Association of cardiometabolic multimorbidity with all-cause and cardiovascular disease mortality among Chinese hypertensive patients.

BACKGROUND: Hypertension usually clusters with multiple comorbidities. However, the association between cardiometabolic multimorbidity (CMM) and mortality in hypertensive patients is unclear. This study aimed to investigate the association between CMM and all-cause and cardiovascular disease (CVD) mortality in Chinese patients with hypertension. METHODS: The data used in this study were from the China National Survey for Determinants of Detection and Treatment Status of Hypertensive Patients with Multiple Risk Factors (CONSIDER), which comprised 5006 participants aged 19-91 years. CMM was defined as the presence of one or more of the following morbidities: diabetes mellitus, dyslipidemia, chronic kidney disease, coronary heart disease, and stroke. Cox proportional hazard models were used to calculate the hazard ratios (HR) with 95% CI to determine the association between the number of CMMs and both all-cause and CVD mortality. RESULTS: Among 5006 participants [mean age: 58.6 ± 10.4 years, 50% women (2509 participants)], 76.4% of participants had at least one comorbidity. The mortality rate was 4.57, 4.76, 8.48, and 16.04 deaths per 1000 person-years in hypertensive patients without any comorbidity and with one, two, and three or more morbidities, respectively. In the fully adjusted model, hypertensive participants with two cardiometabolic diseases (HR = 1.52, 95% CI: 1.09-2.13) and those with three or more cardiometabolic diseases (HR = 2.44, 95% CI: 1.71-3.48) had a significantly elevated risk of all-cause mortality. The findings were similar for CVD mortality but with a greater increase in risk magnitude. CONCLUSIONS: In this study, three-fourths of hypertensive patients had CMM. Clustering with two or more comorbidities was associated with a significant increase in the risk of all-cause and cardiovascular mortality among hypertensive patients, suggesting more intensive treatment and control in this high-risk patient group.

The association between the AIP and undiagnosed diabetes in ACS patients with different body mass indexes and LDL-C levels: findings from the CCC-ACS project.

BACKGROUND: The atherogenic index of plasma (AIP) has been demonstrated to be significantly associated with the incidence of prediabetes and diabetes. This study aimed to investigate the association between the AIP and undiagnosed diabetes in acute coronary syndrome (ACS) patients. METHODS: Among 113,650 ACS patients treated with coronary angiography at 240 hospitals in the Improving Care for Cardiovascular Disease in China-ACS Project from 2014 to 2019, 11,221 patients with available clinical and surgical information were included. We analyzed these patients' clinical characteristics after stratification according to AIP tertiles, body mass index (BMI) and low-density lipoprotein cholesterol (LDL-C) levels. RESULTS: The AIP was independently associated with a greater incidence of undiagnosed diabetes. The undiagnosed diabetes was significantly greater in the T3 group than in the T1 group after adjustment for confounders [T3 OR 1.533 (1.199-1.959) p < 0.001]. This relationship was consistent within normal weight patients and patients with an LDL-C level ≥ 1.8 mmol/L. In overweight and obese patients, the AIP was significantly associated with the incidence of undiagnosed diabetes as a continuous variable after adjustment for age, sex, and BMI but not as a categorical variable. The area under the receiver operating characteristic curve (AUC) of the AIP score, triglyceride (TG) concentration, and HDL-C concentration was 0.601 (0.581-0.622; p < 0.001), 0.624 (0.603-0.645; p < 0.001), and 0.493 (0.472-0.514; p = 0.524), respectively. A nonlinear association was found between the AIP and the incidence of undiagnosed diabetes in ACS patients (p for nonlinearity < 0.001), and this trend remained consistent between males and females. The AIP may be a negative biomarker associated with undiagnosed diabetes ranging from 0.176 to 0.738. CONCLUSION: The AIP was significantly associated with the incidence of undiagnosed diabetes in ACS patients, especially in those with normal weight or an LDL-C level ≥ 1.8 mmol/L. A nonlinear relationship was found between the AIP and the incidence of undiagnosed diabetes, and this trend was consistent between male and female patients. The AIP may be a negative biomarker associated with undiagnosed diabetes and ranges from 0.176 to 0.738.

