Proline metabolic reprogramming modulates cardiac remodeling induced by pressure overload in the heart.

Metabolic reprogramming is critical in the onset of pressure overload-induced cardiac remodeling. Our study reveals that proline dehydrogenase (PRODH), the key enzyme in proline metabolism, reprograms cardiomyocyte metabolism to protect against cardiac remodeling. We induced cardiac remodeling using transverse aortic constriction (TAC) in both cardiac-specific PRODH knockout and overexpression mice. Our results indicate that PRODH expression is suppressed after TAC. Cardiac-specific PRODH knockout mice exhibited worsened cardiac dysfunction, while mice with PRODH overexpression demonstrated a protective effect. In addition, we simulated cardiomyocyte hypertrophy in vitro using neonatal rat ventricular myocytes treated with phenylephrine. Through RNA sequencing, metabolomics, and metabolic flux analysis, we elucidated that PRODH overexpression in cardiomyocytes redirects proline catabolism to replenish tricarboxylic acid cycle intermediates, enhance energy production, and restore glutathione redox balance. Our findings suggest PRODH as a modulator of cardiac bioenergetics and redox homeostasis during cardiac remodeling induced by pressure overload. This highlights the potential of PRODH as a therapeutic target for cardiac remodeling.

Immobilization of Cr(VI)-containing tailings by using slag-cementing materials for cemented paste backfill: influence of sulfate and limestone addition.

Heavy metals in mine tailings lead to serious environmental problems. Cemented paste backfill (CPB) is widely used for treating the mine tailing. The high cost of ordinary Portland cement (OPC) reduces the profit of mine production. The work investigates the treatment of Cr(VI)-containing tailings by using slag-based cementitious materials for CPB. Flue gas desulfurization gypsum (FGDG) and limestone were used to modify the properties of samples. Results showed that the coupling addition of 6 wt% FGDG and 3 wt% limestone (A6L3) led to the highest compressive strength of CPB samples, which also presented satisfactory immobilization effects for Cr(VI). The compressive strength of CPB samples using A6L3 as a binder was comparable to the OPC-based sample, reaching about 5.53 MPa; the immobilization efficiency for Cr(VI) was about 99.5%. The effects of FGDG and limestone were twofold: the addition of FGDG favored the formation of ettringite and then contributed to a more compact structure; besides, incorporating limestone increased the packing density of the CPB system by decreasing the loosening and wedge effect.

Prognostic significance of troponin increment after percutaneous coronary intervention: A retrospective study.

Objective: The prognostic significance of troponin elevation following percutaneous coronary intervention (PCI) remains debated. This study aimed to evaluate the association between different thresholds of post-PCI cardiac troponin I (cTnI) and mortality. Methods: From January 2012 to July 2017, 5,218 consecutive patients undergoing elective PCI with pre-PCI cTnI < 99th percentile of the upper reference limit (URL) were included. Levels of cTnI were measured before PCI and every 8 h for 24 h after procedural. The outcomes were 3-year cardiac mortality. Results: Patients had a mean age of 66.2 years, 27.6% were women, 67.0% had hypertension, and 26.2% had diabetes mellitus. During the 3 years of follow-up, cardiac death occurred in 0.86%, 1.46%, 1.69%, 2.36%, and 2.86% of patients with cTnI < 1, ≥ 1 to < 5, ≥ 5 to < 35, ≥ 35 to < 70, and ≥ 70 times URL. The cardiac mortality rate was moderately increased with higher peak cTnI values, but the Kaplan-Meier curve demonstrated no significant association between any increment of cTnI and either cardiac or non-cardiac mortality. Isolated cTnI increment of ≥ 5 × URL, ≥ 35 × URL, and ≥ 70 × URL was occurred in 1,379 (26.4%), 197 (3.8%), and 70 (1.3%) patients, respectively. In multivariate Cox regression analysis and Fine-Gray model, none of the above cTnI thresholds was significantly associated with an increased risk of cardiac death. Conclusion: In patients who underwent elective PCI, post-PCI cTnI elevation is not independently associated with cardiac mortality.

Association Between Contrast Volume-to-Creatinine Clearance Ratio and the Risk of Perioperative Myocardial Infarction After Elective Percutaneous Coronary Intervention.

