Association between non-alcoholic fatty liver disease and risk of incident heart failure: a meta-analysis of observational studies.

Background and aims: Recent research has associated non-alcoholic fatty liver disease (NAFLD) with an increased risk of atherosclerotic cardiovascular disease. Previous studies that evaluated the association between NAFLD and risk of heart failure (HF) yielded inconsistent results, however. This meta-analysis aimed to evaluate the association between NAFLD and the risk of HF. Methods: We searched multiple electronic databases, including PubMed, Google Scholar, Embase and Web of Science for potential studies published from inception until 30 October 2021. Cohort studies reported multivariable-adjusted risks of incident HF in NAFLD patients comparing those without NAFLD were included. Results: Six cohort studies comprising 10,979,967 participants (women = 55.5%) were included in the study. The median prevalence of NAFLD in these studies was 22.2%. During a median follow-up duration of 7.0 years, 92,915 HF cases were detected. In the unadjusted model, patients with NAFLD had a greater risk of incident HF [random-effect hazard ratio (HR) = 1.47, 95% confidence interval (CI) = 1.25-1.75, I 2 = 99%], compared with those without NAFLD. After multivariable adjustment of confounding risk factors, NAFLD was still linked with a higher risk of HF incidence (random-effect HR = 1.36, 95% CI = 1.16-1.58, I 2 = 98%). The risk of HF was increased not only in patients with progressive NAFLD severity but also in those with simple steatosis. The absolute risk difference of HF in NAFLD patients compared with those without NAFLD was 11.0 (95% CI = 4.9-17.7) per 10,000 person-years after multivariable adjustment. Conclusion: This meta-analysis suggests that NAFLD may be associated with an increased risk of incident HF. Owing to the high heterogeneity of the published studies, however, further high-quality studies are still needed.

Long-chain omega-3 polyunsaturated fatty acids and the risk of heart failure.

Aims: Adequate intake of long-chain (LC) omega-3 polyunsaturated fatty acids (n-3 PUFAs) is considered important for cardiovascular health. However, the effects of LC n-3 PUFAs on the risk of heart failure (HF) remain unclear. This systematic review and meta-analysis aimed to determine the role of LC n-3 PUFAs in the incidence of HF. Materials and Methods: Electronic databases were searched for studies up to 31 July 2021. Studies were included for the meta-analysis if they reported the adjusted associations between different dietary intakes or circulating concentrations of LC n-3 PUFAs and the risk of HF. A random-effect model was used to calculate the pooled estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for higher LC n-3 PUFA concentrations. Results: Thirteen studies were included in the meta-analysis. Eight studies comprising 316,698 individuals (11,244 incident HF cases), with a median follow-up of 10.7 years, showed that a higher dietary intake of LC n-3 PUFAs was associated with a lower risk of HF (highest versus lowest quintile: HR = 0.84, 95% CI = 0.75-0.94). Six studies, comprising 17,163 participants (2520 HF cases) with a median follow-up of 9.7 years, showed that higher circulating LC n-3 PUFA concentrations were associated with a lower risk of HF (highest versus lowest quintile: HR = 0.59, 95% CI = 0.39-0.91). Higher circulating docosahexaenoic acid concentrations were associated with a decreased risk of HF (top versus bottom quintile: HR = 0.44, 95% CI = 0.26-0.77). The associations between eicosapentaenoic acid (HR = 0.58, 95% CI = 0.26-1.25), docosahexaenoic acid (HR = 0.66, 95% CI = 0.24-1.82), and the risk of HF were not significant. Conclusion: High LC n-3 PUFA concentrations measured by dietary intake or circulating biomarkers are associated with a lower risk of developing HF.

Non-alcoholic fatty liver disease is associated with increased risk of chronic kidney disease.

