BACKGROUND & AIMS:Metabolic dysfunction-associated steatotic liver disease is a known risk factor for type 2 diabetes. However, whether metabolic dysfunction-associated steatotic liver disease onset age modifies type 2 diabetes risk remains poorly understood. We aimed to determine the association of metabolic dysfunction-associated steatotic liver disease onset age and risk of incident type 2 diabetes in a large prospective cohort. METHODS:A total of 58,814 metabolic dysfunction-associated steatotic liver disease- and type 2 diabetes-free participants at the first health examination (2006-2007) in the Kailuan Study were included. By December 31, 2015, 29,016 new-onset metabolic dysfunction-associated steatotic liver disease cases were identified. Each metabolic dysfunction-associated steatotic liver disease case was randomly matched to a metabolic dysfunction-associated steatotic liver disease-free control by age (±1 year) and sex. After excluding participants who developed type 2 diabetes within the first 2 years of follow-up, 19,378 metabolic dysfunction-associated steatotic liver disease cases and 19,483 controls were included. All participants were followed for incident type 2 diabetes until December 31, 2020. Cox proportional hazards models estimated hazard ratios and 95% confidence intervals. RESULTS:During a median follow-up of 11.8 years, 2301 incident type 2 diabetes cases were documented. Compared with non-metabolic dysfunction-associated steatotic liver disease, patients with metabolic dysfunction-associated steatotic liver disease with onset age <40 years had the highest risk of type 2 diabetes (hazard ratio, 6.18; 95% confidence interval, 4.28-8.93), followed by gradually attenuated elevated risks in older onset age groups: 40 to <50 years (hazard ratio, 3.29; 95% confidence interval, 2.70-4.00), 50 to <60 years (hazard ratio, 3.14; 95% confidence interval, 2.69-3.66), 60 to <70 years (hazard ratio, 2.94; 95% confidence interval, 2.39-3.62), and ≥70 years (hazard ratio, 2.17; 95% confidence interval, 1.56-3.01). CONCLUSIONS:Metabolic dysfunction-associated steatotic liver disease onset at any age is associated with increased risk of type 2 diabetes, with earlier onset conferring progressively greater risk. This highlights the importance of preventing, or at least delaying, metabolic dysfunction-associated steatotic liver disease onset, particularly in young adults.

Background: The American Heart Association developed Life’s Essential 8 (LE8) to improve the predictive ability of cardiovascular health (CVH). Aims: We sought to investigate whether a 10-year CVH trajectory is associated with the prevalence of aortic valve calcification (AVC), an early manifestation of calcific aortic valve disease (CAVD). Methods: The current study included 8047 participants who participated in the surveys at baseline (2006) and during follow-up periods (2008, 2010, 2012, 2014 and 2016). Repeated measurements of LE8 components including body mass index, cigarette smoking, diet quality, physical activity, sleep health, lipids, blood glucose and blood pressure, were used to construct the CVH trajectories. Ten-year CVH trajectory patterns from 2006 to 2016 were constructed using latent mixture models. AVC was diagnosed by echocardiography from 2016 to 2023. Results: During an eight-year follow-up period, 1005 AVC cases were identified. Compared to the moderate-decrease trajectory, the low-stable trajectory was associated with higher odds of AVC (odd ratio (OR): 1.46; 95% confidence interval (CI): 1.17, 1.83). Participants in the groups of moderate-increasing trajectory (OR: 0.78; 95%CI: 0.62, 0.98), moderate-stable trajectory (OR: 0.62; 95%CI: 0.52, 0.74), and high-stable trajectory (OR: 0.30; 95%CI: 0.20, 0.43) had lower odds of AVC compared with those in the moderate-decreasing trajectory group. The association between the CVH trajectory and AVC prevalence was more pronounced in men, younger individuals and those without chronic kidney disease. Conclusions: Maintaining or improving CVH was associated with lower odds of AVC. Our findings suggest optimizing CVH may provide a primordial preventive benefit against subclinical CAVD.

