Association Between Systemic Immune Inflammation Level and Poor Prognosis Across Different Glucose Metabolism Status in Coronary Artery Disease Patients.

Background: Blood glucose levels significantly affect the clinical prognosis of patients with coronary artery disease (CAD), and systemic immune inflammation is a common risk factor for both CAD and diabetes. However, the relationship between immune inflammation levels and poor prognosis in patients with CAD with different glucose metabolic statuses remains unclear. Methods: Between January 2007 and December 2020, we recruited 84,645 patients with CAD. The systemic immune inflammation index (SII) was used to comprehensively reflect the immune and inflammatory levels of patients and was calculated using the following formula: neutrophils × platelets/lymphocytes. The patients were classified into nine groups according to their glucose metabolism status (diabetes mellitus [DM], pre-diabetes mellitus [pre-DM], and normal glucose regulation [NGR]). Cox regression models and competing risk Fine and Gray models were used to investigate the association between SII and clinical outcomes. Results: During the follow-up period, 12,578 patients died, including 5857 cardiovascular-related and 1251 cancer-related deaths. The risk of all-cause and cause-specific mortality increased with increasing SII tertiles in CAD patients with NGR, pre-DM, and DM. When considering glucose metabolism status, the multivariate cox regression revealed that CAD patients with DM and SII-H levels had the highest risk of all-cause mortality (1.69 [1.56-1.83]), cardiovascular mortality (2.29 [2.02-2.59]), and cancer mortality (1.29 [1.01-1.66]). Moreover, incorporating the SII into traditional risk factor models significantly improved the C-index for predicting all-cause and cardiovascular mortality. Conclusion: Systemic immune inflammation levels on admission were correlated with a higher risk of all-cause and cause-specific mortality in patients with CAD, particularly in those with DM.

Effect of kidney disease on all-cause and cardiovascular mortality in patients undergoing coronary angiography.

Acute kidney injury (AKI) occurred in 12.8% of patients undergoing surgery and is associated with increased mortality. Chronic kidney disease (CKD) is a well-known risk for death and cardiovascular disease (CVD). Effects of AKI and CKD on patients undergoing coronary angiography (CAG) remain incompletely defined. The aim of our study was to investigate the relationship between acute and CKD and mortality in patients undergoing CAG. The cohort study included 49,194 patients in the multicenter cohort from January 2007 to December 2018. Cox regression analyses and Fine-Gray proportional subdistribution risk regression analysis are used to examine the association between kidney disease and all-cause and cardiovascular mortality. In the present study, 13,989 (28.4%) patients had kidney disease. During follow-up, 6144 patients died, of which 4508 (73.4%) were due to CVD. AKI without CKD (HR: 1.54, 95% CI: 1.36-1.74), CKD without AKI (HR: 2.02, 95% CI: 1.88-2.17), AKI with CKD (HR: 3.26, 95% CI: 2.90-3.66), and end-stage kidney disease (ESKD; HR: 5.63, 95% CI: 4.40-7.20) were significantly associated with all-cause mortality. Adjusted HR (95% CIs) for cardiovascular mortality was significantly elevated among patients with AKI without CKD (1.78 [1.54-2.06]), CKD without AKI (2.28 [2.09-2.49]), AKI with CKD (3.99 [3.47-4.59]), and ESKD (6.46 [4.93-8.46]). In conclusion, this study shows that acute or CKD is present in up to one-third of patients undergoing CAG and is associated with a substantially increased mortality. These findings highlight the importance of perioperative management of kidney function, especially in patients with CKD.Impact StatementWhat is already known on this subject? Acute kidney injury (AKI) occurred in 12.8% of patients undergoing surgery and is linked to a 22.2% increase in mortality. Chronic kidney disease (CKD) is a well-known risk for death and cardiovascular events. Effects of AKI and CKD on patients undergoing coronary angiography (CAG) remain incompletely defined.What do the results of this study add? This study shows that kidney disease is present in up to one-third of patients undergoing CAG and is associated with a substantially increased mortality. AKI and CKD are independent predicators for mortality in patients undergoing CAG.What are the implications of these findings for clinical practice and/or further research? These findings highlight the importance of perioperative management of kidney function, especially in patients with CKD.

