Factors associated with risk analysis for asymptomatic left ventricular diastolic dysfunction in nondialysis patients with chronic kidney disease.

Heart failure (HF) constitutes a major determinant of outcome in chronic kidney disease (CKD) patients. The main pattern of HF in CKD patients is preserved ejection fraction (HFpEF), and left ventricular diastolic dysfunction (LVDD) is a frequent pathophysiological mechanism and specific preclinical manifestation of HFpEF. Therefore, exploring and intervention of the factors associated with risk for LVDD is of great importance in reducing the morbidity and mortality of cardiovascular disease (CVD) complications in CKD patients. We designed this retrospective cross-sectional study to collect clinical and echocardiographic data from 339 nondialysis CKD patients without obvious symptoms of HF to analyze the proportion of asymptomatic left ventricular diastolic dysfunction (ALVDD) and its related factors associated with risk by multivariate logistic regression analysis. Among the 339 nondialysis CKD patients, 92.04% had ALVDD. With the progression of CKD stage, the proportion of ALVDD gradually increased. The multivariate logistic regression analysis revealed that increased age (OR 1.237; 95% confidence interval (CI) 1.108-1.381, per year), diabetic nephropathy (DN) and hypertensive nephropathy (HTN) (OR 25.000; 95% CI 1.355-48.645, DN and HTN vs chronic interstitial nephritis), progression of CKD stage (OR 2.785; 95% CI 1.228-6.315, per stage), increased mean arterial pressure (OR 1.154; 95% CI 1.051-1.268, per mmHg), increased urinary protein (OR 2.825; 95% CI 1.484-5.405, per g/24 h), and low blood calcium (OR 0.072; 95% CI 0.006-0.859, per mmol/L) were factors associated with risk for ALVDD in nondialysis CKD patients after adjusting for other confounding factors. Therefore, dynamic monitoring of these factors associated with risk, timely diagnosis and treatment of ALVDD can delay the progression to symptomatic HF, which is of great importance for reducing CVD mortality, and improving the prognosis and quality of life in CKD patients.

CircHECTD1 promoted MIRI-associated inflammation via inhibiting miR-138-5p and upregulating ROCK2.

Myocardial ischemia-reperfusion injury (MIRI) was often observed after surgeries, causing a lot of suffering to patients. Inflammation and apoptosis were critical determinants during MIRI. We conveyed experiments to reveal the regulatory functions of circHECTD1 in MIRI development. The Rat MIRI model was established and determined by 2,3,5-triphenyl tetrazolium chloride (TTC) staining. We analyzed cell apoptosis using TUNEL and flow cytometry. Proteins expression was evaluated by western blot. The RNA level was determined by qRT-PCR. Secreted inflammatory factors were analyzed by ELISA assay. To predict the interaction sequences on circHECTD1, miR-138-5p, and ROCK2, bioinformatics analysis was performed. Dual-luciferase assay was used to confirm these interaction sequences. CircHECTD1 and ROCK2 were upregulated in the rat MIRI model, while miR-138-5p was decreased. CircHECTD1 knockdown alleviated H/R-induced inflammation in H9c2 cells. Direct interaction and regulation of circHECTD1/miR-138-5p and miR-138-5p/ROCK2 were confirmed by dual-luciferase assay. CircHECTD1 promoted H/R-induced inflammation and cell apoptosis by inhibiting miR-138-5p. miR-138-5p alleviated H/R-induced inflammation, while ectopic ROCK2 antagonized such effect of miR-138-5p. Our research suggested that the circHECTD1-modulated miR-138-5p suppressing is responsible for ROCK2 activation during H/R-induced inflammatory response, providing a novel insight into MIRI-associated inflammation.

Prolonged dual antiplatelet therapy for Chinese ACS patients undergoing emergency PCI with drug-eluting stents: Benefits and risks.