Although the use of iodinated contrast for percutaneous coronary intervention (PCI) has known toxicity issues, the association between the contrast volume-to-creatinine clearance (V/CrCl) ratio and perioperative myocardial infarction (PMI) is unclear. The present study is aimed to investigate the predictive value of V/CrCl ratio on the incidence of PMI, and to determine a relatively safe contrast media V/CrCl ratio cut-off value to prevent PMI undergoing elective PCI. The V/CrCl ratio were obtained from 5970 patients undergoing elective PCI for single-vessel lesions. Cardiac troponin I (cTnI) were measured at baseline, 8, 16, and 24 hours after PCI. PMI was defined as postprocedural > 5 × upper limit of normal. Receiver operating characteristic (ROC) curves were performed to identify the optimal sensitivity for the V/CrCl range. Multivariate regression model were used to assess the association between V/CrCl ratios and PMI. Eight hundred and ninety-seven patients (15.0%) developed PMI. There was a significant association between higher V/CrCl ratio and the development of PMI (P < 0.001 for the trend). ROC curve analysis indicated that V/CrCl ratio of 2.05 was a discriminator for PMI (area under the curve = 0.674). After adjusting for other potential risk factors, V/CrCl ratio > 2.05 remained significant associated with PMI (odds ratio, 1.921; 95% confidence interval, 1.311-2.815; P = 0.001). The finding of this study suggests the importance of minimizing the contrast media dose to avoid PMI development. Use of a contrast media dose based on renal function with a V/CrCl value < 2.05 might be valuable in preventing PMI.

Mitochondrial dysfunction in heart failure and its therapeutic implications.

The ATP consumption in heart is very intensive to support muscle contraction and relaxation. Mitochondrion is the power plant of the cell. Mitochondrial dysfunction has long been believed as the primary mechanism responsible for the inability of energy generation and utilization in heart failure. In addition, emerging evidence has demonstrated that mitochondrial dysfunction also contributes to calcium dysregulation, oxidative stress, proteotoxic insults and cardiomyocyte death. These elements interact with each other to form a vicious circle in failing heart. The role of mitochondrial dysfunction in the pathogenesis of heart failure has attracted increasing attention. The complex signaling of mitochondrial quality control provides multiple targets for maintaining mitochondrial function. Design of therapeutic strategies targeting mitochondrial dysfunction holds promise for the prevention and treatment of heart failure.

Gensini score values for predicting periprocedural myocardial infarction: An observational study analysis.

The Gensini score (GS) is a convenient, powerful tool for assessing the severity and complexity of coronary artery diseases. Our research investigated the relationship between the GS and periprocedural myocardial infarction (PMI). We recruited 4949 patients (3366 men, 1583 women; mean age 66.45 ± 10.09 years) with a single coronary artery revascularization. Based on the tertile of the GS 20 and 36, the population was divided into 3 groups: Low Group (0 < GS ≤ 20, N = 1809); Intermediate Group (20 < GS ≤ 36, N = 1579); High Group (GS > 36, N = 1561). PMI3 represented the endpoint for cTnI > 3-fold upper reference limit, while PMI5 represented the endpoint for cTnI > 5-fold upper reference limit. The incidence of PMI of High Group was statistically higher than that of Intermediate Group (P < .05), while that of Intermediate Group was statistically higher than Low Group (P < .05). With the adjustment of some general variables, GS was an independent significantly predictor for PMI3 (ß = 0.006, P < .05) and PMI5 (ß = 0.007, P < .05). Following receiver operating characteristic curve analysis, the optimal cut-off value to predict PMI are 22.5 for PMI3 and 27 for PMI5. The GS was an independent predictor of PMI in the single-coronary revascularization population. Additionally, the 22.5 of GS was the optimal cut-off value for determining the presence of PMI3, while the 27 of GS for PMI5.

Systemic Immune-Inflammation Index Predicts Contrast-Induced Acute Kidney Injury in Patients Undergoing Coronary Angiography: A Cross-Sectional Study.

