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Background: Patients with myocardial infarction (MI) frequently experience a heightened incidence of depression, thereby increasing the risk of adverse cardiovascular events. Consequently, early detection and intervention in depressive symptoms among patients with MI are imperative. Shexiang Baoxin Pills (SBP), a Chinese patent medicine employed for the treatment of MI, exhibits diverse mechanisms targeting this condition. Nevertheless, its therapeutic efficacy on postmyocardial infarction depressive symptoms remains unclear. The aim of this study is to investigate the effectiveness and mechanism of SBP in managing depression during acute myocardial infarction (AMI)., Methods: A rat model combining MI and depression was established, and the rats were randomly divided into four groups: the model (MOD) group, SBP group, Fluoxetine (FLX) group, and Sham group. After 28 days of drug intervention, cardiac function was assessed using echocardiography while behavior was evaluated through sucrose preference test (SPT), forced swimming test (FST), and open-field test (OFT). Additionally, levels of inflammatory factors in serum and hippocampus were measured along with NLRP3 inflammasome-related protein expression via Western blotting and immunofluorescence., Results: SBP can enhance cardiac function in rats with AMI and depression, while significantly ameliorating depressive-like behavior. Compared to the Sham group, levels of IL-1β, IL-18, TNF-α, and other inflammatory factors were markedly elevated in the MOD group. However, expressions of these inflammatory factors were reduced to varying degrees following treatment with SBP or FLX. Analysis of NLRP3 inflammasome-related proteins in the hippocampus revealed a significant upregulation of IL-1β, IL-18, NLRP3, ASC, caspase-1, and GSDMD in the MOD group; conversely, these measures were significantly attenuated after SBP intervention., Conclusion: We have observed a significant amelioration in depression-like behavior upon SBP administration during the treatment of AMI, suggesting that this effect may be attributed to the inhibition of NLRP3-mediated pyroptosis. (The main findings are summarized in the graphical abstract in the supplementary file.)., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

Purpose: The atherogenic index of plasma (AIP) has been shown to be related to cardiovascular disease risk, but evidence on the longitudinal pattern of AIP during follow-up is limited. We aimed to explore the associations of baseline and long-term AIP with the risk of myocardial infarction (MI)., Methods: We included 98,861 participants in the Kailuan Study who were free of MI at baseline. AIP was calculated as log (triglyceride/high-density lipoprotein cholesterol). Long-term AIP included the long-term mean AIP (mean AIP from baseline to the first occurrence of MI or the end of follow-up) and number of visits with high AIP (above the cutoff value at the first three visits). The baseline and updated mean AIP were in operationalized as quartiles. Cox proportional hazard models were used to determine the associations between AIP and risk of MI. We excluding all deaths during the follow-up visits in the sensitivity analysis., Results: During a median follow-up of 12.80 years, 1804 participants developed MI. Compared with quartile 1, the adjusted hazard ratios in baseline and updated mean AIP quartile 4 were 1.63 (95% CI, 1.41-1.88) and 1.59 (95% CI, 1.37-1.83), respectively. Compared with participants who did not have a high AIP, the HR among individuals with AIP elevated by three times was 1.94 (95% CI,1.55-2.45). The sensitivity analysis showed similar associations., Conclusions: Elevated levels of both baseline and long-term AIP increased the risk of MI., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Background: The association between obesity and cardiovascular disease (CVD) in people without traditional CVD risk factors is unclear. This study aimed to investigate the association of obesity with CVD and its subtypes in people without traditional CVD risk factors., Methods: Based on the Kailuan cohort study, the included participants were divided into different groups according to levels of body mass index (BMI) and waist height ratio (WHtR), respectively. Multivariate Cox proportional hazard models were used to evaluate the