Correlation between systolic blood pressure and mortality in heart failure patients with hypertension.

BACKGROUND: The correlation between systolic blood pressure (SBP) and mortality in hypertensive patients with different phenotypes of heart failure (HF) has not been adequately studied, and optimal blood pressure control targets remain controversial. To explore the link between SBP and prognosis in all or three ejection fraction (EF) phenotypes of HF patients with hypertension. METHODS: We analyzed 1279 HF patients complicated by hypertension in a retrospective cohort. The SBP <130 mmHg group included 383 patients, and the SBP ≥130 mmHg group included 896 patients. The major end point was all-cause mortality. RESULTS: Of the 1279 study patients, with a median age of 66.0 ±â€Š12.0 years, 45.3% were female. The proportions of the three subtypes of heart failure complicated with hypertension (HFrEF, HEmrEF, and HFpEF) were 26.8%, 29.3%, and 43.9%, respectively. During the 1-year follow-up, 223 patients experienced all-cause death, and 133 experienced cardiovascular death. Restricted cubic splines showed that the risk of all-cause and cardiovascular death increased gradually as the SBP level decreased in patients with HFrEF and HFmrEF. Furthermore, the multivariate Cox proportional hazards model revealed that SBP <130 mmHg was also associated with an increased risk of all-cause death [hazard ratio (HR) 2.53, 95% confidence interval (CI) 1.23-5.20, P  = 0.011] and cardiovascular death (HR 1.91, 95% CI 1.01-3.63, P  = 0.047) in HFrEF patients. A trend toward increased risk was observed among HFmrEF patients, but it was not statistically significant. This trend was not observed in HFpEF patients. CONCLUSION: In HFrEF patients, SBP <130 mmHg was associated with an increased risk of all-cause and cardiovascular mortality. A trend toward increased risk was observed among HFmrEF patients, but not among HFpEF patients.

Higher Peripheral Thyroid Sensitivity Is Linked to a Lower Risk of Heart Failure After Acute Myocardial Infarction.

CONTEXT: It is still not clear how the free triiodothyronine (FT3) to free thyroxine (FT4) ratio affects the prognosis of acute myocardial infarction (AMI), especially the risk of heart failure (HF) subsequent to AMI. OBJECTIVE: The purpose of this study was to see how peripheral sensitivity to thyroid hormones, as measured by the FT3/FT4 ratio, affected HF and mortality after AMI. METHODS: Our study was a retrospective cohort study. The primary endpoint was HF after AMI during and after hospitalization. The secondary endpoints were all-cause death and cardiovascular death after hospitalization. RESULTS: The main sample included 3648 inpatients with AMI with a median age of 61.0 years; 68.9% were male. In the fully adjusted model, compared with patients in the lowest Q1 of the FT3/FT4 ratio, the risk of in-hospital HF in the highest Q4 patients was reduced by 44% (OR 0.56, 95% CI 0.44-0.72, P trend < .001), the risk of out-of-hospital HF was reduced by 37% (HR 0.63, 95% CI 0.48-0.84, P trend < .001), and the risks of all-cause and cardiovascular death were also significantly reduced. The analysis of different subgroups is consistent with the overall results. Furthermore, the sensitivity analysis of the euthyroid sample of 2484 patients was consistent with the main sample. Mediation analysis showed that altered levels of amino-terminal pro-B-type natriuretic peptide were mediators between the FT3/FT4 ratio and all endpoints in our study. CONCLUSION: The thyroid hormone peripheral sensitivity of the FT3/FT4 ratio is an independent predictor of HF and mortality after AMI.

Increased serum albumin corrected anion gap levels are associated with increased incidence of new-onset HF and poor prognosis in patients with acute myocardial infarction.

