Phenome-Wide Investigation of the Causal Associations Between Pre-Pregnancy Obesity Traits and Gestational Diabetes: A Two-Sample Mendelian Randomization Analyses.

Pre-pregnancy obesity was associated with gestational diabetes in observational studies, but whether this relationship is causal remains to be determined. To evaluate whether pre-pregnancy obesity traits causally affect gestational diabetes risk, a two-sample Mendelian randomization (MR) analysis was performed utilizing summary-level statistics from published genome-wide association studies (GWAS). Obesity-related traits included body mass index (BMI), overweight, obesity, obesity class 1, obesity class 2, obesity class 3, childhood obesity, waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), percent liver fat, visceral adipose tissue volume, abdominal subcutaneous adipose tissue volume. Effect estimates were evaluated using the inverse-variance weighting method. Weighted median, MR-Egger, simple mode, and weighted mode were performed as sensitivity analyses. Genetically predicted pre-pregnancy BMI [odds ratio (OR) = 1.68; 95% confidence interval (CI): 1.45-1.95; P = 9.13 × 10-12], overweight (OR = 1.49; 95% CI: 1.21-1.85; P = 2.06 × 10-4), obesity (OR = 1.25; 95% CI: 1.18-1.33; P = 8.01 × 10-13), obesity class 1 (OR = 1.31; 95% CI: 1.17-1.46; P = 1.49 × 10-6), obesity class 2 (OR = 1.26; 95% CI: 1.16-1.37; P = 5.23 × 10-8), childhood obesity (OR = 1.33; 95% CI: 1.23-1.44; P = 4.06 × 10-12), and WHR (OR = 2.35; 95% CI: 1.44-3.83; P = 5.89 × 10-4) were associated with increased risk of gestational diabetes. No significant association was observed with obesity class 3, WC, HC, percent liver fat, visceral adipose tissue volume, or abdominal subcutaneous adipose tissue volume. Similar results were observed in sensitivity analyses. Therefore, genetically predicted pre-pregnancy obesity traits may increase the risk of gestational diabetes. Weight control before pregnancy may be beneficial to prevent gestational diabetes.

Burden of cardiac arrhythmias in patients with acute myocardial infarction and their impact on hospitalization outcomes: insights from China acute myocardial infarction (CAMI) registry.

BACKGROUND: The coexistence of cardiac arrhythmias in patients with acute myocardial infarction (AMI) usually exhibits poor prognosis. However, there are few contemporary data available on the burden of cardiac arrhythmias in AMI patients and their impact on in-hospital outcomes. METHODS: The present study analyzed data from the China Acute Myocardial Infarction (CAMI) registry involving 23,825 consecutive AMI patients admitted to 108 hospitals from January 2013 to February 2018. Cardiac arrhythmias were defined as the presence of bradyarrhythmias, sustained atrial tachyarrhythmias, and sustained ventricular tachyarrhythmias that occurred during hospitalization. In-hospital outcome was defined as a composite of all-cause mortality, cardiogenic shock, re-infarction, stroke, or heart failure. RESULTS: Cardiac arrhythmia was presented in 1991 (8.35%) AMI patients, including 3.4% ventricular tachyarrhythmias, 2.44% bradyarrhythmias, 1.78% atrial tachyarrhythmias, and 0.73% ≥2 kinds of arrhythmias. Patients with arrhythmias were more common with ST-segment elevation myocardial infarction (83.3% vs. 75.5%, P < 0.001), fibrinolysis (12.8% vs. 8.0%, P < 0.001), and previous heart failure (3.7% vs. 1.5%, P < 0.001). The incidences of in-hospital outcomes were 77.0%, 50.7%, 43.5%, and 41.4%, respectively, in patients with ≥ 2 kinds of arrhythmias, ventricular tachyarrhythmias, bradyarrhythmias, and atrial tachyarrhythmias, and were significantly higher in all patients with arrhythmias than those without arrhythmias (48.9% vs. 12.5%, P < 0.001). The presence of any kinds of arrhythmia was independently associated with an increased risk of hospitalization outcome (≥ 2 kinds of arrhythmias, OR 26.83, 95%CI 18.51-38.90; ventricular tachyarrhythmias, OR 8.56, 95%CI 7.34-9.98; bradyarrhythmias, OR 5.82, 95%CI 4.87-6.95; atrial tachyarrhythmias, OR4.15, 95%CI 3.38-5.10), and in-hospital mortality (≥ 2 kinds of arrhythmias, OR 24.44, 95%CI 17.03-35.07; ventricular tachyarrhythmias, OR 13.61, 95%CI 10.87-17.05; bradyarrhythmias, OR 7.85, 95%CI 6.0-10.26; atrial tachyarrhythmias, OR 4.28, 95%CI 2.98-6.16). CONCLUSION: Cardiac arrhythmia commonly occurred in patients with AMI might be ventricular tachyarrhythmias, followed by bradyarrhythmias, atrial tachyarrhythmias, and ≥ 2 kinds of arrhythmias. The presence of any arrhythmias could impact poor hospitalization outcomes. REGISTRATION: Clinical Trial Registration: Identifier: NCT01874691.

