Association of Stroke With Metabolic Dysfunction-Associated Fatty Liver Disease With and Without CKD.

RATIONALE & OBJECTIVE: Metabolic dysfunction-associated fatty liver disease (MAFLD), a risk factor for stroke and all-cause mortality, is highly prevalent among patients with chronic kidney disease (CKD), but it is unclear whether the association of MAFLD with stroke and all-cause mortality differs within and outside of the setting of CKD. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: We enrolled 95,353 participants from the Kailuan Cohort Study, among whom 35,749 had CKD at baseline or developed CKD during the follow-up period, and 59,604 individuals who had no CKD at baseline or during the follow-up period. EXPOSURE: MAFLD. OUTCOME: Stroke (ischemic stroke, hemorrhagic stroke), all-cause mortality. ANALYTICAL APPROACH: Adjusted Cox regression models were used to estimate the influence of MAFLD on stroke outcomes within the subgroups defined by the presence of CKD. RESULTS: After a median follow-up of 12.8 years, 6,140 strokes (6.4%) and 11,975 deaths from any cause (12.6%) occurred. After adjusting for potential confounders, MAFLD was associated with an increased incidence of stroke among the participants with CKD (HR, 1.34 [95% CI, 1.23-1.45]) but not among those without CKD (HR, 1.05 [95% CI, 0.97-1.15]; Pinteraction<0.001). This association was principally related to ischemic stroke (HR, 1.38 [95% CI, 1.26-1.51]) and not hemorrhagic stroke (HR, 1.04 [95% CI, 0.85-1.26]). No association was found between MAFLD and all-cause mortality in the participants with CKD (HR,1.04 [95% CI, 0.98-1.10]) or those without CKD (HR,1.03 [95% CI, 0.97-1.09]). Among the participants with CKD, compared with non-MAFLD, MAFLD with diabetes (HR,1.36 [95% CI, 1.23-1.50]) or overweight/obesity (HR,1.30 [95% CI, 1.14-1.50]) was associated with a higher risk of stroke whereas MAFLD without overweight/obesity or diabetes was not associated with a higher risk (HR,1.08 [95% CI, 0.81-1.43]). LIMITATIONS: This was an observational study and included individuals with CKD who had a relatively high estimated glomerular filtration rate. CONCLUSIONS: MAFLD was associated with an increased risk of stroke in individuals with CKD but not in those without CKD. PLAIN-LANGUAGE SUMMARY: Metabolic dysfunction-associated fatty liver disease (MAFLD), which is recognized as a risk factor for stroke in the general population, is highly prevalent among individuals with chronic kidney disease (CKD). However, the impact of MAFLD on the risk of stroke in patients with CKD remains uncertain. We investigated the association of MAFLD with stroke in individuals with and without CKD. Our analysis revealed that MAFLD was associated with a significantly increased risk of stroke in individuals with CKD, and the magnitude of this increased risk was greater in the setting of CKD. These findings highlight the need for increased attention to MAFLD in patients with CKD and emphasize that addressing and preventing MAFLD in this population may contribute to reduced morbidity from stroke.

Impact of Heating Conventional Cigarettes with a Novel Device on Health-related Biomarkers and Cigarette Use Patterns among Chinese Adult Smokers Unwilling to Quit: A Pilot Randomized Controlled Trial.