Background and Aims: Systemic immune-inflammation index (SII) is an emerging indicator and correlated to the incidence of cardiovascular diseases. This study aimed to explore the association between SII and contrast-induced acute kidney injury (CI-AKI). Methods: In this retrospective cross-sectional study, 4,381 subjects undergoing coronary angiography (CAG) were included. SII is defined as neutrophil count × platelet count/lymphocyte count. CI-AKI was determined by the elevation of serum creatinine (Scr). Multivariable linear and logistic regression analysis were used to determine the relationship of SII with Scr and CI-AKI, respectively. Receiver operator characteristic (ROC) analysis, structural equation model analysis, and subgroup analysis were also performed. Results: Overall, 786 (17.9%) patients suffered CI-AKI after the intravascular contrast administration. The subjects were 67.1 ± 10.8 years wold, with a mean SII of 5.72 × 1011/L. Multivariable linear regression analysis showed that SII linearly increased with the proportion of Scr elevation (ß [95% confidence interval, CI] = 0.315 [0.206 to 0.424], P < 0.001). Multivariable logistic regression analysis demonstrated that higher SII was associated with an increased incidence of CI-AKI ([≥12 vs. <3 × 1011/L]: odds ratio, OR [95% CI] = 2.914 [2.121 to 4.003], P < 0.001). Subgroup analysis showed consistent results. ROC analysis identified a good predictive value of SII on CI-AKI (area under the ROC curve [95% CI]: 0.625 [0.602 to 0.647]). The structural equation model verified a more remarkable direct effect of SII (ß = 0.102, P < 0.001) on CI-AKI compared to C-reactive protein (ß = 0.070, P < 0.001). Conclusions: SII is an independent predictor for CI-AKI in patients undergoing CAG procedures.

Effects of bilirubin on perioperative myocardial infarction and its long-term prognosis in patients undergoing percutaneous coronary intervention.

BACKGROUND: Although bilirubin is known to be an antioxidant, any relationship with coronary heart disease remains controversial. To the best of our knowledge, no previous study has investigated the association between bilirubin and perioperative myocardial infarction (PMI), including its long-term prognosis. AIM: To investigate the impact of bilirubin levels on PMI in patients undergoing percutaneous coronary intervention (PCI), and long-term prognosis in post-PMI patients. METHODS: Between January 2014 and September 2018, 10236 patients undergoing elective PCI were enrolled in the present study. Total bilirubin (TB) and cardiac troponin I (cTnI) levels were measured prior to PCI and cTnI at further time-points, 8, 16 and 24 h after PCI. Participants were stratified by pre-PCI TB levels and divided into three groups: < 10.2; 10.2-14.4 and > 14.4 µmol/L. PMI was defined as producing a post-procedural cTnI level of > 5 × upper limit of normal (ULN) with normal baseline cTnI. Major adverse cardiovascular events (MACEs) included cardiac death, MI, stroke and revascularization during a maximum 5-year follow-up. RESULTS: PMI was detected in 526 (15.3%), 431 (12.7%) and 424 (12.5%) of patients with pre-PCI TB levels of < 10.2, 10.2-14.4 and > 14.4 µmol/L (P = 0.001), respectively. Multivariate logistical analysis indicated that patients with TB 10.2-14.4 and > 14.4 µmol/L had a lower incidence of PMI [TB 10.2-14.4 µmol/L: Odds ratio (OR): 0.854; 95% confidence interval (CI): 0.739-0.987; P = 0.032; TB > 14.4 µmol/L: OR: 0.846; 95%CI: 0.735-0.975; P = 0.021] compared with patients with TB < 10.2 µmol/L. Construction of a Kaplan-Meier curve demonstrated a higher MACE-free survival time for patients with higher TB than for those with lower TB (log-rank P = 0.022). After adjustment for cardiovascular risk factors and angiographic characteristics, multivariate Cox analysis showed that a TB level > 14.4 µmol/L was associated with a reduced risk of MACEs compared with a TB level < 10.2 µmol/L (hazard ratio 0. 667; 95%CI: 0.485-0.918; P = 0.013). CONCLUSION: Bilirubin was a protective factor in PMI prediction. For post-PMI patients, elevated bilirubin levels were independently associated with a reduced risk of MACEs during long-term follow-up.

Admission electrolyte and osmotic pressure levels are associated with the incidence of contrast-associated acute kidney injury.

