Development and Validation of a Predictive Model for Intracranial Haemorrhage in Patients on Direct Oral Anticoagulants.

BACKGROUND: Intracranial haemorrhage (ICH) poses a significant threat to patients on Direct Oral Anticoagulants (DOACs), with existing risk scores inadequately predicting ICH risk in these patients. We aim to develop and validate a predictive model for ICH risk in DOAC-treated patients. METHODS: 24,794 patients treated with a DOAC were identified in a province-wide electronic medical and health data platform in Tianjin, China. The cohort was randomly split into a 4:1 ratio for model development and validation. We utilized forward stepwise selection, Least Absolute Shrinkage and Selection Operator (LASSO), and eXtreme Gradient Boosting (XGBoost) to select predictors. Model performance was compared using the area under the curve (AUC) and net reclassification index (NRI). The optimal model was stratified and compared with the DOAC model. RESULTS: The median age is 68.0 years, and 50.4% of participants are male. The XGBoost model, incorporating six independent factors (history of hemorrhagic stroke, peripheral artery disease, venous thromboembolism, hypertension, age, low-density lipoprotein cholesterol levels), demonstrated superior performance in the development dateset. It showed moderate discrimination (AUC: 0.68, 95% CI: 0.64-0.73), outperforming existing DOAC scores (ΔAUC = 0.063, P = 0.003; NRI = 0.374, P < 0.001). Risk categories significantly stratified ICH risk (low risk: 0.26%, moderate risk: 0.74%, high risk: 5.51%). Finally, the model demonstrated consistent predictive performance in the internal validation. CONCLUSION: In a real-world Chinese population using DOAC therapy, this study presents a reliable predictive model for ICH risk. The XGBoost model, integrating six key risk factors, offers a valuable tool for individualized risk assessment in the context of oral anticoagulation therapy.

Triglyceride levels and risk of cardiovascular disease and all-cause mortality in Chinese adults younger than 40 years old: a prospective cohort study.

Background: Data on the associations of triglyceride (TG) levels with cardiovascular disease (CVD) and all-cause mortality mainly focused on the middle-aged or elderly population, with limited information available for younger adults. This study aimed to identify such associations among Chinese young adults. Methods: This study included Chinese adults younger than 40 years free of CVD, cancer, and lipid-lowering agents at baseline in the Kailuan study who were enrolled during 2006 through 2016. All participants were biennially followed up till December 2020. The enzymatic colorimetric method was used to measure baseline fasting TG. Participants were categorized into four groups by quartiles of TG, with the lowest quartile (Q1) as the reference group. The primary outcomes were CVD [composite of myocardial infarction (MI) and ischemic stroke] and all-cause mortality. CVD and mortality risks were estimated with Cox regression models. Results: A total of 43,882 participants were included. Their mean age was 30.6±5.56 years, and 80.2% were males. During a median follow-up of 11.2 years, 298 CVD events and 345 deaths occurred. The incidences of CVD and all-cause mortality were 0.67 and 0.76 per 1,000 person-years, respectively. Compared with individuals in the lowest quartile (Q1), participants in the highest quartile (Q4) showed a 126% higher risk of developing CVD [adjusted hazard ratio (HR) 2.26; 95% confidence interval (CI): 1.56 to 3.29; P=0.001] and a 61% higher risk of all-cause mortality (adjusted HR 1.61; 95% CI: 1.14 to 2.28; P=0.007). In addition, analyses of CVD subtypes showed that adjusted HRs (Q4 vs. Q1) were 3.25 (95% CI: 1.33 to 7.97; P=0.01) for MI, and 1.88 (95% CI: 1.16 to 3.04; P=0.01) for ischemic stroke. Conclusions: Among Chinese young adults, elevated fasting TG levels were associated with increased CVD and all-cause mortality risks.

Risk and effect modifiers for poor glycemic control among the chinese diabetic adults on statin therapy: the kailuan study.