This study aimed to explore the association between dietary fiber intake and the risk of metabolic dysfunction-associated steatotic liver disease (MASLD), as well as liver fat content, while considering genetic predispositions of MASLD, gut microbial abundance, and butyrate levels. This study analyzed data from 190,276 participants in the UK Biobank. Dietary fiber intake was assessed using 24-h dietary recall. MASLD cases were diagnosed through hospital admission records and death registries, and liver fat content was measured via magnetic resonance imaging. The genetic predispositions of MASLD, gut microbial abundance, and butyrate levels were evaluated using single nucleotide polymorphisms. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95 % confidence intervals (CIs). Over a median follow-up of 10.49 years, 1423 MASLD cases were recorded. Elevated dietary fiber intake was associated with a reduced risk of MASLD (HR: 0.72; 95 % CI: 0.58, 0.90) and a lower level of liver fat content (β: -0.97; 95 % CI: -1.21, -0.73) (all P for trend <0.05). Restricted cubic spline analyses further confirmed the linear inverse associations between fiber intake and the risk of MASLD. Notably, the negative associations between dietary fiber intake and both MASLD and liver fat content were consistent across different genetic predispositions of gut microbial abundance and butyrate levels. Moreover, the inverse association between dietary fiber intake and liver fat was strengthened by high genetic susceptibility of MASLD and elevated body mass index (both P for interaction <0.05). Overall, increased dietary fiber consumption was associated with a lower MASLD risk and decreased liver fat content regardless of genetic predispositions of gut microbial abundance and butyrate levels.

Introduction and objectives: The CHA2DS2-VASc score, used to assess the risk of left atrial appendage thrombus (LAAT) formation in patients with atrial fibrillation (AF), has limited predictive value. Moreover, transesophageal echocardiography imaging, the gold standard diagnostic method to identify thrombi, is semi-invasive. Consequently, there is a need for alternative and noninvasive diagnostic methods for LAAT risk assessment. Methods: Deep proteomic analysis was conducted in plasma samples from 8 patients with nonvalvular AF, divided into thrombus and control groups (4 patients in each group) based on the presence or absence of LAAT. Biomarkers associated with LAAT were validated using an enzyme-linked immunosorbent assay in a cohort of 179 patients with available clinical, transthoracic, and transesophageal echocardiography data. Predictive models were developed to assess the improvement in LAAT identification. Results: The LAAT group had higher CHA2DS2-VASc scores, larger LA diameter, and lower LAA flow velocities. Deep proteomic analysis identified 30 differentially expressed proteins, including myosin light chain 4, prenylcysteine oxidase 1 (PCYOX1), and decorin as potential diagnostic biomarkers of LAAT. The model showed that PCYOX1 and decorin provided an area under the curve (AUC) of 0.970 for LAAT prediction compared with 0.672 in a model including the CHA2DS2-VASc score and LAA cauliflower morphology. The incremental value of proteomic biomarkers for LAAT in patients with nonvalvular AF was further confirmed with the net reclassification improvement and integrated discrimination improvement indices. Conclusions: Protein levels of PCYOX1 and decorin improve the predictive performance for LAAT in patients with nonvalvular AF. (c) 2024 Sociedad Espanola de Cardiologi. Published by Elsevier Espana, S.L.U. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Background Patients with hypertension face a significantly elevated risk of renal dysfunction. However, whether this risk can be mitigated by joint risk factor control remains uncertain. Methods Using Cox proportional hazards models, this study investigated the association between the number of controlled baseline risk factors (systolic blood pressure, low‐density lipoprotein cholesterol, fasting blood glucose, and body mass index) and the development and progression of chronic kidney disease. Results We analyzed 77 356 participants with hypertension and 1:1 age‐ and sex‐matched counterparts without hypertension for incident chronic kidney disease over a median follow‐up of 13.40 years. Among participants with hypertension, each additional controlled risk factor was associated with an 18% lower risk of chronic kidney disease (hazard ratio [HR], 0.82 [95% CI, 0.81–0.84]), and controlling all 4 factors (versus ≤1) reduced the risk by 42% (HR, 0.58 [95% CI, 0.52–0.63]). Effective multifactorial management progressively narrowed the risk gap between hypertensive and normotensive individuals. Chronic kidney disease progression was assessed in 9543 participants with hypertension and 6799 participants without hypertension over 11.88 years. Each additional controlled risk factor was associated with an 18% lower progression risk (HR, 0.82 [95% CI, 0.78–0.86]). Controlling 3 factors was sufficient to eliminate the excess progression risk between groups with hypertension and groups without hypertension, while controlling all 4 factors lowered the risk by 31% (HR, 0.69 [95% CI, 0.53–0.89]). Conclusions This study demonstrates a clear dose–response relationship between the number of controlled risk factors and the magnitude of kidney risk reduction. A comprehensive, multifactorial control strategy can progressively reduce and potentially normalize the excess kidney risk in hypertensive individuals. These findings support a more quantitative and stage‐specific approach to hypertension management.

