Cardiology最新文献

Introduction: Atrial fibrillation (AF) is a prevalent cardiac arrhythmia with significant clinical implications. The potential influence of lipid-lowering therapies, specifically PCSK9 inhibitors (PCSK9i) and HMG-CoA reductase inhibitors (statins), on AF risk remains a topic of interest. This mendelian randomization (MR) study aimed to elucidate the causal relationship between genetically predicted inhibition of PCSK9 and HMG-CoA reductase and the risk of AF.

Methods: Utilizing publicly available, summary-level genome-wide association study data, we employed single-nucleotide polymorphisms associated with lower LDL-C levels as instruments for gene-simulated inhibition of PCSK9 and HMG-CoA reductase. Multiple MR techniques were applied to estimate the causal effects, and sensitivity analyses were conducted to validate the results.

Results: Genetically predicted inhibition of PCSK9 demonstrated a reduced risk of AF, with an odds ratio (OR) of 0.92 (95% CI: 0.85-0.99, p = 0.01) using the inverse variance-weighted (IVW) method. In contrast, the inhibition of HMG-CoA reductase did not exhibit a statistically significant association with AF risk (IVW: OR = 1.11, 95% CI: 1.00-1.22, p = 0.05).

Conclusion: Our MR study suggests that genetically predicted inhibition of PCSK9, but not HMG-CoA reductase, is associated with a lower risk of AF. These findings provide evidence for a causal protective effect of PCSK9i on AF and support the use of PCSK9i for AF prevention in patients with dyslipidemia. Further studies are needed to elucidate the mechanisms underlying the differential effects of PCSK9i and statins on AF and to confirm the clinical implications of our findings.

Introduction: End-stage renal disease is a major risk factor for cardiovascular morbidity and mortality, which can be partially eliminated by kidney transplantation. Systolic heart failure might be considered contraindication for kidney transplant, although some patients demonstrate myocardial recovery post-transplant. We aimed to identify and characterize the phenomenon of reverse myocardial remodeling in kidney transplanted patients.

Methods: The study is a retrospective cohort of patients undergoing kidney transplants between 2016 and 2019 (n = 604) at Rabin Medical Center. Patients were assessed according to availability of two echocardiographic examinations: pre- and post-kidney transplant. The change in estimated ejection fraction (EF) and possible predictors of myocardial recovery were examined.

Results: Data of 293 patients was available for the final analysis. Eighty-one (28%) patients had a LVEF improvement equal to or above 5%, whereas 36 (12%) patients had a LVEF improvement of 10% or more post-transplantation. Twenty-five patients (8.5%) had moderate or severe systolic heart failure with LVEF reduced to 40% or less at baseline. 13 of them (52%) had a LVEF improvement of ≥5%, and 10 patients (40%) had an improvement of ≥10% in their EF. Cox regression analyses identified female gender as the only independent variable associated with LVEF improvement of at least 10%.

Conclusion: Renal transplantation might lead to improved LV systolic function in some patients.

Introduction: Calcific aortic valve disease (CAVD) is the third most common cardiovascular disease in aging populations. Despite a growing number of biomarkers having been shown to be associated with CAVD, a marker suitable for routine testing in clinical practice is still needed. Plasma cell-free DNA (cfDNA) has been suggested as a biomarker for diagnosis and prognosis in multiple diseases. In this study, we aimed to test whether cfDNA could be used as a biomarker for the diagnosis of CAVD.

Methods: Serum samples were collected from 137 diagnosed CAVD patients and 180 normal controls. The amount of cfDNA was quantified by amplifying a short fragment (ALU 115) and a long fragment (ALU 247) using quantitative real-time PCR. The cfDNA integrity (cfDI) was calculated as the ratio of ALU247 to ALU115. The association between CAVD and cfDI was evaluated using regression analysis.

Results: CAVD patients had increased ALU 115 fragments (median, 185.14 (416.42) versus 302.83 (665.41), p < 0.05) but a decreased value of cfDI (mean, 0.50 ± 0.25 vs. 0.41 ± 0.26, p < 0.01) in their serum when compared to controls. This difference was more dramatic in non-rheumatic CAVD patients (p < 0.001) versus rheumatic CAVD patients (no significant difference). Similarly, CAVD patients with bicuspid aortic valve (BAV) (p < 0.01) showed a greater difference than non-BAV CAVD patients (p < 0.05). Linear regression and logistic regression showed that cfDI was independently and significantly associated with the presence of CAVD (95% CI, 0.096 to 0.773, p < 0.05). The ROC assay revealed that cfDI combined with clinical characteristics had a better diagnostic value than cfDI alone (AUC = 0.6191, p < 0.001).

Conclusion: cfDI may be a potential biomarker for diagnosis of CAVD.

Introduction: Adiponectin is a cellular protein secreted by adipocytes, which is closely related to a variety of diseases, including atrial fibrillation (AF). Idiopathic atrial fibrillation (IAF) is defined as AF without hypertension, diabetes, and other underlying diseases. Genetic polymorphism of adiponectin affects serum adiponectin concentration. However, the association of serum adiponectin concentration and its genetic polymorphism with IAF has not been studied. This study investigated the relationship between serum levels of adiponectin, adiponectin gene polymorphisms, and the risk of developing IAF in a Chinese Han population.