This retrospective study aimed to explore the relationships between electrolytes and osmotic pressure homeostasis with contrast-associated acute kidney injury (CA-AKI) risk in patients with percutaneous coronary intervention or coronary angiography. We totally enrolled 4386 hospitalized patients, who were categorized into five groups based on the predetermined cutoff values of electrolytes and osmotic pressure. CA-AKI was defined as an increase in serum creatine by 0.5 mg/dL (44.2 mol/L) or a 25% increase of the highest level post-operation compared to baseline. Multivariable logistic analysis was used to examine the association of CA-AKI incidence with electrolytes and osmotic pressure levels. Piecewise linear regression models and restricted cubic spline analysis were further utilized to determine the nonlinear relationship. The results showed U-shaped relationships between sodium, chloride, magnesium, and osmotic pressure levels and CA-AKI incidence. The lowest incidence was observed in the categories of 139-141.9 mmol/L, 107.0-109.9 mmol/L, 0.91-1.07 mmol/L, and 290.0-299.9 mOsm/kg, respectively. J-shaped associations were observed for potassium and phosphate levels and CA-AKI incidence, with the lowest incidence in the categories of 3.50-4.09 mmol/L and 0.96-1.28 mmol/L, respectively. A negative correlation was observed between calcium level and CA-AKI incidence, with the lowest CA-AKI risk in the category of ≥ 2.58 mmol/L. In conclusion, abnormally higher or lower sodium, chloride, magnesium, phosphate, and osmotic pressure levels on admission were associated with increased risks of CA-AKI. While for potassium and calcium, the status of hyperkalemia and hypocalcemia on admission showed more susceptibility for CA-AKI.

Erratum: Metoprolol and bisoprolol ameliorate hypertrophy of neonatal rat cardiomyocytes induced by high glucose via the PKC/NF-κB/c-fos signaling pathway.

[This corrects the article DOI: 10.3892/etm.2019.8312.].

Elevation of Hemoglobin A1c Increases the Atherosclerotic Plaque Vulnerability and the Visit-to-Visit Variability of Lipid Profiles in Patients Who Underwent Elective Percutaneous Coronary Intervention.

BACKGROUND: Increased plaque vulnerability and higher lipid variability are causes of adverse cardiovascular events. Despite a close association between glucose and lipid metabolisms, the influence of elevated glycated hemoglobin A1c (HbA1c) on plaque vulnerability and lipid variability remains unclear. METHODS: Among subjects undergoing percutaneous coronary intervention (PCI) from 2009 through 2019, 366 patients received intravascular optical coherence tomography (OCT) assessment and 4,445 patients underwent the scheduled follow-ups within 1 year after PCI. Vulnerability features of culprit vessels were analyzed by OCT examination, including the assessment of lipid, macrophage, calcium, and minimal fibrous cap thickness (FCT). Visit-to-visit lipid variability was determined by different definitions including standard deviation (SD), coefficient of variation (CV), and variability independent of the mean (VIM). Multivariable linear regression analysis was used to verify the influence of HbA1c on plaque vulnerability features and lipid variability. Exploratory analyses were also performed in non-diabetic patients. RESULTS: Among enrolled subjects, the pre-procedure HbA1c was 5.90 ± 1.31%, and the average follow-up HbA1c was 5.98 ± 1.16%. By OCT assessment, multivariable linear regression analyses demonstrated that patients with elevated HbA1c had a thinner minimal FCT (ß = -6.985, P = 0.048), greater lipid index (LI) (ß = 226.299, P = 0.005), and higher macrophage index (ß = 54.526, P = 0.045). Even in non-diabetic patients, elevated HbA1c also linearly decreased minimal FCT (ß = -14.011, P = 0.036), increased LI (ß = 290.048, P = 0.041) and macrophage index (ß = 120.029, P = 0.048). Subsequently, scheduled follow-ups were performed during 1-year following PCI. Multivariable linear regression analyses proved that elevated average follow-up HbA1c levels increased the VIM of lipid profiles, including low-density lipoprotein cholesterol (ß = 2.594, P < 0.001), high-density lipoprotein cholesterol (ß = 0.461, P = 0.044), non-high-density lipoprotein cholesterol (ß = 1.473, P < 0.001), total cholesterol (ß = 0.947, P < 0.001), and triglyceride (ß = 4.217, P < 0.001). The result was consistent in non-diabetic patients and was verified when SD and CV were used to estimate variability. CONCLUSION: In patients undergoing elective PCI, elevated HbA1c increases the atherosclerotic plaque vulnerability and the visit-to-visit variability of lipid profiles, which is consistent in non-diabetic patients.