associations., Results: This study included 31,955 participants [men 63.99%; mean age (48.14 ± 3.33) years]. During a median follow-up period of 12.97 (interquartile range: 12.68-13.17) years, 1298 cases of CVD were observed. Compared with the normal BMI group, the hazard ratios (HRs) for CVD, stroke, and myocardial infarction (MI) in the BMI obese group were 1.31 (95% confidence interval [CI] 1.11-1.55), 1.21 (95%CI 1.01-1.46), 1.62 (95%CI 1.13-2.33), respectively. Compared with the WHtR non-obese group, the HRs for CVD, stroke, and MI in the obese group were 1.25(95%CI 1.11-1.41), 1.18 (95%CI 1.03-1.34), 1.57 (95%CI 1.18-2.09), respectively. There was an interaction between age and WHtR (P for interaction was 0.043). The association between WHtR and CVD was stronger in people under 60 years old, with a HR of 1.44 (95%CI 1.24-1.67)., Conclusion: We found that obesity increased the risk of CVD in people without traditional CVD risk factors. The association of WHtR with CVD was stronger in people under 60 years old., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Atherogenic index of plasma (AIP) has been confirmed as a novel marker for myocardial infarction (MI), but few evidence on the long-term AIP and MI risk in general populations. We thus aimed to evaluate the relationships of cumulative exposure to AIP and its accumulation time course with the risk of MI., Methods: A total of 54,440 participants were enrolled in the Kailuan study. Time-weighted cumulative AIP was calculated as the weighted sum of the mean AIP value for each time interval, then normalized by total exposure duration, the exposure duration was from 2006 to 2010. Duration of high AIP exposure was defined as the duration with high AIP and ranged from 0 to 6 years. The time course of AIP accumulation was categorized by the combination of time-weighted cumulative AIP < or ≥ median (- 0.12) and AIP slope., Results: After 11.05 years of follow-up, 766 incident MI cases were documented. After adjustment for potential confounders, higher risk of MI was observed in participants with the highest time-weighted cumulative AIP quartile (HR, 1.89; 95% CI 1.47-2.43), the longest exposure duration of high AIP (HR, 1.52; 95% CI 1.18-1.95), and those with high time-weighted cumulative AIP and negative slope (HR, 1.42; 95% CI 1.13-1.79)., Conclusions: Long-term cumulative exposure to AIP and the time course of AIP accumulation increased the risk of MI. High AIP earlier resulted in a greater risk increase than later in life with the same time-weighted cumulative AIP, emphasizing the importance of controlling atherogenic dyslipidemia early in life., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Long-term patterns of serum uric acid (SUA) and their association with the risk of myocardial infarction (MI) and mortality are poorly characterized as prior studies measured SUA at a single time point. This study aimed to identify SUA trajectories and determine their associations with incident MI and all-cause mortality., Methods: We included 85,503 participants who were free of MI in or prior 2012 from the Kailuan study. SUA trajectories during 2006-2012 were identified by group-based trajectory modeling. Cox proportional hazard models were used to assess the association of SUA trajectories with MI and all-cause mortality., Results: We identified three SUA trajectories during 2006-2012: low-stable (n=44,124, mean SUA: 236-249 μmol/L), moderate-stable (n=34,431, mean SUA: 324-354 μmol/L) and high-stable (n=6,984, mean SUA: 425-463 μmol/L). During a median follow-up of 6.8 years, we documented 817 (0.96%) incident MI and 6498 (7.60%) mortality. Compared with the low-stable group, high-stable group experienced a higher risk of MI (hazard ratio [HR], 1.35; 95% confidence [CI], 1.07-1.71) and all-cause mortality (HR, 1.22; 95% CI, 1.12-1.33). Multiple sensitivity analyses yielded similar results. Additionally, the association of SUA trajectory with MI and all-cause mortality was more pronounced in individuals without a history of hypertension (P-interaction=0.0359) and those aged <60 years (P-interaction<0.0001), respectively., Conclusions: Higher SUA trajectories were associated with altered risk of MI and all-cause mortality, suggesting that monitoring SUA trajectory may assist in identifying subpopulations at higher risk of MI and all-cause mortality., (© 2022. The Author(s).)

