a newly recruited dataset for validation, the diagnostic sensitivity, specificity, precision, and AUC were 0.792, 0.808, 0.748 and 0.880, respectively. CONCLUSIONS: The XGBoost model established in the present study had certain predictive value for elderly patients with DM complicated with CHD.

Revealing the Critical Regulators of Modulated Smooth Muscle Cells in Atherosclerosis in Mice.

Background: There are still residual risks for atherosclerosis (AS)-associated cardiovascular diseases to be resolved. Considering the vital role of phenotypic switching of smooth muscle cells (SMCs) in AS, especially in calcification, targeting SMC phenotypic modulation holds great promise for clinical implications. Methods: To perform an unbiased and systematic analysis of the molecular regulatory mechanism of phenotypic switching of SMCs during AS in mice, we searched and included several publicly available single-cell datasets from the GEO database, resulting in an inclusion of more than 80,000 cells. Algorithms implemented in the Seurat package were used for cell clustering and cell atlas depiction. The pySCENIC and SCENIC packages were used to identify master regulators of interested cell groups. Monocle2 was used to perform pseudotime analysis. clusterProfiler was used for Gene Ontology enrichment analysis. Results: After dimensionality reduction and clustering, reliable annotation was performed. Comparative analysis between cells from normal artery and AS lesions revealed that three clusters emerged as AS progression, designated as mSMC1, mSMC2, and mSMC3. Transcriptional and functional enrichment analysis established a continuous transitional mode of SMCs' transdifferentiation to mSMCs, which is further supported by pseudotime analysis. A total of 237 regulons were identified with varying activity scores across cell types. A potential core regulatory network was constructed for SMC and mSMC subtypes. In addition, module analysis revealed a coordinate regulatory mode of regulons for a specific cell type. Intriguingly, consistent with gain of ossification-related transcriptional and functional characteristics, a corresponding small set of regulators contributing to osteochondral reprogramming was identified in mSMC3, including Dlx5, Sox9, and Runx2. Conclusion: Gene regulatory network inference indicates a hierarchical organization of regulatory modules that work together in fine-tuning cellular states. The analysis here provides a valuable resource that can provide guidance for subsequent biological experiments.

MicroRNA miR-27a-3p accelerates cardiac hypertrophy by targeting neuro-oncological ventral antigen 1.

MiRNAs are a class of small non-coding RNAs (ncRNAs) responsible for post-transcriptional regulation of target genes. Accumulating evidence indicates that miRNAs are implicated in the progression of cardiac hypertrophy. Therefore, understanding the molecular mechanisms how these miRNAs regulate cardiac hypertrophy is useful for diagnosis and monitoring of disease progression. In this study, to investigate the effect of miR-27a-3p, we established an in vitro cardiac hypertrophy model by treating H9c2 cardiomyocytes with angiotensin II (Ang II) and an in vivo model through the chronic infusion of Ang II into mice. As revealed by our experimental results, miR-27a-3p expression was significantly increased in clinical samples, animal and cell models of cardiac hypertrophy. Inhibiting miR-27a-3p mitigated cardiac hypertrophy phenotype induced by Ang II. Additionally, our work identified NOVA1 (neuro-oncological ventral antigen 1) as a downstream target of miR-27a-3p. miR-27a-3p overexpression reduced NOVA1 protein level and mRNA expression. Consistently, NOVA1 silencing promoted cardiac hypertrophy phenotype induced by Ang II. In summary, these results suggest that the upregulation of miR-27a-3p may serve as a diagnostic factor for cardiac hypertrophy, and miR-27a-3p upregulation promotes cardiac hypertrophy by targeting NOVA1.

Acute Lower Respiratory Tract Infection Increased the Risk of Cardiovascular Events and All-Cause Mortality in Elderly Patients With Stable Coronary Artery Disease.