Dendritic cell-mediated chronic low-grade inflammation is regulated by the RAGE-TLR4-PKCß1 signaling pathway in diabetic atherosclerosis.

BACKGROUND: The unique mechanism of diabetic atherosclerosis has been a central research focus. Previous literature has reported that the inflammatory response mediated by dendritic cells (DCs) plays a vital role in the progression of atherosclerosis. The objective of the study was to explore the role of DCs in diabetes mellitus complicated by atherosclerosis. METHODS: ApoE-/- mice and bone marrow-derived DCs were used for in vivo and in vitro experiments, respectively. Masson's staining and Oil-red-O staining were performed for atherosclerotic lesion assessment. The content of macrophages and DCs in plaque was visualized by immunohistochemistry. The expression of CD83 and CD86 were detected by flow cytometry. The fluctuations in the RNA levels of cytokines, chemokines, chemokine receptors and adhesions were analyzed by quantitative RT-PCR. The concentrations of IFN-γ and TNF-α were calculated using ELISA kits and the proteins were detected using western blot. Coimmunoprecipitation was used to detect protein-protein interactions. RESULTS: Compared with the ApoE-/- group, the volume of atherosclerotic plaques in the aortic root of diabetic ApoE-/- mice was significantly increased, numbers of macrophages and DCs were increased, and the collagen content in plaques decreased. The expression of CD83 and CD86 were significantly upregulated in splenic CD11c+ DCs derived from mice with hyperglycemia. Increased secretion of cytokines, chemokines, chemokine receptors, intercellular cell adhesion molecule (ICAM), and vascular cell adhesion molecule (VCAM) also were observed. The stimulation of advanced glycation end products plus oxidized low-density lipoprotein, in cultured BMDCs, further activated toll-like receptor 4, protein kinase C and receptor of AGEs, and induced immune maturation of DCs through the RAGE-TLR4-PKCß1 signaling pathway that was bound together by intrinsic structures on the cell membrane. Administering LY333531 significantly increased the body weight of diabetic ApoE-/- mice, inhibited the immune maturation of spleen DCs, and reduced atherosclerotic plaques in diabetic ApoE-/- mice. Furthermore, the number of DCs and macrophages in atherosclerotic plaques was significantly reduced in the LY333531 group, and the collagen content was increased. CONCLUSIONS: Diabetes mellitus aggravates chronic inflammation, and promotes atherosclerotic plaques in conjunction with hyperlipidemia, which at least in part through inducing the immune maturation of DCs, and its possible mechanism of action is through the RAGE-TLR4-pPKCß1 signaling pathway.

Association of the classification and severity of heart failure with the incidence of contrast-induced acute kidney injury.

Congestive heart failure (HF) is a known risk factor of contrast-induced acute kidney injury (CI-AKI). However, the relationship of the classification and severity of HF with CI-AKI remains under-explored. From January 2009 to April 2019, we recruited patients undergoing elective PCI who had complete pre- and post-operative creatinine data. According to the levels of ejection fraction (EF), HF was classified as HF with reduced EF (HFrEF) [EF < 40%], HF with mid-range EF (HFmrEF) [EF 40-49%] and HF with preserved EF (HFpEF) [EF ≥ 50%]. CI-AKI was defined as an increase of either 25% or 0.5 mg/dL (44.2 µmoI/L) in serum baseline creatinine level within 72 h following the administration of the contrast agent. A total of 3848 patients were included in the study; mean age 67 years old, 33.9% females, 48.1% with HF, and 16.9% with CI-AKI. In multivariate logistic regression analysis, HF was an independent risk factor for CI-AKI (OR 1.316, p value < 0.05). Among patients with HF, decreased levels of EF (OR 0.985, p value < 0.05) and elevated levels of N-terminal pro b-type natriuretic peptide (NT-proBNP) (OR 1.168, p value < 0.05) were risk factors for CI-AKI. These results were consistent in subgroup analysis. Patients with HFrEF were more likely to develop CI-AKI than those with HFmrEF or HFpEF (OR 0.852, p value = 0.031). Additionally, lower levels of EF were risk factors for CI-AKI in the HFrEF and HFmrEF groups, but not in the HFpEF group. NT-proBNP was an independent risk factor for CI-AKI in the HFrEF, HFmrEF and HFpEF groups. Elevated levels of NT-proBNP are independent risk factors for CI-AKI irrespective of the classification of HF. Lower levels of EF were risk factors for CI-AKI in the HFrEF and HFmrEF groups, but not in the HFpEF group.

