Association Between Heart Rate and Major Adverse Cardiovascular Events Among 9,991 Hypertentive Patients: A Multicenter Retrospective Follow-Up Study

Objective: To assess the effect of heart rate at baseline on major adverse cardiovascular events (MACEs) among hypertensive patients in China.Methods: A multicenter retrospective study was conducted with a 24 month follow-up period. A total of 10,031 hypertensive patients treated with standard antihypertensive drugs were grouped according to their heart rate before treatment: <65 beats per min (bpm), 65–69 bpm, 70–74 bpm, 75–79 bpm, and ≥80 bpm. The occurrence of any of MACEs was as the endpoint event during the 24 month follow-up period. The effect of heart rate at baseline on MACEs was analyzed using univate and multivariable Cox proportional regression analyses, with hazard ratios (HRs) and 95% confidence intervals (CIs). The restricted cubic spline (RCS) model was used to fit the Cox proportional harzard model with 5 knots at the 5th, 25th, 50th, 75th, and 95th percentiles of heart rate.Results: Totally 9,991 patients were finally enrolled with the mean systolic pressure (SBP)/diastolic pressure (DBP) of 130.59 ± 7.13/77.66 ± 5.99 mmHg at 24 month follow-up. The incidence of MACEs was 4.80% (n = 480). After adjustment for age, gender, baseline blood pressure, alcohol drinking, smoking, hyperlipidemia, diabetes, coronary heart disease, cerebrovascular disease and antihypertensive drug use, patients with heart rate <65 bpm (HR = 1.450, 95% CI: 1.098–1.915) and ≥80 bpm (HR = 1.391, 95% CI: 1.056–11.832) showed 0.45 fold and 0.391 fold increases of MACE risks, compared with patients with heart rate of 70–74 bpm. Furthermore, MACE risks were increased by 86.0% and 65.4% in men, and 59.3% and 69.0% in elderly patients aged ≥65 years at heart rate <65 bpm or ≥80 bpm, respectively. We also found a non-liner U-shaped correlation between heart rate and the occurrence of MACEs.Conclusions: Heart rate might be an independent risk factor for MACEs in hypertensive patients. An appropriate range of heart rate control may offer guidance to hypertension treatment.

The Value of Left Internal Mammary Artery Velocity in Predicting the Prognosis of Patients After CABG

Objectives: The purpose of this study was to explore the value of the LIMAV measured by ultrasound before CABG in predicting the prognosis of patients after LIMA bypass grafting. Methods: 104 patients who underwent CABG with LIMA as the bridge vessel in the cardiovascular surgery department of our hospital between May 2018 and June 2019 were selected. All patients underwent transthoracic Doppler ultrasonography to measure LIMAV preoperatively. Intraoperatively, MGF and PI of the LIMA bridge were measured using TTFM. The primary endpoint event in this study was cardiac death within 18 months after surgery. Results: The Cox survival analysis showed that the MGF , the LIMAV and LVEF were risk factors for death after CABG . The cut-offs of MGF ,LIMAV and LVEF for the prediction of death after CABG were ≤14 ml/min [AUC: 0.830; Sensitivity:100%; Specificity: 65.6%], ≤60cm/s (AUC: 0.759; Sensitivity:65.5%; Specificity:85.3%) and ≤44%（AUC:0.724; Sensitivity:50%; Specificity: 88.5% ）respectively. Compared with the use of MGF, MGF+LIMAV, combination of the MGF+LIMAV+LVEF （AUC:0.929; Sensitivity:100%; Specificity: 81.1%）resulted in a stronger predictive value（MGF vs MGF+LIMAV+LVEF: p=0.02）. Conclusion: LIMAV measured by transthoracic ultrasound pre-operation combined with intraoperative MGF and LVEF may have a greater value in predicting patients' risk of cardiac death after CABG.