Establishment and assessment of a preclinical model of acute kidney injury induced by contrast media combined acute myocardial ischemia reperfusion surgery.

Acute kidney injury (AKI) is a common complication after acute myocardial infarction (AMI) in clinical practice, and the majority of previous preclinical models were induced by a single factor. The objective of the present study was to establish a stable preclinic model of AKI induced by contrast media (CM) with acute myocardial ischemia reperfusion surgery and to identify the effect of oxidative stress on kidney injury. Rats were treated individually or with CM or myocardial ischemia reperfusion surgery. Renal baseline and AKI parameters, the level of oxidative stress and histopathological images were examined along with AKI biomarkers. Results showed the incidence of AKI in the CM group and ischemia reperfusion injury (IRI) group was 40%, χ2 test (P<0.05 vs. CM-IRI) and 35%, χ2 test (P<0.05 vs. CM-IRI) and the combination group had the highest incidence rate 75%. IRI surgery combined with CM diminished kidney function and induced oxidative stress by increasing creatinine, blood urea nitrogen and reactive oxygen species levels. Western blotting showed that the early AKI biomarker of NGAL and KIM-1 increased and that the combination group had the highest value. Pathology damage exhibited severe kidney damage in the combination group compared with other control groups. The present research established a reliable preclinic model of post-AMI AKI with a stable and high postoperative AKI rate. Additionally, CM was demonstrated to exacerbate AKI caused by acute myocardial infarction through oxidative stress and, thus, oxidative stress may be a potential therapeutic target.

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.

Elevated systemic immune inflammation level increases the risk of total and cause-specific mortality among patients with chronic kidney disease: a large multi-center longitudinal study.

BACKGROUND: Chronic kidney disease (CKD) is inherently a complex immune-inflammatory condition, and heightened inflammation and immune dysfunction are closely related to an increased risk of death. However, evidence regarding the relationship between immune-inflammatory levels and all-cause, cardiovascular, and cancer mortality among patients with CKD is scarce. METHODS: Patients with non-dialysis dependent CKD undergoing coronary angiography (CAG) were included from five Chinese tertiary hospitals. Systemic immune inflammation index (SII) was calculated by multiplying peripheral platelet count with neutrophil-to-lymphocyte ratio, and patients were categorized into four groups by SII quartiles. Cox regression models and competing risk Fine and Gray models were used to examining the relationships between SII levels and all-cause, cardiovascular, and cancer mortality. RESULTS: A total of the 19,327 patients (68.8 ± 10.03 years, female 32.0%) were included in this study. During a median follow-up of 4.5 years, 5,174 deaths occurred, including 2,861 cardiovascular deaths and 375 cancer deaths. Controlling for confounders, all-cause mortality (Q2, Q3, Q4: hazard ratio(HR) [95 CI%] = 1.15 [1.06-1.26], 1.30 [1.19-1.42], 1.48 [1.35-1.62], respectively; p for trend < 0.001) and cardiovascular mortality (Q2, Q3, Q4: HR [95 CI%] = 1.16 [1.03-1.31], 1.40 [1.24-1.58], 1.64 [1.44-1.85], respectively; p for trend < 0.001) increased with higher SII levels, and SII levels was related to cancer mortality comparing last quartile to first quartile of SII (Q2, Q3, Q4: HR [95 CI%] = 1.12 [0.83-1.52], 1.22 [0.90-1.67], 1.50 [1.09-2.08], respectively; p for trend < 0.001). CONCLUSION: Elevated immune inflammation level on admission was an independent risk factor for all-cause, cardiovascular, and cancer mortality among CKD patients. Further research is needed to validate the predictive value of SII for mortality risk among CKD patients.

Association between triglyceride glucose index and worsening heart failure in significant secondary mitral regurgitation following percutaneous coronary intervention.

