Life's Essential 8 Trajectories and Risk of Stroke: A Prospective Cohort Study.

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.

BMI-based metabolic syndrome severity score and arterial stiffness in a cohort Chinese study.

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.

Uric acid and risk of incident heart failure in individuals with cardiovascular disease.

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 1215 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.

Association of Life's Essential 8 with all-cause mortality and risk of cancer: a prospective cohort study.

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.

The effect of exogenous dihydroxyacetone and methylglyoxal on growth, anthocyanin accumulation, and the glyoxalase system in Arabidopsis.

Dihydroxyacetone (DHA) occurs in wide-ranging organisms, including plants, and can undergo spontaneous conversion to methylglyoxal (MG). While the toxicity of MG to plants is well-known, the toxicity of DHA to plants remains to be elucidated. We investigated the effects of DHA and MG on Arabidopsis. Exogenous DHA at up to 10 mm did not affect the radicle emergence, the expansion of green cotyledons, the seedling growth, or the activity of glyoxalase II, while DHA at 10 mm inhibited the root elongation and increased the activity of glyoxalase I. Exogenous MG at 1.0 mm inhibited these physiological responses and increased both activities. Dihydroxyacetone at 10 mm increased the MG content in the roots. These results indicate that DHA is not so toxic as MG in Arabidopsis seeds and seedlings and suggest that the toxic effect of DHA at high concentrations is attributed to MG accumulation by the conversion to MG.

Elevated levels of body mass index and waist circumference, but not high variability, are associated with an increased risk of atrial fibrillation.

BACKGROUND: Although obesity has been associated with risk of atrial fibrillation (AF), the associations of variability of obesity measures with AF risk are uncertain, and longitudinal studies among Chinese population are still lacking. We aimed to evaluate the impacts of obesity and variability of body mass index (BMI) and waist circumference (WC) on the risk of atrial fibrillation (AF) in a large Chinese cohort study. METHODS: A total of 44,135 participants of the Kailuan Study who were free of cancer and cardiovascular disease and underwent three consecutive surveys from 2006 to 2010 were followed for incident AF until 2020. Average BMI and WC over time and variability were calculated. Cox proportional hazards regression models were used to assess hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of obesity and variability in BMI and WC with AF risk. RESULTS: During a mean follow-up of 9.68 years, there were 410 cases of incident AF. In multivariable-adjusted models, compared with normal BMI/WC, individuals with general obesity and abdominal obesity had increased risk of AF, with corresponding HRs of 1.73 (95% CI: 1.31-2.30) and 1.38 (95% CI: 1.11-1.60), respectively. The short-term elevation in AF risk persisted for the obese even after adjustment for updated biologic intermediaries and weight. Variability in BMI and WC were not associated with the risk of AF. The restricted cubic spline models indicated significant linear relationships between levels of WC and BMI and risk of AF. CONCLUSIONS: Elevated levels of BMI and WC were associated with an increased risk of AF, whereas variability in BMI and WC were not. Therefore, achieving optimal levels of BMI and WC could be valuable in AF prevention.

Bcl-2-associated athanogene 5 overexpression attenuates catecholamine-induced vascular endothelial cell apoptosis.

Bcl-2 associated athanogene 5 (Bag5) is a novel endoplasmic reticulum (ER) regulator. However, its role in catecholamine-induced endothelial cells damage has not been fully understood. In our study, catecholamine was used to mimic hypertension-related endothelial cell damage. Then, western blots, enzyme-linked immunosorbent assay, immunofluorescence, quantitative polymerase chain reaction and pathway analysis were conducted to analyze the role of Bag5 in endothelial cell damage in response to catecholamine. Our results indicated that the endothelial cell viability was impaired by catecholamine. Interestingly, Bag5 overexpression significantly reversed endothelial cell viability. Mechanistically, Bag5 overexpression inhibited ER stress, attenuated oxidative stress and repressed inflammation in catecholamine-treated endothelial cells. These beneficial effects finally contributed to endothelial cell survival under catecholamine treatment. Pathway analysis demonstrated that Bag5 was under the control of the mitogen-activated protein kinase (MAPK)-extracellular-signal-regulated kinase (ERK) signaling pathway. Reactivation of the MAPK-ERK pathway could upregulate Bag5 expression and thus promote endothelial cell survival through inhibiting oxidative stress, ER stress, and inflammation. Altogether, our results illustrate that Bag5 overexpression sustains endothelial cell survival in response to catecholamine treatment. This finding identifies Bag5 downregulation and the inactivated MAPK-ERK pathway as potential mechanisms underlying catecholamine-induced endothelial cell damage.

