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.

Discovery of novel ocotillol derivatives modulating glucocorticoid receptor/NF-κB signaling for the treatment of sepsis.

Glucocorticoids (GCs) have been used in the treatment of sepsis because of their potent anti-inflammatory effects. However, their clinical efficacy against sepsis remains controversial because of glucocorticoid receptor (GR) downregulation and side effects. Herein, we designed and synthesized 30 ocotillol derivatives and evaluated their anti-inflammatory activities. Ocotillol 24(R/S) differential isomers were stereoselective in their pharmacological action. Specifically, 24(S) derivatives had better anti-inflammatory activity than their corresponding 24(R) derivatives. Compound 20 most effectively inhibited NO release (85.97% reduction), and it exerted dose-dependent inhibitory effects on interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels. Mechanistic studies revealed that compound 20 reduces the degradation of GR mRNA and GR protein. Meanwhile, compound 20 inhibited the activation of nuclear factor-κB (NF-κB) signaling, thereby inhibiting the nuclear translocation of p65 and attenuating the inflammatory response. In vivo studies revealed that compound 20 attenuated hepatic, pulmonary, and renal pathology damage in mice with sepsis and suppressed the production of inflammatory mediators. These results indicated that compound 20 is a promising lead compound for designing and developing anti-sepsis drugs.

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.

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.

CENPL accelerates cell proliferation, cell cycle, apoptosis, and glycolysis via the MEK1/2-ERK1/2 pathway in hepatocellular carcinoma.

Centromere protein L (CENPL) is involved in the mitotic process of eukaryotic cells and the development of various types of cancer. However, its role in hepatocellular carcinoma (HCC) remains unclear. This study aimed to investigate the expression and clinical significance of CENPL in HCC, and explore its involvement in regulating HCC cell proliferation, apoptosis, cell cycle, and glycolysis both in vivo and in vitro. CENPL expression was analyzed in HCC and normal liver tissues using The Cancer Genome Atlas, Gene Expression Omnibus mining, real-time quantitative polymerase chain reaction, and immunohistochemistry. Functional assays were used to assess the role of CENPL in HCC cell proliferation, apoptosis, cell cycle, and glycolysis. The potential pathways underlying the regulatory effects of CENPL, as well as the expression of mitogen-activated protein kinase (MAPK) signaling pathway-related molecules and markers of proliferation and glycolysis were investigated. CENPL was significantly upregulated in HCC tissue and associated with multiple clinicopathological features and poor patient prognosis. Univariate and multivariate analyses demonstrated that CENPL may serve as an independent prognostic factor for HCC. Upregulation of CENPL in HCC regulated tumor proliferation and glycolytic processes. Mechanistic studies revealed that differentially expressed genes between the CENPL-overexpressing and control groups were mainly concentrated in the MAPK signaling pathway. Pathway inhibition analysis indicated that CENPL activated the MEK1/2-ERK1/2 signaling pathway to promote proliferation and glycolysis in HCC cells. This study elucidated the role of CENPL in regulating cell proliferation, apoptosis, cell cycle, and glycolysis in HCC. CENPL may represent a therapeutic target and prognostic biomarker for HCC.

Role of ST-Segment Resolution Alone and in Combination With TIMI Flow After Primary Percutaneous Coronary Intervention for ST-Segment-Elevation Myocardial Infarction.

Background To evaluate the role of ST-segment resolution (STR) alone and in combination with Thrombolysis in Myocardial Infarction (TIMI) flow in reperfusion evaluation after primary percutaneous coronary intervention (PPCI) for ST-segment-elevation myocardial infarction by investigating the long-term prognostic impact. Methods and Results From January 2013 through September 2014, we studied 5966 patients with ST-segment-elevation myocardial infarction enrolled in the CAMI (China Acute Myocardial Infarction) registry with available data of STR evaluated at 120 minutes after PPCI. Successful STR included STR ≥50% and complete STR (ST-segment back to the equipotential line). After PPCI, the TIMI flow was assessed. The primary outcome was 2-year all-cause mortality. STR < 50%, STR ≥50%, and complete STR occurred in 20.6%, 64.3%, and 15.1% of patients, respectively. By multivariable analysis, STR ≥50% (5.6%; adjusted hazard ratio [HR], 0.45 [95% CI, 0.36-0.56]) and complete STR (5.1%; adjusted HR, 0.48 [95% CI, 0.34-0.67]) were significantly associated with lower 2-year mortality than STR <50% (11.7%). Successful STR was an independent predictor of 2-year mortality across the spectrum of clinical variables. After combining TIMI flow with STR, different 2-year mortality was observed in subgroups, with the lowest in successful STR and TIMI 3 flow, intermediate when either of these measures was reduced, and highest when both were abnormal. Conclusions Post-PPCI STR is a robust long-term prognosticator for ST-segment-elevation myocardial infarction, whereas the integrated analysis of STR plus TIMI flow yields incremental prognostic information beyond either measure alone, supporting it as a convenient and reliable surrogate end point for defining successful PPCI. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01874691.