Predictive Efficacy of Serum Lipoprotein(A) Combined with TSH in Patients with Acute Coronary Syndrome After Coronary Angiography

Backgroud： Elevated lipoprotein(a) [Lp(a)] and thyroid stimulating hormone (TSH) are both associated with coronary artery disease (CAD), but it was controversial in ACS patients. Moreover, patients with elevated plasma TSH tend to have higher levels of lipoprotein. We supposed that patients with elevated LP (a) and TSH may have a adverse prognosis after coronary angiography.Methods: We consecutively recruited 1756 patients who underwent coronary angiography, of which 1473 patients with ACS were eventually enrolled. Major adverse cardiovascular events (MACEs) contained a complex of non-fatal stroke, non-fatal myocardial infarction, ischemic cardiovascular events, and cardiovascular death. According to the occurrence of end events within 27.4 months, the patients were split into two groups: non-endpoint event group (n = 1288) and endpoint event group (n = 185). The date between the two groups were compared. Serum LP (a) was measured by latex agglutination immunoassay (Roche Diagnostics GmbH, Mannheim, Germany).Results: During a median follow-up of 27.4 months, 185 (12.56%) MACEs occurred. Compared with the non-endpoints group，patients in the end-points group had higher level of preoperative LP (a), LDL and TSH (all P<0.05). Multivariate Cox proportional hazard model showed that LP (a) was an independent risk factor for adverse prognosis after coronary angiography in ACS patients, LP (a) > 53.8nmol/L (highest tertile ) predicted 1.704-fold risk for adverse prognosis of ACS (95%CI 1.194~2.433；P＜0.05); Interestingly, patients with elevated LP (a) and TSH concomitantly conferred the highest risk for adverse prognosis OR=3.090 95%CI 1.657~5.765；P＜0.001).Conclusion: LP (a) was an independent risk factor for adverse prognosis after coronary angiography in ACS patients, and the predictive efficacy was enhanced by TSH.

Adjudicating mild cognitive impairment due to Alzheimer’s disease as a novel endpoint event in the TOMMORROW prevention clinical trial

Background The onset of mild cognitive impairment (MCI) is an essential outcome in Alzheimer’s disease (AD) prevention trials and a compelling milestone for clinically meaningful change. Determining MCI, however, may be variable and subject to disagreement. Adjudication procedures may improve the reliability of these determinations. We report the performance of an adjudication committee for an AD prevention trial. Methods The TOMMORROW prevention trial selected cognitively normal participants at increased genetic risk for AD and randomized them to low-dose pioglitazone or placebo treatment. When adjudication criteria were triggered, a participant’s clinical information was randomly assigned to a three-member panel of a six-member independent adjudication committee. Determination of whether or not a participant reached MCI or AD proceeded through up to three review stages – independent review, collaborative review, and full committee review – requiring a unanimous decision and ratification by the chair. Results Of 3494 participants randomized, the committee adjudicated on 648 cases from 386 participants, resulting in 96 primary endpoint events. Most participants had cases that were adjudicated once (n = 235, 60.9%); the rest had cases that were adjudicated multiple times. Cases were evenly distributed among the eight possible three-member panels. Most adjudicated cases (485/648, 74.8%) were decided within the independent review (stage 1); 14.0% required broader collaborative review (stage 2), and 11.1% needed full committee discussion (stage 3). The primary endpoint event decision rate was 39/485 (8.0%) for stage 1, 29/91 (31.9%) for stage 2, and 28/72 (38.9%) for stage 3. Agreement between the primary event outcomes supported by investigators’ clinical diagnoses and the decisions of the adjudication committee increased from 50% to approximately 93% (after around 100 cases) before settling at 80–90% for the remainder of the study. Conclusions The adjudication process was designed to provide independent, consistent determinations of the trial endpoints. These outcomes demonstrated the extent of uncertainty among trial investigators and agreement between adjudicators when the transition to MCI due to AD was prospectively assessed. These methods may inform clinical endpoint determination in future AD secondary prevention studies. Reliable, accurate assessment of clinical events is critical for prevention trials and may mean the difference between success and failure. Trial registration: NCT01931566