Objective: To investigate the predictors of acute cardiovascular events within 90 days after an acute lower respiratory tract infection (ALRTI) in elderly patients with stable coronary artery disease (sCAD). Methods: Observational analyses were conducted in a prospective cohort of the elderly with sCAD, during 90 days after they were hospitalized for ALRTI. Multiple logistic regression analysis was performed to identify predictors for acute cardiovascular events and all-cause mortality. Results: The present study comprised 426 patients with sCAD (median age: 88 years; IQR: 84-91; range: 72-102). Among these patients, 257 suffering from ALRTI were enrolled in the infection group. Meanwhile, 169 patients who did not suffer from ALRTI were regarded as the non-infection group. Compared with the non-infection group, patients in the infection group had a higher incidence of acute cardiovascular events (31.9 vs. 13.6%, p < 0.001) and all-cause mortality (13.2 vs. 1.8%, p < 0.001) during the 90-day follow-up. In addition, in the infection group, the incidence of cardiovascular events was also higher than those in the non-infection group during the 7-day and 30-day follow-up (10.9 vs. 2.4%, p = 0.001; 20.6 vs. 6.5%, p < 0.001). The same difference in the incidence of all-cause mortality during 7 and 30 days (1.2 vs. 0%, p = 0.028; 3.9 vs. 0.6%, p = 0.021) was observed between the two groups. Furthermore, multiple regression analysis found that ALRTI was independently associated with increased risk of cardiovascular events and all-cause mortality in elderly patients with sCAD. Conclusion: In elderly patients with sCAD, ALRTI was an independent predictor for both cardiovascular events and all-cause mortality.

Functions of Monocytes and Macrophages and the Associated Effective Molecules and Mechanisms at the Early Stage of Atherosclerosis.

OBJECTIVE: This study aimed to explore the functions and possible underlying regulatory molecules and mechanisms of monocytes and macrophages under early atherosclerotic conditions. METHODS: THP-1-derived monocytes or macrophages were induced by 50 µg/ml oxidized low density lipoprotein (ox-LDL) for 24 hours, and the degree of lipid metabolism and inflammation were determined. In addition, we identified differentially expressed genes, noncoding ribonucleic acids (RNAs), pathways and mechanisms by RNA sequencing, and performed further correlation analysis and molecular expression verification. RESULTS: Monocytes could not form foam cells with oil red O staining directly and had low levels of lipids as determined by total cholesterol and triglycerides assays, cholesterol uptake molecules CD36, the class A macrophage scavenger receptor and lectin-like oxidized low-density lipoprotein receptor-1 and cholesterol efflux molecules ATP binding cassette transporter A1, ATP binding cassette transporter G1 and liver X receptor α, and inflammatory factors, which were markedly different from those in macrophages. Additionally, sequencing data showed obviously differentially expressed genes, microRNAs and long noncoding RNAs in the atherosclerotic group. We identified 15 upregulated and downregulated genes, and 10 biological processes and pathways involved in atherosclerosis. Specifically, fatty acid desaturase 2 and apolipoprotein A1 in the peroxisome proliferator-activated receptor signaling pathway were differentially expressed in stimulated macrophages, whereas no changes were observed in the monocyte groups. Furthermore, correlation analysis showed differential expressed lncRNAs targeting miRNAs and mRNAs, and 24 competing endogenous RNA (ceRNA) networks of long noncoding RNA-microRNA-messenger RNA in early oxidative macrophages. CONCLUSIONS: Monocytes did not directly participate in lipid metabolism before differentiation into macrophages at the early stage in vitro. Furthermore, noncoding RNAs and ceRNA networks might play important roles in regulating the lipid metabolism of macrophages at the early stage of atherosclerosis.

The miR-182/Myadm axis regulates hypoxia-induced pulmonary hypertension by balancing the BMP- and TGF-ß-signalling pathways in an SMC/EC-crosstalk-associated manner.

We recently identified oncologic miR-182 as a new regulator of pulmonary artery hypertension (PAH) that targets myeloid-associated differentiation marker (Myadm), which is expressed in bone marrow stem cells and multipotent progenitors. Both miR-182 and Myadm are expressed in the cardiopulmonary system and correlated with the balance between the bone morphogenetic protein (BMP) and the transforming growth factor (TGF)-ß signalling pathways, which are disturbed in PAH. We hypothesize that miR-182/Myadm are involved in BMP-TGF-ß-signalling way in PAH. Hypoxia triggered pathological progression in cardiopulmonary PAH in vivo and in vitro; these changes were accompanied by strongly dowregulated BMP/SMAD1/5/8 expression and enhanced TGF-ß/SMAD2/3 signalling pathway, favouring SMAD4/SMAD2 transcript formation and inhibiting the PAH negative regulator Id1 expression. miR-182 gain-of-function significantly inhibited the pathological progression in hypoxia-induced PAH (HPH) in vivo and in vitro, with a restoration of the balance in BMP-TGF-ß signalling pathway. This recovery was abrogated by overexpression of Myadm. Conversely, loss-of-function of miR-182 increased the pathological progression of HPH followed by severe disturbance of BMP and TGF-ß signal transduction and reduced Id1 expression, which was restored by Myadm knockdown. We also showed that the miR-182/Myadm relate BMP-TGF-ß pathway is associated with NOS3/NO/cGMP via the crosstalk between endothelial cells and smooth muscle cells. Our findings further support the therapeutic significance of miR-182/Myadm in PAH via the balance of BMP- and TGF-ß-associated mechanisms.