Machine learning for prediction of bleeding in acute myocardial infarction patients after percutaneous coronary intervention.

Background: Prediction of bleeding is critical for acute myocardial infarction (AMI) patients after percutaneous coronary intervention (PCI). Machine learning methods can automatically select the combination of the important features and learn their underlying relationship with the outcome. Objectives: We aimed to evaluate the predictive value of machine learning methods to predict in-hospital bleeding for AMI patients. Design: We used data from the multicenter China Acute Myocardial Infarction (CAMI) registry. The cohort was randomly partitioned into derivation set (50%) and validation set (50%). We applied a state-of-art machine learning algorithm, eXtreme Gradient Boosting (XGBoost), to automatically select features from 98 candidate variables and developed a risk prediction model to predict in-hospital bleeding (Bleeding Academic Research Consortium [BARC] 3 or 5 definition). Results: A total of 16,736 AMI patients who underwent PCI were finally enrolled. 45 features were automatically selected and were used to construct the prediction model. The developed XGBoost model showed ideal prediction results. The area under the receiver-operating characteristic curve (AUROC) on the derivation data set was 0.941 (95% CI = 0.909-0.973, p < 0.001); the AUROC on the validation set was 0.837 (95% CI = 0.772-0.903, p < 0.001), which was better than the CRUSADE score (AUROC: 0.741; 95% CI = 0.654-0.828, p < 0.001) and ACUITY-HORIZONS score (AUROC: 0.731; 95% CI = 0.641-0.820, p < 0.001). We also developed an online calculator with 12 most important variables (http://101.89.95.81:8260/), and AUROC still reached 0.809 on the validation set. Conclusion: For the first time, we developed the CAMI bleeding model using machine learning methods for AMI patients after PCI. Trial registration: NCT01874691. Registered 11 Jun 2013.

Development and validation of dynamic models to predict postdischarge mortality risk in patients with acute myocardial infarction: results from China Acute Myocardial Infarction Registry.

OBJECTIVES: The risk of adverse events and prognostic factors are changing in different time phases after acute myocardial infarction (AMI). The incidence of adverse events is considerable in the early period after AMI hospitalisation. Therefore, dynamic risk prediction is needed to guide postdischarge management of AMI. This study aimed to develop a dynamic risk prediction instrument for patients following AMI. DESIGN: A retrospective analysis of a prospective cohort. SETTING: 108 hospitals in China. PARTICIPANTS: A total of 23 887 patients after AMI in the China Acute Myocardial Infarction Registry were included in this analysis. PRIMARY OUTCOME MEASURES: All-cause mortality. RESULTS: In multivariable analyses, age, prior stroke, heart rate, Killip class, left ventricular ejection fraction (LVEF), in-hospital percutaneous coronary intervention (PCI), recurrent myocardial ischaemia, recurrent myocardial infarction, heart failure (HF) during hospitalisation, antiplatelet therapy and statins at discharge were independently associated with 30-day mortality. Variables related to mortality between 30 days and 2 years included age, prior renal dysfunction, history of HF, AMI classification, heart rate, Killip class, haemoglobin, LVEF, in-hospital PCI, HF during hospitalisation, HF worsening within 30 days after discharge, antiplatelet therapy, ß blocker and statin use within 30 days after discharge. The inclusion of adverse events and medications significantly improved the predictive performance of models without these indexes (likelihood ratio test p<0.0001). These two sets of predictors were used to establish dynamic prognostic nomograms for predicting mortality in patients with AMI. The C indexes of 30-day and 2-year prognostic nomograms were 0.85 (95% CI 0.83-0.88) and 0.83 (95% CI 0.81-0.84) in derivation cohort, and 0.79 (95% CI 0.71-0.86) and 0.81 (95% CI 0.79-0.84) in validation cohort, with satisfactory calibration. CONCLUSIONS: We established dynamic risk prediction models incorporating adverse event and medications. The nomograms may be useful instruments to help prospective risk assessment and management of AMI. TRIAL REGISTRATION NUMBER: NCT01874691.