BACKGROUND: The triglyceride glucose (TyG) index is an alternative to insulin resistance (IR) as an early indicator of worsening heart failure (HF). Patients with secondary mitral regurgitation (sMR) often experience progressive deterioration of cardiac function. This study aimed to investigate the relationship between the TyG index and worsening of HF in significant sMR (grade ≥ 2) following percutaneous coronary intervention (PCI). METHODS: This study enrolled participants with significant sMR following PCI from a multicenter cohort study. The patients were divided into the following 3 groups according to tertiles of TyG index: T1, TyG ≤ 8.51; T2, TyG > 8.51 to ≤ 8.98; and T3, TyG > 8.98. The main clinical outcome was worsening HF including unplanned rehospitalization or unscheduled physician office/emergency department visit due to HF and unplanned mitral valve surgery. RESULTS: A total of 922 patients (mean ± SD age, 64.1 ± 11.0 years; 79.6% male) were enrolled. The incidence of worsening HF was 15.5% in T1, 15.7% in T2, and 26.4% in T3. In the multivariable model, the highest TyG tertile (T3 group) was more strongly correlated with worsening HF than the lowest tertile (T1 group) after adjusting for confounders (adjusted hazard ratio, 2.44; 95% confidence interval, 1.59-3.72; P < 0.001). The addition of TyG to risk factors such as N-terminal pro brain natriuretic peptide and clinical models improved the predictive ability of TyG for worsening HF. CONCLUSIONS: Elevated preprocedural TyG index is a significant and independent risk factor for worsening HF in sMR following PCI that can be used for risk stratification.

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.

Sex Difference Trend in 5-Year Mortality Among Patients With Coronary Artery Disease: A 24,432 Chinese Cohort Study From 2007 to 2014.

Background: The sex difference trend of short-term mortality in coronary artery disease (CAD) is narrowing, which has been reported in the previous studies. However, no studies assess the sex difference temporal trends of CAD mortality in China especially long-term mortality trend. Methods: Based on the registry at Guangdong Provincial People's Hospital which is the largest cardiovascular center in South China, this retrospective cohort study included 24,432 hospitalized patients with CAD confirmed by coronary angiography from January 2007 to December 2014. Women and men were followed for 1-year and 5-year all-cause mortality. Results: From 2007 to 2014, 5-year age-standardized mortality increased from 10.0 to 11.7% in men (p for trend < 0.001) and from 11.5 to 8.1% in women (p for trend = 0.99). The multivariable-adjusted hazard ratios (95% CI), which compare women with men, were from 1.02 (0.39-2.67) to 0.66 (0.39-1.12) for 1-year all-cause mortality and 1.23 (0.64-2.36) to 0.59 (0.44-0.79) for 5-year all-cause mortality (p for trend = 0.04). Conclusion: Our study found that the mortality risk among men and women was similar in the 1-year prognosis of CAD, and there was no significant downward trend. In the 5-year long-term prognosis of CAD, the mortality risk among men continued to rise, while women had reached the peak, which means that the mortality risk continues to be higher among men than women.

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.].

Dilated Left Ventricular End-Diastolic Diameter Is a New Risk Factor of Acute Kidney Injury Following Coronary Angiography.