BACKGROUND: There is scant evidence on a relationship between metabolic acid load and acute myocardial infarction (AMI). We evaluated the relationship between serum albumin corrected anion gap (ACAG), a metabolic acid load biomarker, and post-myocardial infarction heart failure (post-MI HF) in patients with AMI. METHODS: This prospective, single-center study enrolled 3,889 patients with AMI. The primary endpoint was the incidence of post-MI HF. Serum ACAG levels were calculated with the following formula: ACAG = AG + (40 - [albuminemia in g/l]) × 0.25. RESULTS: After correction for multiple confounding factors, patients in the fourth quartile of ACAG (highest serum ACAG levels) showed 33.5% higher risk of out-of-hospital HF [hazard ratio (HR) = 1.335, 95% CI = 1.034-1.724, p = 0.027], and 60% higher risk of in-hospital HF [odds ratio (OR) = 1.600, 95% CI = 1.269-2.017, p < 0.001] than those in the first quartile of ACAG (lowest serum ACAG levels). Altered levels of eGFR mediated 31.07% and 37.39% of the association between serum ACAG levels with out-of-hospital HF and in-hospital HF, respectively. Furthermore, altered levels of hs-CRP mediated 20.85% and 18.91% of the association between serum ACAG levels with out-of-hospital and in-hospital HF, respectively. CONCLUSION: Our study showed that higher metabolic acid load was associated with increased incidences of post-MI HF in the AMI patients. Furthermore, deterioration of renal function and the hyperinflammatory state partially mediated the association between metabolic acid load and the incidence of post-MI HF.

Role of mitochondrial metabolic disorder and immune infiltration in diabetic cardiomyopathy: new insights from bioinformatics analysis.

BACKGROUND: Diabetic cardiomyopathy (DCM) is one of the common cardiovascular complications of diabetes and a leading cause of death in diabetic patients. Mitochondrial metabolism and immune-inflammation are key for DCM pathogenesis, but their crosstalk in DCM remains an open issue. This study explored the separate roles of mitochondrial metabolism and immune microenvironment and their crosstalk in DCM with bioinformatics. METHODS: DCM chip data (GSE4745, GSE5606, and GSE6880) were obtained from NCBI GEO, while mitochondrial gene data were downloaded from MitoCarta3.0 database. Differentially expressed genes (DEGs) were screened by GEO2R and processed for GSEA, GO and KEGG pathway analyses. Mitochondria-related DEGs (MitoDEGs) were obtained. A PPI network was constructed, and the hub MitoDEGs closely linked to DCM or heart failure were identified with CytoHubba, MCODE and CTD scores. Transcription factors and target miRNAs of the hub MitoDEGs were predicted with Cytoscape and miRWalk database, respectively, and a regulatory network was established. The immune infiltration pattern in DCM was analyzed with ImmuCellAI, while the relationship between MitoDEGs and immune infiltration abundance was investigated using Spearman method. A rat model of DCM was established to validate the expression of hub MitoDEGs and their relationship with cardiac function. RESULTS: MitoDEGs in DCM were significantly enriched in pathways involved in mitochondrial metabolism, immunoregulation, and collagen synthesis. Nine hub MitoDEGs closely linked to DCM or heart failure were obtained. Immune analysis revealed significantly increased infiltration of B cells while decreased infiltration of DCs in immune microenvironment of DCM. Spearman analysis demonstrated that the hub MitoDEGs were positively associated with the infiltration of pro-inflammatory immune cells, but negatively associated with the infiltration of anti-inflammatory or regulatory immune cells. In the animal experiment, 4 hub MitoDEGs (Pdk4, Hmgcs2, Decr1, and Ivd) showed an expression trend consistent with bioinformatics analysis result. Additionally, the up-regulation of Pdk4, Hmgcs2, Decr1 and the down-regulation of Ivd were distinctly linked to reduced cardiac function. CONCLUSIONS: This study unraveled the interaction between mitochondrial metabolism and immune microenvironment in DCM, providing new insights into the research on potential pathogenesis of DCM and the exploration of novel targets for medical interventions.

NOX1 promotes myocardial fibrosis and cardiac dysfunction via activating the TLR2/NF-κB pathway in diabetic cardiomyopathy.

