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Background: Previous studies have shown that remnant cholesterol (RC) was associated with cardiovascular disease (CVD) among middle-aged or older adults. However, lack of evidence on long-term exposures to RC and their role in CVD risk among young adults. We thus aimed to explore the association between cumulative RC burden and CVD in young adults., Methods: We enrolled participants younger than 45 years free of CVD history in the Kailuan Study who completed the first three health examinations from 2006 to 2010. Cumulative RC burden included cumulative RC burden score, time-weighted cumulative RC, exposure duration of high RC, and time course of RC accumulation. The outcome was the incidence of CVD. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) between cumulative RC burden and CVD risk., Results: A total of 15,219 participants were included (73.70% male, median age 39.13 years). During a median follow-up duration of 8.71 years (interquartile range: 8.4-9.15 years), 502 individuals developed CVD. After adjustment for traditional cardiovascular risk factors, highest risk of CVD was observed in participants with the highest cumulative RC burden score (HR, 1.66; 95% CI, 1.29-2.12), the highest quartile time-weighted cumulative RC (HR,1.50; 95% CI, 1.15-1.96), the longest exposure duration of high RC (HR, 1.71; 95% CI, 1.21-2.42), and those with cumulative RC burden and positive slope (HR, 1.79; 95% CI, 1.35-2.36)., Conclusions: Cumulative RC burden increased the risk of CVD among young adults, suggesting that maintaining low RC levels throughout young adulthood may minimize CVD risk., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Currently, the special blood pressure (BP) target for normotensive diabetic patients has not been recommended. We investigated the optimal systolic blood pressure (SBP) for lower cardiovascular disease (CVD) risk in normotensive diabetic patients., Methods: In this 12-year follow-up study using the participants of the Kailuan Study, we mainly compared which SBP, 90-119 mmHg or 120-129 mmHg, had a lower risk of occurrence of CVD (stroke and myocardial infarction) in the 3072 normotensive diabetic participants and 21,532 normotensive and non-diabetic participants, respectively. The SBP was expressed as a mean time-weighted cumulative (MTWC) SBP, calculated from the multiple measurements of SBP during the follow-up. Multivariate competing risk regression analyses were used for the analysis., Results: We found that in normotensive diabetic participants, MTWC SBP of 120-129 mmHg was associated with a lower risk of CVD (HR = 0.69 [0.50-0.95]), myocardial infarction (HR = 0.48 [0.24-0.96]), and trending towards lower risk of stroke (HR = 0.80 [0.55-1.16]), compared to MTWC SBP of 90-119 mmHg. Sensitivity analyses confirmed the relationship between low SBP and increased CVD risk. Whereas, in the normotensive and non-diabetic participants, MTWC SBP of 90-119 mmHg vs 120-129 mmHg did not exhibit any difference in the risk of CVD occurrence (HR = 0.99 [0.83-1.18])., Conclusions: The higher level of SBP in normotensive diabetic patients is especially associated with a lower risk of CVD occurrence., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Although arterial stiffness measured by brachial-ankle pulse wave velocity (baPWV) and blood pressure (BP) significantly correlated, the relationship between baPWV and BP variation (BPV) was unclear. This study aimed to examine the temporal relationship between brachial-ankle pulse wave velocity (baPWV) and systolic blood pressure variation (SBPV) and their joint effect on the development of cardiovascular disease (CVD). This study included 6632 participants with repeated assessments of baPWV and BP during 2006 to 2018. The baseline and follow-up SBPV was calculated as absolute SBP difference divided by mean SBP over sequential visits, using data between 2006-2010 and 2014-2018, respectively. Cross-lagged analysis was used to assess the temporal relation between baPWV and SBPV, and logistic analysis was used to assess the joint effect of baPWV and SBPV on CVD. After adjustment for confounder, the path coefficient from baseline baPWV to follow-up SBPV (β 1  = 0.040; P = 0.0012) was significantly had greater than the path from baseline SBPV to follow-up baPWV (β 2  = 0.009; P = 0.3830), with P = 0.0232 for the difference between β 1 and β 2 . This unidirectional relationship from baseline baPWV to follow-up SBPV was consistent in patients without hypertension, with isolated systolic, high systolic and diastolic, uncontrolled and controlled hypertension. In addition, participants with high levels of baseline baPWV and follow-up SBPV had greater risk of CVD (odds ratio, 5.82; 95% confidence interval, 2.50-12.60) than those with low-low levels. The findings suggested that arterial stiffness appeared to precede the increase in SBPV and their joint effect is predictive of the development of CVD., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Purpose: To evaluate the association of body mass index (BMI) with risk of first cardiometabolic disease (FCMD), cardiometabolic multimorbidity (CMM) and death., Methods: 87,512 participants free of CMD were included from the Kailuan cohort, which was established during 2006-2007 and followed up until 2020. BMI was classified as underweight ( < 18.5 kg/m 2 ), healthy weight (18.5-23.9 kg/m 2 ), overweight (24.0-27.9 kg/m 2 ), mildly obese (28.0-31.9 kg/m 2 ), and severely obese ( ≥ 32.0 kg/m 2 ). FCMD was defined as the first onset of diabetes, heart disease, or stroke, and CMM as the coexistence of at least two CMD. The hazard ratio (HR) and 95% confidence interval (95%CI) were estimated with multi-state models., Results: 20,577 participants developed FCMD, 2232 developed CMM afterwards, and 10,191 died. Individuals with higher BMI was more likely to develop FCMD and CMM. Compared with healthy weight, the HR (95%CI) of severe obesity for transition from health to FCMD and from FCMD to CMM was 3.12 (2.91, 3.34) and 1.92 (1.60, 2.31), respectively. On the other hand, underweight was consistently associated with higher mortality risk regardless of initial status, whereas severe obesity was only related to increased risk for transition from health to death (HR: 1.36; 95%CI: 1.17, 1.56) but not for transition from FCMD (HR: 0.70; 95%CI: 0.57, 0.87) or CMM (HR: 0.80; 95%CI: 0.54, 1.19) to death., Conclusion: Our findings highlighted the importance of maintaining healthy weight for primary and secondary prevention of CMD and reflected the demand for more accurate measurement and comprehensive management of obesity for CMD patients., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Although sleep duration and depression were correlated, their temporal sequence and how the sequence influence on future risk of cardiovascular disease (CVD) remained undetermined. This study aimed to explore the temporal relationship between sleep duration and depression, and its association with future CVD risk., Methods: We included 10,629 middle-aged and elderly participants with repeated measurements of sleep duration and depressive symptoms (measured by Center for Epidemiological Studies-Depression scale [CESD]) at the first two visits from the China Health and Retirement Longitudinal Study. Cross-lagged analysis and mediation analysis were used to examine the temporal relationship between sleep duration and depression and its impact on future risk of CVD., Results: The adjusted cross-lagged path coefficient from baseline sleep duration to follow-up CES-D (β 1  = -0.191; 95 % confidence interval [CI], -0.239 to -0.142) was significantly greatly than that from baseline CES-D to follow-up sleep duration (β 2  = -0.031; 95 % CI, -0.031 to -0.024) (P difference  < 0.0001). Similarly, the path coefficient from baseline sleep duration to annual changes in CES-D was significantly greater than that from baseline CES-D to annual changes in sleep duration (β 1  = -0.093 versus β 2  = -0.015, P difference  < 0.0001). The path coefficient from baseline sleep duration to follow-up CES-D in CVD group was significantly greater than that in those without CVD (P difference of β 1  = 0.0378). Furthermore, 27.93 % of the total association of sleep duration with CVD was mediated by depression symptoms., Conclusions: The findings provide evidence that decrease in sleep duration probably precedes the increased in depressive symptoms, and depression partially mediated the pathway from sleep duration to incident CVD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Objective: The objective of this study was to evaluate the associations of general and central obesity with risk of first cardiometabolic disease (FCMD), cardiometabolic multimorbidity (CMM), and death., Methods: A total of 86,169 participants who were CMD-free were included from the Kailuan cohort and categorized into four groups by quartiles of BMI, waist to hip ratio (WHR), weight-adjusted waist index, and waist to height ratio. We defined FCMD as the first onset of diabetes, stroke, or myocardial infarction and CMM as co-occurrence of at least two CMDs. Multistate models were used to estimate hazard ratios and 95% CI., Results: A total of 18,461 participants developed FCMD, of whom 1476 progressed to CMM, and 10,009 died during follow-ups. Both general and central adiposity indices increased the risk of transition from baseline to FCMD and from FCMD to CMM. However, compared with the first quartile, the hazard ratio (95% CI) of the fourth quartile of BMI was 0.86 (95% CI: 0.80-0.91) for transition from health to death and 0.66 (95% CI: 0.59-0.74) from FCMD to death, whereas the corresponding estimates of WHR were 1.22 (95% CI: 1.14-1.31) and 1.16 (95% CI: 1.02-1.32), respectively., Conclusions: Central adiposity indices such as WHR were associated with an increased risk of CMD and mortality, showing no evidence for the obesity paradox and thereby supporting a shift of public focus from BMI only to both general obesity and adiposity distribution., (© 2024 The Obesity Society.)