Percutaneous Coronary Intervention in Acute Coronary Syndrome with Mild-to-Moderate Thrombocytopenia.

BACKGROUND: Baseline thrombocytopenia is commonly observed in patients with acute coronary syndrome (ACS) requiring percutaneous coronary intervention (PCI). AIM: The purpose of this analysis was to investigate safety and effectiveness of PCI in ACS patients with baseline mild-to-moderate thrombocytopenia. METHODS: The data were collected from the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome project. A total of 50,009 ACS patients were recruited between July 2017 and December 2019. Among them, there were 6,413 patients with mild-to-moderate thrombocytopenia, defined as a platelet count of ≥50 × 109/L and <150 × 109/L on admission. The primary outcome was in-hospital net adverse clinical events (NACE), consisting of major adverse cardiac events (MACE) and major bleeding events. The associations between PCI and in-hospital outcomes were analyzed by inverse probability treatment weighting (IPTW) method. RESULTS: PCI was performed in 4,023 of 6,413 patients (62.7%). The IPTW analysis showed that PCI was significantly associated with a reduced risk of in-hospital MACE (odd ratio [OR]: 0.45; 95% confidence interval [CI]: 0.31-0.67; p < 0.01) and NACE (OR: 0.59; 95% CI: 0.42-0.83; p < 0.01). PCI was also associated with an increased risk of any bleeding (OR: 1.56; 95% CI: 1.09-2.22; p = 0.01) and minor bleeding (OR: 1.52; 95% CI: 1.00-2.30; p = 0.05), but not major bleeding (OR: 1.51; 95% CI: 0.76-2.98; p = 0.24). CONCLUSION: Compared with medical therapy alone, PCI is associated with better in-hospital outcomes in ACS patients with mild-to-moderate thrombocytopenia. Further studies with long-term prognosis are needed.

Oral anti-coagulants use in Chinese hospitalized patients with atrial fibrillation.

BACKGROUND: Oral anti-coagulants (OAC) are the intervention for the prevention of stroke, which consistently improve clinical outcomes and survival among patients with atrial fibrillation (AF). The main purpose of this study is to identify problems in OAC utilization among hospitalized patients with AF in China. METHODS: Using data from the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation (CCC-AF) registry, guideline-recommended OAC use in eligible patients was assessed. RESULTS: A total of 52,530 patients with non-valvular AF were enrolled from February 2015 to December 2019, of whom 38,203 were at a high risk of stroke, 9717 were at a moderate risk, and 4610 were at a low risk. On admission, only 20.0% (6075/30,420) of patients with a diagnosed AF and a high risk of stroke were taking OAC. The use of pre-hospital OAC on admission was associated with a lower risk of new-onset ischemic stroke/transient ischemic attack among the diagnosed AF population (adjusted odds ratio: 0.54, 95% confidence interval: 0.43-0.68; P  <0.001). At discharge, the prescription rate of OAC was 45.2% (16,757/37,087) in eligible patients with high stroke risk and 60.7% (2778/4578) in eligible patients with low stroke risk. OAC utilization in patients with high stroke risk on admission or at discharge both increased largely over time (all P  <0.001). Multivariate analysis showed that OAC utilization at discharge was positively associated with in-hospital rhythm control strategies, including catheter ablation (adjusted odds ratio [OR] 11.63, 95% confidence interval [CI] 10.04-13.47; P <0.001), electronic cardioversion (adjusted OR 2.41, 95% CI 1.65-3.51; P <0.001), and anti-arrhythmic drug use (adjusted OR 1.45, 95% CI 1.38-1.53; P <0.001). CONCLUSIONS: In hospitals participated in the CCC-AF project, >70% of AF patients were at a high risk of stroke. Although poor performance on guideline-recommended OAC use was found in this study, over time the CCC-AF project has made progress in stroke prevention in the Chinese AF population.Registration:ClinicalTrials.gov, NCT02309398.

Asymptomatic atrial fibrillation among hospitalized patients: clinical correlates and in-hospital outcomes in Improving Care for Cardiovascular Disease in China-Atrial Fibrillation.