ß-blocker use before elective percutaneous coronary intervention as a risk factor for periprocedural myocardial injury incidence in male patients below 75 years old: a single-center retrospective study.

BACKGROUND: ß-blockers are indicated in several cardiovascular diseases. However, data are limited on their effect on the periprocedural myocardial injury (PMI) incidence. This study was designed to evaluate the impact of using ß-blockers before elective percutaneous coronary intervention (PCI) on PMI incidence. METHODS: This study included 4,027 patients who underwent elective PCI and had no elevated serum troponin I (TnI) or creatine kinase-MB (CK-MB) levels before PCI. Patients were divided into four groups based on gender and age (cut-off point 75 years). Serum TnI and CK-MB levels were measured before and every eight hours after the procedure. PMI was defined as postprocedural TnI or CK-MB ≥5 times the upper limits of normal (ULN) values. Logistic regression analysis including factors such as age, sex, prior ß-blocker therapy, previous MI, length of implanted stents, characteristics of lesion and so on was performed to assess the effects of prior ß-blocker therapy on the incidence of PMI. RESULTS: In 2,332 male patients <75 years old, PMI incidence was higher in the ß-blocker pre-usage subgroup than the no ß-blocker pre-usage subgroup (16.4% vs. 11.7%, respectively; P=0.001). For the female patients ≥75 years old, the ß-blocker pre-usage subgroup had a lower PMI incidence compared with the no ß-blocker pre-usage subgroup (18.2% vs. 31.7%, respectively; P=0.012). In logistic regression analysis, the total length of implanted stents was a risk factor for PMI incidence in all patients. Also, ß-blocker pre-usage was an independent risk factor for PMI in male patients <75 years old (HR =1.424, 95% CI: 1.088-1.864; P=0.01). However, we did not observe a significant effect in female patients ≥75 years old. CONCLUSIONS: Our study indicates that the PCI-PMI association depends on age and gender groups, ß-blocker use before PCI is associated with increased PMI incidence in male patients <75 years old.

Safety and Efficacy of Perioperative Use of Evolocumab in Myocardial Infarction Patients: Study Protocol for a Multicentre Randomized Controlled Trial.

INTRODUCTION: The SECURE-PCI study supports a perioperative loading dose of statins, although whether an intensive lipid-lowering strategy prior to percutaneous coronary intervention further benefits acute coronary syndrome patients remains controversial. Evolocumab, a proprotein-converting enzyme subtilisin/kexin type 9 (PCSK9) inhibitor, acts more quickly and effectively than statins and reduces the risk of cardiovascular events in post-myocardial infarction (MI) patients. Nonetheless, whether it can be safely used in perioperative MI patients and whether perioperative application can benefit patients are still unknown. This study aims to evaluate the safety and efficacy of this treatment regimen. METHODS: A multicentre, prospective, randomized, controlled superiority trial will be conducted in 530 statin-naïve MI patients. All eligible patients will be randomized to the evolocumab group (140 mg subcutaneously injected once before revascularization + 14 days after the first dose) or the control group (no evolocumab injection). Evolocumab will then be administered depending on the patient's lipid profile. Both groups will be treated simultaneously with standardized secondary preventive medications. The primary end points are major adverse cardiovascular events (a composite of death, recurrent MI, unanticipated revascularization, stroke and any rehospitalization for ischaemic causes) within 12 months. The secondary end point is post-infarction angina after pain relief. The safety end points include myopathy, impaired liver or renal function, and other adverse events during the follow-up period. OUTCOMES: This is the first trial to evaluate the safety and efficacy of evolocumab pre-treatment on prognosis in MI patients. Perioperative evolocumab injection may be a new, safe way to improve prognosis. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( http://www.chictr.org.cn ; ChiCTR1900024526). Registered on 13 July 2019 and updated on 31 May 2020. The study is currently recruiting patients.