Premature coronary heart disease complicated with hypertension in hospitalized patients: Incidence, risk factors, cardiovascular-related comorbidities and prognosis, 2008-2018.

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.

Combined effect of time in target range and variability of systolic blood pressure on cardiovascular outcomes and mortality in patients with hypertension: A prospective cohort study.

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.

Proteomic biomarkers for noninvasive left atrial appendage thrombus prediction in patients with atrial fibrillation.

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.

Association of Estimated Glomerular Filtration Rate Trajectories with Atrial Fibrillation Risk in Populations with Normal or Mildly Impaired Renal Function.

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.

The relation between estimated glomerular filtration rate (eGFR) within the normal or mildly impaired range and risk of atrial fibrillation (AF) in former studies is controversial, and data on longitudinal pattern of eGFR in such topic is sparse. In this cohort study, we identified 4 trajectories of eGFR in populations with normal or mildly impaired renal function. Relative to populations with high-stable pattern of eGFR, those with low-stable pattern, high-decreasing pattern and moderate-increasing pattern were associated with 128%, 92%, and 70% higher risk of AF, respectively. These findings suggested that monitoring eGFR trajectories is an important approach for AF prediction in populations with normal or mildly impaired renal function. Decreasing and consistently low eGFR trajectories within the currently designated normal or mildly impaired range may still significantly increase the risk of AF.

In-hospital systolic blood pressure lowering patterns and risk of rehospitalization for angina in patients with hypertension and coronary artery disease.

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.

Study on the pharmacological mechanisms of sodium-glucose co-transporter 2 inhibitors in obesity-related atrial fibrillation based on network pharmacology and experimental verification.

Background: Obesity is an independently risk factor of atrial fibrillation (AF). It is likely that the global burden of AF will escalate due to the current obesity epidemic. Weight loss can effectively reduce the risk of AF, while sodium-glucose co-transporter 2 inhibitors (SGLT2i) can reduce body weight, so SGLT2i are potentially effective for obesity-related AF. SGLT2i are a novel type of oral medication. This current study used network pharmacology to examine the potential mechanisms of SGLT2i in the treatment of obesity-related AF, and the therapeutic effects were assessed in vivo. Methods: Potential gene targets for SGLT2i in treating obesity-related AF were identified from public database. Cytoscape V3.7.1 was used to construct the "Drug-Target" and "Drug-Target-Disease" networks. The STRING database was applied to investigate the protein-protein interactions (PPIs). Additionally, the Bioconductor tools were used to analyze the Gene Ontology (GO) biological functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. The efficacy of SGLT2i in treating obesity-related AF was investigated in vivo using a diet-induced obese C57BL/6J male mouse model. A number of indicators were assessed, including invasive electrophysiology, testing of blood samples, and expression detection of pathway targets. These experiments were used to verify the targets mined by network pharmacology. Results: The results indicated that SGLT2i had 80 potential target genes during the treatment of obesity-related AF, and 10 hub genes were obtained by further screening. It was predicted that the treatment of obesity-related AF by SGLT2i involved the advanced glycation end product (AGE)-receptor for advanced glycation end product (RAGE) signaling pathway and other signaling pathways. In in vivo experiments, administration of SGLT2i (the SGLT2i + DIO group) resulted in a lower AF induction rate (P<0.05), decreased serum AGEs/soluble RAGE (sRAGE) ratio (P<0.01), and decreased expression of NADPH oxidase 2 (NOX2) (P<0.05) compared to untreated DIO mice (the DIO group). Conclusions: In this study, pharmacological network analysis and in vivo experiments demonstrated that SGLT2i acts on obesity-related AF by inhibiting the AGE-RAGE signaling pathway. These results offer fresh perspectives on the pharmacological actions of SGLT2i in treating obesity-related AF.