Background: In patients with acute coronary syndrome (ACS), prolonged dual antiplatelet therapy (DAPT) may reduce ischemic events and increase the risks of bleeding events differently in different ethnic groups. However, whether prolonged DAPT in Chinese patients with ACS following emergency percutaneous coronary intervention (PCI) with drug-eluting stents (DES) will be beneficial or dangerous remains unclear. This study aimed to examine the potential benefits and risks of prolonged DAPT in Chinese patients with ACS who have undergone emergency PCI with DES. Methods: This study included 2,249 patients with ACS who underwent emergency PCI. If DAPT was continued for 12 or 12-24 months, it was classified as the standard (n = 1,011) or prolonged (n = 1,238) DAPT group, respectively. The incidence of the following endpoint events was determined and compared between the two groups: composite bleeding event (BARC 1 or 2 types of bleeding and BARC 3 or 5 types of bleeding) and major adverse cardiovascular and cerebrovascular events (MACCEs) [ischemia-driven revascularization, non-fatal ischemia stroke, non-fatal myocardial infarction (MI), cardiac death, and all-cause death]. Results: After a median period of 47 months of follow-up [47 (40, 54)], the rate of composite bleeding events was 13.2% (n = 163) in the prolonged DAPT group and 7.9% (n = 80) in the standard DAPT group [odds ratio (OR) 1.765, 95% confidence interval (CI) 1.332-2.338, p < 0.001]. The rate of MACCEs was 11.1% (n = 138) in the prolonged DAPT group and 13.2% (n = 133) in the standard DAPT group (OR 0.828, 95% CI 0.642-1.068, p = 0.146). The DAPT duration was further shown to be insignificantly correlated with MACCEs as per the multivariable Cox regression model (HR, 0.813; 95% CI, 0.638-1.036; p = 0.094). No statistically significant difference was observed between the two groups. However, the DAPT duration was a separate predictor of composite bleeding events according to the multivariable Cox regression model (HR 1.704, 95% CI 1.302-2.232, p < 0.001). Compared with the standard DAPT group, the prolonged DAPT group had substantially more BARC 3 or 5 types of bleeding events (3.0 vs. 0.9% in those with standard DAPT, OR 3.430, 95% CI 1.648-7.141, p < 0.001) and BARC 1 or 2 types of bleeding events (10.2 vs. 7.0% in those with standard DAPT, OR 1.500, 95% CI 1.107-2.032, p = 0.008). Conclusion: The prolonged DAPT group had a considerably greater incidence of composite bleeding events than the standard DAPT group. No statistically significant difference was observed in the incidence of MACCEs between the two groups.

High triglyceride-glucose index is associated with poor cardiovascular outcomes in Chinese acute coronary syndrome patients without diabetes mellitus who underwent emergency percutaneous coronary intervention with drug-eluting stents.

Background: Previous research has supported the association between the triglyceride-glucose index (TyG index) and the incidence and prognosis of cardiovascular disease. However, the association between the TyG index and the prognosis of patients with acute coronary syndrome (ACS) without diabetes mellitus (DM) who underwent emergency percutaneous coronary intervention (PCI) with drug-eluting stents (DESs) has not been thoroughly investigated, and these patients may easily be neglected. Therefore, this study aimed to investigate the association between the TyG index and major adverse cardiovascular and cerebrovascular events (MACCEs) in Chinese ACS patients without DM who underwent emergency PCI with DES. Methods: The total number of ACS patients without DM who underwent emergency PCI with DES for this study was 1650. Ln [fasting triglycerides (mg/dL) ×fasting plasma glucose (mg/dL)/2] is the formula used to calculate the TyG index. According to the TyG index, we classified the patients into two groups. The frequency of the following endpoint events was calculated and compared between the two groups: all-cause death, non-fatal myocardial infarction (MI), non-fatal ischemia stroke, ischemia-driven revascularization and cardiac rehospitalization. Results: After a median of 47 months of follow-up [47 (40, 54)], 437 (26.5%) endpoint events were recorded in total. The TyG index was further demonstrated to be independent of MACCE by multivariable Cox regression analysis (hazard ratio [HR], 1.493; 95% confidence interval [CI], 1.230-1.812; p<0.001). The TyG index≥7.08 group had a considerably greater incidence of MACCE (30.3% vs. 22.7% in the TyG index<7.08 group, p<0.001), cardiac death (4.0% vs. 2.3% in the TyG index<7.08 group, p=0.047), and ischemia-driven revascularization (5.7% vs. 3.6% in the TyG index<7.08 group, p=0.046) than the TyG index<7.08 group. Between the two groups, there was no discernible difference in all-cause death (5.6% vs. 3.8% in the TyG index<7.08 group, p=0.080), non-fatal MI (1.0% vs. 0.2% in the TyG index<7.08 group, p=0.057), non-fatal ischemic stroke (1.6% vs. 1.0% in the TyG index<7.08 group, p=0.272), and cardiac rehospitalization (16.5% vs. 14.1% in the TyG index<7.08 group, p=0.171). Conclusion: For ACS patients without DM who received emergency PCI with DES, the TyG index might be an independent predictor of MACCE.

