Roles of general and central adiposity in cardiometabolic multimorbidity: revisiting the obesity paradox using a multistate model.

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.

Longitudinal cardiovascular health measured by life's essential 8 metrics with incident diabetes: A 13-year prospective cohort study.

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.

Temporal relationship between arterial stiffness and blood pressure variability and joint effect on cardiovascular disease.

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 (ß1 = 0.040; P = 0.0012) was significantly had greater than the path from baseline SBPV to follow-up baPWV (ß2 = 0.009; P = 0.3830), with P = 0.0232 for the difference between ß1 and ß2. 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.

Magnitude and time course of insulin resistance accumulation with the risk of cardiovascular disease: an 11-years cohort study.

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.

Association of cumulative blood glucose load with cardiovascular risk and all-cause mortality.

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.

Cardiovascular health and life expectancy with and without cardiovascular disease in the middle-aged and elderly Chinese population.

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.

Association of Vascular Aging With Cardiovascular Disease in Middle-Aged Chinese People: A Prospective Cohort Study.

Background: Whether middle-aged individuals with a greater difference between chronological age and vascular age show a lower cardiovascular disease risk remains to be clarified. Objectives: This study sought to examine whether individuals with supernormal vascular aging (VA) have a lower cardiovascular disease risk than do individuals with normal VA. Methods: This prospective cohort study included 20,917 middle-aged (40-60 years) participants from the Kailuan Study. VA was defined as the predicted age in a multivariate regression model, including classic cardiovascular risk factors and pulsed wave velocity. The chronological age minus the VA was defined as the Δ-age, and the 10th and 90th percentiles of the Δ-age were used as cutoffs to define early VA and supernormal VA, respectively. The outcome was a composite of myocardial infarction, hospital admission for heart failure, and stroke. The study used Cox proportional hazards regression to examine the association between the VA categories and the incident cardiovascular outcome. Results: During the median 4.6-year follow-up period, 584 endpoint events were observed. After adjusting for potential variables, when compared with the normal VA group, the supernormal VA group had a decreased rate of cardiovascular events (HR: 0.47; 95% CI: 0.35-0.64), and the early VA group had an increased rate (HR: 1.90; 95% CI: 1.22-2.95) of cardiovascular events. Conclusions: Individuals with supernormal VA are at a lower risk of cardiovascular events, and individuals with early VA are at a higher risk of cardiovascular events than individuals with normal VA. Further characterization may provide novel insight into future preventive strategies against cardiovascular disease.

Baseline and longitudinal cardiovascular health using Life's Essential 8 metrics with the risk of incident hypertension.

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 (Ptrend < 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 (Pinteraction < 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.

Association of body mass index with risk of cardiometabolic disease, multimorbidity and mortality: a multi-state analysis based on the Kailuan cohort.

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/m2), healthy weight (18.5-23.9 kg/m2), overweight (24.0-27.9 kg/m2), mildly obese (28.0-31.9 kg/m2), and severely obese ( ≥ 32.0 kg/m2). 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.

Early versus delayed antihypertensive treatment in patients with acute ischaemic stroke: multicentre, open label, randomised, controlled trial.

OBJECTIVES: To compared the effect of early antihypertensive treatment started within 24-48 h of stroke onset versus delaying treatment until day eight on reducing dependency or death. DESIGN: Multicentre, randomised, open label trial. SETTING: 106 hospitals in China between 13 June 2018 and 10 July 2022. PARTICIPANTS: 4810 patients (≥40 years) were enrolled with acute ischaemic stroke within 24-48 h of symptom onset and elevated systolic blood pressure between 140 mm Hg and <220 mm Hg. INTERVENTIONS: Patients were randomly assigned to receive antihypertensive treatment immediately after randomisation (aimed at reducing systolic blood pressure by 10%-20% within the first 24 h and a mean blood pressure <140/90 mm Hg within seven days) or to discontinue antihypertensive medications for seven days if they were taking them, and then receive treatment on day 8 (aimed at achieving mean blood pressure <140/90 mm Hg). MAIN OUTCOME MEASURES: The primary outcome was the combination of functional dependency or death (modified Rankin scale score ≥3) at 90 days. Intention to treat analyses were conducted. RESULTS: 2413 patients were assigned to the early treatment group and 2397 were assigned to the delayed treatment group. Mean systolic blood pressure was reduced by 9.7% (from 162.9 mm Hg to 146.4 mm Hg) in the early treatment group and by 4.9% (from 162.8 mm Hg to 154.3 mm Hg) in the delayed treatment group within 24 h after randomisation (P for group difference <0.001). Mean systolic blood pressure was 139.1 mm Hg in the early treatment group and 150.9 mm Hg in the delayed treatment group on day seven (P for group difference <0.001). Additionally, 54.6% of patients in the early treatment group and 22.4% in the delayed treatment group had blood pressure of less than 140/90 mm Hg (P<0.001 for group difference) on day seven. At day 90, 289 trial participants (12.0%) in the early treatment group, compared with 250 (10.5%) in the delayed treatment group, had died or experienced a dependency (odds ratio 1.18 (95% confidence interval 0.98 to 1.41), P=0.08). No significant differences in recurrent stroke or adverse events were reported between the two groups. CONCLUSIONS: Among patients with mild-to-moderate acute ischaemic stroke and systolic blood pressure between 140 mm Hg and <220 mm Hg who did not receive intravenous thrombolytic treatment, early antihypertensive treatment did not reduce the odds of dependency or death at 90 days. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03479554.