Background: Long-term patterns of the triglyceride-glucose index (TyG index) and their effects on cardiovascular disease (CVD) among normal-weight adults are poorly characterized. This study aimed to identify TyG index trajectories in normal-weight adults and to determine their association with the risk of incident CVD., Methods: This study included 40,473 normal-weight participants who were free of stroke and myocardial infarction prior to or in 2012. The TyG index was calculated as ln (fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2), and the TyG index trajectories during 2006-2012 were identified by latent mixture modeling., Results: We identified five distinct TyG index trajectories according to TyG index range and changing pattern over time: low-stable (n = 9,806; mean TyG index 7.84-7.93), moderate-stable (n = 22,066; mean TyG index 8.43-8.52), high-decreasing (n = 1,469; mean TyG index 9.83-8.75), moderate-increasing (n = 5,842; mean TyG index 8.98-9.26), and high-stable (n = 1,290; mean TyG index 9.91-10.07). During 6.74 years of follow-up, we documented 1,577 incident CVD events. Compared with the low-stable pattern, the highest risk of CVD was observed in the high-stable pattern (hazard ratio [HR], 2.24; 95% confidence interval [CI]: 1.73-2.90), followed by the moderate-increasing pattern (HR, 1.70; 95% CI, 1.43-2.04), the high-decreasing pattern (HR, 1.45; 95% CI, 1.11-1.89), and the moderate-stable pattern (HR, 1.25; 95% CI, 1.08-1.44). Similar results were also observed for stroke and myocardial infarction., Conclusions: Distinct TyG index trajectories were significantly associated differently subsequent risk of CVD in normal-weight individuals. These observations suggested that long-term trajectories of TyG index may be useful for predicting CVD among normal-weight adults., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Aims: The role of serum uric acid (SUA) in stroke remains controversial and analyses of changes in SUA and stroke are limited. The objective of the study was to investigate the associations of changes in SUA with stroke and its subtypes (ischemic and hemorrhagic stroke)., Methods and Results: A total of 51 441 participants (mean age 52.69 ± 11.71 years) without history of myocardial infarction or stroke were enrolled. Participants were divided into four groups based on SUA level changes during 2006 and 2010: stable low, increasing, decreasing, and stable high. SUA score was quantified on a 3-point scale with 1 point awarded for hyperuricemia at either year 2006, 2008 or 2010. Multivariate Cox proportion models were used to calculated hazard ratios (HRs) and their 95% confidence intervals (CIs). During 7.03-year follow up, 1611 stroke (1410 ischemic stroke, 199 hemorrhagic stroke, and 47 subarachnoid hemorrhage) were identified. Participants with stable high SUA had higher risk of hemorrhagic stroke, the HR was 1.93 (95% CI: 1.06-3.51), compared to those with stable low SUA. Furthermore, cumulative high SUA exposure also increased the risk of hemorrhagic stroke, the HR (95%CI) was 2.99 (1.55-5.74), compared with cumulative low SUA exposure. However, no significant evidence indicated changes in SUA was associated with the risk of total and ischemic stroke, the HRs (95% CIs) were 0.98 (0.74-1.29) and 0.88 (0.65-1.19), respectively., Conclusions: Stable high SUA was positively associated with the risk of hemorrhagic stroke, but not with total and ischemic stroke risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background Serum uric acid (SUA) has been demonstrated as a risk factor for myocardial infarction (MI) and all-cause mortality; however, the impact of cumulative SUA (cumSUA) remains unclear. We aimed to investigate the association of cumSUA with MI risk and all-cause mortality, and to further explore the effects of SUA accumulation time course. Methods and Results The study enrolled 53 463 participants without a history of MI, and these participants underwent 3 examinations during 2006 to 2010. cumSUA from baseline to the third examination was calculated, multiplying mean values between consecutive examinations by time intervals between visits. Cox models estimated hazard ratios (HRs) and 95% CIs of MI and all-cause mortality for cumSUA quartiles, hyperuricemia exposure duration, and SUA accumulation time course. During a median follow-up of 7.04 years, 476 incident MIs and 2692 deaths occurred. In the fully adjusted model, a higher MI risk was observed in the highest cumSUA quartile (HR, 1.48; 95% CI, 1.10-1.99), in participants with longer hyperuricemia exposure duration (HR, 1.71; 95% CI, 1.06-2.73), and in participants with cumSUA≥median and a negative slope (HR, 1.58; 95% CI, 1.18-2.11). Similar associations persisted for all-cause mortality. Conclusions The risk of MI and all-cause mortality increased with higher cumSUA and was affected by the SUA accumulation time course. Early SUA accumulation contributed more to MI risk and all-cause mortality than later SUA accumulation with the same overall cumulative exposure, emphasizing the importance of optimal SUA control early in life.