Methods: Patients with IAF (n = 172, IAF group) and healthy individuals (n = 150, control group) were consecutively and randomly recruited and fasting peripheral blood samples were collected. All participants were examined for serum adiponectin concentrations and the polymorphisms SNP45T>G (SmaI locus, rs2241766) and SNP276G>T (BsmI locus, rs1501299) of the adiponectin gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Related clinical data from the two groups were also collected.

Results: Plasma adiponectin levels in the IAF group were significantly lower than those in the control group (9.9 ± 2.6 mg/L vs. 16.1 ± 7.0 mg/L, p = 0.006). There were no significant differences among the three genotypes (wild type, mutant heterozygote, and homozygote) of SNP45T>G or SNP276G>T in the prediction value of IAF. The frequency of the T allele of SNP45 T>G was 70.3% in the IAF group and significantly different from that of the control group (71.3%; p = 0.02). In the case of SNP276G>T, the frequency of the G allele was 68.61% in patients with IAF compared to 73.34% in the control group (p = 0.35). Furthermore, a comparison of the clinical data of individuals in the two groups revealed that the left atrial diameter (LAD) in patients in the IAF group was obviously higher than that in the control group (43.3 ± 6.7 mm vs. 37.9 ± 5.1 mm, respectively; p < 0.001). The left ventricular ejection fraction (LVEF) in the IAF group was obviously reduced than that in the control group (54.7 ± 11.9% vs. 60.2 ± 5.6%, respectively; p < 0.001).

Conclusions: Low plasma adiponectin levels were significantly associated with IAF. Hypoadiponectinemia can thus serve as an important factor for the incidence of IAF. The genotypes of SNP45T>G and SNP276G>T in the adiponectin gene may not correlate with the occurrence of IAF. However, our results demonstrate that the T allele of SNP45T>G may be responsible for IAF development in the Chinese Han population.

Introduction: Acute myocardial infarction (AMI) is a main contributor of sudden cardiac death worldwide. The discovery of new biomarkers that can improve AMI risk prediction meets a major clinical need for the identification of high-risk patients and the tailoring of medical treatment. Previously, we reported that autophagy a highly conserved catabolic mechanism for intracellular degradation of cellular components is involved in atherosclerotic plaque phenotype and cardiac pathological remodeling. The crucial role of autophagy in the normal and diseased heart has been well described, and its activation functions as a pro-survival process in response to myocardial ischemia. However, autophagy is dysregulated in ischemia/reperfusion injury, thus promoting necrotic or apoptotic cardiac cell death. Very few studies have focused on the plasma levels of autophagy markers in cardiovascular disease patients, even though they could be companion biomarkers of AMI injury. The aims of the present study were to evaluate (1) whether variations in plasma levels of two key autophagy regulators autophagy-related gene 5 (ATG5) and Beclin 1 (the mammalian yeast ortholog Atg6/Vps30) are associated with AMI and (2) their potential for predicting AMI risk.

Methods: The case-control study population included AMI patients (n = 100) and control subjects (n = 99) at high cardiovascular risk but without known coronary disease. Plasma levels of ATG5 and Beclin 1 were measured in the whole population study by enzyme-linked immunosorbent assay.

Results: Multivariate analyses adjusted on common cardiovascular factors and medical treatments, and receiver operating characteristic curves demonstrated that ATG5 and Beclin 1 levels were inversely associated with AMI and provided original biomarkers for AMI risk prediction.

Conclusion: Plasma levels of autophagy regulators ATG5 and Beclin 1 represent relevant candidate biomarkers associated with AMI.

Introduction: Amyloidosis caused by TTR mutations (ATTRv) is a rare inherited and autosomal dominant disease. More than 150 mutants of TTR have been reported, whereas some of them remain to be investigated.

Methods: A 52-year-old male presented with heart failure and clinically diagnosed ATTR cardiac amyloidosis (ATTR-CA) was recruited. Whole-exome sequencing (WES) was performed. Biochemical and biophysical experiments characterized protein stability using urea-mediated tryptophan fluorescence. Drug response was analyzed by fibril formation assay. Finally, tetramer TTR concentration in patient's serum sample was measured by ultra-performance liquid chromatography (UPLC).

Results: For the proband, WES revealed a mutation (c.200G>T; p.Gly67Val and referred to as G47V) in TTR gene. Biochemical and biophysical kinetics study showed that the thermodynamic stability of G47V-TTR (Cm = 2.4 m) was significantly lower than that of WT-TTR (Cm = 3.4 m) and comparable to that of L55P-TTR (Cm = 2.3 m), an early age-of-onset mutation. G47V:WT-TTR heterozygous tetramer kinetic stability (t1/2 = 1.4 h) was further compromised compared to that of the homozygous G47V-TTR (t1/2 = 3.1 h). Among three small molecule stabilizers, AG10 exhibited the best inhibition of the fibrillation of G47V-TTR homozygous protein. Using a UPLC assay, nearly 40% of TTR in this patient was calculated to be non-tetrameric.

Conclusion: In this work, we reported a patient presented early onset of clinically typical ATTR-CA due to G47V-TTR mutation. Our work for the first time not only characterized the biochemical properties of G47V-TTR mutation, but also provided hints for the pathogenicity of this mutation.