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Recently, the identification of autoantibodies (AT1-AA) targeting the second extracellular loop of angiotensin II type 1 receptor (AT1R-ECII) in patients with coronary heart disease (CHD) offers a novel perspective on the interplay between immunity and cardiovascular disease. However, much remains unknown regarding the functional diversity of AT1-AA. In this study, we measured the levels of AT1-AA in the sera of 306 CHD patients and purified AT1-AA from patient's sera (n = 127). The subclasses of AT1-AA were categorized based on their impact on intracellular calcium ([Ca 2+ ] i ) levels in mouse arterial smooth muscle cells (MASMCs). Our findings revealed 4 distinct [Ca 2+ ] i response patterns indicating the existence of 4 functional subclasses named H1-, H2-, H3-, and H4-AT1-AA. The correlation analysis demonstrated a positive association between H1-AT1-AA and endogenous coagulation, as well as between H2-AT1-AA and exogenous coagulation; no significant correlation was observed between H3-AT1-AA and the indicators we analyzed. Conversely, H4-AT1-AA exhibited a negative correlation with both leukocyte number and bile acid levels. Logistic regression analysis showed that H2-AT1-AA possessed predictive value for severe CHD. Furthermore, in vitro experiments indicated that both H1- and H2-AT1-AA exerted cytotoxic effects on MASMCs, while H4-AT1-AA increased cell viability. Additionally, an AT1-AA-positive rat model was established by subcutaneously injecting with AT1R-ECII peptide, which produced four similar functional subclasses of rat AT1-AA upon active immunization. This study suggested that classifying different functional subclasses of AT1-AAs can facilitate more accurate evaluation of the condition and prognosis in patients with CHD, thereby providing a novel basis for clinical diagnosis and treatment., 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 © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Coronary heart disease (CHD) is one of the most common cardiovascular diseases. This study analyzed the diagnostic value of echocardiography combined with serum homocysteine (Hcy) and proprotein convertase subtilisin 9 (PCSK9) in CHD. Here, 108 CHD patients were selected as the study group. Additionally, 108 patients with suspected CHD excluded by coronary angiography were selected as the control group. Serum Hcy and PCSK9 levels were detected by circulating enzymatic and biochemical analysis assay. The contrast echocardiography showed that the contrast agent filling velocity (β) and the maximum number of microbubbles (A) in the study group were declined compared to the control group. Serum Hcy and PCSK9 levels in the study group were higher than those in the control group. In addition, β, A, Hcy and PCSK9 are important influencing factors of CHD. The coronary artery disease branch numbers and the degree of stenosis in CHD patients were negatively correlated with β and A values, and positively correlated with serum Hcy and PCSK9 levels. β, A combined with serum Hcy and PCSK9 levels have diagnostic value for CHD, and are significantly correlated with the severity of CHD.

Background: Depression, anxiety and high-sensitivity C-reactive protein (hs-CRP) are individually associated with poor prognosis in patients with coronary heart disease (CHD). However, the combined effects of depression with inflammation or anxiety with inflammation on the prognosis have been rarely explored., Methods: This prospective cohort study included 414 patients diagnosed with CHD. The Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) were used to assess depression and anxiety. A score ≥ 5 points was defined as elevated depression or anxiety. High hs-CRP was defined as ≥ 3 mg/L. Follow-up was performed 2 years after the patients were discharged. The clinical results included noncardiac readmission, cardiac readmission, major cardiovascular events (MACEs), and composite events. The composite events included noncardiac readmission and MACEs. The Cox proportional hazard regression model was used to analyze the prognostic risk., Results: After full adjustment, patients with elevated depression and high hs-CRP had a higher risk in predicting noncardiac readmission (hazard ratio (HR) = 3.87, 95% confidence interval (CI) = 1.10-9.02, p = 0.002) and composite events (HR = 1.93, 95% CI = 1.13-3.30, p = 0.016) than those with high hs-CRP alone. For the anxiety and hs-CRP group, high hs-CRP alone predicted a higher risk of noncardiac readmission (HR = 3.32, 95% CI = 1.57-7.03, p = 0.002) and composite events (HR = 1.75, 95% CI = 1.12-2.76, p = 0.015) than references. Elevated anxiety had no significant effects on all the endpoints. Furthermore, we didn't find interactions between depression and hs-CRP or anxiety and hs-CRP., Conclusion: In patients with CHD, elevated depression with high hs-CRP was found to be significant in predicting the risk of noncardiac readmission and composite events. Early diagnosis and treatment of depression with inflammation are necessary in CHD patients., (© 2024. The Author(s).)