Predictors of recurrent angina in patients with no need for secondary revascularization.

BACKGROUND: Approximately 20% to 30% of patients with coronary artery disease (CAD) develop recurrent angina pectoris following successful and complete coronary revascularization utilizing percutaneous coronary intervention (PCI). We aim to investigate predictors of recurrent angina pectoris in patients who have undergone successful coronary revascularization using PCI, but on repeat coronary angiography have no need for secondary revascularization. METHODS: The study comprised 3,837 patients with CAD, who were enrolled from January 2007 to June 2019. They had undergone successful PCI; some of them redeveloped angina pectoris within one year after the procedure, but on repeat coronary angiography had no need for revascularization. Thrombolysis in myocardial infarction (TIMI) frame count was used to evaluate the velocity of coronary blood in the follow-up angiogram. Multivariate logistic regression was used to investigate risk factors for recurrent angina pectoris. Similarly, predictors of recurrent angina according to the TIMI frame count were assessed using multivariate linear regression. RESULTS: In this retrospective study, 53.5% of patients experienced recurrent angina pectoris. By multivariate logistic regression, the following characteristics were statistically identified as risk factors for recurrent angina pectoris: female sex, older age, current smoking, low-density lipoprotein cholesterol (LDL-C) ≥1.8 mmol/L, and an elevated TIMI frame count (P for all <0.05). Similarly, using multivariate linear regression, the statistical risk factors for TIMI frame count included: female sex, older age, diabetes, body mass index (BMI), post-procedural treatment without the inclusion of dual antiplatelet therapy. CONCLUSIONS: Patient characteristics of female sex, older age, diabetes, and elevated BMI are associated with an increased TIMI frame count, coronary microcirculation dysfunction, and recurrent angina pectoris after initially successful PCI. In addition, current smoking and LDL-C ≥1.8 mmol/L are risk factors for recurrent angina pectoris. In contrast, the treatment with dual antiplatelet therapy is negatively correlated with a higher TIMI frame count and the risk of recurrent angina pectoris.

Impact of increased inflammation biomarkers on periprocedural myocardial infarction in patients undergoing elective percutaneous coronary intervention: a cohort study.

BACKGROUND: The fact that each inflammatory indicator has a forecasting capacity on the occurrence of periprocedural myocardial infarction (PMI) has a controversial existence. The purpose of this study was to explore the role of inflammation biological indicators on PMI in a group of patients undergoing selective percutaneous coronary intervention (PCI). METHODS: The study was carried out both in a retrospective and prospective manner in 7,413 and 1,189 subjects, respectively. In the retrospective cohort study, the association between inflammation biomarkers and PMI was assessed by univariate and multivariate logistic regression. WBC, CRP, and NLR were distributed using k-means clustering into a virtual variable "Inflammatory Trend", and multivariate logistic regression and subgroup analysis were performed. In the prospective cohort study, the endpoints were PMI, cardiovascular death or cardiac arrest. The chi-square test was performed to calculate the relative risk (RR). RESULTS: In the retrospective cohort study, except WBC, CRP, NLR and virtual variable "Inflammatory trend" were independent risk factors for PMI. The subgroup analysis revealed that CRP can serve as the most stable predictor. In the prospective cohort study, WBC (RR =1.134, P=0.416) has no effect on the incidence of PMI. However, an elevation in the incidence of PMI was observed with an increase of NLR (RR =1.354, P=0.041) and CRP (RR =1.412, P=0.025). CONCLUSIONS: In patients with elective PCI for single-vessel lesions, high CRP increases the risk for PMI. The increase of NLR was an independent risk factor for PMI, especially for patients with hypertension and under the age of 70. WBC has no influence on the occurrence of PMI.

Variability in blood lipids affects the neutrophil to lymphocyte ratio in patients undergoing elective percutaneous coronary intervention: a retrospective study.

