Aims  Emerging evidence has linked cholesterol metabolism with platelet responsiveness. We sought to examine the dose–response relationship between low-density lipoprotein cholesterol (LDL-C) and major in-hospital bleeds in acute coronary syndrome (ACS) patients. Methods and results  Among 42 378 ACS patients treated with percutaneous coronary intervention (PCI) enrolled in 240 hospitals in the Improving Care for Cardiovascular Disease in China-ACS project from 2014 to 2019, a total of 615 major bleeds, 218 ischaemic events, and 337 deaths were recorded. After controlling for baseline variables, a non-linear relationship was observed for major bleeds, with the higher risk at lower LDL-C levels. No dose–response relationship was identified for ischaemic events and mortality. A threshold value of LDL-C <70 mg/dL was associated with an increased risk for major bleeds (adjusted odds ratio: 1.49; 95% confidence interval: 1.21–1.84) in multivariable-adjusted logistic regression models and in propensity score-matched cohorts. The results were consistent in multiple sensitivity analyses. Among ticagrelor-treated patients, the LDL-C threshold for increased bleeding risk was observed at <88 mg/dL, whereas for clopidogrel-treated patients, the threshold was <54 mg/dL. Across a full spectrum of LDL-C levels, the treatment effect size associated with ticagrelor vs. clopidogrel on major bleeds favoured clopidogrel at lower LDL-C levels, but no difference at higher LDL-C levels. Conclusions  In a nationwide ACS registry, a non-linear association was identified between LDL-C levels and major in-hospital bleeds following PCI, with the higher risk at lower levels. As the potential for confounding may exist, further studies are warranted. Trial registration ClinicalTrials.gov Identifier: NCT02306616

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.

Background Immune abnormalities and inflammatory responses play critical roles in progression of hypertension. Basic studies have confirmed that Th17 cell and related cytokines are important in promoting hypertension-mediated organ damage, but few clinical evidences have been published. Therefore, our study aimed to investigate the relationship between Th17 cell and its related cytokines and hypertension-mediated organ damage in human. Methods This study enrolled 179 patients with hypertension (including 92 with hypertension-mediated organ damage and 87 without hypertension-mediated organ damage) and 63 healthy participants. The proportion of Th17 cells in peripheral blood mononuclear cells was measured by flow cytometry. The concentrations of interleukin-17 and interleukin-23 were detected by enzyme-linked immunosorbent assay. Real time-polymerase chain reaction was used to detect the mRNA expression levels of interleukin-17, retinoic acid-related orphan receptor (ROR) γt and signal transducer and activator of transcription-3 (STAT-3). Results The proportion of Th17 cells, the concentration of interleukin-17 and interleukin-23 and the mRNA expression levels of interleukin-17, retinoic acid-related orphan receptor γt and signal transducer and activator of transcription-3 were significantly increased in hypertension-mediated organ damage group compared with those in non-hypertension-mediated organ damage group and control group (P < 0.005). Conclusion Th17 cells and their associated cytokines may be involved in hypertension-mediated organ damage formation and may be able to serve as new biomarkers of hypertension-mediated organ damage and potential therapeutic targets.

Aims Information regarding β-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 β-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 β-blocker, we examined the association between early oral β-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 β-blocker and 637 major bleeds were recorded. Compared with non-users, early oral β-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 β-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 &lt;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 β-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