AIMS: The clinical correlates and outcomes of asymptomatic atrial fibrillation (AF) in hospitalized patients are largely unknown. We aimed to investigate the clinical correlates and in-hospital outcomes of asymptomatic AF in hospitalized Chinese patients. METHODS AND RESULTS: We conducted a cross-sectional registry study of inpatients with AF enrolled in the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation Project between February 2015 and December 2019. We investigated the clinical characteristics of asymptomatic AF and the association between the clinical correlates and the in-hospital outcomes of asymptomatic AF. Asymptomatic and symptomatic AF were defined according to the European Heart Rhythm Association score. Asymptomatic patients were more commonly males (56.3%) and had more comorbidities such as hypertension (57.4%), diabetes mellitus (18.6%), peripheral artery disease (PAD; 2.3%), coronary artery disease (55.5%), previous history of stroke/transient ischaemic attack (TIA; 17.9%), and myocardial infarction (MI; 5.4%); however, they had less prevalent heart failure (9.6%) or left ventricular ejection fractions ≤40% (7.3%). Asymptomatic patients were more often hospitalized with a non-AF diagnosis as the main diagnosis and were more commonly first diagnosed with AF (23.9%) and long-standing persistent/permanent AF (17.0%). The independent determinants of asymptomatic presentation were male sex, long-standing persistent AF/permanent AF, previous history of stroke/TIA, MI, PAD, and previous treatment with anti-platelet drugs. The incidence of in-hospital clinical events such as all-cause death, ischaemic stroke/TIA, and acute coronary syndrome (ACS) was higher in asymptomatic patients than in symptomatic patients, and asymptomatic clinical status was an independent risk factor for in-hospital all-cause death, ischaemic stroke/TIA, and ACS. CONCLUSION: Asymptomatic AF is common among hospitalized patients with AF. Asymptomatic clinical status is associated with male sex, comorbidities, and a higher risk of in-hospital outcomes. The adoption of effective management strategies for patients with AF should not be solely based on clinical symptoms.

In-hospital therapies and determinants of treatment strategy selection in patients with atrial fibrillation and left ventricular systolic dysfunction in China: a retrospective study based on the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation (CCC-AF) project, 2015-2019.

OBJECTIVES: The optimal treatment strategy remains debatable in patients with atrial fibrillation (AF) and heart failure. Our objectives were to summarise in-hospital therapies and determine factors associated with treatment strategy selections. DESIGN: A retrospective study analysing the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation (CCC-AF) project from 2015 to 2019. SETTING: The CCC-AF project included patients from 151 tertiary and 85 secondary hospitals across 30 provinces in China. PARTICIPANTS: Patients with AF and left ventricular systolic dysfunction (LVSD, defined as left ventricular ejection fraction<50%) were included, with 5560 patients in the study sample. METHODS: Patients were classified by treatment strategies. In-hospital treatments and trends of therapies were analysed. Multiple logistic regression models were used to find determinants of treatment strategies. RESULTS: Rhythm control therapies were used in 16.9% of patients with no significant trends (p trend=0.175). Catheter ablation was used in 5.5% of patients, increasing from 3.3% in 2015 to 6.6% in 2019 (p trend<0.001). Factors negatively associated with rhythm control included increased age (OR 0.973, 95% CI 0.967 to 0.980), valvular AF (OR 0.618, 95% CI 0.419 to 0.911), AF types (persistent: OR 0.546, 95% CI 0.462 to 0.645; long-standing persistent: OR 0.298, 95% CI 0.240 to 0.368), larger left atrial diameters (OR 0.966, 95% CI 0.957 to 0.976) and higher Charlson Comorbidity Index scores (CCI 1-2: OR 0.630, 95% CI 0.529 to 0.750; CCI≥3: OR 0.551, 95% CI 0.390 to 0.778). Higher platelet counts (OR 1.025, 95% CI 1.013 to 1.037) and prior rhythm control attempts (electrical cardioversion: OR 4.483, 95% CI 2.369 to 8.483; catheter ablation: OR 4.957, 95% CI 3.072 to 7.997) were positively associated with rhythm control strategies. CONCLUSION: In China, non-rhythm control strategy remained the dominant choice in patients with AF and LVSD. Age, AF types, prior treatments, left atrial diameters, platelet counts and comorbidities were major determinants of treatment strategies. Guideline-adherent therapies should be further promoted. STUDY REGISTRATION NUMBER: NCT02309398.

