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Background Recent studies have suggested elevated blood eosinophils are independent predictors of response to corticosteroid therapy in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Smoking status has been shown to affect corticosteroid response. Whether the association between high blood eosinophils and corticosteroid treatment failure is modified by smoking has not been fully investigated so far.Objectives This study aimed to assess whether the association between high blood eosinophils and corticosteroid treatment failure is modified by smoking.Methods We included 3402 inpatients with AECOPD treated with corticosteroids at Beijing Chao-Yang Hospital from July 2013 to June 2021. Blood eosinophil counts were measured within 24 hours of admission. An eosinophil percentage ≥2% was considered as high eosinophilic. Smokers in this study were defined as current or former smokers. Treatment failure was defined as a worsening of AECOPD that led to adverse clinical outcomes or required further treatment or an extended hospital stay or hospitalisation following the exacerbation. Multivariate-adjusted logistic models were used to estimate the OR and 95% CI associated with treatment failure.Results There were 958 (28.2%) treatment failure events occurring. Patients with high eosinophils had a lower risk of treatment failure (OR 0.74, 95% CI 0.63 to 0.87) than patients with low eosinophils. Compared with never smoking and low eosinophilic group, the ORs for treatment failure were 0.70 (95% CI 0.52 to 0.96) for never smoking and high eosinophilic group, 0.82 (95% CI 0.64 to 1.05) for smoking and low eosinophilic group and 0.62 (95% CI 0.47 to 0.81) for smoking and high eosinophilic group. Furthermore, there was no significant interaction between eosinophils and smoking status in relation to treatment failure (p for interaction=0.73). Similar results were obtained from multiple secondary outcomes and subgroup analyses.Conclusion Elevated blood eosinophils are associated with a lower rate of corticosteroid treatment failure, regardless of smoking status. Smoking does not modify the association between blood eosinophil level and corticosteroid treatment failure among inpatients with AECOPD.

AbstractBackground Limited studies are available concerning on the earlier identification of AKI with sepsis. The aim of the study was to identify the risk factors of AKI early which depended on the timing onset and progression of AKI and investigate the effects of timing onset and progression of AKI on clinical outcomes.Methods Patients who developed sepsis during their first 48-h admission to ICU were included. The primary outcome was major adverse kidney events (MAKE) consisted of all-cause mortality, RRT-dependence, or an inability to recover to 1.5 times of the baseline creatinine value up to 30 days. We determined MAKE and in-hospital mortality by multivariable logistic regression and explored the risk factors of early persistent-AKI. C statistics were used to evaluate model fit.Results 58.7% sepsis patients developed AKI. According to the timing onset and progression of AKI, Early transient-AKI, early persistent-AKI, late transient-AKI, late persistent-AKI were identified. Clinical outcomes were quite different among subgroups. Early persistent-AKI had 3.0-fold (OR 3.04, 95% CI 1.61 − 4.62) risk of MAKE and 2.6-fold (OR 2.60, 95%CI 1.72 − 3.76) risk of in-hospital mortality increased compared with the late transients-AKI. Older age, underweight, obese, faster heart rate, lower MAP, platelet, hematocrit, pH and energy intake during the first 24 h on ICU admission could well predict the early persistent-AKI in patients with sepsis.Conclusion Four AKI subphenotypes were identified based on the timing onset and progression of AKI. Early persistent-AKI showed higher risk of major adverse kidney events and in-hospital mortality.Trial registration This study was registered in the Chinese Clinical Trials Registry (www.chictr.org/cn) under registration number ChiCTR-ECH-13003934.

Abstract Background and aims Developing accessible, affordable, and effective approaches to smoking cessation is crucial for tobacco control. Mobile health (mHealth) based interventions have the potential to aid smokers in quitting, and integrating treatments from multiple sources may further enhance their accessibility and effectiveness. As part of our efforts in smoking cessation, we developed a novel behavioral intervention delivery modality for smoking cessation that integrated three interventions using the WeChat app, called the “Way to Quit” modality (WQ modality). It is presented here the protocol for a randomized controlled trial evaluating the effectiveness, feasibility, and cost-effectiveness of the WQ modality in Chinese smokers. Methods Eligible participants (n = 460) will be recruited via online advertisement in Beijing, China. They will be randomly assigned to receive either quitline-based treatment (QT, n = 230) or WQ modality-based treatment (WQ, n = 230) using a block randomization method. Participants in the QT group will receive telephone-assisted treatment over a four-week period (multi-call quitline protocol), while those in the WQ group will receive integrated interventions based on the WQ modality for four weeks. A four-week supply of nicotine replacement therapy (gums) will be provided to all participants. Participants will be asked to complete phone or online follow-up at 1, 3, 6, and 12-months. At 1-month follow-up, individuals with self-reported smoking abstinence for more than 7 days will be invited to receive an exhaled carbon monoxide (CO) test for biochemical validation. The primary aim is to determine whether the WQ modality is effective in assisting smokers in quitting smoking. The secondary aims are to evaluate the acceptability, satisfaction, and cost-effectiveness of the WQ modality. Discussion If the WQ modality is determined to be effective, acceptable, and affordable, it will be relatively easy to reach and provide professional cessation treatments to the communities, thus helping to reduce the disparities in smoking cessation services between different regions and socioeconomic groups. Trial registration Chinese Clinical Trial Registry: ChiCTR2200066427, Registered December 5, 2022.