Fibrinolytic therapy use for ST-segment elevation myocardial infarction and long-term outcomes in China: 2-year results from the China Acute Myocardial Infarction Registry.

BACKGROUND: Data on fibrinolytic therapy use for ST-segment elevation myocardial infarction (STEMI) and long-term clinical outcomes in developing countries are limited. We aimed to investigate the management and 2-year mortality of fibrinolytic-treated patients in China. METHODS: A total of 19,112 patients with STEMI from 108 hospitals participated in the China Acute Myocardial Infarction registry between January 2013 and September 2014. We investigated the 2-year all-cause mortality among patients treated with fibrinolysis. Non-invasive clinical indexes were used to diagnose successful fibrinolysis or not. RESULTS: Only 1823 patients (9.5%) enrolled in the registry underwent fibrinolysis and 679 (37.2%) could be treated within 3 h after symptom onset. The overall use of rescue percutaneous coronary intervention was 8.9%. Successful fibrinolysis, which could be achieved in 1428 patients (78.3%), was related to types of fibrinolytic agents, symptom to needle time, infarction site, and Killip class. Follow-up data were available for 1745 patients (95.7%). After multivariate adjustment, successful fibrinolysis was strongly associated with a decreased risk of death compared with failed fibrinolysis at 2 years (8.5% vs. 29.0%, hazard ratio: 0.27, 95% confidence interval: 0.20-0.35). CONCLUSION: Within a minority of STEMI patients in the CAMI registry underwent fibrinolysis, most of them could achieve successful clinical reperfusion, presenting a much benign 2-year survival outcome than those with failed fibrinolysis. Quality improvement initiatives focusing on fibrinolysis are warranted to achieve its promise fully. TRIAL REGISTRATION: URL: https// www. CLINICALTRIALS: gov . Unique identifier: NCT01874691. Registered 11/06/2013.

Design and synthesis of hederagenin derivatives modulating STING/NF-κB signaling for the relief of acute liver injury in septic mice.

Systemic inflammatory responses often result in sepsis and inhibition of inflammation is one strategy for sepsis treatment. In this study, we designed and synthesized 32 novel hederagenin (HD) derivatives with modifications at the A-ring, C-28, and C-23 positions and screened their anti-inflammatory activities in vitro, finding multiple compounds with potential anti-inflammatory activity. Of these, compound 1 was the most effective and was used for subsequent investigations into its mechanism of action and in vivo activity. In vivo assessments of anti-inflammatory activity showed that compound 1 reduced inflammation in a mouse model of sepsis with acute liver injury caused by lipopolysaccharide (LPS). Compound 1 also inhibited STING, p-IRF3, p-TBK1, p-p65, and p-IκB proteins in cGAS-STING-associated signaling. These findings indicated that compound 1 reduced inflammation through inhibition of STING expression and hence reducing activation of STING and nuclear factor-κB (NF-κB) signaling. Our work demonstrated that compound 1 is a promising lead compound for designing and developing anti-sepsis drugs.

Use of Mendelian randomization to evaluate the effect of atrial fibrillation on cardiovascular diseases and cardiac death.