Diabetic cardiomyopathy (DCM) is a prevalent complication in patients with diabetes, resulting in high morbidity and mortality. However, the molecular mechanisms of diabetic cardiomyopathy have yet to be fully elucidated. In this study, we investigated a novel target, NOX1, an isoform of superoxide-producing NADPH oxidase with key functional involvement in the pathophysiology of DCM. The DCM rat model was established by a high-fat diet combined with streptozotocin injections. DCM rats elicited myocardial fibrosis exacerbation, which was accompanied by a marked elevation of NOX1 expression in cardiac tissue. In particular, a specific NOX1 inhibitor, ML171, effectively decreased myocardial fibrosis and protected against cardiac dysfunction in DCM rats. Rat neonatal cardiac fibroblasts were incubated with high glucose (HG, 33 mM) as an in vitro model of DCM. We also observed that the expression of NOX1 was upregulated in HG-cultured cardiac fibroblasts. Silencing of NOX1 was found to attenuate myocardial fibrosis and oxidative stress in HG-induced cardiac fibroblasts. Furthermore, the upregulation of NOX1 by hyperglycemia induced activation of the TLR2/NF-κB pathway both in vitro and in vivo, whereas these effects were significantly attenuated with NOX1 gene silencing and further enhanced with NOX1 gene overexpression. In summary, we demonstrated that NOX1 induced activation of the TLR2/NF-κB pathway and increased reactive oxygen species production accumulation, which ultimately increased myocardial fibrosis and deteriorated cardiac function in diabetic cardiomyopathy. Our study revealed that NOX1 was a potential therapeutic target for DCM.

Corrigendum: Higher serum phosphorus and calcium levels provide prognostic value in patients with acute myocardial infarction.

[This corrects the article DOI: 10.3389/fcvm.2022.929634.].

Higher serum phosphorus and calcium levels provide prognostic value in patients with acute myocardial infarction.

Background: Although traditional cardiovascular risk factors are closely related to the poor prognosis of acute myocardial infarction (AMI) patients, there are few studies on the relationship of serum phosphorus and calcium with prognosis in AMI patients. The relationship of serum phosphorus and calcium with prognostic biomarkers in AMI remains unclear. Methods and results: A total of 3,891 AMI patients were enrolled from a prospective cohort study. We investigated the association of serum phosphorus and calcium with prognostic biomarkers. The risk of in-hospital heart failure (HF), post-discharge HF, all-cause mortality and cardiac mortality was estimated across quartiles of serum phosphorus and calcium levels. Serum phosphorus and calcium levels were associated with biomarkers of prognosis. Overall, 969 patients developed in-hospital HF during hospitalization, 549 patients developed post-discharge HF during a median follow-up of 12 months, and 252 patients died, with 170 cardiac deaths since admission. In the fully adjusted model, compared with patients in quartile 2 (Q2), patients with serum phosphorus levels in Q4 were at greater risk of post-discharge HF [sub-distributional hazard ratios (SHR) 1.55; 95% confidence interval (CI), 1.21-1.99], in-hospital HF [odds ratio (OR) 1.84; 95% CI, 1.47-2.31], all-cause mortality (HR 1.59; 95% CI, 1.08-2.32), and cardiac mortality (SHR 1.68; 95% CI, 1.03-2.75). Compared with patients in Q2, patients with corrected calcium levels in Q4 had a higher risk of in-hospital HF (OR 1.62; 95% CI, 1.29-2.04), all-cause mortality (HR 1.99; 95% CI, 1.37-2.88), and cardiac mortality (SHR 1.87; 95% CI, 1.19-2.96; all p-trend < 0.05). Conclusion: Serum phosphorus and calcium levels were associated with AMI prognostic biomarkers in AMI. Higher serum phosphorus was independently related to the increased risk of in-hospital HF, postdischarge HF, all-cause mortality and cardiac mortality, and higher serum calcium was independently related to the increased risk of in-hospital HF, all-cause mortality and cardiac mortality after AMI.

FT3/FT4 ratio is correlated with all-cause mortality, cardiovascular mortality, and cardiovascular disease risk: NHANES 2007-2012.

Background: Thyroid hormones play a vital role in maintaining the homeostasis of the cardiovascular system. The FT3/FT4 ratio can be used to evaluate the rate of T4-to-T3 conversion, reflecting the peripheral sensitivity of thyroid hormones. There is no study to investigate its relationship with death and cardiovascular disease (CVD) in the general population. Methods: This retrospective cohort study involved 8,018 participants with measured thyroid function and no prior thyroid disease who participated in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2012. Mortality status was determined by routine follow-up using the National Death Index through December 31, 2015. Results: During a median of 87 months of follow-up, we observed 699 all-cause deaths, including 116 cardiovascular deaths. In multivariate adjusted models, higher free thyroxine (FT4) was linked to increased all-cause mortality (HR, 1.15 per SD; 95% CI, 1.09-1.22), cardiovascular mortality (HR, 1.18 per SD; 95% CI, 1.01-1.39), and CVD risk (HR, 1.17 per SD; 95% CI, 1.08-1.27). Higher free triiodothyronine (FT3) was linked to decreased all-cause mortality (HR 0.81 per SD; 95% CI, 0.70-0.93). Higher FT3/FT4 ratio was linked to decreased all-cause mortality (HR, 0.77 per SD; 95% CI, 0.69-0.85), cardiovascular mortality (HR, 0.79 per SD; 95% CI, 0.62-1.00), and CVD risk (HR, 0.82 per SD; 95% CI, 0.74-0.92). The FT3/FT4 ratio stratified findings were broadly consistent with the overall results. Conclusions: FT3, FT4, and the FT3/FT4 ratio were all independent predictors of all-cause death. FT4 and the FT3/FT4 ratio, but not FT3, were independent predictors of cardiovascular mortality and CVD risk. Along with FT3 and FT4, we should pay equal attention to the FT3/FT4 ratio in the general population.