BACKGROUND AND AIM:This study aimed to explore the effect and potential mechanism of mineralocorticoid receptor (MR) in vascular impairment in mice with metabolic disorders(obesity and hypertension). METHODS AND RESULTS:C57BL/6 mice were used in this study. D12492 were used to fed the mice for obesity for more than 4 months and AngII was used to induce hypertension. Blood pressure, body fat, pulse wave velocity (PWV) of the aorta, aldosterone and metabolic parameters in the plasma were all measured. HE staining and immunofluorescence staining assessed the changes of vascular structure and MR expression. Endothelial cell (EC)-specific MR knockout mice were created for further investigation. For vivo experiments, we used Human umbilical vein endothelial cells(HUVECs) in the study. In mice with hypertension and obesity, blood pressure, body fat, PWV and other metabolic parameters were elevated compared to controls. Aldosterone level and MR expression were both found to be higher in mice with metabolic disorders, correlating with impaired vascular relaxation and thickened wall of the aorta. However, EC-specific MR knockdown could reverse these vascular dysfunctions, also decreased the expression of autophagy related proteins (LC3 and mTOR) in the aorta. In HUVECS, aldosterone increased autophagy levels but it was mitigated by the MR antagonist finerenone. Additionally, finerenone treatment altered eNOS phosphorylation levels in HUVECs in this study. CONCLUSION:MR modulation mitigated vascular damage and autophagy impairment associated with metabolic disorders. Thus, autophagy might play a crucial role in MR activation-induced vascular pathology.

AIMS:This study aims to explore the relationship between Life's Essential 8 (LE8) and aortic valve calcification (AVC). METHODS AND RESULTS:The study included 30 561 participants from the Kailuan cohort who completed the Kailuan Health examination and underwent contemporaneous ultrasound assessment. A multifactorial logistic regression analysis was used to assess the relationship between LE8 score and AVC, along with subgroup analyses and an analysis of the impact of each component of LE8 on AVC. Among the 30 561 participants, 3717 (12.16%) cases of AVC were detected, with a detection rate of 12.16%. The detection rate of AVC significantly decreased with increased LE8 score (P < 0.001). The presence of AVC was reduced by 34% in the moderate cardiovascular health (CVH) group [odds ratio (OR) = 0.66, 95% confidence interval (CI) 0.60-0.72] and by 63% in the high CVH group (OR = 0.37, 95% CI 0.27-0.50). For each standard deviation increase in the LE8 score, the presence of AVC decreased by 23% (OR = 0.77, 95% CI 0.74-0.80). Analysis of the individual components of LE8 revealed that diet, exercise, body mass index, blood lipids, blood glucose, and blood pressure were all associated with the reduced presence of AVC. In contrast, no impact of sleep and smoking on AVC presence was observed. CONCLUSION:The study indicates that a higher LE8 score was associated with lower the presence of AVC.

AIMS:Calcific aortic valve disease (CAVD) is the most common valve disease. The impact of long-term glycemic exposure and glycemic control on the risk of CAVD remains poorly understood, particularly in Asian populations. We examined the association of serum levels of glucose and its long-term changes with the risk of CAVD. MATERIALS AND METHODS:This study recruited 10 309 participants without cardiovascular disease and free of CAVD at initial echocardiographic examination from the Kailuan Study. CAVD cases were ascertained through linkage with hospitals' electronic medical record system. Data from three consecutive surveys prior to the recruitment were used to calculate the changes in glucose. Data were analysed using Cox proportional hazards regression. All participants were monitored biennially until 31 December 2023. RESULTS:A total of 2062 patients developed CAVD during a median follow-up of 4.62 years. In multivariable Cox proportional hazards regression models, the hazard ratios for CAVD were as follows: 1.42 (95% CI, 1.29-1.57) for type 2 diabetes, 1.20 (95% CI, 1.01-1.44) for time weighted average (TWA) FBG level, 1.37 (95% CI, 1.14-1.65) for cumulative fasting blood glucose (FBG) level and 0.72 (95% CI, 0.60-0.86) for FBG time in target range (TTR). CONCLUSION:Type 2 diabetes, long-term elevated FBG and FBG change are associated with CAVD risk. Efforts to attain healthy glucose status may be an effective strategy to prevent CAVD.