BACKGROUND: Limited studies have investigated the association between statin therapy and poor glycemic control, especially in the Chinese diabetic population. METHODS: Two prospective diabetes cohorts were drawn from the Kailuan Cohort. In Cohort 1, linear regression models were used to evaluate the association between statin therapy and glycated hemoglobin (HbA1c) level change. In Cohort 2, new user design and conditional logistic models were used to assess associations between statin initiation and poor glycemic control which was a composite outcome comprised of hypoglycemic agent escalation and new-onset hyperglycemia. RESULTS: Among 11,755 diabetic patients with medication information, 1400 statin users and 1767 statin nonusers with repeated HbA1c measurements were included in Cohort 1 (mean age: 64.6 ± 10.0 years). After a median follow-up of 3.02 (1.44, 5.00) years, statin therapy was associated with higher HbA1c levels (ß: 0.20%; 95%CI: 0.05% to 0.34%). In Cohort 2, 1319 pairs of matched cases/controls were included (mean age: 61.6 ± 9.75 years). After a median follow-up of 4.87 (2.51, 8.42) years, poor glycemic control occurred in 43.0% of statin new users and 31.8% of statin nonusers (OR: 1.69; 95% CI: 1.32 to 2.17; P < 0.001). The statin-associated poor glycemic control risk was significantly higher among patients with lower body mass index (Pint = 0.089). Furthermore, a nonlinear association was observed between statin therapy duration and poor glycemic control (P = 0.003). CONCLUSIONS: Among Chinese diabetic adults, statin therapy was associated with a higher level of HbA1c, and a higher risk of hypoglycemic agent escalation and new-onset hyperglycemia, especially among those who had lower body mass index levels and longer statin therapy duration.

Patterns of Circulating Microbiota during the Acute Phase Following ST-Segment Elevation Myocardial Infarction Predict Long-Term Cardiovascular Events.

Limited information exists regarding whether circulating microbiota could predict long-term clinical outcomes following ST-segment elevation myocardial infarction (STEMI). A total of 244 consecutive patients with STEMI were followed for 2.8 years, and 64 first major adverse cardiovascular events (MACEs) were recorded. Both microbiota abundance [Corynebacterium tuberculostearicum (HR, 1.28; 95% CI, 1.03-1.58) and Staphylococcus aureus (S. aureus) (HR, 1.16; 95% CI, 1.02-1.33) ] and microbiota clusters (Cluster 2 versus Cluster 1: HR, 1.84; 95% CI, 1.04-3.27) could independently predict MACE. Furthermore, a model based on established independent predictors alone was significantly improved by the addition of different microbiota patterns. In addition, CD14++CD16+ monocytes (Mon2) had a significant mediation effect on the microbiota patterns → MACE association. The present study demonstrated that the abundance and clusters of circulating microbiota are associated with future adverse cardiovascular events independent of traditional risk factors, which were partially mediated by an increase in Mon2.

Third-Trimester Maternal Serum Chemerin and Hypertension After Preeclampsia: A Prospective Cohort Study.

Background Limited data are available for postpartum hypertension prediction after preeclampsia. Methods and Results We examined the association between maternal serum chemerin levels in patients with preeclampsia and blood pressure (BP) levels after delivery in a prospective birth cohort of 15 041 singleton pregnant women. A total of 310 cases among 322 patients with preeclampsia (follow-up rate, 96.3%) were followed up during a mean 2.8 years after delivery. Compared with matched uncomplicated controls (n=310), serum chemerin measured at ≈35 gestational weeks was significantly increased in preeclampsia (171.8±49.2 versus 140.2±53.5 ng/mL; P<0.01) and positively correlated with the occurrence of postpartum hypertension, defined as either BP ≥130/80 mm Hg (per 1-SD increase: odds ratio [OR], 4.01 [95% CI, 2.77-5.81]) or as BP ≥140/90 mm Hg (per 1-SD increase: OR, 1.70 [95% CI, 1.28-2.25]) in patients with preeclampsia. The addition of chemerin levels improved the predictive performance of the clinical variable-derived prediction models for postpartum hypertension (for BP ≥130/80 mm Hg: area under the curve, 0.903 [95% CI, 0.869-0.937], Δ area under the curve, 0.070, P<0.001; for BP ≥140/90 mm Hg: area under the curve, 0.852 [95% CI, 0.803-0.902], Δ area under the curve, 0.030, P=0.002). The decision curve analysis revealed a net benefit of the chemerin-based prediction model for postpartum BP ≥130/80 mm Hg. Conclusions This study provides the first evidence supporting the independent predictive role of third-trimester maternal chemerin levels for postpartum hypertension after preeclampsia. Future study is warranted for external validation of this finding.

Antithrombotic therapy and bleeding risk in the era of aggressive lipid-lowering: current evidence, clinical implications, and future perspectives.