Current status of emergency medical service use in ST-segment elevation myocardial infarction in China: Findings from China Acute Myocardial Infarction (CAMI) Registry.

BACKGROUND: The mortality rate of myocardial infarction in China has increased dramatically in the past three decades. Although emergency medical service (EMS) played a pivotal role for the management of patients with ST-segment elevation myocardial infarction (STEMI), the corresponding data in China are limited. METHODS: An observational analysis was performed in 26,305 STEMI patients, who were documented in China acute myocardial infarction (CAMI) Registry and treated in 162 hospitals from January 1st, 2013 to January 31th, 2016. We compared the differences such as demographic factors, social factors, medical history, risk factors, socioeconomic distribution and treatment strategies between EMS transport group and self-transport group. RESULTS: Only 4336 patients (16.5%) were transported by EMS. Patients with symptom onset outside, out-of-hospital cardiac arrest and presented to province-level hospital were more likely to use EMS. Besides those factors, low systolic blood pressure, severe dyspnea or syncope, and high Killip class were also positively related to EMS activation. Notably, compared to self-transport, use of EMS was associated with a shorter prehospital delay (median, 180 vs. 245 min, P < 0.0001) but similar door-to-needle time (median, 45 min vs. 52 min, P = 0.1400) and door-to-balloon time (median, 105 min vs. 103 min, P = 0.1834). CONCLUSIONS: EMS care for STEMI is greatly underused in China. EMS transport is associated with shorter onset-to-door time and higher rate of reperfusion, but not substantial reduction in treatment delays or mortality rate. Targeted efforts are needed to promote EMS use when chest pain occurs and to set up a unique regionalized STEMI network focusing on integration of prehospital care procedures in China. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01874691), retrospectively registered June 11, 2013.

Post-procedural elevated cardiac troponin I and the association with 5-year mortality in patients undergoing elective PCI.

Background: The clinically meaningful cardiac troponin I (cTnI) threshold associated with the long-term prognosis in patients undergoing elective percutaneous coronary intervention (PCI) is still debated. Objective: To assess the association between different thresholds for post-procedural cTnI and 5-year mortality. Methods: The study included 4059 consecutive patients with normal baseline cTnI values who underwent elective PCI. The post-procedural cTnI level was measured at 8-48 h after PCI. The main study endpoints were 5-year all-cause mortality and cardiovascular mortality. Results: A cTnI ≥5 times the upper reference limit (URL) as defined by the fourth universal definition of myocardial infarction (4th UDMI), ≥35 times as defined by the Academic Research Consortium-2 criteria, and ≥70 times as defined by the Society for Cardiovascular Angiography and Interventions (SCAI [2014]) was identified in 33%, 6.6%, and 3.3% of patients, respectively. During 5 years of follow-up, the all-cause mortality rate was 3.4% (n = 132) and the cardiovascular mortality rate was 2.0% (n = 77). Both all-cause mortality and cardiovascular mortality increased with higher peak cTnI, and were independently predicted by a cTnI ≥70 times the URL (adjusted hazard ratio [HR] 2.45, 95% confidence interval [CI] 1.20-5.02 and adjusted HR 3.17, 95% CI 1.31-7.67, respectively; reference, cTnI <1 × URL]. The SCAI (2014) threshold was significantly associated with 5-year cardiovascular mortality (adjusted HR 2.66, 95% CI 1.20-5.89; reference, cTnI, <70 × URL) and all-cause mortality (adjusted HR 2.23, 95% CI 1.16-4.30; reference, cTnI <70 × URL). Conclusion: In patients with normal pre-procedural cTnI who underwent elective PCI, a post-procedural cTnI ≥70 times the URL independently predicted 5-year all-cause and cardiovascular mortality. Therefore, only the SCAI (2014) post-procedural cTnI threshold was independently associated with long-term mortality.

Inflammation modifies the platelet reactivity among thrombocytopenia patients undergoing percutaneous coronary intervention.