Plasma Homocysteine Is a Predictive Factor for Accelerated Renal Function Decline and Chronic Kidney Disease in a Community-Dwelling Population.

BACKGROUND: Whether elevated plasma total homocysteine (tHcy) is a risk factor for the progression of kidney disease in general population has not been well established. The purpose of this study was to investigate the prognostic properties of plasma tHcy for renal function decrement and early chronic kidney disease (CKD) in community-dwelling populations with normal renal function at baseline. METHODS: A total of 1,426 participants were enrolled and followed for a median of 4.8 years (interquartile range, 4.5-5.2), and estimated glomerular filtration rate (eGFR) was evaluated. One main outcome was the rapid eGFR decline defined as a decline in eGFR of >3 mL/min per 1.73 m2 per year; the other was the new incidence of CKD. RESULTS: At the end of follow-up, the incidence of rapid eGFR decline and new-onset CKD was 20.7 and 5.6%, respectively. In multivariate linear regression analysis, age, central pulse pressure, fasting blood glucose, and concentration of tHcy were independent determinants of the change in eGFR. There was a graded association between tHcy quartiles and eGFR decline. Compared with participants with the lowest quartile of tHcy levels, those with the highest quartile had significantly increased risk for rapid eGFR decline (adjusted odds ratio [aOR] = 1.81; 95% confidence interval [CI]: 1.25-2.94) and new onset of CKD (adjusted hazard ratio = 4.29; 95% CI: 1.42-12.99) after adjusting for various confounders. Similarly, significant associations were also found when baseline tHcy was classified as hyperhomocysteinemia (>15 µmol/L) versus normal tHcy level (≤15 µmol/L). However, there was only association between the change in tHcy levels and new occurrence of CKD but not with rapid eGFR decline (aOR = 0.99, p = 0.613). CONCLUSIONS: In this prospective cohort of individuals from community-based population, elevated plasma tHcy emerged as an independent predictor of renal function decline and incident CKD, which might support selection of at-risk individuals.

Effects of sodium-glucose cotransporter 2 inhibitors on cardiovascular outcomes in elderly patients with comorbid coronary heart disease and diabetes mellitus.

OBJECTIVE: To investigate the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on cardiovascular outcomes in elderly Chinese patients with comorbid coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). METHODS: A retrospective cohort study was conducted on 501 elderly inpatients (≥ 60 years) with comorbid CHD/T2DM in Department of Cardiovascular Medicine and Endocrinology, Chinese PLA General Hospital from January 2018 to December 2019. These patients were divided into two groups according to the administration of SGLT2i. All the demographic characteristics and clinical data were collected. Cardiovascular outcomes, including all-cause mortality, major adverse cardiovascular events (MACE), and hospitalization for heart failure (HHF), were followed up. RESULTS: In the cohort, there were 167 patients in the SGLT2i group and 334 patients in the control group. In the efficacy analyses, the incidence of MACE was lower in the SGLT2i group than in the control group: 3.6% vs. 9.3% (P = 0.022). A lower risk of MACE was observed in the SGLT2i group [hazard ratio (HR) = 0.40, 95% CI: 0.17-0.95]. There was no significant difference in the incidence of all-cause mortality or HHF between the two groups. No significant difference of HR was observed for all-cause mortality (HR = 0.41, 95% CI: 0.12-1.41) or HHF (HR = 0.58, 95% CI: 0.12-2.81). CONCLUSIONS: SGLT2i treatment exhibited benefits for elderly patients with comorbid CHD/T2DM with a lower risk for MACE.

