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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. Graphical Abstract:

It has not been fully investigated whether improved arterial stiffness (AS) can reduce the clinical outcomes risk in community population-based study. In this prospective study, a total of 5247 individuals with abnormal AS (at baseline) and repeated brachial-ankle pulse wave velocity (baPWV) measurement before 2018 years were enrolled from the Kailuan Study. According the second baPWV measurement, we divided the participants into two groups, improved AS (defined as transfer elevated AS status to normal) and persistent AS (defined as maintaining elevated AS status). The outcome was a composite event of stroke, myocardial infraction, and all-cause mortality. We used Cox proportional hazards regression to examine the association between AS status at the follow-up and the subsequent outcome. During a median of 5.2 years follow-up, we observed 413 end point events. After adjusted for potential confounders, comparing with the persistent AS group, individuals in the improved AS group had a 43% (hazard ratio [HR], 0.57; 95% confidence interval [CI] 0.35–0.94) decreased the risk of the primary composite events. We also found a baPWV decrease of 1 m/s was associated with a 3% decreased risk (HR, 0.97; 95% CI 0.94–0.99) for primary composite events. We further demonstrated that younger than 60 years, non-smoker, non-hypertension, and non-diabetes were associated with improved the AS status. In conclusion, improving AS status may reduce the risk of clinical events. In the future, more research should be performed to explore the target for improving the AS status.

Cross-sectional studies have shown that remnant cholesterol (RC) was associated with arterial stiffness. The present study evaluated the association of RC and the discordance between RC and low-density lipoprotein cholesterol (LDL-C) with arterial stiffness progression.

Purpose: The purpose of this study is to explore the association between adiposity indices and blood lipid indices and prediabetes. We compare the predictive value of new adiposity indices and traditional adiposity indices and blood lipid indices in the diagnosis of prediabetes. Methods: This is a prospective cohort study of 7953 participants. The follow-up time was 3 years. The eight adiposity indices included the following: body mass index (BMI), waist circumference (WC), body roundness index (BRI), A Body Shape Index (ABSI), visceral adiposity index (VAI), lipid accumulation product (LAP), fatty liver index (FLI), and triglyceride-to-glucose fasting index (TyG), as well as four blood lipid indices as follows: total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C).The association between adiposity indices and blood lipid indices for diagnosis of prediabetes was estimated using a logistic regression model to obtain the odds ratio (OR) and its 95% confidence interval (CI). We calculated the area under the curve (AUC) of receiver operating characteristic (ROC) curve analysis to measure the predictive value of adiposity indices and blood lipid indicators for the diagnosis of prediabetes in the general population stratified by gender. Results: The median age of the participants was 56 years old, men accounting for 35.3% of the final group. After adjusting for confounding factors, association of BMI, BRI, VAI, LAP, TyG, TC, TG, and LDL-C with prediabetes status was assessed at both baseline and follow-up. TyG (AUC, overall: 0.677 (95% CI, 0.665, 0.689), male: 0.645 (95% CI, 0.624–0.667), and female: 0.693 (95% CI, 0.678–0.708)) have better diagnostic value for prediabetes than VAI, LAP, FLI, TC, TG, HDL-C, and LDL-C. The predictive value of the combination of TyG, BRI, VAI, and TG significantly improves the power of any single index in the diagnosis of prediabetes. The AUC and corresponding 95% CI of TyG, BRI, VAI, and TG and the combination of these four indicators to diagnose prediabetes were 0.677 (0.665, 0.689), 0.630 (0.617, 0.643), 0.618 (0.606, 0.631), 0.622 (0.609, 0.635), and 0.728 (0.716, 0.739), respectively. Conclusions: Among the eight adiposity indices and four blood lipid indices evaluated in the study, TyG had the highest diagnostic value for prediabetes in isolated indexes, and the combination of TyG, BRI, VAI, and TG significantly improved the diagnostic value for prediabetes of any single indicator.