BACKGROUND: Atherosclerosis is associated with chronic inflammation and lipid metabolism. The neutrophil to lymphocyte ratio (NLR) as an indicator of inflammation has been confirmed to be associated with cardiovascular disease prognosis. However, few studies have explored the effects of blood lipid variability on NLR. The aim of this study was to explore the relationship between variability in blood lipid levels and NLR. METHODS: The association between variability in blood lipids and NLR was assessed with both univariate and multivariate linear regression. Multivariate linear regression was also performed for a subgroup analysis. RESULTS: The variability of high-density lipoprotein cholesterol (HDL-C) (regression coefficients [ß] 4.008, standard error (SE) 0.503, P-value< 0.001) and low-density lipoprotein cholesterol (LDL-C) ([ß] 0.626, SE 0.164, P-value< 0.001) were risk factors for the NLR value, although baseline LDL-C and HDL-C were not risk factors for NLR values. Variability of HDL-C ([ß] 4.328, SE 0.578, P-value< 0.001) and LDL-C ([ß] 0.660, SE 0.183, P-value< 0.001) were risk factors for NLR variability. Subgroup analysis demonstrated that the relationship between variability of LDL-C and NLR was consistent with the trend of the total sample for those with diabetes mellitus, controlled blood lipid, statins, atorvastatin. The relationship between the variability of HDL-C and NLR was consistent with the trend of the total sample in all subgroups. CONCLUSION: The variability of HDL-C and LDL-C are risk factors for the value and variability of NLR, while the relationship between variability of HDL-C and NLR is more stable than the variability of LDL-C in the subgroup analysis, which provides a new perspective for controlling inflammation in patients undergoing PCI.

Primary prevention of myocardial infarction: aspirin is not as useful as it seems.

BACKGROUND: Aspirin has not been reliably shown to reduce all-cause and cardiovascular mortality but can prevent symptomatic myocardial infarction. However, silent myocardial infarction (SMI) is not uncommon in clinical practice. No meta-analysis has compared the effect of aspirin administration on primary prevention of all myocardial infarctions, including SMI. METHODS: We systematically searched PubMed, Embase, Web of Science, Cochrane Library and Google Scholar for randomized double-blind controlled trials evaluating the effect of aspirin on primary prevention of all myocardial infarctions, including SMI. RESULTS: The current meta-analysis included 9 trials involving 67,486 patients and 67,557 controls on aspirin primary prevention of all myocardial infarctions. When SMI was included in the total number of myocardial infarctions, the aspirin effect on the primary prevention of myocardial infarction was not as significant as expected [risk ratio (RR): 0.883; 95% confidence interval (CI): 0.780 to 1.001; P=0.052]. CONCLUSIONS: Aspirin may not provide a primary preventive effect in all myocardial infarction patients. Previously demonstrated reductions in myocardial infarction are not present when SMI is included.

Rosuvastatin Reverses Hypertension-Induced Changes in the Aorta Structure and Endothelium-Dependent Relaxation in Rats Through Suppression of Apoptosis and Inflammation.

Vascular remodeling is one of the most critical complications caused by hypertension. Previous studies have demonstrated that rosuvastatin has anti-inflammatory, antioxidant, and antiplatelet effects and therefore can be used to treat cardiovascular disease. In this study, we explored the beneficial effects of rosuvastatin in reversing aortic remodeling in spontaneously hypertensive rats. After treating with different doses of rosuvastatin, its antilipid, antiapoptosis, and anti-inflammatory effects were determined. We also examined whether rosuvastatin can improve the structure and function of the aorta. We found that rosuvastatin treatment of spontaneously hypertensive rats for 2 months at 2 different doses can effectively reduce the media thickness of the aorta compared with the control group. Similarly, rosuvastatin improved the vascular relaxation function of the aortic rings at a high level of acetylcholine in vitro. Mechanistically, it was found that rosuvastatin increased the expression of endothelial nitric oxide synthase and plasma nitrite/nitrate levels. Besides, rosuvastatin suppressed the apoptosis and inflammation and upregulated the expression of gap-junction complex connexin 43 both in media and endothelium. Finally, rosuvastatin inhibited the AT1R/PKCα/HSP70 signaling transduction pathway. In summary, these findings demonstrated that rosuvastatin could improve the vascular structure and function mainly by increasing endothelial nitric oxide synthase expression and preventing apoptosis and inflammation. This study provided evidence that rosuvastatin has beneficial effects in reversing the remodeling of the aorta due to hypertension.