Increased Risk of Cardiometabolic Disease in Ideal Weight Adults With History of Overweight/Obesity in China: A Prospective Cohort Study.

BACKGROUND: Overweight and obesity represent critical modifiable determinants in the prevention of cardiometabolic disease (CMD). However, the long-term impact of prior overweight/obesity on the risk of CMD in later life remains unclear. We aimed to investigate the association between longitudinal transition of body mass index (BMI) status and incident CMD. METHODS AND RESULTS: This prospective cohort study included 57 493 CMD-free Chinese adults from the Kailuan Study. BMI change patterns were categorized according to the BMI measurements obtained during the 2006 and 2012 surveys. The primary end point was a composite of myocardial infarction, stroke, and type 2 diabetes. Cox regression models were used to evaluate the associations of transitions in BMI with overall CMD events and subtypes, with covariates selected on the basis of the directed acyclic graph. During a median follow-up of 7.62 years, 8412 participants developed CMD. After considering potential confounders, weight gain pattern (hazard ratio [HR], 1.34 [95% CI, 1.23-1.46]), stable overweight/obesity (HR, 2.12 [95% CI, 2.00-2.24]), and past overweight/obesity (HR, 1.73 [95% CI, 1.59-1.89]) were associated with the incidence of CMD. Similar results were observed in cardiometabolic multimorbidity, cardiovascular disease, and type 2 diabetes. Additionally, triglyceride and systolic blood pressure explained 8.05% (95% CI, 5.87-10.22) and 12.10% (95% CI, 9.19-15.02) of the association between past overweight/obesity and incident CMD, respectively. CONCLUSIONS: A history of overweight/obesity was associated with an increased risk of CMD, even in the absence of current BMI abnormalities. These findings emphasize the necessity for future public health guidelines to include preventive interventions for CMD in individuals with past overweight/obesity.

Bioinformatics proved the existence of potential hub genes activating autophagy to participate in cartilage degeneration in osteonecrosis of the femoral head.

The obvious degeneration of articular cartilage occurs in the late stage of osteonecrosis of the femoral head (ONFH), which aggravates the condition of ONFH. This study aimed to demonstrate aberrant activation of autophagy processes in ONFH chondrocytes through bioinformatics and to predict and identify relevant hub genes and pathways. Differentially expressed genes (DEGs) were identified using R software in the GSE74089 dataset from the GEO database. DEGs were crossed with the Human Autophagy Database (HADb) autophagy genes to screen out autophagy-related differential genes (AT-DEGs). GSEA, GSVA, GO, and KEGG pathway enrichment analyses of AT-DEGs were performed. The STRING database was used to analyze the protein-protein interaction (PPI) of the AT-DEGs network, and the MCODE and CytoHubba plugin in the Cytoscape software was used to analyze the key gene cluster module and screen the hub genes. The PPI network of hub genes was constructed using the GeneMANIA database, and functional enrichment and gene connectivity categories were analyzed. The expression levels of hub genes of related genes in the ONFH patients were verified in the dataset GSE123568, and the protein expression was verified by immunohistochemistry in tissues. The analysis of DEGs revealed abnormal autophagy in ONFH cartilage. AT-DEGs in ONFH have special enrichment in macroautophagy, autophagosome membrane, and phosphatidylinositol-3-phosphate binding. In the GSE123568 dataset, it was also found that ATG2B, ATG4B, and UVRAG were all significantly upregulated in ONFH patients. By immunohistochemistry, it was verified that ATG2B, ATG4B, and UVRAG were significantly overexpressed. These three genes regulate the occurrence and extension of autophagosomes through the PI3KC3C pathway. Finally, we determined that chondrocytes in ONFH undergo positive regulation of autophagy through the corresponding pathways involved in three genes: ATG2B, ATG4B, and UVRAG.

Excessive weight gain onset-age and risk of developing diabetes mellitus: a large, prospective Chinese cohort study.

