Effect of Urinary Albumin Creatinine Ratio on Cardiovascular Morbidity and Mortality in Diabetes Patients with Atherosclerotic Disease.

Background: Diabetes mellitus (DM) patients with increased urinary albumin creatinine ratio (uACR) have higher risk of mortality, while it is unclear in DM patients with atherosclerotic cardiovascular disease (ASCVD). Methods: We analysed 2832 DM patients with ASCVD in this multi-center registry cohort study Cardiorenal ImprovemeNt II (CIN-II) in 5 Chinese tertiary hospitals from 2007 to 2020. Patients were divided into 3 groups according to their uACR level (normal group: uACR <30mg/g, moderately increased group: 30mg/g≤ uACR <300mg/g, severely increased group: 300mg/g≤ uACR). The main outcome of the study was cardiovascular mortality and all-cause mortality. Results: During a median follow-up of 2.1 years, among 2832 patients (mean age: 63.3 ± 9.9 years, 29.1% women), 434 patients (15.3%) had moderately increased uACR, and 203 patients (7.2%) had severely increased uACR. Compared to patients in normal group, patients had higher cardiovascular mortality in moderately increased group and severely increased group (2.5% vs 9.9% vs 16.7%, P < 0.001), as well as all-cause mortality. After adjusting confounders, the risk of cardiovascular mortality remained higher in moderately increased group (adjusted hazard ratio [aHR]: 3.13; 95% confidence interval [CI]: 2.04-4.81) and severely increased group (aHR: 4.54; 95% CI: 2.58-8.01) than in normal group, as well as all-cause mortality. Conclusion: In our study, we found nearly a quarter of DM patients with ASCVD had increased uACR, and they have over 2- or 3-fold risk of cardiovascular mortality than those with normal uACR. UACR is a helpful indicator for risk stratification and treatment target for DM patients with ASCVD.

Elevation of hemoglobin A1c increases the risk of decline in left ventricular systolic function among patients with coronary artery disease.

AIMS: The aim of this study was to investigate the association of HbA1c and left ventricular (LV) systolic function among patients with coronary artery disease (CAD). METHODS: CAD patients from the Cardiorenal ImprovemeNt II (CIN-II, NCT05050877) registry were included in the study. They were separated into four groups based on HbA1c levels (Q1: HbA1c<5.7%; Q2: 5.7% ≤ HbA1c < 6.1%; Q3: 6.1% ≤ HbA1c < 6.9%; Q4: HbA1c ≥ 6.9%). The endpoint was decline in LV systolic function, defined as an absolute decrease in LV ejection fraction (LVEF) ≥10% from baseline to follow-up with 3-12 months. The association of HbA1c and LVEF was assessed by logistics regression models. RESULTS: CAD patients (n = 3,994) (age 62.9 ± 10.6 years; 22.2% female) were included in the final analysis. A decline in LV systolic function was recorded in 429 (11%) patients during follow-up. After fully adjusting for confounders, HbA1c was significantly associated with the high risk of decline in LV systolic function (OR 1.12 [95%CI 1.05-1.20] P = 0.001). By stratifying HbA1c as four groups, there is a significantly increased risk of decline in LV systolic function when HbA1c ≥6.1% (Q2, Q3 and Q4 vs Q1, with OR 1.22 [0.88-1.68] P = 0.235; OR 1.48 [1.07-2.05] P = 0.019; OR 1.60 [1.160-2.22] P = 0.004, respectively). Meanwhile, patients with decline in LV systolic function had a higher risk of cardiovascular death. CONCLUSIONS: Elevated HbA1c is a predictor of decline in LV systolic function in CAD patients. Clinicians should be aware of the risk of decline in LV systolic function in CAD patients with elevated HbA1c, and take measures as soon as possible.

The association between prothrombin time-international normalized ratio and long-term mortality in patients with coronary artery disease: a large cohort retrospective study with 44,662 patients.