The impact of serum acid, arterial stiffness, and hypertension as a mediating factor: A cohort study.

BACKGROUND: Serum uric acid (SUA) has been associated with arterial stiffness. However, previous studies were limited to contradicting cross-sectional studies. This study aimed to examine the longitudinal association between SUA and the progression of arterial stiffness and the potential mechanisms. METHODS: Based on the Kailuan study, arterial stiffness progression was assessed by the annual growth rate of repeatedly measured brachial-ankle pulse wave velocity (baPWV). Generalized linear regression models were used to estimate the association of SUA with baseline arterial stiffness (n = 37,659) and arterial stiffness progression (n = 16,506), and Cox regressions were used to investigate the risk of incident arterial stiffness (n = 13,843). Mediation analysis was used to explore the potential mediators of the associations. RESULTS: Per standard deviation increase in SUA was associated with an 11.89 cm/s increment (95% confidence interval [CI], 8.60-15.17) in baseline baPWV and a 2.67 cm/s/yr increment in the annual growth rate of baPWV. During the 5.77-year follow-up, there were 1953 cases of incident arterial stiffness. Participants in the highest quartile of SUA had a 39% higher risk of arterial stiffness (HR, 1.39; 95% CI, 1.21-1.60), as compared with those in the lowest quartile of SUA. Furthermore, the observed associations were more pronounced in women than in men (Pint<0.05). The pathological pathway from high SUA to arterial stiffness was mainly mediated through hypertension (mediated proportion: 24.74%). CONCLUSIONS: Our study indicates that SUA was positively associated with the risk of arterial stiffness and its progression, especially in women. The association was mainly mediated through hypertension.

Association between cumulative atherogenic index of plasma exposure and risk of myocardial infarction in the general population.

BACKGROUND: Atherogenic index of plasma (AIP) has been confirmed as a novel marker for myocardial infarction (MI), but few evidence on the long-term AIP and MI risk in general populations. We thus aimed to evaluate the relationships of cumulative exposure to AIP and its accumulation time course with the risk of MI. METHODS: A total of 54,440 participants were enrolled in the Kailuan study. Time-weighted cumulative AIP was calculated as the weighted sum of the mean AIP value for each time interval, then normalized by total exposure duration, the exposure duration was from 2006 to 2010. Duration of high AIP exposure was defined as the duration with high AIP and ranged from 0 to 6 years. The time course of AIP accumulation was categorized by the combination of time-weighted cumulative AIP < or ≥ median (- 0.12) and AIP slope. RESULTS: After 11.05 years of follow-up, 766 incident MI cases were documented. After adjustment for potential confounders, higher risk of MI was observed in participants with the highest time-weighted cumulative AIP quartile (HR, 1.89; 95% CI 1.47-2.43), the longest exposure duration of high AIP (HR, 1.52; 95% CI 1.18-1.95), and those with high time-weighted cumulative AIP and negative slope (HR, 1.42; 95% CI 1.13-1.79). CONCLUSIONS: Long-term cumulative exposure to AIP and the time course of AIP accumulation increased the risk of MI. High AIP earlier resulted in a greater risk increase than later in life with the same time-weighted cumulative AIP, emphasizing the importance of controlling atherogenic dyslipidemia early in life.

Visit-to-visit blood pressure variability and the risk of cardiovascular disease: a prospective cohort analysis.

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 (Pint = 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.