Associations of Serum Vitamin B6 Status and Catabolism With All-Cause Mortality in Patients With T2DM.

CONTEXT: There is little evidence regarding the association between serum vitamin B6 status and catabolism and all-cause mortality in patients with type-2 diabetes mellitus (T2DM). OBJECTIVE: We aimed to ascertain if the serum level of vitamin B6 and catabolism, including pyridoxal 5'-phosphate (PLP) and 4-pyridoxic acid (4-PA), were associated with risk of all-cause mortality in T2DM patients. METHODS: This prospective cohort study involved 2574 patients with T2DM who participated in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2010. The serum concentrations of PLP and 4-PA were used to assess the serum level of vitamin B6. Mortality status was determined by routine follow-up using the National Death Index through December 31, 2015. RESULTS: Over a median follow-up of 85 months, there were 588 deaths. The fully adjusted Cox model indicated that the highest serum PLP concentrations (> 63.6 nmol/L) were associated with a decrease in all-cause mortality (hazard ratio [HR], 0.74; 95% CI, 0.55-0.99, P trend = .035). The risk for all-cause mortality was 59% higher for participants with the highest quartile of 4-PA level compared with the lowest quartile (HR, 1.62; 95% CI, 1.12-2.35; P trend = .003). The sensitivity and specificity of the combination of PLP and 4-PA levels for the prediction of all-cause mortality were 59.5% and 60.9%, respectively (area under the receiver operating characteristic curve = 0.632). The Kaplan-Meier method was used to estimate overall survival for patients based on different combinations of PLP level and 4-PA level. Patients with PLP less than 24.3 nmol/L and 4-PA greater than or equal to 25.4 nmol/L had the worst outcomes (log-rank P < .001). CONCLUSION: Overall, our data suggest that a low serum level of PLP and high serum level of 4-PA, which represent the serum level of vitamin B6, increases the risk of all-cause mortality significantly in patients with T2DM.

Poor Sleep Quality Associated With High Risk Of Ventricular Tachycardia After Acute Myocardial Infarction.

BACKGROUND: Sleep disorders (SDs) are usually associated with an increase in frequency of ventricular tachycardia (VT). However, the relationship between SDs and the prevalence of VT within the first week of acute myocardial infarction (AMI) remains unclear. This study aimed to evaluate their associations and potential mechanisms. METHODS: This structured questionnaire-based cross-sectional study enrolled 303 patients with AMI from a hospital in northern China. Pittsburgh Sleep Quality Index (PSQI) was used to determine sleep quality of subjects. Heart rate variability (HRV) of patients was investigated by ambulatory electrocardiography recorders. Enzyme-linked immunosorbent assay was used to measure the plasma levels of catecholamine in a subgroup including 80 patients with AMI. RESULTS: After adjusting to basic cardiovascular characteristics, results of multivariate logistic regression demonstrated that the global PSQI score and its main components were positively associated with VT prevalence in inpatients with AMI. There were significantly different HRV parameters interpreted as autonomic nerve activity in two groups of AMI patients with different sleep quality. In addition, we found the influence of sleep quality on plasma concentrations of adrenaline and norepinephrine in AMI patients. CONCLUSION: Sleep status was significantly associated with the initiation of VT within the first week of AMI, probably due to the effect of SDs on sympathetic nerve activity. Amelioration of sleep quality and sympathetic hyperactivity may be prospective strategy to curb arrhythmias after AMI.