Analysis of onset-to-door time and its influencing factors in Chinese patients with acute ischemic stroke during the 2020 COVID-19 epidemic: a preliminary, prospective, multicenter study.

BACKGROUND: Pre-hospital delay in China is a serious issue with unclear relevant reasons, seriously impeding the adoption of appropriate measures. Herein, we analyzed the onset-to-door time (ODT) in Chinese patients with acute ischemic stroke (AIS) and its influencing factors. METHODS: We prospectively recruited 3,459 patients with AIS from nine representative tertiary general hospitals in China between January and June 2022. Patients were divided into ODT ≤ 3 h and ODT > 3 h groups. Following single-factor analysis, binary logistic regression analysis was performed to evaluate the risk factors leading to pre-hospital delay. RESULTS: In total, 763 (21.83%) patients arrived at the hospital within 3 h of onset. After adjusting for confounding factors, the risk factors for ODT were residence in rural areas (odds ratio [OR]: 1.478, 95% credibility interval [CI]: 1.024-2.146) and hospital transfer (OR: 7.479, 95% CI: 2.548-32.337). The protective factors for ODT were location of onset ≤ 20 km from the first-visit hospital (OR: 0.355, 95% CI: 0.236-0.530), transportation by emergency medical services (OR: 0.346, 95% CI: 0.216-0.555), history of atrial fibrillation (OR: 0.375, 95% CI: 0.207-0.679), moderate stroke (OR: 0.644, 95% CI: 0.462-0.901), and severe stroke (OR: 0.506, 95% CI: 0.285-0.908). CONCLUSIONS: Most patients with AIS fail to reach a hospital within the critical 3-h window. The following measures are recommended to reduce pre-hospital delays: reasonable distribution of hospitals accessible to nearby residents, minimizing interhospital transfer, paying attention to patients with mild stroke, and encouraging patients to use ambulance services. Pre-hospital delays for patients can be reduced by implementing these measures, ultimately improving the timeliness of treatment and enhancing patient prognosis. This study was carried out amid the COVID-19 pandemic, which presented challenges and constraints.

Synchronous multimode ultrasound for assessing right-to-left shunt: a prospective clinical study.

Background: Right-to-left shunt (RLS) is associated with several conditions and causes morbidity. In this study, we aimed to evaluate the effectiveness of synchronous multimode ultrasonography in detecting RLS. Methods: We prospectively enrolled 423 patients with high clinical suspicion of RLS and divided them into the contrast transcranial Doppler (cTCD) group and synchronous multimode ultrasound group, in which both cTCD and contrast transthoracic echocardiography (cTTE) were performed during the same process of contrast-enhanced ultrasound imaging. The simultaneous test results were compared with those of cTCD alone. Results: The positive rates of grade II (22.0%:10.0%) and III (12.7%:10.8%) shunts and the total positive rate (82.1748%) in the synchronous multimode ultrasound group were higher than those in the cTCD alone group. Among patients with RLS grade I in the synchronous multimode ultrasound group, 23 had RLS grade I in cTCD but grade 0 in synchronous cTTE, whereas four had grade I in cTCD but grade 0 in synchronous cTTE. Among patients with RLS grade II in the synchronous multimode ultrasound group, 28 had RLS grade I in cTCD but grade II in synchronous cTTE. Among patients with RLS grade III in the synchronous multimode ultrasound group, four had RLS grade I in cTCD but grade III in synchronous cTTE. Synchronous multimode ultrasound had a sensitivity of 87.5% and specificity of 60.6% in the patent foramen ovale (PFO) diagnosis. Binary logistic regression analyses showed that age (odds ratio [OR] = 1.041) and risk of paradoxical embolism score ≥ 7 (OR = 7.798) were risk factors for stroke recurrence, whereas antiplatelets (OR = 0.590) and PFO closure with antiplatelets (OR = 0.109) were protective factors. Conclusion: Synchronous multimodal ultrasound significantly improves the detection rate and test efficiency, quantifies RLS more accurately, and reduces testing risks and medical costs. We conclude that synchronous multimodal ultrasound has significant potential for clinical applications.