Aims: To investigate the associations of baseline and longitudinal cardiovascular health (CVH) measured by 'Life's Essential 8' (LE8) metrics with the risk of diabetes in Chinese people with normoglycaemia or prediabetes., Materials and Methods: A total 86,149 participants without diabetes were enroled from the Kailuan study and were stratified by baseline glycaemic status (normoglycaemia or prediabetes). Cardiovascular health score ranged from 0 to 100 points was categorised into low (0-49), middle (50-79), and high (80-100) CVH status. Cox regressions were used to assess the associations of baseline and time-updated CVH status with incident diabetes in the overall cohort and across baseline glycaemic statuses., Results: During a median follow-up of 12.94 (interquartile rage: 12.48-13.16) years, we identified 13,097 (15.20%) cases of incident diabetes. Baseline and time-updated high CVH status was associated with a lower risk of diabetes, the corresponding hazard ratio (HR) versus low CVH status was 0.27 (95% confidence interval [CI], 0.23-0.31) and 0.26 (95% CI, 0.23-0.30) in the overall cohort, respectively. Additionally, the effect of high CVH on diabetes was more prominent in participants with normoglycaemia than those with prediabetes (P < 0.0001), with an HR of 0.26 (95% CI, 0.22-0.31) versus 0.50 (95% CI, 0.41-0.62) for baseline CVH, and 0.25 (95% CI, 0.21-0.30) versus 0.39 (95% CI, 0.32-0.48) for time-updated CVH., Conclusions: Elevated baseline and longitudinal CVH score assessed by LE8 metrics is associated with a lower risk of subsequent diabetes, especially in normoglycaemic adults., (© 2023 John Wiley & Sons Ltd.)