Purpose: Left ventricular end-diastolic diameter (LVEDD) is a common indicator in echocardiogram, and dilated LVEDD was correlated with left ventricular insufficiency. However, it is uncertain whether dilated LVEDD is associated with increasing the risk of contrast-associated acute kidney injury (CA-AKI) in patients with coronary artery disease (CAD). Patients and Methods: We enrolled 8,189 patients with CAD undergoing coronary angiography (CAG) between January 2007 and December 2018. Patients were divided into two groups according to the LVEDD length (normal LVEDD: men: LVEDD ≤56 mm, women: LVEDD ≤51 mm; dilated LVEDD: men: LVEDD >56 mm, women: LVEDD >51 mm). The endpoints were CA-AKI0350 and CA-AKI0525 (CA-AKI0350: an increase in the serum creatinine (Scr) level by >0.3 mg/dl or >50% within the first 48 h after CAG; CA-AKI0525: an absolute Scr increase ≥ 0.5 mg/dl or a relative increase ≥ 25% within 72 h after contrast medium exposure). In-hospital dialysis, 30-day mortality, and 1-year mortality were contained as well. Univariate and multivariable logistic regressions were used to assess the association between LVEDD and CA-AKI. Results: Among 8,189 participants (men: 76.6%, mean age: 64.4 ± 10.7 years), 1,603 (19.6%) presented with dilated LVEDD. In addition, the dilated LVEDD group indicated an elevation of CA-AKI0350 (12.4 vs. 6.2%, p < 0.001) and CA-AKI0525 (15.0 vs. 8.8%; p < 0.001) when compared with the normal group. According to multivariable logistic analysis, dilated LVEDD was an independent predictor of CA-AKI0350 [adjusted odds ratio (aOR): 1.31; 95% confidence interval (CI): 1.06-1.61, p = 0.010) and CA-AKI0525 (aOR: 1.32; 95% CI: 1.04-1.67; p = 0.020). Conclusion: In conclusion, these results demonstrated that the dilated LVEDD was a significant and independent predictor of CA-AKI following CAG in patients with CAD. Further verifications are needed to verify the association between LVEDD and CA-AKI.

Malnutrition in patients with coronary artery disease: Prevalence and mortality in a 46,485 Chinese cohort study.

BACKGROUND AND AIMS: Malnutrition is associated with poor prognosis in a wide range of illnesses. However, its long-term prognostic impact in general coronary artery disease (CAD) patients is not well known. We aim to report the prevalence and long-term mortality of malnutrition in the whole general population. METHODS AND RESULTS: In this retrospective cohort study, the controlling nutritional status (CONUT) score was applied to 46,485 consecutive patients undergoing coronary angiography (CAG) and diagnosed with CAD from January 2007 to July 2018. Patients were stratified as having no malnutrition (n = 19,780), mild (n = 21,092), moderate (n = 5286) and severe malnutrition (n = 327), based on CONUT score. Overall, mean age was 63.1 ± 10.7 years, and 75.8% of patients (n = 35,250) were male. 45.4% of patients were mildly malnourished and 12.1% were moderately or severely malnourished. During a median follow-up of 5.1 years (interquartile range: 3.0-7.7 years), 6093 (17.3%) patients died. After adjusting for confounders, malnutrition risk was associated with significantly increased risk for all-cause death (mild vs. normal, HR = 1.19,95% confidence interval [CI]: 1.12 to 1.28; moderate vs. normal, HR = 1.42,95% CI: 1.30 to 1.55; severe vs. Normal, HR = 1.95, 95% CI: 1.57 to 2.41) (p for trend<0.001). The similar result on all-cause mortality was also found in different subgroups stratified by gender, chronic kidney disease, anemia, percutaneous coronary intervention. CONCLUSIONS: Malnutrition is a common complication among patients with CAD, and is strongly associated with increased mortality. Further studies need to explore the efficacy of nutritional interventions on long-term prognosis among CAD patients. This study was registered at Clinicaltrials.gov as NCT04407936.

Incidence and mortality of acute kidney disease following coronary angiography: a cohort study of 9223 patients.

PURPOSE: Acute kidney disease (AKD) is an important state in the evolving kidney diseases. However, there is limited data on the incidence and prognosis of AKD following coronary angiography (CAG). Therefore, we aim to characterize the incidence and prognosis of AKD across a large population of CAG patients. METHODS: The consecutive patients with baseline and following measurement of serum creatinine (Scr) between 7 and 90 days after CAG procedure were included. The AKD was defined as a decrease in glomerular filtration rate by > 35%, or an increase in Scr of > 50% (from 7 to 90 days). Survival curves, univariate and multivariable cox regressions were used to assess the association between AKD and mortality. RESULTS: Among 9223 patients (male, 60.3%, mean age, 61.7 ± 9.6), 1540 had AKD. During a median follow-up of 5.4 (IQR 2.2-8.6) years, 1562 (16.9%) patients died. The mortality among the patients with AKD was higher than the non-AKD group (24.8% vs. 15.4%, p < 0.001). AKD was independently associated with a significantly increased risk of all-cause mortality (adjusted hazard ratio [aHR], 1.57; 95% CI 1.39-1.78; p < 0.001). CONCLUSIONS: Our study suggested that AKD is commonly observed after CAG and increased half mortality risk than those without AKD. More attention needs to be paid to patients suffering from AKD.