Background: Excessive weight gain and obesity are widely accepted as risk factors for diabetes mellitus, and the age at which obesity onsets may be related to the development of cardiovascular diseases and certain cancers. Here, we aimed to investigate associations between the onset-age of overweight/obesity and risk of developing diabetes mellitus in China. Methods: 42,144 people with the normal weight range and without diabetes at baseline, were enrolled from the Kailuan cohort which began on the 1st June 2006. All participants were followed-up, biennially, until 31st December 2017. During follow-up, 11,220 participants had become overweight/obese. For each case, one normal-weight control was matched according to age ( ± 1 year) and sex. Our final analysis included 10,858 case-control pairs. An age-scaled Cox model was implemented to estimate hazard ratios (HR) with corresponding 95% confidence intervals (CI) for diabetes mellitus incidence across age-groups. Results: At a median follow-up of 5.46 years, 1,403 cases of diabetes mellitus were identified. After multivariate adjustments, age-scaled Cox modelling suggested that risk gradually attenuated with every 10 year increase in age of onset of overweight/obesity. Diabetes mellitus adjusted HRs (aHRs) for new-onset overweight/obesity at <45years, 45-54 years, and 55-64 years were 1.47 (95%CI, 1.12-1.93), 1.38 (95%CI, 1.13-1.68), 1.32 (95%CI, 1.09-1.59), respectively. However, new-onset of overweight/obesity at ≥65 years did not relate to diabetes mellitus (aHR, 1.20; 95%CI, 0.92-1.57). This trend was not observed in women or the new-onset obesity subgroup but was evident in men and the new overweight onset subgroup. Conclusion: Participants with early onset of excessive weight gain issues are at considerably higher risk of developing diabetes mellitus compared to those who maintain a normal weight.

Accumulated exposure to high non-high-density lipoprotein cholesterol increases the risk of cardiovascular diseases in hypertensive individuals: An 11-year prospective cohort study.

BACKGROUND: The relationship of cumulative non high-density lipoprotein-cholesterol (Cum-non-HDL-C) concentration with the risk of cardiovascular disease (CVD) in individuals with hypertension remains unclear. METHODS: In total 27 234 participants for whom three consecutive total cholesterol and HDL-C concentrations were available, and who did not have CVD, comprising 13 617 with hypertension and 13 617 without from 2006 to 2010. Participants were placed into four groups according to Cum-non-HDL-C. Cox proportional hazards models were used to evaluate the relationship between Cum-non-HDL-C and the risk of CVD. RESULTS: Over a median 11 years, 1,298 participants with hypertension developed CVD. After adjustment for multiple potential confounding factors, compared with participants with hypertension and Cum-non-HDL-C < 130 mg/dl, the fully adjusted hazard ratios and 95% confidence intervals of CVD associated with Cum-non-HDL-C values of 130-159 mg/dl, 160-189 mg/dl, and ≥ 190 mg/dl were 1.23 (1.01, 1.34), 1.27 (1.04, 1.56), and 1.51 (1.13, 2.01), respectively. Compared with participants without hypertension and a Cum-non-HDL-C < 130 mg/dl, the fully adjusted hazard ratios (95% confidence intervals) for the participants with hypertension and Cum-non-HDL-Cs < 130 mg/dl, 130-159 mg/dl, 160-189 mg/dl, and ≥ 190 mg/dl were 1.84 (1.55, 2.18), 2.16 (1.81, 2.59), 2.17 (1.73, 2.70), and 2.45 (1.12, 3.29), respectively. CONCLUSIONS: A consistently high non-HDL-C concentration increases the risk of CVD in individuals with hypertension, as does prolonged exposure to a high non-HDL-C concentration. Thus, the achievement of target blood pressure and non-HDL-C concentrations should help reduce the risk of CVD in individuals with hypertension.

Relationship between cumulative exposure to triglyceride-glucose index and heart failure: a prospective cohort study.