Lipoprotein(a) Is Associated With the Progression and Vulnerability of New-Onset Carotid Atherosclerotic Plaque.

BACKGROUND: Although important progress has been made in understanding Lp(a) (lipoprotein[a])-mediated stroke risk, the contribution of Lp(a) to the progression of vulnerable plaque features associated with stroke risk remains unclear. This study aims to evaluate whether Lp(a) is associated with carotid plaque progression, new-onset plaque features, and plaque vulnerability in a prospective community-based cohort study. METHODS: Baseline Lp(a) levels were measured using latex-enhanced turbidimetric immunoassay among 804 participants aged 45 to 74 years and free of cardiovascular disease in the Chinese Multi-provincial Cohort Study-Beijing project. Carotid atherosclerosis was measured twice by B-mode ultrasonography over a 10-year interval during the 2002 and 2012 surveys to assess the progression of total, vulnerable and stable plaques, and plaque vulnerability. The total plaque area and plaque vulnerability score were calculated. RESULTS: The median baseline Lp(a) level was 10.20 mg/dL (interquartile range, 6.20 to 17.18 mg/dL). Modified Poisson regression analysis showed that Lp(a) ≥50 mg/dL was significantly associated with 10-year progression of total carotid plaque (relative risk [RR], 1.41 [95% CI, 1.21-1.64]; E-value=2.17), vulnerable plaque (RR, 1.93 [95% CI, 1.54-2.41]), and stable plaque (RR, 1.51 [95% CI, 1.11-2.07]) compared with Lp(a) <50 mg/dL. Moreover, among participants without plaque at baseline, Lp(a) ≥50 mg/dL was related to an increased total plaque area (ß=0.36 [95% CI, 0.06-0.65]; P=0.018) and increased plaque vulnerability score (ß=0.30 [95% CI, 0.01-0.60]; P=0.045) in multivariable linear regression. CONCLUSIONS: Elevated Lp(a) levels were associated with 10-year carotid plaque progression and plaque vulnerability, providing a basis for Lp(a) as a treatment target for stroke prevention.

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.

Endovascular Repair Versus Open Surgical Repair for Complex Abdominal Aortic Aneurysms: A Systematic Review and Meta-Analysis.

BACKGROUND: The purpose of this systematic review and meta-analysis was to compare the short and long-term outcomes of endovascular repair (ER) versus open surgical repair (OSR) for complex abdominal aortic aneurysms (CAAAs), using propensity-matched and nonpropensity-matched methods. METHODS: PubMed, OVID, Embase, ELSEVIER and Cochrane library were searched for the studies that compared ER versus OSR for CAAAs from January 1999 to December 2020. CAAAs were defined as short neck, juxtarenal, pararenal and suprarenal abdominal aortic aneurysms. The primary outcomes were 30-day mortality, 30-day reintervention, medium and long-term survival. We pooled outcomes of original studies and also performed subgroup analyses using RevMan. The analysis of statistical heterogeneity was performed with STATA 16.0. RESULTS: A total of 21 studies with 12,049 patients (3847 ERs, 8202 OSRs) were included in this meta-analysis. In general, the patients undergoing ER were significantly older and likely to be man; more common with diabetes mellitus, congestive heart failure, renal failure, but smaller aortic aneurysms. In the nonpropensity-matched subgroup analysis of ER versus OSR, ER was associated with significantly decreased 30-day mortality (odds ratio [OR]: 0.60; 95% confidence interval [CI]: 0.49-0.74; P<0.001; I2 = 4%) and 30-day reintervention (OR: 0.59; 95% CI: 0.40-0.87; P = 0.007; I2 = 56%); lower rate of long-term survival (hazard ratio [HR]: 1.73; 95% CI: 1.21-2.47; P = 0.002; I2 = 0%); less perioperative comorbidities including myocardial infarction, arrhythmia, acute kidney injury, permanent dialysis, wound complications, bowel ischemia; and shorter hospital length of stay. In the propensity-matched subgroup, ER was associated with poorer long-term survival (HR: 1.80; 95% CI: 1.06-3.06; P = 0.03; I2 = 0%), higher incidences of lower extremity ischemia (OR: 12.25; 95% CI: 1.54-97.48; P = 0.02; I2 = 16%) and renal artery restenosis (OR: 7.63; 95% CI: 1.35-43.24; P = 0.02). However, there was no significant difference in 30-day mortality (OR: 1.31; 95% CI: 0.65-2.66; P = 0.45; I2 = 0%), 30-day reintervention (OR: 1.58; 95% CI: 0.62-4.03; P = 0.34; I2 = 26%), mid-term survival (HR: 1.03; 95% CI: 0.30-3.56; P = 0.96; I2 = 0%) between ER and OSR groups. CONCLUSIONS: Our analyses suggest that OSR of CAAAs, compared with ER, is associated with improved long-term survival without increasing of perioperative deaths. ER may be considered in the patients who are high-risk for open repair.

