Predictive values of novel high­density lipoprotein­related inflammatory indices in in­stent restenosis among patients undergoing elective percutaneous coronary intervention.

Inflammation and disorders in lipid metabolism play pivotal roles in the development and progression of in-stent restenosis (ISR). The present study aimed to investigate the association between the high-density lipoprotein (HDL)-related inflammatory indices and the risk of developing ISR among patients undergoing elective percutaneous coronary intervention (PCI). A sum of 1,471 patients undergoing elective PCI were retrospectively included and classified by tertiles of HDL-related inflammatory indices. The study endpoint was ISR. The multivariable Cox proportional hazards regression analysis with restricted cubic splines (RCS) was used to assess the associations. During a median follow-up of 62.27 months, 251 (17.06%) patients experienced ISR. The incidence of ISR increased with the increasing white blood cell-to-HDL ratio (WHR) tertiles (log-rank test, overall P=0.0082). After full adjustment, the highest tertile of WHR was significantly associated with a 1.603-fold risk of ISR (hazard ratio, 1.603; 95% confidence interval, 1.152-2.231; P=0.005) in contrast to the lowest tertile of the WHR. Results of RCS further indicated that the association between WHR and ISR was in a non-linear and dose-dependent manner (non-linear P=0.034; P overall=0.019). The lymphocyte-to-HDL ratio (LHR) and neutrophil-to-HDL ratio (NHR) were also significantly and positively associated with the risk of ISR, of which the third tertiles were at increased risk of 41.2 and 44.7% after full adjustment, respectively. Overall, lipid metabolism disorders and inflammation were interconnected in the development of ISR; therefore, HDL-related inflammatory indices, including WHR, LHR and NHR, might be potential predictors in the prognosis of elective PCI.

Association of Cardiovascular Health with Cognitive Function in US Older Adults: A Population-Based Cross-Sectional Study.

INTRODUCTION: Promoting cardiovascular health (CVH) by Life's Simple 7 is associated with better cognitive function. In 2022, the American Heart Association (AHA) prompted Life's Essential 8 (LE8) to strengthen CVH assessment. This study investigated the association between the new CVH metrics assessed by LE8 and cognitive function, thus providing evidence for implementing LE8 in the primordial prevention of cognitive impairment. METHODS: 2,050 participants aged 60 and older from National Health and Nutrition Examination Survey 2011-2014 were included. Cognitive function was measured by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST). The overall and domain-specific cognitive function z-score was created. CVH score was calculated following AHA's advisory. The multivariable linear regression model estimated the associations. RESULTS: The CVH score assessed by LE8 was independently, positively, and linearly associated with the overall cognitive function. A per-10 point increase in CVH was associated with higher overall cognitive z-scores (ß, 0.06; 95% confidence interval [CI], 0.03, 0.09), and participants with moderate (ß, -0.14; 95% CI, -0.22, -0.05) and low CVH (ß, -0.27; 95% CI, -0.37, -0.16) had lower overall cognitive z-scores compared to participants with high CVH. Similar patterns of associations were observed between CVH of AFT and DSST. Components of CVH were further associated with different domain-specific cognitive functions. CONCLUSION: Maintaining an ideal CVH improves cognitive function in older adults. Ideal adherence to individual components of LE8 was associated with improved overall and domain-specific cognitive functions. Therefore, promoting CVH according to LE8 might benefit cognitive function in the elderly.

Reply to Siyu Tan: Associations of cardiovascular health assessed by life's essential 8 with diabetic retinopathy and mortality in type 2 diabetes. The author's reply.

The present study is a reply of authors regarding the commentary from Siyu Tan. In this study, we paid specific attention to (1) highlight the inclusion criterion and diagnosis of Type 2 diabetes mellitus; (2) explain the assessments of cardiovascular health and diabetic retinopathy.

Associations of cardiovascular health assessed by life's essential 8 with diabetic retinopathy and mortality in type 2 diabetes.