Visit-to-Visit Variability in Fasting Blood Glucose Predicts the New-Onset Heart Failure: Results From Two Large Chinese Cohorts.

Previous studies have hypothesized an association between higher fasting blood glucose (FBG) and heart failure (HF). However, FBG values fluctuate continuously over time, the association between FBG variability and the risk of HF is uncertain. We investigated the relationship between visit-to-visit variability in FBG and the risk of new-onset HF. This cohort study used data from a prospective Kailuan cohort (recruited during 2006-2007) and a retrospective cohort of family medicine patients from Hong Kong (recruited during 2000-2003) were followed up until December 31st, 2016, and December 31st, 2019, respectively, for the outcome of incident HF. Four indexes of variability were used, including standard deviation (SD), coefficient of variation (CV), variability independent of the mean (VIM), and average real variability (ARV). Cox regression was used to identify HF. In total, 98,554 and 22,217 subjects without preexisting HF from the Kailuan and Hong Kong cohorts were analyzed, respectively, with 1218 cases of incident HF in the former and 4,041 in the latter. Subjects in the highest quartile of FBG-CV had the highest risk of incident HF in both cohorts (Kailuan: HR 1.245, 95% CI 1.055-1.470); Hong Kong: HR 1.362, 95%CI 1.145-1.620; compared with the lowest quartile). Similar results were observed when using FBG-ARV, FBG-VIM, and FBG-SD. Meta-analysis showed similar results (highest versus lowest quartile: HR 1.30, 95%CI 1.15-1.47, P < 0.0001). As observed from 2 large, geographically distinct Chinese cohorts, a higher FBG variability was independently associated with higher risk of incident HF.

Association of proteinuria and risk of incident atrial fibrillation in the general population: A prospective study of Kailuan study participants.

BACKGROUND: Proteinuria is a well-known cardiovascular risk factor, but whether it independently increases the risk for atrial fibrillation (AF) in Chinese population is unknown. To address this deficiency, herein, we investigated the association between proteinuria detected using urine dipstick test and the risk of AF. METHODS: This was a prospective cohort study of Kailuan study participants who underwent the 2006-2007 and 2010-2011 health checkups and was free from AF. Participants were classified into four groups based on the level of proteinuria: [-, trace (±), 1+, ≥2+]. The outcome was incident AF as confirmed by 12-lead electrocardiography. RESULTS: During a median of 11.90 years of follow-up, we documented 514 incident AF cases among 60,599 participants. Proteinuria was found in 6302 (10.40%) participants. Relative to participants without proteinuria at the baseline, those with proteinuria (≥2+) had an 83.9% higher risk (95% confidence interval [CI], 1.073-3.154, p = .0267) of developing AF, after adjusted for confounding variables. The result was consistent in the sensitivity analysis. Compared to consistently negative proteinuria, the risk of AF significantly increased in the aggravated proteinuria group (hazard ratio [HR] 1.552, 95% CI 1.140-2.114) and the persistent proteinuria group (HR 2.485, 95% CI 1.414-4.366). Among participants with resolved proteinuria (from positive to negative), the risk of incident AF was not significantly increased compared to those with persistently negative proteinuria (HR 1.300, 95% CI 0.743-2.276). CONCLUSIONS: Proteinuria could be a modifiable risk factor for predicting AF development. Knowing the presence of proteinuria may improve risk stratification for decision-making about AF prevention.

Proteinuria, Body Mass Index, and the Risk of New-Onset Heart Failure: A Prospective Cohort Study in Northern China.