ABSTRACT: The clinical efficacy of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in reducing major cardiovascular adverse events related to atherosclerotic cardiovascular disease (ASCVD) has been well established in recent large randomized outcome trials. Although the cardiovascular and all-cause mortality benefit of PCSK9i remains inconclusive, current cholesterol management guidelines have been modified toward more aggressive goals for lowering low-density lipoprotein cholesterol (LDL-C). Consequently, the emerging concept of "the lower the better" has become the paradigm of ASCVD prevention. However, there is evidence from observational studies of a U-shaped association between baseline LDL-C levels and all-cause mortality in population-based cohorts. Among East Asian populations, low LDL-C was associated with an increased risk for hemorrhagic stroke in patients not on antithrombotic therapy. Accumulating evidence showed that low LDL-C was associated with an enhanced bleeding risk in patients on dual antiplatelet therapy following percutaneous coronary intervention. Additionally, low LDL-C was associated with a higher risk for incident atrial fibrillation and thereby, a possible increase in the risk for intracranial hemorrhage after initiation of anticoagulation therapy. The mechanism of low-LDL-C-related bleeding risk has not been fully elucidated. This review summarizes recent evidence of low-LDL-C-related bleeding risk in patients on antithrombotic therapy and discusses potential measures for reducing this risk, underscoring the importance of carefully weighing the pros and cons of aggressive LDL-C lowering in patients on antithrombotic therapy.

Renin-angiotensin system inhibition and in-hospital mortality in acute coronary syndrome patients with advanced renal dysfunction: findings from CCC-ACS project and a nationwide electronic health record-based cohort in China.

AIMS: In acute coronary syndrome (ACS) patients without advanced renal dysfunction [estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2], early (within 24 h of admission) angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) is the guideline-directed medical therapy. The clinical efficacy of early ACEI/ARB therapy among ACS patients with advanced renal dysfunction remains unclear. METHODS AND RESULTS: Among 184 850 ACS patients hospitalized from July 2014 to December 2018 in the Chinese National Electronic Disease Surveillance System Platform (CNEDSSP) cohort and 113 650 ACS patients enrolled from November 2014 to December 2019 in the Improving Care for Cardiovascular Disease in China-ACS Project (CCC-ACS) cohort, we identified 3288 and 3916 ACS patients with admission eGFR < 30 mL/min/1.73 m2 [2647 patients treated with ACEI/ARB (36.7%)], respectively. After 1:1 propensity score matching (PSM) in each cohort, Kaplan-Meier analysis showed that early ACEI/ARB use was associated with a 39% [hazard ratio (HR): 0.61, 95% confidence interval (95% CI): 0.45-0.82] and a 34% (HR: 0.66, 95% CI: 0.46-0.95) reduction in in-hospital mortality in CNEDSSP and CCC-ACS cohorts, respectively, which was consistent in multiple sensitivity analyses. A random effect meta-analysis of the two cohorts after PSM revealed a 32% reduction (risk ratio: 0.68, 95% CI: 0.55-0.84) in in-hospital mortality among ACEI/ARB users. CONCLUSIONS: Based on two nationwide cohorts in China in contemporary practice, we demonstrated that ACEI/ARB therapy initiated within 24 h of admission is associated with a reduction in in-hospital mortality in ACS patients with advanced renal dysfunction. CLINICAL TRIAL REGISTRATION: CCC-ACS project was registered at URL: https://www.clinicaltrials.gov. (Unique identifier: NCT02306616).

Early Guideline-Directed Medical Therapy and in-Hospital Major Bleeding Risk in ST-Elevation Myocardial Infarction Patients Treated with Percutaneous Coronary Intervention: Findings from the CCC-ACS Project.

PURPOSE: Previous reports demonstrated a bleeding avoidance potential of angiotensin converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) and ß-blocker. It remains unclear whether early guideline-directed medical therapy [GDMT, i.e., the combined use of ß-blocker, angiotensin converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) and statin] confers protection against bleeding in the setting of high-intensity antithrombotic therapy. METHODS: We assessed associations between the use of early (within the first 24 h) GDMT and in-hospital major bleeds, ischemic events and mortality among ST-elevation myocardial infarction (STEMI) patients treated with percutaneous coronary intervention (PCI) in the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome project. RESULTS: Among 34,538 STEMI patients without contra-indications to GDMT and eligible for analysis, 35.5% received early GDMT. In a 1-to-2 propensity-score matched cohort, compared with non-early GDMT, early GDMT was associated with a 25% reduction in major bleeds [odds ratio (OR) 0.75, 95% confidence interval (CI) 0.60-0.94], with parallel reductions in ischemic events (OR 0.60, 95%CI 0.45-0.78) and in-hospital mortality (OR 0.43, 95%CI 0.31-0.61). Early GDMT-associated reduction in major bleeds was generally consistently observed across different major bleeding definitions and in sensitivity analyses. Additionally, no significant interaction was observed in subgroup analyses. CONCLUSION: In a large nationwide registry, early initiation of GDMT was associated with reduced risk for in-hospital major bleeds in STEMI patients treated with PCI. To improve the outcome of STEMI, further effort should be made to reinforce the early use of GDMT in this patient population.

