Age-Related Effect of Uric Acid on Contrast-Induced Acute Kidney Injury of Patients Undergoing Coronary Angiography.

Background: The association between uric acid (UA) and contrast-induced acute kidney injury (CI-AKI) following coronary angiography (CAG) has been established. However, whether the association would vary with age remained undetermined. Methods: We performed the retrospective analysis based on the Cardio-renal Improvement II study, (ClinicalTrials.gov NCT05050877), which enrolled consecutive patients undergoing coronary angiography in 5 teaching hospitals in China from 2007 to 2020. The primary outcome was CI-AKI defined as the rise of serum creatinine (SCr) ≥ 0.5 mg/dL or 25% compared with the baseline value within 48 hours following CAG. The effect of age on the association between uric acid and CI-AKI was assessed by the logistic regression model. Results: A total of 36,550 patients (mean age 63.08±5.6-year-old, 41.7% men) were included in the study. After adjusting for the confounders, the risk of CI-AKI between each quartile of uric acid was insignificant in the young group. In patients of the middle group, lower UA was associated with a lower risk of CI-AKI while higher UA was associated with a higher risk (Q1 OR: 0.853, 95% CI: 0.734-0.993; Q4 OR: 1.797, 95% CI: 1.547-2.09). In patients of the elder group, lower and higher UA were both associated with a higher risk of CI-AKI (Q1 OR: 1.247, 95% CI: 1.003-1.553; Q4 OR: 1.688, 95% CI: 1.344-2.124). The restricted cubic spline indicated a non-linear association between UA and CI-AKI in middle and elder age groups but a linear association in the young age group. Conclusion: The association between uric acid and CI-AKI vary in patients of different age. Patients with elder age should maintain a middle level of uric acid while patients with middle age should consider a lower level of uric acid to reduce the risk of CI-AKI. The level of UA was an insignificant risk factor for CI-AKI in young patients.

The aggregate index of systemic inflammation (AISI): a novel predictor for hypertension.

Objective: Inflammation plays an important role in the pathophysiology of hypertension (HTN). Aggregate index of systemic inflammation (AISI), as a new inflammatory and prognostic marker has emerged recently. Our goal was to determine whether there was a relationship between HTN and AISI. Methods: We analyzed patients with HTN from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. The primary end point was cardiovascular mortality. A total of 23,765 participants were divided into four groups according to the AISI quartile level. The association between AISI and cardiovascular mortality in patients with HTN was assessed by survival curves and Cox regression analyses based on NHANES recommended weights. Results: High levels of AISI were significantly associated with cardiovascular mortality in patients with HTN. After full adjustment for confounders, there was no significant difference in the risk of cardiovascular mortality in Q2 and Q3 compared to Q1, while Q4 (HR: 1.91, 95% CI: 1.42-2.58; P < 0.001) had a higher risk of cardiovascular mortality compared to Q1. Results remained similar in subgroup analyses stratified by age (P for interaction = 0.568), gender (P for interaction = 0.059), and obesity (P for interaction = 0.289). Conclusions: In adults with HTN, elevated AISI levels are significantly associated with an increased risk of cardiovascular mortality and may serve as an early warning parameter for poor prognosis.

Predictors of mortality in heart failure with reduced ejection fraction: interaction between diabetes mellitus and impaired renal function.