BACKGROUND:Atrial fibrillation (AF) is characterized by progressive atrial fibrosis, leading to increased morbidity and mortality. While the novel adipokine Omentin-1 demonstrates anti-fibrotic potential across organ systems, its role in AF pathogenesis remains unclear. This study investigates Omentin-1's therapeutic effects and the underlying mechanisms in angiotensin II (Ang II)-induced atrial fibrosis and AF. METHODS:Atrial fibrosis was induced in C57BL/6 mice via continuous Ang II infusion for 4 weeks. Omentin-1 overexpression was achieved using adeno-associated virus serotype 2/9 (AAV2/9). AF susceptibility was assessed by programmed electrical stimulation, and atrial fibrosis was quantified using histological staining and western blot analysis. Immunofluorescence co-localization assessed cell-type specific expression of Omentin-1, and proteomic analysis of atrial fibroblasts was conducted to explore molecular pathways involved. In vitro studies using primary fibroblasts were conducted to validate Omentin-1's effects. RESULTS:Omentin-1 levels were significantly decreased in both serum and atrial tissue of Ang II-treated mice. Omentin-1 overexpression reduced AF inducibility, decreased atrial fibrosis, and improved left atrial strain parameters. Immunofluorescence showed that Omentin-1 predominantly localized to atrial fibroblasts. Mechanistically, Omentin-1 regulated collagen metabolism by targeting fibroblasts, with Src kinase acting as a critical mediator of fibroblast activation through the PI3K/Akt signaling pathway. CONCLUSION:Omentin-1 attenuates atrial fibrosis and AF susceptibility through regulation of the Src/PI3K/Akt signaling pathway in atrial fibroblasts. These findings suggest that Omentin-1 may represent a potential therapeutic target for the prevention and treatment of AF.

Aims The impact of Life's Essential 8 (LE8) on heart failure (HF) remains poorly understood. We examined the associations between three forms of LE8 measurements and HF.Methods and results A total of 35 896 participants without a prior history of HF from the Kailuan community were included. The LE8 status was measured in 2014. A latent mixture model was employed to identify the trajectories of LE8 during 2006 to 2014. The LE8 annual change rate was defined as the slope of the linear regression equation fitted by five LE8 measurements. Cox proportional hazards models were used to assess the risk of HF associated with LE8, after adjusting for potential confounding variables. The predictive performance was quantified and compared using the C-index. Five distinct LE8 trajectories were identified. 461 HF events documented during follow-up. The LE8 trajectories presenting an upward trend in LE8 were associated with a reduced risk of HF, even when the initial LE8 level was low [HR (95% confidence interval) for moderate-increasing vs. moderate-decreasing trajectory was 0.43 (0.34, 0.55)]. The LE8 status was inversely associated with HF risk. A higher LE8 annual increase was associated with a lower risk of HF. The LE8 trajectory was more accurate in predicting the risk of HF compared with LE8 status.Conclusion LE8 was inversely associated with HF risk. Individuals with initially low LE8 levels experienced a reversal in HF risk upon improvement. Both LE8 trajectories and status are practicable in identifying individuals at high risk of HF, LE8 trajectories may provide added prognostic information. The Life's Essential 8 (LE8) can serve as a convenient and precise tool, offering a scientific foundation for the public to meet their health needs and for health managers to promptly enforce health policies. This study focuses on the effect of LE8 on the prevention and prediction of heart failure (HF) within the general population, utilizing repeated measurements of LE8. Individuals with higher LE8 scores had a reduced risk of HF, while those with initially lower LE8 levels experienced a decline in HF risk with LE8 improvement. Both the trajectories and status of LE8 prove effective in identifying individuals at high risk of HF, with LE8 trajectories offering additional predictive information. Compared with people aged over 55 years, a stronger association between LE8 trajectory and HF risk was observed among those aged <= 55 years. This highlights the importance of initiating LE8 improvement efforts as early as possible. Our study first observed changes in LE8 and identified five distinct LE8 trajectories. Despite the initial low level of LE8, improvement in LE8 attenuates or even reverses the risk of HF, especially among individuals who younger than 55 years.Life's Essential 8 is a powerful predictor, with LE8 trajectory maintaining better performance than LE8 status for predicting HF.