AIMS: Several observational studies indicated that atrial fibrillation might aggravate other cardiovascular diseases apart from ischaemic stroke. However, it remains to be determined whether these associations reveal independent causation. Using Mendelian randomization (MR), we systematically investigated how genetically predicted atrial fibrillation affected other cardiovascular diseases and cardiac death. METHODS AND RESULTS: Summary-level data for atrial fibrillation and other cardiovascular diseases were obtained from public genome-wide association study data. The random inverse-variance weighted method was treated as the primary analysis. Sensitivity analyses (including weighted median, MR-Egger, and multivariable MR methods) were also performed. Atrial fibrillation was significantly associated with higher risks of heart failure [odds ratio (OR): 1.24; 95% confidence interval (CI): 1.19-1.28; P < 0.001], ischaemic stroke (OR: 1.21; 95% CI: 1.17-1.25; P < 0.001), transient ischaemic attack (OR: 1.10; 95% CI: 1.05-1.15; P < 0.001), peripheral artery diseases (OR: 1.09; 95% CI: 1.03-1.15; P = 0.002), cardiac death (OR: 1.08; 95% CI: 1.02-1.15; P = 0.008), and hypertension (OR: 1.06; 95% CI: 1.01-1.11; P = 0.010), without effects on coronary heart disease or pulmonary embolism. Associations for heart failure and ischaemic stroke remained robust to the sensitivity analyses. MR-Egger method (P > 0.05) and funnel plot yielded no indication of directional pleiotropy. The leave-one-out analysis suggested that the causal associations were not driven by individual single nucleotide polymorphism. CONCLUSIONS: This comprehensive MR analysis verified the causal associations between atrial fibrillation and high risks of heart failure, ischaemic stroke, transient ischaemic attack, peripheral artery diseases, cardiac death, and hypertension. Interventions to reduce cardiovascular diseases beyond ischaemic stroke are warranted in patients with atrial fibrillation.

Coronary Intervention in ST-Segment Elevation Myocardial Infarction Patients With Symptom Onset >12 Hours: Data from China Acute Myocardial Infarction Registry.

To determine whether late percutaneous coronary intervention (PCI) of an infarct-related artery >12 h after ST-segment elevation myocardial infarction onset is beneficial, patients were included from the prospective, nationwide, multicenter China Acute Myocardial Infarction registry. The number of patients who underwent PCI or received drug therapy alone was 4791 and 1149, respectively. Hazard ratio (HR) and associated 95% confidence interval (CI) were calculated. Compared with drug therapy, PCI was associated with lower incidences of 2-year major adverse cardiac and cerebrovascular events (MACCE; 6.43 vs 20.19%; HR, .27; 95% CI, .23-.32; P < .001), all-cause death (4.13 vs 15.74%; HR, .24; 95% CI, .20-.30; P < .001), myocardial infarction (1.73 vs 3.31%; HR, .49; 95% CI, .33-.72; P = .0003), stroke (1.02 vs 2.00%; HR, .47; 95% CI, .28-.77; P = .0026), and revascularization (10.96 vs 27.56%; HR, .32; 95% CI, .26-.39; P < .001). Subgroup analysis consistently indicated that PCI was superior to drug therapy. Moreover, the left ventricular ejection fraction in the PCI group was increased after 2-year follow-up, whereas there was no significant increase in the drug therapy group. In conclusion, late PCI is common in Chinese clinical practice, and it is associated with significant improvements in cardiac function and survival compared with drug therapy alone.

Orbital solitary fibrous tumours: clinicopathological characteristics and recurrence prediction.

BACKGROUND: SFTs are thought to have an unpredictable clinical course and currently have no recognized prognostic criterion. Our study aimed to determine the relationship between clinicopathological characteristics and the prognosis of patients with orbital SFTs. METHODS: The clinicopathological features of these patients were extracted from clinical records. The relationships between these features and prognosis were analysed. RESULTS: The positive rates of CD34, CD99, Blc2, and STAT6 expression were 90.3%, 90.3%, 83.9%, and 100%, respectively. The tumour recurrence rate was 38.7%. A higher recurrence rate was observed in patients with Ki67 index ≥ 5 (56.25% vs. 20%, P = 0.038). CONCLUSION: A Ki67 index ≥ 5 was an effective parameter for predicting tumour recurrence of orbital SFTs. Close follow-up is needed for these patients.

Beta-Blocker Use after Discharge in Patients with Acute Myocardial Infarction in the Contemporary Reperfusion Era.