Higher serum triglyceride can predict recurrent coronary revascularization events in patients undergoing percutaneous coronary intervention with baseline LDL-C <55 mg/dL.

Patients with low baseline low-density lipoprotein cholesterol (LDL-C) but experiencing recurrent coronary revascularization events have been rarely investigated. In this retrospective cohort study, we enrolled patients undergoing percutaneous coronary intervention (PCI) with baseline LDL-C <55 mg/dL at the First Affiliated Hospital of Xi'an Jiaotong University between January and December 2017. Subsequent ischemia-driven coronary revascularization events and all-cause death were documented during a 4-year follow-up. Cox analysis was used to evaluate the association between baseline clinical characteristics and long-term events. As a result, among 388 patients (mean age 63 years; 79.1% male) enrolled, 32 patients underwent recurrent revascularization events, and 38 patients occurred all-cause death. After adjustment for age, diabetes mellitus, multi-vessel disease, and lipoprotein(a), multivariate Cox analysis showed that baseline serum triglyceride (TG) (HR 1.691, 95% CI 1.178 to 2.428, p=0.004) was an independent predictor of recurrent coronary revascularization events. Kaplan-Meier analysis revealed that a higher TG level (≥1.17 mmol/L, determined by receiver operating characteristic curve) was associated with increased risk of recurrent revascularization events than lower TG level (<1.17 mmol/L) (p=0.021). Female (HR 2.647, 95% CI 1.350 to 5.190, p=0.005) and previous atrial fibrillation (HR 3.163, 95% CI 1.403 to 7.132, p=0.006) were associated with increased risk of all-cause death. In conclusion, for patients undergoing PCI with baseline LDL-C <55 mg/dL, higher baseline TG can predict recurrent coronary revascularization events.

In-hospital initiation of PCSK9 inhibitor and short-term lipid control in patients with acute myocardial infarction.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to improve cardiovascular outcomes when added to conventional statin therapy. This study aims to investigate the efficacy and safety of in-hospital initiation of PCSK9 inhibitors among patients with acute myocardial infarction (AMI) based on real-world experience. METHODS AND RESULTS: Data were collected from the Biobank of the First Affiliated Hospital of Xi'an Jiaotong University between January 2016 and December 2020. A total of 7556 AMI patients were screened for eligibility. Propensity Score Match (PSM) was employed, and covariates were age, sex, admission blood pressure and lipid profiles. Eligible participants were (1) propensity-matched 1:2:2 of statin plus evolocumab (dual therapy) vs. statin vs. statin plus ezetimibe. Ninety-five statin plus evolocumab users achieved significantly decreased low density lipoprotein (LDL) levels (0.92 ± 0.62 mmol/L in the 1st month and 1.17 ± 0.73 in the 3rd month) and a promising attainment rate of LDL (79.5% in the 1st month and 80.0% in the 3rd month) compared to the other two groups. (2) Propensity-matched 1:2:2 of statin plus ezetimibe evolocumab (triple therapy) vs. statin vs. statin plus ezetimibe. Similarly, 75 triple medication users achieved significantly decreased LDL levels and a promising attainment rate of LDL compared to the other two groups. In-hospital mortality and readmission rates within 3 months were then analyzed, and a decreased readmission rate was observed with PCSK9i therapy. CONCLUSIONS: Based on the present single-center real-world PSM-adjusted study, PCSK9i has been effective in short-term lipid control among AMI patients. The long-term effectiveness for reducing major cardiovascular events among AMI patients based on real-world experience remains to be explored. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov, ClinicalTrials.gov ID: NCT05184530.

Association between Cystatin C and Cardiac Function in Acute Myocardial Infarction Patients: A Real-World Analysis.