Effects of exogenous plant regulators on growth and development of "Kyoho" grape under salt alkali stress.

Salinity is one of the major abiotic stresses besides drought and cold stress. The application of plant growth regulators (PGRs) is an effective method to mitigate yield losses caused by salinity. However, we investigated the effects of exogenous regulatory substances (γ-aminobutyric acid (GABA), salicylic acid (SA), and brassinolide (BR) on the growth and development of "Kyoho" grapevine under salt stress. The results showed that exogenous regulators GABA, SA, and BR alleviated the inhibition of grape growth by saline stress and regulated the effects of salinity stress on grape fruit development and quality. All three regulators significantly increased fruit set, cross-sectional diameter, weight per unit, and anthocyanin content. In conclusion, this study provides a theoretical basis for grape production practices by using exogenous aminobutyric acid (GABA), salicylic acid (SA), and brassinolide (BR) to mitigate the hazards of salinity stress.

Association Between New-Onset Type 2 Diabetes and Cardiac Conduction Diseases: A Prospective Cohort Study.

BACKGROUND: Cardiac conduction diseases can lead to life-threatening outcomes. However, the evidence on risk factors for conduction disease that is needed to underpin prevention strategies is limited. The present study aimed to determine the association between type 2 diabetes and cardiac conduction diseases. METHODS AND RESULTS: This study included 101 080 participants free of prevalent diabetes and cardiac conduction diseases at baseline from the Kailuan Study. All participants were monitored biennially until December 31, 2020. During follow-up, 14 397 participants were diagnosed as having type 2 diabetes. For each case subject, 1 control subject was randomly selected, matched for age (±1 year) and sex. The final analysis comprised 10 744 case-control pairs. Cox regression models with age as the underlying time scale were used. During a median follow-up of 5.46 years, 571 incident events occurred, including 164 atrioventricular blocks, 414 bundle-branch blocks (BBBs), 274 right BBBs, and 210 left BBBs. After adjustment for potential confounders, participants with type 2 diabetes diagnosed had greater relative risks for most outcomes relative to controls, with hazard ratios of 1.42 (95% CI, 1.18-1.67) for conduction diseases, 1.40 (95% CI, 1.00-1.96) for atrioventricular blocks, 1.43 (95% CI, 1.16-1.75) for BBBs, and 1.69 (95% CI, 1.15-2.49) for left BBBs. In contrast, no association between diabetes and right BBB was observed. CONCLUSIONS: In this study, participants with type 2 diabetes are at an increased risk of cardiac conduction disease but not associated with the development of right BBB.

Prevalence and clinical characteristics of atrial fibrillation in hospitalized patients with coronary artery disease and hypertension: a cross-sectional study from 2008 to 2018.