Background Although computed tomography (CT)-defined emphysema is considered a predictor of lung cancer risk, it is not fully clear whether CT-defined emphysema is associated with the prognosis of lung cancer. We aimed to assess the clinical impact of CT-defined emphysema on the survival of lung cancer. Methods In the prospective cohort study of nonsmall cell lung cancer (NSCLC), the correlation between CT-defined emphysema and clinical variables was analysed. A multivariable Cox regression model was built to assess the association between CT-defined emphysema and overall survival (OS) for up to 8.8 years. The differences in survival analyses were derived by Kaplan–Meier analysis and log-rank testing. Low attenuation area (LAA%) was defined as the per cent of voxels below −950 HU. Results 854 patients were included and CT-defined emphysema was present in 300 (35.1%) at diagnosis. Epidermal growth factor receptor (EGFR) wild-type (OR 1.998; p17% displayed poorer survival than those with LAA% ≤17% (median 432 versus 670 days; HR 1.564; p=0.020). Conclusions CT-defined emphysema, especially CLE with LAA%>17%, is an independent predictor of NSCLC prognosis. Moreover, prospective studies are needed to further explore this association.

Abstract Background Patients with type 2 diabetes mellitus (T2DM) usually have higher blood viscosity attributed to high blood glucose that can decrease blood supply to the pancreas. A mild increase in blood pressure (BP) has been reported as a potential compensatory response that can maintain blood perfusion in the islet. However, how BP influences beta-cell function in T2DM subjects remains inconsistent. This study aimed to examine the relationship between BP and beta-cell function in patients with T2DM under different HbA1c levels. Methods This is a cross-sectional study of 615 T2DM patients, whose clinical data were extracted from hospital medical records. Beta-cell function was assessed by insulin secretion-sensitivity index-2 (ISSI2). Multivariable linear regression analysis and restricted cubic splines (RCS) analysis were performed to identify the association between systolic BP (SBP) and ISSI2. Mediation analysis was performed to determine whether higher SBP could reduce blood glucose by enhancing beta-cell function. Results After adjustment of potential confounders, in participants with HbA1c ≥ 10%, the SBP between 140 to150 mmHg had the highest log ISSI2 (b = 0.227, 95% CI 0.053–0.402), an association specific to participants with

Abstract Background Risk profiles for premature cardiovascular disease (CVD) are unclear. This study aimed to examine baseline risk profiles for incident CVD by age at onset in Chinese population. Methods A total of 97,841 participants without CVD were enrolled from the Kailuan cohort study. Four age groups were examined (

Abstract Background Long-term patterns of serum uric acid (SUA) and their association with the risk of myocardial infarction (MI) and mortality are poorly characterized as prior studies measured SUA at a single time point. This study aimed to identify SUA trajectories and determine their associations with incident MI and all-cause mortality. Methods We included 85,503 participants who were free of MI in or prior 2012 from the Kailuan study. SUA trajectories during 2006–2012 were identified by group-based trajectory modeling. Cox proportional hazard models were used to assess the association of SUA trajectories with MI and all-cause mortality. Results We identified three SUA trajectories during 2006–2012: low-stable (n=44,124, mean SUA: 236–249 μmol/L), moderate-stable (n=34,431, mean SUA: 324–354 μmol/L) and high-stable (n=6,984, mean SUA: 425–463 μmol/L). During a median follow-up of 6.8 years, we documented 817 (0.96%) incident MI and 6498 (7.60%) mortality. Compared with the low-stable group, high-stable group experienced a higher risk of MI (hazard ratio [HR], 1.35; 95% confidence [CI], 1.07–1.71) and all-cause mortality (HR, 1.22; 95% CI, 1.12–1.33). Multiple sensitivity analyses yielded similar results. Additionally, the association of SUA trajectory with MI and all-cause mortality was more pronounced in individuals without a history of hypertension (P-interaction=0.0359) and those aged

Abstract Background Recent studies have suggested that triglyceride-glucose (TyG) index is an independent predictor of cardiovascular disease (CVD). However, the impact of long-term visit-to-visit variability in TyG index on the risk of CVD is not known. We aimed to investigate the longitudinal association between baseline and mean TyG index as well as TyG index variability and incident CVD in a Chinese population. Methods We included 49,579 participants without previous history of CVD in the Kailuan study who underwent three health examinations (2006, 2008, and 2010) and were followed up for clinical events until 2019. TyG index was calculated as Ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. We measured TyG index variability as the SD of the residuals obtained from a linear regression on the three TyG index measurements for each individual. Multivariate-adjusted Cox models were used to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) with incident CVD. Results During a median follow-up time of 9.0 years, 2404 developed CVD. The highest tertile (T3) of baseline and mean TyG index were each associated with higher CVD incidence as compared with the lowest tertile (T1): aHR, 1.25; 95% CI 1.11–1.42; and aHR 1.40; 95% CI 1.24–1.58, respectively. Tertile 3 of TyG index variability was associated with increased CVD incidence compared to T1 group (aHR, 1.12; 95% CI 1.01–1.24). Similar findings were observed in a series of sensitivity analyses. Conclusion Higher TyG index level and greater TyGindex variability were each independently associated with a higher incidence of CVD.

Background and aims: Urine ketone bodies have been considered as predictors of stroke in diabetic patients, however, the role of urine ketone bodies in the prognosis of stroke has not been investigated well. This study aimed to investigate the association between urine ketone bodies and adverse outcomes in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA). Methods: This study enrolled 14 015 patients with AIS or TIA who screened for urine ketone bodies from the Third China National Stroke Registry. Status of urine ketone bodies were classified into negative, suspicious positive and positive. The outcomes were all-cause death and poor functional outcomes (modified Rankin Scale [mRS] 2–6/3-6) at 3 months and 1 year. Multivariable Cox proportional hazards regressions and logistic regressions were adopted to explore the associations. Results: Participants with negative, suspicious positive and positive urine ketone bodies were 12979 (92.61%), 480 (3.42%) and 556 (3.97%). After multivariate adjustment, patients with positive urine ketone bodies had a higher risk of all-cause death (hazard ratio, 1.74; confidence interval [CI], 1.07–2.83), a higher proportion of mRS score 2–6 (Odds ratio [OR], 1.85; 95% CI, 1.51–2.27), mRS score 3–6 (OR, 2.00; 95% CI, 1.61–2.48) at 3 months, compared to those with negative urine ketone bodies. Significant associations persisted at 1 year. Furthermore, there was no significant interaction of diabetes status and alcohol use with urine ketone bodies. Conclusions: Positive urine ketone bodies can independently predict all-cause death and poor functional outcomes in patients with AIS or TIA.

