Transcription factor 21 rs12190287 polymorphism is related to stable angina and ST elevation myocardial infarction in a Chinese Population.

Background: Transcription factor 21 (TCF21, epicardin, capsuling, pod-1) is expressed in the epicardium and is involved in the regulation of cell fate and differentiation via epithelial-mesenchymal transformation during development of the heart. In addition, TCF21 can suppress the differentiation of epicardial cells into vascular smooth muscle cells and promote cardiac fibroblast development. This study aimed to explore whether TCF21 gene (12190287G/C) variants affect coronary artery disease risk. Methods: We enrolled 381 patients who had stable angina, 138 with ST elevation myocardial infarction (STEMI), and 276 healthy subjects. Genotyping of rs12190287 of the TCF21 gene was performed. Results: Higher frequencies of the CC genotype were found in the patients with stable angina/STEMI than in the healthy controls. After adjusting for diabetes mellitus, hypertension, age, sex, smoking, body mass index and hyperlipidemia, the patients with the CC genotype of the TCF21 gene were associated with 2.49- and 9.19-fold increased risks of stable angina and STEMI, respectively, compared to the patients with the GG genotype. Furthermore, TCF21 CC genotypes showed positive correlations with both stable angina and STEMI, whereas TCF21 GG genotypes exhibited a negative correlation with STEMI. Moreover, the stable angina and STEMI patients with the CC genotype had significantly elevated high-sensitivity C-reactive protein levels than those with the GG genotype. In addition, significant associations were found between type 2 diabetes mellitus, hypertension, and hyperlipidemia with TCF21 gene polymorphisms (p for trend < 0.05). Conclusion: TCF21 gene polymorphisms may increase susceptibility to stable angina and STEMI.

ER ribosomal-binding protein 1 regulates blood pressure and potassium homeostasis by modulating intracellular renin trafficking.

BACKGROUND: Genome-wide association studies (GWASs) have linked RRBP1 (ribosomal-binding protein 1) genetic variants to atherosclerotic cardiovascular diseases and serum lipoprotein levels. However, how RRBP1 regulates blood pressure is unknown. METHODS: To identify genetic variants associated with blood pressure, we performed a genome-wide linkage analysis with regional fine mapping in the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) cohort. We further investigated the role of the RRBP1 gene using a transgenic mouse model and a human cell model. RESULTS: In the SAPPHIRe cohort, we discovered that genetic variants of the RRBP1 gene were associated with blood pressure variation, which was confirmed by other GWASs for blood pressure. Rrbp1- knockout (KO) mice had lower blood pressure and were more likely to die suddenly from severe hyperkalemia caused by phenotypically hyporeninemic hypoaldosteronism than wild-type controls. The survival of Rrbp1-KO mice significantly decreased under high potassium intake due to lethal hyperkalemia-induced arrhythmia and persistent hypoaldosteronism, which could be rescued by fludrocortisone. An immunohistochemical study revealed renin accumulation in the juxtaglomerular cells of Rrbp1-KO mice. In the RRBP1-knockdown Calu-6 cells, a human renin-producing cell line, transmission electron and confocal microscopy revealed that renin was primarily retained in the endoplasmic reticulum and was unable to efficiently target the Golgi apparatus for secretion. CONCLUSIONS: RRBP1 deficiency in mice caused hyporeninemic hypoaldosteronism, resulting in lower blood pressure, severe hyperkalemia, and sudden cardiac death. In juxtaglomerular cells, deficiency of RRBP1 reduced renin intracellular trafficking from ER to Golgi apparatus. RRBP1 is a brand-new regulator of blood pressure and potassium homeostasis discovered in this study.

Elevated plasma leptin levels are associated with vascular access dysfunction in patients on maintenance hemodialysis.