Percutaneous coronary intervention (PCI) patients combined with thrombocytopenia (TP) are usually considered to be at low ischemic risk, receiving less proper antiplatelet therapy. However, recent studies reported a paradoxical phenomenon that PCI patients with TP were prone to experience thrombotic events, while the mechanisms and future treatment remain unclear. We aim to investigate whether inflammation modifies platelet reactivity among these patients. Consecutive 10 724 patients undergoing PCI in Fuwai Hospital were enrolled throughout 2013. High-sensitivity C-reactive protein (hsCRP) ≥2 mg/L was considered inflammatory status. TP was defined as platelet count <150×109/L. High on-treatment platelet reactivity (HTPR) was defined as adenosine diphosphate-induced platelet maximum amplitude of thromboelastogram >47mm. Among 6617 patients finally included, 879 (13.3%) presented with TP. Multivariate logistic regression demonstrated that patients with TP were associated with a lower risk of HTPR (odds ratio [OR] 0.64, 95% confidence interval [CI] 0.53-0.76) than those without TP in the overall cohort. In further analysis, among hsCRP <2 mg/L group, patients with TP exhibited a decreased risk of HTPR (OR 0.53, 95% CI 0.41-0.68); however, in hsCRP ≥2mg/L group, TP patients had a similar risk of HTPR as those without TP (OR 0.83, 95% CI 0.63-1.08). Additionally, these results remain consistent across subgroups, including patients presenting with acute coronary syndrome and chronic coronary syndrome. Inflammation modified the platelet reactivity of PCI patients with TP, providing new insights into the mechanisms of the increased thrombotic risk. Future management for this special population should pay more attention to inflammation status and timely adjustment of antiplatelet therapy in TP patients with inflammation.

What is the context? Recent studies reported a paradoxical phenomenon that percutaneous coronary intervention (PCI) patients with thrombocytopenia (TP) were prone to experience thrombotic events. The potential mechanisms underlying the increased thrombotic risk and how to manage antiplatelet therapy in PCI patients with TP remain unclear.Growing attention has been paid to immunothrombosis. Inflammation is closely associated with high-on treatment platelet reactivity (HTPR) and thrombotic risk.HTPR is an independent risk factor of thrombosis and can provide information for guiding antiplatelet therapy.What is new? This prospective cohort study enrolled 10 724 patients undergoing PCI in Fuwai Hospital (National Center for Cardiovascular Diseases, Beijing, China), with HTPR risk being the study endpoint of interest.We first reported that inflammation significantly modified the platelet reactivity of PCI patients with TP.When hsCRP level <2 mg/L, PCI patients with TP had a decreased risk of HTPR. However, when hsCRP ≥2 mg/L, TP patients had similar HTPR risk as those without TP.HsCRP levels could modify the relationship between TP and HTPR risks both in patients with acute coronary syndrome and chronic coronary syndrome.What is the impact? These results provide insights into potential mechanisms of the increased thrombotic risk in PCI patients with TP. Specifically, inflammation might be involved in the thrombotic risk of PCI patients with TP by modifying the platelet reactivity.As for future management, personalized antiplatelet therapy should be administrated to TP patients with inflammation status.

Renal function alters the association of lipoprotein(a) with cardiovascular outcomes in patients undergoing percutaneous coronary intervention: a prospective cohort study.

Background and hypothesis: Lipoprotein(a) [Lp(a)] and renal dysfunction are both independent risk factors for cardiovascular disease. However, it remains unclear whether renal function mediates the association between Lp(a) and cardiovascular outcomes in patients undergoing percutaneous coronary intervention (PCI). Methods: From a large prospective cohort study, 10 435 eligible patients undergoing PCI from January 2013 to December 2013 were included in our analysis. Patients were stratified into three renal function groups according to their baseline estimated glomerular filtration rate (eGFR) (<60; 60-90; ≥90 ml/min/1.73 m2). The primary endpoint was a composite of all-cause death, nonfatal MI, ischemic stroke, and unplanned revascularization [major adverse cardiac and cerebrovascular events (MACCE)]. Results: Over a median follow-up of 5.1 years, a total of 2144 MACCE events occurred. After multivariable adjustment, either eGFR <60 ml/min/1.73 m2 or elevated Lp(a) conferred a significantly higher MACCE risk. Higher Lp(a) was significantly associated with an increased risk of MACCE in patients with eGFR <60 ml/min/1.73 m2. However, this association was weakened in subjects with only mild renal impairment and diminished in those with normal renal function. A significant interaction for MACCE between renal categories and Lp(a) was observed (P = 0.026). Patients with concomitant Lp(a) ≥30 mg/dl and eGFR <60 ml/min/1.73 m2 experienced worse cardiovascular outcomes compared with those without. Conclusion: The significant association between Lp(a) and cardiovascular outcomes was mediated by renal function in patients undergoing PCI. Lp(a)-associated risk was more pronounced in patients with worse renal function, suggesting close monitoring and aggressive management are needed in this population.