BACKGROUND: The association between prothrombin time-international normalized ratio (PT-INR) and long-term prognosis among patients with coronary artery disease (CAD) without atrial fibrillation or anticoagulant therapy was still unclear. We analyzed the association of PT-INR levels and long-term mortality in a large cohort of CAD patients without atrial fibrillation or using of anticoagulant drugs. METHODS: We obtained data from 44,662 patients who were diagnosed with CAD and had follow-up information from January 2008 to December 2018. The patients were divided into 4 groups (Quartile 1: PT-INR ≤ 0.96; Quartile2: 0.96 < PT-INR ≤ 1.01; Quartile3: 1.01 < PT-INR ≤ 1.06; Quartile4: PT-INR > 1.06). The main endpoint was long-term all-cause death. Kaplan-Meier curve analysis and Cox proportional hazards models were used to investigate the association between quartiles of PT-INR levels and long-term all-cause mortality. RESULTS: During a median follow-up of 5.25 years, 5613 (12.57%) patients died. We observed a non-linear shaped association between PT-INR levels and long-term all-cause mortality. Patients in high PT-INR level (Quartile4: PT-INR > 1.06) showed a significantly higher long-term mortality than other groups (Quartile2 or 3 or 4), (Compared with Quartile 1, Quartile 2 [0.96 < PT-INR ≤ 1.01], aHR = 1.00, 95% CI 0.91-1.00, P = 0.99; Quartile 3 [1.01 < PT-INR ≤ 1.06], aHR = 1.10, 95% CI 1.01-1.20, P = 0.03; Quartile 4 [PT-INR > 1.06], aHR = 1.33, 95% CI 1.22-1.45, P < 0.05). CONCLUSIONS: Our study demonstrates high levels of PT-INR were associated with an increased risk of all-cause mortality.

Comparison Between Two Definitions of Contrast-Associated Acute Kidney Injury in Patients With Congestive Heart Failure.

Background: Different definitions of contrast-associated acute kidney injury (CA-AKI) have different predictive effects on prognosis. However, few studies explored the relationship between these definitions and long-term prognosis in patients with congestive heart failure (CHF). Thus, we aimed to evaluate this association and compared the population attributable risks (PAR) of different CA-AKI definitions. Methods: This study enrolled 2,207 consecutive patients with CHF undergoing coronary angiography (CAG) in Guangdong Provincial People's Hospital. Two different definitions of CA-AKI were used: CA-AKIA was defined as an increase ≥.5 mg/dl or > 25% in serum creatinine (SCr) from baseline within 72 h after CAG, and CA-AKIB was defined as an increase of ≥.3 mg/dl or > 50% in SCr from baseline within 48 h after CAG. Kaplan-Meier methods and Cox regression were applied to evaluate the association between CA-AKI with long-term mortality. Population attributable risk (PAR) of different definitions for long-term prognosis was also calculated. Results: During the 3.8-year median follow-up (interquartile range 2.1-6), the overall long-term mortality was 24.9%, and the long-term mortality in patients with the definitions of CA-AKIA and CA-AKIB were 30.4% and 34.3%, respectively. We found that CA-AKIA (HR: 1.44, 95% CI 1.19-1.74) and CA-AKIB (HR: 1.48, 95% CI 1.21-1.80) were associated with long-term mortality. The PAR was higher for CA-AKIA (9.6% vs. 8%). Conclusions: Our findings suggested that CA-AKI was associated with long-term mortality in patients with CHF irrespective of its definitions. The CA-AKIA was a much better definition of CA-AKI in patients with CHF due to its higher PAR. For these patients, cardiologists should pay more attention to the presence of CA-AKI, especially CA-AKIA.

Elevation of Preprocedural Systemic Immune Inflammation Level Increases the Risk of Contrast-Associated Acute Kidney Injury Following Coronary Angiography: A Multicenter Cohort Study.

Background: Inflammation and immune responses play an important role in the pathophysiology of contrast-associated acute kidney injury (CA-AKI), and systemic immune inflammation index (SII) has recently emerged as a new parameter for immune and inflammatory response evaluation. However, limited research has been undertaken to explore the relationship between SII and CA-AKI following coronary angiography (CAG). Patients and Methods: From January 2007 to December 2020, 46,333 patients undergoing CAG were included from 5 Chinese tertiary hospitals. SII was calculated as total peripheral platelets count × neutrophil-to-lymphocyte ratio. Patients were categorized by preprocedural SII quartiles: Q1 ≤404.5, Q2 >404.5 and ≤631.7, Q3 >631.7 and ≤1082.8, Q4 >1082.8. Univariable and multivariable logistic regression were used to reveal the link between preprocedural SII and CA-AKI. Results: A total of the 46,333 patients (62.9 ± 11.5 years, female 28.1%) were included in the study. The incidence of CA-AKI was 8.4% in Q1 group, 8.7% in Q2 group, 9.4% in Q3 group, 15.1% in Q4 group. In the multivariable model, comparing the highest (Q4 group) to lowest (Q1 group) SII level categories, preprocedural SII was related to a higher risk of CA-AKI after fully adjusting for well-known confounders, and there was no statistically difference in the other two SII level categories (Q2 and Q3 groups) compared with Q1 group (adjusted model 3: Q2 group: OR: 0.98, 95% CI: 0.87-1.11, P = 0.771; Q3 group: OR: 1.04, 95% CI: 0.92-1.18, P = 0.553; Q4: OR: 1.65, 95% CI: 1.45-1.88, p < 0.001; P for trend < 0.001). Similar results were found for all the subgroups analysis except for patients undergoing PCI, and the interaction analyses for age, PCI and AMI were significant. In addition, Kaplan-Meier curves demonstrated that the lowest quartile group showed the worst all-cause mortality in a significant SII level-dependent manner among the four groups (Log rank test; p < 0.0001). Conclusion: Elevated preprocedural SII level was a significant and independent risk factor for CA-AKI following CAG. Higher-quality prospective studies are needed to validate the predictive value of SII for CA-AKI.