INTRODUCTION: We evaluated the impact of heating conventional cigarettes with a novel heated tobacco product (HTP) device on biomarkers and cigarette use patterns in Chinese adult smokers unwilling to quit smoking. METHODS: In this pilot randomized controlled trial, 50 eligible participants were allocated to either Control group (smoking conventional cigarettes) or HTP device group (switching to using heated conventional cigarettes by the HTP device). Participants in the HTP device group went through a 2-day run-in period then used heated conventional cigarettes exclusively for 5 days, followed by flexible use for 14 days. Five biomarkers of exposure (BoEs) were measured at baseline and on Day 7. Thirteen biomarkers of biological effect (BoBEs) were measured at baseline and on Day 21. Safety, daily cigarette consumption, craving, withdrawal symptoms, and device acceptability, were assessed. RESULTS: BoE levels decreased by 26.4 % to 71.4% from baseline in the HTP device group, while BoBE levels did not significantly change in either group. In the HTP group, 56% exclusively used heated conventional cigarettes during the flexible use period, experiencing reduced cravings and withdrawal symptoms, while dual users consumed more cigarettes. Mild to moderate device-related reactions were reported in 36% of users. Satisfaction, taste, and harm reduction belief scores averaged 7.4, 6.6, and 8.7 (out of 10), respectively. CONCLUSIONS: Switching to heated cigarettes with the HTP device may reduce short-term exposure to smoke toxicants. However, it can lead to increased tobacco use among dual users. Further investigation is needed to confirm these preliminary findings. IMPLICATIONS: This study is the first to evaluate the impact of heating conventional cigarettes with a novel heated tobacco product (HTP) device on health-related biomarkers and cigarette use patterns among Chinese adult smokers. This novel HTP device can directly heat conventional cigarettes without the necessity for specifically designed tobacco products, avoiding potential additive risks of traditional HTPs. If the results of this study could be further verified by randomized controlled clinical trials with larger sample sizes, this novel HTP device could serve as a short-term harm reduction alternative for smokers unwilling to quit.

Bleeding Risk of Dual Antiplatelet Therapy after Minor Stroke or Transient Ischemic Attack.

OBJECTIVE: This study was undertaken to identify the risk of bleeding events and potential risk factors within 90 days in patients who carried CYP2C19 loss-of-function alleles and received dual antiplatelet therapy after minor stroke or transient ischemic attack. METHODS: A total of 6,412 patients were enrolled from the CHANCE-2 (Clopidogrel with Aspirin in High-Risk Patients with Acute Non-disabling Cerebrovascular Events II) trial. The main outcome was any bleeding within 90 days defined by the criteria from GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries). RESULTS: A total of 250 (3.9%) bleeding events were reported, which occurred mainly within the 21 days of dual antiplatelet therapy (200 cases, 3.1%). Minor bleeding of the skin bruises, epistaxis, and gum bleeding were most frequent. Multivariate analysis showed that treatment with ticagrelor-aspirin compared with clopidogrel-aspirin was associated with increased bleeding (hazard ratio [HR] = 2.21, 95% confidence interval [CI] = 1.68-2.89, p < 0.001). Current smoking was associated with a lower risk of bleeding (HR = 0.70, 95% CI = 0.52-0.95, p = 0.02). Additionally, ticagrelor-aspirin compared with clopidogrel-aspirin was associated with higher risk of bleeding in patients aged <65 years (HR = 2.87, 95% CI = 1.95-4.22) and those without diabetes mellitus (HR = 2.65, 95% CI = 1.88-3.73; p for interaction = 0.04 and 0.03, respectively). INTERPRETATION: Bleeding events mostly occurred within the 21-day dual antiplatelet therapy stage and were generally mild. The risk of bleeding was greater in nonsmoking patients, and was associated with treatment with ticagrelor-aspirin compared with clopidogrel-aspirin, particularly in patients aged <65 years and nondiabetic patients. ANN NEUROL 2022;91:380-388.

Association between residual islet beta-cell function and achieving the target of time in range in inpatients with type 2 diabetes undergoing antidiabetic treatment: An observation study.

AIM: To assess whether the beta-cell function of inpatients undergoing antidiabetic treatment influences achieving time in range (TIR) and time above range (TAR) targets. MATERIALS AND METHODS: This cross-sectional study included 180 inpatients with type 2 diabetes. TIR and TAR were assessed by a continuous glucose monitoring system, with target achievement defined as TIR more than 70% and TAR less than 25%. Beta-cell function was assessed by the insulin secretion-sensitivity index-2 (ISSI2). RESULTS: Following antidiabetic treatment, logistic regression analysis showed that lower ISSI2 was associated with a decreased number of inpatients achieving TIR (OR = 3.10, 95% CI: 1.19-8.06) and TAR (OR = 3.40, 95% CI: 1.35-8.55) targets after adjusting for potential confounders. Similar associations still existed in those participants treated with insulin secretagogues (TIR: OR = 2.91, 95% CI: 0.90-9.36, P = .07; TAR, OR = 3.14, 95% CI: 1.01-9.80) or adequate insulin therapy (TIR: OR = 2.84, 95% CI: 0.91-8.81, P = .07; TAR, OR = 3.24, 95% CI: 1.08-9.67). Furthermore, receiver operating characteristic curves showed that the diagnostic value of the ISSI2 for achieving TIR and TAR targets was 0.73 (95% CI: 0.66-0.80) and 0.71 (95% CI: 0.63-0.79), respectively. CONCLUSIONS: Beta-cell function was associated with achieving TIR and TAR targets. Stimulating insulin secretion or exogenous insulin treatment could not overcome the disadvantage of lower beta-cell function on glycaemic control.