Prognostic Value of Plasma NT-proBNP levels in Hospitalized Patients Older than 80 Years of Age in a Hospital in Beijing, China. / Valor Prognóstico dos Níveis Plasmáticos de NT-proBNP em Pacientes Hospitalizados com Mais de 80 Anos de Idade em um Hospital em Pequim, China.

BACKGROUND: Despite growing evidence that N-terminal pro-brain natriuretic peptide (NT-proBNP) has an important prognostic value in older adults, there is limited data on its prognostic predictive value. OBJECTIVES: The aim of this study is to evaluate the clinical significance of NT-proBNP in hospitalized patients older than 80 years of age in Beijing, China. METHODS: This prospective, observational study was conducted in 724 very elderly patients in a geriatric ward (age ≥80 years, range, 80100 years, mean, 86.6 3.0 years). Multivariate linear regression analysis was used to screen for factors independently associated with NT-proBNP, and the Cox proportional hazard regression model was used to screen for relationships between NT-proBNP levels and major endpoints. The major endpoints assessed were all-cause death and MACEs. P values < 0.05 were considered statistically significant. RESULTS: The prevalence rates of coronary heart disease, hypertension, and diabetes mellitus were 81.4%, 75.1%, and 41.2%, respectively. The mean NT-proBNP level was 770 ± 818 pg/mL. Using multivariate linear regression analyses, correlations were found between plasma NT-proBNP and body mass index, atrial fibrillation, estimated glomerular filtration rate, left atrial diameter, left ventricular ejection fraction, use of betablocker, levels of hemoglobin, plasma albumin, triglycerides, serum creatinine, and blood urea nitrogen. The risk of all-cause death (HR, 1.63; 95% CI, 1.0052.642; P = 0.04) and major adverse cardiovascular events (MACE; HR, 1.77; 95% CI, 1.2893.531; P = 0.04) in the group with the highest NT-proBNP level was significantly higher than that in the group with the lowest level, according to Cox regression models after adjusting for multiple factors. As expected, echocardiography parameters adjusted the prognostic value of NT-proBNP in the model. CONCLUSIONS: NT-proBNP was identified as an independent predictor of all-cause death and MACE in hospitalized patients older than 80 years of age.

FUNDAMENTO: Apesar das evidências crescentes de que o peptídeo natriurético N-terminal pró-cérebro (NT-proBNP) tem um valor prognóstico importante em adultos mais velhos, há dados limitados sobre seu valor preditivo prognóstico. OBJETIVOS: O objetivo deste estudo é avaliar o significado clínico do NT-proBNP em pacientes hospitalizados com mais de 80 anos de idade em Pequim, China. MÉTODOS: Este estudo prospectivo e observacional foi conduzido em 724 pacientes muito idosos em uma enfermaria geriátrica (idade ≥80 anos, variação, 80-100 anos, média, 86,6±3,0 anos). A análise de regressão linear multivariada foi utilizada para rastrear os fatores independentemente associados ao NT-proBNP, e o modelo de regressão de risco proporcional de Cox foi utilizado para rastrear as associações entre os níveis de NT-proBNP e os principais endpoints . Os principais endpoints avaliados foram mortes por todas as causas e ECAM. Valores de p <0,05 foram considerados estatisticamente significativos. RESULTADOS: As taxas de prevalência de doença cardíaca coronariana, hipertensão e diabetes mellitus foram 81,4%, 75,1% e 41,2%, respectivamente. O nível médio de NT-proBNP foi 770±818 pg/mL. Utilizando análises de regressão linear multivariada, foram encontradas correlações entre o NT-proBNP plasmático e índice de massa corporal, fibrilação atrial, taxa de filtração glomerular estimada, diâmetro do átrio esquerdo, fração de ejeção do ventrículo esquerdo, uso de betabloqueador, níveis de hemoglobina, albumina plasmática, triglicérides, creatinina sérica, e nitrogênio uréico no sangue. O risco de morte por todas as causas (HR, 1,63; IC 95%, 1,005-2,642; p = 0,04) e eventos cardiovasculares adversos maiores (ECAM; HR, 1,77; IC 95%, 1,289-3,531; p = 0,04) no grupo com o nível mais alto NT-proBNP foi significativamente maior do que no grupo com NT-proBNP mais baixo, de acordo com os modelos de regressão de Cox após o ajuste para vários fatores. Como esperado, os parâmetros da ecocardiografia ajustaram o valor prognóstico do NT-proBNP no modelo. CONCLUSÕES: O NT-proBNP foi identificado como um preditor independente de morte por todas as causas e ECAM em pacientes hospitalizados com mais de 80 anos de idade.