Background: The association between obesity and cardiovascular disease (CVD) in people without traditional CVD risk factors is unclear. This study aimed to investigate the association of obesity with CVD and its subtypes in people without traditional CVD risk factors., Methods: Based on the Kailuan cohort study, the included participants were divided into different groups according to levels of body mass index (BMI) and waist height ratio (WHtR), respectively. Multivariate Cox proportional hazard models were used to evaluate the associations., Results: This study included 31,955 participants [men 63.99%; mean age (48.14 ± 3.33) years]. During a median follow-up period of 12.97 (interquartile range: 12.68-13.17) years, 1298 cases of CVD were observed. Compared with the normal BMI group, the hazard ratios (HRs) for CVD, stroke, and myocardial infarction (MI) in the BMI obese group were 1.31 (95% confidence interval [CI] 1.11-1.55), 1.21 (95%CI 1.01-1.46), 1.62 (95%CI 1.13-2.33), respectively. Compared with the WHtR non-obese group, the HRs for CVD, stroke, and MI in the obese group were 1.25(95%CI 1.11-1.41), 1.18 (95%CI 1.03-1.34), 1.57 (95%CI 1.18-2.09), respectively. There was an interaction between age and WHtR (P for interaction was 0.043). The association between WHtR and CVD was stronger in people under 60 years old, with a HR of 1.44 (95%CI 1.24-1.67)., Conclusion: We found that obesity increased the risk of CVD in people without traditional CVD risk factors. The association of WHtR with CVD was stronger in people under 60 years old., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: The quantification of cardiovascular health (CVH) was updated by the American Heart Association recently by using the "Life's Essential 8" (LE8) score. We aimed to investigate the associations of baseline and longitudinal CVH status measured by the new LE8 score (except for blood pressure) with the risk of hypertension., Methods: A total of 52 990 participants with complete data on LE8 metrics and without hypertension were enrolled from the Kailuan study, Tangshan, China. The associations of incident hypertension with the overall baseline, time-updated, and time-varying CVH score (ranging 0 [lowest] to 100 [highest]), and each component of LE8, were assessed by Cox regressions., Results: During a median follow-up of 10.73 years 28 380 cases of incident hypertension were identified. The risk of hypertension attenuated with increased CVH score (P trend < 0.0001), the hazard ratios (HRs) in high CVH versus low CVH group was 0.54 (95% confidence interval [CI], 0.51-0.57) for baseline CVH, 0.47 (95% CI, 0.45-0.50) for time-updated CVH, and 0.59 (95% CI, 0.55-0.63) for time-varying CVH. The predictive value of CVH in predicting hypertension improved by using LE8 than using Life's Simple 7 metrics. Among LE8 components, body mass index score was the strongest risk factor for hypertension. Subgroup analyses showed that the benefit of a higher CVH score on hypertension was more prominent in young adults and in women (P interaction < 0.05)., Conclusions: A higher CVH score assessed by new LE8 is associated with a lower risk of subsequent hypertension, especially young adults and women.

Background: High cardiovascular health (CVH) was associated with lower risk of cardiovascular disease (CVD) and longer life expectancy. However, whether life years lived without CVD could increase faster than or at least at the same pace as total lifespan remains unknown. We aimed to explore the associations of CVH status with total life expectancy and life years lived with and without CVD among middle-aged and elderly men and women., Methods: We included 65,587 participants aged ≥ 45 years from Kailuan study, who were recruited during June 2006 to October 2007. CVH was scored and classified (low [0-49 points], moderate [50-79 points] and high [80-100 points]) with Life's Essential 8, incorporating evaluations of health behaviors and factors. All-cause mortality and incident non-fatal CVD were recorded from baseline to December 31, 2020. The multi-state life table was adopted to explore the associations of CVH status with total life expectancy and life years lived with and without CVD., Results: Six thousand fifty eight cases of incident non-fatal CVD and 10,580 cases of deaths were identified. Men aged 45 years with low, moderate, and high CVH had a life expectancy of 33.0, 36.5 and 38.5 years, of which 7.8 (23.6%), 6.0 (16.3%) and 3.7 years (9.6%) were spent with CVD. For women, the corresponding life expectancy was 36.6, 43.6 and 48.6 years, and the remaining life years lived with CVD were 7.8 (21.3%), 6.0 (13.7%) and 4.5 years (9.3%), respectively. The benefits of high CVH were persistent across lifespan from age 45 to 85 years and consistent when CVH was evaluated with health behaviors and factors alone., Conclusions: High CVH compared with low CVH was associated with longer total life expectancy and fewer years spent with CVD, indicating that promoting CVH is of great importance for CVD prevention and healthy ageing in China., (© 2023. The Author(s).)

Background: The risk of cardiovascular disease (CVD) depended on the magnitude and exposure duration of insulin resistance (IR). This study aimed to investigate the associations of cumulative metabolic score for IR (cumMETS-IR) with incident CVD, and to further explore the modulated effects of time course of METS-IR accumulation., Methods: We enrolled 47,270 participants without CVD and underwent three examinations during 2006-2010 from the Kailuan study. CumMETS-IR from 2006 to 2010 were calculated as the mean values of METS-IR between consecutive examinations multiplying by time intervals between visits. Time course of METS-IR accumulation was calculated as the slope of METS-IR versus time. Hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD risk were calculated with multivariable-adjusted Cox regressions., Results: During a median follow-up of 10.99 years, we identified 3184 cases of incident CVD. The risk of incident CVD increased with increasing cumMETS-IR (HR, 1.77; 95% CI 1.58-1.98 for the Q4 versus Q1 group), exposure duration (HR, 1.60; 95% CI 1.45-1.77 for 6 years versus 0 years), and cumulative burden (HR, 1.49; 95% CI 1.37-1.61 for burden ≥ 0 versus < 0). A positive slope was associated with 14% higher risk of CVD (HR, 1.14; 95% CI 1.07-1.22). When combining cumMETS-IR and slope, those with cumMETS-IR ≥ median (142.78) and slope ≥ 0 had the highest risk of CVD (HR,1.38; 95% CI 1.25-1.53)., Conclusions: The risk of CVD increased with elevated cumMETS-IR and an increasing trend over time, emphasizing the importance of maintaining optimal METS-IR levels across life span., (© 2023. The Author(s).)