Introducción y objetivos: La escala CHA2DS2-VASc, utilizada para evaluar el riesgo de formación de trombos en la orejuela izquierda (TOI) de pacientes con fibrilación auricular (FA), muestra poco valor predictivo. Además, el ecocardiograma transesofágico, utilizado para identificar los TOI, es semiinvasivo. Esto hace que el desarrollo de métodos alternativos para identificar TOI tenga un alto potencial clínico.Métodos: Se realizó un análisis proteómico avanzado en muestras de plasma de 8 pacientes con FA no valvular, divididos en grupos con TOI y controles sin trombos (4 pacientes por grupo). Los biomarcadores asociados con TOI se validaron mediante inmunoenzimoanálisis en una cohorte de 179 pacientes con datos clínicos y de ecocardiografías transtorácica y transesofágica disponibles. Se desarrollaron modelos predictivos para evaluar la mejora en la predicción de TOI.Resultados: El grupo de TOI mostró valores más altos de CHA2DS2-VASc y de diámetro de la aurícula izquierda y menores velocidades de flujo en la orejuela izquierda. El análisis proteómico identificó 30 proteínas de expresión diferenciada, entre ellas la miosina de cadena ligera (MYL4), la prenilcisteína oxidasa 1 (PCYOX1) y la decorina como potenciales biomarcadores de TOI. El desarrollo de modelos predictivos mostró que la PCYOX1 y la decorina proporcionaron un área bajo la curva (AUC) de 0,970 para la predicción de TOI comparado con 0,672 en el modelo que incluyó CHA2DS2-VASc y morfología en coliflor de la orejuela izquierda. El valor incremental de los biomarcadores proteómicos para la predicción de TOI en pacientes con FA no valvular se confirmó con análisis estadísticos adicionales mediante el índice de mejora de la discriminación y de la reclasificación.Conclusiones: Las concentraciones de las proteínas PCYOX1 y decorina mejoran la capacidad predictiva de TOI en pacientes con FA no valvular.

Time in target range (TTR) and blood pressure variability (BPV) of systolic blood pressure (SBP) are independent risk factors for major adverse cardiovascular events (MACE) and all-cause mortality in hypertensive patients. However, the association of the combination of low TTR and high BPV of SBP with the risk of MACE and all-cause mortality is unclear. This study sought to investigate the combined effect of the TTR and BPV on the risk of MACE and all-cause mortality in patients with hypertension. A total of 11 496 hypertensive patients from the Kailuan cohort study were included in our study. All participants were divided into four groups according to their TTR and BPV levels. Cox proportional hazards regression models were used to calculate the hazard ratios (HRs) and 95% confidence interval (CI) for incident MACE and all-cause mortality. During a median follow-up of 5.64 years, 839 MACEs (included 99 cases of myocardial infarction, 591 cases of stroke, and 191 cases of heart failure) and 621 deaths occurred. Compared with the high-TTR and low-BPV group, the HRs (95% CI) of MACE and all-cause mortality were 1.309 (1.025-1.671) and 1.842 (1.373-2.473) for the high-TTR and high-BPV group, 1.692 (1.347-2.125) and 1.731 (1.298-2.309) for the low-TTR & low-BPV group, 2.132 (1.728-2.629) and 2.247 (1.722-2.932) for the low-TTR & high-BPV group. Our study suggests that the combination of low TTR and high BPV of SBP was associated with a higher risk of MACE and all-cause mortality in patients with hypertension.