BACKGROUND: Inflammation has been associated with vascular access (VA) dysfunction. The adipocytokine leptin can directly induce pro-inflammatory T helper 1 immune responses and the pathogenesis of chronic inflammation. We explored the association between plasma leptin and VA dysfunction in patients on maintenance hemodialysis (HEMO). METHODS: A total of 344 consecutive patients who received anastomosis for VA at a single HEMO center between June 1, 2010 and December 31, 2021 were screened. Of these patients, 267 met the inclusion criteria and were included. ELISA was used to measure circulating levels of leptin. RESULTS: The VA dysfunction group had a higher leptin level than the patent VA group. A higher concentration of leptin was independently and significantly associated with an elevated risk of VA dysfunction. Multiple logistic regression analysis showed that leptin, female sex, and hypertension were independently associated with VA dysfunction, even after adjusting for known biomarkers. We then evaluated the ability of leptin, female sex, and hypertension to predict the risk of VA dysfunction, and the area under the curve (AUC) for leptin was 0.626 (p = 0.0001). When leptin, female sex, and hypertension were added to this multivariate model, the AUC increased to 0.679 (p = 0.001) for leptin and hypertension, and 0.690 for leptin, hypertension, and female sex (p = 0.004). In addition, plasma leptin levels were associated with sex, body mass index, and hemoglobin. CONCLUSIONS: In addition to the association between leptin and VA dysfunction, hypertension and female sex independently predicted VA dysfunction in patients with HEMO.

Association of plasma fatty acid-binding protein 3 with estimated glomerular filtration rate in patients with type 2 diabetes mellitus.

Background: Fatty acid-binding protein 3 (FABP3) located in renal mesangial and distal tubular cells, and had been shown to be a sensitive marker of renal injury, potentially be a mediator in pathogenesis of chronic kidney disease (CKD). Our previous study revealed that plasma FABP1 and FABP2 were independently associated with CKD, however, little is known about the relationship between plasma FABP3 level and CKD. The aim of this study was therefore to evaluate the plasma levels of FABP3 at different stages of estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 334 subjects with T2DM who enrolled in a disease management program were included in this study and stratified according to eGFR. Plasma FABP3 concentrations were measured by an enzyme-linked immunosorbent assay. Results: FABP3 levels increased in parallel with the eGFR level. Increasing concentrations of FABP3 were independently and significantly associated with eGFR stage G2-G4. Age- and sex-adjusted FABP3 levels were positively associated with uric acid, urinary albumin-to-creatinine ratio, FABP1, FABP2, and fatty liver index, but negatively associated with eGFR and hemoglobin. Conclusion: Our results indicate that circulating FABP3 in patients with T2DM is associated with eGFR, which suggests that increased plasma FABP3 may be involved in the pathogenesis of CKD.

Circulating hepassocin level in patients with stable angina is associated with fatty liver and renal function.

Background: Chronic kidney disease (CKD) is a major risk factor for coronary artery disease and it is often associated with hepatic steatosis. Hepassocin (also known as hepatocyte-derived fibrinogen related protein or fibrinogen-like 1) is a novel hepatokine that causes hepatic steatosis and induces insulin resistance. However, the role of hepassocin in renal function status remains unclear. Our objective was to investigate the association of plasma hepassocin level with fatty liver and renal function status in patients with stable angina. Methods: Plasma hepassocin levels were determined by enzyme-linked immunosorbent assays in 395 consecutive patients with stable angina. Renal function was defined as an estimated glomerular filtration rate (eGFR). Fatty liver was defined by ultrasonography and fibrosis-4 (FIB-4) index. Results: With increasing hepassocin tertiles, patients had higher prevalence of fatty live, an increased waist-to-hip ratio, and neutrophil count, monocyte count, and FIB-4 index, higher levels of uric acid, blood urine nitrogen and higher sensitivity C-reactive protein. They also had incrementally lower eGFR, serum hemoglobin and albumin levels. In multiple linear stepwise regression analysis, only eGFR was significantly independent negatively associated with plasma hepassocin levels. Conclusion: Our results indicate that circulating hepassocin in patients with stable angina is associated with fatty liver and renal function, which suggests that increased plasma hepassocin may be involved in the pathogenesis of fatty liver and CKD.