Reduced serum calcium is associated with a higher risk of retinopathy in non-diabetic individuals: The Chinese Multi-provincial Cohort Study.

Aims: As a common micro-vascular disease, retinopathy can also present in non-diabetic individuals and increase the risk of clinical cardiovascular disease. Understanding the relationship between serum calcium and retinopathy would contribute to etiological study and disease prevention. Methods: A total of 1836 participants (aged 55-84 years and diabetes-free) from the Chinese Multi-Provincial Cohort Study-Beijing Project in 2012 were included for analyzing the relation between serum calcium level and retinopathy prevalence. Of these, 1407 non-diabetic participants with data on serum calcium in both the 2007 and 2012 surveys were included for analyzing the association of five-year changes in serum calcium with retinopathy risk. The retinopathy was determined from retinal images by ophthalmologists and a computer-aided system using convolutional neural network (CNN). The association between serum calcium and retinopathy risk was assessed by multivariate logistic regression. Results: Among the 1836 participants (male, 42.5%), 330 (18.0%) had retinopathy determined by CNN. After multivariate adjustment, the odds ratio (OR) comparing the lowest quartiles (serum calcium < 2.38 mmol/L) to the highest quartiles (serum calcium ≥ 2.50 mmol/L) for the prevalence of retinopathy determined by CNN was 1.58 (95% confidence interval [CI]: 1.10 - 2.27). The findings were consistent with the result discerned by ophthalmologists, and either by CNN or ophthalmologists. These relationships are preserved even in those without metabolic risk factors, including hypertension, high hemoglobin A1c, high fasting blood glucose, or high low-density lipoprotein cholesterol. Over 5 years, participants with the sustainably low levels of serum calcium (OR: 1.58; 95%CI: 1.05 - 2.39) and those who experienced a decrease in serum calcium (OR: 1.56; 95%CI: 1.04 - 2.35) had an increased risk of retinopathy than those with the sustainably high level of serum calcium. Conclusions: Reduced serum calcium was independently associated with an increased risk of retinopathy in non-diabetic individuals. Moreover, reduction of serum calcium could further increase the risk of retinopathy even in the absence of hypertension, high glucose, or high cholesterol. This study suggested that maintaining a high level of serum calcium may be recommended for reducing the growing burden of retinopathy. Further large prospective studies will allow more detailed information.

Inter-hospital transfer in patients with acute myocardial infarction in China: Findings from the improving care for cardiovascular disease in China-acute coronary syndrome project.