Diagnostic performance of intravascular ultrasound-based fractional flow reserve in evaluating of intermediate left main stenosis.

BACKGROUND: The recently introduced ultrasonic flow ratio (UFR), is a novel fast computational method to derive fractional flow reserve (FFR) from intravascular ultrasound (IVUS) images. In the present study, we evaluate the diagnostic performance of UFR in patients with intermediate left main (LM) stenosis. METHODS: This is a prospective, single center study enrolling consecutive patients with presence of intermediated LM lesions (diameter stenosis of 30%-80% by visual estimation) underwent IVUS and FFR measurement. An independent core laboratory assessed offline UFR and IVUS-derived minimal lumen area (MLA) in a blinded fashion. RESULTS: Both UFR and FFR were successfully achieved in 41 LM patients (mean age, 62.0 ± 9.9 years, 46.3% diabetes). An acceptable correlation between UFR and FFR was identified (r = 0.688, P < 0.0001), with an absolute numerical difference of 0.03 (standard difference: 0.01). The area under the curve (AUC) in diagnosis of physiologically significant coronary stenosis for UFR was 0.94 (95% CI: 0.87-1.01), which was significantly higher than angiographic identified stenosis > 50% (AUC = 0.66, P < 0.001) and numerically higher than IVUS-derived MLA (AUC = 0.82; P = 0.09). Patient level diagnostic accuracy, sensitivity and specificity for UFR to identify FFR ≤ 0.80 was 82.9% (95% CI: 70.2-95.7), 93.1% (95% CI: 82.2-100.0), 58.3% (95% CI: 26.3-90.4), respectively. CONCLUSION: In patients with intermediate LM diseases, UFR was proved to be associated with acceptable correlation and high accuracy with pressure wire-based FFR as standard reference. The present study supports the use of UFR for functional evaluation of intermediate LM stenosis.

Nicorandil-Pretreated Mesenchymal Stem Cell-Derived Exosomes Facilitate Cardiac Repair After Myocardial Infarction via Promoting Macrophage M2 Polarization by Targeting miR-125a-5p/TRAF6/IRF5 Signaling Pathway.

Background: Exosomes derived from bone marrow mesenchymal stem cells (MSC-exo) have been considered as a promising cell-free therapeutic strategy for ischemic heart disease. Cardioprotective drug pretreatment could be an effective approach to improve the efficacy of MSC-exo. Nicorandil has long been used in clinical practice for cardioprotection. This study aimed to investigate whether the effects of exosomes derived from nicorandil pretreated MSC (MSCNIC-exo) could be enhanced in facilitating cardiac repair after acute myocardial infarction (AMI). Methods: MSCNIC-exo and MSC-exo were collected and injected into the border zone of infarcted hearts 30 minutes after coronary ligation in rats. Macrophage polarization was detected 3 days post-infarction, cardiac function as well as histological pathology were measured on the 28th day after AMI. Macrophages were separated from the bone marrow of rats for in vitro model. Exosomal miRNA sequencing was conducted to identify differentially expressed miRNAs between MSCNIC-exo and MSC-exo. MiRNA mimics and inhibitors were transfected to MSCs or macrophages to explore the specific mechanism. Results: Compared to MSC-exo, MSCNIC-exo showed superior therapeutic effects on cardiac functional and structural recovery after AMI and markedly elevated the ratio of CD68+ CD206+/ CD68+cells in infarcted hearts 3 days post-infarction. The notable ability of MSCNIC-exo to promote macrophage M2 polarization was also confirmed in vitro. Exosomal miRNA sequencing and both in vivo and in vitro experiments identified and verified that miR-125a-5p was an effector of the roles of MSCNIC-exo in vivo and in vitro. Furthermore, we found miR-125a-5p promoted macrophage M2 polarization by inhibiting TRAF6/IRF5 signaling pathway. Conclusion: This study suggested that MSCNIC-exo could markedly facilitate cardiac repair post-infarction by promoting macrophage M2 polarization by upregulating miR-125a-5p targeting TRAF6/IRF5 signaling pathway, which has great potential for clinical translation.

The prevalence and outcomes in STEMI patients aged ≥75 undergoing primary percutaneous coronary intervention in China.