Evidence is lacking about the role of serum uric acid (SUA) in the progression from prehypertension to hypertension. Herein, we aimed to investigate the association of both baseline and dynamic change in SUA with the risk of hypertension developing from prehypertension. The study enrolled 11,488 participants with prehypertension during 2006–2010 from the Kailuan study. Change in SUA was assessed as % change of SUA from 2006 (baseline) to 2010. Participants were categorized into four groups by quartiles of baseline and change in SUA, separately. Multivariable logistic regressions were used to calculation the odds ratio (OR) and 95% confidence interval (CI). During a median follow-up of 7.06 years, 2716 (23.64%) participants developed hypertension from prehypertension. In the multivariable-adjusted model, the OR for hypertension comparing participants in the highest versus the lowest quartile of baseline SUA were 1.18 (95% CI, 1.02–1.36). Increased SUA over time was also associated with elevated risk of hypertension (OR in the highest quartile was 1.41 [95% CI, 1.23–1.62] versus the lowest quartile), especially in those with baseline SUA ≥ median (OR, 1.48; 95% CI, 1.21–1.81). Moreover, the addition of SUA to a conventional risk model had an incremental effect on the predictive value for hypertension (integrated discrimination improvement 0.30%, P< 0.0001; category-free net reclassification improvement 12.36%, P< 0.0001). Both high initial SUA and increased SUA over time can independently predict the progression from prehypertension to hypertension. Strategies aiming at controlling SUA level in prehypertensive subjects may impede the onset of hypertension.

Purpose: To investigate whether non-high-density lipoprotein cholesterol (Non-HDL-C), remnant cholesterol (RC), and the ratios of lipid indexes are more closely associated with early progression of kidney dysfunction than traditional lipid indexes; and to explore the association between changes in serum lipids during follow-up and annual decline rate in estimated glomerular filtration rate (eGFR). Methods: In this prospective cohort study, 3909 participants with normal eGFR and age≥40 years at baseline were followed for 3.3 years. Progression of kidney dysfunction was assessed as annual decline rate in eGFR. Spearman correlation analysis, linear correlation models, and multiple logistic regression were used to assess the associations between lipid indexes at baseline/both baseline and follow-up and the annual decline rate in eGFR. Results: Compared with ΔLDL-C (β= 0.412), other lipid indexes such as ΔLDL-C/HDL-C (β= 0.565), ΔTC/HDL-C (β = 0.448), and ΔNon-HDL-C/HDL-C (β= 0.448) were more closely associated with annual decline rate in eGFR. High TG/HDL-C (OR = 1.699(1.177–2.454)) and TC/HDL-C (OR = 1.567(1.095–2.243)) at baseline, as well as high TC/HDL-C (OR = 1.478 (1.003–2.177)) and TG/HDL-C (OR = 1.53(1.044–2.244)) at both baseline and follow-up were associated with the annual decline rate in eGFR &lt;0.5. High Non-HDL-C (OR = 1.633(1.025–2.602)) and LCI (OR = 1.631(1.010–2.416)) at both baseline and follow-up resulted in a 63% increase in risk of annual decline rate in eGFR >1. Conclusion: High Non-HDL-C, RC and the ratios of lipid indexes were more closely associated with early progression of kidney injury than the increase of traditional lipid indexes. These lipid indexes should be monitored, even in participants with normal traditional serum lipid levels.

Multifocal atherosclerosis has dramatically increased annual risk of adverse cardiovascular events than single artery affected. Triglyceride-rich lipoprotein (TRL) has been implicated in the early development of atherosclerosis.

Purpose: This study aimed to assess the cross-sectional and longitudinal associations of the triglyceride glucose (TyG) index, a simple surrogate marker of insulin resistance, with intra-cranial and extra-cranial artery stenosis (ICAS and ECAS) in Chinese adults. Methods: Participants were recruited from the Asymptomatic Polyvascular Abnormalities Community study, 5381 participants were enrolled in the cross-sectional analysis, then 3447 and 1853 participants in the longitudinal analysis for incident ICAS and ECAS, respectively. The TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Multivariable logistic analysis was used to calculate odds ratio (OR) and 95% confidence interval (CI). Results: The results of the cross-sectional and longitudinal analysis were basically the same, as the fully adjusted OR comparing participants in the highest tertile versus lowest tertile of the TyG index was 1.34 (95% CI, 1.13–1.59) for the prevalence of ECAS and 1.85 (95% CI, 1.26–2.71) for incident ECAS, respectively. The addition of TyG index to a conventional model had an incremental effect on the predictive value for ECAS. However, we did not observe any significant association between the TyG index and ICAS. Conclusions: Elevated TyG index was significantly associated with a higher risk of ECAS, but not with ICAS in Chinese adults. This conclusion lends support to the clinical significance of the TyG index for the assessment of artery stenosis, especially for ECAS.