BACKGROUND AND AIMS: Whether non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of incident chronic kidney disease (CKD) independent of established cardio-renal risk factors remains controversial. We aimed to provide a quantitative estimate of the association and strength between NAFLD and risk of CKD after adjustment for multiple cardio-renal risk factors. METHODS: We searched electronic databases (PubMed, Embase, and Google Scholar) for studies published from database inception until 30 November 2020. Analysis included cohort studies that reported multivariable-adjusted risk ratios [including odds ratios, relative risks (RRs), or hazard ratios] and 95% confidence intervals (CIs) for CKD of NAFLD compared with individuals without NAFLD. RESULTS: A total of 11 cohort studies were included comprising 1,198,242 participants (46.3% women) for analysis. The median follow-up duration was 3.7 years, with 31,922 cases of incident CKD. Compared with individuals without NAFLD, unadjusted models showed that NAFLD was associated with a higher risk of CKD (RR 1.54, 95% CI 1.38-1.71). After adjusting for multiple cardio-renal risk factors, the CKD risk was still significantly increased in patients with NAFLD (RR 1.39, 95% CI 1.27-1.52). Compared with individuals without NAFLD, the adjusted absolute risk increase in NAFLD for CKD was 5.1 (95% CI 3.5-6.8) per 1000 person-years. CONCLUSION: NAFLD is associated with an increased risk of incident CKD independent of established cardio-renal risk factors.

Prediabetes and the risk of heart failure: A meta-analysis.

AIM: To determine the role of prediabetes in the incidence of heart failure (HF). MATERIALS AND METHODS: We searched electronic databases (PubMed, Embase, Google Scholar and OpenGrey) for studies up to 31 December 2020. Studies were included for meta-analysis if they reported adjusted relative risks (RRs) and 95% confidence intervals (CIs) for the risk of HF for prediabetes compared with normoglycaemia. Prediabetes was defined as impaired fasting glucose (IFG) according to the World Health Organization (WHO) criteria (IFG-WHO), or according to the American Diabetes Association (ADA) definition (IFG-ADA), impaired glucose tolerance (IGT), raised HbA1c according to the ADA criteria (HbA1c-ADA), or according to the International Expert Committee (IEC) recommendation (HbA1c-IEC). RESULTS: A total of 15 studies comprising 9,827,430 individuals provided data for this analysis. The median follow-up duration of the included studies was 8.0 years. Compared with normoglycaemia, prediabetes was associated with an increased risk for HF: IFG-ADA (RR: 1.09, 95% CI: 1.05-1.13), IFG-WHO (RR: 1.18, 95% CI: 1.07-1.30), IGT (RR 1.58, 95% CI 1.04-2.39), HbA1c-ADA (RR 1.28, 95% CI 1.16-1.41) or HbA1c-IEC (RR 1.40, 95% CI 1.09-1.79), respectively. CONCLUSIONS: Prediabetes is associated with an increased risk of HF. Future studies are needed to evaluate effective treatments for prediabetes to prevent the development and progression of HF.

Electrophysiological manifestations of rare supra-ventricular tachycardias with concealed nodo-ventricular fibers.

PURPOSE: To clarify the electrophysiological mechanism of supra-ventricular tachycardias (SVT) with concealed nodo-ventricular (NV) fibers. METHODS: We studied the intra-cardiac electrograms during electrophysiological study (EPS) of three cases of SVT which concerned concealed NV fibers. Electrophysiological maneuvers including right ventricular apex entrainments, RS2 stimuli, adenosine triphosphate injection and so on were done for differential diagnosis before ablation. RESULTS: Among these patients, one had atrio-ventricular nodal reentrant tachycardia (AVNRT) with a bystander NV fiber; the other 2 had NV fiber mediated orthodromic reentrant tachycardias (NVRT). VA dissociation was observed during SVT in all 3 cases with an antegrade His bundle conduction sequence. Ventricular stimulation at His refractory period reset the H-H intervals and the V-V intervals sequentially, suggesting the existence of a retrogradely conductive accessory pathway. Adenosine injection could terminate these tachycardias. The cycle length of an NVRT prolonged during the status of functional right bundle branch block, suggesting that the fiber located on the right side. Multiple QRS fusion morphologies during ventricular entrainments or ventricular stimulation at His refractory period at a fixed position could be observed in these cases. CONCLUSIONS: Concealed NV fibers can either mediate orthodromic reentrant tachycardia or be a bystander of AVNRT. V-A dissociation usually occur during such SVTs. Dissociation of H and V due to entrainment of right ventricular apex is a newly discovered maneuver to differentiate AVNRT from NVRT.

α-Linolenic Acid and Risk of Heart Failure: A Meta-Analysis.