Evaluation of an innovative mHealth-based integrated modality for smoking cessation in Chinese smokers: protocol for a randomized controlled trial.

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.

Ticagrelor-Aspirin Versus Clopidogrel-Aspirin Among CYP2C19 Loss-of-Function Carriers With Minor Stroke or Transient Ischemic Attack in Relation to Renal Function: A Post Hoc Analysis of the CHANCE-2 Trial.

BACKGROUND: Evidence on the risk-benefit ratio of dual antiplatelet therapies among patients with stroke and impaired renal function is limited and inconsistent. OBJECTIVE: To investigate the effect of renal function on the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin treatment. DESIGN: Post hoc analysis of a multicenter, randomized, double-blind, placebo-controlled trial. (ClinicalTrials.gov: NCT04078737). SETTING: 202 centers in China. PATIENTS: CYP2C19 loss-of-function allele carriers with minor stroke or transient ischemic attack. INTERVENTION: Ticagrelor-aspirin and clopidogrel-aspirin. MEASUREMENTS: Renal function was evaluated by estimated glomerular filtration rate (eGFR) levels. The primary efficacy and safety outcomes were recurrent stroke and severe or moderate bleeding within 90 days, respectively. RESULTS: Among 6378 patients, 4050 (63.5%) had normal (eGFR ≥90 mL/min/1.73 m2), 2010 (31.5%) had mildly decreased (eGFR 60 to 89 mL/min/1.73 m2), and 318 (5.0%) had moderately to severely decreased (eGFR <60 mL/min/1.73 m2) renal function. The corresponding differences in recurrent stroke between ticagrelor-aspirin and clopidogrel-aspirin for normal, mildly decreased, and moderately to severely decreased renal function was -2.8 percentage points (95% CI, -4.4 to -1.3 percentage points) (hazard ratio [HR], 0.63 [CI, 0.49 to 0.81]), -0.2 percentage point (CI, -2.4 to 2.0 percentage points) (HR, 0.98 [CI, 0.69 to 1.39]), and 3.7 percentage points (CI, -2.3 to 10.1 percentage points) (HR, 1.31 [CI, 0.48 to 3.55]), respectively. Rates of severe or moderate bleeding did not substantially differ by treatment assignments across eGFR categories. LIMITATION: Renal function was only evaluated by using eGFR, and the proportion of patients with severely decreased renal function was low. CONCLUSION: Patients with normal, rather than impaired, renal function received greater benefit from ticagrelor-aspirin versus clopidogrel-aspirin. PRIMARY FUNDING SOURCE: Ministry of Science and Technology of the People's Republic of China.

The effects of timing onset and progression of AKI on the clinical outcomes in AKI patients with sepsis: a prospective multicenter cohort study.

BACKGROUND: 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.

U-Shaped Relationship of High-Density Lipoprotein Cholesterol and Incidence of Total, Ischemic and Hemorrhagic Stroke: A Prospective Cohort Study.