Elevated plasma fatty acid-binding protein 3 is related to prolonged corrected QT interval and reduced ejection fraction in patients with stable angina.

Background: Higher concentrations of plasma fatty acid-binding protein 3 (FABP3) play a role in the development of cardiovascular events, cerebrovascular deaths, and acute heart failure. However, little is known about the relationship between plasma FABP3 level and prolonged QT interval and reduced ejection fraction (EF). This study aimed to investigate the relationship between plasma FABP3 level and prolonged corrected QT (QTc) interval and reduced EF in patients with stable angina. Inflammatory cytokine and adipocytokine levels were also measured to investigate their associations with plasma FABP3. Methods: We evaluated 249 consecutive patients with stable angina. Circulating levels of FABP3 were measured by ELISA. In addition, 12-lead ECG and echocardiography recordings were obtained from each patient. Results: Multiple regression analysis showed that high-density lipoprotein cholesterol, high sensitivity C-reactive protein (hs-CRP), white blood cell (WBC) count, visfatin, adiponectin, FABP4, heart rate, QTc interval, left atrial diameter, left ventricular mass index, end-systolic volume, end-systolic volume index, fractional shortening, and EF were independently associated with FABP3 (all p<0.05). Patients with an abnormal QTc interval had a higher median plasma FABP3 level than those with a borderline and normal QTc interval. With increasing FABP3 tertiles, the patients had higher frequencies of abnormal QTc interval, left ventricular systolic dysfunction, and all-cause mortality, incrementally lower EF, higher WBC count, and higher levels of hs-CRP, visfatin, adiponectin, and FABP4. Conclusion: This study indicates that plasma FABP3 may act as a surrogate parameter of prolonged QTc interval and reduced EF in patients with stable angina, partially through the effects of inflammation or cardiomyocyte injury. Further studies are required to elucidate whether plasma FABP3 plays a role in the pathogenesis of QTc prolongation and reduced EF.

Elevated plasma level of neutrophil gelatinase-associated lipocalin (NGAL) in patients with breast cancer.

Background: Neutrophil gelatinase­associated lipocalin (NGAL), also known as lipocalin 2, siderocalin, 24p3 or uterocalin, plays a key role in inflammation and in different types of cancer. In this study, we investigated whether plasma NGAL levels were altered in patients with breast cancer. The relationship between plasma NGAL levels and pretreatment hematologic profile was also explored. Methods: Plasma NGAL concentrations were measured using ELISA in breast cancer patients and control subjects. A total of 75 patients with breast cancer and 65 age- and body mass index-matched control subjects were studied. All of the study subjects were female. Results: Plasma NGAL level was found to be elevated in the patients with breast cancer compared to the control subjects (94.3 ng/mL (interquartile range 39.3-207.6) vs. 55.0 ng/mL (interquartile range 25.8-124.7), p = 0.007). Multiple logistic regression analysis revealed that NGAL was independently associated with breast cancer, even after adjusting for known biomarkers. Furthermore, NGAL level was elevated in the breast cancer patients who were negative progesterone receptor status, had a histologic grade ≥ 2, clinical stage III, and pathologic stage T2+T3+T4. In addition, NGAL level was significantly correlated with white blood cell (WBC) count, monocyte count, neutrophil count, and platelet count (all p < 0.01). Moreover, WBC count, neutrophil count, monocyte count, lymphocyte count, platelet count, and NGAL level gradually increased as the stage progressed. Conclusions: Increased plasma NGAL levels were associated with breast cancer independently of risk factors, and were correlated with inflammatory biomarkers. These results suggest that NGAL may act through inflammatory reactions to play an important role in the pathogenesis of breast cancer.

Expedition to the missing link: Long noncoding RNAs in cardiovascular diseases.