Background: The α-linolenic acid is a plant origin n-3 fatty acid that may reduce the risk of cardiovascular disease. However, the effect of α-linolenic acid (ALA) on the risk of heart failure (HF) remains unclear. In this meta-analysis, we aimed to determine the role of ALA in the risk of incident HF. Methods: Electronic databases were searched for studies up to August 10, 2021. Studies were included for meta-analysis if the adjusted risk of HF in different dietary intake or circulating levels of ALA was reported. We used the random-effects model to calculate the estimated hazard ratios (HRs) and 95% CI for higher ALA. Results: A total of 6 studies (7 cohorts) comprising 135,270 participants were included for meta-analysis. After a median follow-up duration of 10 years, 5,905 cases of HF were recorded. No significant heterogeneity was observed among all the included studies. Random-effects model analyses showed that there was no significant association between ALA and the risk of incident HF, either assessed as quintiles (highest quintile vs. lowest quintile: HR = 0.95, 95% CI = 0.86-1.06) or per 1 SD increment (HR = 0.99, 95% CI = 0.95-1.01). Furthermore, we did not observe any association between ALA and the risk of HF in subgroup analyses performed according to age, sex, follow-up duration, and measuring method of ALA. Conclusions: We found no association between ALA and the risk of incident HF, suggesting that ALA might not be effective in the prevention of HF.

The YAP/SERCA2a signaling pathway protects cardiomyocytes against reperfusion-induced apoptosis.

Mitochondria and the endoplasmic reticulum (ER) are known to promote cardiac ischemia/reperfusion (I/R) injury. Overexpression of yes-associated protein (YAP) and/or sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) has been shown to protect cardiomyocytes against I/R-induced injury. Here, we show that activation of the YAP/SERCA2a pathway attenuated mitochondrial damage and ER stress (ERS) to maintain cardiomyocyte viability in the setting of I/R injury. Our results demonstrate that I/R treatment reduced the transcription and expression of YAP and SERCA2a, along with a decline in cardiomyocyte viability. The overexpression of YAP promoted SERCA2a transcription, whereas SERCA2a upregulation did not affect the YAP transcription, suggesting that YAP functions upstream of SERCA2a. Activation of the YAP/SERCA2a pathway suppressed mitochondrial damage by sustaining the mitochondrial redox balance and restoring mitochondrial bioenergetics. Additionally, its activation repressed ERS, reduced calcium overload, and eventually blocked caspase activation. The knockdown of SERCA2a suppressed the protective effects of YAP overexpression on mitochondrial damage and ERS. Overall, our findings reveal that the YAP/SERCA2a pathway attenuates the mitochondrial damage and ERS in response to cardiac I/R injury by regulating the mitochondria-ER communication.

Nonalcoholic fatty liver disease is associated with increased risk of atrial fibrillation.

BACKGROUND & AIMS: Whether nonalcoholic fatty liver disease (NAFLD) is associated with risk of incident atrial fibrillation (AF) independent of established cardiovascular risk factors remains controversial. We aimed to provide a quantitative estimate of the association between NAFLD and risk of AF after adjustment for cardiometabolic risk factors. METHODS: In this study, we searched PubMed and Embase for studies published from database inception until January 31, 2020. Cohort studies reported adjusted relative risks (RRs) and 95% confidence intervals (CIs) for AF of NAFLD compared with non-NAFLD were included for analysis. RESULTS: A total of 6 cohort studies were included, comprising 614 673 individuals for analysis. The median follow-up duration was 10.0 years with 7271 cases of incident AF. Compared with non-NAFLD, minimally adjusted models without adjustment for cardiometabolic risk factors showed that NAFLD was associated with increased risk of AF (RR 1.65, 95% CI 1.23-2.20, I2  = 63.0%). After adjustment for multiple cardiometabolic risk factors, the association between NAFLD and risk of AF was still higher than that in non-NAFLD (RR 1.19, 95% CI 1.04-1.31, I2  = 54.0%). There was significant heterogeneity for the risk of AF between minimally and maximally adjusted models (I2  = 77.1%, P for heterogeneity = 0.04). Compared with non-NAFLD, the absolute risk increase in NAFLD for AF was 1.3 (95% CI 0.5-2.1) per 1000 person-years. CONCLUSIONS: NAFLD is associated with increased risk of incident AF. The strength of the association between NAFLD and AF is partially attributed to the co-existing cardiometabolic risk factors.

Piwi-interacting RNAs play a role in vitamin C-mediated effects on endothelial aging.