Mortality in patients with atrial fibrillation with or without heart failure following hospital discharge

Background The association of heart failure (HF) with the prognosis of atrial fibrillation (AF) remains unclear. OBJECTIVES To assess all-cause mortality in patients following hospitalization with comorbid AF in relation to the presence of HF. Methods We performed a cross-sectional analysis of data from 977 patients discharged from the cardiology ward of a single tertiary center between 2015 and 2018 and followed for a median of 2 years. The association between HF and the primary endpoint of death from any cause was assessed using multivariable Cox regression. Results HF was documented in 505 (51.7%) of AF cases at discharge, including HFrEF (17.9%), HFmrEF (16.5%) and HFpEF (25.2%). A primary endpoint event occurred in 212 patients (42%) in the AF-HF group and in 86 patients (18.2%) in the AF-no HF group (adjusted hazard ratio [aHR] 2.27; 95% confidence interval [CI], 1.65 to 3.13; P&lt;0.001). HF was associated with a higher risk of the composite secondary endpoint of death from any cause, AF or HF-specific hospitalization (aHR 1.69; 95% CI 1.32 to 2.16 p&lt;0.001). The associations of HF with the primary and secondary endpoints were significant and similar for AF-HFrEF, AF-HFmrEF, AF-HFpEF. Conclusions HF was present in half of the patients discharged from the hospital with comorbid AF. The presence of HF on top of AF was independently associated with a significantly higher risk of all-cause mortality than did absence of HF, irrespective of HF subtype. Funding Acknowledgement Type of funding source: None

Encephaloduroarteriosynangiosis (EDAS) revascularization for symptomatic intracranial atherosclerotic steno-occlusive (ERSIAS) Phase-II objective performance criterion trial

Background Intracranial atherosclerotic disease (ICAD) is one of the most challenging stroke etiologies, with frequent recurrences despite optimized medical management. Encephaloduroarteriosynangiosis (EDAS) is an indirect revascularization method that produces extra-cranial collaterals to intracranial vessels. We present the results of a phase-II trial of EDAS in intracranial atherosclerotic disease patients. Aims To evaluate the feasibility, safety, and preliminary efficacy of EDAS in intracranial atherosclerotic disease patients. Methods ERSIAS was a prospective objective-performance-criterion trial of EDAS plus intensive medical management (IMM) in intracranial atherosclerotic disease (ICAD) patients failing medical treatment. Primary endpoint was any stroke/death within 30-days post-surgery or stroke in the territory of the qualifying artery beyond 30 days. The primary analysis compared event rates through one year with an objective-performance-criterion based on a 10% reduction from the 20% rate in the intensive medical management arm of the stenting versus aggressive medical management for preventing recurrent stroke in intracranial stenosis trial (SAMMPRIS) in patients with poor collaterals. Event rates through two years were compared with propensity-score-matched (PSM) medically treated patients from SAMMPRIS and the carotid occlusion surgery study (COSS). Results During a median follow-up of 24.5 months, 5 (9.6%) of 52 patients had a primary endpoint event. The primary endpoint rate at one year met the threshold for nonfutility and advancement to phase III (<10%). In the sensitivity analysis, primary endpoint event rate at two years was lower than in PSM controls, 9.6% versus 21.2% (p < 0.07). Overall, 86% of EDAS-plus-intensive medical management patients were functionally independent at last follow-up and 89% demonstrated neovascularization. There were two (3.8%) surgical complications and no intracranial hemorrhages. Conclusion ERSIAS phase II provides evidence of safety and strong signals of efficacy of EDAS-plus-intensive medical management, supporting advancement to a seamless phase-IIb/III trial. Clinical Trial Registration URL: https://www.clinicaltrials.gov.NCT01819597 .