BACKGROUND: The harmful effect of diabetes mellitus (DM) on mortality in patients with heart failure with reduced ejection fraction (HFrEF) remains controversial. Furthermore, it seems that no consistent conclusion on whether chronic kidney disease (CKD) modifies the relationship of DM and poor prognosis in patients with HFrEF. METHODS: We analyzed the individuals with HFrEF from the Cardiorenal ImprovemeNt (CIN) cohort between January 2007 and December 2018. The primary endpoint was all-cause mortality. The patients were divided into four groups (control vs. DM alone vs. CKD alone vs. DM and CKD). Multivariate Cox proportional hazards analysis was conducted to examine the association among DM, CKD and all-cause mortality. RESULTS: There were 3,273 patients included in this study (mean age: 62.7 ± 10.9 years, 20.4% were female). During a median follow-up of 5.0 years (interquartile range: 3.0-7.6 years), 740 (22.6%) patients died. Patients with DM have a higher risk of all-cause mortality (HR [95% confidence interval (CI)]:1.28[1.07-1.53]) than those without DM. In patients with CKD, DM had a 61% (HR [95% CI]:1.61[1.26-2.06]) increased adjusted risk of death relative to non-DM, while in patients with non-CKD, there was no significantly difference in risk of all-cause mortality (HR [95% CI]:1.01[0.77-1.32]) between DM and non-DM (p for interaction = 0.013). CONCLUSIONS: Diabetes is a potent risk factor for mortality in patients with HFrEF. Furthermore, DM had a substantially different effect on all-cause mortality depending on CKD. The association between DM and all-cause mortality was only observed in patients with CKD.

The advanced lung cancer inflammation index predicts long-term outcomes in patients with hypertension: National health and nutrition examination study, 1999-2014.

Background: Malnutrition and systemic inflammation are associated with poor outcomes in patients with hypertension, and the two often coexist. However, few studies have combined nutritional and inflammatory status to assess the prognosis of patients with hypertension. The present study aimed to investigate the association between advanced lung cancer inflammation index (ALI), as a factor assessment the nutritional and inflammatory status, and long-term all-cause mortality of patients with hypertension. Materials and methods: Data from the National Health and Nutrition Examination Survey (NHANES) 1999-2014 with mortality follow-up through December 31, 2015, were analyzed. A total of 15,681 participants were evaluated. The patients were grouped based on the ALI tertiles as follows: T1 (ALI ≤ 49.41, n = 5,222), T2 (ALI > 49.41 and ≤ 76.29, n = 5,221), and T3 (ALI > 76.29, n = 5,237) groups. Survival curves and Cox regression analysis based on the NHANES recommended weights were used to assess the relationship between nutritional and inflammatory status and long-term all-cause mortality. Results: Advanced lung cancer inflammation index was significantly associated with long-term all-cause mortality in patients with hypertension. After adjustment for related factors, the T2 [hazard ratio (HR): 0.69, 95% confidence interval (CI): 0.58-0.83; P < 0.001) and T3 (HR: 0.59, 95% CI: 0.47-0.74; P < 0.001) groups were significantly associated with a decreased risk of all-cause mortality compared to the lower ALI level group (T1). Conclusion: Advanced lung cancer inflammation index was a comprehensive index of nutrition and inflammation and an independent significant prognostic factor in hypertension patients in the American community. Systemic inflammatory and nutritional status assessment and monitoring are essential for the health of hypertensive patients.

Identification and Validation of Immune Markers in Coronary Heart Disease.

Background: Coronary heart disease (CHD) is an ischemic heart disease involving a variety of immune factors. This study was aimed at investigating unique immune and m6A patterns in patients with CHD by gene expression in peripheral blood mononuclear cells (PBMCs) and at identifying novel immune biomarkers. Methods: The CIBERSORT algorithm and single-sample gene set enrichment analysis (ssGSEA) were applied to assess the population of specific infiltrating immunocytes. Weighted Gene Coexpression Network Analysis (WGCNA) was utilized on immune genes matching CHD. A prediction model based on core immune genes was constructed and verified by a machine learning model. Unsupervised cluster analysis identified various immune patterns in the CHD group according to the abundance of immune cells. Methylation of N6 adenosine- (m6A-) related gene was identified from the literature, and t-distributed stochastic neighbor embedding (t-SNE) analysis was used to determine the rationality of the m6A classification. The association between m6A-related genes and various immune cells was estimated using heat maps. Results: 22/28 immune-associated cells differed between the CHD and normal groups, and a significant difference was detected in the expression of 21 m6A-related genes. The proportion of immune-related cells (activated CD4+ T cells and CD8+ T cells) in the peripheral blood of the CHD group was lower than that of the normal group. The immune genes were divided into four modules, of which the turquoise modules showed a significant association with coronary heart disease. Eight hub immune genes (PDGFRA, GNLY, OSMR, NUDT6, FGFR2, IL2RB, TPM2, and S100A1) can well distinguish the CHD group from the normal group. Two different immune patterns were identified in the CHD group. Interestingly, a significant association was detected between the m6A-related genes and immune cell abundance. Conclusion: In conclusion, we identified different immune and m6A patterns in CHD. Thus, it could be speculated that the immune system plays a crucial role in CHD, and m6A is correlated with immune genes.