BACKGROUND: High triglyceride-glucose index (TyG) is a major risk factor for heart failure, but the long-term effect of high TyG index on the risk of developing heart failure remains unclear. Therefore, we aimed to determine the relationship between the cumulative exposure to TyG index and the risk of heart failure. METHODS: A total of 56,149 participants from the Kailuan Study, who participated in three consecutive health examinations in 2006, 2008, and 2010 and had no history of heart failure or cancer were recruited for this study. The cumulative TyG index was calculated as the weighted sum (value × time) of the mean TyG index for each time interval. The participants were placed into quartiles based on their cumulative TyG index. The study ended on December 31, 2020, and the primary outcome was new-onset heart failure during the follow-up period. In addition, a Cox proportional hazards regression model and a restricted cubic spline analysis were used to further evaluate the relationship between cumulative TyG index and the risk of heart failure. RESULTS: During a median follow-up period of 10.04 years, a total of 1,312 new heart failure events occurred. After adjustment for potential confounding factors, the Cox regression analysis showed that the hazard ratios (95% confidence intervals) for the risk of heart failure in the Q2, Q3, and Q4 groups were 1.02 (0.83,1.25), 1.29 (1.07,1.56) and 1.40 (1.15,1.71), respectively, vs. the Q1 group. The subgroup analysis showed a significant interaction between cumulative TyG index and BMI or waist circumference, but there was no interaction between age, sex and cumulative TyG index. The restricted cubic spline analysis showed a dose-response relationship between cumulative TyG index and the risk of heart failure. In addition, the sensitivity analysis generated results that were consistent with the primary results. CONCLUSIONS: High cumulative TyG index is associated with a higher risk of heart failure. Thus, the TyG index may be useful for the identification of individuals at high risk of heart failure. The present findings emphasize the importance of the long-term monitoring of the TyG index in clinical practice.

Cumulative exposure to high remnant-cholesterol concentrations increases the risk of cardiovascular disease in patients with hypertension: a prospective cohort study.

BACKGROUND: The relationship of cumulative remnant-cholesterol (Cum-RC) concentration with the risk of cardiovascular disease (CVD) in patients with hypertension remains unclear. METHODS: We studied data for 28,698 individuals for whom three consecutive total cholesterol, high-density lipoprotein-cholesterol (HDL-C), and triglyceride concentrations were available, and who did not have CVD (14,349 with hypertension and 14,349 without), that was collected between 2006 and 2010. Participants with hypertension were placed into four groups based on Cum-RC quartile: a Q1 group (< 26.40 mg/dl), a Q2 group (26.40-39.56 mg/dl), a Q3 group (39.57-54.65 mg/dl), and a Q4 group (≥ 54.66 mg/dl). Cox proportional hazards models were used to evaluate the relationship between Cum-RC and the risk of CVD. RESULTS: Over a median 10.9 (interquartile range, 10.5-11.3) years, 1,444 participants with hypertension developed CVD. After adjustment for multiple potential confounding factors, and compared with the Q1 Cum-RC group of the participants with hypertension, the adjusted hazard ratios for CVD for the Q2-Q4 groups were 1.07(0.92,1.26), 1.08(0.91,1.28), and 1.26(1.03,1.54) (P = 0.0405); those for myocardial infarction were 1.51(1.00,2.31), 2.02(1.22,3.27), and 2.08(1.41,3.28) (P < 0.0001); and those for ischemic stroke were 1.02(0.84,1.24), 1.04(0.86,1.25), and 1.29(1.02,1.62), respectively (P = 0.0336). However, no significant relationship was found between Cum-RC and the risk of hemorrhage stroke. At the same Cum-RC, the risk of CVD was significantly higher in participants with hypertension than in those without. CONCLUSIONS: A consistently high remnant-cholesterol concentration increases the risk of CVD in individuals with hypertension. Therefore, the achievement of blood pressure and RC concentration targets should help reduce the risk of CVD in individuals with hypertension.

Age-dependent changes in the risk of weight gain in Chinese adults: results from the Kailuan cohort study.

OBJECTIVES: Over the past decades, China has seen a dramatic epidemic of overweight and obesity. However, the optimal period for interventions to prevent overweight/obesity in adulthood remains unclear, and little is known regarding the joint effect of sociodemographic factors on weight gain. We aimed to investigate the associations of weight gain with sociodemographic factors, including age, sex, educational level, and income. STUDY DESIGN: This was a longitudinal cohort study. METHODS: This study included 121,865 participants aged 18-74 years from the Kailuan study who attended health examinations over the period 2006-2019. Multivariate logistic regression and restricted cubic spline were used to evaluate the associations of sociodemographic factors with body mass index (BMI) category transitions over two, six, and 10 years. RESULTS: In the analysis of 10-year BMI changes, the youngest age group had the highest risks of shifting to higher BMI categories, with odds ratio of 2.42 (95% confidence interval 2.12-2.77) for a transition from underweight or normal weight to overweight or obesity and 2.85 (95% confidence interval 2.17-3.75) for a transition from overweight to obesity. Compared with baseline age, education level was less related to these changes, whereas gender and income were not significantly associated with these transitions. Restricted cubic spline analyses suggested reverse J-shaped associations of age with these transitions. CONCLUSIONS: The risk of weight gain in Chinese adults is age dependent, and clear public healthcare messaging is needed for young adults who are at the highest risk of weight gain.