Background and objectives: The effect of beta-blocker use after discharge on patients with acute myocardial infarction (AMI) in the contemporary reperfusion era remains ambiguous. By applying meta-analysis, we sought to assess the role of beta-blockers in the contemporary reperfusion era. Materials and Methods: Randomized controlled trials (RCT) and observational studies using propensity score matching, comparing use of beta-blockers with non-use of beta-blockers, in patients with AMI after discharge. The primary outcome was all-cause mortality. Odds ratios (OR) and associated 95% confidence intervals (CI) were calculated. Results: One RCT and eight observational studies, containing 47,339 patients with AMI, were included. Compared with non-use of beta-blockers, beta-blocker use after discharge may have reduced the risk of all-cause mortality (OR: 0.70, 95% CI: 0.61 to 0.80, I2 = 14.4%), cardiac death (OR: 0.63, 95% CI: 0.44 to 0.91, I2 = 22.8%), myocardial infarction (OR: 0.73, 95% CI: 0.62 to 0.86, I2 = 0), and revascularization (OR: 0.92, 95% CI: 0.85 to 0.99, I2 = 0). No significant differences were found in major adverse cardiovascular events (MACE, OR: 0.88, 95% CI: 0.66 to 1.17, I2 = 78.4%), heart failure (OR: 0.56, 95% CI: 0.29 to 1.08, I2 = 0) or stroke (OR: 1.13, 95% CI: 0.92 to 1.39, I2 = 0). For patients with preserved left ventricular function, beta-blocker use after discharge may have also reduced the risk of all-cause mortality (OR: 0.61, 95% CI: 0.44 to 0.84, I2 = 0). Conclusions: Use of beta-blockers after discharge may still be beneficial for AMI patients in the contemporary reperfusion era, with or without preserved left ventricular function.

The Optimal Strategy of Dual Antiplatelet Therapy after Percutaneous Coronary Intervention with Drug-Eluting Stent.

Objective: To test the optimal strategy of dual antiplatelet therapy (DAPT) after implantation of drug-eluting stents (DESs) according to specific DAPT time and subsequent monotherapy. Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, and Web of Science to identify randomized controlled trials (RCTs). Six DAPT strategies were compared: 1-month DAPT followed by P2Y12 inhibitor monotherapy, 3-month DAPT followed by P2Y12 inhibitor monotherapy, 3-month DAPT followed by aspirin monotherapy, 6-month DAPT followed by aspirin monotherapy, 12-month DAPT, and >12-month DAPT. Pooled odd ratios (ORs) with 95% credible intervals (CrIs) were calculated to summarize the effect of each strategy tested. Results: We identified 24 RCTs containing 81,405 patients. In comparison with 12-month DAPT, 3-month DAPT followed by P2Y12 inhibitor monotherapy reduced net clinical events (OR: 0.72; CrI: 0.55−0.94). Major bleeding (OR: 0.57; CrI: 0.34−1.00) was marginally decreased without impact on ischemic events (OR: 0.93; CrI: 0.68−1.29). Moreover, the benefits of 3-month DAPT (P2Y12 inhibitor) were consistent for male patients with acute coronary disease, young age, complex lesion, single-vessel disease, low body mass index, and without diabetes. Although >12-month DAPT was associated with a lower risk of myocardial infarction (OR: 0.67; CrI: 0.51−0.93), the risk of major bleeding (OR: 1.70; CrI: 1.10−2.70) was increased. Conclusion: Among patients treated with DESs, 3-month DAPT followed by P2Y12 inhibitor monotherapy may be the optimal antiplatelet strategy, while DAPT beyond 1 year reduces myocardial infarction at the expense of increased major bleeding.

Causal Associations between Paternal Longevity and Risks of Cardiovascular Diseases.

BACKGROUND: Observational studies have suggested that paternal longevity is associated with reduced risks of cardiovascular diseases, yet the causal association remains to be determined. OBJECTIVES: To investigate whether Mendelian randomization (MR) results support a causal role of paternal longevity for risks of cardiovascular diseases. METHODS: Genetic variants associated with paternal longevity and cardiovascular diseases were obtained from public genome-wide association study data. We used inverse variance weighted MR under a random-effects model to provide causal estimates between paternal longevity and cardiovascular diseases. RESULTS: Paternal longevity was associated with decreased risks of coronary heart disease (odds ratio (OR): 0.08; 95% confidence interval (CI): 0.02-0.37; p = 0.001) and peripheral artery disease (OR: 0.15; 95% CI: 0.03-0.65; p = 0.011). No significant differences were observed in hypertension, atrial fibrillation, heart failure, transient ischemic attack, ischemic stroke, or cardiac death. The weighted median method revealed consistent results between genetically instrumented paternal longevity and decreased risk of coronary heart disease and peripheral artery disease. No significant differences were observed in the MR-Egger results. Multivariable MR consistently indicated causal associations between paternal longevity and decreased cardiovascular diseases. The leave-one-out analysis suggested that the causal associations were not affected by individual single-nucleotide polymorphisms. The intercept of the MR-Egger estimator and funnel plot revealed no indication of horizontal pleiotropic effects. CONCLUSIONS: Our MR analyses supported a causal role of paternal longevity for decreased risks of coronary heart disease and peripheral artery disease, which highlighted the need for better monitoring and intervention of cardiovascular diseases in populations with premature paternal death.