Prevalence and Prognostic Impact of Malnutrition in Critical Patients With Acute Myocardial Infarction: Results From Chinese CIN Cohort and American MIMIC-III Database.

Background: Malnutrition is associated with poor prognosis in patients with acute myocardial infarction (AMI). However, the prognostic impact of malnutrition in critical patients with AMI has not been well addressed. Methods: We analyzed two critical AMI cohorts from Cardiorenal ImprovemeNt (CIN) in China and Medical Information Mark for Intensive Care-III (MIMIC-III) in the United States. The primary outcome was all-cause mortality. Cox proportional hazards models were constructed to examine the risk of malnutrition for mortality in critical patients with AMI. Results: There were 2,075 critical patients with AMI (mean age, 62.5 ± 12.3 years, 20.00% were female) from the CIN cohort and 887 critical patients with AMI (mean age, 70.1 ± 12.9 years, 37.43% were female) from MIMIC-III included in this study. Based on the Controlling Nutritional Status (CONUT) score, of the Chinese patients with AMI, the prevalence was 47.5, 28.3, and 3.5% for mild, moderate, and severe malnutrition, respectively. The percentage of mild, moderate, and severe malnutrition was 41.60, 30.55, and 7.32% in the MIMIC-III cohort, respectively. Controlling for confounders, worse nutritional state was significantly associated with increased risk for all-cause mortality [an adjusted hazard ratio for mild, moderate, and severe malnutrition, respectively, 1.10 (95% confidence interval (CI): 0.76-1.59), 1.49 (95% CI: 1.02-2.19), and 1.70 (95% CI: 1.00-2.88) in the CIN cohort and 1.41 (95% CI: 0.95-2.09), 1.97 (95% CI: 1.32-2.95), and 2.70 (95% CI: 1.67-4.37) in the MIMIC-III cohort]. Conclusion: Malnutrition was independently associated with an increased risk of all-cause mortality in critical patients with AMI after full adjustments. Further trials are needed to prospectively evaluate the efficacy of nutritional interventions in critical patients with AMI.

A Synergistic Association Between Inflammation, Malnutrition, and Mortality in Patients With Diabetics.

Background: Although inflammation is a known predictor for poor prognosis in patients with diabetics, few data report the synergistic association between inflammation, malnutrition, and mortality in patients with diabetics. We aim to explore whether malnutrition modifies the predictor of inflammation on prognosis. Methods: Nutritional status and inflammation were measured in 6,682 patients with diabetics undergoing coronary angiography or percutaneous coronary intervention between January 2007 to December 2018 from Cardiorenal Improvement Registry. Malnutrition was defined as Controlling Nutritional Status (CONUT) score, which was more than 1. High-sensitivity C-reactive protein (hs-CRP) exceeding the median was assessed as a high-risk inflammation. Cox regression models were used to estimate hazard ratios (HR) for mortality across combined hs-CRP and CONUT score categories. Results: During a median follow-up of 5.0 years (interquartile range: 3.0-7.6 years), 759 (11.36%) patients died. The mortality of the four groups (normal nutrition and low hs-CRP level; normal nutrition and high hs-CRP level; malnutrition and low hs-CRP level; and malnutrition and high hs-CRP level) were 7.29, 7.12, 10.71, and 17.31%, respectively. Compared with normal nutrition and low hs-CRP level, an isolated condition of either malnutrition or high hs-CRP level was not associated with any significant risk for all-cause mortality. However, concomitant presence of both high hs-CRP level and malnutrition condition was associated with a significantly increased risk of all-cause mortality (HR: 1.51; 95% CI: 1.20-1.89; p < 0.001). The p-value for interaction between nutritional status and hs-CRP level on all-cause mortality was 0.03. Conclusion: The interplay of inflammation and malnutrition in patients with diabetics significantly amplifies the deleterious effects of each as distinct disease entities. A prospective randomized clinical trial is needed in the future to verify the results.