Background: Acute myocardial infarction (AMI), as well as its long-term and short-term complications, is known to present with high morbidity and mortality. Cardiac function deterioration and ventricular remodelling after AMI are known to be correlated to worse long-term outcomes. However, the underlying mechanism remains elusive and there is a shortage of serum prediction markers. This study investigates the relationship between in-hospital Cystatin C (CysC) and cardiac function and subsequent prognosis among AMI patients. Research Design and Methods. We measured admission CysC and cardiac function parameters, including ejection fraction (EF) and pro-BNP value in 5956 patients diagnosed with AMI. Simple and multiregression analyses were performed to investigate the correlation between CysC and cardiac function in AMI patients. Major adverse cardiovascular events (MACE), cardiovascular, and all-cause mortality were documented, and 351 participants with high cystatin (≥1.09 mg/L) and 714 low cystatin (<1.09 mg/L) were investigated for survival analysis during a 48-month follow-up. Results: 5956 patients with AMI were enrolled in the initial observational analysis, and 1065 patients of the whole cohort were included in the follow-up survival analysis. The admission CysC level was found to be significantly positively correlated to the pro-BNP level (R square = 0.2142, 95% CI 4758 to 5265, p < 0.0001) and negatively correlated to the EF value (R square = 0.0095, 95% CI -3.503 to -1.605, p < 0.0001). Kaplan-Meier survival analysis revealed significantly increased MACE incidence (HR = 2.293, 95% CI 1.400 to 3.755, p < 0.0001), cardiovascular mortality (HR = 3.016, 95% CI 1.694 to 5.371, p = 0.0002), and all-cause mortality (HR = 3.424, 95% CI 2.010 to 5.835, p < 0.0001) in high-admission CysC cohort with AMI at the end of 4-year follow-up. Conclusions: Admission CysC is negatively correlated with cardiac function in AMI patients and acts as a novel predictor for MACE incidence in the whole population. Further studies are needed to investigate the specific mechanism of CysC in the cardiac function deterioration among AMI patients.

ARNI versus ACEI/ARB in Reducing Cardiovascular Outcomes after Myocardial Infarction.

AIMS: This study aimed to compare the efficacy of angiotensin receptor-neprilysin inhibitor (ARNI) therapy with angiotensin converting enzyme inhibitor or angiotensin receptor blocker (ACEI/ARB) therapy for cardiovascular outcomes in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: Data were collected from the Biobank of the First Affiliated Hospital of Xi'an Jiaotong University between January 2016 and December 2020. A total of 7556 AMI patients were screened for eligibility. Propensity score matching based on age, sex, blood pressure, kidney function, baseline left ventricular ejection fraction (LVEF), and cardiovascular medication were conducted, resulting in 291 patients with AMI being assigned to ARNI, ACEI, and ARB group, respectively. Patients receiving ARNI had significantly lower rates of the composite cardiovascular outcome than ACEI {hazard ratio [HR] 0.51, [95% confidence interval (CI), 0.27-0.95], P = 0.02}, and ARB users [HR 0.47, (95%CI, 0.24-0.90), P = 0.02]. Patients receiving ARNI showed lower rates of cardiovascular death than ACEI [HR 0.37, (95%CI, 0.18-0.79), P = 0.01] and ARB users [HR 0.41, (95%CI, 0.18-0.95), P = 0.04]. Subgroup analysis indicated that patients with LVEF no more than 40% tend to benefit more from ARNI as compared with ACEI [HR 0.30, (95%CI, 0.11-0.86), P = 0.01] or ARB [HR 0.21, (95%CI, 0.04-1.1), P = 0.05]. Patients aged no more than 60 years exhibited reduced composite endpoints [HR for ARNI vs. ARB: 0.11, (95%CI, 0.03-0.46), P = 0.002]. CONCLUSIONS: In patients with AMI, ARNI was superior to ACEI/ARB in reducing the long-term adverse cardiovascular outcomes. Subgroup analysis further indicates that ARNI is more likely to benefit patients with LVEF less than 40% and aged less than 60 years.

Clinical characteristics and protective factors in patients with acute myocardial infarction undergoing in-hospital myocardial free wall rupture: a single-center, retrospective analysis.