Treatment Adherence and Secondary Prevention of Ischemic Stroke Among Discharged Patients Using Mobile Phone- and WeChat-Based Improvement Services: Cohort Study

Background Real-world studies have indicated that adherence is important for guaranteeing medication effectiveness. Few studies have tested the feasibility and efficacy of WeChat-based improvement services, via mobile phone, in secondary prevention-specific follow-up among discharged stroke patients. Objective We evaluated a quadruple-domain, WeChat-based service for ischemic stroke secondary prevention designed to improve treatment adherence of discharged patients. This service focuses on sending reminders for drug use, blood pressure recording, and glucose recording; it also records medication use. We compared the endpoint event rate between WeChat self-monitoring and traditional monitoring. Methods A cohort study was used to determine the feasibility of a physician-assisted, WeChat-based improvement service and follow-up self-monitoring platform for the secondary prevention of ischemic stroke. The platform was developed by the Peking University Third Hospital based on the information-motivation-behavioral skills model. The overall adherence rate was calculated as the proportion of medication doses verified via uploading. The ischemic endpoint event rate and medication noncompliance rate were compared between traditional prevention monitoring and WeChat self-monitoring. Factors influencing adherence were summarized. Results The 1-year follow-up event rate of the WeChat self-monitoring group was 11.9% (12/101), which was less than that of the traditional group (21/157, 13.4%). Compared with the traditional group, the risk ratio of the WeChat group was 0.983 (95% CI 0.895-1.080); this difference was not noted to be significant. The 1-year medication noncompliance ratio tended to be lower in the WeChat monitoring group (3/101, 3.0%) than in the traditional group (11/157, 7.0%; χ2=1.9, df=1, P=.16). Of the platform registry participants, 89.7% (210/234: 167 hospital-based and 43 community-based participants) adhered to inputting information into WeChat for 8-96 weeks. The average adherence time was 16.54 (SD 0.80, range 2-24) months. The average decrease in adherence was 4 participants (1.1%) per month. Being a member of a community-based population was an influencing factor for good adherence at the 2-year follow-up (OR 2.373, 95% CI 1.019-5.527, P=.045), whereas transient ischemic attack was an influencing factor for poor adherence at the 2-year follow-up (OR 0.122, 95% CI 0.016-0.940, P=.04). Conclusions Use of WeChat self-monitoring showed a trend of increasing medication compliance and decreasing ischemic endpoint event rate compared with traditional monitoring. However, there were ceiling effects in the outcomes, and a relatively small sample size was used. Male participants displayed better adherence to WeChat self-monitoring. The community-based population displayed good adherence when using WeChat self-monitoring. Trial Registration ClinicalTrials.gov NCT02618265; https://clinicaltrials.gov/ct2/show/NCT02618265

Prognostic Factors in Patients With Osteosarcoma With the Surveillance, Epidemiology, and End Results Database

Background: Osteosarcoma is a rare type of bone tumor, and this study aimed to assess the clinicopathologic features and prognoses of osteosarcoma patients. Methods: Clinicopathologic and survival data of 1025 patients between 2010 and 2016, 230 between 2008 and 2009 were downloaded and analyzed from the SEER database. Patients’ survival was analyzed using the Kaplan-Meier analysis; prognostic factors were assessed using the Cox regression hazards model. The 1-, 3-, and 5-year survival rates were estimated with nomogram. Competitive risk models were used to identify prognostic risk factors related to endpoint events of osteosarcoma patients. Results: Overall, 722 samples were obtained from the extremities, 134 from the axial bones, and 119 from the cranial and mandible in SEER (2010-2016 cohort). After the preliminary diagnosis, the median survival time of patients with osteosarcoma was 39 months, and the 1-, 3-, and 5-year survival rates were 87.3%, 67.2%, and 58.0%, respectively (P < 0.001). The competitive risk model revealed no competitive risks of the endpoint event. Conclusion: Our study found out the prognostic factors in patients with Osteosarcoma by Cox regression hazards model, after that, nomogram was established to predict the 1-, 3-, and 5-year survival rates, which may help oncologists to understand the highly malignant tumor.