Background: Little is known about the current scenario of inter-hospital transfer for patients with acute myocardial infarction (AMI) in China. Methods: From November 2014 to December 2019, 94,623 AMI patients were enrolled from 241 hospitals in 30 provinces in China. We analyzed the pattern of inter-hospital transfer, and compared in-hospital treatments and outcomes between transferred patients and directly admitted patients. Results: Of these patients, 40,970 (43.3%) were transferred from hospitals that did not provide percutaneous coronary intervention (PCI). The proportion of patients who were transferred from non-PCI hospital was 46.3% and 11.9% (P < 0.001) in tertiary hospitals and secondary hospitals, respectively; 56.2% and 37.3% (P < 0.001) in hospitals locating in low-economic regions and affluent areas, respectively. Compared with directly admitted patients, transferred patients had lower rates of reperfusion for STEMI (57.8% vs. 65.2%, P < 0.001) and timely PCI for NSTEMI (34.7%vs. 41.1%, P < 0.001). The delay for STEMI patients were long, with 6.5h vs. 4.5h from symptom onset to PCI for transferred and directly admitted patients, respectively. The median time-point was 9 days for in-hospital outcomes. Compared with direct admission, the hazard ratios and 95% confidence intervals associated with inter-hospital transfer were 0.87 (0.75-1.01) and 0.87 (0.73-1.03) for major adverse cardiovascular events and total mortality, respectively, in inverse probability of treatment weighting models in patients with STEMI, and 1.02 (0.71-1.48) and 0.98 (0.70-1.35), respectively, in patients with NSTEMI. Conclusion: More than 40% of the hospitalized AMI patients were transferred from non-PCI-capable hospitals in China. Further strategies are needed to enhance the capability of revascularization and reduce the inequality in management of AMI.

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.

In-hospital outcomes of ticagrelor versus clopidogrel in patients 75 years or older with acute coronary syndrome: findings from the Improving Care for Cardiovascular Disease in China (CCC)-Acute Coronary Syndrome Project.

BACKGROUND: The evidence for the comparative effectiveness and safety of ticagrelor versus clopidogrel in older patients with acute coronary syndrome (ACS) is limited, especially in the acute phase of ACS. This study aimed to compare the in-hospital outcomes of ticagrelor versus clopidogrel in older patients with ACS. METHODS: Hospitalised ACS patients aged ≥75 years who were recruited to the Improving Care for Cardiovascular Disease in China-ACS project between November 2014 and December 2019 and received aspirin and P2Y12 receptor inhibitors within 24 h after first medical contact were included. The primary outcomes were in-hospital major adverse cardiovascular events (MACE) and major bleeding. Multivariable Cox regression was performed to evaluate the comparative effectiveness and safety of ticagrelor and clopidogrel. Inverse probability of treatment weighting (IPTW) and propensity score matching analyses were performed to evaluate the robustness of the results. RESULTS: Of 18,244 ACS patients, 18.5% received ticagrelor. Multivariable-adjusted analysis revealed comparable risks of in-hospital MACE between patients receiving ticagrelor and clopidogrel (hazard ratio [HR] 1.12, 95% confidence interval [CI] 0.92-1.35). However, ticagrelor use was associated with 45% higher risk of in-hospital major bleeding compared with clopidogrel use (HR 1.45, 95% CI 1.09-1.91). Similar results were found in the IPTW analysis. CONCLUSIONS: ACS patients aged ≥75 years receiving ticagrelor during the acute phase had similar risk of in-hospital MACE, but higher risk of in-hospital major bleeding compared with those receiving clopidogrel. More evidence is needed to guide the use of P2Y12 receptor inhibitors during hospitalisation in older patients with ACS. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02306616.

The Level of Remnant Cholesterol and Implications for Lipid-Lowering Strategy in Hospitalized Patients with Acute Coronary Syndrome in China: Findings from the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome Project.