Cumulative Serum Uric Acid Exposure and Its Time Course With the Risk of Incident Stroke.

BACKGROUND: Evidence on the longitudinal associations between serum uric acid (SUA) and stroke was limited and yielded inconsistent conclusions. We aimed to investigate the associations of cumulative SUA (cumSUA), incorporating the time course of cumSUA accumulation, with the risk of stroke. METHODS: The prospective cohort study enrolled 50 871 participants from Kailuan, China. CumSUA from 2006 to 2010 was derived by calculating the means of SUA values between consecutive examinations and multiplying by time intervals between visits. Time course of cumSUA accumulation was categorized as the slope of SUA versus time or by splitting the overall accumulation into an early (cumSUA06-08) and late accumulation (cumSUA08-10). Participants were classified by cumSUA quartiles, SUA slope (negative versus positive), and the combined median cumSUA (1105.21 µmol/L×year) with SUA slope, respectively. The associations with incident stroke between 2010 and 2019 were evaluated with competing risk model. RESULTS: During a median follow-up of 9.02 years, 2217 cases of incident stroke were identified. In the multivariable-adjusted model, a higher risk of stroke was observed in participants with the highest quartile versus the lowest quartile of cumSUA (subdistribution hazard ratio, 1.15 [95% CI, 1.01-1.31]), and those with a negative versus positive SUA slope (subdistribution hazard ratio, 1.09 [95% CI, 1.01-1.19]). Consistently, a later accumulation of SUA was not associated with the risk of stroke after adjustment for an early accumulation, indicating early accumulation may contribute more to the risk of stroke than later accumulation. When cumSUA was incorporated with its time course, those with changes in cumSUA suggesting early accumulation had elevated risk of stroke (subdistribution hazard ratio, 1.17 [95% CI, 1.03-1.33]). Similar results were observed for ischemic stroke. CONCLUSIONS: Incident stroke risk was associated with cumulative exposure to SUA and its accumulation time course. Early SUA accumulation resulted in a greater risk compared with later accumulation, underscoring the importance of early control of SUA to an optimal level.

Discordance between remnant cholesterol and low-density lipoprotein cholesterol predicts arterial stiffness progression.

BACKGROUND: 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. METHODS: Data were derived from the Kailuan study. RC was calculated as total cholesterol - high-density lipoprotein cholesterol - LDL-C. Discordant RC with LDL-C were defined by residuals, cutoff points, and median values. Arterial stiffness progression was assessed by the brachial-ankle pulse wave velocity (baPWV) change, baPWV change rate, and increase/persistently high baPWV. Multivariable linear regression models and logistic regression models were used to explore the association of RC and discordant RC versus LDL-C with the arterial stiffness progression. RESULTS: A total of 10,507 participants were enrolled in this study, with the mean age of 50.8 ± 11.8 years, 60.9% (6,396) of male. Multivariable regression analyses showed that, each 1 mmol/L increase in the RC level was associated with a 12.80 cm/s increase in baPWV change, a 3.08 cm/s/year increase in the baPWV change rate, and 13% (95% CI, 1.05-1.21) of increase in the risk for increase in/persistently high baPWV. Discordant high RC was associated with a 13.65 cm/s increase in baPWV change and 19% (95% CI, 1.06-1.33) of increase in the risk for increase in/persistently high baPWV compared to those with concordant group. CONCLUSION: Discordantly high RC with LDL-C was associated with an increased risk of arterial stiffness progression. The findings demonstrated that RC may be an important marker of future coronary artery disease risk.

Association of Normal Serum Uric Acid Level and Cardiovascular Disease in People Without Risk Factors for Cardiac Diseases in China.

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 (Ptrend=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.

Association of Cardiovascular Health Assessed by the New Life's Essential 8 Metrics With Years Lived Without Cardiovascular Disease.

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.

Association of Multitrajectories of Lipid Indices With Premature Cardiovascular Disease: A Cohort Study.

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.

Temporal relationship between hyperuricemia and hypertension and its impact on future risk of cardiovascular disease.

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 (ß1) from baseline SUA to follow-up SBP and DBP were significantly greatly than path coefficients (ß2) from baseline SBP and DBP to follow-up SUA (ß1=0.041 versus ß2=0.003; Pdifference<0.0001 for SBP; ß1=0.040 versus ß2=0.000; Pdifference<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 (Pdifference of ß1 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.

Serum uric acid variation and the risk of cardiovascular disease: A prospective cohort study.

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 (Pint=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.