The underlying mechanisms that mediate the effects of vitamin C on endothelial cell aging are widely unknown. To investigate whether Piwi-interacting RNAs (piRNAs) are involved in this process, an endothelial aging model was induced in vitro using H2O2 in human umbilical vein endothelial cells (HUVECs) and then treated with vitamin C (VC). Untreated HUVECs without H2O2 exposure were used to serve as the negative control group. Cell cycle, cell viability, and aging-associated protein expression were assessed, and RNA sequencing was performed to reveal the piRNA profile. Functional and regulatory networks of the different piRNA target genes were predicted by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and Gene Ontology (GO) analysis. H2O2 induced G1 phase cell arrest, decreased cell viability, and upregulated the senescence marker p16 in HUVECs. We found that VC treatment inhibited G1 phase cell arrest, increased the number of cells in the S and G2/M phases, increased cell viability, and decreased p16 expression. The piRNA expression profiles revealed that a large proportion of piRNAs that were differentially expressed in H2O2-treated HUVECs were partly normalized by VC. Furthermore, a number of piRNAs associated with the response to VC in H2O2-treated HUVECs were linked with senescence and cell cycle-related pathways and networks. These results indicate that the ability of VC to attenuate H2O2-mediated endothelial cell senescence may be associated with changes in expression of piRNAs that are linked to the cell cycle.

MicroRNA-208-5p regulates myocardial injury of sepsis mice via targeting SOCS2-mediated NF-κB/HIF-1α pathway.

BACKGROUND: Accumulating evidence has revealed the roles of microRNAs (miRs) in sepsis, hence, the aim of the present study was to investigate whether miR-208a-5p affects sepsis whilst attempting to elucidate the mechanisms by which the suppressors of cytokine signaling 2 (SOCS2)-mediated nuclear factor-kappaB/hypoxia-inducible factor-1α (NF-κB/HIF-1α) pathway is implicated in this process. METHODS: The sepsis model was established by cecal ligation and puncture in mice. Serum levels of myocardial enzyme cardiac Troponin-I (cTnI) and brain natriuretic peptide (BNP) in mice were measured. Malondialdehyde (MDA), lactate dehydrogenase (LDH) activity, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), NF-κB p65, HIF-1α and superoxidedismutase (SOD) activity in myocardial tissues were determined. Furthermore, the swelling degree of mitochondria and the apoptosis of cardiomyocytes was measured. The expression of miR-208a-5p, SOCS2, Bcl-2, Bax, NF-κB p65 and HIF-1α in myocardial tissues of mice were detected. RESULTS: Down-regulation of miR-208a-5p and up-regulation of SOCS2 raised the activity of SOD, while reduced the activity of LDH and MDA and the concentrations of cTnI, BNP, TNF-α, IL-6, NF-κB p65 and HIF-1α in mice with sepsis. Down-regulated miR-208a-5p and up-regulated SOCS2 reduced degree of mitochondria swelling, and suppressed cardiomyocytes apoptosis in mice with sepsis. MiR-208a-5p, NF-κB p65 and HIF-1α expression were raised while SOCS2 expression was depressed in myocardial tissues of mice with sepsis. CONCLUSION: This study suggests that high expression of SOCS2 or inhibition of miR-208a-5p alleviates the myocardial injury of sepsis mice via modulating NF-κB/HIF-1α pathway, which are potential candidate markers and therapeutic targets for sepsis mice.

Combination of melatonin and irisin ameliorates lipopolysaccharide-induced cardiac dysfunction through suppressing the Mst1-JNK pathways.

Despite significant advances in therapies in past decades, the mortality rate of septic cardiomyopathy remains high. The aim of this study is to explore the therapeutic effects of combined treatment using melatonin and irisin in a mouse model of lipopolysaccharide (LPS)-mediated septic cardiomyopathy. Our data found that melatonin and irisin could further attenuate LPS-induced myocardial depression. Molecular investigation illustrated that melatonin and irisin cotreatment sustained cardiomyocyte viability and improved mitochondrial function under LPS stress. Pathway analysis demonstrated that macrophage-stimulating 1 (Mst1), which was significantly activated by LPS, was drastically inhibited by melatonin/irisin cotreatment. Mechanically, Mst1 activated c-Jun N-terminal kinase (JNK) pathway and the latter induced oxidative stress, adenosine triphosphate metabolism disorder, mitochondrial membrane potential reduction, and cardiomyocyte death activation. Melatonin and irisin cotreatment effectively inhibited the Mst1-JNK pathway and, thus, promoted cardiomyocyte survival and mitochondrial homeostasis. Interestingly, Mst1 overexpression abolished the beneficial effects of melatonin and irisin in vivo and in vitro. Altogether, our results confirmed that melatonin and irisin combination treatment could protect heart against sepsis-induced myocardial depression via modulating the Mst1-JNK pathways.