A lower mortality rate from coronary artery disease (CAD) and a more favourable lipid profile have been reported in Afro-Caribbeans compared with people of European ancestry. The aim of this study was to determine whether common lipid variants identified in other populations are associated with lipid levels and CAD in Afro-Caribbeans. We studied 705 Afro-Caribbeans (192 with CAD) who were genotyped for 13 lipid-associated variants. We calculated three polygenic risk scores (PRSs) for elevated LDL (LDL-PRS), decreased HDL (HDL-PRS), and elevated triglycerides (TG-PRS). LDL-PRS, HDL-PRS, and TG-PRS were associated with LDL, HDL, and TG levels, respectively. The LDL-PRS was positively associated with LDL > 2.6 mmol/L and with LDL > 3.0 mmol/L with ORs (odds ratios) of 1.33 (95% confidence interval (CI) = 1.14-1.56) and 1.40 (CI = 1.21-1.62), respectively. The HDL-PRS was associated with a low HDL category (HDL < 1.03 mmol/L) with an OR of 1.3 (CI = 1.04-1.63) and inversely associated with a high HDL category (HDL > 1.55 mmol/L) with an OR of 0.79 (CI = 0.65-0.96). The LDL-PRS was positively associated with CAD after adjustment for age, gender, hypertension, diabetes, and smoking with an OR of 1.27 (CI = 1.06-1.51) but not the HDL-PRS nor the TG-PRS. Results of the present study indicate that common lipid variants are associated with lipid levels and prevalent CAD in Afro-Caribbeans.

Increased platelet activity is a risk factor of thrombotic events in cardiovascular patients. We studied the relationship between platelet function, platelet size, and the content of reticulated platelets (RP) in patients with coronary heart disease (CHD, n = 55) and acute coronary syndrome (ACS, n = 95) receiving acetylsalicylic acid + clopidogrel or ticagrelor, respectively. The control group consisted of patients with risk factors for CHD, but with no CHD/ACS and free of antiplatelet drugs (n = 66). Platelet function was evaluated by the exposure of activated glycoprotein (GP) IIb-IIIa and P-selectin. In the control group, platelets were activated by TRAP (Thrombin Receptor Activating Peptide) 10 µM, and ADP 20, 5, 2.5 µM, and in the CHD/ACS groups, by TRAP 10 µM, and ADP 20 5 µM (±epinephrine 20 µM). Platelet size was assessed by the mean volume, % large forms, and forward scattering. RP were stained by thiazole orange. In the control group, activated GP IIb-IIIa and P-selectin correlated with platelet size and RP content after platelet activation by all agonists. Despite the decrease in platelet activity by antiplatelet drugs, most correlations (primarily for activated GP IIb-IIIa) were preserved in the CHD/ACS patients. In conclusion, increased platelet size and RP content are associated with increased platelet activity and the reduced efficacy of antiplatelet therapy.