With the advances in deep sequencing-based transcriptome profiling technology, it is now known that human genome is transcribed more pervasively than previously thought. Up to 90% of the human DNA is transcribed, and a large proportion of the human genome is transcribed as long noncoding RNAs (lncRNAs), a heterogenous group of non-coding transcripts longer than 200 nucleotides. Emerging evidence suggests that lncRNAs are functional and contribute to the complex regulatory networks involved in cardiovascular development and diseases. In this article, we will review recent evidence on the roles of lncRNAs in the biological processes of cardiovascular development and disorders. The potential applications of lncRNAs as biomarkers and targets for therapeutics are also discussed.

FABP1 and FABP2 as markers of diabetic nephropathy.

Background: Diabetes mellitus is the leading cause of diabetic nephropathy and a major public health issue worldwide. Approximately 20-30% of patients with type 2 diabetes mellitus (T2DM) have renal impairment. Fatty acid-binding protein 1 (FABP1) is expressed in renal proximal tubule cells and released into urine in response to hypoxia caused by decreased peritubular capillary blood flow, and FABP2 is responsible for the transport of free fatty acids in the intestinal endothelium cells. There is increasing evidence that FABP1 and FABP 2 play a role in the development and progression of chronic kidney disease. The aim of this study was to investigate the relation of circulating FABP1 and FABP2 levels to nephropathy in patients with T2DM. Methods: For this study, 268 subjects with T2DM who were enrolled in a disease management program were stratified according to urinary microalbumin and serum creatinine measurements. The plasma FABP1 and FABP2 concentrations were examined by enzyme-linked immunosorbent assay. Demographic and potential metabolic confounding factors were analyzed with logistic regression to calculate the effects of FABP1 and FABP2 levels on diabetic nephropathy. Results: The FABP1 and FABP2 levels increased in parallel with the advancement of diabetic nephropathy. Increasing concentrations of FABP1 and FABP2 were independently and significantly associated with diabetic nephropathy. Multiple logistic regression analysis revealed FABP1 and FABP2 as an independent association factor for diabetic nephropathy, even after full adjustment of known biomarkers. Furthermore, receiver operating characteristic curve analysis showed that a FABP1 level of >33.8 ng/mL and a FABP2 level of >2.8 ng/mL were associated with diabetic nephropathy. Conclusion: Our results suggest that FABP1 and FABP2 may be novel biomarkers of diabetic nephropathy.

Glossogyne tenuifolia Attenuates Proliferation and Migration of Vascular Smooth Muscle Cells.

The proliferation and migration of vascular smooth muscle cells (VSMCs) are essential in the pathogenesis of various vascular diseases, such as atherosclerosis and restenosis. Among the mediators of VSMC during atherosclerosis development, platelet-derived growth factor (PDGF)-BB is a potent mitogen for VSMCs and greatly contributes to the intimal accumulation of VSMCs. Glossogyne tenuifolia (GT, Xiang-Ru) is a traditional antipyretic and hepatoprotective herb from Penghu Island, Taiwan. This study evaluated the inhibitory effect of GT ethanol extract (GTE) and GT water extract (GTW) on proliferative and migratory activities in PDGF-BB-induced VSMCs. The experimental results demonstrated that GTE significantly inhibited the PDGF-BB-stimulated VSMC proliferation and migration, as shown by MTT, wound healing, and Boyden chamber assays. GTE was found to have a much more potent inhibitory activity than GTW. Based on the Western blot analysis, GTE significantly blocked the PDGF-BB-induced phosphorylation of NF-κB and mitogen-activated protein kinase (MAPK) pathways, including extracellular signal-regulated kinase (ERK), p38, and JNK, in VSMCs. In addition, GTE retarded the PDGF-BB-mediated migration through the suppression of matrix metalloproteinase (MMP)-2 and MMP-9 expression in VSMCs. Three main ingredients of GT-chlorogenic acid, luteolin-7-glucoside, and luteolin-all showed significant anti-proliferative effects on PDGF-BB-induced VSMCs. As a whole, our findings indicated that GTE has the potential to be a therapeutic agent to prevent or treat restenosis or atherosclerosis.

Early detection of myocardial infarction following blunt chest trauma by computed tomography: a case report.