Some studies have reported that body-mass index (BMI) and proteinuria are risk factors for heart failure (HF). However, the combined effect of BMI and proteinuria on HF is still unclear. We aimed to investigate the association of BMI and proteinuria levels with the risk of HF in a large community-based population. A total of 61, 113 individuals aged ≥18 years from the prospective Kailuan cohort (recruited during 2006-2007) without preexisting heart failure were included. Each participant was categorized into 4 groups according to BMI (< 25 kg/m2 or ≥ 25 kg/m2) and the urine dipstick test results (negative or positive). The primary outcome was HF. We performed multivariable Cox regression analyses to identify the association between BMI and proteinuria category and incident HF. Over a mean follow-up of 9.97±0.75 years, a total of 987 individuals developed incident HF, 1.62 per 1000 person-years. Compared to BMI < 25 kg/m2 and absence of proteinuria, the risk of HF was higher for BMI ≥ 25 kg/m2 and positive proteinuria (HR 2.630, 95% CI 1.982-3.490, P < 0.0001) (P for trend < 0.0001). Degree of proteinuria in participants was associated with a significantly higher rate of incident HF in dose dependent manner. Compared to consistently negative proteinuria, the risk of HF increased by 75.0% (HR 1.750, 95% CI 1.368-2.239, P < 0.0001) and 127.0% (HR 2.270, 95% CI 1.540-3.347, P < 0.0001) in the proteinuria aggravated group and persistent positive group, respectively. Proteinuria combined with a high BMI level is associated with an increased risk for HF in the Chinese population. However, the mechanism is unknown and awaits further study.

Clinical factors associated with cerebral autoregulation in ischemic stroke related to small artery occlusion.

BACKGROUND: Existing data suggest that cerebral autoregulation (CA) varies among different subtypes of ischaemic stroke. CA is globally impaired in patients with small artery occlusion (SAO). However, the factors influencing CA impairment in patients remains to be elucidated. METHODS: Stroke patients with SAO who underwent brain magnetic resonance imaging (MRI) were prospectively studied. Within 7 days after stroke onset, CA was recorded from the middle cerebral artery blood flow velocity and arterial blood pressure was simultaneously measured. Transfer function analysis was used to derive CA parameters, including gain and phase. Clinical characteristics, mean arterial pressure (MAP), biochemical findings, and cerebral small vessel disease (CSVD) markers on MRI were assessed in each patient. Factors associated with CA parameters were investigated. Univariate and multivariate linear regression analyses were conducted to determine the relationship between clinical factors and CA parameters. RESULTS: Sixty-three SAO patients (age, 56.3 ± 9.9 years; 55 men) were enrolled in the study. In the multiple linear regression analysis, after controlling for relevant clinical factors, MAP on admission (ipsilateral OR = 0.99 and contralateral OR = 0.99, both P < 0.005) was a significant independent predictor of bilateral gain. MAP > 105 mmHg on admission (OR = 0.77, P = 0.019) was significantly associated with ipsilateral gain. Diabetes mellitus was a significant predictive factor for bilateral gain (ipsilateral OR = 1.32 and contralateral OR = 1.22, both P < 0.005). No correlations were found between CA parameters and CSVD characteristics. CONCLUSION: In SAO-related ischaemic stroke, patients with MAP > 105 mmHg on admission tended to have better ipsilateral CA. Diabetes mellitus appears to be an independent risk factor for CA impairment in patients with SAO-related stroke. CSVD may not be the main factor affecting bilateral CA in patients with SAO.

Risk Factors for Incident Stroke and Its Subtypes in China: A Prospective Study.

Background Managing risk factors is crucial to prevent stroke. However, few cohort studies have evaluated socioeconomic factors together with conventional factors affecting incident stroke and its subtypes in China. Methods and Results A 2014 to 2016 prospective study from the China National Stroke Screening and Intervention Program comprised 437 318 adults aged ≥40 years without stroke at baseline. There were 2429 cases of first-ever stroke during a median follow-up period of 2.1 years, including 2206 ischemic strokes and 237 hemorrhagic strokes. The multivariable Cox regression analysis indicated that age 50 to 59 years (versus 40-49 years), primary school or no formal education (versus middle school), having >1 child (versus 1 child), living in Northeast, Central, East, or North China (versus Southwest China), physical inactivity, hypertension, diabetes mellitus, and obesity were positively associated with the risk of total and ischemic stroke, whereas age 60 to 69 years and living with spouse or children (versus living alone) were negatively associated with the risk of total and ischemic stroke. Men, vegetable-based diet, underweight, physical inactivity, hypertension, living in a high-income region, having Urban Resident Basic Medical Insurance, and New Rural Cooperative Medical System were positively associated with the risk of hemorrhagic stroke, whereas age 60 to 69 years was negatively associated with the risk of hemorrhagic stroke. Conclusions We identified socioeconomic factors that complement traditional risk factors for incident stroke and its subtypes, allowing targeting these factors to reduce stroke burden.