Association Between Platelet Glycoprotein IIb/IIIa Inhibition and In-Hospital Outcomes in ST-Elevation Myocardial Infarction Patients Treated with Coronary Thrombus Aspiration: Findings from the CCC-ACS Project.

PURPOSE: Thrombus aspiration in ST-elevation myocardial infarction (STEMI) with high thrombus burden did not improve clinical outcomes. The clinical efficacy of the bailout use of platelet glycoprotein IIb/IIIa inhibitors (GPIs) in this clinical scenario remains unknown. METHODS: We assessed associations between GPI use and in-hospital major bleeds, ischemic events, and mortality among STEMI patients treated with percutaneous coronary intervention (PCI) and thrombus aspiration in a nationwide acute coronary syndrome registry (the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome project). RESULTS: A total of 5896 STEMI patients who received thrombus aspiration were identified, among which 56.3% received GPI therapy. In a 1-to-1 propensity-score-matched cohort, compared with STEMI patients not treated with GPI, GPI use was associated with a 69% increase in major in-hospital bleeds, with an odds ratio (OR) of 1.69, a 95% confidence interval (CI) of 1.08 to 2.65, and a nonsignificant reduction in ischemic events (OR: 0.61, 95% CI: 0.36 to 1.06), as well as a neutral effect on mortality (OR: 0.93, 95% CI: 0.55 to 1.58). However, among patients aged < 60 years, GPI use was associated with a reduction in ischemic events (OR: 0.27, 95% CI: 0.08 to 0.98), and no significant increase in major bleeds was observed. CONCLUSION: In a nationwide registry, routine use of GPI following thrombus aspiration was not associated with reduced in-hospital ischemic events and mortality but at the cost of increased major bleeding. However, for patients aged < 60 years, there may be a potential net benefit.

Early Statin Therapy and In-Hospital Outcomes in Acute Coronary Syndrome Patients Presenting with Advanced Killip Class at Admission: Findings from the CCC-ACS Project.

PURPOSE: It is unknown if acute coronary syndrome (ACS) patients presenting with advanced Killip class (III/IV) would benefit from early statin therapy. Therefore, we aimed to explore the relationship between statin therapy within the first 24 h of medical contact and in-hospital outcomes in this patient population in a nationwide registry. METHOD: In the Improving Care for Cardiovascular Disease in China-ACS project, among ACS patients presenting with Killip class III/IV, we performed the following three analyses: (i) the associations between early statin therapy and risks for in-hospital mortality and ischaemic events; (ii) the dose effect of statins on mortality and (iii) the interaction between low-density lipoprotein cholesterol (LDL-C) levels and statins on mortality. RESULT: Among 104,516 ACS patients, 12,149 presented with advanced Killip class and 89.3% received early statins. Multivariable-adjusted logistic regression models revealed a 69% reduction in mortality in the statin group (adjusted odds ratio [OR] 0.31; 95% confidence interval [CI] 0.25-0.39), parallel with a reduction in ischaemic events (adjusted OR 0.50, 95% CI 0.33-0.74), compared with those not receiving early statins, which was consistent in multiple sensitivity analyses. Additionally, the protective association of early statins on in-hospital mortality was observed even among patients that received a low-to-moderate dose. Finally, the short-term survival benefit of early statins was independent of LDL-C. CONCLUSION: In a nationwide ACS registry, statin therapy initiated within the first 24 h of medical contact was associated with a reduced risk of in-hospital mortality in ACS patients presenting with advanced Killip class.

Long-term risks for cardiovascular disease and mortality across the glycaemic spectrum in a male-predominant Chinese cohort aged 75 years or older: the Kailuan study.