Background: Incorporation both the magnitude and duration of exposure to elevated fasting blood glucose (FBG) into a single risk parameter (cumulative FBG load) for future diseases is intuitively appealing, although a data-based demonstration of the utility of this metric is not available. This study aimed to investigate the associations with cumulative FBG load with the risk of cardiovascular diseases (CVD) and all-cause mortality in the general population., Methods: This prospective cohort study included 41,728 participants who were free of CVD and underwent four health examinations from 2006 to 2012. Cumulative FBG load during 2006-2012 was calculated as the area under curve for FBG values ≥ 5.6 mmol/L divided by the total area curve. We also compared the predicting value cumulative FBG load with other FBG metrics., Results: During a median follow-up of 6.75 years, we identified 2323 cases of CVD and 1724 cases of all-cause mortality. Per 1-standard deviation increase in cumulative FBG load was associated with a 16 % higher risk of CVD (hazard ratio [HR]: 1.16; 95 % confidence interval [CI], 1.13-1.20) and 20 % higher risk of all-cause mortality (HR, 1.20; 95 % CI, 1.16-1.25). For the prediction of cardiovascular outcomes and all-cause mortality, cumulative FBG load outperformed FBG time-in-target, visit-to-visit FBG variability, and mean FBG in terms of C-statistics and reclassification indexes., Conclusions: Cumulative FBG load may provide a better prediction of cardiovascular outcomes compared with other FBG metrics in the general population. These findings emphasized the important role of cumulative FBG load in assessing cardiovascular and mortality risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Large blood pressure (BP) variability contributed to subclinical brain disease thus may be implicated in the development of cardiovascular disease (CVD). This study included 64,810 CVD-free participants who attended the first two examinations from the Kailuan study to investigate the association of BP variation, considering its magnitude, direction, and time interval prior to CVD diagnosis, with the risk of CVD in Chinese population. Magnitude and directional BP variability was calculated as absolute BP difference or BP difference value divided by mean BP over 2 sequential visits, respectively. During a median follow-up of 10.91 years, a total of 4129 cases of CVD. A large SBP variability (the highest vs the lowest tertile) was associated with a higher risk of CVD (adjusted HR, 1.31; 95% CI, 1.22-1.41). The associations were stronger with longer time intervals, the hazard ratio (HR) with 95% confidence interval (CI) for CVD was 1.30 (95% CI, 1.20-1.39) at 1 years, 1.32 (1.18-1.40) at 3 years, and 1.34 (1.20-1.45) at 5 years. For directional SBP variability, rise in SBP was associated with an increased risk of CVD (HR, 6.17; 95% CI, 5.65-6.75), while fall in SBP was associated with a decreased risk of CVD (HR, 0.52; 95% CI, 0.46-0.59). Subgroup analysis showed the significant associations were only observed in men (P int  = 0.0010). Similar patterns were observed for DBP variability and CVD subtypes. The results indicated that a large SBP variation in rise direction was associated with an increased risk of incident CVD, especially in men., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background The American Heart Association recently proposed an updated definition of cardiovascular health (CVH) named as Life's Essential 8. We aimed to explore the association between this latest published CVH measurement and years lived without cardiovascular disease (CVD) among the Chinese population. Methods and Results We included 89 755 adults free of CVD at baseline from the Kailuan study. The CVH of each participant was scored (from 0 point to 100 points) and classified (low [0-49 points], moderate [50-79 points], and high [80-100 points]) according to Life's Essential 8, which incorporated 8 components covering health behaviors and health factors. Incident CVD was documented through follow-ups from baseline (June 2006 to October 2007) until December 31, 2020. CVD-free life years from age 30 to 80 years associated with different CVH scores were estimated using flexible parametric survival models. A total of 9977 incident CVDs were recorded. We observed a gradient relationship between CVH score and years lived without CVD. The age- and sex-adjusted CVD-free life years (95% CI) were 40.7 (40.3-41.0) years for low CVH, 43.3 (43.0-43.5) years for moderate CVH, and 45.5 (45.1-45.9) years for high CVH. Similar trends were noted when individual subtypes of CVD were investigated, and high CVH evaluated by health behaviors and health factors was also related to longer CVD-free life years. Conclusions A higher CVH evaluated by the updated Life's Essential 8 metrics was significantly associated with a greater number of life years without CVD, indicating the importance of promoting CVH for healthy aging in China.