Prevalence and Mortality of Moderate or Severe Mitral Regurgitation Among Patients Undergoing Percutaneous Coronary Intervention With or Without Heart Failure: Results From CIN Study With 28,358 Patients.

Aim: This study investigated the prevalence and mortality associated with moderate or severe mitral regurgitation (MR) among patients undergoing percutaneous coronary intervention (PCI), with or without heart failure (HF). Methods: We analyzed patients undergoing PCI without mitral valve surgery from the Cardiorenal ImprovemeNt (CIN) study (ClinicalTrials.gov NCT04407936). Patients without echocardiography to determine MR occurrence or lacking follow-up death data were excluded. Primary endpoints were 1-year and long-term all-cause mortality, with a median follow-up time of 5 years (interquartile range: 3.1-7.6). Results: Of 28,358 patients undergoing PCI treatment [mean age: 62.7 ± 10.7; women: 6,749 (25.6%)], 3,506 (12.4%) had moderate or severe MR, and there was a higher rate of moderate or severe MR in HF group than non-HF group (28.8 vs. 5.6%, respectively). Regardless of HF conditions, patients with moderate or severe MR were older and had worse cardio-renal function and significantly increased 1-year mortality [adjusted hazard ratio (aHR): 1.82, 95% confidence interval (CI): 1.51-2.2], and long-term mortality [aHR: 1.43, 95% CI: 1.3-1.58]. There was no significant difference between patients with HF and those with non-HF (P for interaction > 0.05). Conclusion: One-eighth of the patients undergoing PCI had moderate or severe MR. Furthermore, one-third and one-seventeenth experienced moderate or severe MR with worse cardiorenal function in the HF and non-HF groups, and increased consistent mortality risk. Further studies should explore the efficacy of mitral interventional procedures for moderate or severe MR after PCI treatment, regardless of HF.

Are There Any Differences in the Prognostic Value of Left Ventricular Ejection Fraction in Coronary Artery Disease Patients With or Without Moderate and Severe Mitral Regurgitation?

Background: Left ventricular ejection fraction (LVEF) is a vital variable to describe left ventricle systolic function and contractility of left ventricle. However, the association between LVEF and the prognostic effect in patients with moderate or severe mitral regurgitation (MR) is still controversial. Methods: This study comprised 30,775 coronary artery disease (CAD) patients who underwent coronary arteriography (CAG) in the Cardiorenal ImprovemeNt (CIN) registry from January 2007 to December 2018. Patients were divided into none or mild MR group and moderate or severe MR group, and 3 levels of LVEF ≥50, 40-50%, and <40% were further distinguished according to hospital baseline. Univariate and multivariate Cox proportional analyses were used to investigate the association between LVEF levels and long-term all-cause mortality in patients with different MR severities. Results: Of 30,775 CAD patients (62.9 ± 10.6 years, females 23.8%), 26,474 (86.0%) patients had none or mild MR. Compared with none or mild MR patients, patients with moderate or severe MR were older and had worse cardio-renal function. In multivariable Cox proportional analysis, LVEF <40% was independently associated with higher mortality compared with LVEF ≥ 50% in all kinds of MR severity {none or mild MR [adjusted hazard ratio (HR): 1.79; 95% CI: 1.56-2.05, p < 0.001], moderate or severe MR [adjusted HR: 1.57; 95% CI: 1.29-1.91, p < 0.001]}. Conclusions: LVEF is a reliable prognostic index in CAD patients, even in those with moderate or severe MR. LVEF monitoring would still be clinically useful in CAD patients with moderate or severe MR. Clinical trials are needed to prospectively evaluate the optimal threshold for LVEF in patients with moderate or severe MR.