Abstract Background The impact of long-term serum uric acid (SUA) exposure and time course of SUA accumulation on diabetes mellitus (DM) is unknown. This study aimed to evaluate the association of cumulative SUA (cumSUA) exposure and its accumulation time course with risk of DM. Methods This prospective study included 46,434 participants without DM and underwent three examinations at 2006, 2008, and 2010. CumSUA from 2006 to 2010 was calculated, multiplying mean values between consecutive examinations by time intervals between visits. Time course of SUA accumulation was categorized as the slope of SUA versus time from 2006 to 2010, or by splitting the overall accumulation into an early (cumSUA06-08) and late accumulation (cumSUA08-10). Results During 6.99 years of follow-up, we identified 2971 incident DM cases. In the fully adjusted model, a higher risk of DM was observed in participants with the highest quartile of cumSUA (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.17–1.46), cumulative burden >0 (HR, 1.23; 95% CI, 1.08–1.40), and with 6 year of hyperuricemia exposure duration (HR, 1.25; 95% CI, 1.01–1.55). When considering the time course of SUA accumulation, participants with a negative slope (HR, 1.05; 95% CI, 1.01–1.12), or combined with cumSUA ≥ median and a negative slope had elevated risk of DM (HR, 1.58; 95% CI, 1.18–2.11). Conclusions Incident DM risk depends on cumulative exposure of SUA and time course of SUA accumulation. Early SUA accumulation resulted in a greater risk increase compared with later accumulation, emphasizing the importance of optimal SUA control early in life.

Background: Multifocal atherosclerosis has dramatically increased annual risk of adverse cardiovascular events than single artery affected. Triglyceride-rich lipoprotein (TRL) has been implicated in the early development of atherosclerosis.However, evidence on the effect of remnant cholesterol, a major atherogenic component of TRL, on multifocal atherosclerosis in Chinese health asymptomatic subjects is insufficient. This study aimed to investigate the association of remnant cholesterol with intra- and extra-cranial atherosclerosis in Chinese population. Methods: This study enrolled 3665 participants (median age 52.31 years) from the Asymptomatic Polyvascular Abnormalities Community study. Parameters of intra- and extra-cranial atherosclerosis includes intracranial artery stenosis (ICAS), carotid plaque, carotid artery stenosis (CAS), and carotid hypertrophy (intima-media thickness >0.9 mm). Logistic regression was used to assess these associations. Results: The prevalence of vascular atherosclerosis significantly increased with increasing remnant cholesterol quartiles (P for trend

Background and aims: High remnant cholesterol is associated with cardiovascular disease (CVD), but whether CVD risk attributable to remnant cholesterol vary between young and later adults remains unknown. The study aimed to assess age differences in the association between remnant cholesterol and CVD. Methods: This prospective study included 95 663 participants without CVD and lipid-lowering treatment at baseline, including 16 254 young adults (age 18–39 years) and 79 409 later adults (age ≥40 years). Individuals were grouped by clinically meaningful remnant cholesterol concentrations of

Abstract Background The prognostic value of serum bilirubin in stroke is controversial, since bilirubin has both neuroprotective and neurotoxic properties. We aimed to investigate the association between serum bilirubin, including total bilirubin (TBIL), direct bilirubin (DBIL) and indirect bilirubin (IBIL) and poor functional outcomes in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA). Methods All patients with AIS or TIA were recruited from the Third China National Stroke Registry. The poor functional outcomes included modified Rankin Scale (mRS) score 2–6 and 3–6 at 3 months and 1 year. Multivariable logistic regression was used to investigate the associations of TBIL, DBIL, and IBIL with poor functional outcomes. Results Among 11,121 enrolled patients, the median (interquartile range) of TBIL, DBIL, and IBIL was 13.30 (9.90–17.70), 3.80 (2.70–5.30), and 9.30 (6.70–12.80) µmol/L. After adjustment for conventional confounding factors, patients in the highest TBIL quartile had the highest proportion of mRS score 2–6 at 3 months (odds ratio [OR], 1.37; 95 % confidence interval [CI], 1.19–1.59) and 1 year (OR, 1.31; 95 % CI, 1.13–1.52), and mRS score 3–6 at 3 months (OR, 1.33; 95 % CI, 1.11–1.59) and 1 year (OR, 1.28; 95 % CI, 1.07–1.53), when compared to patients in the lowest TBIL quartile. Similar results were observed for DBIL and IBIL. We also found J-shaped associations between serum bilirubin levels and each outcome. Conclusions Elevated levels of serum bilirubin were significantly associated with poor functional outcomes in patients with AIS or TIA at 3 months and 1 year.

