RhPro-UK in acute ischemic stroke within 4.5 hours of stroke onset trial-2(The PROST-2 study): Rationale and design of a multicenter, prospective, randomized, open-label, blinded-endpoint, controlled phase 3 non-inferiority trial.

BACKGROUND: Recombinant human prourokinase (rhPro-UK) is a specific plasminogen activator, which has been approved to treat acute myocardial infarction in China. AIM: This phase III trial aimed to further demonstrate the efficacy and safety of rhPro-UK in patients with acute ischemic stroke (AIS) within 4.5 hours of symptom onset. METHODS AND DESIGN: RhPro-UK in AIS within 4.5 hours of stroke onset trial-2 (PROST-2) is a multicenter, prospective randomized, open-label, blinded end-point, non-inferiority, recombinant tissue plasminogen activator (rt-PA)-controlled, phase 3 trial. A total of 1,552 patients who are eligible for intravenous thrombolytic therapy from 72 clinical sites will be randomly assigned to receive either rhPro-UK 35 mg (15 mg bolus+ 20 mg infusion/30 minutes) or rt-PA 0.9 mg/kg (10% bolus +90% infusion/1 hour). STUDY OUTCOMES: The primary outcome is the proportion of patients with a modified Rankin Scale (mRS) score of 0-1 at 90 days. Secondary efficacy outcomes include the proportion of patients with mRS score of 0-2, the distribution of mRS, self-care ability in daily life on the Barthel Index at 90 days, the proportion of subjects with ≥ 4 points decrease in National Institutes of Health Stroke Scale (NIHSS) score or NIHSS score ≤ 1 from baseline at 24 hours and 7 days after treatment. Safety outcomes are symptomatic intracranial hemorrhage (sICH) and major systematic bleeding within 7 days as well as death from all causes within 90 days. DISCUSSION: The results from the PROST-2 trial will comprehensively elucidate the efficacy and safety profile of rhPro-UK as a potential alternative agent for stroke thrombolysis. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT05700591.

Controlling Risk Factors Reduces Cancer Risk in Patients with Atherosclerotic Cardiovascular Disease: A Cohort Study.

BACKGROUND: The association of atherosclerotic cardiovascular disease (ASCVD) with cancer occurrence is not well examined, and the impact of common risk factors on the risk of cancer in ASCVD patients is not known. This study aimed to explore the effect and possible causes of ASCVD on cancer risk through a cohort study. METHODS: A total of 14,665 age- and sex-matched pairs of participants were recruited from the Kailuan cohort (ASCVD vs non-ASCVD). A competing risk model was used to calculate the risk of cancer after ASCVD. RESULTS: A total of 1124 cancers occurred after 5.80 (3.05-9.44) years of follow-up. The ASCVD group had a reduced risk of cancer (hazard ratio 0.74; 95% confidence interval, 0.65-0.85). Also, the risk of cancer in the digestive system, respiratory system, urinary system, and reproductive system was reduced by 17%, 16%, 14%, and 52%, respectively. According to the status of systolic and diastolic blood pressure, fasting blood glucose, high-sensitivity C-reactive protein and body mass index after ASCVD, the risk of overall cancer and digestive system cancer decreased with the increase in the number of ideal indicators (P for trend < .01). With the increase of follow-up time, the risk of cancer and the 5 site-specific cancers gradually decreased. CONCLUSIONS: Cancer risk can be reduced by controlling for common risk factors after ASCVD event. This risk reduction is site-specific-, time-, and the number of ideal indicator-dependent.

[Egg consumption and non-alcoholic fatty liver disease: a prospective cohort study].