Valor Prognóstico dos Níveis Plasmáticos de NT-proBNP em Pacientes Hospitalizados com Mais de 80 Anos de Idade em um Hospital em Pequim, China / Prognostic Value of Plasma NT-proBNP levels in Hospitalized Patients Older than 80 Years of Age in a Hospital in Beijing, China

Resumo Fundamento Apesar das evidências crescentes de que o peptídeo natriurético N-terminal pró-cérebro (NT-proBNP) tem um valor prognóstico importante em adultos mais velhos, há dados limitados sobre seu valor preditivo prognóstico. Objetivos O objetivo deste estudo é avaliar o significado clínico do NT-proBNP em pacientes hospitalizados com mais de 80 anos de idade em Pequim, China. Métodos Este estudo prospectivo e observacional foi conduzido em 724 pacientes muito idosos em uma enfermaria geriátrica (idade ≥80 anos, variação, 80-100 anos, média, 86,6±3,0 anos). A análise de regressão linear multivariada foi utilizada para rastrear os fatores independentemente associados ao NT-proBNP, e o modelo de regressão de risco proporcional de Cox foi utilizado para rastrear as associações entre os níveis de NT-proBNP e os principais endpoints . Os principais endpoints avaliados foram mortes por todas as causas e ECAM. Valores de p <0,05 foram considerados estatisticamente significativos. Resultados As taxas de prevalência de doença cardíaca coronariana, hipertensão e diabetes mellitus foram 81,4%, 75,1% e 41,2%, respectivamente. O nível médio de NT-proBNP foi 770±818 pg/mL. Utilizando análises de regressão linear multivariada, foram encontradas correlações entre o NT-proBNP plasmático e índice de massa corporal, fibrilação atrial, taxa de filtração glomerular estimada, diâmetro do átrio esquerdo, fração de ejeção do ventrículo esquerdo, uso de betabloqueador, níveis de hemoglobina, albumina plasmática, triglicérides, creatinina sérica, e nitrogênio uréico no sangue. O risco de morte por todas as causas (HR, 1,63; IC 95%, 1,005-2,642; p = 0,04) e eventos cardiovasculares adversos maiores (ECAM; HR, 1,77; IC 95%, 1,289-3,531; p = 0,04) no grupo com o nível mais alto NT-proBNP foi significativamente maior do que no grupo com NT-proBNP mais baixo, de acordo com os modelos de regressão de Cox após o ajuste para vários fatores. Como esperado, os parâmetros da ecocardiografia ajustaram o valor prognóstico do NT-proBNP no modelo. Conclusões O NT-proBNP foi identificado como um preditor independente de morte por todas as causas e ECAM em pacientes hospitalizados com mais de 80 anos de idade.

Abstract Background Despite growing evidence that N-terminal pro-brain natriuretic peptide (NT-proBNP) has an important prognostic value in older adults, there is limited data on its prognostic predictive value. Objectives The aim of this study is to evaluate the clinical significance of NT-proBNP in hospitalized patients older than 80 years of age in Beijing, China. Methods This prospective, observational study was conducted in 724 very elderly patients in a geriatric ward (age ≥80 years, range, 80100 years, mean, 86.6 3.0 years). Multivariate linear regression analysis was used to screen for factors independently associated with NT-proBNP, and the Cox proportional hazard regression model was used to screen for relationships between NT-proBNP levels and major endpoints. The major endpoints assessed were all-cause death and MACEs. P values < 0.05 were considered statistically significant. Results The prevalence rates of coronary heart disease, hypertension, and diabetes mellitus were 81.4%, 75.1%, and 41.2%, respectively. The mean NT-proBNP level was 770 ± 818 pg/mL. Using multivariate linear regression analyses, correlations were found between plasma NT-proBNP and body mass index, atrial fibrillation, estimated glomerular filtration rate, left atrial diameter, left ventricular ejection fraction, use of betablocker, levels of hemoglobin, plasma albumin, triglycerides, serum creatinine, and blood urea nitrogen. The risk of all-cause death (HR, 1.63; 95% CI, 1.0052.642; P = 0.04) and major adverse cardiovascular events (MACE; HR, 1.77; 95% CI, 1.2893.531; P = 0.04) in the group with the highest NT-proBNP level was significantly higher than that in the group with the lowest level, according to Cox regression models after adjusting for multiple factors. As expected, echocardiography parameters adjusted the prognostic value of NT-proBNP in the model. Conclusions NT-proBNP was identified as an independent predictor of all-cause death and MACE in hospitalized patients older than 80 years of age.