BACKGROUND: We aimed to investigate the association between serially measured HDL-C (high-density lipoprotein cholesterol) levels and stroke risk in a prospective cohort study. METHODS: We included 96 258 individuals (79.6% men, mean age 51.5 years) without a history of stroke, myocardial infarction, or cancer at baseline from the Kailuan Study, with repeated measurements of HDL-C in 2006, 2008, 2010, 2012, 2014, and 2016. Cumulatively, averaged HDL-C concentrations were calculated using all available HDL-C measurements before incidence stroke or end of follow-up (December 31, 2017). Incident stroke cases were confirmed by review of medical records and further subclassified into ischemic or hemorrhagic stroke. Cox proportional hazards regression and restricted cubic splines were used to examine these associations. RESULTS: During a median follow-up of 10.7 years, 5012 incident stroke cases occurred. Restricted cubic splines analysis suggested a U-shaped association between concentrations of cumulatively averaged HDL-C and risk of stroke (Pnonlinearity <0.001), with the nadir of risk at 1.29 mmol/L. After adjustment for cardiovascular risk factors, individuals with cumulatively averaged HDL-C ≤1.06 mmol/L or ≥2.05 mmol/L had hazard ratios for total stroke of 1.31 (95% CI, 1.15-1.49) and 1.85 (1.63-2.09) compared with those with HDL-C of 1.26 to 1.39 mmol/L. Corresponding hazard ratios were 1.29 (1.11-1.48) and 1.84 (1.60-2.11) for ischemic stroke and 1.54 (1.12-2.12) and 2.29 (1.73-3.04) for hemorrhagic stroke, respectively. CONCLUSIONS: Both low and high cumulatively averaged HDL-C were associated with an increased risk of ischemic and hemorrhagic strokes.

Effect of Hypertension on Efficacy and Safety of Ticagrelor-Aspirin Versus Clopidogrel-Aspirin in Minor Stroke or Transient Ischemic Attack.

BACKGROUND: Hypertension is a risk factor of poor stroke outcomes and associated with antiplatelet resistance. This study aimed to explore the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in patients with different hypertension status, using randomized trial data from the CHANCE-2 trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events-II). METHODS: A total of 6412 patients with minor stroke or transient ischemic attack who carried CYP2C19 loss-of-function alleles were enrolled and randomized to either ticagrelor-aspirin or clopidogrel-aspirin group. Hypertension status were classified into no, newly diagnosed, and previously diagnosed hypertension according to medical history, blood pressure, and antihypertensive medications during hospitalization. The primary efficacy and safety outcomes were stroke recurrence and moderate to severe bleeding risk within 90-day follow-up. RESULTS: Ticagrelor-aspirin was associated with reduced risk of new stroke in patients without hypertension (32 [4.8%] versus 60 [7.2%]; hazard ratio, 0.55 [95% CI, 0.35-0.86]), but not in those with a newly diagnosed hypertension (20 [5.3%] versus 36 [9.1%]; hazard ratio 0.59 [95% CI, 0.33-1.07]), or those with a previously diagnosed hypertension (139 [7.0%] versus 147 [7.4%]; hazard ratio, 0.93 [95% CI, 0.74-1.18]) compared with clopidogrel-aspirin (P=0.04 for interaction). The risk of bleeding for ticagrelor-aspirin was not associated with hypertension status (0.1% versus 0.4%; 0.3% versus 0.5%, 0.4% versus 0.3%, P=0.50 for interaction). All the efficacy and safety outcomes between treatments did not differ by blood pressure levels on admission. CONCLUSIONS: In the CHANCE-2 trial, patients without hypertension received a significantly greater benefit from ticagrelor- aspirin than those with previous hypertension after minor stroke or transient ischemic attack, and a similar benefit trend was observed in those with newly diagnosed hypertension. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04078737.

Association of lipid, inflammatory, and metabolic biomarkers with age at onset for incident cardiovascular disease.

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 (< 55, 55 to < 65, 65 to < 75, and ≥ 75 years) for CVD onset. Risk profiles included clinical, lipid, metabolic, and inflammatory risk factors and biomarkers. RESULTS: Of the clinical factors, diabetes was associated with the highest relative risk for incident CVD in participants younger than 55 years (sub-distributional hazard ratio [sHR], 4.08; 95% confidence interval [CI], 3.47-4.80). Risk factors that were also noted for CVD onset in participants younger than 55 years included hypertension, metabolism syndrome, overweight or obese, dyslipidemia, and smoking. Among the biomarkers, insulin resistance measured by triglyceride-glucose index had the highest sHR (1.42; 95% CI, 1.35-1.49) for CVD in participants younger than 55 years. In comparison, weaker but significant associations with CVD in participants younger than 55 years were noted for most lipids, metabolic biomarkers, and inflammatory biomarkers. Most risk factors and biomarkers had associations that attenuated with increasing age at onset. Some biomarkers had similar CVD age association, while a few had no association with CVD onset at any age. CONCLUSIONS: These findings showed that diabetes and insulin resistance, in addition to hypertension, metabolism syndrome, overweight or obese, dyslipidemia, and smoking, appeared to be the strongest risk factors for premature onset of CVD, and most risk factors had attenuated relative rates at older ages.