BACKGROUND: Blunt cardiac trauma encompasses a wide range of clinical entities, including myocardial contusion, cardiac rupture, valve avulsion, pericardial injuries, arrhythmia, and even myocardial infarction. Acute myocardial infarction due to coronary artery dissection after blunt chest trauma is rare and may be life threatening. Differential diagnosis of acute myocardial infarction from cardiac contusion at this setting is not easy. CASE PRESENTATION: Here we demonstrated a case of blunt chest trauma, with computed tomography detected myocardium enhancement defect early at emergency department. Under the impression of acute myocardial infarction, emergent coronary angiography revealed left anterior descending artery occlusion. Revascularization was performed and coronary artery dissection was found after thrombus aspiration. Finally, the patient survived after coronary stenting. CONCLUSION: Perfusion defects of myocardium enhancement on CT after blunt chest trauma can be very helpful to suggest myocardial infarction and facilitate the decision making of emergent procedure. This valuable sign should not be missed during the initial interpretation.

Glossogyne tenuifolia Extract Inhibits TNF-α-Induced Expression of Adhesion Molecules in Human Umbilical Vein Endothelial Cells via Blocking the NF-kB Signaling Pathway.

Chronic inflammation plays a pivotal role in the development of atherosclerosis, where the pro-inflammatory cytokine-induced expression of endothelial adhesion molecules and the recruitment of monocytes are the crucial events leading to its pathogenesis. Glossogyne tenuifolia ethanol extract (GTE) is shown to have potent anti-inflammatory and antioxidant activities. We evaluated the effects of GTE and its major components, luteolin (lut), luteolin-7-glucoside (lut-7-g), and oleanolic acid (OA) on TNF-α-induced expression of adhesion molecules in human umbilical vein endothelial cells (HUVECs). The results demonstrated that GTE, lut, and lut-7-g attenuated the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in TNF-α-activated HUVECs, and inhibited the adhesion of monocytes to TNF-α-activated HUVECs. The TNF-α-induced mRNA expression of ICAM-1 and VCAM-1 was also suppressed, revealing their inhibitory effects at the transcriptional level. Furthermore, GTE, lut, and lut-7-g blocked the TNF-α-induced degradation of nuclear factor-kB inhibitor (IkB), an indicator of the activation of nuclear factor-kB (NF-kB). In summary, GTE and its bioactive components were effective in preventing the adhesion of monocytes to cytokine-activated endothelium by the inhibition of expression of adhesion molecules, which in turn is mediated through blocking the activation and nuclear translocation of NF-kB. The current results reveal the therapeutic potential of GTE in atherosclerosis.

Aibika Flower Flavonoid Extract Exhibits Antiulcer Activity in a Murine Model of Ethanol-Induced Acute Gastric Injury.

Aibika (Abelmoschus manihot (L.) Medic) is a garden vegetable whose flower has been shown to have various bioactivities. This study investigated the protective effect of aibika flower flavonoid extract (AFF) on ethanol-induced gastric injury in mice. The experimental results showed that pre-feeding 125 and 250 mg AFF/kg BW for 1 week significantly reduced the gastric injury area in the negative control group from 19.2% to 6.7% and 0.6%, respectively. The results of the pathological sections staining also showed that AFF had a protective ability against alcohol-induced injury of gastric tissue and liver tissue. When the mice were exposed to high concentrations of ethanol, AFF pretreatment significantly upregulated the expression of antioxidant enzymes. The pretreatment also promoted the production of the intracellular antioxidant, reduced glutathione, in both gastric tissue and serum. On the contrary, AFF delayed the lipid peroxidation process, which, in turn, reduced the damage to the gastric mucosa. When acute inflammation was induced by ethanol stimulation, AFF significantly downregulated the proinflammatory cytokines and mediators such as TNF-α, IL-1ß, IL-6, NF-κB, COX-2, and iNOS. Furthermore, AFF pretreatment greatly promoted the production of healing factors, such as matrix metalloproteinase (MMP)-2, MMP-7, and MMP-9, in the gastric tissue. In addition, AFF significantly reduced gastric cell apoptosis induced by ethanol stimulation. These results demonstrate that AFF has a good protective effect on alcohol-induced gastric ulcer and has the potential to be used in gastrointestinal health care.