Myocardial free wall rupture (MFWR) refers to laceration of the heart ventricle or atria, which is a rare but fatal complication of acute myocardial infarction (AMI). In this study, we aim to identify the clinical characteristics and protective factors of free wall rupture after myocardial infarction. This is a single-center, retrospective observational analysis. The study screened all patients admitted to the cardiology department of the First Affiliated Hospital of Xi'an Jiaotong University between January 2013 and April 2018. The biochemical, clinical, angiographic and echocardiographic features of these patients were then collected and analyzed. Among the 5946 screened patients with AMI, 23 patients with a diagnosis of MFWR after AMI were enrolled in the present study. 18 (78.3%) patients were diagnosed with acute ST segment elevated myocardial infarction and the remaining 5 (21.7%) have acute non-ST segment elevated myocardial infarction. Early-phase MFWR happened in 12 (52.2%) and late-phase accounted for 8 (34.8%) in total. Late-phase MFWR had lower left ventricle ejection fraction value (45.8%±5.6% vs 63.0±3.8%, p<0.001) as compared with early-phase. Patients who survived from MFWR has higher ACE inhibitor/angiotensin II receptor blocker (ACEI/ARB) and ß-blocker coverage in the in-hospital treatment of AMI (ACEI/ARB: 100.0% vs 35.3%, p=0.014; ß-blocker: 100.0% vs 47.1%, p=0.048). The present study provides evidence for better understanding of the clinical characteristics and protective functions in MFWR after AMI. Reduced cardiac function is correlated with higher incidence of later phase free wall rupture. Higher ACEI/ARB and ß-blocker coverage in the AMI treatment strategy is associated with lower MFWR incidence.

The effect of statin therapy on plaque regression following acute coronary syndrome: a meta-analysis of prospective trials.

OBJECTIVE: To investigate the effect of statins on plaque regression after acute coronary syndrome (ACS). METHODS: We carried out a meta-analysis to assess the change in plaque and plaque components in patients with ACS under statin therapy. This meta-analysis combined data of 1623 participants from eight randomized-controlled trials and seven observational studies. RESULTS: The benefits of high-intensity statin therapy on plaque regression occurred after 6 months [standardized mean difference (SMD): -0.27; 95% confidence interval (CI): -0.43 to -0.12; P=0.0006] and were sustained over 12 months (SMD: -0.14; 95% CI: -0.25 to -0.03; P=0.01). No significant decrease was observed in the plaque volume and percent plaque volume under low-dose statin treatment. After 6 months of intensive statin treatment, the plaque volume reduced significantly in patients whose follow-up LDL cholesterol levels did (SMD: -0.16; 95% CI: -0.29 to -0.03; P=0.02) or did not (SMD: -0.21; 95% CI: -0.32 to -0.09; P=0.0007) decrease to 70 mg/dl or less. There was no significant change in plaque composition volumes, but an increase was found in the percent dense calcium volume of 1.31% (95% CI: 0.55-2.07%; P=0.0007). CONCLUSION: Intensive statin therapy duration over 6 months may be as important as achieved LDL-C of less than or equal to 70 mg/dl in plaque regression following ACS. Intensive statin treatment may lead to an earlier regression compared with low-dose statin therapy.

Curcumin Attenuates Rapamycin-induced Cell Injury of Vascular Endothelial Cells.

Although drug-eluting stents (DES) effectively improve the clinical efficacy of percutaneous coronary intervention, a high risk of late stent thrombosis and in-stent restenosis also exists after DES implantation. Anti-smooth muscle proliferation drugs, such as rapamycin, coating stents, not only inhibit the growth of vascular smooth muscle cells but also inhibit vascular endothelial cells and delay the reendothelialization. Therefore, the development of an ideal agent that protects vascular endothelial cells from rapamycin-eluting stents is of great importance for the next generation of DES. In this study, we demonstrated that rapamycin significantly inhibited the growth of rat aortic endothelial cells in both dose- and time-dependent manner in vitro. Cell apoptosis was increased and migration was decreased by rapamycin treatments in rat aortic endothelial cells in vitro. Surprisingly, treatment with curcumin, an active ingredient of turmeric, significantly reversed these detrimental effects of rapamycin. Moreover, curcumin increased the expression of vascular nitric oxide synthases (eNOS), which was decreased by rapamycin. Furthermore, caveolin-1, the inhibitor of eNOS, was decreased by curcumin. Knockdown of eNOS by small interfering RNA significantly abrogated the protective effects of curcumin. Taken together, our results suggest that curcumin antagonizes the detrimental effect of rapamycin on aortic endothelial cells in vitro through upregulating eNOS. Therefore, curcumin is a promising combined agent for the rescue of DES-induced reendothelialization delay.