Ethnopharmacological Relevance: Danqi Pill, composed of the root of Salvia miltiorrhiza Bunge and the root of Panax notoginseng, is effective in the clinical treatment of myocardial ischemia in coronary heart diseases. A number of studies have shown that autophagy plays an essential role in cardiac function and energy metabolism, and disordered autophagy is associated with the progression of heart failure. However, the effect and mechanism of Danqi pill on autophagy have not been reported yet., Aim of the Study: This study aims to elucidate whether Danqi pill restores autophagy to protect against HF and its potential mechanism., Materials and Methods: Left anterior descending ligation was established to induce an HF rat model, H 2 O 2 -stimulated H9C2 cells model was conducted to clarify the effects and potential mechanism of Danqi pill. In vivo, Danqi pill (1.5 g/kg) were orally administered for four weeks and Fenofibrate (10 mg/kg) was selected as a positive group. In vitro, Danqi pill (10-200 μg/mL) was pre-cultured for 24 h and co-cultured with H 2 O 2 stimulation for 4 h. Importantly, transmission electron microscopy and fluorescence GPF-mRFP-LC3 reporter system were combined to monitor autophagy flux. Furtherly, we utilized Compound C, a specific AMPK inhibitor, to validate whether the autophagy was mediated by AMPK-TSC2-mTOR pathway., Results: Danqi pill significantly improved cardiac function and myocardial injury in HF rats. Intriguingly, Danqi pill potently regulated autophagy mainly by promoting the formation of autophagosomes in vivo. Further results demonstrated that expressions of p-AMPK (P < 0.001) and p-TSC2 (P < 0.001) in cardiac tissue were upregulated by Danqi pill, accompanied with downregulation of p-mTOR (P < 0.01) and p-ULK1(P < 0.01). In parallel with the vivo experiment, in vitro study indicated that Danqi pill dramatically restored autophagy flux and regulated expressions of critical autophagy-related molecules. Finally, utilization of Compound C abrogated the effects of Danqi pill on autophagy flux and the expressions of p-TSC2 (P < 0.05), p-mTOR (P < 0.01) and p-ULK1 (P < 0.05)., Conclusion: Danqi pill could improve cardiac function and protect against cardiomyocytes injury by restoring autophagy via regulating the AMPK-TSC2-mTOR signaling pathway., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The relationship between estimated glomerular filtration rate (eGFR) trajectories and myocardial infarction (MI) has so far been unclear in people with diabetes or prediabetes. We aimed to identify common eGFR trajectories in people with diabetes or prediabetes and to examine their association with MI risk., Methods: The data of this analysis were derived from the Kailuan study, which was a prospective community-based cohort study. The eGFR trajectories of 24 723 participants from the year 2006 to 2012 were generated by latent mixture modeling. Cox proportional hazards models were used to calculate hazard ratios (HR) and their 95% CI for the subsequent risk of MI of different eGFR trajectories., Results: We identified five distinct eGFR trajectories during 2006 to 2012 and named them according to their eGFR range and pattern over time: low-stable (9.4%), moderate-stable (31.4%), moderate-increasing (29.5%), high-decreasing (13.9%), and high-stable (15.8%). During a mean follow-up of 4.61 years, there were a total of 235 incident MI. Although the high-decreasing group had similar eGFR levels to the moderate-stable group during the last exposure period, the risk was much higher (adjusted HR, 3.57; 95% CI, 1.63-7.85 vs adjusted HR, 2.88; 95% CI, 1.36-6.08). Notably, the moderate-increasing group had reached the normal range, but still had a significantly increased risk (adjusted HR, 2.63; 95% CI, 1.24-5.55)., Conclusions: eGFR trajectories were associated with MI risk in people with diabetes or prediabetes. These observations