Individual and combined contributions of non-high-density lipoprotein cholesterol and brachial-ankle pulse wave velocity to cardiovascular disease risk: Results of a prospective study using the Kailuan cohort.

Objective: We aimed to characterize the relationship of a combination of circulating non-high-density lipoprotein-cholesterol (non-HDL-C) concentration and brachial-ankle pulse wave velocity (baPWV) with cardiovascular disease (CVD). Methods: We performed a prospective cohort study of the residents of the Kailuan community, with data from a total of 45,051 participants being included in the final analysis. The participants were allocated to four groups according to their non-HDL-C and baPWV status, each of which was categorized as high or normal. Cox proportional hazards models were used to explore the relationships of non-HDL-C and baPWV, individually and in combination, with the incidence of CVD. Results: During the 5.04-year follow-up period, 830 participants developed CVD. Compared with the Normal non-HDL-C group independently, the multivariable adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD in the High non-HDL-C was 1.25 (1.08-1.46). Compared with the Normal baPWV group independently, the HRs and 95% CIs for CVD in the High baPWV was 1.51 (1.29-1.76). In addition, compared with the Normal both non-HDL-C and baPWV group, the HRs and 95% CIs for CVD in the High non-HDL-C and normal baPWV, Normal non-HDL-C and high baPWV, and High both non-HDL-C and baPWV groups were 1.40 (1.07-1.82), 1.56 (1.30-1.88), and 1.89 (1.53-2.35), respectively. Conclusion: High non-HDL-C concentration and high baPWV are independently associated with a higher risk of CVD, and individuals with high both non-HDL-C and baPWV are at a still higher risk of CVD.

Temporal relationship between atherogenic dyslipidemia and inflammation and their joint cumulative effect on type 2 diabetes onset: a longitudinal cohort study.

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 (ß1) 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 (ß2) 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 ß1 (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.

Effect of Aerobic Exercise on Arterial Stiffness in Individuals with Different Smoking Statuses.

This study aimed to investigate the immediate effects of acute bout of aerobic exercise on arterial stiffness in individuals with different smoking statuses. A total of 940 male individuals (mean age of 36.82±7.76 years) in the Kailuan study cohort were selected to participate in the fifth National Physical Fitness Monitoring. All participants completed measurements of brachial - ankle pulse wave velocity (baPWV) before and after twice-quantitative cycle ergometer exercise. Four groups were defined: (1) non-smokers (n=231), (2) former smokers (n=165), (3) light smokers (1-10 cigarettes/day, n=254), (4) heavy smokers (>10 cigarettes/day, n=290). Generalized linear models were established to analyze between-group differences in the change in baPWV before and after acute aerobic exercise in individuals with different smoking statuses. Overall, after acute aerobic exercise, baPWV was immediately decreased significantly (-33.55 cm/s [95% CI, - 39.69 to -27.42]). Compared with non-smokers, former smokers, light smokers, and heavy smokers showed a greater decrease in baPWV (-12.17 cm/s [95%CI, - 30.08 to 5.75], - 18.43 cm/s [95%CI, -34.69 to - 2.16], and -22.46 cm/s [95%CI, - 38.39 to - 6.54]) respectively. There is a transient decrease in baPWV in individuals with different smoking statuses. Compared with non-smokers, baPWV decreased more significantly in light and heavy smokers.

Estimated pulse wave velocity can predict the incidence of new-onset atrial fibrillation: A 11-year prospective study in a Chinese population.