Distinct triglyceride-glucose trajectories are associated with different risks of incident cardiovascular disease in normal-weight adults.

BACKGROUND: Long-term patterns of the triglyceride-glucose index (TyG index) and their effects on cardiovascular disease (CVD) among normal-weight adults are poorly characterized. This study aimed to identify TyG index trajectories in normal-weight adults and to determine their association with the risk of incident CVD. METHODS: This study included 40,473 normal-weight participants who were free of stroke and myocardial infarction prior to or in 2012. The TyG index was calculated as ln (fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2), and the TyG index trajectories during 2006-2012 were identified by latent mixture modeling. RESULTS: We identified five distinct TyG index trajectories according to TyG index range and changing pattern over time: low-stable (n = 9,806; mean TyG index 7.84-7.93), moderate-stable (n = 22,066; mean TyG index 8.43-8.52), high-decreasing (n = 1,469; mean TyG index 9.83-8.75), moderate-increasing (n = 5,842; mean TyG index 8.98-9.26), and high-stable (n = 1,290; mean TyG index 9.91-10.07). During 6.74 years of follow-up, we documented 1,577 incident CVD events. Compared with the low-stable pattern, the highest risk of CVD was observed in the high-stable pattern (hazard ratio [HR], 2.24; 95% confidence interval [CI]: 1.73-2.90), followed by the moderate-increasing pattern (HR, 1.70; 95% CI, 1.43-2.04), the high-decreasing pattern (HR, 1.45; 95% CI, 1.11-1.89), and the moderate-stable pattern (HR, 1.25; 95% CI, 1.08-1.44). Similar results were also observed for stroke and myocardial infarction. CONCLUSIONS: Distinct TyG index trajectories were significantly associated differently subsequent risk of CVD in normal-weight individuals. These observations suggested that long-term trajectories of TyG index may be useful for predicting CVD among normal-weight adults.

Triglyceride-glucose index variability and incident cardiovascular disease: a prospective cohort study.

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.

Higher systolic blood pressure is specifically associated with better islet beta-cell function in T2DM patients with high glycemic level.

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 < 1 year duration of diabetes. RCS analyses demonstrated an inverted U-shaped association between SBP and ISSI2 with the SBP at 144 mmHg corresponding to the best beta-cell function. This higher SBP was "paradoxically" associated with lower 2 h postprandial blood glucose (PBG) when SBP < 150 mmHg that was almost exclusively mediated by ISSI2 (mediating effect = - 0.043, 95%CI - 0.067 to - 0.018; mediating effect percentage = 94.7%, P < 0.01). SBP was however not associated with improvement in ISSI2 or 2 h PBG in participants with HbA1c < 10%. CONCLUSIONS: In early stage of diabetes, a slightly elevated SBP (140-150 mmHg) was transiently associated with better beta-cell function in T2DM patients with HbA1c ≥ 10% but not in those with HbA1c < 10%.

Prediabetes and risk of stroke and its subtypes by hypertension status.