This study aimed to examine the association between in-hospital systolic blood pressure (SBP) lowering patterns and rehospitalization for angina in patients with hypertension and coronary artery disease (HT-CAD). This prospective cohort study was conducted in Chinese PLA General Hospital, Beijing, China. We included 730 patients with HT-CAD, who were hospitalized between August 2020 and September 2022. The in-hospital SBP lowering patterns were identified according to SBP level at admission, SBP level at discharge, and the difference between them: normal-stable SBP, more-intensive SBP reduction, less-intensive SBP reduction, and non-reduced SBP. We used Cox proportional hazards regression to estimate the risk of rehospitalization for angina according to SBP lowering patterns. We identified 121 cases of rehospitalization for angina in a median follow-up of 28.2 months. Patients with more-intensive SBP reduction had the lowest incidence rate of rehospitalization for angina, followed by those with normal-stable SBP, less-intensive SBP reduction, and non-reduced SBP. After adjusting for potential confounders, we found that compared with patients with more-intensive SBP reduction, the hazard ratios and 95% confidence intervals of rehospitalization for angina were 1.35 (0.78-2.35) for patients with normal-stable SBP, 2.17 (1.14-4.14) for patients with less-intensive SBP reduction, and 2.99 (1.57-5.68) for patients with non-reduced SBP. This association was more pronounced in patients with multi-vessel stenosis than in patients with single-vessel stenosis. In conclusion, in-hospital SBP lowering patterns were associated with risk of rehospitalization for angina. These results highlighted the importance of intensive in-hospital SBP control in patients with HT-CAD.

Obesity is associated with abnormal repolarization manifested by QT interval prolongation, and oxidative stress is an important link between obesity and arrhythmias. However, the underlying electrophysiological and molecular mechanisms remain unclear. The aim of this study is to evaluate the role of obesity in potassium current in ventricular myocytes and the potential mechanism of NADPH oxidase 2 (Nox2). We investigated the effect of Nox2 on cardiac repolarization without compromising its expression and function in other systems using mice with conditional cardiac-specific deletions of Nox2 (knockout [KO]). Wild-type, KO, and Flox littermate mice were randomized to either the control or high-fat diet (HFD) groups. Surface electrocardiograms were recorded to analyze repolarization in vivo. Whole-cell patch-clamp techniques were used to evaluate the electrophysiological phenotype of isolated myocytes in vitro. Western blotting was performed to assess protein expression levels. Compared with the control mice, the HFD group had a prolonged QTc. The consequences of an HFD were not attributed to delayed rectifier K+ and inward-rectifier K+ currents but were associated with reduced peak outward KV and fast transient outward K+ currents. Downregulated expression of KV4.2 and KChIP2, comprising functional Ito channel pore-forming (α) and accessory (β) subunits, was detected in HFD mice. Nox2-KO reversed the effect of obesity on Ipeak and Ito amplitude. Our data demonstrate that obesity mediates impaired cardiac repolarization in mice, manifested by QTc at the whole organism level and action potential duration at the cellular level, and correlated with Nox2. The electrophysiological and molecular aspects of this phenomenon were mediated by repolarizing outward K+ currents.

BACKGROUND:No study has concentrated on the association of LE8 with cancer risk and death. We aim to examine the association of LE8 with death and cancer. METHODS:A total of 94733 adults aged 51.42 ± 12.46 years and 77551 participants aged 54.09±12.06 years were enrolled in longitudinal and trajectory analysis respectively. Baseline LE8 was divided into three groups based on the American Heart Association criteria and three trajectory patterns by latent mixture models. We reviewed medical records and clinical examinations to confirm incident cancer during the period from 2006 to 2020. Death information was collected from provincial vital statistics offices. Cox models were used. RESULTS:12807 all-cause deaths and 5060 cancers were documented during a 14-year follow-up. Relative to participants with high LE8 at baseline, participants with lower levels of LE8 have a significantly increased risk of mortality and incident cancer. All these risks have an increasing trend with LE8 level decreasing. Meanwhile, the trajectory analysis recorded 7483 all-cause deaths and 3037 incident cancers after approximately 10 years. The associations of LE8 with death and cancer were identical to the longitudinal study. In the subtype cancer analysis, LE8 has a strong effect on colorectal cancer risk. Moreover, the cut point is 56.67 in the association between LE8 and death, while the cut point altered to 64.79 in the association between LE8 and incident cancers. These associations were enhanced among younger adults. CONCLUSIONS:There was a significant association of LE8 with death and cancer risk, especially for the young population.