BACKGROUND: Vascular complications are the leading causes of reduced life quality and mortality in type 2 diabetes mellitus (T2DM). Life's Essential 8 (LE8) is a newly modified measurement of cardiovascular health (CVH) by American Heart Association (AHA). Promoting CVH has been previously shown to improve the prognosis of T2DM. However, studies regarding the effects of CVH by LE8 on diabetic retinopathy (DR), a major microvascular complication, and death from the cardiovascular and overall causes in T2DM are currently lacking. This study aimed to investigate these associations thus providing preliminary evidence. METHODS: A total of 3192 participants from the National Health and Nutrition Examination Survey (NHANES) were included in the final analysis. Records of mortality during follow-up were obtained by linking to the National Death Index. The multivariable logistic regression and Cox proportional hazard regression with restricted cubic splines were used to estimate the associations. Subgroup analyses were performed to examine the effects of gender, age, and duration of T2DM. RESULTS: 648 individuals had DR at baseline. During a median follow-up of 76 months, 645 overall deaths (incidence per 1000 person-years, 26.53%; 95% confidence interval (CI), 26.50-26.56) were ascertained, including 216 from cardiovascular causes (incidence per 1000 person-years, 8.96%; 95% CI, 8.94-8.98). The multivariable-adjusted odds ratio (OR) per 100-point increase of LE8 was 0.80 (95% CI, 0.71-0.90) for DR, and participants with high levels of LE8 were associated with 47% risk reduction (OR, 0.53; 95% CI, 0.40-0.70). The multivariable-adjusted hazard ratio (HR) per 100-point increase of LE8 was 0.71 (95% CI, 0.62-0.81) and 0.68 (95% CI, 0.58-0.85) for all-cause mortality and cardiovascular mortality, respectively. Similar patterns of inverse associations were observed in participants with moderate and high levels of LE8 for all-cause and cardiovascular mortality. Notably, stronger associations between LE8 and mortality were discovered in participants below 60 years (P < 0.05 for interaction). Moreover, LE8 was correlated with all-cause mortality in a linear way (P for nonlinear=0.32). CONCLUSION: The AHA's newly prompted LE8 was strongly and inversely associated with the risk of DR, all-cause mortality, and cardiovascular-specific mortality in T2DM. LE8 may be a feasible and effective approach in the tertiary prevention of T2DM.

Triglyceride-glucose index for predicting repeat revascularization and in-stent restenosis in patients with chronic coronary syndrome undergoing percutaneous coronary intervention.

BACKGROUND: The triglyceride-glucose (TyG) index, a reliable surrogate indicator of insulin resistance, is independently associated with coronary artery disease of various clinical manifestations. This study aimed to investigate the prognostic value of the TyG index in predicting repeat revascularization and in-stent restenosis (ISR) in chronic coronary syndrome (CCS) patients undergoing percutaneous coronary intervention (PCI). METHODS: A total of 1414 participants were enrolled and divided into groups according to the tertiles of the TyG index. The primary endpoint was a composite of PCI complications, including repeat revascularization and ISR. The associations between the TyG index and the primary endpoint were assessed by multivariable Cox proportional hazards regression analysis with restricted cubic splines (RCS). The TyG index was calculated as Ln (fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2). RESULTS: Over a median follow-up of 60 months, 548 (38.76%) patients had experienced at least one primary endpoint event. The follow-up incidence of the primary endpoint increased with the TyG index tertiles. After adjusting for potential confounders, the TyG index was independently associated with the primary endpoint in CCS patients (HR, 1.191; 95% CI 1.038-1.367; P = 0.013). Additionally, the highest tertile of the TyG group was correlated with a 1.319-fold risk of the primary endpoint compared with the lowest tertile of the TyG group (HR, 1.319; 95% CI 1.063-1.637; P = 0.012). Furthermore, a linear and dose-response relationship was observed between the TyG index and the primary endpoint (non-linear P = 0.373, P overall = 0.035). CONCLUSIONS: An increased TyG index was associated with elevated risk for long-term PCI complications, including repeat revascularization and ISR. Our study suggested that the TyG index could be a potent predictor in evaluating the prognosis of CCS patients undergoing PCI.

Inflammation in coronary artery disease-clinical implications of novel HDL-cholesterol-related inflammatory parameters as predictors.

Coronary artery disease (CAD) is the leading cause of death worldwide. Inflammation and atherosclerotic plaques are the primary pathological mechanisms of CAD. Upon stimulation by deposited lipids and damaged endothelium, innate and adaptive immune cells are activated and recruited to initiate plaque development. Therefore, inflammatory cells and mediators are used to identify inflammatory risk in CAD patients. HDL-cholesterol (HDL-C) is demonstrated to have anti-inflammatory roles in atherosclerosis by interfering with plasma membrane lipid rafts of immune cells. Based on this, novel inflammatory parameters such as monocyte to HDL-C ratio are explored to improve the risk estimation of CAD prognosis. Moreover, with the advance in treatment strategies targeting the inflammatory process in atherosclerosis, identifying CAD patients with increased inflammatory risk by novel inflammatory parameters is of great importance in guiding CAD management. Therefore, this review aims to summarize the current information regarding inflammatory activation and HDL-C in atherosclerosis with a particular focus on the clinical implication of the novel HDL-C-related inflammatory parameters in CAD.