Background: The association of serum uric acid (SUA) with cardiovascular disease (CVD) is inconsistent and limited by a single measurement of SUA. This study aimed to investigate the association of SUA variation, considering its magnitude and direction, with the risk of CVD., Methods: This study included 41,578 participants with four biennial measurements of SUA during 2006-2012 from the Kailuan study. SUA variation was measured using the coefficient of variation (primary index), standard deviation, average real variability, and variability independent of mean, and the direction of variation was also assessed. Multivariate-adjusted Cox regressions were used to assess the associations, and Bayesian network was utilized to find the most important pathway from SUA variation to CVD., Results: During a median follow-up of 6.74 (interquartile range: 6.45-7.03) years, we identified 1,852 (4.45%) cases of incident CVD. A large SUA variation (top vs. bottom tertiles) was associated with a higher risk of CVD (hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.11-1.40), especially in older adults than that in young adults (P int =0.0137). The higher risk of CVD was observed with both large rises (HR, 1.24; 95% CI, 1.10-1.39) and falls (HR, 1.19; 95% CI, 1.03-1.38) in SUA variation. The hazardous effect of SUA variation on CVD was mainly induced by excessive inflammation and elevated blood pressure. Similar results were observed for CVD subtypes., Conclusions: Elevated SUA variation was associated with a higher risk of CVD, irrespective of the direction of SUA variation, and inflammation played an important role in the pathway., Competing Interests: Declaration of Competing Interest These authors declare that they have no conflicts of interests., (Copyright © 2023 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background Healthy individuals with normal level of serum uric acid (SUA) may not be truly at the lowest risk of cardiovascular disease (CVD). This study aimed to assess the association of SUA levels with CVD and its subtypes in people without CVD risk factors and determine a suitable target of SUA to prevent CVD. Methods and Results We enrolled 25 284 participants who were free of CVD, absent of CVD risk factors, and with an SUA level between 180 and 359 μmol/L (3-6 mg/dL) at baseline from the Kailuan study. Cox proportional hazards models were applied to calculated adjusted hazard ratio (HR) and 95% CI for the risk of CVD and its subtypes. During a median follow-up of 12.97 years (interquartile range, 12.68-13.16 years), we identified 1007 cases of CVD. There was an increase in the risk of incident CVD with increasing SUA levels ( P trend =0.0011). Compared with participants with SUA levels of 180 to 239 μmol/L (3-4 mg/dL), the HR of CVD was 1.12 (95% CI, 0.96-1.31) and 1.28 (95% CI, 1.08-1.52) for SUA levels of 240 to 299 μmol/L (4-5 mg/dL) and 300 to 359 μmol/L (5-6 mg/dL), respectively. A multivariable-adjusted spline regression model showed a J-shaped association between SUA and the risk of CVD. Similar results were observed for stroke and myocardial infarction. Conclusions The risk of incident CVD increased with elevating SUA levels among individuals without hyperuricemia or other traditional CVD risk factors. These findings highlighted the importance of primordial prevention for SUA level increase along with other traditional CVD risk factors.

Aims: Whereas cardiovascular disease (CVD) metrics define risk in individuals aged over 40 years, the earliest lesions of CVD appear well before this age. Cardiovascular health (CVH) was proposed to improve cardiovascular risk factors and was updated recently. This study aimed to explore the associations of baseline and long-term CVH assessed by 'Life's Essential 8' metrics with premature CVD and all-cause mortality in young Chinese adults., Methods and Results: A total of 16 011 CVD-free participants aged 18-40 years were enrolled from the Kailuan cohort study. The CVH score ranged from 0 to 100 and was categorized into low, moderate, and high. Cox regressions were used to assess the hazard ratios (HRs) for the associations of baseline, time-updated mean, and time-varying CVH with the risk of outcomes. During a median follow-up of 13 years, we identified 271 cases (1.7%) of CVD and 219 cases (1.4%) of all-cause mortality. A lower CVH was associated with a higher risk of CVD and all-cause mortality; the adjusted HR in the low CVH vs. the high CVH group was 7.34 [95% confidence interval (CI), 3.19-16.89] and 2.54 (95% CI, 1.27-5.06) for baseline CVH, 4.38 (95% CI, 2.14-8.97) and 1.99 (95% CI, 1.06-3.71) for time-updated CVH, and 8.19 (95% CI, 2.70-24.88) and 4.28 (95% CI, 1.70-10.81) for time-varying CVH, respectively., Conclusion: We observed an inverse gradient association of baseline and long-term CVH with the risk of premature CVD and all-cause mortality in young adults, emphasizing the importance of keeping health behaviours and factors earlier in life., Lay Summary: This longitudinal prospective cohort study showed an inverse gradient association of baseline and long-term cardiovascular health, as measured by the new updated Life's Essential 8 metrics, with the risk of premature cardiovascular disease and all-cause mortality in Chinese young adults, emphasizing the importance of keeping health behaviours and factors earlier in life.Baseline and longitudinal low cardiovascular health (CVH) status (measured by time-updated mean and time-varying CVH score) was associated with a higher risk of cardiovascular disease (CVD) and all-cause mortality in young adults aged <40 years.Among the eight metrics of LE8, lower scores of health factors were associated with a higher risk of CVD and all-cause mortality in young adults, while the associations of health behaviours with CVD and all-cause mortality were non-significant., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background The multitrajectory model can identify joint longitudinal patterns of different lipids simultaneously, which might help better understand the heterogeneous risk of premature cardiovascular disease (CVD) and facilitate targeted prevention programs. This study aimed to investigate the associations between multitrajectories of lipids with premature CVD. Methods and Results The study enrolled 78 526 participants from the Kailuan study, a prospective cohort study in Tangshan, China. Five distinct multitrajectories of triglyceride, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol over 6-year exposure were identified on the basis of Nagin's criteria, using group-based multitrajectory modeling. During a median follow-up of 6.75 years (507 645.94 person-years), 665 (0.85%) premature CVDs occurred. After adjustment for confounders, the highest risk of premature CVD was observed in group 4 (the highest and increasing triglyceride, optimal and decreasing LDL-C, low and decreasing high-density lipoprotein cholesterol) (hazard ratio [HR], 2.13 [95% CI, 1.36-3.32]), followed by group 5 (high and decreasing triglyceride, optimal and increasing LDL-C, low and decreasing high-density lipoprotein cholesterol) (HR, 2.07 [95% CI, 1.45-2.98]), and group 3 (optimal and increasing triglyceride, borderline high and increasing LDL-C, optimal and decreasing high-density lipoprotein cholesterol) (HR, 1.90 [95% CI, 1.32-2.73]). Conclusions Our results showed that the residual risk of premature CVD caused by increasing triglyceride levels remained high despite the fact that LDL-C levels were optimal or declining over time. These findings emphasized the importance of assessing the joint longitudinal patterns of lipids and undertaking potential interventions on triglyceride lowering to reduce the residual risk of premature CVD, even among individuals with optimal LDL-C levels.