CPE Regulates Proliferation and Apoptosis of Primary Myocardial Cells Mediated by Ischemia and Hypoxia Injury.

Objective: To observe the effect of carboxypeptidase E (CPE) on the ischemia and hypoxia (I/H) injury of primary cardiomyocytes. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) technology was used to detect the expression of CPE in sham and myocardial infarction (MI) rat heart tissue, and the plasmid was transferred into primary cardiomyocytes by transfection technology. The apoptosis rate of cardiomyocytes was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining, Annexin V-PI staining, and Cell Counting Kit-8 (CCK-8) assay. In addition, Caspase kit and qRT-PCR technology were used to detect the expression of apoptosis-related factors. The cell proliferation was detected by 5-ethynyl-2'-deoxyuridine (EdU) staining, flow cytometry, and qRT-PCR technology. In addition, Western blotting (WB) and qRT-PCR techniques were used to detect the Wnt/ß-catenin pathway. Results: First, we found that the expression of CPE in the marginal zone of MI was obviously reduced. Overexpression of CPE in primary cardiomyocytes can effectively inhibit ischemia/hypoxia (I/H)-induced apoptosis and decreased cell activity. In addition, CPE can promote cell proliferation and relieve the inhibitory effect of I/H on cardiomyocytes. At the same time, CPE can promote the expression of ß-catenin and c-myc. Conclusion: Overexpression of CPE in primary cardiomyocytes can effectively alleviate the decreased cell activity, increased apoptosis, and decreased proliferation caused by I/H and regulated by Wnt/ß-catenin pathway.

Predictors and Mortality for Worsening Left Ventricular Ejection Fraction in Patients With HFpEF.

Background: Definitions of declined left ventricular ejection fraction (LVEF) vary across studies and research results concerning the association of mortality with declined LVEF are inconsistent. Thus, this study aimed to assess the impact of early worsening LVEF on mortality in patients with heart failure (HF) with preserved ejection fraction (HFpEF) and to establish independent predictors of early worsening LVEF. Methods and Results: A total of 1,418 consecutive patients with HFpEF with LVEF remeasurement from the Cardiorenal Improvement registry were included in this study. Worsening LVEF was defined as an absolute decline ≥ 5% from baseline LVEF within 3 to 12 months after discharge. The Cox and logistic regression analyses were performed to assess prognostic effects and predictors for worsening LVEF, respectively. Among 1,418 patients with HFpEF, 457 (32.2%) patients exhibited worsening LVEF. During a median follow-up of 3.2 years (interquartile range: 2.3-4.0 years), 92 (6.5%) patients died. Patients with HFpEF with worsening LVEF had higher mortality relative to those with nonworsening LVEF [9.2 vs. 5.2%; adjusted hazard ratio (aHR): 2.18, 95% CI: 1.35-3.52]. In the multivariate binary logistic regression analysis, baseline left ventricular end-diastolic dimension (LVEDD), LVEF, high-density lipoprotein cholesterol (HDL-C), atrial fibrillation (AF), and diabetes mellitus (DM) emerged as predictive factors of worsening LVEF. Conclusion: This study demonstrated that about one out of three patients with HFpEF experiences worsening LVEF during follow-up, which is associated with 2.2-fold increased mortality. Increased LVEDD and LVEF, low HDL-C levels, AF, and DM were predictors of worsening LVEF. Further studies are needed to prospectively assess the efficacy of early active management on prognosis in patients with HF with worsening LVEF. Registration: ClinicalTrials.gov, identifier NCT04407936.