Objective: To investigate the prevalence and outcomes of primary percutaneous coronary intervention (PCI) in Chinese patients with ST-segment elevation myocardial infarction (STEMI) aged ≥75 years. Methods: We identified STEMI patients aged ≥75 years between 2013 and 2014 from a multicenter registry. The primary outcome was all-cause mortality. The secondary outcome was major adverse cardiac and cerebrovascular event (MACCE) including a composite of all-cause mortality, cardiac death, recurrent MI, stroke, revascularization, and major bleeding. Hazard ratios (HR) and associated 95% confidence interval (CI) were calculated. Results: Approximately 32.9% (n = 999) patients received primary PCI. Primary PCI was associated with lower risks of two-year all-cause mortality (18.0% vs. 36.4%; adjusted HR: 0.54, 95% CI: 0.45 to 0.65, P < 0.0001), MACCE (28.7% vs. 43.5%; adjusted HR: 0.68, 95% CI: 0.59 to 0.80, P < 0.0001), and cardiac death (10.0% vs. 23.6%; adjusted HR: 0.49, 95% CI: 0.38 to 0.62, P < 0.0001) relative to no reperfusion (n = 2041) in patients aged ≥75 years. The better outcomes in two-year all-cause mortality, MACCE, and cardiac death were consistently observed in STEMI patients aged ≥85 years. No differences were observed in recurrent MI, stroke, revascularization, and major bleeding between the two groups. Additionally, in patients with relatively high-risk profiles such as cardiogenic shock or delaying hospital admission, primary PCI was also superior to no reperfusion. Conclusion: Primary PCI may decrease two-year all-cause mortality, MACCE, and cardiac death in STEMI patients aged ≥75 years, even in these with age ≥85 years, cardiogenic shock, or delaying hospital admission. However, primary PCI was underutilized in Chinese clinical practice.

Causal associations between atrial fibrillation and breast cancer: A bidirectional Mendelian randomization analysis.

BACKGROUND: Previous observational studies indicated that atrial fibrillation may increase the risk of breast cancer. Following a breast cancer diagnosis, the chance of developing atrial fibrillation may increase as well. However, it is uncertain whether the link is causal or just due to confounding factors. OBJECTIVE: Using bidirectional Mendelian randomization (MR) analysis, we sought to assess the bidirectional causal relationship between atrial fibrillation and breast cancer from a genetic level. METHODS: Large genome-wide association studies yielded summary-level data for atrial fibrillation and breast cancer. The preliminary estimate was inverse variance weighted (IVW) under a random model. MR-Egger, weighted median, simple mode, weighted mode, and multivariable MR (adjusting body mass index, smoking, and alcohol drinking) were performed as sensitivity analyses. RESULTS: Genetically predicted atrial fibrillation presented no statistically significant association with overall breast cancer (odds ratio [OR] = 1.00; 95% confidence interval [CI]: 0.97-1.04; p = 0.79), estrogen receptor (ER) + (OR = 1.00; 95% CI: 0.96-1.03; p = 0.89) or ER- subtypes (OR = 1.00; 95% CI: 0.97-1.04; p = 0.89). Similarly, genetically predicted overall breast cancer (OR = 1.01; 95% CI: 0.98-1.04; p = 0.37), ER+ (OR = 1.02; 95% CI: 0.99-1.05; p = 0.16) or ER- (OR = 0.98; 95% CI: 0.93-1.02; p = 0.32) subtypes had no causal effect on atrial fibrillation. Sensitivity analyses yielded similar results. Individual single nucleotide polymorphism had little effect on the total estimate. We did not observe any evidence of horizontal pleiotropy. CONCLUSIONS: Our bidirectional MR studies revealed that there may be no causal links between atrial fibrillation and breast cancer.

The prognostic value of collateral circulation in coronary chronic total occlusion underwent percutaneous coronary intervention.

BACKGROUND: The prognostic value of coronary collateral circulation (CC) in patients undergoing chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is underdetermined. The purpose of the study was to assess the prognostic value of current two CC grading systems and their association with long-term outcomes in patients with CTO underwent PCI. METHODS: We consecutively enrolled patients with single-vessel CTO underwent PCI between January 2010 and December 2013. All patients were categorized into well-developed or poor-developed collaterals group according to angiographic Werner's CC (grade 2 vs. grade 0-1) or Rentrop (grade 3 vs. grade 0-2) grading system. The primary endpoint was 5-year cardiac death. RESULTS: Of 2452 enrolled patients, the overall technical success rate was 74.1%. Well-developed collaterals were present in 686 patients (28.0%) defined by Werner's CC grade 2, and in 1145 patients (46.7%) by Rentrop grade 3. According to Werner's CC grading system, patients with well-developed collaterals had a lower rate of 5-year cardiac death compared with those with poor-developed collaterals (1.6% vs. 3.3%, P = 0.02), those with suboptimal recanalization was associated with higher rate of 5-year cardiac death compared with optimal recanalization (4.7% vs. 0.8%, P = 0.01) and failure patients (4.7% vs. 1.6%, P = 0.12). However, the similar effect was not shown in Rentrop grading system. CONCLUSIONS: In patients with the single-vessel CTO underwent PCI, well-developed collaterals by Werner's CC definition were associated with lower rate of 5-year cardiac death. Werner's CC grading system had a greater prognostic value than Rentrop grading system in patients with CTO underwent PCI.