Background: Although hyperuricemia and hypertension are significantly correlated, their temporal relationship and whether this relationship is associated with risk of cardiovascular disease (CVD) are largely unknown. This study aimed to examine temporal relationship between hyperuricemia and hypertension, and its association with future risk of CVD., Methods: This study included 60,285 participants from the Kailuan study. Measurement of serum uric acid (SUA), systolic and diastolic blood pressure (SBP and DBP) were obtained twice at 2006 (baseline) and 2010. Cross-lagged and mediation analysis were used to examine the temporal relationship between hyperuricemia and hypertension, and the association of this temporal relationship with CVD events risk after 2010., Results: After adjusting for covariates, the cross-lagged path coefficients (β 1 ) from baseline SUA to follow-up SBP and DBP were significantly greatly than path coefficients (β 2 ) from baseline SBP and DBP to follow-up SUA (β 1 =0.041 versus β 2 =0.003; P difference <0.0001 for SBP; β 1 =0.040 versus β 2 =0.000; P difference <0.0001 for DBP). The path coefficients from baseline SUA to follow-up SBP and DBP in group with incident CVD were significantly greatly than that in group without incident CVD (P difference of β 1 in the two groups was 0.0018 for SBP and 0.0340 for DBP). Furthermore, SBP and DBP partially mediated the effect of SUA on incident CVD, the mediation effect was 57.64% for SBP and 46.27% for DBP. Similar mediated results were observed for stroke and myocardial infarction., Conclusion: Increased SUA levels probably precede elevated BP, and BP partially mediates the pathway from SUA to incident CVD., Competing Interests: Declaration of Competing Interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2023 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background: The mechanisms linking obesity to cardiovascular disease (CVD) are still not clearly defined. Individuals who are overweight or obese often develop insulin resistance, mediation of the association between obesity and CVD through the insulin resistance seems plausible and has not been investigated. This study aimed to evaluate whether and to what extend the effect of general and central obesity on cardiovascular disease (CVD) is mediated by insulin resistance., Methods: A total of 94,136 participants without CVD at baseline were recruited from the Kailuan study. Insulin resistance was evaluated by the triglyceride-glucose (TyG) index, calculating as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Mediation analysis using a new 2-stage regression method for survival data proposed by Valeri and VanderWeele was to explore the mediating effects of the TyG index on the association between obesity and CVD., Results: During a median follow-up of 13.01 years, we identified 7327 cases of CVD. Mediation analyses showed that 47.81% of the total association (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.12-1.24) between overweight and CVD was mediated through the TyG index (HR [indirect association], 1.07; 95% CI, 1.07-1.09), and the proportion mediated was 37.94% for general obesity. For central obesity, analysis by waist circumference, waist/hip, and waist/height categories yielded an attenuated proportion mediated of 32.01, 35.02, and 31.06% for obesity, taken normal weight as reference., Conclusions: The association between obesity and CVD was mediated by TyG index, suggesting proper control of insulin resistance can be effective to reduce the effects of obesity on CVD., (© 2022. The Author(s).)

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 (&lt; 55, 55 to &lt; 65, 65 to &lt; 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., (© 2022. The Author(s).)

Background: Future risk of cardiovascular disease (CVD) and mortality is associated with cumulative amount TyG index (cumTyG) exposure, while whether time course of TyG accumulation modulates the risk remains unclear. This study sought to examine the associations of cumTyG index accumulation time course with the risk of CVD and all-cause mortality., Methods: We enrolled 51,734 participants free of CVD and underwent three examinations at year 2006, 2008, and 2010. CumTyG from baseline to the third examination was calculated. Time course of cumTyG accumulation was calculated as the slope of TyG versus time from 2006 to 2010, or as splinting the overall TyG index accumulation into early (cumTyG 06 - 08 ) and late accumulation (cumTyG 08 - 10 ). Participants were categorized by the combination of cumTyG < or ≥ median (34.44 × years) and a negative or positive TyG slope., Results: During a median follow-up of 9.04 years, we identified 3,602 incident CVD cases and 3,165 deaths. The risk of CVD and all-cause mortality increased with decreased TyG slope, the corresponding adjusted hazard ratio (aHR) with 95% confidence interval (CI) was 1.11 (1.04-1.19) and 1.18 (1.10-1.26) for patients with a negative TyG slope, respectively. Consistently, a later accumulation of TyG index was not associated with the risk of CVD and all-cause mortality after adjustment for an early accumulation. When considering the combination of cumTyG index and time course, participants with a cumTyG ≥ median and a negative TyG slope had elevated risk of CVD (aHR, 1.37; 95% CI, 1.24-1.51) and all-cause mortality (aHR, 1.28; 95% CI, 1.15-1.43). Additionally, the association was more prominent in young adults., Conclusion: Early TyG index accumulation resulted in a greater risk of CVD and all-cause mortality than later TyG later accumulation with the same overall cumulative exposure, emphasizing the importance of optimal TyG index control earlier in life., (© 2022. The Author(s).)