Background: Arterial stiffness, a risk factor for atrial fibrillation (AF), is rarely applied in clinical practice because of the difficulty and high cost of its measurement. Estimated pulse wave velocity (ePWV) is a simple, reproducible, and non-invasive index of arterial stiffness. This study was to assess the predictive value of ePWV for the risk of new-onset AF. Methods: Subjects were selected from the Kailuan cohort study population who underwent initial physical examination between 2006 and 2008. A total of 96,561 subjects were ultimately included in the final analysis. ePWV was divided into four groups according to quartiles. The Kaplan-Meier method was used to calculate the cumulative incidence of AF. A Cox regression model was used to assess the predictive value of estimated arterial stiffness for new-onset AF. Results: Mean age of subjects was 51.47 ± 9.68 years, while 76,968 (79.65%) were male and 19,663 (20.35%) were female. During mean follow-up period of 11.77 years, 1,215 AF events occurred. Results of the Kaplan-Meier analysis showed that the incidence of new-onset AF increased with increase in ePWV. Cox regression analysis showed that in the total population, the incidence of new-onset AF was 1.64, 1.90, and 2.64 times higher in the medium, medium-high, and high ePWV groups, respectively, compared with the low ePWV group. When stratified according to sex, ePWV had higher predictive value in the female population. Conclusions: Increased ePWV increases the incidence of new-onset AF, and may promote application of more aggressive primary prevention. Trial registry name: Risk factors and intervention for cardiology, cerebrovascular and related disease (Kailuan Study); URL: http://www.chictr.org.cn/showproj.aspx?proj=8050; Registration number: ChiCTR-TNRC-11001489.

Association of Cardiovascular Health Score Trajectory With Incident Myocardial Infarction in Hypertensive Patients.

BACKGROUND: The association between changes in cardiovascular health score (CHS) over time and myocardial infarction (MI) risk in hypertensive patients remains unclear. METHOD: This was a prospective study comprising 17 374 hypertensive patients from the Kailuan study cohort who underwent 3 surveys and were identified to be free of MI, stroke, or cancer from 2006 to 2010. CHS consisted of 7 cardiovascular health metrics (plasma glucose, total cholesterol, blood pressure, smoking, body mass index, physical activity, salt intake), ranging from 0 (worst) to 13 (best) in the study. CHS trajectories were developed during 2006 to 2010 to predict the MI risk from 2010 to 2020. Additionally, the Cox proportional hazard model was established to calculate the hazard ratio and 95% CI of incident MI in different trajectory groups. RESULT: This study identified the 5 CHS trajectories from 2006 to 2010: low-stable (n=1161; range, 4.7-4.5), moderate-decreasing (n=3928; decreased from 6.9 to 6.0), moderate-increasing (n=1014; increased from 5.6 to 7.8), high-stable I (n=7940; range, 8.1-8.2), and high-stable II (n=3331; range, 9.2-9.7). During the median follow-up of 10.04 years, 288 incident MI cases were identified. After adjusting for potential confounders, compared with low-stable group, the hazard ratio and 95% CI of MI were 0.24 (0.15-0.40) for high-stable II, 0.36 (0.24-0.54) for high-stable I, 0.46 (0.25-0.83) for moderate-increasing, and 0.61 (0.41-0.90) for moderate-decreasing, respectively. CONCLUSIONS: In hypertensive patients, high-stable CHS or improvement in CHS is associated with a lower risk of incident MI, when compared with low-stable CHS trajectory over time.

Changes in Impaired Fasting Glucose and Borderline High Low-Density Lipoprotein-Cholesterol Status Alter the Risk of Cardiovascular Disease: A 9-Year Prospective Cohort Study.

Background: We aimed to characterize the relationships of the changes in impaired fasting glucose (IFG) and borderline high low-density lipoprotein-cholesterol (LDL-C) status with cardiovascular disease (CVD). Methods: A total of 36,537 participants who did not have previous CVD, diabetes mellitus, or high LDL-C (≥ 4.1 mmol/L), nor were taking lipid-lowering drugs were recruited from the Kailuan study. The participants were allocated to six groups according to their baseline and follow-up fasting blood glucose (FBG) and LDL-C concentrations: (1) both were normal; (2) both normal at baseline, one abnormality subsequently; (3) both normal at baseline, both abnormal subsequently; (4) at least one abnormality that became normal; (5) at least one abnormality at baseline, a single abnormality subsequently; and (6) at least one abnormality, two abnormalities subsequently. The outcomes were CVD and subtypes of CVD (myocardial infarction and stroke). Multiple Cox regression models were used to calculate adjusted hazard ratio (HR) and confidence interval (95% CI). Results: During a median follow-up period of 9.00 years, 1,753 participants experienced a CVD event. After adjustment for covariates, participants with IFG in combination with a borderline high LDL-C status at baseline and follow-up had higher risks of CVD (HR: 1.52; 95% CI: 1.04-2.23 and HR: 1.38, 95% CI: 1.13-1.70, respectively) compared with those with normal fasting blood glucose and LDL-C. Compared with participants that remained normal, those who changed from normality to having two abnormalities were at a higher risk of CVD (HR: 1.26; 95% CI: 0.98-1.61), as were those who changed from at least one abnormality to two abnormalities (HR: 1.48, 95% CI: 1.02-2.15). Conclusion: Changes in IFG and borderline high LDL-C status alter the risk of CVD and its subtype, implying that it is important to focus on such individuals for the prevention and control of CVD.