Background Oxidized low‐density lipoprotein (oxLDL) and hs‐CRP (high‐sensitivity C‐reactive protein) plays an important role in cardiovascular diseases though inflammation and oxidative stress, etc. However, evidence on their combined effects on stroke prognosis is still limited. We aimed to explore the joint association of oxLDL and hs‐CRP with outcomes of minor stroke or transient ischemic attack. Methods and Results A subgroup of 3019 patients from the CHANCE trial (Clopidogrel in High‐Risk Patients With Acute Nondisabling Cerebrovascular Events) were analyzed. Baseline oxLDL and hs‐CRP levels were measured. The primary outcome was any stroke within 90 days. The secondary outcomes included any stroke within 1 year, and ischemic stroke, combined vascular events, and poor functional outcomes (modified Rankin Scale 2–6 or 3–6) at 90 days and 1 year. Vascular events outcomes were analyzed with Cox proportional hazards and poor functional outcomes with logistic models. Elevated oxLDL (>28.81 μg/dL) and hs‐CRP (>4.20 mg/L) was observed in 624 (20.67%) of the 3019 patients. Patients with oxLDL >28.81 μg/dL and hs‐CRP >4.20 mg/L had a higher risk of recurrent stroke within 90 days (adjusted hazard ratio, 1.52; 95% CI, 1.17–1.97), compared with those with oxLDL ≤28.81 μg/dL and hs‐CRP ≤4.20 mg/L, after adjusting relevant confounding factors (P=0.002). Similar results were observed for secondary outcomes (P

Abstract Prehypertension is a risk factor for cardiovascular disease (CVD) and all‐cause mortality. However, it is unclear whether prehypertension combined with diabetes associate with a higher risk for cardiovascular disease and all‐cause mortality. The purpose of this study was to explore the relationship between prehypertension and the risk of CVD and all‐cause mortality was different among individuals with or without diabetes. In the prospective community‐based Kailuan study, 67 344 participants without hypertension or a history of CVD at baseline (2006) were included. Prehypertension was defined as systolic blood pressure of 120–139 mmHg or diastolic blood pressure of 80–89 mmHg. The outcomes were CVD and all‐cause mortality were followed up through December 31, 2017. We performed Cox proportional hazards models to evaluate the relationships between prehypertension and CVD and all‐cause mortality by diabetes status. During a median follow‐up of 11.03 years, 2981 CVD events and 4655 all‐cause mortality occurred. After adjusting age, sex, and other factors, the associations of prehypertension with risk of CVD and all‐cause mortality were significant in participants without diabetes (hazard ratio and 95% confidence interval: 1.54 [1.38–1.71] and 1.27 [1.17–1.38]), but not in participants with diabetes (1.20 [0.93–1.56] and 0.88 [0.73–1.07]). The interactions between prehypertension and diabetes for the risk of CVD and all‐cause mortality were all significant (all p

Abstract Background Previous studies has shown a significant relationship between baseline triglyceride-glucose (TyG) index and subsequent cardiovascular disease (CVD). However, the effect of longitudinal changes in TyG index on the risk of CVD remains uncertain. This study aimed to investigate the association between change in TyG index and the risk of CVD in the general population. Methods The current study included 62,443 Chinese population who were free of CVD. The TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2], and change in TyG index was defined as the difference between the TyG index in 2010 and that in 2006. Multivariable-adjusted Cox proportional hazard models and restricted cubic spline analysis were used to examine the association between change in TyG index and the risk of CVD. Results During a median follow-up of 7.01 years, 2530 (4.05%) incident CVD occurred, including 2018 (3.23%) incident stroke and 545 (0.87%) incident myocardial infarction (MI). The risk of developing CVD increased with the quartile of change in TyG index, after adjustment for multiple potential confounders, the hazard ratios for the Q4 group versus the Q1 group were 1.37 (95% confidence interval [CI], 1.21–1.54) for the overall CVD, 1.38 (95% CI, 1.19–1.60) for stroke, and 1.36 (95% CI, 1.05–1.76) for MI. Restricted cubic spline analysis also showed a cumulative increase in the risk of CVD with increases in the magnitude of change in TyG index. The addition of change in TyG index to a baseline risk model for CVD improved the C-statistics (P = 0.0097), integrated discrimination improvement value (P

Abstract Background Evidence on longitudinal variability of serum uric acid (SUA) and risk of all-cause mortality in the general population is limited, as many prior studies focused on a single measurement of SUA. Methods A total of 53,956 participants in the Kailuan study who underwent three health examinations during 2006 to 2010 were enrolled. Variability of SUA was measured using the coefficient of variation (primary index), standard deviation, average real variability, and variability independent of the mean. Cox proportional hazard regressions were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) for the association of variability of SUA with subsequent risk of all-cause mortality, considering its magnitude and the direction and across different baseline SUA categories. Results Over a median follow-up of 7.04 years, 2728 participants died. The highest variability of SUA was associated with an increased risk of all-cause mortality, the HR was 1.33 (95% CI, 1.20–1.49) compared with the lowest variability. In this group, both a large fall (HR, 1.28; 95% CI, 1.14–1.44) and rise (HR, 1.18; 95% 1.05–1.32) in SUA were related to risk of all-cause mortality. These associations were similar across different baseline SUA categories. Consistent results were observed in alternative measures of SUA variability. Moreover, individuals with higher variability in SUA were more related to common risk factors than those with stable SUA. Conclusions Higher variability in SUA was independently associated with the risk of all-cause mortality irrespective of baseline SUA and direction of variability in the general population.