Chronic Kidney Disease Increases Risk of Incident HFrEF Following Percutaneous Coronary Intervention.

Background: Chronic kidney disease (CKD) is very common in patients who are at a high risk of developing incident heart failure with reduced ejection fraction (HFrEF). However, the harmful effect of CKD on incident HFrEF has not yet been examined among patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). Methods: Patients undergoing PCI with baseline left ventricular ejection fraction (LVEF) ≥ 40% were included from January 2007 to December 2018 (ClinicalTrials.gov NCT04407936). We defined incident HFrEF as a follow-up LVEF of <40% within 3-12 months after discharge. Multivariable logistical regression was performed to examine the association of CKD with incident HFrEF. Results: Overall, of 2,356 patients (mean age 62.4 ± 10.7 years, 22.2% women), 435 (18.5%) had CKD, and 83 (3.5%) developed incident HFrEF following PCI. The rate of incident HFrEF in the CKD group was higher than that in the non-CKD group (6.9 vs. 2.8%; p < 0.001). Multivariate logistic regression analysis indicated that CKD was an independent risk factor of incident HFrEF [adjusted odds ratio (aOR) = 1.75; 95% CI, 1.03-2.92; p = 0.035] after adjustment for confounders including age, gender, diabetes, hypertension, atrial fibrillation, congestive heart failure (CHF), baseline LVEF, ACEI/ARB, and statins. Furthermore, patients with incident HFrEF have a higher ratio of all-cause mortality compared to those without HFrEF (26.5 vs. 8.1%; p < 0.001). Conclusions: Our results suggested that CKD was associated with increased risk of incident HFrEF, which was related to higher all-cause mortality in patients with CAD undergoing PCI. On this basis, more aggressive measures should be taken to prevent patients with CKD undergoing PCI from developing HFrEF.

Corrigendum: Association of Malnutrition, Left Ventricular Ejection Fraction Category, and Mortality in Patients Undergoing Coronary Angiography: A Cohort With 45,826 Patients.

[This corrects the article DOI: 10.3389/fnut.2021.740746.].

Association Between Non-Recovered Contrast-Associated Acute Kidney Injury and Poor Prognosis in Patients Undergoing Coronary Angiography.

Background: Previous studies have shown that renal function recovery after acute kidney injury (AKI) was associated with decreased risk of all-cause mortality. However, little is known about the correlation between renal function recovery and long-term prognosis in patients with contrast-associated acute kidney injury (CA-AKI) undergoing coronary angiography (CAG). Methods: We retrospectively enrolled 5,865 patients who underwent CAG. CA-AKI was defined as an increase in serum creatinine (SCr) ≥ 50% or ≥ 0.3 mg/dl from baseline within 72 h post procedure. Recovered CA-AKI was defined as a decrease in SCr to baseline or no CA-AKI level. The first endpoint was long-term all-cause mortality. Kaplan-Meier analysis and Cox regression analysis were used to investigate the association between kidney function recovery and long-term mortality. Results: During the median follow-up period of 5.25 years, the overall long-term mortality was 20.07%, and the long-term mortality in patients with recovered CA-AKI and non-recovered CA-AKI was 17.46 and 27.44%, respectively. After multivariate Cox hazard regression, non-recovered CA-AKI was significantly associated with long-term mortality, while recovered CA-AKI was not [recovered CA-AKI vs. no CA-AKI, hazard ratio (HR) = 1.06, 95% confidence interval (CI): 0.81-1.39, p = 0.661; non-recovered CA-AKI vs. no CA-AKI, HR = 1.39, 95% CI: 1.21-1.60, p < 0.001]. In the subgroup of CAD, both recovered CA-AKI and non-recovered CA-AKI were associated with increased risk of long-term all-cause mortality. However, in other subgroup analyses, only non-recovered CA-AKI was associated with increased risk of long-term all-cause mortality. Conclusion: Our results found that non-recovered CA-AKI is significantly associated with long-term mortality. In patients with CAD, recovered CA-AKI can still increase the risk of all-cause mortality. Clinicians need to pay more attention to patients suffering from CA-AKI, whose kidney function has not recovered. In addition, active prevention treatments should be taken by patients with CAD.