Pretreatment Circulating Albumin, Platelet, and RDW-SD Associated with Worse Disease-Free Survival in Patients with Breast Cancer.

Objective: Breast cancer is the second most common malignancy globally and a leading cause of cancer death in women. Analysis of factors related to disease-free survival (DFS) has improved understanding of the disease and characteristics related to recurrence. The aim of this study was to investigate the predictors of DFS in patients with breast cancer to enable the identification of patients at high risk who may benefit from prevention interventions. Methods: We retrospectively analyzed 559 women with breast cancer who underwent treatment between 2004 and 2022. The study endpoint was DFS. Recurrence was defined as local recurrence, regional recurrence, distant metastases, contralateral breast cancer, other second primary cancer, and death. Baseline tumor-related characteristics, treatment-related characteristics, sociodemographic and biochemical data were analyzed using Cox proportional hazards analysis. Results: The median DFS was 45 months (range, 2 to 225 months). Breast cancer recurred in 86 patients (15.4%), of whom 10 had local recurrence, 10 had regional recurrence, 17 had contralateral breast cancer, 29 had distant metastases, 10 had second primary cancer, and 10 patients died. Multivariate forward stepwise Cox regression analysis showed that AJCC stage III, Ki67 ≥14%, albumin, platelet, and red cell distribution width-standard deviation (RDW-SD) were predictors of worse DFS. In addition, the effects of albumin, platelet, and RDW-SD on disease recurrence were confirmed by structural equation model (SEM) analysis. Conclusion: In addition to the traditional predictors of worse DFS such as AJCC stage III and Ki67 ≥14%, lower pretreatment circulating albumin, higher pretreatment circulating platelet count and RDW-SD could significantly predict worse DFS in this study, and SEM delineated possible causal pathways and inter-relationships of albumin, platelet, and RDW-SD contributing to the disease recurrence among Chinese women with breast cancer.

Tissue Expression of Growth Differentiation Factor 11 in Patients with Breast Cancer.

Protein growth differentiation factor 11 (GDF11) plays crucial roles in cellular processes, including differentiation and development; however, its clinical relevance in breast cancer patients is poorly understood. We enrolled 68 breast cancer patients who underwent surgery at our hospital and assessed the expression of GDF11 in tumorous, ductal carcinoma in situ (DCIS), and non-tumorous tissues using immunohistochemical staining, with interpretation based on histochemical scoring (H-score). Our results indicated higher GDF11 expressions in DCIS and normal tissues compared to tumorous tissues. In addition, the GDF11 H-score was lower in the patients with a tumor size ≥ 2 cm, pathologic T3 + T4 stages, AJCC III-IV stages, Ki67 ≥ 14% status, HER2-negative, and specific molecular tumor subtypes. Notably, the patients with triple-negative breast cancer exhibited a loss of GDF11 expression. Spearman correlation analysis revealed associations between GDF11 expression and various clinicopathological characteristics, including tumor size, stage, Ki67, and molecular subtypes. Furthermore, GDF11 expression was positively correlated with mean corpuscular hemoglobin concentration and negatively correlated with neutrophil count, as well as standard deviation and coefficient of variation of red cell distribution width. These findings suggest that a decreased GDF11 expression may play a role in breast cancer pathogenesis.

Psychiatric disorders of patients seeking obesity treatment.