Number of standard modifiable risk factors and mortality in patients with first-presentation ST-segment elevation myocardial infarction: insights from China Acute Myocardial Infarction registry.

BACKGROUND: Recent publications reported a paradoxical finding that there was an inverse association between the number of standard modifiable risk factors (SMuRFs; smoking, hypertension, diabetes, and hyperlipidemia) and mortality in patients with myocardial infarction. However, the current evidence is only limited to those highly developed countries with advanced medical management systems. METHODS: The China Acute Myocardial Infarction registry is a prospective observational study including patients with acute myocardial infarction from three-level hospitals across 31 administrative regions throughout mainland China. A total of 16,228 patients with first-presentation ST-elevation myocardial infarction (STEMI) admitted to hospitals from January 2013 to September 2014 were enrolled in the current analysis. Cox proportional hazard models adjusting for baseline characteristics, clinical profiles at presentation, and in-hospital treatments were used to assess the association of the number of SMuRFs with all-cause mortality at 30 days after STEMI presentation. RESULTS: A total of 1918 (11.8%), 11,503 (70.9%), and 2807 (17.3%) patients had 0, 1-2, and 3-4 SMuRFs at presentation, respectively. Patients with fewer SMuRFs were older and more likely to be females, experienced longer pre-hospital delays, and were less likely to receive primary percutaneous coronary intervention and evidence-based medications. Compared with those without any SMuRF, patients with 1-2 SMuRFs and 3-4 SMuRFs were associated with an HR of 0.74 (95% CI, 0.63-0.87) and 0.63 (0.51-0.77) for all-cause mortality up to 30 days in the unadjusted model (Ptrend < 0.0001). However, after multivariate adjustment, the number of SMuRFs was positively associated with increased mortality risk (HR for 1-2 SMuRFs, 1.15 [0.95-1.39]; HR for 3-4 SMuRFs, 1.31 [1.02-1.68]; Ptrend = 0.03), and the association was only significant among patients admitted to hospitals beyond 12 h from onset (HR for 1-2 SMuRFs, 1.39 [1.03-1.87]; HR for 3-4 SMuRFs, 2.06 [1.41-3.01]) but not their counterparts (Pinteraction = 0.01). CONCLUSIONS: The increased crude mortality risk among patients without SMuRFs is explained by confounding factors related to their poor risk profiles (old age, longer pre-hospital delays, and poor clinical management). After multivariate adjustment, a higher risk-factor burden was associated with poor prognosis among patients with STEMI.

Effect of Cheese Intake on Cardiovascular Diseases and Cardiovascular Biomarkers.

BACKGROUND: A growing number of cohort studies revealed an inverse association between cheese intake and cardiovascular diseases, yet the causal relationship is unclear. OBJECTIVE: To assess the causal relationship between cheese intake, and cardiovascular diseases and cardiovascular biomarkers. METHODS: A two-sample Mendelian randomization (MR) analysis based on publicly available genome-wide association studies was employed to infer the causal relationship. The effect estimates were calculated using the random-effects inverse-variance-weighted method. RESULTS: Cheese intake per standard deviation increase causally reduced the risks of type 2 diabetes (odds ratio (OR) = 0.46; 95% confidence interval (CI), 0.34-0.63; p = 1.02 × 10-6), heart failure (OR = 0.62; 95% CI, 0.49-0.79; p = 0.0001), coronary heart disease (OR = 0.65; 95% CI, 0.53-0.79; p = 2.01 × 10-5), hypertension (OR = 0.67; 95% CI, 0.53-0.84; p = 0.001), and ischemic stroke (OR = 0.76; 95% CI, 0.63-0.91; p = 0.003). Suggestive evidence of an inverse association between cheese intake and peripheral artery disease was also observed. No associations were observed for atrial fibrillation, cardiac death, pulmonary embolism, or transient ischemic attack. The better prognosis associated with cheese intake may be explained by lower body mass index (BMI; effect estimate = -0.58; 95% CI, from -0.88 to -0.27; p = 0.0002), waist circumference (effect estimate = -0.49; 95% CI, from -0.76 to -0.23; p = 0.0003), triglycerides (effect estimate = -0.33; 95% CI, from -0.50 to -0.17; p = 4.91 × 10-5), and fasting glucose (effect estimate = -0.20; 95% CI, from -0.33 to -0.07; p = 0.0003). There was suggestive evidence of a positive association between cheese intake and high-density lipoprotein. No influences were observed for blood pressure or inflammation biomarkers. CONCLUSIONS: This two-sample MR analysis found causally inverse associations between cheese intake and type 2 diabetes, heart failure, coronary heart disease, hypertension, and ischemic stroke.