Effect of Household Income on Cardiovascular Diseases, Cardiovascular Biomarkers, and Socioeconomic Factors.

PURPOSE: To examine whether household income is causally related to cardiovascular diseases and investigate the potential reasons. METHODS: Using 2-sample Mendelian randomization analyses, we obtained summary statistics from genome-wide association studies of household income and a range of cardiovascular diseases, biomarkers, and socioeconomic factors. FINDINGS: Higher household income was causally associated with lower risks of coronary heart disease (odd ratio [OR] = 0.63; 95% CI: 0.49-0.79; P = 0.0001), myocardial infarction (OR = 0.64; 95% CI: 0.50-0.82; P = 0.0003), and hypertension (OR = 0.71; 95% CI: 0.58-0.88; P = 0.0015). With increasing household income, the cardiovascular biomarkers including triglycerides, C-reactive protein, body mass index, fasting glucose were decreased whereas telomere length and high-density lipoprotein cholesterol were increased. Besides, individuals with higher household income were less likely to smoke (ß = -0.34; 95% CI: -0.47 to -0.21; P = 1.91×10-07), intake salt (ß = -0.14; 95% CI: -0.21 to -0.07; P = 0.0001), or be exposed to air pollution (ß = -0.10; 95% CI: -0.15 to -0.06; P = 8.81×10-06) or depression state (ß = -0.03; 95% CI: -0.04 to -0.02; P = 5.16×10-07). They were more likely to take physical activity (ß = 0.06; 95% CI: 0.02 to 010; P = 0.0016) and have long years of schooling (ß = 0.70; 95% CI: 0.62 to 0.78; P = 5.32×10-67). IMPLICATIONS: Higher household income is causally associated with better socioeconomic factors and improved cardiovascular biomarkers, which translates into a reduced prevalence of cardiovascular diseases. Policies to improve income equality may result in a reduced burden of cardiovascular diseases.

Prolonged Dual Antiplatelet Therapy in Acute Myocardial Infarction Patients Without Revascularization: China Acute Myocardial Infarction Registry Study.

At least 12 months of dual antiplatelet therapy (DAPT) is 1 of the standards of care following percutaneous coronary intervention in patients with acute coronary syndrome. However, study on prolonged DAPT for patients with acute myocardial infarction (AMI) without revascularization is limited. We studied 1,744 patients with AMI without revascularization from the China Acute Myocardial Infarction registry between January 2013 and September 2014. These patients were on DAPT and did not experience AMI, stroke, or bleeding events at the 12-month follow-up. We divided them into 2 groups: 12-month DAPT group (DAPT for at least 12 months but <18 months) and 18-month DAPT group (DAPT for at least 18 months). The primary outcome was 24-month all-cause death. Overall, 1,221 patients (70.0%) took DAPT for ≥12 months but <18 months, whereas 523 patients (30.0%) took DAPT for ≥18 months. The proportion of patients at high ischemic risk and the proportion of patients at high bleeding risk were similar in the 2 groups. At 24 months, the all-cause mortality rate of the 18-month DAPT group was significantly lower than that for the 12-month DAPT group (3.7% vs 5.9%, p = 0.0471). The adjusted hazard ratio for all-cause death also showed statistical significance (0.59, 95% confidence interval 0.35 to 0.99, p = 0.0444). In conclusion, DAPT for at least 18 months appears to be associated with lower 24-month mortality for non-revascularization AMI patients without events within 12 months after onset.

Association between living alone and all-cause mortality of young and middle-aged patients with acute myocardial infarction: analysis of the China Acute Myocardial Infarction (CAMI) registry.