Abstract Background Triglyceride-glucose (TyG) index was recently suggested to be a reliable surrogate marker of insulin resistance. We aim to investigate the associations between baseline and long-term TyG index with subsequent stroke and its subtypes in a community-based cohort. Methods A total of 97,653 participants free of history of stroke in the Kailuan Study were included. TyG index was calculated as ln (fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2). Baseline TyG index was measured during 2006–2007. Updated cumulative average TyG index used all available TyG index from baseline to the outcome events of interest or the end of follow up. The outcome was the first occurrence of stroke, including ischemic stroke, intracerebral hemorrhage and subarachnoid hemorrhage. The associations of TyG index with outcomes were explored with Cox regression. Results During a median of 11.02 years of follow-up, 5122 participants developed stroke of whom 4277 were ischemic stroke, 880 intracerebral hemorrhage, and 144 subarachnoid hemorrhage. After adjusting for confounding variables, compared with participants in the lowest quartile of baseline TyG index, those in the third and fourth quartile were associated with an increased risk of stroke (adjusted hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.12–1.33, and adjusted HR 1.32, 95% CI 1.21–1.44, respectively, P for trend

Abstract Background The triglyceride–glucose (TyG) index, which is a simple surrogate marker of insulin resistance, has been suggested as a contributor of cardiovascular disease. However, evidence on the effect of long-term elevation of the TyG index exposure on myocardial infarction (MI) is limited. The current study aimed to evaluate the association of baseline and long-term elevation of the TyG index exposure with the risk of MI. Methods A total of 98,849 participants without MI at baseline (2006) were enrolled from the Kailuan study. The baseline TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. The long-term TyG index was characterized in two ways as follows. The updated mean TyG index was calculated as the mean of TyG index at all previous visits before MI occurred or the end of follow-up; alternatively, the TyG index was calculated as the number of visits with a high TyG index in 2006, 2008, and 2010, ranging from 0 (no exposure) to 3 (had high TyG index at all three study visits). Hazard ratio (HR) and 95% confidence interval (CI) was estimated using multivariable Cox proportion hazard models. Results During a median follow-up of 11.03 years, 1555 incident MI occurred. In the multivariable-adjusted model, the risk of MI increased with quartiles of the baseline and updated mean TyG index, the HR in quartile 4 versus quartile 1 was 2.08 (95% CI,1.77–2.45) and 1.58 (1.18–2.12), respectively. Individuals with a high TyG index at all three visits had a 2.04-fold higher risk (95% CI, 1.63–2.56) of MI compared with no exposure. Subgroup analyses showed that the associations were more pronounced in women than in men (P interaction = 0.0411). Conclusions Elevated levels of the baseline and long-term TyG index are associated with an increased risk of MI. This finding indicates that the TyG index might be useful in identifying people at high risk of developing MI.

Abstract Background Prediabetes has become a pandemic. This study aimed to identify a better predictor for the incidence of prediabetes, which we hypothesize to be the triglyceride-glucose (TyG) index, a simplified insulin resistance index. We compared its predictive value with the other common risk factors of prediabetes. Methods The participants of this analysis were derived from the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal (REACTION) study. A total of 4543 participants without initial prediabetes or diabetes were followed up for 3.25 years. Using multivariate logistic regression model, the associations between baseline obesity, lipid profiles and non-insulin-based insulin resistance indices with the incidence of prediabetes were analyzed. To assess which is better predictor for the incidence of prediabetes, the area under curves (AUCs) calculated from the receiver operating characteristic curve analyses were used to evaluate and compare with the predictive value of the different indices. Results During the 3.25 years, 1071 out of the 4543 participants developed prediabetes. Using the logistic regression analysis adjusted for some potential confounders, the risk of incidence of prediabetes increased 1.38 (1.28–1.48) fold for each 1–SD increment of TyG index. The predictive ability (assessed by AUCs) of TyG index for predicting prediabetes was 0.60 (0.58–0.62), which was superior to the indices of obesity, lipid profiles and other non-insulin-based insulin resistance indices. Although the predictive ability of the TyG index was overall similar to fasting plasma glucose (FPG) (P = 0.4340), TyG index trended higher than FPG in females (0.62 (0.59–0.64) vs. 0.59 (0.57–0.61), P = 0.0872) and obese subjects (0.59 (0.57–0.62) vs. 0.57 (0.54–0.59), P = 0.1313). TyG index had superior predictive ability for the prediabetic phenotype with isolated impaired glucose tolerance compared with FPG (P

Background and Purpose Previous studies suggested increased visit-to-visit variability of total cholesterol (TC) is associated with stroke. This study aimed to investigate the associations of various lipids measurements variability and the risk of stroke and stroke type (ischemic and hemorrhagic stroke). Methods Fifty-one thousand six hundred twenty participants in the Kailuan Study without history of myocardial infarction, stroke, and cancer who underwent three health examinations during 2006 to 2010 were followed for incident stroke. Variability in TC, triglycerides, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) measurements were measured using the coefficient of variation (CV), standard deviation (SD), variability independent of the mean (VIM), and average real variability (ARV). Results During a median of 6.04 years of follow-up, 1,189 incident stroke (1,036 ischemic and 160 hemorrhagic stroke) occurred. In the multivariable-adjusted model, the hazard ratio (HR) comparing participants in the highest versus lowest quartile of CV of HDL-C were 1.21 (95% confidence interval [CI], 1.02 to 1.45; P for trend=0.013) for ischemic stroke. The highest quartile of CV of LDL-C was associated with 2.17-fold risk of hemorrhagic stroke (HR, 2.17; 95% CI, 1.25 to 3.75; P for trend=0.002) compared with the lowest quartile. We did not observe any significant association between TC and triglycerides variability with any of stroke. Consistent results were obtained when calculating variability index using SD, VIM, or ARV. Conclusions These findings suggest the high visit-to-visit HDL-C and LDL-C variability were associated with an increased incidence of ischemic and hemorrhagic stroke, respectively.