Elevated remnant cholesterol is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). We aimed to evaluate the concentrations and general distribution of remnant cholesterol at admission in patients hospitalized for acute coronary syndrome (ACS), and those in patients who reached the low-density lipoprotein cholesterol (LDL-C) target or non-high-density lipoprotein cholesterol (non-HDL-C) target. Patients with ACS who were enrolled in the Improving Care for Cardiovascular Disease in China­ACS project from 2014 to 2019 were included. Elevated remnant cholesterol concentrations were defined as ≥1.0 mmol/L. Among 94,869 patients, the median (interquartile range) remnant cholesterol concentration at admission was 0.6 mmol/L (0.4−0.9 mmol/L) and 19.2% had elevated remnant cholesterol concentrations. Among patients with LDL-C concentrations < 1.4 mmol/L, 24.4% had elevated remnant cholesterol concentrations, while the proportion was 13.3% among patients with LDL-C concentrations between 1.4 and 1.7 mmol/L. Among patients with non-HDL-C concentrations < 2.6 mmol/L, 2.9% had elevated remnant cholesterol concentrations but 79.6% had LDL-C concentrations ≥ 1.4 mmol/L. Even among patients with LDL-C < 1.4 mmol/L and non-HDL-C < 2.6 mmol/L, 10.9% had elevated remnant cholesterol. In conclusion, one fifth of patients with ACS have elevated remnant cholesterol concentrations at admission. Elevated remnant cholesterol concentrations are present in patients with LDL-C or/and non-HDL-C concentrations within the target, which represents an unmet need to add remnant cholesterol as a target for the secondary prevention of ASCVD.

Prevalence, awareness, treatment, and control rates of hypertension in patients hospitalized with atrial fibrillation in China: Findings from the CCC-AF project.

Background: The status of hypertension in patients with atrial fibrillation (AF) remains unknown in China. Methods: This study used data from patients hospitalized with AF recruited by the Improving Care for Cardiovascular Disease in China-AF (CCC-AF) project from 236 hospitals enrolled by geographic-economic level in China from 2015 to 2019. The prevalence, awareness, treatment, and control rates of hypertension in patients hospitalized with AF were estimated. Multivariable logistic regression was used to analyze the factors associated with uncontrolled hypertension. Results: Among 60,390 patients hospitalized with AF, the prevalence of hypertension according to the 2018 Chinese hypertension guidelines was 66.1%. The awareness, treatment, and control rates of hypertension were 80.3, 55.8, and 39.9%, respectively. Among patients treated for hypertension, the treatment control rate was 46.2%. These rates varied according to patient clinical characteristics and geographic regions. The young (18-44 and 45-54 years old), rural insurance, alcohol drinking, history of heart failure, valvular AF, first diagnosed AF, and permanent AF, were associated with uncontrolled hypertension. Under the 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension guidelines, the prevalence of hypertension was 79.3%, and the control and treatment control rates dropped to 16.7 and 21.2%, respectively. Conclusion: Hypertension is common in patients hospitalized with AF in China. Although most patients were aware of their hypertensive status, the treatment and control rates of hypertension were still low. The management of hypertension in patients with AF needs to be further improved.

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.

Association between Early Oral ß-Blocker Therapy and Risk for In-Hospital Major Bleeding after Percutaneous Coronary Intervention for Acute Coronary Syndrome: Findings from CCC-ACS Project.

AIMS: Information regarding ß-blocker use and bleeding risk in patients on antithrombotic therapy in contemporary practice is limited. We examined the association between early (within the first 24 hours) oral ß-blocker therapy and major in-hospital bleeds among acute coronary syndrome (ACS) patients treated with percutaneous coronary intervention (PCI). METHODS AND RESULTS: In the Improving Care for Cardiovascular Disease in China-ACS project, among patients without contraindications to ß-blocker, we examined the association between early oral ß-blocker exposure [users/non-users, dosing, and type (metoprolol vs. bisoprolol)] and major in-hospital bleeds. Of the 43,640 eligible patients, 36.0% patients received early oral ß-blocker and 637 major bleeds were recorded. Compared with non-users, early oral ß-blocker was associated reduced risks for major bleeds [odds ratio (OR): 0.48; 95% confidence interval (CI): 0.38-0.61] and in-hospital mortality (OR: 0.47; 95%CI: 0.34-0.64) in multivariable-adjusted logistic regression models. Early oral ß-blocker use associated reduction in major bleeding was evident both in high-dose (defined by metoprolol-equivalent dose ≥50 mg/day) users (OR: 0.47; 95%CI: 0.33-0.68) and in low-dose users (metoprolol-equivalent dose <50 mg/day; OR: 0.61; 95%CI: 0.47-0.79). No significant difference was observed between metoprolol and bisoprolol in terms of reductions in major bleeding and mortality. Analyses based on inverse-probability-of-treatment-weighted regression adjustment and propensity-score matching yielded consistent findings. CONCLUSION: In this retrospective study based on the nationwide ACS registry, among patients treated by PCI, in addition to a reduction in in-hospital mortality, oral ß-blocker therapy initiated within the first 24 hours was associated with a reduced risk for major in-hospital bleeds. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02306616.