Background: Triglyceride (TG) and its related metabolic indices are recognized as important biomarker gauging cardiovascular diseases. This study aimed to explore the association between multiple TG-derived metabolic indices including the atherogenic index of plasma (AIP), triglyceride-glucose (TyG) index, triglyceride glucose-body mass index (TyG-BMI) and cardiovascular outcomes to identify valuable predictors for cardiovascular prognosis in patients with type 2 diabetes (T2DM) and coronary heart disease (CHD)., Methods: Data of 1034 patients with T2DM and CHD from China-Japan Friendship Hospital between January 2019 and March 2022 were collected and analyzed. Multivariate Cox proportional hazards models and restricted cubic spline (RCS) analysis were conducted to examine the associations between AIP, TyG index, TyG-BMI and major adverse cardiac and cerebrovascular events (MACCEs). The area under the receiver operating characteristic (ROC) curve (AUC) was used to screen the most valuable predictor. Kaplan-Meier curve analysis was employed to examine the relationship between the predictor and prognosis. The goodness-of-fit of models was evaluated using the calibration curve and χ 2 likelihood ratio test. Subgroup analysis and interaction test were performed to control for confounding factors., Results: The overall incidence of MACCEs was 31.04% during a median of 13.3 months of follow-up. The results showed that AIP, TyG index and TyG-BMI were all positively correlated with the risk of MACCEs in patients with T2DM and CHD (P < 0.05). Furthermore, ROC (AUC = 0.899) suggested that AIP had the strongest ability to predict the risk of MACCEs, and the highest AIP values enhanced the risk by 83.5% in the population. RCS model demonstrated that AIP was nonlinearly associated with the incident cardiovascular outcomes (P for nonlinear = 0.0118). The Kaplan-Meier analysis for MACCEs grouped by the AIP tertiles indicated that the probability of cumulative incidences of MACCEs was significantly higher in patients with a higher AIP (all Log rank P < 0.001). Meanwhile, the calibration curve demonstrated an excellent goodness-of-fit of the multivariate model (χ 2  = 13.210, P = 0.105). Subgroup analysis revealed that the trend of positive association of AIP with cardiovascular risk was similar across subgroups except in non-hypertensive individuals., Conclusion: Our study, for the first time, may provide valuable information that multiple TG-derived metabolic indices play a crucial role in the risk of MACCEs and it is recommended to monitor the AIP for lipid management in patients with established T2DM and CHD., (© 2024. The Author(s).)

Coronary heart disease (CHD) is a global health concern, with inflammation significantly contributing to its pathogenesis. It is crucial to understand the relationship between inflammatory cytokines and CHD. This study investigates the causal correlations between circulating inflammatory cytokines and CHD using Mendelian randomization (MR), assessing both causative and resultant roles of these cytokines in CHD. In this bidirectional MR analysis, we used genetic data from a genome-wide association study (GWAS) of 60,801 CHD cases and 123,504 controls of European ancestry. We derived inflammatory cytokine data from a GWAS summary of 14,824 participants. The primary analytical approach was the inverse variance-weighted (IVW) method, supported by MR-Egger, weighted median, and weighted mode analyses. Heterogeneity was assessed using the Cochrane Q test, and horizontal pleiotropy was evaluated through the MR-Egger intercept and the MR-PRESSO global test, ensuring robustness against potential pleiotropic bias. This study pinpointed several cytokines as key upstream influencers on the risk of CHD, including eotaxin (CCL11) (odds ratio [OR]: 1.10, 95% confidence interval [CI]: 1.03-1.18, P = .003), C-C motif chemokine ligand 20 (CCL20) (OR: 1.15, 95% CI: 1.05-1.25, P = .002), macrophage colony-stimulating factor 1 (CSF1) (OR: 1.09, 95% CI: 1.01-1.17, P = .020), Fibroblast growth factor 21 (FGF21) (OR: 1.14, 95% CI: 1.01-1.29, P = .038), Fms-related tyrosine kinase 3 ligand (FLT3LG) (OR: 1.26, 95% CI: 1.09-1.44, P = .001), neurotrophin-3 (NT-3) (OR: 1.12, 95% CI: 1.01-1.24, P = .026), and leukemia inhibitory factor (LIF) (OR: 0.89, 95% CI: 0.80-0.99, P = .029). Conversely, T-cell surface glycoprotein CD5 (CD5) (beta: -0.15, 95% CI: -0.29 to -0.01, P = .042) were identified as downstream factors impacted by CHD. No evidence of