BACKGROUND: This study aimed to investigate whether the relationship of prediabetes with the risk of stroke and its subtypes differed among individuals with or without hypertension. METHODS: This prospective study included 85,763 participants without diabetes or a history of stroke at the baseline from the Kailuan study (2006). Prediabetes was defined as a fasting plasma glucose concentration between 5.6 and 6.9 mmol/L. We performed multiplicative and additive interaction analyses to assess the interaction effect between prediabetes and hypertension on the risk of incident stroke. RESULTS: We found that 47.13% of all participants had no prediabetes or hypertension, 11.45% had prediabetes alone, 30.12% had hypertension alone, and 11.31% had both prediabetes and hypertension at baseline. During a median follow-up period of 11.05 years, we documented 3972 events of incident stroke. We found that hypertension modified the relationship of prediabetes with total stroke and ischaemic stroke (p for interaction <0.05). After adjustment for potential confounders, prediabetes was significantly associated with the risk of total stroke (hazard ratio [HR] 1.33, 95% confidence interval [CI] 1.18-1.52], p for interaction = 0.0147) and ischaemic stroke (HR 1.33, [95% CI 1.16-1.54], p for interaction = 0.0413) among participants without hypertension, but not among participants with hypertension. However, no interaction effect of the association between prediabetes and hypertension was observed on the risk of haemorrhagic stroke. CONCLUSIONS: Hypertension modified the association between prediabetes and risk of total and ischaemic stroke. Prediabetes was associated with an increased risk of total and ischaemic stroke only in the non-hypertension population.

Lower Serum Potassium Levels at Admission are Associated with the Risk of Recurrent Stroke in Patients with Acute Ischemic Stroke or Transient Ischemic Attack.

INTRODUCTION: Serum potassium abnormality is a risk factor of incident stroke, but whether it is associated with recurrent stroke in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) remains unknown. This study aimed to investigate the association of serum potassium with the risk of recurrent stroke in patients with AIS or TIA. METHODS: We included 12,425 patients from the China National Stroke Registry III. Patients were classified into 3 groups according to tertiles of potassium. The outcomes were recurrence of stroke and combined vascular events at 1 year. Cox proportional hazards regression was adopted to explore the associations by calculating hazard ratios (HRs) and their 95% confidence intervals (CIs). RESULTS: Among 12,425 enrolled patients, the median (interquartile range) of potassium was 3.92 (3.68-4.19) mmol/L. Compared with the highest tertile, after adjusted for confounding factors, the lowest tertile potassium was associated with increased risk of recurrent stroke at 1 year. The adjusted HR with 95% CI was 1.21 (1.04-1.41). There was an independent, linear association between serum potassium and stroke recurrence. Per 1 mmol/L decrease of potassium was associated with 19% higher risk of recurrent stroke (HR, 1.19; 95% CI, 1.04-1.37). Similar trends were found in ischemic stroke and combined vascular events. CONCLUSIONS: Lower serum potassium level was independently associated with elevated risk of recurrent stroke in patients with AIS or TIA. The finding suggested that monitoring serum potassium may help physicians to identify patients at high risk of recurrent stroke and to stratify risk for optimal management.

Low density lipoprotein cholesterol is associated with increased risk of cardiovascular disease in participants over 70 years old: A prospective cohort study.

BACKGROUND AND AIMS: Previous studies have indicated that the association of elevated low-density lipoprotein cholesterol (LDL-C) with cardiovascular disease (CVD) varies greatly with age, with the association being much stronger in younger than older individuals. To estimate the relationship between LDL-C and CVD risk in a contemporary population aged over 70 years in China. METHODS AND RESULTS: In this analysis, participants of China Health and Retirement Longitudinal Study (CHARLS) who did not take statins and did not have heart disease and stroke in 2011 were include and were followed up to 2018. The outcome of this analysis was the occurrence of CVD. Cox regression was used to assess the effect of LDL-C on CVD. We calculated E-values to quantify the effect of unmeasured confounding. In the 9,631 participants, 15.2% (N = 1,463) were aged over 70 years. During follow-up of 7 years, 1,437 participants had a first CVD attack. The Risk of CVD increased with each 10 mg/mL elevation in LDL-C in whole participants and all age groups. We noted a U-shaped relationship between LDL-C and risk of CVD in group over 70 years old, however, we further found that in the left side of U-shape curve, LDL-C was not associated with CVD, which indicated that a lower level of LDL-C could not increase the risk of CVD. E-value analysis suggested robustness to unmeasured confounding. CONCLUSIONS: In a contemporary society of China, elevated the level of LDL-C also increased the risk of CVD in participants over 70 years old. These results should strengthen guideline recommendations for the use of lipid-lowering therapies in those elderly.

Effect of changes in serum uric acid on the risk of stroke and its subtypes.