Pre-hospital delay in patients with acute myocardial infarction in China: findings from the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS) project.

OBJECTIVE: To describe the duration of the pre-hospital delay time and identify factors associated with prolonged pre-hospital delay in patients with acute myocardial infarction (AMI) in China. METHODS: Data were collected from November 2014 to December 2019 as part of the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS) project. A total of 33,386 patients with AMI admitted to the index hospitals were included in this study. Two-level logistic regression was conducted to explore the factors associated with the pre-hospital delay and the associations between different pre-hospital delay and in-hospital outcomes. RESULTS: Of the 33,386 patients with AMI, 70.7% of patients arrived at hospital ≥ 2 h after symptom onset. Old age, female, rural medical insurance, symptom onset at early dawn, and non-use of an ambulance predicted a prolonged pre-hospital delay (all P < 0.05). Hypertension and heart failure at admission were only significant in predicting a longer delay in patients with ST-segment elevation myocardial infarction (STEMI) (all P < 0.05). A pre-hospital delay of ≥ 2 h was associated with an increased risk of mortality [odds ratio (OR) = 1.36, 95% CI: 1.09-1.69, P = 0.006] and major adverse cardiovascular events (OR = 1.22, 95% CI: 1.02-1.47, P = 0.033) in patients with STEMI compared with a pre-hospital delay of < 2 h. CONCLUSIONS: Prolonged pre-hospital delay is associated with adverse in-hospital outcomes in patients with STEMI in China. Our study identifies that patient characteristics, symptom onset time, and type of transportation are associated with pre-hospital delay time, and provides focuses for quality improvement.

Association Between Early Oral ß-Blocker Therapy and In-Hospital Outcomes in Patients With ST-Elevation Myocardial Infarction With Mild-Moderate Heart Failure: Findings From the CCC-ACS Project.

Background: There are limited data available on the impact of early (within 24 h of admission) ß-blocker therapy on in-hospital outcomes of patients with ST-elevation myocardial infarction (STEMI) and mild-moderate acute heart failure. This study aimed to explore the association between early oral ß-blocker therapy and in-hospital outcomes. Methods: Inpatients with STEMI and Killip class II or III heart failure from the Improving Care for Cardiovascular Disease in China project (n = 10,239) were enrolled. The primary outcome was a combined endpoint composed of in-hospital all-cause mortality, successful cardiopulmonary resuscitation after cardiac arrest, and cardiogenic shock. Inverse-probability-of-treatment weighting, multivariate Cox regression, and propensity score matching were performed. Results: Early oral ß-blocker therapy was administered to 56.5% of patients. The incidence of the combined endpoint events was significantly lower in patients with early therapy than in those without (2.7 vs. 5.1%, P < 0.001). Inverse-probability-of-treatment weighting analysis demonstrated that early ß-blocker therapy was associated with a low risk of combined endpoint events (HR = 0.641, 95% CI: 0.486-0.844, P = 0.002). Similar results were shown in multivariate Cox regression (HR = 0.665, 95% CI: 0.496-0.894, P = 0.007) and propensity score matching (HR = 0.633, 95% CI: 0.453-0.884, P = 0.007) analyses. A dose-response trend between the first-day ß-blocker dosages and adverse outcomes was observed in a subset of participants with available data. No factor could modify the association of early treatment and the primary outcomes among the subgroups analyses. Conclusion: Based on nationwide Chinese data, early oral ß-blocker therapy is independently associated with a lower risk of poor in-hospital outcome in patients with STEMI and Killip class II or III heart failure.