Background: The STEP trial (Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients) showed that older hypertensive patients might benefit from a target systolic blood pressure (SBP) of 110 to <130 mm Hg. We examined whether this target SBP is associated with a decreased risk of cardiovascular disease (CVD) and all-cause mortality among elderly Chinese in real-world settings., Methods: This prospective study included 13 383 CVD-free participants aged 60 to 80 years and with SBP within 110 to <150 mm Hg at baseline. Inverse probability of treatment weighting was used to adjust for baseline differences. Weighted Cox proportional hazards models yielded adjusted hazard ratios (HRs) and 95% CIs of CVD and all-cause mortality associated with normalized SBP (110 to <130 mm Hg)., Results: During a median follow-up of 13.01 years, we identified 1727 cases of CVD and 3742 deaths. After inverse probability of treatment weighting, compared with non-normalized SBP, normalized SBP was associated with a decreased risk of CVD (HR, 0.81 [95% CI, 0.76-0.87]) and all-cause mortality (HR, 0.89 [95% CI, 0.85-0.93]). Beneficial effects of longitudinal normalized SBP presented by the updated mean SBP were also observed for CVD (HR, 0.88 [95% CI, 0.78-0.93]) and all-cause mortality (HR, 0.93 [95% CI, 0.88-0.97]). Multiple sensitivity analyses yielded similar results., Conclusions: The SBP target of 110 to <130 mm Hg recommended by the STEP trial was associated a lower risk of CVD and all-cause mortality than was SBP of 130 to <150 mm Hg among elderly Chinese in real-world settings.

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., (© 2022. The Author(s).)

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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The association between impaired fasting glucose and cardiovascular disease (CVD) in participants without atherosclerotic CVD (ASCVD) risk factors based on current definitions is unclear. The study aimed to examine the association of fasting glucose levels with CVD and its subtypes in persons without ASCVD risk factors., Methods: This study included 38 297 participants [men 62.1%; mean age 47.9 (12.9) years] who were free of a history of CVD and absent of ASCVD risk factors and had a fasting plasma glucose (FPG) level between 70 to 125 mg/dL at baseline from Kailuan Study during 2006 and 2007. Participants were followed until new-onset CVD event, death, or December 31, 2017. Cox proportional hazards models were performed to evaluate the associations., Results: During a median follow-up of 11.0 years (interquartile range 10.7-11.2 years), we observed 1217 incident CVD events. Compared with participants with FPG 70 to 99 mg/dL, the multivariable adjusted hazard ratios for CVD among participants with FPG 100 to 109 mg/dL and 110 to 125 mg/dL were 1.18 (95% CI 1.02-1.38) and 1.27 (95% CI 1.03-1.55), respectively. Multivariable-adjusted spline regression model showed a J-shaped association between FPG and the risk of CVD., Conclusions: We found that among individuals without diabetes or other traditional ASCVD risk factors, there is an increased risk of incident CVD with increasing abnormal FPG levels. These results highlight the importance of primordial prevention for FPG level increases along with other traditional ASCVD risk factors., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: We aimed to identify the joint associations of modifiable lifestyle and metabolic factors with the incidences of cardiovascular disease and all-cause mortality., Methods: We recruited 94,831 participants (men, 79.76%; median age, 51.60 [43.47-58.87]) without a history of cardiovascular disease from the Kailuan study during 2006 and 2007 and followed them until a cardiovascular disease event, or death occurred, or until December 31, 2017. Baseline metabolic health status was assessed using Adult Treatment Panel III criteria, and details of the lifestyles of the participants were recorded using a self-reported questionnaire. We used Cox proportional hazards models to evaluate the joint associations., Results: During a median follow-up of 11.03 years, we recorded 6590 cardiovascular disease events and 9218 all-cause mortality. Participants with the most metabolic risk components and the least healthy lifestyle had higher risk of cardiovascular disease (hazard ratio 2.06 [95% confidence interval (CI) 1.77-2.39]) and mortality (HR 1.53 [95% CI 1.31-1.78]), than participants with fewer metabolic risk components and the healthiest lifestyle. Compared with those in participants with the healthiest lifestyle, the HRs for cardiovascular disease in participants with the least healthy lifestyle were 1.26 (95% CI 1.17-1.37), 1.16 (95% CI 1.03-1.31), and 1.07 (95% CI 0.90-1.27) for those with low, medium, and high metabolic risk, respectively., Conclusion: Healthy lifestyle is associated with a lower risk of cardiovascular disease and there is no significant interaction between metabolic risk and a healthy lifestyle. Therefore, a healthy lifestyle should be promoted, even for people with high metabolic risk., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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

Prehypertension is a risk factor for cardiovascular disease (CVD) and all-cause mortality. However, it is unclear whether prehypertension combined with diabetes associate with a higher risk for cardiovascular disease and all-cause mortality. The purpose of this study was to explore the relationship between prehypertension and the risk of CVD and all-cause mortality was different among individuals with or without diabetes. In the prospective community-based Kailuan study, 67 344 participants without hypertension or a history of CVD at baseline (2006) were included. Prehypertension was defined as systolic blood pressure of 120-139 mmHg or diastolic blood pressure of 80-89 mmHg. The outcomes were CVD and all-cause mortality were followed up through December 31, 2017. We performed Cox proportional hazards models to evaluate the relationships between prehypertension and CVD and all-cause mortality by diabetes status. During a median follow-up of 11.03 years, 2981 CVD events and 4655 all-cause mortality occurred. After adjusting age, sex, and other factors, the associations of prehypertension with risk of CVD and all-cause mortality were significant in participants without diabetes (hazard ratio and 95% confidence interval: 1.54 [1.38-1.71] and 1.27 [1.17-1.38]), but not in participants with diabetes (1.20 [0.93-1.56] and 0.88 [0.73-1.07]). The interactions between prehypertension and diabetes for the risk of CVD and all-cause mortality were all significant (all p < .05). Prehypertension was only associated with an increased risk for CVD and all-cause mortality in non-diabetes participants. Diabetes modifies the relation of prehypertension with the risk of CVD and all-cause mortality., (© 2021 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

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.

