Abstract Aim The association between magnesium and outcomes after stroke is uncertain. We aimed to investigate the association of serum magnesium with all‐cause mortality and poor functional outcome. Methods We included patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) from the China National Stroke Registry III. We used Cox proportional hazards model for all‐cause mortality and logistic regression model for poor functional outcome (modified Rankin Scale [mRS] 2–6/3–6) to examine the relationships. Results Among the 6483 patients, the median (interquartile range) magnesium was 0.87 (0.80–0.93) mmol/L. Patients in the first quartile had a higher risk of mRS score 3–6/2–6 at 3 months (adjusted odds ratio [OR]: 1.30; 95% confidence interval [CI]: 1.02, 1.64; adjusted OR: 1.29; 95% CI: 1.04–1.59) compared with those in the fourth quartile. Similar results were found for mRS score 26 at 1 year. The age‐ and sex‐adjusted hazard ratio (HR) with 95% CI in first quartile magnesium was 1.40 (1.02–1.93) for all‐cause mortality within 1 year, but became insignificant (HR: 1.03; 95% CI: 0.71–1.50) after adjusting for potential variables. Conclusions Low serum magnesium was associated with a high risk of poor functional outcome in patients with AIS or TIA.
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.
Abstract Background It is uncertain whether measurement of circulating total atherogenic lipoprotein particle cholesterol mass (non-high-density lipoprotein cholesterol [non-HDL-C]) or particle concentration (apolipoprotein B [Apo B]) more accurately reflects risk of incident cardiovascular disease (CVD). We evaluated CVD risk among China population in whom these markers where discordant. Methods In total, 7,117 initially healthy participants from the China Health and Nutrition Survey were included. Logistic regressions among Apo B, non-HDL-C, and LDL-C, respectively, were used to examined CVD risk by categories of concordant and discordant values defined by residual differences. Mediation analysis was performed to explore the intermediary effect of Apo B between the obesity and the risk of CVD. Results Although all 3 biomarkers were correlated (r ≥ 0.81), discordance occurred in approximately 16% of China participants. Participants with discordant high Apo B were more likely to have higher proportion of traditional risk factors and dyslipidemia. During a follow-up of 6 years, 207 CVD cases were identified. High LDL-C, non-HDL-C and Apo B were associated with increased risk of CVD. Participants with discordant high Apo B relative to LDL-C or non-HDL-C had increased CVD risk compared with concordant levels, odds ratios were 1.38 (95% CI: 1.01 to 1.87), 1.40 (95% CI: 1.01 to 1.94), respectively. Furthermore, mediation analyses revealed 16.67% of association between obesity with CVD was mediated by Apo B. Conclusions Discordance analysis demonstrates that Apo B is a more accurate marker of CVD risk in China healthy participants than LDL-C and non-HDL-C. Direct measurement of lipoprotein particle concentration might help better inform clinical risk assessment and guide clinical decision making.
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.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.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.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.This study was registered in the Chinese Clinical Trials Registry (www.chictr.org/cn) under registration number ChiCTR-ECH-13003934.
We aimed to investigate the association between serially measured HDL-C (high-density lipoprotein cholesterol) levels and stroke risk in a prospective cohort study.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.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.Both low and high cumulatively averaged HDL-C were associated with an increased risk of ischemic and hemorrhagic strokes.
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 ABCD 2 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 ABCD 2 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 ABCD 2 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 ABCD 2 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 ABCD 2 score. This finding emphasizes the importance of early brain and vascular imaging evaluation for risk stratification in patients with TIA or MIS.