suggest that long-term trajectories of eGFR may be important for risk prediction of MI and should be highlighted in primary prevention., (© 2020 Ruijin Hospital, Shanghai JiaoTong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: The triglyceride-glucose (TyG) index, which is a simple surrogate marker of insulin resistance, has been suggested as a contributor of cardiovascular disease. However, evidence on the effect of long-term elevation of the TyG index exposure on myocardial infarction (MI) is limited. The current study aimed to evaluate the association of baseline and long-term elevation of the TyG index exposure with the risk of MI., Methods: A total of 98,849 participants without MI at baseline (2006) were enrolled from the Kailuan study. The baseline TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. The long-term TyG index was characterized in two ways as follows. The updated mean TyG index was calculated as the mean of TyG index at all previous visits before MI occurred or the end of follow-up; alternatively, the TyG index was calculated as the number of visits with a high TyG index in 2006, 2008, and 2010, ranging from 0 (no exposure) to 3 (had high TyG index at all three study visits). Hazard ratio (HR) and 95% confidence interval (CI) was estimated using multivariable Cox proportion hazard models., Results: During a median follow-up of 11.03 years, 1555 incident MI occurred. In the multivariable-adjusted model, the risk of MI increased with quartiles of the baseline and updated mean TyG index, the HR in quartile 4 versus quartile 1 was 2.08 (95% CI,1.77-2.45) and 1.58 (1.18-2.12), respectively. Individuals with a high TyG index at all three visits had a 2.04-fold higher risk (95% CI, 1.63-2.56) of MI compared with no exposure. Subgroup analyses showed that the associations were more pronounced in women than in men (P interaction  = 0.0411)., Conclusions: Elevated levels of the baseline and long-term TyG index are associated with an increased risk of MI. This finding indicates that the TyG index might be useful in identifying people at high risk of developing MI.

Background: The role of serum uric acid (SUA) in development of myocardial infarction (MI) is controversial. The current study aimed to investigate the association between both baseline SUA and changes in SUA and the risk of MI., Methods: The current study included 71,449 Chinese participants (mean age, 50.9 years) free of MI during the time of follow-up. Participants were divided into 4 categories according to the SUA levels between baseline and the second follow-up: stable low, elevated, reduced and stable high. Multivariate Cox proportion models were used to calculated hazard ratios (HRs) and their 95% confidence intervals (CIs) for MI., Results: During a median follow-up of 8.96 years, 837 MI cases were identified. After adjustment for potential confounders, MI risk was only associated with stable high SUA, the HR was 1.42 (95%CI: 1.02-1.92, p = 0.03), compared with those with stable low SUA. However, there was no association between hyperuricemia at baseline and MI, the HR was 1.14 (95%CI: 0.91-1.42, p = 0.19) compared with those with normal SUA. Subgroup analyses stratified by age, sex, hypertension, diabetes and estimated glomerular filtration rate were also confirmed no significant difference (p-interaction >0.05 for all). Furthermore, mediation analyses revealed 14.14% of association was mediated by hypertension., Conclusions: Only stable high SUA was associated with increased higher risk of MI. Changes in SUA levels in any other direction or high SUA levels at baseline were not associated with risk of MI., Competing Interests: Declaration of competing interest The authors report no relationships that could be construed as a conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background and Aims: Although serum lipids are widely accepted as independent