Paradoxical Association Between Baseline Apolipoprotein B and Prognosis in Coronary Artery Disease: A 36,460 Chinese Cohort Study.

BACKGROUND: Apolipoprotein B (ApoB) and low-density lipoprotein cholesterol (LDL-C) were identified targets for blood lipid management among coronary artery disease (CAD) patients. However, previous studies reported an inverse correlation between baseline LDL-C concentration and clinical outcomes. This study aims to explore the definite association between baseline ApoB and long-term prognosis. METHODS: A total of 36,460 CAD patients admitted to Guangdong Provincial People's Hospital were enrolled and categorized into two groups: high ApoB (≥65 mg/dL) group and low ApoB (<65 mg/dL) group. The association between baseline ApoB and long-term all-cause mortality was evaluated by the Kaplan-Meier method, Cox regression analyses and restricted cubic splines. RESULTS: The overall mortality was 12.49% (n = 4,554) over a median follow-up period of 5.01 years. Patients with low baseline ApoB levels were paradoxically more likely to get a worse prognosis. There was no obvious difference in risk of long-term all-cause mortality when only adjusted for age, gender, and comorbidity (aHR: 1.07, 95% CI: 0.99-1.16). When CONUT and total bilirubin were adjusted, the risk of long-term all-cause mortality would reduce in the low-ApoB (<65 mg/dL) group (aHR: 0.86, 95% CI: 0.78-0.96). In the fully covariable-adjusted model, patients in the ApoB <65 mg/d group had a 10.00% lower risk of long-term all-cause mortality comparing to patients with ApoB ≥65 mg/dL (aHR: 0.90; 95% CI:0.81-0.99). CONCLUSION: This study found a paradoxical association between baseline ApoB and long-term all-cause mortality. Malnutrition and bilirubin mainly mediate the ApoB paradox. Increased ApoB concentration remained linearly associated with an increased risk of long-term all-cause mortality.

Non-HDL cholesterol paradox and effect of underlying malnutrition in patients with coronary artery disease: A 41,182 cohort study.

BACKGROUND & AIMS: Non-high-density lipoprotein cholesterol (non-HDL-C) and low-density lipoprotein cholesterol (LDL-C) were established as the target for blood lipid management among patients with coronary artery disease (CAD). Previous study reported a negative relation between baseline LDL-C levels and long-term prognosis. However, the association between baseline non-HDL-C concentration and clinical outcomes is unknown. METHODS: A total of 41,182 CAD patients admitted to Guangdong Provincial People's Hospital in China were included in this study from January 2007 to December 2018 and divided into two groups (non-HDL-C < 2.2 mmol/L, n = 3236; non-HDL-C ≥ 2.2 mmol/L, n = 37,946). The Kaplan-Meier method, Cox regression analyses and restricted cubic splines were used to assess the association between non-HDL-C levels and long-term all-cause mortality. RESULTS: The overall mortality was 12.74% (n = 5247) over a median follow-up period of 5.20 years. Kaplan-Meier analysis showed that low non-HDL-C levels were paradoxically associated with a worse prognosis. After adjustment for baseline confounders (e.g., age, sex and comorbidities, etc.), multivariate Cox regression analysis revealed that low non-HDL-C levels (<2.2 mmol/L) were not significantly associated with all-cause mortality (adjusted HR, 1.03; 95% CI, 0.93-1.14). After adjustment for nutritional status, the risk of all-cause mortality in patients with low non-HDL-C levels decreased (adjusted HR, 0.86; 95% CI, 0.78-0.95). In the final multivariate Cox model adjusting for full covariates, low non-HDL-C level was related to better prognosis (adjusted HR, 0.88; 95% CI, 0.80-0.98). CONCLUSION: This study found a paradoxical association between baseline non-HDL-C concentration and long-term all-cause mortality. Malnutrition mainly mediates to the non-HDL-C paradox. Elevated non-HDL-C concentration is still a risk factor of long-term all-cause mortality after considering nutritional status.

A Bioinformatics Investigation into the Pharmacological Mechanisms of Sodium-Glucose Co-transporter 2 Inhibitors in Diabetes Mellitus and Heart Failure Based on Network Pharmacology.