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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.

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Metabolic dysfunction-associated fatty liver disease (MAFLD) is a risk factor for stroke and all-cause mortality and highly prevalent among patients with chronic kidney disease (CKD). It is unclear whether the association of MAFLD with stroke and all-cause mortality differs within and outside of the setting of CKD.

Background: Long-term patterns of serum uric acid (SUA) and their association with the risk of myocardial infarction (MI) and mortality are poorly characterized as prior studies measured SUA at a single time point. This study aimed to identify SUA trajectories and determine their associations with incident MI and all-cause mortality. Methods: We included 85,503 participants who were free of MI in or prior 2012 from the Kailuan study. SUA trajectories during 2006–2012 were identified by group-based trajectory modeling. Cox proportional hazard models were used to assess the association of SUA trajectories with MI and all-cause mortality. Results: We identified three SUA trajectories during 2006–2012: low-stable (n=44,124, mean SUA: 236–249 μmol/L), moderate-stable (n=34,431, mean SUA: 324–354 μmol/L) and high-stable (n=6,984, mean SUA: 425–463 μmol/L). During a median follow-up of 6.8 years, we documented 817 (0.96%) incident MI and 6498 (7.60%) mortality. Compared with the low-stable group, high-stable group experienced a higher risk of MI (hazard ratio [HR], 1.35; 95% confidence [CI], 1.07–1.71) and all-cause mortality (HR, 1.22; 95% CI, 1.12–1.33). Multiple sensitivity analyses yielded similar results. Additionally, the association of SUA trajectory with MI and all-cause mortality was more pronounced in individuals without a history of hypertension (P-interaction=0.0359) and those aged &lt;60 years (P-interaction&lt;0.0001), respectively. Conclusions: Higher SUA trajectories were associated with altered risk of MI and all-cause mortality, suggesting that monitoring SUA trajectory may assist in identifying subpopulations at higher risk of MI and all-cause mortality.

Urine ketone bodies have been considered as predictors of stroke in diabetic patients, however, the role of urine ketone bodies in the prognosis of stroke has not been investigated well. This study aimed to investigate the association between urine ketone bodies and adverse outcomes in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA).

Background: Evidence on longitudinal variability of serum uric acid (SUA) and risk of all-cause mortality in the general population is limited, as many prior studies focused on a single measurement of SUA. Methods: A total of 53,956 participants in the Kailuan study who underwent three health examinations during 2006 to 2010 were enrolled. Variability of SUA was measured using the coefficient of variation (primary index), standard deviation, average real variability, and variability independent of the mean. Cox proportional hazard regressions were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) for the association of variability of SUA with subsequent risk of all-cause mortality, considering its magnitude and the direction and across different baseline SUA categories. Results: Over a median follow-up of 7.04 years, 2728 participants died. The highest variability of SUA was associated with an increased risk of all-cause mortality, the HR was 1.33 (95% CI, 1.20–1.49) compared with the lowest variability. In this group, both a large fall (HR, 1.28; 95% CI, 1.14–1.44) and rise (HR, 1.18; 95% 1.05–1.32) in SUA were related to risk of all-cause mortality. These associations were similar across different baseline SUA categories. Consistent results were observed in alternative measures of SUA variability. Moreover, individuals with higher variability in SUA were more related to common risk factors than those with stable SUA. Conclusions: Higher variability in SUA was independently associated with the risk of all-cause mortality irrespective of baseline SUA and direction of variability in the general population.

High remnant cholesterol is associated with cardiovascular disease (CVD), but whether CVD risk attributable to remnant cholesterol vary between young and later adults remains unknown. The study aimed to assess age differences in the association between remnant cholesterol and CVD.