Construction of a Non-Mutually Exclusive Decision Tree for Medication Recommendation of Chronic Heart Failure.

Objective: Although guidelines have recommended standardized drug treatment for heart failure (HF), there are still many challenges in making the correct clinical decisions due to the complicated clinical situations of HF patients. Each patient would satisfy several recommendations, meaning the decision tree of HF treatment should be nonmutually exclusive, and the same patient would be allocated to several leaf nodes in the decision tree. In the current study, we aim to propose a way to ensemble a nonmutually exclusive decision tree for recommendation system for complicated diseases, such as HF. Methods: The nonmutually exclusive decision tree was constructed via knowledge rules summarized from the HF clinical guidelines. Then similar patients were defined as those who followed the same pattern of leaf node allocation according to the decision tree. The frequent medication patterns for each similar patient were mined using the Apriori algorithms, and we also carried out the outcome prognosis analyses to show the capability for the evidence-based medication recommendations of our nonmutually exclusive decision tree. Results: Based on a large database that included 29,689 patients with 84,705 admissions, we tested the framework for HF treatment recommendation. In the constructed decision tree, the HF treatment recommendations were grouped into two independent parts. The first part was recommendations for new cases, and the second part was recommendations when patients had different historical medication. There are 14 leaf nodes in our decision tree, and most of the leaf nodes had a guideline adherence of around 90%. We reported the top 10 popular similar patients, which accounted for 32.84% of the whole population. In addition, the multiple outcome prognosis analyses were carried out to assess the medications for one of the subgroups of similar patients. Our results showed even for the subgroup of the same similar patients that no one medication pattern would benefit all outcomes. Conclusion: In the present study, the methodology to construct a nonmutually exclusive decision tree for medication recommendations for HF and its application in CDSS was proposed. Our framework is universal for most diseases and could be generally applied in developing the CDSS for treatment.

Effect of Xuezhikang Therapy on Expression of Pulmonary Hypertension Related miR-638 in Patients With Low HDL-C Levels.

Objective: Low plasma level of high-density lipoprotein cholesterol (HDL-C) associated with poor outcomes in several cardiovascular diseases, including pulmonary arterial hypertension (PAH). Regulation of miR-638 have been proved to be associated with PAH. The aim of this study was to evaluate the expression of miR-638 after Xuezhikang (XZK) therapy in patients with low HDL-C. Methods: Plasma levels of miR-638 were quantified by real-time polymerase chain reactions in 20 patients with PAH and 30 healthy controls. A total of 40 subjects with low HDL-C were assigned to receive an XZK therapy for 6 months. The miR-638 expression profiles were detected in PAH patients, XZK-treated subjects and lovastatin treated pulmonary arterial smooth muscle cells (PA-SMCs). Results: The relative expression level of miR-638 in the plasma was lower in the PAH patients than that in the controls (p < 0.001). An increase of 11.2% from baseline in the HDL-C level was found after XZK therapy (p < 0.001). The relative expression of miR-638 was increased after XZK treatment (p < 0.01). The changes of miR-638 were inversely associated with baseline HDL-C levels. A significantly reduction in miR-638 expression were found in PDGF-BB-treated hPA-SMCs compared to the control cells, and the pre-treatment of the cells with lovastatin significantly re-gain the expression levels in miR-638. Conclusion: In patients with low HDL-C levels, XZK therapy raised the expression of miR-638, suggesting that the potential therapeutic effect of XZK in PAH patients with low serum HDL-C levels deserves further exploration.

Correlation between serum free triiodothyronine levels and risk stratification in Chinese patients with acute coronary syndrome receiving percutaneous coronary intervention.