predictors of myocardial infarction (MI), there is insufficient evidence for associations of changes in lipid levels with MI. The present study aimed at investigating the associations between changes in lipids and incidence of MI in people without lipid-lowering therapy., Methods: 64,031 Chinese participants (mean age: 53.42 ± 11.95 years) without previous MI were enrolled in the study. The participants were divided into four categories based on quartiles of lipid changes. Multivariable Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for MI., Results: During a median follow-up of 7.03 years, 599 individuals developed MI. After adjustment for covariates, increased total cholesterol (TC), increased low-density lipoprotein cholesterol (LDL-C), increased non-high-density lipoprotein cholesterol (non-HDL-C), and decreased high-density lipoprotein cholesterol (HDL-C) were associated with elevated risk of MI, with HRs (95% CIs) in the highest quartile group compared with the lowest quartile group of 1.56 (1.21-2.01), 1.96 (1.49-2.57), 1.95 (1.52-2.50), and 0.69 (0.53-0.90), respectively. However, changes in triglyceride (TG) were not associated with MI risk (p = 0.8030)., Conclusions: Changes in levels of TC, LDL-C, non-HDL-C, and HDL-C, but not TG, were associated with risk of MI. Early detection and control of lipid levels may be beneficial and necessary for young people and those with healthy lipid levels at baseline., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Triglyceride glucose (TyG) index and its related parameters have been introduced as cost-effective surrogate indicators of insulin resistance, while prospective evidence of their effects on atherosclerotic cardiovascular disease (ASCVD) remained scattered and inconsistent. We aimed to evaluate the association of TyG and its related parameters with new-onset ASCVD, and the predictive capacity were further compared. Method: A total of 95,342 ASCVD-free participants were enrolled from the Kailuan study. TyG and its related parameters were defined by fasting blood glucose, triglyceride, body mass index (BMI), waist circumstance (WC) and waist-to-height ratio (WHtR). The primary outcome was incident ASCVD, comprising myocardial infarction (MI) and ischemic stroke (IS). Cox proportional hazard models and restricted cubic spline (RCS) analyses were adopted to investigate the association between each index and ASCVD. The C-index, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were used for comparison of their predictive value for ASCVD. Results: During a median follow-up of 15.0 years, 8,031 new cases of ASCVD were identified. The incidence rate of ASCVD increased along with elevated levels of each index, and the relationships were found to be nonlinear in the RCS analyses. The hazard ratio (HR) and 95% confidence interval (95% CI) for ASCVD was 1.39 (1.35, 1.43), 1.46 (1.41, 1.50), 1.50 (1.46, 1.55), and 1.52 (1.48, 1.57) per 1 IQR increase of baseline TyG, TyG-BMI, TyG-WC, and TyG-WHtR, respectively, and the association were more pronounced for females and younger individuals aged < 60 years (Pfor interaction<0.05). Using the updated mean or time-varying measurements instead of baseline indicators did not significantly alter the primary findings. Additionally, TyG-WC and TyG-WHtR showed better performance in predicting risk of ASCVD than TyG, with the IDI (95% CI) of 0.004 (0.001, 0.004) and 0.004 (0.001, 0.004) and the category-free NRI (95% CI) of 0.120 (0.025, 0.138) and 0.143 (0.032, 0.166), respectively. Similar findings were observed for MI and IS. Conclusions: Both the TyG index and its related parameters were significantly and positively associated with ASCVD. TyG-WC and TyG-WHtR had better performance in predicting incident ASCVD than TyG, which might be more suitable indices for risk stratification and enhance the primary prevention of ASCVD. [ABSTRACT FROM AUTHOR]