OBJECTIVE: To explore the association between egg consumption and the risk of non-alcoholic fatty liver disease(NAFLD), which will provide epidemiological evidence for NAFLD prevention. METHODS: A total of 6734 non-NAFLD participants(5500 men and 1234 women, aged(45±14) years old)in the Kailuan cohort followed up in 2014-2015 were enrolled. Semi-quantitative food frequency questionnaires were used to collect the diet frequency, including the consumption of eggs, over the past years. Then the score of dietary approaches to stop hypertension(DASH) was calculated. Abdominal ultrasound was applied for fatty liver diagnosis. The Kaplan-Meier method was used to estimate the cumulative incidences of NAFLD for the three groups(0-4, 5-7 and >7 eggs/week). Furthermore, Cox regression models under various adjusted factors were used to compare the risks of NAFLD. RESULTS: During the median follow-up of 45 months, 1484 NAFLDs were identified among 6734 non-NAFLD participants. The 4-year cumulative incidence rates of NAFLD for the individuals consuming 0-4, 5-7, and >7 eggs/week were 27.1%, 19.9% and 29.6%(P<0.05). The DASH score was significantly higher in those who consumed 5-7 eggs/week than in the other two groups(P<0.001). After adjusting confounders, including DASH score and dietary cholesterol, we found that compared with those consuming 5-7 eggs/week, the individuals with 0-4 and >7 eggs/week had a higher NAFLD hazard, with hazard ratios(95% confidence interval) of 1.20(1.03, 1.41) and 1.25(1.06, 1.47), respectively. The association was more significant in the population with a higher DASH score(P_(interaction)=0.02). CONCLUSION: Eating 5-7 eggs/week may have the lowest risk of NAFLD, suggesting taking a moderate amount of eggs to prevent NAFLD, even if the overall diet quality is relatively healthy.

Effect of cumulative body mass index exposure and long-term related change on incident non-alcoholic fatty liver disease.

BACKGROUND: To evaluate the association between cumulative body mass index (BMI) and long-term BMI change with non-alcoholic fatty liver disease (NAFLD). METHODS: We included 19 477 adult participants (12 556 men and 6921 women) from the Kailuan study from January 2006 to December 2013. Cumulative BMI was assessed using a quadratic mixed-effects method by sex before the index year; then, the NAFLD outcome was followed till December 2019. The long-term BMI change was calculated as the percentage change in average cumulative BMI from the baseline BMI. RESULTS: During a median follow-up of 5.63 years, 6229 individuals developed incident NAFLD. Independent of baseline BMI, the NAFLD risk escalated with the cumulative BMI with adjusted hazard ratios (HRs) (95% confidence interval [CI]) of 1.60 (1.48-1.73) and 2.28 (2.06-2.53) for the intermediate tertile and the highest tertile (Ptrend <0.001). The association is amplified in women and the young. Compared to a stable weight (BMI change: -3% to 3%), NAFLD risk increased in the baseline BMI < 24 kg/m2 group with weight gain (BMI change: >3%) and decreased in BMI ≥24 kg/m2 group with weight loss (BMI change: <-3%) for men and women. However, we only observed a decreased NAFLD risk in men (HR: 0.82, 95% CI: 0.69-0.97) with BMI < 24 kg/m2 and weight loss. CONCLUSIONS: Monitoring cumulative BMI may help to identify high-risk NAFLD populations. The association between weight gain or loss varies by sex and baseline BMI, suggesting the importance of individualized weight management for NAFLD prevention.

Neutrophil to high-density lipoprotein cholesterol ratio predicts adverse cardiovascular outcomes in subjects with pre-diabetes: a large cohort study from China.

BACKGROUND: This study aimed to examine whether the neutrophil to high-density lipoprotein cholesterol ratio (NHR) can predict cardiovascular outcomes in normoglycemic individuals with elevated fasting glucose levels. METHODS: A total of 130,801 participants with normal blood glucose levels were enrolled in the Kailuan study. Participants were categorized according to NHR quartiles and further divided into normal glucose regulation (NGR) and pre-diabetes (pre-DM) subgroups. The follow-up endpoint was major adverse cardiovascular events (CVE), including stroke and myocardial infarction. RESULTS: Over a median of 12.53 (8.95-13.08) years of follow-up, subjects with NHR levels in the highest quartile experienced more CVE than those with NHR levels in the lowest quartile. Multivariate Cox analyses showed that continuous changes in NHR (hazard ratio, 1.21; 95% confidence interval [CI], 1.15-1.28) and the highest quartile of NHR (hazard ratio, 1.30; 95% CI, 1.21-1.39) were independent predictors of CVE (all P < 0.001). Furthermore, when participants were categorized by both NHR quartile and glucose metabolism status, the NHR level in the highest quartile plus pre-DM group was associated with a 1.60-fold (95% CI, 1.38-1.86; P < 0.001] higher risk of CVE than that in the lowest quartile plus normoglycemic group. Significantly, the addition of NHR only, presence of pre-DM only, or combination of NHR and pre-DM to the prediction algorithm, including traditional risk factors, improved the C-statistic by 0.19, 0.05, and 0.23 (all P < 0.001). CONCLUSIONS: Elevated NHR or fasting blood glucose level were independently associated with a higher risk of CVE among normoglycemic individuals. Moreover, pre-DM participants with high NHR levels tended to have worse prognosis, suggesting that NHR could provide greater risk stratification value than traditional risk factors for subjects with pre-DM.