BACKGROUND: The clinical characteristics of patients with the comorbidities of hypertension and coronary artery disease (HT-CAD) and atrial fibrillation (AF) are largely unknown. This study aimed to investigate the prevalence of AF in patients with HT-CAD and clinical characteristics of patients with both HT-CAD and AF. METHODS: This cross-sectional study was conducted in Chinese People's Liberation Army General Hospital in Beijing, China, and included 20,747 inpatients with HT-CAD with or without AF from August 2008 to July 2018. We examined the overall prevalence, clinical characteristics, comorbidity profiles, treatment patterns, and blood pressure (BP) control of patients with both HT-CAD and AF. Multivariate logistic regression was used to investigate the associations of cardiovascular risk factors with AF in patients with HT-CAD. RESULTS: The overall prevalence of AF in patients with HT-CAD was 4.87% (1011/20,747), and this increased with age; to be specific, the prevalence in women and men increased from 0.78% (2/255) and 1.02% (26/2561) at the age of <50 years to 8.73% (193/2210) and 10.28% (298/2900) at the age of ≥70 years, respectively. HT-CAD patients who had AF had a higher prevalence of cardiovascular-related comorbidities than those without AF. Multivariate logistic regression showed that age, gender (male), body mass index, heart failure, and chronic kidney disease were independently associated with the risk of AF in patients with HT-CAD. For those with both HT-CAD and AF, 73.49% (743/1011) had a CHA 2 DS 2 -VASc score of ≥4, and only about half of them had the BP controlled at <140/90 mmHg, which indicated a high risk of thromboembolism and stroke. The use of oral anticoagulation increased during the study period (10.00% [20/200] in 2008 to 2011 vs. 30.06% [159/529] in 2015 to 2018, P  < 0.01), but remained at a relatively low level. CONCLUSIONS: AF is highly prevalent among patients with HT-CAD. Patients with both HT-CAD and AF have a higher prevalence of cardiovascular-related comorbidities, lower BP control rate, and lower use of oral anticoagulation.

Association of Resting Heart Rate Trajectories With Cardiovascular Disease and Mortality in Patients With Diabetes Mellitus.

CONTEXT: Longitudinal patterns of resting heart rate (RHR) in patients with diabetes mellitus and their association with health outcomes are not well-characterized. OBJECTIVE: We sought to explore the RHR trajectories in patients with diabetes mellitus and their association with cardiovascular disease (CVD) and all-cause mortality. DESIGN: The Kailuan Study is a prospective cohort study. Participants underwent health examinations biennially starting in 2006 and were followed until December 31, 2020. SETTING: General community. PARTICIPANTS: A total of 8218 diabetic participants who attended at least 3 of the examinations conducted in 2006, 2008, 2010, and 2012 were included. MAIN OUTCOME MEASURES: CVD and all-cause mortality. RESULTS: We identified 4 RHR trajectories in participants with diabetes mellitus between 2006 and 2012: low-stable (range, 66.83-64.91 beats/min; n = 1705), moderate-stable (range, 76.30-76.95 beats/min; n = 5437), high-decreasing (mean decreased from 92.14 to 85.60 beats/min; n = 862), and high-increasing (mean increased from 84.03 to 111.62 beats/min; n = 214). During an average follow-up of 7.25 years, 977 cases of CVD and 1162 deaths were identified. Compared with the low-stable trajectory, adjusted hazard ratios (HRs) for CVD were 1.48 (95% CI, 1.02-2.14; P = .04) for the high-increasing trajectory, adjusted HRs for all-cause mortality were 1.34 (95% CI, 1.14-1.58; P < .01) for the moderate-stable trajectory, 1.68 (95% CI, 1.35-2.10; P < .01) for the high-decreasing trajectory, and 2.47 (95% CI, 1.85-3.31; P < .01) for the high-increasing trajectory. CONCLUSIONS: RHR trajectories were associated with the subsequent risks of CVD and all-cause mortality in patients with diabetes mellitus.

Transitions in Metabolic Health and Onset Age of Cardiovascular Diseases.

INTRODUCTION: The cardiometabolic risk associated with metabolically healthy obesity remains the subject of debate. It is unclear whether changes in metabolically healthy obesity status affect premature cardiovascular disease (CVD) risk. Authors aimed to investigate the association of metabolically healthy obesity and its transition over time with incident CVD by age at onset. METHODS: In a community-based, prospective cohort study, 54,441 adults without CVD in or before 2010 were followed for incident CVD until 2020. This sample was analyzed in 2022. Four age groups were examined (<55, 55-65, 65-75, and ≥75 years) for CVD onset. In each age group, participants were cross-classified by BMI categories and metabolic health. The Cox proportional hazards model with age as the underlying time scale was used to examine the associations of metabolic health status and its transition with CVD across BMI categories. RESULTS: During a median follow-up of 9.59 years, 3,038 participants developed CVD. Individuals with metabolically unhealthy obesity at baseline had the highest hazard ratio for CVD onset at any age, ranging from 2.68 (95% CI=2.02, 3.55) for CVD onset in those aged <55 years to 1.55 (95% CI=1.09, 2.10) for CVD onset in those aged ≥75 years. Individuals who had metabolically healthy obesity at baseline or even remained metabolically healthy during 2006-2010 were still at increased risk of premature CVD, and the association attenuated with increasing age of CVD onset. CONCLUSIONS: The metabolically healthy obesity phenotype is dynamic and its transition to a metabolically unhealthy phenotype or even stable metabolically healthy obesity is associated with an increased risk of CVD. The associations were more evident for CVD onset at younger ages.