Genotype data of the Clopidogrel with Aspirin in Acute Minor Stroke or Transient Ischemic Attack (CHANCE) trial showed that efficacy of clopidogrel aspirin depended on CYP2C19 genotype and risk profile. A stratification of patients who carried CYP2C19 loss-of-function (LOF) alleles according to the risk of recurrent stroke may be important for selecting optimal antiplatelet therapy. We aimed to compare the efficacy and safety of ticagrelor aspirin with clopidogrel aspirin in CYP2C19 LOF carriers with minor stroke or transient ischemic attack (TIA) stratified by risk profile.Data were obtained from Ticagrelor or Clopidogrel with Aspirin in High-Risk Patients with Acute Nondisabling Cerebrovascular Events II (CHANCE-2) trial. Low-risk and high-risk profiles were defined by Essen Stroke Risk Score (ESRS) (<3 [low risk] and ≥3 [high risk], respectively).A total of 6,412 CYP2C19 LOF carriers were enrolled; ticagrelor aspirin was associated with a reduced risk of primary outcome (new stroke within 90-day follow-up) in patients at low risk (hazard ratio [HR], 0.65; 95% CI, 0.48-0.82), but not in those at high risk (HR, 0.97; 95% CI, 0.73-1.29), compared with clopidogrel aspirin (p = 0.02 for interaction). Secondary outcomes generally went in the same direction as the primary outcome. The primary safety outcome of severe or moderate bleeding did not differ based on risk profile (p = 0.24 for interaction), although the incidence of total bleeding was greater with ticagrelor aspirin than with clopidogrel aspirin among patients at low risk (p < 0.01 for interaction). Analysis in the per-protocol population yielded similar results.This post hoc analysis of CHANCE-2 trial showed that CYP2C19 LOF carriers with minor stroke or TIA at low risk of recurrent stroke received a greater benefit from ticagrelor aspirin than from clopidogrel aspirin.This study provides Class II evidence that CYP2C19 LOF carriers with minor stroke or TIA at low risk, but not at high risk, of recurrent stroke (by the ESRS) received a greater benefit from ticagrelor aspirin than from clopidogrel aspirin.URL: www.gov. Unique identifier: NCT04078737.
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 (< 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.
Background: Intracranial Atherosclerotic Stenosis (ICAS) is a prevalent etiology of acute ischemic stroke (AIS), leading to significant morbidity and mortality. The accurate diagnosis and treatment of ICAS-induced AIS are critical to improving outcomes. This study assesses the application of Computed Tomography Perfusion (CTP) in predicting ICAS in AIS patients and its potential impact on patient management. Methods: A retrospective analysis was conducted on 224 AIS patients who underwent endovascular therapy (EVT) at one single Chinese Stroke Center between April 2022 and December 2023. Clinical and radiological data were collected, including patients’ demographics, CTP parameters, and 90-day modified Rankin Scale (mRS) scores. Logistic regression and receiver operating characteristic (ROC) curves evaluated the predictive power of CTP parameters for ICAS. Results: CTP analysis revealed significant differences in perfusion parameters between ICASinduced AIS and other etiologies. ICAS patients had a smaller ischemic volume on admission and higher mismatch ratios [Time to Maximum, Tmax>6s: Other Causes: 132.4 [70.5, 183.3] mL, ICAS: 96.3 [79.8, 107.3] mL, P=0.0064; relative cerebral blood flow, rCBF<30%: Other Causes: 2.4 [0.0, 10.8] mL, ICAS: 0.6 [0.0, 7.0] mL, p =0.0145; mismatch ratio: 7.4 [2.5, 15.0], ICAS: 11.0 [4.6, 17.8], p =0.0285], indicating more salvageable brain tissue. The 90-day mRS showed better functional outcomes in the ICAS group, with a higher likelihood of minimal to no disability [mRS 90 equals 0-1: ICAS: 53.0% vs. Other Causes: 36.3%, p =0.0122]. The predictive model for ICAS, combining clinical manifestations and CTP parameters, yielded an area under the curve (AUC) of 0.7779, demonstrating good diagnostic performance. Conclusion: CTP is a valuable diagnostic tool for ICAS-induced AIS, offering the potential for early identification and informing the decision for endovascular treatment. The positive correlation between CTP findings and patient outcomes supports its utility in clinical practice.