Excessive Supraventricular Ectopic Activity and Adverse Cardiovascular Outcomes: a Systematic Review and Meta-analysis.

PURPOSE OF REVIEW: Excessive supraventricular ectopic activity (ESVEA), in the form of frequent premature atrial contractions (PACs) and runs of PACs, is commonly observed in clinical practice and is frequently considered to be benign. Yet, recent studies have demonstrated a link between ESVEA and adverse cardiovascular outcomes. The aim of this meta-analysis was to examine the association between ESVEA and the risk of atrial fibrillation (AF), stroke, and mortality. RECENT FINDINGS: A systematic search was performed in PubMed, EMBASE, and the Cochrane Library up to December 2017 to identify studies assessing adverse cardiovascular outcomes in patients with ESVEA, recorded on ambulatory electrocardiography. ESVEA was defined as a burden of PACs > 30 PACs/h or any runs of ≥20 PACs. The risk estimates for EVSEA and each clinical endpoint were pooled and analyzed separately. RESULTS: Five studies comprising 7545 participants were included in this meta-analysis. The pooled analysis showed that ESVEA doubled the risk of AF (HR 2.19, 95% CI 1.70-2.82). ESVEA was also associated with a higher incidence of stroke (HR 2.23, 95% CI 1.24-4.02). Finally, ESVEA was associated with higher all-cause mortality (HR 1.61, 95% CI 1.25-2.07). Our meta-analysis found that ESVEA is closely associated with AF, stroke, and all-cause mortality. Further studies are required to examine the implication of therapeutic strategies in patients with ESVEA, in order to prevent potential subsequent adverse cardiovascular outcomes.

The effect of hypothermia during cardiopulmonary bypass on three electro-encephalographic indices assessing analgesia and hypnosis during anesthesia: consciousness index, nociception index, and bispectral index.

The depth of anesthesia is commonly assessed in clinical practice by the patient's clinical signs. However, during cardiopulmonary bypass and hypothermia, common symptoms of nociception such as tachycardia, hypertension, sweating, or movement have low sensitivity and specificity in the description of the patient nociception and hypnosis, in particular, detecting nociceptive stimuli. Better monitoring of the depth of analgesia during hypothermia under cardiopulmonary bypass will avoid underdosage or overdosage of analgesia, especially opioids. Induced hypothermia has a multifactorial effect on the level of analgesia and hypnosis. Thermoregulatory processes appear essential for the activation of analgesic mechanisms, ranging from a physiological strong negative affiliation between nerve conduction velocity and temperature, until significant repercussions on the pharmacological dynamics of the analgesic drugs, the latter decreasing the clearance rate with a subsequent increase in the effect-site concentrations. Under the hypothesis that deep hypothermia induces massive effects on the analgesia and hypnosis levels of the patient, we studied whether hypothermia effects were mirrored by several neuromonitoring indices: two hypnosis indices, consciousness index and bispectral index, and a novel nociception index designed to evaluate the analgesic depth. In this clinical trial, 39 patients were monitored during general anesthesia with coronary atherosclerosis cardiopathy who were elective for on-pump coronary artery bypass graft surgery under hypothermia. The changes and correlation between the consciousness index, bispectral index, and nociception index with respect to the temperature were compared in different timepoints at basic state, during cardiopulmonary bypass and after cardiopulmonary bypass. While the three neuromonitoring indices showed significant correlations with respect to the temperature, the nociception index and consciousness index showed the strongest sensitivities, indicating that these two indices could be an important means of intraoperative neuromonitoring during induced hypothermia under cardiopulmonary bypass.