Introduction:The association between the longitudinal patterns of estimated glomerular filtration rate (eGFR) and risk of atrial fibrillation (AF) in populations with normal or mildly impaired renal function is not well characterized. We sought to explore the eGFR trajectories in populations with normal or mildly impaired renal function and their association with AF. Methods:This prospective cohort study included 62,407 participants who were free of AF, cardiovascular diseases, and moderate to severe renal insufficiency (eGFR <60 mL/min/1.73 m2) before 2010. The eGFR trajectories were developed using latent mixture modeling based on examination data in 2006, 2008, and 2010. Incident AF cases were identified in biennial electrocardiogram assessment and a review of medical insurance data and discharge registers. We used Cox regression models to estimate the hazard ratios and 95% confidence intervals (CIs) for incident AF. Results:According to survey results for the range and changing pattern of eGFR during 2006-2010, four trajectories were identified: high-stable (range, 107.47-110.25 mL/min/1.73 m2; n = 11,719), moderate-increasing (median increase from 83.83 to 100.37 mL/min/1.73 m2; n = 22,634), high-decreasing (median decrease from 101.72 to 89.10 mL/min/1.73 m2; n = 7,943), and low-stable (range, 73.48-76.78 mL/min/1.73 m2; n = 20,111). After an average follow-up of 9.63 years, a total of 485 cases of AF were identified. Compared with the high-stable trajectory, the adjusted hazard ratios of AF were 1.70 (95% CI, 1.09-2.66) for the moderate-increasing trajectory, 1.92 (95% CI, 1.18-3.13) for the high-decreasing trajectory, and 2.28 (95% CI, 1.46-3.56) for the low-stable trajectory. The results remained consistent across a number of sensitivity analyses. Conclusion:The trajectories of eGFR were associated with subsequent AF risk in populations with normal or mildly impaired renal function.

BACKGROUND AND AIMS:To investigate the relationship between metabolic syndrome severity z score(MetS-Z) and arterial stiffness(AS). METHODS AND RESULTS:A total of 7621 participants who took three physical examination and brachial-ankle pulse wave velocity(ba-pwv) test from 2006 were enrolled. Cumulative MetS-Z(cMetS-Z) was calculated by using blood pressure, triglycerides, HDL cholesterol, blood glucose and BMI. AS was assessed by ba-pwv. Cox regression model was used to evaluate the risk of AS. All participants were divided into four groups according to cMetS-Z(Q1-Q4). The average age of the participants was 43.06 ± 8.91 years old. During a median follow-up of 6.27 years, 1831cases of AS were identified. The incident rate of AS increased gradually from group Q1 to Q4. Compared with the lowest cMetS-Z(group Q1), the adjusted hazard ratio (HR) and 95% confidence interval (CI) of group Q2-Q4 for AS were 1.27 (1.09-1.47),1.28(1.10-1.48) and 1.45 (1.24-1.69) respectively. The cubic spline model indicated cMetS-Z had a liner relationship with AS and the cut-off value was lower than zero. Sub-group analysis suggested cMetS-Z was related to AS especially among participants who were younger and without obesity or hypertension or diabetes. CONCLUSION:Higher cMetS-Z was associated with an increased risk of AS in this cohort community study, and this relationship seemed to be stronger among normal healthy subjects. REGISTRATION NUMBER:ChiCTR-TNC-11001489. CLINICAL TRIAL:January 1st 2006, ChiCTR-TNC-11001489 and 2011.