Xinfuli granule alleviates metabolic remodeling through inhibition of endoplasmic reticulum stress and mitochondrial injury in heart failure.

ETHNOPHARMACOLOGICAL RELEVANCE: "Qi deficiency-blood stasis-water retention syndrome" was the most frequent syndrome among heart failure(HF) patients according to Traditional Chinese Medicine (TCM) theory. Xinfuli Granule (XG) was constructed on the basis of classical formula "Baoyuan decoction" to enhance the function of nourishing Qi, activating blood and removing water retention. XG treatment has obtained clinical effect on HF patients. AIM OF THE STUDY: The regulation of XG on energy metabolism of HF was investigated with special focus on endoplasmic reticulum stress (ERS) and mitochondrial function. MATERIALS AND METHODS: Components of XG was acquired by UPLC/Q-TOF-MS Analysis, left anterior descending ligation(LAD)-induced HF rats model and hypoxia-ischemia(H-I)-induced H9c2 cells model were constructed to evaluate the effect of XG treatment. Cardiac function was evaluated by echocardiographic parameters, energy metabolism was evaluated by metabolites and ATP/ADP/AMP levels in blood samples, cardiomyocyte morphology and myocardial fibrosis were assessed by HE staining and Masson staining, mitochondrial ultrastructure was observed under Transmission Electron Microscope, viability and apoptosis rate of H9c2 cells was detected by cell counting kit-8 reaction and flow cytometry analysis, respectively. Mitochondrial membrane potential (MMP) of H9c2 cells was observed by JC-1 kit under fluorescent microscope, expression of peroxisome-proliferator-activated receptor (PPAR)-coactivator (PGC1α), ERS-related genes and RHOA/ROCK pathway were analysed by Quantitative Real-time PCR (RT-qPCR) and Western Blot. RESULTS: Here, we showed that XG alleviated cardiac metabolic remodeling and stimulated ATP production through elevated expression of PGC1α in HF rats. XG also helped recover mitochondrial deformation and decrease apoptosis rate accompanied by an increase of the Bcl2/Bax ratio and the mitochondrial membrane potential in hypoxia-ischemia (H-I) H9c2 cells. In addition, we found that XG downregulated ERS-related proteins ATF4, CHOP, Phospho-eIF2α, and Phospho-PERK, and suppressed the RHOA/ROCK pathway, which served as a potential mediator of ERS. CONCLUSIONS: we found that XG improved energy production by alleviating mitochondrial injury and inhibiting ERS in heart failures mediated by the RHOA/ROCK pathway.

High-density lipoprotein-related inflammatory indices predict repeat revascularization in coronary drug-eluting stenting.

Background: HDL-C-related inflammatory indices are potential predictors of repeat revascularization (RR) after coronary drug-eluting stenting. Methods: Multivariable Cox regression with restricted cubic splines and receiver operating curve was used. Results: The median follow-up was 50 months. A total of 521 (35.42%) patients experienced RR. The incidence of RR was positively associated with the monocyte-to-HDL-C ratio, neutrophil-to-HDL-C ratio and lymphocyte-to-HDL-C ratio (log-rank p < 0.05). After being fully adjusted, the largest tertile of monocyte-to-HDL-C ratio, neutrophil-to-HDL-C ratio, white blood cell-to-HDL-C ratio and lymphocyte-to-HDL-C ratio increased the risk by 38, 30, 28 and 37%, respectively. Monocyte-to-HDL-C ratio was dose-responsive and linearly correlated with RR. HDL-C-related inflammatory indices had over 60% predictive ability. Conclusion: HDL-C-related inflammatory indices independently predicted RR after coronary drug-eluting stenting.

Complement use of Chinese herbal medicine after percutaneous coronary intervention: a prospective observational study.