Upstream therapeutic strategies of valsartan and fluvastatin on hypertensive patients with non-permanent atrial fibrillation.

AIM: To investigate the upstream therapeutic effects of fluvastatin and valsartan on hypertensive patients with non-permanent atrial fibrillation (AF). METHODS: A total of 189 patients who were admitted to outpatient and inpatient department from eight medical centers in China, diagnosed as hypertension with non-permanent AF, were divided into four groups randomly: the CCBs group (group A, n = 45); CCB + fluvastatin group (group B, n = 48); valsartan group (group C, n = 46); valsartan + fluvastatin group (group D, n = 50). The four groups were followed up for 24 months. The blood routine, biochemical examination, echocardiography, high sensitive C-reactive protein (hs-CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP), the maintenance rate of sinus rhythm, and the recurrence of paroxysmal AF or persistent AF incidence were observed in these groups before and after 24 months' treatment. RESULTS: After 24 months of follow-up, there were 178 cases of patients who have completed the study. (a) There was no significant difference in blood routine, liver, and renal function in each group (P > 0.05). (b) The blood lipids level in groups B and D was significantly reduced after treatment (P < 0.01). There was no significant difference of hs-CRP level in group A (P > 0.05). The left ventricular remodeling was significantly alleviated in group C and group D (P < 0.05). The NT-ProBNP level was significantly decreased in group D (P < 0.05). (c) The sinus rhythm maintenance rate of group B, group C, and group D was higher than group A (77.78%, 70.45%, 79.17% vs 43.90%), the occurrence of persistent AF was significantly lower than group A (11.11%, 14.29%, 8.33% vs 31.71%; P < 0.05). CONCLUSIONS: CCB plus fluvastatin and valsartan can reduce the recurrence rate of non-permanent AF and to delay the progression from non-permanent AF to permanent AF in patients with hypertension. The combined application of valsartan and fluvastatin is more effective than valsartan or CCB alone in the upstream therapies of AF.

Peak circulatory power is a strong prognostic factor in patients with idiopathic pulmonary arterial hypertension.

BACKGROUND: Studies have shown that peak circulatory power (peak CircP; peak oxygen uptake × peak systolic blood pressure) is a variable predictor of prognosis in patients with left heart failure. It remains unknown whether peak CircP also predicts outcome in patients with idiopathic pulmonary arterial hypertension (IPAH). METHODS: Patients with newly diagnosed IPAH who underwent symptom-limited cardiopulmonary exercise testing (CPET) from 1 January 2011 to 1 January 2014 in Fuwai Hospital were prospectively enrolled and followed for up to 66 months for cardiac events (mortality and lung transplantation). RESULTS: One hundred forty patients with IPAH (104 female, mean age: 33 ±â€¯11 years) were studied. During follow-up (mean: 42 ±â€¯14 months), 24 patients died and 1 patient underwent lung transplantation. In the univariate analysis, peak oxygen uptake(VO2), oxygen uptake at anaerobic threshold, ventilation (VE)/carbon dioxide output (VCO2) slope, end-tidal partial pressure of carbon dioxide at anaerobic threshold, peak systolic blood pressure (SBP), the change of SBP, the change of heart rate, peak work rate, peak CircP, pulmonary vascular resistance, cardiac index and World Health Organization functional class were predictive of cardiac events (all P < .05).In the multivariate analysis, Peak CircP in the fourth model had the highest significance compared with peak VO2 and VE/VCO2 slope in the second and third model (chi-square = 5.26, P < .02, HR: 0.99, 95% CI: 0.99 to 1.00). CONCLUSIONS: Peak CircP, better than peak VO2 and VE/VCO2slope, was a strong predictor of cardiac events among exercise parameters in patients with IPAH.

Serum glycated hemoglobin level as a predictor of atrial fibrillation: A systematic review with meta-analysis and meta-regression.