BACKGROUND: Ageing and diabetes are growing global health burdens. The current understanding of cardiovascular disease (CVD) and mortality risk across the glycaemic spectrum in older populations is limited. OBJECTIVES: This study sought to characterise CVD and all-cause mortality risk across the glycaemic spectrum among Chinese adults aged 75 years or older in a community-based setting over10 years. METHODS: The 3,989 adults in the Kailuan Study were aged over 75 years (median age was 79 years [interquartile range: 76-82]; 2,785 normoglycaemic, 691 prediabetic and 513 diabetic, determined by fasting blood glucose levels) at baseline, predominantly male (92.9% male) and followed until December 2019. Time-varying Cox regression and competing-risk models were used to examine the hazard ratio (HR) of incident CVD and mortality across the glycaemic exposures. RESULTS: During median follow-up of 11.3 years, 433 first CVD and 2,222 deaths were recorded. Compared with normoglycaemia, multivariable-adjusted models revealed the following: (i) prediabetes was not associated with future risks for CVD (HR: 1.17; 95% CI 0.82-1.69) and all-cause mortality (HR 1.06; 95% CI 0.70-1.60); (ii) diabetes-associated enhanced risks for CVD and all-cause mortality were mainly confined to those exhibiting low-grade inflammation (high-sensitivity C-reactive protein ≥2.0 mg/L) levels. The results were consistent after multiple sensitivity analyses. CONCLUSIONS: Among a male-predominant Chinese population aged 75 years or older, compared with normoglycaemic participants, prediabetes was not associated with an enhanced 10-year CVD and all-cause mortality risk, and diabetes-associated enhanced 10-year risk was mainly confined to individuals exhibiting low-grade inflammation.

Revisiting the lipid paradox in ST-elevation myocardial infarction in the Chinese population: findings from the CCC-ACS project.

AIMS: Previous observations revealed a negative association between low-density lipoprotein cholesterol (LDL-C) and clinical outcomes following myocardial infarction, i.e., the lower level the higher mortality, which was referred to as lipid paradox. We sought to re-evaluate this association in ST-elevation myocardial infarction (STEMI) in contemporary practice. METHODS AND RESULTS: We examined the association between admission LDL-C and in-hospital mortality among 44 563 STEMI patients enrolled from 2014 to 2019 in a nationwide registry in China. A total of 43 covariates, which were temporally classified into the following three domains were used for adjustment: (i) pre-admission characteristics; (ii) percutaneous coronary intervention (PCI)-related variables; and (iii) other in-hospital medications. In-hospital mortality was 2.01% (897/44 563). When no covariate adjustment was performed, an inversely 'J-shaped' curve was observed between admission LDL-C levels and in-hospital mortality by restricted cubic spline in logistic regression, with a threshold value of <75 mg/dL that associated with increased risk for in-hospital mortality. However, a gradual attenuation for this association was noted when step-wise adjustments were performed, with the threshold values for LDL-C decreasing from 75 mg/dL to 70 mg/dL after accounting for pre-admission characteristics, further to 65 mg/dL after accounting for PCI-related variables, and finally to no statistical association after further adjustment for other in-hospital medications. CONCLUSIONS: In a nationwide registry in China, our findings do not support the lipid paradox in terms of in-hospital mortality in STEMI patients in contemporary practice. Previous findings in this scenario are possibly due to inadequate control for confounders.

Thrombosis and Coagulopathy in COVID-19: Current Understanding and Implications for Antithrombotic Treatment in Patients Treated With Percutaneous Coronary Intervention.

Coronavirus disease 2019 (COVID-19), a respiratory syndrome, is a global pandemic. Therefore, there is an urgent need to explore mechanisms implicated in the pathogenesis of the disease. Clinical and autopsy studies show a complex chain of events preceding COVID-19-related death. The disease is characterized by endothelial dysfunction, platelet activation, thrombosis, coagulopathy, and multiple organ failure. Globally, millions of patients with coronary heart disease undergo percutaneous coronary intervention (PCI) each year. These patients undergo high-intensity antithrombotic therapy during hospitalization and dual antiplatelet therapy (DAPT) for at least 6 months post PCI. COVID-19 is characterized by changes in platelet counts. Treatment of ischemic events that occur during stent implantation is associated with bleeding complications in patients following PCI complicated by COVID-19. This review summarizes recent progress in activation status and levels of COVID-19-related platelet changes. These findings will provide information on the effectiveness of antithrombotic therapy for the management of platelet changes in COVID-19 patients.