Platelet-to-hemoglobin ratio as a valuable predictor of long-term all-cause mortality in coronary artery disease patients with congestive heart failure.

BACKGROUND: The platelet-to-hemoglobin ratio (PHR) has emerged as a prognostic biomarker in coronary artery disease (CAD) patients after PCI but not clear in CAD complicated with congestive heart failure (CHF). Hence, we aimed to assess the association between PHR and long-term all-cause mortality among CAD patients with CHF. METHODS: Based on the registry at Guangdong Provincial People's Hospital in China, we analyzed data of 2599 hospitalized patients who underwent coronary angiography (CAG) and were diagnosed with CAD complicated by CHF from January 2007 to December 2018. Low PHR was defined as ˂ 1.69 (group 1) and high PHR as ≥ 1.69 (group 2). Prognosis analysis was performed using Kaplan-Meier method. To assess the association between PHR and long-term all-cause mortality, a Cox-regression model was fitted. RESULTS: During a median follow-up of 5.2 (3.1-7.8) years, a total of 985 (37.9%) patients died. On the Kaplan-Meier analysis, patients in high PHR group had a worse prognosis than those in low PHR group (log-rank, p = 0.0011). After adjustment for confounders, high PHR was correlated with an increased risk of long-term all-cause mortality in CAD patients complicated with CHF. (adjusted hazard ratio [aHR], 1.31; 95% confidence interval [CI], 1.13-1.52, p < 0.0001). CONCLUSION: Elevated PHR is correlated with an increased risk of long-term all-cause mortality in CAD patients with CHF. These results indicate that PHR may be a useful prognostic biomarker for this population. Meanwhile, it is necessary to take effective preventive measures to regulate both hemoglobin levels and platelet counts in this population.

Impact of the Malnutrition on Mortality in Elderly Patients Undergoing Percutaneous Coronary Intervention.

PURPOSE: Malnutrition has been shown to be related to adverse clinical outcomes in patients with heart failure, hypertension, atrial fibrillation and other cardiovascular diseases. However, in the patients with coronary artery disease (CAD) undergoing percutaneous coronary interventions (PCI), especially in the elderly, the association of nutritional state and all-cause mortality remains unknown. We aimed to investigate the association of malnutrition with all-cause mortality in the elder patients undergoing PCI. PATIENTS AND METHODS: Based on the largest retrospective and observational cohort study from January 2007 to December 2017, the Controlling Nutritional Status (CONUT) score was applied to 21,479 consecutive patients with age ≥60 who undergoing PCI for nutritional assessment. Participants were classified as absent, mild, moderate and severe malnutrition by CONUT score. The Kaplan-Meier method was used to compare all-cause mortality among the above four groups. Multivariable Cox proportional hazard regression analyses were performed to examine the association of malnutrition with all-cause mortality. RESULTS: According to the CONUT score, 48.19%, 15.08% and 0.94% patients were mildly, moderately and severely malnourished, respectively. During a median follow-up of 5.16 years (interquartile range: 3.02 to 7.89 years), 3173 (14.77%) patients died. Kaplan-Meier analysis showed that the risk of all-cause mortality was significantly higher in patients with a worse nutritional status. Compared with normal nutritional state, malnutrition was associated with significantly increased risk for all-cause mortality (adjusted hazard ratio for mild, moderate and severe degrees of malnutrition, respectively: 1.20 [95% confidence interval (CI): 1.09 to 1.33], 1.32 [95% CI: 1.17 to 1.49] and 1.76 [95% CI: 1.33 to 2.33]). CONCLUSION: Malnutrition is prevalent among elderly patients with CAD undergoing PCI, and is strongly related to the all-cause mortality increasing. For elderly patients with CAD undergoing PCI, it is necessary to assess the status of nutrition, and evaluate the efficacy of nutritional interventions.