Triglyceride-glucose index trajectory and stroke incidence in patients with hypertension: a prospective cohort study.

BACKGROUND: It has been suggested that the baseline triglyceride-glucose (TyG) index, a simple surrogate measure for insulin resistance, is significantly associated with the occurrence of stroke. Nevertheless, the impact of longitudinal patterns of TyG on the stroke risk in hypertensive patients is still unknown. Hence, this study aimed to investigate the association between TyG index trajectory and stroke risk among hypertensive patients. METHODS: This prospective study included 19,924 hypertensive patients from the Kailuan Study who underwent three waves survey and were free of myocardial infarction, cancer and stroke before or during 2010. The TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting plasma glucose (mg/dL)/2], and latent mixed modelling was used to identify the trajectory of TyG during the exposure period (2006-2010). Furthermore, the Cox proportional hazard models were applied to estimate the hazard ratio (HR) and 95% confidence interval (CI) for incident stroke of different trajectory groups. RESULTS: Five distinct TyG trajectory were identified during 2006-2010: low-stable (n = 2483; range, 8.03-8.06), moderate low-stable (n = 9666; range, 8.58-8.57), moderate high-stable (n = 5759; range, 9.16-9.09), elevated-stable (n = 1741; range, 9.79-9.75), and elevated-increasing (n = 275; range, 10.38-10.81). During the median follow-up of 9.97 years, 1,519 cases of incident stroke were identified, including 1,351 with ischemic stroke and 215 with hemorrhage stroke. After adjusting for confounding variables, the HR and 95% CI of stroke were 2.21 (1.49,3.28) for the elevated-increasing group, 1.43 (1.13,1.83) for the elevated-stable group, 1.35 (1.10,1.64) for the moderate high-stable group, 1.26 (1.06,1.52) for the moderate low-stable group, respectively, when compare with the low-stable group. Similar results were observed in ischemic stroke, but a significant association was not found between TyG trajectory and risk of hemorrhage stroke. CONCLUSION: A long-term elevated TyG index in hypertensive patients is associated with an increased risk of stroke, especially ischemic stroke. This finding implies that regular monitoring of TyG index may assist in identifying individuals at a higher risk of stroke among patients with hypertension.

Remnant Cholesterol Variability and Incident Ischemic Stroke in the General Population.

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.

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

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

Association of Age of Metabolic Syndrome Onset With Cardiovascular Diseases: The Kailuan Study.

Background: Metabolic syndrome (MetS) is associated with an increased risk of incident cardiovascular diseases (CVD), but the association between the new-onset MetS at different ages and the CVD risk remain unclear. Methods: This was a prospective study comprising a total of 72,986 participants without MetS and CVD who participated in the Kailuan study baseline survey (July 2006 to October 2007). All participants received the biennial follow-up visit until December 31, 2019. In addition, 26,411 patients with new-onset MetS were identified from follow-up, and one control participant was randomly selected for each of them as a match for age ( ± 1 year) and sex. In the end, a total of 25,125 case-control pairs were involved. Moreover, the Cox proportional hazard model was established to calculate the hazard ratios (HR) for incident CVD across the onset age groups. Results: According to the median follow-up for 8.47 years, 2,319 cases of incident CVD occurred. As MetS onset age increased, CVD hazards gradually decreased after adjusting for potential confounders. Compared with non-MetS controls, the HR and the 95% confidence interval (CI) for CVD were 1.84 (1.31-2.57) in the MetS onset age <45 years group, 1.67 (1.42-1.95) for the 45-54 years group, 1.36 (1.18-1.58) for the 55-64 years group, and 1.28 (1.10-1.50) for the ≥65 years group, respectively (p for interaction = 0.03). Conclusions: The relative risks of CVD differed across MetS onset age groups, and the associations was more intense in the MetS onset group at a younger age.