Combined effect of inter-arm systolic blood pressure difference and carotid artery plaque on cardiovascular diseases and mortality: A prospective cohort study.

Objectives: Previous studies have confirmed the relations between inter-arm systolic blood pressure difference (IASBPD) and carotid artery plaque with the risk of cardiovascular diseases (CVD). But it is unclear whether the combined effect of IASBPD and carotid artery plaque further increases the risk of CVD and all-cause mortality. Materials and methods: We enrolled 4,970 participants (≥40 years old) in the prospective Kailuan study. All participants underwent dual-arm blood pressure and carotid artery ultrasounds. IASBPD was the absolute value of the difference between dual-arm blood pressure. All the participants were divided into four groups according to their IASBPD levels and the presence or absence of carotid artery plaque and Cox proportional hazards models were used to calculate the hazard ratios (HRs) and 95% confidence interval (CI) for incident CVD and all-cause mortality. Results: During a median follow-up of 7 years, 179 CVD events and 266 deaths occurred. Multivariable Cox Regression showed that participants with IASBPD ≥ 10 mmHg and plaque had a significantly higher incidence of CVD, cerebral infarction (CI), and myocardial infarction (10, 7.27, and 1.36%, respectively). After adjusting for covariates, the IASBPD ≥ 10 mmHg and carotid plaque group significantly increased risks for CVD (HR 2.38; 95% CI, 1.40∼4.05), CI (HR, 2.47; 95% CI, 1.31∼4.67), and all-cause mortality (HR, 2.08; 95% CI, 1.20∼3.59). Conclusion: Our study indicated that the combination of IASBPD and carotid artery plaque was associated with incident CVD and all-cause mortality.

Visit-to-visit SBP variability and risk of atrial fibrillation in middle-aged and older populations.

OBJECTIVE: We sought to examine the relationship between visit-to-visit variability of SBP and incident atrial fibrillation in middle-aged and older population. METHODS: This prospective cohort study included 26 999 participants aged 50 years or older at study entry. Visit-to-visit variability of SBP was defined as the average real variability (ARV) of three values of SBP from the examinations of 2006, 2008, and 2010. We categorized participants into four groups according to the quartiles of ARV. Incident atrial fibrillation cases were identified via ECG during biennial resurveys, and reviewing medical insurance record and discharge registers. We used Cox regression models to evaluate the hazard ratios and 95% confidence intervals (CI) for incident atrial fibrillation. RESULTS: After an average follow-up of 9.24 years, a total of 420 atrial fibrillation cases were identified. The incidence of atrial fibrillation from the lowest to the highest quartiles of SBP variability were 1.23, 1.53, 1.81 and 2.19 per 1000 person-years, respectively. After adjusting for potential confounders, including mean blood pressure, we found a graded association between SBP variability and risk of atrial fibrillation. Participants in the third quartile and the highest quartile were associated with 35 and 53% higher risk of developing atrial fibrillation, respectively, compared with participants in the lowest quartile [hazard ratio (95% CI), 1.35 (1.01-1.82) and 1.53 (1.15-2.04)]. The results persisted across sensitivity analyses. CONCLUSION: Increased visit-to-visit variability of SBP is a strong predictor of incident atrial fibrillation in middle-aged and older population. Evaluation of long-term SBP variability could help to identify individuals at higher risk of atrial fibrillation.