Clinical Outcomes Following Hemodynamic Parameter or Intravascular Imaging-Guided Percutaneous Coronary Intervention in the Era of Drug-Eluting Stents: An Updated Systematic Review and Bayesian Network Meta-Analysis of 28 Randomized Trials and 11,860 Patients.

Background: Coronary angiography (CAG) is the standard imaging modality for guiding percutaneous coronary interventions (PCI). Intracoronary imaging techniques such as intravascular ultrasound (IVUS) and optical coherence tomography (OCT), and hemodynamic parameter like fractional flow reserve (FFR) can overcome some limitations of CAG. Objective: We sought to explore the clinical outcomes of different PCI guidance modalities in the era of drug-eluting stent (DES). Methods: A network meta-analysis of 28 randomized trials and 11,860 patients undergoing different modalities-guided PCI in the era of DES was performed. Odds ratio (OR) with 95% credible interval (CrI) were calculated. Results: In comparison with CAG, IVUS was associated with a significant reduction in major adverse cardiovascular events (MACE, OR: 0.60; 95% CrI: 0.46-0.79), cardiovascular death (OR: 0.46; 95% CrI: 0.20-0.94), target vessel/lesion revascularization (TVR/TLR, OR: 0.55; 95% CrI: 0.41-0.74), and a trend toward decreased risk of stent thrombosis (OR: 0.44; 95% CrI: 0.17 to 1.00). FFR/quantitative flow ratio (QFR) could significantly reduce stroke compared with CAG, IVUS, and OCT/optical frequency domain imaging (OFDI). However, myocardial infarction (MI), all-cause death, stent thrombosis, and any revascularization presented similar risks for different PCI guidance modalities. Conclusion: In the era of DES, IVUS led to lower risks of MACE than CAG, which was mainly due to lower risks of cardiovascular death and TVR/TLR. A trend toward decreased risk of stent thrombosis was also observed with IVUS. Hemodynamic parameter (FFR/QFR)-guided PCI could significantly reduce the stroke risk compared with CAG, IVUS, and OCT/OFDI. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42021291442].

A Nomogram for Predicting Survival in Patients With Colorectal Cancer Incorporating Cardiovascular Comorbidities.

Background: Cardiovascular comorbidities (CVCs) affect the overall survival (OS) of patients with colorectal cancer (CRC). However, a prognostic evaluation system for these patients is currently lacking. Objectives: This study aimed to develop and validate a nomogram, which takes CVCs into account, for predicting the survival of patients with CRC. Methods: In total, 21,432 patients with CRC were recruited from four centers in China between January 2011 and December 2017. The nomogram was constructed, based on Cox regression, using a training cohort (19,102 patients), and validated using a validation cohort (2,330 patients). The discrimination and calibration of the model were assessed by the concordance index and calibration curve. The clinical utility of the model was measured by decision curve analysis (DCA). Based on the nomogram, we divided patients into three groups: low, middle, and high risk. Results: Independent risk factors selected into our nomogram for OS included age, metastasis, malignant ascites, heart failure, and venous thromboembolism, whereas dyslipidemia was found to be a protective factor. The c-index of our nomogram was 0.714 (95% CI: 0.708-0.720) in the training cohort and 0.742 (95% CI: 0.725-0.759) in the validation cohort. The calibration curve and DCA showed the reliability of the model. The cutoff values of the three groups were 68.19 and 145.44, which were also significant in the validation cohort (p < 0.001). Conclusion: Taking CVCs into account, an easy-to-use nomogram was provided to estimate OS for patients with CRC, improving the prognostic evaluation ability.