Background The serum uric acid/serum creatinine ratio (SUA/SCr), which represents renal function‐normalized SUA, is associated with diverse adverse outcomes. The aim of this study was to investigate the association between SUA/SCr and cardiovascular disease (CVD), and determine whether and to what extent this association is mediated by cardiometabolic factors. Methods and Results This prospective study enrolled 96 378 participants from the Kailuan study without stroke and myocardial infarction at baseline (2006). Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Mediation analyses were conducted to separately explore the mediating effects of cardiometabolic factors on the association between SUA/SCr and CVD. During median follow up of 11.01 years, 6315 (6.55%) individuals developed incident CVD. After adjustment for potential confounders, the highest quartile of SUA/SCr was associated with the highest risk of CVD (HR, 1.15; 95% CI, 1.07–1.23), stroke (HR, 1.16; 95% CI, 1.07–1.26), ischemic stroke (HR, 1.12; 95% CI, 1.02–1.22), and hemorrhagic stroke (HR, 1.36; 95% CI, 1.11–1.65), but not with myocardial infarction (HR, 1.07; 95% CI, 0.92–1.25). The association was consistent across different degrees of kidney function and glucose tolerance statuses. Additionally, the association between high SUA/SCr and CVD was partially mediated by triglycerides (30.74%), body mass index (BMI) (19.52%), total cholesterol (15.06%), hs‐CRP (high‐sensitivity C‐reactive protein) (13.06%), diastolic blood pressure (11.75%), and blood glucose (−16.38%). Conclusions SUA/SCr and CVD were positively associated. Furthermore, this association was partially mediated through blood lipids, BMI, blood pressure, hs‐CRP, and blood glucose.

Introduction: Glomerular hyperfiltration (GHF) is an early kidney injury. We investigated whether GHF is associated with arterial stiffness expressed by increase of brachial–ankle pulse wave velocity (baPWV) and pulse pressure (PP), and whether the coexistence of GHF and abnormal metabolism increases the risk of arterial stiffness.Methods: In this prospective cohort study, 2,133 non-chronic kidney disease (CKD) participants aged ≥40 years were followed for a mean period of 3.3 years. The extent of arterial stiffness was expressed by measures of baPWV and PP. GHF was defined as eGFR exceeding the age- and sex-specific 90th percentile. Multivariate logistic regression models were used to assess the association between GHF/abnormal metabolism and increased baPWV/PP. The interaction indexes of GHF and abnormal metabolism on arterial stiffness were calculated based on the OR in a multivariate logistic regression model.Results: GHF alone was not associated with increased baPWV or PP in all participants in this study. However, when GHF coexisted with abnormal metabolism, the risk of increased PP increased 3.23-fold [OR = 3.23(1.47–7.13)] compared with participants with normal filtration and normal metabolism, in which the interaction accounted for 55.1% of the total effect and 79.8% of the effect from GHF and abnormal metabolism. After subtracting the independent effects of GHF and abnormal metabolism, their combined effect still resulted in a 1.78-fold increase in PP.Conclusion: GHF could interact with abnormal metabolism to significantly enhance arterial stiffness. Since abnormal metabolism commonly exists in the general population, even slight changes in renal function should be distinguished to prevent arterial stiffness risk.

Background: Both baseline blood pressure (BP) and cumulative BP have been used to estimate cardiovascular event (CVE) risk of higher BP, but which one is more reliable for recommendation to routine clinical practice is unclear.Methods: In this prospective study, conducted in the Kailuan community of Tanshan City, China, a total of 95,702 participants free of CVEs at baseline (2006–2007) were included and followed up until 2017. Time-weighted cumulative BP that expresses the extent of cumulative BP exposure is defined as the sum of the mean of two consecutive systolic or diastolic BP times the interval between the two determinations, then normalized by the total follow-up duration. Incident CVEs during 2006–2017 were confirmed by review of medical records. We performed a competing risk regression analysis to assess CVE risk of the different durations of higher BP exposure. ROC analysis was performed to assess the predictive value of higher BP on CVE occurrence.Results: We found that when the risk of higher BP on CVE occurrence was estimated based on time-weighted cumulative BP, the hazard ratios (HRs) increased with the increase in duration of higher BP exposure in each of the four BP groups:

Background and Purpose: Compared with one single measurement, dynamic change of lipid parameter calculated by repeated measurements has been recognized as a potential biometric to make stroke risk assessments. Total cholesterol (TC) is an important risk factor for stroke, but the relationship between TC change and incident stroke has not been investigated thoroughly. We thus aimed to explore the association between 2-year TC change and the risk of incident stroke, both ischemic and hemorrhagic, in the general population.Methods: From June 2006 to October 2007, a total of 70,999 participants with complete TC value at baseline (2006–2007) and the second examination (2008–2009) were included in our study. The change of TC was calculated as the 2-year follow-up TC subtracting baseline TC. Cox proportional hazards regression analysis was used to evaluate the association between the tertile of TC change and risk of incident stroke and stroke subtypes.Results: A total of 2,815 cases of stroke events were identified with a median follow-up period of 9.0 years. After adjusting for baseline TC and confounding factors, 2-year TC change was independently associated with increased risk of total stroke (HR 1.07, 95% CI 1.02–1.12) and ischemic stroke (HR 1.08, 95% CI 1.03–1.13) per SD (1.04 mmol/L) increase, while no significant association was obtained between TC change and intracerebral hemorrhage (p = 0.659).Conclusions: Increased 2-year TC change is associated with an elevated risk of incident total stroke and ischemic stroke, irrespective of the baseline TC value. Maintaining a sustained ideal level of TC is important for stroke prevention.