Association between age at onset of overweight and risk of hypertension across adulthood.

OBJECTIVE: The aim of this study was to examine the association between age at onset of overweight and incident hypertension. METHODS: We 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. RESULTS: Over 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. CONCLUSIONS: Younger 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.

Visit-to-visit variability in triglyceride-glucose index and diabetes: A 9-year prospective study in the Kailuan Study.

Instruction/Aims: It is unknown whether variability in the triglyceride-glucose index (TyG-index) is associated with the risk of diabetes. Here, we sought to characterize the relationship between TyG-index variability and incident diabetes. Methods: We performed a prospective study of 48,013 participants in the Kailuan Study who did not have diabetes. The TyG-index was calculated as ln [triglyceride (TG, mg/dL) concentration × fasting blood glucose concentration (FBG, mg/dL)/2]. The TyG-index variability was assessed using the standard deviation (SD) of three TyG-index values that were calculated during 2006/07, 2008/09, and 2010/11. We used the Cox proportional hazard models to analyze the effect of TyG-index variability on incident diabetes. Results: A total of 4,055 participants were newly diagnosed with diabetes during the study period of 8.95 years (95% confidence interval (CI) 8.48-9.29 years). After adjustment for confounding factors, participants in the highest and second-highest quartiles had significantly higher risks of new-onset diabetes versus the lowest quartile, with hazard ratios (95% CIs) of 1.18 (1.08-1.29) and 1.13 (1.03-1.24), respectively (P trend< 0.05). These higher risks remained after further adjustment for the baseline TyG-index. Conclusions: A substantial fluctuation in TyG-index is associated with a higher risk of diabetes in the Chinese population, implying that it is important to maintain a normal and consistent TyG-index.

CAR-T therapy followed by allogeneic hematopoietic stem cell transplantation for refractory/relapsed acute B lymphocytic leukemia: Long-term follow-up results.

Background: Patients with refractory/relapsed (r/r) acute B lymphocytic leukemia (B-ALL) can achieve complete response (CR) after chimeric antigen receptor T-cell (CAR-T) therapy, but recurrence occurs in the short term. To reduce recurrence and improve survival, CAR-T therapy followed by transplantation is a feasible option. We analyzed the long-term follow-up outcomes and the risk factors for allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CR by CAR-T therapy in this study. Methods: A total of 144 patients who underwent allo-HSCT after CAR-T therapy in our hospital were enrolled in this study. Target gene analysis was performed in 137 r/r B-ALL patients receiving allo-HSCT after CR by CAR-T therapy. Among the 137 patients, 87 were evaluated for germline predisposition gene mutations, and 92 were evaluated for tumor somatic gene mutations using NGS. The clinical factors, germline predisposition gene and somatic gene mutations associated with the prognosis of patients receiving transplantation after CAR-T therapy were analyzed using univariate Cox regression. Factors related to disease-free survival (DFS) and overall survival (OS) were analyzed using multivariate Cox regression analysis. Results: In 137 r/r B-ALL patients, the 2-year cumulative incidence of recurrence (CIR), OS and DFS in patients receiving allo-HSCT after CAR-T therapy was 31.5%, 71.4%, and 60.5%, respectively. The 2-year OS and DFS in MRD-negative patients were 80.9% and 69.3%, respectively. Univariate Cox analysis showed that pretransplant MRD positivity, fungal infection, germline EP300 mutation and somatic TP53 mutation were associated with a poor prognosis after transplantation; a TBI-based regimen was a protective factor for survival and recurrence after transplantation. Multivariate Cox regression analysis showed that the TBI-based regimen was an independent protective factor for DFS, fungal infection and MRD positivity were independent risk factors for DFS, and tumor somatic TP53 mutation and germline EP300 mutation were independent risk factors for DFS and OS. Conclusion: Germline EP300 mutation and tumor somatic TP53 mutation are poor prognostic factors for posttransplant recurrence and survival in r/r B-ALL patients achieving CR after CAR-T therapy. The prognostic risk factors should be considered in adjusting treatment strategies to improve the efficacy of clinical diagnosis and treatment.