Relationship of cumulative exposure to the triglyceride-glucose index with ischemic stroke: a 9-year prospective study in the Kailuan cohort.

BACKGROUND: A single measurement of the triglyceride-glucose (TyG) index, a simple and reliable surrogate marker of insulin resistance, is associated with ischemic stroke. However, evidence for an effect of a long-term elevation in TyG index on ischemic stroke is limited. Therefore, we evaluated the relationship between cumulative TyG index exposure and the risk of ischemic stroke. METHODS: A total of 54,098 participants in the Kailuan study who had not experienced ischemic stroke underwent three measurements of fasting blood glucose and triglycerides during 2006-2007, 2008-2009, and 2010-2011. Cumulative exposure to TyG index was calculated as the weighted sum of the mean TyG index value for each time interval (value × time). Participants were placed into four groups according to the quartile of the weighted mean: Q1 group, < 32.01; Q2 group, 32.01-34.45; Q3 group, 34.45-37.47; and Q4 group, ≥ 37.47. Cox proportional hazard models were used to assess the relationships of the cumulative TyG index with incident ischemic stroke by calculating hazard ratios (HRs) and 95% confidence intervals (95% CIs). RESULTS: There were 2083 incident ischemic stroke events over the 9 years of follow-up. The risk of ischemic stroke increased with the quartile of cumulative TyG index. After adjustment for multiple potential confounders, participants in groups Q4, Q3, and Q2 had significantly higher risks of ischemic stroke, with HRs (95% CIs) of 1.30 (1.12-1.52), 1.26 (1.09-1.45), and 1.09 (0.94-1.27), respectively (Ptrend < 0.05), compared with the Q1 group. The longer duration of high TyG index exposure was significantly associated with increased ischemic stroke. CONCLUSIONS: High cumulative TyG index is associated with a higher risk of ischemic stroke. This finding implies that monitoring and the maintenance of an appropriate TyG index may be useful for the prevention of ischemic stroke.

Diabetes awareness, treatment, control rates and associated risk factors among Beijing residents in 2011: A cross-sectional survey.

OBJECTIVE: To examine the awareness, treatment and control rates of diabetes and identify their associated risk factors among Beijing residents. METHODS: A cross-sectional survey was conducted in 2011, using a stratified multistage cluster random sampling method to select a representative sample of 20,242 residents in Beijing aged 18-79 years. Diabetes was defined as fasting blood glucose (FBG) ≥7.0 mmol/L and/or history of diabetes and/or using insulin or hypoglycemic agents. All estimates of awareness, treatment and control rates were weighted by the 2010 Beijing Population Census data and the sampling scheme. Multivariate Logistic regression was used to identify factors associated with awareness, treatment and control rates. RESULTS: A total of 2061 (10.3%) participants were diagnosed as diabetes. The overall awareness, treatment and control rate among patients were 60.9%, 51.3% and 22.4%, respectively, while overall control rate among treated patients was 33.8%. These rates differed across subgroups. Women were more likely to be aware of diabetes status, receive treatment and have better glucose controlled than men (69.5% vs. 54.7% for awareness, 61.0% vs. 44.3% for treatment, and 27.6% vs. 18.6% for control, respectively). In addition, only 22.2% of treated patients had both FBG and hemoglobin A1c (HbA1c) controlled well. Multivariate Logistic regression suggested that old age, women, higher education and family history of diabetes were associated with higher awareness, treatment and control rates (All P < 0.05). Treated individuals living in rural (OR = 0.67(95%CI: 0.47-0.96)) or with dyslipidemia (OR = 0.63 (95%CI: 0.44-0.91)) had a lower diabetic control rate. CONCLUSIONS: Awareness, treatment and control rates of diabetes in Beijing were still low. A comprehensive intervention strategy on diabetes management and control is warranted.