Background and Aim: Longitudinal evidence on change in serum (SUA) with risk of cardiovascular disease (CVD) and all-cause mortality is limited, as many prior studies focused on baseline SUA. Further, the optimal threshold range of SUA change is unclear., Methods and Results: A total of 63,127 participants without history of CVD were enrolled. Change in SUA was determined by the difference of SUA levels between 2006 and 2010, which divided by baseline SUA was percent change in SUA. Multivariable Cox proportional hazards models were used to calculated the hazard ratios (HRs) and 95% confidence intervals (CIs). Our analysis also included restricted cubic spline model and three-piecewise Cox proportion hazards model to address the non-linearity between percent change in SUA and outcomes. During a median follow-up of 7.04 years, 3341 CVD and 3238 deaths occurred. We did not observed a significant association between changes in SUA and CVD. However, changes in SUA at extreme were associated with higher risk of all-cause mortality, the HRs (95% CIs) were 1.15 (1.02-1.29) and 1.20 (1.06-1.35) in the first and fifth quintile group, compared with the third quintile group. We further found a U-shaped association between percent change in SUA and all-cause mortality, and the optimal range was within 20%., Conclusions: Changes in SUA at extreme were risk factors for all-cause mortality, but not for CVD in the general population. The findings are relevant for role of SUA in the management of CVD risk and may contribute to improve identification of patients at higher risk., Competing Interests: Declaration of competing interest The authors have nothing to disclose., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Retinoid X receptors (RXRs) are members of ligand-dependent transcription factors whose effects on a diversity of cellular processes, including cellular proliferation, the immune response, and lipid and glucose metabolism. Knock out of RXRα causes a hypoplasia of the myocardium which is lethal during fetal life. In addition, the heart maintains a well-orchestrated balances in utilizing fatty acids (FAs) and other substrates to meet the high energy requirements. As the master transcriptional regulators of lipid metabolism, RXRs become particularly important for the energy needs of the heart. Accumulating evidence suggested that RXRs may exert direct beneficial effects in the heart both through heterodimerization with other nuclear receptors (NRs) and homodimerization, thus standing as suitable targets for treating in cardiovascular diseases. Although compounds that target RXRs are promising drugs, their use is limited by toxicity. A better understanding of the structural biology of RXRs in cardiovascular disease should enable the rational design of more selective nuclear receptor modulators to overcome these problems. Here, this review summarizes a brief overview of RXRs structure and versatility of RXR action in the control of cardiovascular diseases. And we also discussed the therapeutic potential of RXR ligand., (Copyright © 2021. Published by Elsevier Masson SAS.)

Background: Triglyceride glucose (TyG) index and its related parameters have been introduced as cost-effective surrogate indicators of insulin resistance, while prospective evidence of their effects on atherosclerotic cardiovascular disease (ASCVD) remained scattered and inconsistent. We aimed to evaluate the association of TyG and its related parameters with new-onset ASCVD, and the predictive capacity were further compared. Method: A total of 95,342 ASCVD-free participants were enrolled from the Kailuan study. TyG and its related parameters were defined by fasting blood glucose, triglyceride, body mass index (BMI), waist circumstance (WC) and waist-to-height ratio (WHtR). The primary outcome was incident ASCVD, comprising myocardial infarction (MI) and ischemic stroke (IS). Cox proportional hazard models and restricted cubic spline (RCS) analyses were adopted to investigate the association between each index and ASCVD. The C-index, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were used for comparison of their predictive value for ASCVD. Results: During a median follow-up of 15.0 years, 8,031 new cases of ASCVD were identified. The incidence rate of ASCVD increased along with elevated levels of each index, and the relationships were found to be nonlinear in the RCS analyses. The hazard ratio (HR) and 95% confidence interval (95% CI) for ASCVD was 1.39 (1.35, 1.43), 1.46 (1.41, 1.50), 1.50 (1.46, 1.55), and 1.52 (1.48, 1.57) per 1 IQR increase of baseline TyG, TyG-BMI, TyG-WC, and TyG-WHtR, respectively, and the association were more pronounced for females and younger individuals aged < 60 years (Pfor interaction<0.05). Using the updated mean or time-varying measurements instead of baseline indicators did not significantly alter the primary findings. Additionally, TyG-WC and TyG-WHtR showed better performance in predicting risk of ASCVD than TyG, with the IDI (95% CI) of 0.004 (0.001, 0.004) and 0.004 (0.001, 0.004) and the category-free NRI (95% CI) of 0.120 (0.025, 0.138) and 0.143 (0.032, 0.166), respectively. Similar findings were observed for MI and IS. Conclusions: Both the TyG index and its related parameters were significantly and positively associated with ASCVD. TyG-WC and TyG-WHtR had better performance in predicting incident ASCVD than TyG, which might be more suitable indices for risk stratification and enhance the primary prevention of ASCVD. [ABSTRACT FROM AUTHOR]