BACKGROUND: Lack of social support is a known predictor of the prognosis after acute myocardial infarction (AMI). Although as a common factor associated with social support, there are limited data on long-term prognostic impact of living status in young and middle-aged patients with AMI. METHODS: We analyzed data from the China Acute Myocardial Infarction (CAMI) Registry, consecutive AMI young and middle-aged patients admitted at 108 hospitals in China between January 2013 and September 2014 were included. Eligible patients were assigned to living alone and not living alone groups based on their living status. The primary endpoint was 2-year all-cause mortality. The secondary endpoints included in-hospital mortality and 2-year major adverse cardiac and cerebrovascular events (MACCEs; a composite of all-cause mortality, MI, or stroke). Multilevel logistic and multilevel Cox regression models were used to evaluate the effect of living status on short-term and long-term outcomes. RESULTS: A total of 8307 consecutive AMI young and middle-aged patients were included, 192 (2.3%) patients were living alone. Of the analyzed patients, living alone was associated with 2-year all-cause mortality and MACCEs among all analyzed patients after multivariate adjustment (adjusted hazard ratio [HR] = 2.171 [1.210-3.895], P = 0.009; adjusted HR = 2.169 [1.395-3.370], P = 0.001), but not with poorer in-hospital mortality. CONCLUSIONS: The analysis suggested that living alone was associated with both 2-year all-cause mortality and MACCEs in AMI young and middle-aged patients but did not show an extra effect on the in-hospital mortality after covariate adjustment. TRIAL REGISTRATION: Trial registration number: NCT01874691; Registered 31 October 2012.

Triple Hybrid Cellular Nanovesicles Promote Cardiac Repair after Ischemic Reperfusion.

The management of myocardial ischemia/reperfusion (I/R) damage in the context of reperfusion treatment remains a significant hurdle in the field of cardiovascular disorders. The injured lesions exhibit distinctive features, including abnormal accumulation of necrotic cells and subsequent inflammatory response, which further exacerbates the impairment of cardiac function. Here, we report genetically engineered hybrid nanovesicles (hNVs), which contain cell-derived nanovesicles overexpressing high-affinity SIRPα variants (SαV-NVs), exosomes (EXOs) derived from human mesenchymal stem cells (MSCs), and platelet-derived nanovesicles (PLT-NVs), to facilitate the necrotic cell clearance and inhibit the inflammatory responses. Mechanistically, the presence of SαV-NVs suppresses the CD47-SIRPα interaction, leading to the promotion of the macrophage phagocytosis of dead cells, while the component of EXOs aids in alleviating inflammatory responses. Moreover, the PLT-NVs endow hNVs with the capacity to evade immune surveillance and selectively target the infarcted area. In I/R mouse models, coadministration of SαV-NVs and EXOs showed a notable synergistic effect, leading to a significant enhancement in the left ventricular ejection fraction (LVEF) on day 21. These findings highlight that the hNVs possess the ability to alleviate myocardial inflammation, minimize infarct size, and improve cardiac function in I/R models, offering a simple, safe, and robust strategy in boosting cardiac repair after I/R.

Causal Associations of Education Level With Cardiovascular Diseases, Cardiovascular Biomarkers, and Socioeconomic Factors.

An inverse association of education level with cardiovascular diseases has been documented in observational studies, yet the causality and potential mechanisms remain to be determined. To systematically investigate the causal associations of education level with cardiovascular diseases, cardiovascular biomarkers, and socioeconomic factors, a 2-sample Mendelian randomization was performed. The results revealed that higher genetically determined education level was associated with lower risks of type 2 diabetes mellitus (odds ratio [OR] 0.54, 95% confidence interval [CI] 0.47 to 0.61, p = 3.04 × 10-23), peripheral artery disease (OR 0.62, 95% CI 0.51 to 0.76, p = 2.14 × 10-06), hypertension (OR 0.62, 95% CI 0.56 to 0.70, p = 4.22 × 10-16), coronary heart disease (OR 0.62, 95% CI 0.56 to 0.69, p = 3.50 × 10-19), myocardial infarction (OR 0.62, 95% CI 0.55 to 0.69, p = 2.58 × 10-16), ischemic stroke (OR 0.67, 95% CI 0.62 to 0.74, p = 6.00 × 10-19), deep vein thrombosis (OR 0.69, 95% CI 0.55 to 0.87, p = 0.0017), atrial fibrillation (OR 0.70, 95% CI 0.57 to 0.86, p = 0.0007), cardiac death (OR 0.71, 95% CI 0.60 to 0.86, p = 0.0003), heart failure (OR 0.72, 95% CI 0.65 to 0.79, p = 6.37 × 10-12), transient ischemic attack (OR 0.76, 95% CI 0.64 to 0.90, p = 0.0010), and venous thromboembolism (OR 0.79, 95% CI 0.67 to 0.92, p = 0.0028). Systolic blood pressure, diastolic blood pressure, C-reactive protein, body mass index, waist circumference, and triglycerides were decreased, whereas telomere length was increased. Subjects with higher education were less likely to smoke, intake salt, or be exposed to air pollution and depression state. They were more likely to take physical activity and possess more household income. In conclusion, higher education may causally decrease cardiovascular diseases through socioeconomic factors and cardiovascular biomarkers. Reducing education inequality is important in the management of cardiovascular diseases.

Baseline high-sensitivity C-reactive protein and glycosylated hemoglobinA1c predict adverse outcomes in patients with chronic coronary syndromes undergoing percutaneous coronary intervention.