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.

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.

A Universal New Definition of Heart Failure With Improved Ejection Fraction for Patients With Coronary Artery Disease.

Aims: The aims of this study were to describe the characteristics and outcomes of the universal new definition of heart failure with improved ejection fraction (HFimpEF) and to identify predictors for HFimpEF among patients with coronary artery disease (CAD). Methods: CAD subjects with heart failure with reduced ejection fraction (HFrEF) (EF ≤ 40%) at baseline were enrolled from the real-world registry of the Cardiorenal ImprovemeNt study from January 2007 to December 2018. The new definition of HFimpEF was defined as left ventricular EF (LVEF) of≤40% at baseline and with improvement of up to 40% and at least a ≥ 10% increase during 1 month to 1 year after discharge. Results: Of the 747 CAD patients with HFrEF (86.7% males, mean age: 61.4 ± 11 years), 267 (35.7%) patients conformed to the new HFimpEF definition. Patients with HFimpEF were younger (adjusted odds ratio [aOR]: 0.98 [0.97-0.99]) and had a higher rate of hypertension (aOR:1.43 [1.04-1.98]), lower rate of percutaneous coronary intervention (PCI) treatment at the time of detection of HFrEF (aOR: 0.48 [0.34-0.69]), history of PCI (aOR: 0.51 [0.28-0.88]), history of acute myocardial infarction (aOR: 0.40 [0.21-0.70]), and lower left ventricular end diastolic diameter (aOR: 0.92 [0.90-0.95]). During 3.3-year follow-up, patients with HFimpEF demonstrated lower rates of long-term all-cause mortality (13.1% vs. 20.8%, aHR: 0.61[0.41-0.90]). Conclusion: In our study, CAD patients with HFimpEF achieved a better prognosis compared to those with persistent HFrEF. Patients with CAD meeting the criteria for the universal definition of HFimpEF tended to be younger, presented fewer clinical comorbidities, and had lower left ventricular end diastolic diameter.

Does Diabetes Mellitus Increase the Short- and Long-Term Mortality in Patients With Critical Acute Myocardial Infarction? Results From American MIMIC-III and Chinese CIN Cohorts.

Background: The harmful effect of diabetes mellitus (DM) on mortality in patients with acute myocardial infarction (AMI) remains controversial. Furthermore, few studies focused on critical AMI patients. We aimed to address whether DM increases short- and long-term mortality in this specific population. Methods: We analyzed AMI patients admitted into coronary care unit (CCU) with follow-up of ≥1 year from two cohorts (MIMIC-III, Medical Information Mart for Intensive Care III; CIN, Cardiorenal ImprovemeNt Registry) in the United States and China. Main outcome was mortality at 30-day and 1-year following hospitalization. Kaplan-Meier curves and Cox proportional hazards models were constructed to examine the impact of DM on mortality in critical AMI patients. Results: 1774 critical AMI patients (mean age 69.3 ± 14.3 years, 46.1% had DM) were included from MIMIC-III and 3380 from the CIN cohort (mean age 62.2 ± 12.2 years, 29.3% had DM). In both cohorts, DM group was older and more prevalent in cardio-renal dysfunction than non-DM group. Controlling for confounders, DM group has a significantly higher 30-day mortality (adjusted odds ratio (aOR) (95% CI): 2.71 (1.99-3.73) in MIMIC-III; aOR (95% CI): 9.89 (5.81-17.87) in CIN), and increased 1-year mortality (adjusted hazard ratio (aHR) (95% CI): 1.91 (1.56-2.35) in MIMIC-III; aHR (95% CI): 2.62(1.99-3.45) in CIN) than non-DM group. Conclusions: Taking into account cardio-renal function, critical AMI patients with DM have a higher 30-day mortality and 1-year mortality than non-DM group in both cohorts. Further studies on prevention and management strategies for DM are needed for this population. Clinical Trial Registration: clinicaltrials.gov, NCT04407936.