OBJECTIVE: Low serum free triiodothyronine (FT3) levels are associated with the occurrence of coronary heart disease and with the prognosis of cardiovascular diseases. This study aimed to investigate the relationship between FT3 levels and risk stratification in Chinese Han patients with acute coronary syndrome (ACS) receiving percutaneous coronary intervention (PCI) treatment. METHODS: Plasma FT3 levels and other parameters were measured in 191 patients with ACS who received PCI. The risk of adverse cardiovascular events was assessed using the Age, Creatinine, and Ejection Fraction (ACEF) score. RESULTS: FT3 levels were significantly lower in the high-risk group than in the medium- and low-risk groups. Serum FT3 levels were negatively linearly correlated with the ACEF score (r = -0.590). Stepwise regression analysis showed a negative correlation between FT3 levels and the risk of adverse cardiovascular events as measured by the ACEF score (standardized ß = -0.261). CONCLUSION: Serum FT3 levels are negatively related to risk stratification in patients with ACS. Serum FT3 levels may be used as a potential predictor for adverse outcomes of patients with ACS undergoing PCI.

MicroRNA-29a attenuates angiotensin-II induced-left ventricular remodeling by inhibiting collagen, TGF-ß and SMAD2/3 expression.

BACKGROUND: Left ventricular (LV) remodeling is the most common target organ damage in hypertension. Previously, our study found that plasma microRNA-29a (miR-29a) level was associated with the LV remodeling in hypertensive patients. However, the causal relationship between miR-29a and LV remodeling remains unknown. Thus, the aim of this study was to investigate the regulation mechanism of miR-29a in LV remodeling. METHODS & RESULTS: Overexpression and knockdown miR-29a mice were generated by tail-intravenous injection of miR-29a-mimic and inhibitor lentivirus for one week respectively. Then the mice were subjected to angiotensin-II (AngII) induced LV remodeling by subcutaneous AngII capsule osmotic pumping into AngII for four weeks. AngII-induced LV remodeling mice as the model group (n = 9). Age-matched male SPF C57/BL6J mice (6-8 weeks old) were treated with the pumping of saline as a vehicle (n = 6). In vivo, overexpression miR-29a ameliorated AngII-induced LV remodeling, while knockdown miR-29a deteriorated LV remodeling. Simultaneously, we observed that overexpression miR-29a mice inhibited but knockdown miR-29a mice increased cardiac cross-sectional area, indicating that miR-29a has an antagonistic effect on cardiac hypertrophy. Further studies found that overexpression miR-29a inhibited the content of the LV collagen including collagen I and III. Moreover, the expression of transforming growth factor-ß (TGF-ß) and phosphorylated SMAD2/3 decreased with the down-regulation of collagen I and III in overexpression miR-29a mice. CONCLUSIONS: Our finding indicates that overexpression miR-29a attenuates LV remodeling by inhibiting collagen deposition, TGF-ß, and phosphorylated SMAD2/3 expression. Thus, intervention miR-29a may be a therapeutic target for attenuating LV remodeling.

Noninvasive central pulse pressure is an independent determinant of renal function.

The purpose of this study was to investigate the prognostic properties of different BP measurements for renal function decrement and early chronic kidney disease (CKD) in community-dwelling populations with normal renal function at baseline. A total of 1426 participants were included and followed for a median of 4.8 years (interquartile range, 4.5-5.2), and central hemodynamic profile and estimated glomerular filtration rate (eGFR) were evaluated. One main outcome was the rapid eGFR decline defined as a decline in eGFR of greater than 3 mL/min per 1.73 m2 per year; the other was the new incidence of CKD. At the end of follow-up, mean eGFR decreased from 93.39 ± 13.46 mL/min per 1.73 m2 to 85.72 ± 14.81 mL/min per 1.73 m2 , and the incidence of rapid eGFR decline and CKD were 20.7% and 5.6%, respectively. In multivariate linear regression analysis, central pulse pressure (PP), age, fasting blood glucose, and concentration of homocysteine were independent determinants of the change in renal function. Not only in the prediction of rapid eGFR decline but also in the incident of CKD, baseline central PP was the only BP component that consistently independently associated with both outcomes after adjustment for various confounders. When compared with subjects in the lowest quartile of central PP, those in the highest quartile demonstrated a significantly increased risk of CKD (hazard ratio [HR], 1.57; 95% confidence interval [CI], 1.08-2.96; P = .006). The study showed that central PP emerged as an independent predictor of the decline in renal function.