PURPOSE: Diabetes mellitus (DM) is a major risk factor for the development of heart failure (HF). Sodium-glucose co-transporter 2 (SGLT2) inhibitors have demonstrated consistent benefits in the reduction of hospitalization for HF in patients with DM. However, the pharmacological mechanism is not clear. To investigate the mechanisms of SGLT2 inhibitors in DM with HF, we performed target prediction and network analysis by a network pharmacology method. METHODS: We selected targets of SGLT2 inhibitors and DM status with HF from databases and studies. The "Drug-Target" and "Drug-Target-Disease" networks were constructed using Cytoscape. Then the protein-protein interaction (PPI) was analyzed using the STRING database. Gene Ontology (GO) biological functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed to investigate using the Bioconductor tool for analysis. RESULTS: There were 125 effective targets between SGLT2 inhibitors and DM status with HF. Through further screening, 33 core targets were obtained, including SRC, MAPK1, NARS, MAPK3 and EGFR. It was predicted that the Rap1 signaling pathway, MAPK signaling pathway, EGFR tyrosine kinase inhibitor resistance, AGE-RAGE signaling pathway in diabetic complications and other signaling pathways were involved in the treatment of DM with HF by SGLT2 inhibitors. CONCLUSION: Our study elucidated the possible mechanisms of SGLT2 inhibitors from a systemic and holistic perspective based on pharmacological networks. The key targets and pathways will provide new insights for further research on the pharmacological mechanism of SGLT2 inhibitors in the treatment of DM with HF.

Acute Kidney Injury Increase Risk of Left Ventricular Remodeling: A Cohort of 1,573 Patients.

Background: Acute kidney injury (AKI) is a common complication after coronary angiography (CAG) and associated with heart failure (HF). Left ventricular (LV) remodeling is a vital process in the progression of HF. However, few studies investigate the relationship between AKI and LV remodeling. Methods: We included consecutive patients undergoing CAG from January 2007 to December 2018 at Guangdong Provincial People's Hospital (NCT04407936). AKI was defined as an absolute increase in serum creatinine (Scr) of ≥ 0.3mg/dl or a ≥ 50% increase in Scr from baseline within the first 48-72 h after the procedure. LV remodeling was defined as: (1) an absolute decrease in left ventricular ejection fraction (LVEF) of ≥ 10% compared to baseline, or (2) a follow-up LVEF < 40%. Univariate and multivariate logistical regressions were used to assess the association between AKI and LV remodeling. Results: Of the 1,573 patients (62.2 ± 9.7 years, female 36.7%) included in the study, 231 (14.7%) had AKI. The incidence of LV remodeling was higher in patients with AKI than in those without AKI (24.7% vs. 14.5%). After adjusting for confounding, multivariate logistic regression showed that AKI was associated with a significantly higher risk of LV remodeling [adjusted odds ratio (aOR) 1.87; 95% CI, 1.30-2.66; p < 0.001]. In addition, LV remodeling patients had higher all-cause mortality compared to non-LV remodeling patients (9.7% vs. 19.1%). Conclusion: Our data suggested that AKI is present in up to 15% of patients after CAG and that nearly a quarter of AKI patients suffered LV remodeling and AKI patients have a two-fold risk of developing LV remodeling than non-AKI patients. Our findings suggest that more active measures be taken not only to prevent AKI patient developing into LV remodeling, but to prevent patients undergoing CAG from developing AKI.

Mild Malnutrition Contributes the Greatest to the Poor Prognosis in Coronary Artery Disease With Well-Controlled Low-Density Lipoprotein Cholesterol Levels: A 4,863 Chinese Cohort Study.

Background: Previous studies reported that patients with coronary artery disease (CAD) and well-controlled baseline LDL-C (<1.8 mmol/L) still had higher long-term all-cause mortality. However, no study has been conducted to explore the independent risk factors for long-term mortality. In addition, there also was no study evaluating the population attributable risk (PAR) of independent risk factors in combination with their prevalence and relative risk. Therefore, we aimed to identify the independent risk factors and estimate their PAR in patients with CAD and well-controlled baseline LDL-C (<1.8 mmol/L). Methods: We analyzed 4,863 consecutive CAD patients with well-controlled baseline LDL-C admitted to Guangdong Provincial People's Hospital in China from January 2007 to December 2018. Independent risk factors for long-term all-cause death were evaluated through stepwise approach and multivariable Cox regression analysis. PAR of independent risk factors was calculated with their hazard ratio and prevalence among our cohort. Results: The overall mortality was 16.00% (n = 778) over a median follow-up period of 5.93 years. Independent risk factors for all-cause death included malnutrition, age ≥75 years, congestive heart failure (CHF), chronic kidney disease (CKD) and atrial fibrillation. Among these risk factors of interest, the hazard ratio (HR) of severe malnutrition was the highest (HR 2.82, 95% CI: 1.86-4.26), and the PAR of mild malnutrition was the highest (19.49%, 95% CI: 0.65-36.01%). Conclusion: Malnutrition, age ≥75 years, CHF, CKD and atrial fibrillation were independent predictors for long-term all-cause mortality in CAD patients with well-controlled LDL-C levels. Considering prevalence of these risk factors, more attention should be paid to the occurrence of mild malnutrition for these patients. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT04407936.