Background Serum uric acid (SUA) has been demonstrated as a risk factor for myocardial infarction (MI) and all‐cause mortality; however, the impact of cumulative SUA (cumSUA) remains unclear. We aimed to investigate the association of cumSUA with MI risk and all‐cause mortality, and to further explore the effects of SUA accumulation time course. Methods and Results The study enrolled 53 463 participants without a history of MI, and these participants underwent 3 examinations during 2006 to 2010. cumSUA from baseline to the third examination was calculated, multiplying mean values between consecutive examinations by time intervals between visits. Cox models estimated hazard ratios (HRs) and 95% CIs of MI and all‐cause mortality for cumSUA quartiles, hyperuricemia exposure duration, and SUA accumulation time course. During a median follow‐up of 7.04 years, 476 incident MIs and 2692 deaths occurred. In the fully adjusted model, a higher MI risk was observed in the highest cumSUA quartile (HR, 1.48; 95% CI, 1.10–1.99), in participants with longer hyperuricemia exposure duration (HR, 1.71; 95% CI, 1.06–2.73), and in participants with cumSUA≥median and a negative slope (HR, 1.58; 95% CI, 1.18–2.11). Similar associations persisted for all‐cause mortality. Conclusions The risk of MI and all‐cause mortality increased with higher cumSUA and was affected by the SUA accumulation time course. Early SUA accumulation contributed more to MI risk and all‐cause mortality than later SUA accumulation with the same overall cumulative exposure, emphasizing the importance of optimal SUA control early in life.

Introduction As a neuroprotective medication, butylphthalide (NBP) may help protect against cerebral ischaemic injury. However, evidence on whether NBP influences the outcomes of patients who had acute ischaemic stroke who are receiving revascularisation treatment is limited. This study aims to evaluate whether additional NBP therapy can improve the functional outcome of patients who receive intravenous recombinant tissue plasminogen activator and/or endovascular treatment (EVT).Methods and analysis The study will be a randomised, double-blind, placebo-controlled, multiple-centre, parallel group trial. The sample size is estimated at 1200 patients. Eligible patients will be randomised at a 1:1 ratio to receive either NBP or placebo daily for 90 days, which will include 14 days of injections and 76 days of capsules. The first use of NBP/placebo will be started within 6 hours of onset of ischaemic stroke. The primary outcome is the functional outcome as assessed by the 90-day modified Rankin Scale, adjusted for baseline scores on the National Institutes of Health Stroke Scale. The primary safety outcome is the percentage of serious adverse events during the 90 days of treatment. This trial will determine whether NBP medication benefits patients who had acute ischaemic stroke who receive intravenous thrombolysis or EVT.Ethics and dissemination The protocol was written according to the general ethical guidelines of the Declaration of Helsinki and approved by the Institutional Review Board/Ethics Committee of Beijing Tiantan Hospital, Capital Medical University with approval number KY 2018-003-02. Ethics committees of all participating sites have approved the study . Results of the study will be published in peer-reviewed scientific journals and shared in scientific presentations.Trial registration number NCT03539445.

BACKGROUND Metabolically healthy obesity (MHO) and metabolically healthy overweight (MH-OW) have been suggested to be important and emerging phenotypes with an increased risk of cardiovascular disease (CVD). However, whether MHO and MH-OW are associated with all-cause mortality remains inconsistent.METHODS The association of MHO and MH-OW and all-cause mortality was determined in a Chinese community-based prospective cohort study (the Kailuan study), including 93,272 adults at baseline. Data were analyzed from 2006 to 2017. Participants were categorized into 6 mutually exclusive groups, according to BMI and metabolic syndrome (MetS) status. The primary outcome was all-cause death, and accidental deaths were excluded.RESULTS During a median follow-up of 11.04 years (interquartile range, 10.74–11.22 years), 8977 deaths occurred. Compared with healthy participants with normal BMI (MH-NW), MH-OW participants had the lowest risk of all-cause mortality (multivariate-adjusted HR [aHR], 0.926; 95% CI, 0.861–0.997), whereas there was no increased or decreased risk for MHO (aHR, 1.009; 95% CI, 0.886–1.148). Stratified analyses and sensitivity analyses further validated that there was a nonsignificant association between MHO and all-cause mortality.CONCLUSIONS Overweight and obesity do not predict increased risk of all-cause mortality in metabolic healthy Chinese individuals.FUNDING National Natural Science Foundation of China (NSFC; 81673247, 81872682 and 81773527), the NSFC Joint Project, and the Australian National Health and Medical Research Council (NHMRC; NSFC 81561128020-NHMRC APP1112767).

Background Proteinuria often changes and is known as a “time‐dependent exposure.” The effect of time‐dependent proteinuria on the risk of future stroke remains unclear. Proteinuria is often detected in patients with diabetes mellitus. The present study was designed to evaluate the association between time‐dependent proteinuria and the risk of stroke in a patient cohort with different glucose tolerance status. Methods and Results A total of 82 938 participants, who were free of myocardial infarction or stroke and underwent fasting blood glucose and urinary protein measurements at baseline in the Kailuan study, were enrolled. Proteinuria was determined using urine dipstick tests at baseline and subsequent follow‐ups. Time‐dependent proteinuria was defined as the status of urine protein updated through the follow‐up examinations, separately. Time‐dependent Cox regression models were used to analyze the relationship between time‐dependent proteinuria and the risk of stroke. During a median follow‐up of 8.37 years, 2538 participants developed stroke. After adjusting for confounding factors, the hazard ratio (95% CI) for stroke in time‐dependent proteinuria among all participants, and the normoglycemia, prediabetes, and diabetes mellitus populations were 1.68 (1.49–1.89), 1.73 (1.47–2.05), 2.15 (1.70–2.72), and 1.30 (1.03–1.65), respectively. There were interaction effects in patients with normoglycemia and prediabetes compared with those with diabetes mellitus. Findings were similar for ischemic and hemorrhagic strokes and were confirmed in sensitivity analyses. Conclusions Time‐dependent proteinuria is an independent risk factor of stroke, especially in the normoglycemia and prediabetes populations.