BACKGROUND: Obese and overweight people have a higher risk of both chronic physical illness and mental illness. Obesity is reported to be positively associated with psychiatric disorders, especially in people who seek obesity treatment. At the same time, obesity treatment may be influenced by psychological factors or personality characteristics. This study aimed to understand the prevalence of mental disorders among ethnic Chinese who sought obesity treatment. METHODS: Subjects were retrospectively recruited from an obesity treatment center in Taiwan. The obesity treatments included bariatric surgery and non-surgery treatment. All subjects underwent a standardized clinical evaluation with two questionnaires and a psychiatric referral when needed. The psychiatric diagnosis was made thorough psychiatric clinic interviews using the SCID. A total of 841 patients were recruited. We compared the difference in psychiatric disorder prevalence between patients with surgical and non-surgical treatment. RESULTS: Of the 841 patients, 42% had at least one psychiatric disorder. Mood disorders, anxiety disorders and eating disorders were the most prevalent categories of psychiatric disorders. Females had more mood disorders and eating disorders than males. The surgical group had more binge-eating disorder, adjustment disorder, and sleep disorders than the non-surgical group. CONCLUSION: A high prevalence of psychiatric disorders was found among ethnic Chinese seeking obesity treatment. This is consistent with study results in the US and Europe.

Circulating mannose-binding lectin concentration in patients with stable coronary artery disease is associated with heart failure and renal function.

BACKGROUND: Mannose-binding lectin (MBL) has been associated with cardiovascular disease and its complications, the progression of diabetic nephropathy, and complement-mediated renal interstitial injury. However, the relationship between plasma MBL concentration with both heart failure and renal function is unclear. In this study, we examined associations of plasma MBL with both renal function and heart failure in patients with stable coronary artery disease (CAD). METHODS: We enrolled 348 consecutive stable CAD patients and used ELISA to evaluate plasma concentrations of MBL. Renal function was classified into KDIGO G1, G2 and G3a-G4 groups according to the eGFR of ≥ 90, 60-89 and 15-59, ml/min/1.73 m2, respectively. Patients with a left ventricular ejection fraction (LVEF) ≤ 40 % were classified to have heart failure. RESULTS: A significant positive association was found between MBL with diabetes mellitus, current smoker, blood urea nitrogen, creatinine, and brain natriuretic peptide, and a significant negative association was found between MBL with eGFR and LVEF. KDIGO stage G3a-G4 and heart failure increased along with tertiles of MBL (p for trend < 0.05). Multivariate analysis showed that compared to the patients with a low MBL concentration, the odds ratios of having KDIGO stage G3a-G4 were 1.89 (1.01-3.55) times and 2.37 (1.25-4.59) times higher for those with medium and high MBL concentrations. Furthermore, compared to the patients with a low MBL concentration, the OR of having heart failure were 1.97 (1.01-3.93) times higher for those with high MBL concentrations. Moreover, multivariate analysis showed an independent association between plasma MBL concentration with both KDIGO stage G3a-G4 and heart failure (LVEF < 40 %). In addition, the effect of MBL on both LVEF and eGFR was confirmed by structural equation model analysis. CONCLUSION: There are associations between circulating MBL concentration with both heart failure and renal function in stable CAD patients, suggesting that increased plasma MBL may contribute to the pathogenesis of both chronic kidney disease and heart failure.

Anti-Diabetic Therapy and Heart Failure: Recent Advances in Clinical Evidence and Molecular Mechanism.

Diabetic patients have a two- to four-fold increase in the risk of heart failure (HF), and the co-existence of diabetes and HF is associated with poor prognosis. In randomized clinical trials (RCTs), compelling evidence has demonstrated the beneficial effects of sodium-glucose co-transporter-2 inhibitors on HF. The mechanism includes increased glucosuria, restored tubular glomerular feedback with attenuated renin-angiotensin II-aldosterone activation, improved energy utilization, decreased sympathetic tone, improved mitochondria calcium homeostasis, enhanced autophagy, and reduced cardiac inflammation, oxidative stress, and fibrosis. The RCTs demonstrated a neutral effect of the glucagon-like peptide receptor agonist on HF despite its weight-reducing effect, probably due to it possibly increasing the heart rate via increasing cyclic adenosine monophosphate (cAMP). Observational studies supported the markedly beneficial effects of bariatric and metabolic surgery on HF despite no current supporting evidence from RCTs. Bromocriptine can be used to treat peripartum cardiomyopathy by reducing the harmful cleaved prolactin fragments during late pregnancy. Preclinical studies suggest the possible beneficial effect of imeglimin on HF through improving mitochondrial function, but further clinical evidence is needed. Although abundant preclinical and observational studies support the beneficial effects of metformin on HF, there is limited evidence from RCTs. Thiazolidinediones increase the risk of hospitalized HF through increasing renal tubular sodium reabsorption mediated via both the genomic and non-genomic action of PPARγ. RCTs suggest that dipeptidyl peptidase-4 inhibitors, including saxagliptin and possibly alogliptin, may increase the risk of hospitalized HF, probably owing to increased circulating vasoactive peptides, which impair endothelial function, activate sympathetic tones, and cause cardiac remodeling. Observational studies and RCTs have demonstrated the neutral effects of insulin, sulfonylureas, an alpha-glucosidase inhibitor, and lifestyle interventions on HF in diabetic patients.