Association of Malnutrition, Left Ventricular Ejection Fraction Category, and Mortality in Patients Undergoing Coronary Angiography: A Cohort With 45,826 Patients.

Background: The regulatory effect of the left ventricular ejection fraction (LVEF) categories on the association of malnutrition and all-cause mortality in patients undergoing coronary angiography (CAG) have not been adequately addressed. Methods: Forty-five thousand eight hundred and twenty-six patients consecutively enrolled in the Cardiorenal ImprovemeNt (CIN) study (ClinicalTrials.gov NCT04407936) from January 2008 to July 2018 who underwent coronary angiography (CAG). The Controlling Nutritional Status (CONUT) score was applied to 45,826 CAG patients. The hazard ratios of mortality across combined LVEF and/or malnutrition categories were estimated by Cox regression models. Variables adjusted for in the Cox regression models included: age, gender, hypertension (HT), DM, PCI, coronary artery disease (CAD), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TRIG), chronic kidney disease (CKD), statins, atrial fibrillation (AF), anemia, and stroke. Population attributable risk (PAR) was estimated for eight groups stratified by nutritional status and LVEF categories. Results: In our study, 42,181(92%) of patients were LVEF ≥ 40%, of whom, 41.55 and 9.34% were in mild and moderate or severe malnutrition status, respectively, while 46.53 and 22.28% in mild and moderate or severe malnutritional status among patients with LVEF < 40%. During a median follow-up time of 4.5 years (percentile 2.8-7.1), 5,350 (11.7%) patients died. After fully adjustment, there is no difference of mortality on malnutrition in LVEF < 40% group (mild, moderate and severe vs. normal, HR (95%CI): [1.00 (0.83-0.98)], [1.20 (0.95-1.51)], [1.41 (0.87-2.29)], respectively, p for trend =0.068), but malnutrition was related to markedly increased risk of mortality in LVEF ≥ 40% group (mild, moderate, and severe vs. normal, HR (95%CI): [1.21 (1.12-1.31)], [1.56 (1.40-1.74)], and [2.20(1.67-2.90)], respectively, p for trend < 0.001, and p for interaction < 0.001). Patients with LVEF ≥ 40% had a higher malnutrition-associated risk of mortality and a higher PAR than those with LVEF < 40%. Conclusions: Malnutrition is common in CAG patients and it has a greater effect on all-cause mortality and a higher PAR in patients with LVEF ≥ 40% than LVEF < 40%.

Exploring the Pleiotropic Genes and Therapeutic Targets Associated with Heart Failure and Chronic Kidney Disease by Integrating metaCCA and SGLT2 Inhibitors' Target Prediction.

BACKGROUND: Previous studies have shown that heart failure (HF) and chronic kidney disease (CKD) have common genetic mechanisms, overlapping pathophysiological pathways, and therapeutic drug-sodium-glucose cotransporter 2 (SGLT2) inhibitors. METHODS: The genetic pleiotropy metaCCA method was applied on summary statistics data from two independent meta-analyses of GWAS comprising more than 1 million people to identify shared variants and pleiotropic effects between HF and CKD. Targets of SGLT2 inhibitors were predicted by SwissTargetPrediction and DrugBank databases. To refine all genes, we performed using versatile gene-based association study 2 (VEGAS2) and transcriptome-wide association studies (TWAS) for HF and CKD, respectively. Gene enrichment and KEGG pathway analyses were used to explore the potential functional significance of the identified genes and targets. RESULTS: After metaCCA analysis, 4,624 SNPs and 1,745 genes were identified to be potentially pleiotropic in the univariate and multivariate SNP-multivariate phenotype analyses, respectively. 21 common genes were detected in both metaCCA and SGLT2 inhibitors' target prediction. In addition, 169 putative pleiotropic genes were identified, which met the significance threshold both in metaCCA analysis and in the VEGAS2 or TWAS analysis for at least one disease. CONCLUSION: We identified novel variants associated with HF and CKD using effectively incorporating information from different GWAS datasets. Our analysis may provide new insights into HF and CKD therapeutic approaches based on the pleiotropic genes, common targets, and mechanisms by integrating the metaCCA method, TWAS and VEGAS2 analyses, and target prediction of SGLT2 inhibitors.