Background: The clinical characteristics and risk factors of all-cause mortality in young hospitalized patients with comorbid coronary heart disease and hypertension (CAD + HT) are not well-characterized. Method: A total of 2288 hospitalized CAD patients (age<45 years) with or without hypertension in the Chinese PLA General Hospital from August 5, 2008 to June 22, 2018 were conducted. The risk factors of all-cause mortality were estimated in young CAD + HT patients by COX models. Results: The overall prevalence of hypertension in young CAD patients was 50.83% (n = 1163). CAD + HT patients had older age, higher heart rate, BMI, uric acid, triglyceride and lower level of eGFR and HDL-C than CAD patients (P < 0.05). The proportion of cardiovascular-related comorbidities (including obesity, diabetes mellitus, hyperuricemia and chronic kidney disease [CKD]) in the CAD + HT group was significantly higher than that in CAD group (P < 0.0001). The risk of all-cause mortality was higher in CAD + HT patients, although after adjusting for all covariates, there was no significant difference between the two groups. Furthermore, CKD (HR, 3.662; 95% CI, 1.545-8.682) and heart failure (HF) (HR, 3.136; 95%CI, 1.276-7.703) were associated with an increased risk of all-cause mortality and RAASi (HR, 0.378; 95%CI, 0.174-0.819) had a beneficial impact in CAD + HT patients. Conclusions: Hypertension was highly prevalent in young CAD patients. Young CAD + HT patients had more cardiovascular metabolic risk factors, more cardiovascular-related comorbidities and higher risk of all-cause mortality. CKD and HF were the risk factors, while RAASi was a protective factor, of all-cause mortality in CAD + HT patients.

Background and aims Uric acid has been positively associated with the risk of developing heart failure in the general population. Nevertheless, it remains unclear whether hyperuricemia is an independent risk factor for heart failure and further contributes to the risk of heart failure among the already at-risk cardiovascular disease (CVD) population. This study aimed to evaluate the association between uric acid and incident heart failure in individuals with established CVD. Methods and results Included were 18,438 adults with established CVD but free of heart failure at baseline, from the Kailuan Study. Incident heart failure cases were ascertained by medical records. Cause-specific Cox proportional hazards regression models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of heart failure according to uric acid tertiles. Over a median follow-up of 6.1 years, we identified 1,215 incident heart failure cases. Higher uric acid was associated with a higher risk of incident heart failure, with adjusted HR for the last vs. first tertile of 1.50 (95%CI:1.30-1.73). Higher uric acid concentrations were associated with an increased risk of heart failure in individuals with coronary heart disease, atrial fibrillation, and ischemic stroke, but not in those with hemorrhagic stroke. Moreover, the observed association between uric acid and heart failure risk was more pronounced in individuals diagnosed with heart failure with reduced ejection fraction subtype compared with heart failure with preserved ejection fraction. Conclusions In individuals with CVD, uric acid was positively associated with the risk of heart failure, in a dose-response manner.

BACKGROUND:Evidence is lacking regarding long-term patterns of change in Life's Essential 8 (LE8) and their association with the risk of stroke. We aim to evaluate LE8 trajectories and examine their association with the risk of stroke in China. METHODS:This study, conducted in a workplace setting, recruited 26 719 participants (average age, 46.02±11.27 years and a male population of 73.73%) who had no history of stroke and consecutively participated in 6 surveys from 2006 to 2016. Repeated LE8 measurements were determined by taking the unweighted average of the 8 component scores ranging from 0 to 100. People with higher scores had better overall cardiovascular health. By examining the medical records of the participants, stroke cases were identified for the period from 2016 to 2020. A latent mixture model was applied to classify the trajectory clusters of LE8 from 2006 to 2016, and Cox proportional hazard models were used to analyze the data. RESULTS:Five LE8 trajectories were detected between 2006 and 2016. Four hundred ninety-eight incident strokes including 55 (11.04%) hemorrhagic and 458 (91.97%) ischemic strokes were documented. After adjusting for covariates, the hazard ratios and 95% CIs for the association between stable-low, moderate-increasing, moderate-stable, and high-stable trajectories and incident stroke, compared with the moderate-decreasing trajectory, were 1.42 (1.11-1.84), 0.73 (0.56-0.96), 0.49 (0.39-0.62), and 0.19 (0.11-0.32), respectively. Individuals with high LE8 status (LE8≥80) exhibited a significantly reduced risk of stroke compared with those with low one (LE8≤49; P-trend <0.001). A faster annual growth in LE8 was related to a lower risk of stroke. CONCLUSIONS:Maintaining high LE8 over an extended period and high baseline LE8 status were related to a decreased risk of stroke. Despite the initial low level of LE8, improvement in LE8 attenuates or even reverses the risk of stroke.