Therapeutic contribution of melatonin to the treatment of septic cardiomyopathy: A novel mechanism linking Ripk3-modified mitochondrial performance and endoplasmic reticulum function.

The basic pathophysiological mechanisms underlying septic cardiomyopathy have not yet been completely clarified. Disease-specific treatments are lacking, and care is still based on supportive modalities. The aim of our study was to assess the protective effects of melatonin on septic cardiomyopathy, with a focus on the interactions between receptor-interacting protein kinase 3 (Ripk3), the mitochondria, endoplasmic reticulum (ER) and cytoskeletal degradation in cardiomyocytes. Ripk3 expression was increased in heart samples challenged with LPS, followed by myocardial inflammation, cardiac dysfunction, myocardial breakdown and cardiomyocyte death. The melatonin treatment attenuated septic myocardial injury in a comparable manner to the genetic depletion of Ripk3. Molecular investigations revealed that Ripk3 intimately regulated mitochondrial function, ER stress, cytoskeletal homeostasis and cardioprotective signaling pathways. Melatonin-mediated inhibition of Ripk3 improved mitochondrial bioenergetics, reduced mitochondria-initiated oxidative damage, sustained mitochondrial dynamics, ameliorated ER stress, normalized calcium recycling, and activated cardioprotective signaling pathways (including AKT, ERK and AMPK) in cardiomyocytes. Interestingly, Ripk3 overexpression mediated resistance to melatonin therapy following the infection of LPS-treated hearts with an adenovirus expressing Ripk3. Altogether, our findings identify Ripk3 upregulation as a novel risk factor for the development of sepsis-related myocardial injury, and melatonin restores the physiological functions of the mitochondria, ER, contractile cytoskeleton and cardioprotective signaling pathways. Additionally, our data also reveal a new, potentially therapeutic mechanism by which melatonin protects the heart from sepsis-mediated dysfunction, possibly by targeting Ripk3.

Anticoagulación oral en pacientes con fibrilación auricular e insuficiencia renal terminal: ¿qué es lo más apropiado? / Use of oral anticoagulation for patients with atrial fibrillation and end-stage renal disease: what is needed nowadays?

No disponible

[Effect of hydrogen sulfide on H2O2-stimulated primary neonatal rat cardiomyocytes].

OBJECTIVE: To investigate the effects of hydrogen sulfide (H2S) on H2O2-stimulated primary neonatal rat cardiomyocytes and related mechanism. METHODS: Primary neonatal rat cardiomyocytes were treated with various concentrations of H2O2 (10, 100, 1000 µmol/L) for 24 h to establish the oxidative stress-induced cell injury model after 3 days' conventional culture. In addition, different concentrations of NaHS (1, 10, 100 µmol/L) were added to cardiomyocytes in the absence and presence of 100 µmol/L H2O2 for 24 h. The viability of cardiomyocytes was measured by MTT assay. The SOD vitality was measured by xanthine oxidase method and MDA content was determined by thiobarbituric acid colorimetric method. LDH activity was measured by chemical colorimetric method. The percentage of apoptotic cells was assessed by flow cytometry (FCM). The mitochondrial membrane potential (MMP) was analyzed by rhodamine 123 (Rh123) staining and photofluorography. The level of reactive oxygen species (ROS) in cardiomyocytes was measured by DCFH-DA staining and photofluorography. RESULTS: Cell viability and SOD vitality were significantly reduced while MDA content and LDH activity were significantly increased with increasing H2O2 concentrations. These effects could be partly reduced by cotreatment with H2O2 in a concentration-dependent manner (all P < 0.05). Compared with control group, the DCF fluorescence intensity significantly increased in the 100 µmol/L H2O2 group (P = 0.003), which could be attenuated by NaHS in a dose-dependent manner. Compared with control group, the MMP significantly decreased in the 100 µmol/L H2O2 group (P = 0.000), which could be partly reversed by cotreatment with NaHS in a dose-dependent manner. Moreover, H2O2 treatment also significantly reduced 100 µmol/L H2O2 induced apoptosis in a dose-dependent manner. CONCLUSION: H2S protects primary neonatal rat cardiomyocytes against H2O2-induced oxidative stress injury through inhibition of H2O2 induced overproduction of ROS, dissipation of MMP and apoptosis.