Background High blood pressure variability (BPV) is a novel risk factor for cardiovascular disease. However, the heterogeneity of systolic blood pressure variability (SBPV) and diastolic blood pressure variability (DBPV) for different vascular events remains unclear. This study aims to investigate whether SBPV or DBPV has different contribution to vascular events in patients with acute ischaemic stroke (IS) or transient ischaemic attack (TIA).Methods Data from the BOSS (blood pressure and clinical outcome in TIA or IS) study were examined for vascular events at 3-month and 1-year follow-up. BPV was defined as the SD and coefficient of variation (CV) of day-to-day measurements within 3 months after IS/TIA. Vascular events include cardiovascular events (myocardial infarction, unstable angina, cardiac death and congestive heart failure) and cerebrovascular events (ischaemic or haemorrhagic stroke). Logistic regression model was used to test the associations between BPV and vascular events.Results Of 2325 patients with IS or TIA, 103 (4.43 %) experienced a recurrent stroke and 64 (2.75 %) had cardiovascular events within 3 months. Day-to-day SBPV was only associated with stroke recurrence (BPVSD: OR, 1.72, 95% CI 1.09 to 2.71; BPVCV: 1.86, 95% CI 1.19 to 2.92), but not cardiovascular events (BPVSD: 1.67, 95% CI 0.94 to 2.94; BPVCV: 1.51, 95% CI 0.86 to 2.64). However, DBPV seems to be related to both stroke (BPVSD: 1.60, 95% CI 1.02 to 2.49; BPVCV: 1.53, 95% CI 0.99 to 2.37) and cardiovascular events (BPVSD: 2.48, 95% CI 1.37 to 4.48; BPVCV: 1.92, 95% CI 1.09 to 3.36). Similar results were found at 1 year.Conclusions For patients with IS/TIA, stroke recurrence was associated with both SBPV and DBPV; however, cardiovascular events seem to be only related to DBPV.

Background and purpose The ring finger protein 213 gene (RNF213) p.R4810K variant increased the risk of acute ischaemic stroke (AIS) attributable to intracranial arterial stenosis (ICAS) in the Japanese and Korean populations. In this study, we aimed to examine the prevalence of the RNF213 p.R4810K variant in Chinese patients with AIS or transient ischaemic attack and identify the phenotype of the carriers.Methods We analysed data from the Third China National Stroke Registry. All included participants were divided into two groups by carrier status of the p.R4810K variant. The aetiological classification was conducted according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. The presence of ICAS and extracranial arterial stenosis (ECAS) was defined as 50%–99% stenosis or occlusion of any intracranial and extracranial artery. Logistic regression models and Cox regression models were used to evaluate the association of the p.R4810K variant with TOAST classification, stenosis phenotypes and clinical outcomes.Results A total of 10 381 patients were enrolled, among which 56 (0.5%) had the heterozygote GA genotype for p.R4810K. The variant carriers were younger (p=0.01), and more likely to suffer from peripheral vascular disease (p=0.04). The p.R4810K variant was associated with large-artery atherosclerosis (LAA) (adjusted OR=1.94, 95% CI 1.13 to 3.33), anterior circulation stenosis (adjusted OR=2.12, 95% CI 1.23 to 3.65) and ECAS (adjusted OR=2.29, 95% CI 1.16 to 4.51). Nevertheless, the p.R4810K variant was not associated with recurrence, poor functional outcome and mortality at 3 months and 1 year.Conclusions The RNF213 p.R4810K variant was associated with LAA, anterior circulation stenosis and ECAS in Chinese patients. Given the low carrying rate and only 1-year follow-up information, caution should be taken to interpret our findings in no statistically significant association between the p.R4810K variant and stroke prognosis in Chinese patients.

Background and purpose The clinical significance of carbon dioxide combining power (CO2CP) in ischaemic cerebrovascular disease is not well established, and the role of CO2CP in the prognosis of acute ischaemic stroke (AIS) or transient ischaemic attack (TIA) has not been reported. The objective of the study was to investigate the associations between CO2CP and clinical outcomes in patients with AIS or TIA.Methods Data were derived from the China National Stroke Registry III. Patients were classified into five groups by quintiles of CO2CP levels and three groups according to the normal range of CO2CP (23–29 mmol/L). Multivariable Cox and logistic regressions were adopted to explore the associations of CO2CP levels with all-cause death and poor functional outcomes (modified Rankin Scale (mRS) 3–6/2–6) at 3 months and 1 year.Results Among 9531 patients included in the study, the median (IQR) CO2CP was 24.9 (23.0–27.0) mmol/L. After adjustment for potential confounders, patients in the first CO2CP quintile (21.1–23.3 mmol/L) had higher risk of all-cause death and poor functional outcomes (mRS score of 3–6/2–6) (HR or OR with 95% CI 2.37 (1.32 to 4.25), 1.49 (1.20 to 1.83) and 1.21 (1.03 to 1.42), respectively) compared with those in the fourth quintile. Similar results were found for outcomes at 1 year. Furthermore, all associations were also significant when CO2CP was

Background To examine the relationship of serum albumin with poor functional outcome and mortality in patients with acute ischaemic stroke (AIS) or transient ischaemic attack (TIA), and perform a meta-analysis to summarise the association.Methods We analysed data from the Third China National Stroke Registry (CNSR-Ⅲ). Patients were divided into four groups based on serum albumin levels at admission. The outcomes included poor functional outcome (modified Rankin Scale (mRS) score of 3 to 6) and mortality at 3 months and 1 year. Multiple logistic regression models and Cox regression models were used to evaluate the association, respectively. We used a fixed-effect model to calculate the risk ratio for poor functional outcome and a random-effect model for mortality in the meta-analysis.Results A total of 13 618 patients were enrolled. During the 3-month follow-up period, compared with 40 to 44.9 g/L group, patients in