BACKGROUND AND AIMS: The role of serum uric acid (SUA) in stroke remains controversial and analyses of changes in SUA and stroke are limited. The objective of the study was to investigate the associations of changes in SUA with stroke and its subtypes (ischemic and hemorrhagic stroke). METHODS AND RESULTS: A total of 51 441 participants (mean age 52.69 ± 11.71 years) without history of myocardial infarction or stroke were enrolled. Participants were divided into four groups based on SUA level changes during 2006 and 2010: stable low, increasing, decreasing, and stable high. SUA score was quantified on a 3-point scale with 1 point awarded for hyperuricemia at either year 2006, 2008 or 2010. Multivariate Cox proportion models were used to calculated hazard ratios (HRs) and their 95% confidence intervals (CIs). During 7.03-year follow up, 1611 stroke (1410 ischemic stroke, 199 hemorrhagic stroke, and 47 subarachnoid hemorrhage) were identified. Participants with stable high SUA had higher risk of hemorrhagic stroke, the HR was 1.93 (95% CI: 1.06-3.51), compared to those with stable low SUA. Furthermore, cumulative high SUA exposure also increased the risk of hemorrhagic stroke, the HR (95%CI) was 2.99 (1.55-5.74), compared with cumulative low SUA exposure. However, no significant evidence indicated changes in SUA was associated with the risk of total and ischemic stroke, the HRs (95% CIs) were 0.98 (0.74-1.29) and 0.88 (0.65-1.19), respectively. CONCLUSIONS: Stable high SUA was positively associated with the risk of hemorrhagic stroke, but not with total and ischemic stroke risk.

Imaging Parameters Predict Recurrence After Transient Ischemic Attack or Minor Stroke Stratified by ABCD2 Score.

BACKGROUND AND PURPOSE: Whether imaging parameters would independently predict stroke recurrence in low-risk minor ischemic stroke (MIS) or transient ischemic attack (TIA) according to traditional score system (such as ABCD2 score, which was termed on the basis of the initials of the five factors: age, blood pressure, clinical features, duration, diabetes) remains unclear. We sought to evaluate the association between imaging parameters and 1-year stroke recurrence in patients with TIA or MIS in different risk stratum stratified by ABCD2 score. METHODS: We included patients with TIA and MIS (National Institutes of Health Stroke Scale score ≤3) with complete baseline vessel and brain imaging data from the Third China National Stroke Registry III. Patients were categorized into different risk groups based on ABCD2 score (low risk, 0-3; moderate risk, 4-5; and high risk, 6-7). The primary outcome was stroke recurrence within 1 year. Multivariable Cox proportional-hazards regression models were used to assess whether imaging parameters (large artery stenosis, infarction number) were independently associated with stroke recurrence. RESULTS: Of the 7140 patients included, 584 patients experienced stroke recurrence within 1 year. According to the ABCD2 score, large artery stenosis was associated with higher stroke recurrence in both low-risk (adjusted hazard ratio, 1.746 [95% CI, 1.200-2.540]) and moderate-risk group (adjusted hazard ratio, 1.326 [95% CI, 1.042-1.687]) but not in the high-risk group (P>0.05). Patients with multiple acute infarctions or single acute infarction had a higher risk of recurrent stroke than those with no infarction in both low- and moderate-risk groups, but not in the high-risk group. CONCLUSIONS: Large artery stenosis and infarction number were independent predictors of 1-year stroke recurrence in low-moderate risk but not in high-risk patients with TIA or MIS stratified by ABCD2 score. This finding emphasizes the importance of early brain and vascular imaging evaluation for risk stratification in patients with TIA or MIS.

Triglyceride-glucose index is associated with the risk of myocardial infarction: an 11-year prospective study in the Kailuan cohort.

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 (Pinteraction = 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.

Change in triglyceride-glucose index predicts the risk of cardiovascular disease in the general population: a prospective cohort study.

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 < 0.0001), and category-free net reclassification improvement value (P < 0.0001). Similar results were observed for stroke and MI. CONCLUSIONS: Substantial changes in TyG index independently predict the risk of CVD in the general population. Monitoring long-term changes in TyG may assist with in the early identification of individuals at high risk of CVD.