FABP3, FABP4, and heart rate variability among patients with chronic schizophrenia.

Introduction: The prevalence of cardiovascular disease (CVD) and CVD-related deaths in patients with schizophrenia is high. An elevated risk of CVD has been associated with low heart rate variability (HRV). There is increasing evidence that fatty acid-binding protein (FABP)3 and FABP4 play roles in the development and progression of CVD. This study aimed to explore the association of circulating FABP3/FABP4 levels with HRV in patients with chronic schizophrenia. Methods: We included 265 consecutive patients with chronic schizophrenia who attended a disease management program. We used an enzyme-linked immunosorbent assay for the measurement of plasma concentrations of FABP3 and FABP4. Standard HRV was recorded at baseline following a standard protocol. Mean high- and low-frequency (HF/LF) HRV values were analyzed by tertile of FABP3 and FABP4 using one-way analysis of variance, and linear regression analysis was performed to assess trends. Results: A positive association between FABP3 and creatinine was found in multiple regression analysis. In addition, negative associations between levels of hematocrit, hemoglobin, HF HRV, and estimated glomerular filtration rate (eGFR) with FABP3 were also found. Moreover, positive associations between FABP4 with body mass index, diabetes mellitus, hypertension, systolic blood pressure, low-density lipoprotein-cholesterol, triglycerides, creatinine, and FABP3 were found. Furthermore, negative associations between levels of high-density lipoprotein-cholesterol, eGFR, and HF HRV with FABP4 were found. We also found a significant inverse association between FABP3 and HF HRV (p for trend = 0.008), and significant inverse associations between FABP4 with HF and LF HRV (p for trend = 0.007 and 0.017, respectively). Discussion: Together, this suggests that elevated levels of FABP3 and FABP4 may be linked to health problems related to CVD in patients with chronic schizophrenia.

Emerging Therapy for Diabetic Cardiomyopathy: From Molecular Mechanism to Clinical Practice.

Diabetic cardiomyopathy is characterized by abnormal myocardial structure or performance in the absence of coronary artery disease or significant valvular heart disease in patients with diabetes mellitus. The spectrum of diabetic cardiomyopathy ranges from subtle myocardial changes to myocardial fibrosis and diastolic function and finally to symptomatic heart failure. Except for sodium-glucose transport protein 2 inhibitors and possibly bariatric and metabolic surgery, there is currently no specific treatment for this distinct disease entity in patients with diabetes. The molecular mechanism of diabetic cardiomyopathy includes impaired nutrient-sensing signaling, dysregulated autophagy, impaired mitochondrial energetics, altered fuel utilization, oxidative stress and lipid peroxidation, advanced glycation end-products, inflammation, impaired calcium homeostasis, abnormal endothelial function and nitric oxide production, aberrant epidermal growth factor receptor signaling, the activation of the renin-angiotensin-aldosterone system and sympathetic hyperactivity, and extracellular matrix accumulation and fibrosis. Here, we summarize several important emerging treatments for diabetic cardiomyopathy targeting specific molecular mechanisms, with evidence from preclinical studies and clinical trials.