Introduction: This study explored the ability of high-sensitivity C-reactive protein (hs-CRP) and glycosylated hemoglobin A1c (HbA1c) to predict adverse cardiac and cerebrovascular outcomes in patients with chronic coronary syndromes (CCS) undergoing percutaneous coronary intervention (PCI). Methods: In total, 4083 consecutive patients with CCS undergoing PCI were investigated throughout 2013 at a single center. The primary endpoint was all-cause death at the 5-year follow-up. Hs-CRP and HbA1c data were collected on admission. Results: The highest quartile of hs-CRP had a significantly increased the risk of all-cause death, with an adjusted HR of 1.747 (95 % CI 1.066-2.863), while, there was no difference in all-cause death among the groups of HbA1c after adjustment, with an adjusted HR of 1.383 (95 % CI 0.716-2.674). The highest quartiles for hs-CRP and HbA1c in the study population had a significantly increased risk of major adverse cardiac and cerebrovascular events (MACCE), with an adjusted hazard ratios (HR) of 1.263 (95 % confidence intervals [CI] 1.032-1.545) for hs-CRP and an adjusted HR of 1.417 (95 % CI 1.091-1.840) for HbA1c. Remarkably, the incidence of all-cause death and that of MACCE were significantly increased when both hs-CRP and HbA1c were elevated (HR 1.971, 95 % CI 1.079-3.601, P = 0.027 and HR 1.560, 95 % CI 1.191-2.042), P = 0.001, respectively). Addition of hs-CRP and HbA1c to conventional risk factors significantly improved prediction of the risk of all cause death (net reclassification index 0.492, P < 0.001; integrated discrimination improvement 0.007, P = 0.011) and MACCE (net reclassification index 0.160, P < 0.001; integrated discrimination improvement 0.006, P < 0.001). Conclusions: Hs-CRP and HbA1c can serve as independent predictors of MACCE in patients with CCS undergoing PCI. Furthermore, a combination of hs-CRP and HbA1c could predict all cause death and MACCE better than each component individually.

Top Five Stories of the Cellular Landscape and Therapies of Atherosclerosis: Current Knowledge and Future Perspectives.

Atherosclerosis (AS) is characterized by impairment and apoptosis of endothelial cells, continuous systemic and focal inflammation and dysfunction of vascular smooth muscle cells, which is documented as the traditional cellular paradigm. However, the mechanisms appear much more complicated than we thought since a bulk of studies on efferocytosis, transdifferentiation and novel cell death forms such as ferroptosis, pyroptosis, and extracellular trap were reported. Discovery of novel pathological cellular landscapes provides a large number of therapeutic targets. On the other side, the unsatisfactory therapeutic effects of current treatment with lipid-lowering drugs as the cornerstone also restricts the efforts to reduce global AS burden. Stem cell- or nanoparticle-based strategies spurred a lot of attention due to the attractive therapeutic effects and minimized adverse effects. Given the complexity of pathological changes of AS, attempts to develop an almighty medicine based on single mechanisms could be theoretically challenging. In this review, the top stories in the cellular landscapes during the initiation and progression of AS and the therapies were summarized in an integrated perspective to facilitate efforts to develop a multi-targets strategy and fill the gap between mechanism research and clinical translation. The future challenges and improvements were also discussed.

Association between multiple inflammatory biomarkers and remnant cholesterol levels in patients with percutaneous coronary intervention: A large-scale real-world study.

BACKGROUND AND AIM: Remnant cholesterol (RC) has garnered increasing attention recently due to its association with adverse cardiovascular events. However, the relationship between RC levels and inflammation remains unclear. The goal of this study was to investigate and compare the predictive value of multiple inflammatory biomarkers for high RC in patients with percutaneous coronary intervention (PCI). METHODS AND RESULTS: Initially, a total of 10,724 consecutive individuals hospitalized for PCI at Fu Wai Hospital in 2013 were enrolled. Finally, 9983 patients receiving dual antiplatelet therapy and drug-eluting stent were selected for analysis. The inflammatory biomarkers included high-sensitivity C-reactive protein (hs-CRP), hs-CRP-to-albumin ratio (CAR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), lymphocyte-to-hs-CRP ratio (LCR), and systemic immune-inflammation index (SII). Patients were divided into higher RC and lower RC groups based on the median RC level. Multivariate logistic regression showed that hs-CRP (OR per SD: 1.254), CAR (OR per SD: 1.245), PLR (OR per SD: 1.139), and SII (OR per SD: 1.077) were associated with high RC (≥median), while LCR (OR per SD: 0.792) was associated with low RC (