Hypertension as a Risk Factor for Contrast-Associated Acute Kidney Injury: A Meta-Analysis Including 2,830,338 Patients.

OBJECTIVE: Previous studies have shown that the relationship between hypertension (HT) and contrast-associated acute kidney injury (CA-AKI) is not clear. We apply a systematic review and meta-analysis to assess the association between HT and CA-AKI. METHODS: We searched for articles on the study of risk factors for CA-AKI in the Embase, Medline, and Cochrane Database of Systematic Reviews (by March 25, 2021). Two authors independently performed quality assessment and extracted data such as the studies' clinical setting, the definition of CA-AKI, and the number of patients. The CA-AKI was defined as a serum creatinine (SCr) increase ≥25% or ≥0.5 mg/dL from baseline within 72 h. We used fixed or random models to pool adjusted OR (aOR) by STATA. RESULTS: A total of 45 studies (2,830,338 patients) were identified, and the average incidence of CA-AKI was 6.48%. There was an increased risk of CA-AKI associated with HT (aOR: 1.378, 95% CI: 1.211-1.567, I2 = 67.9%). In CA-AKI with a SCr increase ≥50% or ≥0.3 mg/dL from baseline within 72 h, an increased risk of CA-AKI was associated with HT (aOR: 1.414, 95% CI: 1.152-1.736, I2 = 0%). In CA-AKI with a Scr increase ≥50% or ≥0.3 mg/dL from baseline within 7 days, HT increases the risk of CA-AKI (aOR: 1.317, 95% CI: 1.049-1.654, I2 = 51.5%). CONCLUSION: Our meta-analysis confirmed that HT is an independent risk factor for CA-AKI and can be used to identify risk stratification. Physicians should pay more attention toward prevention and treatment of patients with HT in clinical practice.

Association between Prognostic Nutritional Index and Contrast-Associated Acute Kidney Injury in Patients Complicated with Chronic Kidney Disease and Coronary Artery Disease.

BACKGROUND: Contrast-associated acute kidney injury (CA-AKI) is a major adverse effect of coronary angiography (CAG). Patients with chronic kidney disease (CKD) and coronary artery disease (CAD) are at high risk of CA-AKI. This study aimed to investigate the association between prognostic nutritional index (PNI) and CA-AKI in this high-risk population. METHODS: This study enrolled a total of 4,391 patients. CA-AKI was defined as a serum creatinine increase ≥0.3 mg/dL or 50% from baseline within the first 48 hours following CAG. The PNI was calculated upon hospital admission: serum albumin (g/L) + 5 × total lymphocyte count (109/L). PNI was analysed from the high level to low level as a continuous variable and categorical variable which was divided into four groups by quartile. Restricted cubic splines and logistic regression were applied. RESULTS: Overall, 13.09% (575/4391) of patients developed CA-AKI. PNI score was significantly lower in patients with CA-AKI than that in patients without CA-AKI (P < 0.01). The relationship between PNI score and CA-AKI was linear. A logistic regression model revealed that decreased PNI score was associated with increased risk of CA-AKI [per 1-point decrement; adjusted OR = 1.08, 95% CI, 1.05-1.09; compared with Quartile 1 (PNI ≥ 46.30), Quartile 4 (PNI < 37.90), adjusted OR = 1.88, 95% CI: 1.41-2.51; and Quartile 3 (37.90 ≤ PNI < 42.15), adjusted OR = 1.37, 95% CI: 1.02-1.84]. CONCLUSION: Our study indicated a negative linear relationship between PNI score and CA-AKI in patients undergoing CAG complicated with CKD and CAD. It suggested that malnutrition is associated with increased risk of CA-AKI in this population.

Malnutrition affects cholesterol paradox in coronary artery disease: a 41,229 Chinese cohort study.