BACKGROUND AND AIM: Glycated hemoglobin (HbA1c) is a long-term measure of glucose control. Although recent studies demonstrated a potential association between HbA1c levels and the risk of atrial fibrillation (AF), the results have been inconsistent. The aim of this meta-analysis is to evaluate the utility of HbA1c level in predicting AF. METHODS: PubMed and the Cochrane Library databases were searched for relevant studies up to March 2016. Prospective cohort studies and retrospective case-control studies were included. Relative risk (RR) or odds ratio (OR) with 95% confidence intervals (CIs) of AF development were determined for different HbA1c levels. The random effect model was conducted according to the test of heterogeneity among studies. Subgroup analyses and meta-regression models were carried out to identify potential sources of heterogeneity. RESULTS: Eight prospective cohort studies with 102,006 participants and 6 retrospective case-control studies with 57,669 patients were finally included in the meta-analysis. In the primary meta-analysis, HbA1c levels were not associated with an increased risk of AF whether as a continuous (RR, 1.06; 95% CI, 0.96-1.18) or categorical variable (RR, 0.99; 95% CI, 0.83-1.18). Nevertheless, prospective studies showed about 10% increased risk of AF with elevated HbA1c levels both as a continuous (RR, 1.11; 95% CI, 1.06-1.16) and as a categorical variable (RR, 1.09; 95% CI, 1.00-1.18). In subgroup analyses, pooled results from studies with longer follow-up durations, published after 2012, aged < 63 years, with exclusion of cardiac surgery patients demonstrated an increased risk of AF for every 1% increase in HbA1c levels, while studies conducted in the United States with longer follow-up (more than 96 months), larger sample size and higher quality score (≥6) showed an increased risk of AF for higher HbA1c level as a categorical variable. CONCLUSIONS: Elevated serum HbA1c levels may be associated with an increased risk of AF, but further data are needed. Serum HbA1c levels might be considered as a potential biomarker for prediction of AF.

Upstream therapeutic strategies of Valsartan and Fluvastatin on Hypertensive patients with non-permanent Atrial Fibrillation (VF-HT-AF): study protocol for a randomized controlled trial.

BACKGROUND: Previous studies regarding rhythm control in patients with atrial fibrillation (AF) could not sufficiently demonstrate the efficacy of available anti-arrhythmic drugs. 'Upstream therapy' has emerged as a potential strategy for the prevention and treatment of AF. The use of angiotensin II receptor blockers and statins has been suggested to decrease new-onset AF, but which remains inadequately explored. This study was designed to examine whether valsartan or fluvastatin can reduce the risk of non-permanent AF in patients with hypertension. METHODS/DESIGN: The VF-HT-AF study is a multicenter, randomized, open-label, four-arm parallel group study with comparative evaluation of valsartan and fluvastatin as upstream therapies for the treatment of non-permanent AF complicated by hypertension. The primary outcome measure is change in the development of paroxysmal AF into persistent or permanent AF, the development of persistent AF to permanent AF, and change in incidence of overall and persistent AF recurrence, as evaluated by 7-days ambulatory electrocardiograph monitoring (Holter) and patients' diaries during 2 years' follow-up. Secondary outcome measures of this study include the occurrence of: (1) fatal and nonfatal myocardial infarction; (2) heart failure (New York Heart Association stage III or IV); (3) cardiogenic shock; (4) serious bleeding necessitating hospitalization; (5) malignant ventricular arrhythmia; (6) revascularization therapy; (7) radiofrequency catheter ablation of AF; (8) changes of left atrial dimension, as measured by ultrasound echocardiography; (9) stroke; (10) cardiovascular mortality; and (11) all-cause mortality. A total of 1879 patients will be investigated from 15 medical centers throughout China to obtain the relevant information. DISCUSSION: This is the first study in hypertensive patients complicated non-permanent AF in the Chinese population. Results of this study will inform the use of upstream therapies of AF. TRIAL REGISTRATION: chictr.org, ChiCTR-TRC-12002642.