BACKGROUND: Chinese herbal medicine is widely used as a complement or alternative treatment in coronary artery disease (CAD) patients after percutaneous coronary intervention (PCI) in China. We compared the incidence of the major adverse cardiovascular event (MACE) of CAD patients with or without the complement use of Chinese herbal medicine after PCI. METHODS: In this prospective, observational study that was conducted from September 2016 to August 2019 in Fuwai Hospital (China), we followed up consecutive patients who received PCI treatment for two years. MACE was defined as the composite all-cause mortality, revascularization, and myocardial infarction (MI) and was compared between those using (integrative medicine group) or those not using Chinese herbal medicine as an additional treatment to standard Western medicine, with unadjusted (Kaplan-Meier curves) and risk-adjusted (multivariable Cox regression) analyses. RESULTS: A total of 5942 patients after PCI were enrolled in this study, and 5453 patients were included in the final analysis (4189 [76.8%] male; mean age: 61.9 ± 9.9% years). During the follow-ups, 2932 (53.8%) patients used only Western medicine while 2521(46.2%) patients had used Chinese herbal medicine as an additional treatment to standard Western medicine. Patients in the integrative medicine group (IM group) were older than the Western medicine group (WM group), had more females and less previous MI. The incidence of MACE was 15.3% (449/2932) in WM group and 11.54% (291/2521) in IM group. Cox regression analysis showed that cumulative incidence of MACE was 27% lower in patients of the IM group than those in WM group (hazard ratio = 0.73; 95% CI: 0.63-0.85; P < 0.0001). CONCLUSIONS: For CAD patients after PCI treatment, complement use of Chinese herbal medicine is associated with a lower 2-year MACE incidence. Randomized prospective studies are warranted to provide higher levels of benefit evidence in these patients.

The roles of the circadian hormone melatonin in drug addiction.

Given the devastating social and health consequences of drug addiction and the limitations of current treatments, a new strategy is needed. Circadian system disruptions are frequently associated with drug addiction. Correcting abnormal circadian rhythms and improving sleep quality may thus be beneficial in the treatment of patients with drug addiction. Melatonin, an essential circadian hormone that modulates the biological clock, has anti-inflammatory, analgesic, anti-depressive, and neuroprotective effects via gut microbiota regulation and epigenetic modifications. It has attracted scientists' attention as a potential solution to drug abuse. This review summarized scientific evidence on the roles of melatonin in substance use disorders at the cellular, circuitry, and system levels, and discussed its potential applications as an intervention strategy for drug addiction.

Corrigendum: Menthol Flavor in E-Cigarette Vapor Modulates Social Behavior Correlated With Central and Peripheral Changes of Immunometabolic Signalings.

[This corrects the article DOI: 10.3389/fnmol.2022.800406.].

Menthol Flavor in E-Cigarette Vapor Modulates Social Behavior Correlated With Central and Peripheral Changes of Immunometabolic Signalings.

The use of electronic cigarette (e-cigarette) has been increasing dramatically worldwide. More than 8,000 flavors of e-cigarettes are currently marketed and menthol is one of the most popular flavor additives in the electronic nicotine delivery systems (ENDS). There is a controversy over the roles of e-cigarettes in social behavior, and little is known about the potential impacts of flavorings in the ENDS. In our study, we aimed to investigate the effects of menthol flavor in ENDS on the social behavior of long-term vapor-exposed mice with a daily intake limit, and the underlying immunometabolic changes in the central and peripheral systems. We found that the addition of menthol flavor in nicotine vapor enhanced the social activity compared with the nicotine alone. The dramatically reduced activation of cellular energy measured by adenosine 5' monophosphate-activated protein kinase (AMPK) signaling in the hippocampus were observed after the chronic exposure of menthol-flavored ENDS. Multiple sera cytokines including C5, TIMP-1, and CXCL13 were decreased accordingly as per their peripheral immunometabolic responses to menthol flavor in the nicotine vapor. The serum level of C5 was positively correlated with the alteration activity of the AMPK-ERK signaling in the hippocampus. Our current findings provide evidence for the enhancement of menthol flavor in ENDS on social functioning, which is correlated with the central and peripheral immunometabolic disruptions; this raises the vigilance of the cautious addition of various flavorings in e-cigarettes and the urgency of further investigations on the complex interplay and health effects of flavoring additives with nicotine in e-cigarettes.

Notch and breast cancer metastasis: Current knowledge, new sights and targeted therapy.

Breast cancer is the most common type of invasive cancer in females and metastasis is one of the major causes of breast cancer-associated mortality. Following detachment from the primary site, disseminated tumor cells (DTCs) enter the bloodstream and establish secondary colonies during the metastatic process. An increasing amount of studies have elucidated the importance of Notch signaling in breast cancer metastasis; therefore, the present review focuses on the mechanisms by which Notch contributes to the occurrence of breast cancer DTCs, increases their motility, establishes interactions with the tumor microenvironment, protects DTCs from host surveillance and finally facilitates secondary colonization. Identification of the underlying mechanisms of Notch-associated breast cancer metastasis will provide additional insights that may contribute towards the development of novel Notch-targeted therapeutic strategies, which may aid in reducing metastasis, culminating in an improved patient prognosis.