BACKGROUND: Several studies have found that a low baseline low -density lipoprotein cholesterol (LDL-C) concentration was associated with poor prognosis in patients with acute coronary syndrome (ACS), which is called the "cholesterol paradox". Low LDL-C concentration may reflect underlying malnutrition, which was strongly associated with increased mortality. The aim of this study was to investigate the cholesterol paradox in patients with CAD and the effects of malnutrition. METHOD: A total of 41,229 CAD patients admitted to Guangdong Provincial People's Hospital in China were included in this study from January 2007 to December 2018 and divided into two groups (LDL-C < 1.8 mmol/L, n = 4863; LDL-C ≥ 1.8 mmol/L, n = 36,366). The Kaplan-Meier method and Cox regression analyses were used to assess the association between LDL-C levels and long-term all-cause mortality and the effect of malnutrition. RESULT: In this real-world cohort (mean age 62.9 years; 74.9% male), there were 5257 cases of all-cause death during a median follow-up of 5.20 years [interquartile range (IQR): 3.05-7.78 years]. Kaplan-Meier analysis showed that low LDL-C levels were associated with a worse prognosis. After adjusting for baseline confounders (e.g., age, sex and comorbidities, etc.), multivariate Cox regression analysis revealed that a low LDL-C level (< 1.8 mmol/L) was not significantly associated with all-cause mortality (adjusted HR, 1.04; 95% CI, 0.96-1.24). After adjustment for nutritional status, the risk of all-cause mortality in patients with low LDL-C levels decreased (adjusted HR, 0.90; 95% CI, 0.83-0.98). In the final multivariate Cox model, a low LDL-C level was related to better prognosis (adjusted HR, 0.91; 95% CI, 0.84-0.99). CONCLUSION: This study demonstrated that the cholesterol paradox existed in CAD patients but disappeared after accounting for the effects of malnutrition.

Novel biomarkers for post-contrast acute kidney injury identified from long non-coding RNA expression profiles.

Background: Post-contrast acute kidney injury (PC-AKI) is a severe complication of cardiac catheterization. Emerging evidence indicated that long non-coding RNAs (lncRNAs) could serve as biomarkers for various diseases. However, the lncRNA expression profile and potential biomarkers in PC-AKI remain unclear. This study aimed to investigate novel lncRNA biomarkers for the early detection of PC-AKI. Methods: lncRNA profile in the kidney tissues of PC-AKI rats was evaluated through RNA sequencing. Potential lncRNA biomarkers were identified through human-rat homology analysis, kidney and blood filtering in rats and verified in 112 clinical samples. The expression patterns of the candidate lncRNAs were detected in HK-2 cells and rat models to evaluate their potential for early detection. Results: In total, 357 lncRNAs were found to be differentially expressed in PC-AKI. We identified lnc-HILPDA and lnc-PRND were conservative and remarkably upregulated in both kidneys and blood from rats and the blood of PC-AKI patients; these lncRNAs can precisely distinguish PC-AKI patients (area under the curve (AUC) values of 0.885 and 0.875, respectively). The combination of these two lncRNAs exhibited improved accuracy for predicting PC-AKI, with 100% sensitivity and 83.93% specificity. Time-course experiments showed that the significant difference was first noted in the blood of PC-AKI rats at 12 h for lnc-HILPDA and 24 h for lnc-PRND. Conclusion: Our study revealed that lnc-HILPDA and lnc-PRND may serve as the novel biomarkers for early detection and profoundly affect the clinical stratification and strategy guidance of PC-AKI.

Integrative Analysis of Transcriptome-Wide Association Study and mRNA Expression Profiles Identified Candidate Genes and Pathways Associated With Acute Myocardial Infarction.

BACKGROUND: Acute myocardial infarction (AMI), characterized by an event of myocardial necrosis, is a common cardiac emergency worldwide. However, the genetic mechanisms of AMI remain largely elusive. METHODS: A genome-wide association study dataset of AMI was obtained from the CARDIoGRAMplusC4D project. A transcriptome-wide association study (TWAS) was conducted using the FUSION tool with gene expression references of the left ventricle and whole blood. Significant genes detected by TWAS were subjected to Gene Ontology (GO) enrichment analysis. Then the TWAS results of AMI were integrated with mRNA expression profiling to identify common genes and biological processes. Finally, the identified common genes were validated by RT-qPCR analysis. RESULTS: TWAS identified 1,050 genes for the left ventricle and 1,079 genes for whole blood. Upon comparison with the mRNA expression profile, 4 common genes were detected, including HP (PTWAS = 1.22 × 10-3, PGEO = 4.98 × 10-2); CAMP (PTWAS = 2.48 × 10-2, PGEO = 2.36 × 10-5); TNFAIP6 (PTWAS = 1.90 × 10-2, PGEO = 3.46 × 10-2); and ARG1 (PTWAS = 8.35 × 10-3, PGEO = 4.93 × 10-2). Functional enrichment analysis of the genes identified by TWAS detected multiple AMI-associated biological processes, including autophagy of mitochondrion (GO: 0000422) and mitochondrion disassembly (GO: 0061726). CONCLUSION: This integrative study of TWAS and mRNA expression profiling identified multiple candidate genes and biological processes for AMI. Our results may provide a fundamental clue for understanding the genetic mechanisms of AMI.