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

Background: Studies have demonstrated that remnant cholesterol is correlated with the risk of ischemic stroke. However, it is unknown whether visit-to-visit variability in remnant cholesterol concentration affects ischemic stroke. We sought to examine the role of remnant cholesterol variability in the subsequent development of ischemic stroke in the general population. Methods: We performed a post hoc analysis including eligible participants from the Kailuan Study cohort who underwent 3 health examinations and were free of atrial fibrillation, myocardial infarction, stroke, cancer, or known lipid-medication use from 2006 to 2010. Participants were followed up until the end of 2017. Variability was quantified as variability independent of the mean, average real variability, and SD. Multivariate analysis was performed using the Fine and Gray competing risk model to estimate subhazard ratios assuming death as a competing risk. Results: The final study cohort comprised 38 556 participants. After a median follow-up of 7.0 years, 1058 individuals were newly diagnosed with ischemic stroke. After adjusting for age (time scale), sex, smoking status, alcohol consumption, physical activity, hypertension, diabetes, family history of cardiovascular disease, body mass index, estimated glomerular filtration rate, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and mean remnant cholesterol, the highest quartile (quartile 4) of variability independent of the mean of remnant cholesterol was associated with an increased ischemic stroke risk compared with the lowest quartile (quartile 1), (subhazard ratio, 1.27 [95% CI, 1.06–1.53]). For each 1-SD increase in variability independent of the mean of remnant cholesterol, the risk increased by 9% (subhazard ratio, 1.09 [95% CI, 1.03–1.16]). The association was also significant using average real variability and SD as indices of variability. Conclusions: Greater remnant cholesterol variability was associated with a higher risk of ischemic stroke in the general population.

ObjectiveThe aim of this study was to examine the association between age at onset of overweight and incident hypertension.MethodsWe analysed 4742 participants with new-onset overweight from the Kailuan study between 2006 and 2015 and and 4742 age-matched and sex-matched controls selected randomly from the same cohort but with normal weight. Participants were compared with respect to subsequent risk of hypertension, with sub-HR calculated with the Fine and Gray model, according to age of onset of overweight.ResultsOver a mean follow-up period of 5.17 years, 1642 overweight participants (34.6%) and 1293 normal-weight controls (27.3%) were subsequently diagnosed with hypertension. The median age at onset of overweight was 49.1 years. Compared with normal-weight controls, the multivariable-adjusted sub-HR for hypertension among participants with onset of overweight at 18–39 years of age, 40–49 years of age, 50–59 years of age and ≥60 years of age was 1.38 (95% CI 1.11 to 1.72), 1.27 (95% CI 1.09 to 1.49), 1.23 (95% CI 1.09 to 1.38) and 1.14 (95% CI 0.99 to 1.32), respectively. Onset of overweight in each age range was significantly associated with increased risk of hypertension, except for the group with onset at ≥60 years of age. The risk increased with each decade of attenuation of age at onset, peaking at 18–39 years of age.ConclusionsYounger age at onset of overweight across adulthood was associated with significantly increased risk of hypertension, with the highest relative risk among participants with onset of overweight at 18–39 years of age.

Background Concurrent atherogenic dyslipidemia and elevated inflammation are commonly observed in overt hyperglycemia and have long been proposed to contribute to diabetogenesis. However, the temporal relationship between them and the effect of their cumulative co-exposure on future incident type 2 diabetes (T2D) remains unclear. Methods Longitudinal analysis of data on 52,224 participants from a real-world, prospective cohort study (Kailuan Study) was performed to address the temporal relationship between high-sensitivity C-reactive protein (hsCRP) and the atherogenic index of plasma (AIP, calculated as triglyceride/high-density lipoprotein) in an approximately 4-year exposure period (2006/2007 to 2010/2011). After excluding 8824 participants with known diabetes, 43,360 nondiabetic participants were included for further analysis of the T2D outcome. Cox regression models were used to examine the adjusted hazard ratios (aHRs) upon the cumulative hsCRP (CumCRP) and AIP (CumAIP) in the exposure period. Results In temporal analysis, the adjusted standardized correlation coefficient (β1) of hsCRP_2006/2007 and AIP_2010/2011 was 0.0740 (95% CI, 0.0659 to 0.0820; P < 0.001), whereas the standardized correlation coefficient (β2) of AIP_2006/2007 and hsCRP_2010/2011 was − 0.0293 (95% CI, − 0.0385 to − 0.0201; P < 0.001), which was significantly less than β1 (P < 0.001). During a median follow-up of 7.9 years, 5,118 T2D cases occurred. Isolated exposure to CumAIP or CumCRP was dose-dependently associated with T2D risks, independent of traditional risk factors. Significant interactions were observed between the median CumAIP (− 0.0701) and CumCRP thresholds (1, 3 mg/L) (P = 0.0308). Compared to CumAIP < − 0.0701 and CumCRP < 1 mg/L, those in the same CumAIP stratum but with increasing CumCRP levels had an approximately 1.5-fold higher T2D risk; those in higher CumAIP stratum had significantly higher aHRs (95% CIs): 1.64 (1.45–1.86), 1.87 (1.68–2.09), and 2.04 (1.81–2.30), respectively, in the CumCRP < 1, 1 ≤ CumCRP < 3, CumCRP ≥ 3 mg/L strata. Additionally, the T2D risks in the co-exposure were more prominent in nonhypertensive, nondyslipidemic, nonprediabetic, or female participants. Conclusions These findings suggest a stronger association between elevated hsCRP and future AIP changes than vice versa and highlight the urgent need for combined assessment and management of chronic inflammation and atherogenic dyslipidemia in primary prevention, particularly for those with subclinical risks of T2D.