heterogeneity or horizontal pleiotropy was detected across all results, and a leave-one-out analysis substantiated the robustness of these findings. These findings suggest that CCL11, CCL20, CSF1, FGF21, FLT3LG, NT-3, and LIF may play a crucial role in the pathogenesis of CHD. Additionally, CHD may impact the expression of CD5. Additional research is needed to explore the potential of these biomarkers in the prevention and treatment of CHD., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Human monocytes can be subdivided into phenotypically and functionally different classical, intermediate and non-classical monocytes according to the cell surface expression of CD14 and CD16. A precise identification and characterisation of monocyte subsets is necessary to unravel their role in inflammatory diseases. Here, we compared three different flow cytometric strategies (A-C) and found that strategy C, which included staining against CD11b, HLA-DR, CD14 and CD16, followed by several gating steps, most reliably identified monocyte subtypes in blood samples from healthy volunteers and from patients with stable coronary heart disease (CHD) or ST-elevation myocardial infarction (STEMI). Additionally, we established a fixation and permeabilisation protocol to enable the analysis of intracellular markers. We investigated the phagocytosis of lipid nanoparticles, the uptake of 2-NBD-glucose and the intracellular levels of CD74 and HLA-DM. This revealed that classical and intermediate monocytes from patients with STEMI showed the highest uptake of 2-NBD-glucose, whereas classical and intermediate monocytes from patients with CHD took up the largest amounts of lipid nanoparticles. Interestingly, intermediate monocytes had the highest expression level of HLA-DM. Taken together, we present a robust flow cytometric approach for the identification and functional characterisation of monocyte subtypes in healthy humans and patients with diseases.

Statin-associated muscle symptoms are frequently reported and often lead to discontinuation of statin therapy with an increased risk of cardiovascular events. In vitro studies suggest that statin-mediated inhibition of the mevalonate pathway leads to muscle cell toxicity. We aimed to determine the relationship between mevalonate, LDL-cholesterol, and atorvastatin metabolites in patients with coronary heart disease and self-perceived muscle side effects. Furthermore, we assessed the correlation between mevalonate in blood and muscle and the relationship to statin intolerance due to muscle symptoms. We used blood plasma from a randomized crossover trial (n = 70) and muscle biopsies and plasma from a subgroup in a subsequent open intervention study (n = 26). Both studies tested atorvastatin 40 mg/day. Seven patients did not tolerate ≥3 statins throughout the follow-up and were classified as statin-intolerant. Mevalonate in blood plasma decreased during atorvastatin treatment (median difference -38%, range -77% to 43%, p < 0.001), whereas mevalonate in muscle tissue was not lowered (0.05%, range -47% to 145%). Mevalonate correlated poorly with LDL-cholesterol and atorvastatin metabolites (Spearman's rho -0.28 to 0.10). The statin-intolerant patients had a smaller reduction in circulating mevalonate compared with the tolerant patients; median difference -8.1 (-22 to 3.5) nmol/L versus -25 (-93 to 12) nmol/L, p = 0.028. A similar observation was made for LDL-cholesterol. Cutoffs based on these biomarkers classified >50% correctly as tolerant. Inhibition of the mevalonate pathway does not appear to be the mechanism underlying statin intolerance in the present study. Further studies of mevalonate as a biomarker for statin tolerance are needed to clarify the potential., (© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Coronary heart disease (CHD) patients are considered high cardiovascular risks. Guidelines recommend low-density lipoprotein cholesterol (LDL-C) target levels below 55 mg/dl with > 50% reduction from baselines. These levels can be reached by a combination of statins, ezetimibe, and anti-protein convertase subtilisin/kexin type 9 (anti-PCSK9) agents. Our clinical impression was that CHD patients do not reach LDL-C target levels, despite the wide availability., Objectives: To evaluate whether hospitalization would result in changes in lipid lowering regimens and short-term compliance., Methods: We conducted a retrospective cohort study using data of CHD patients who were admitted to internal medicine wards at Clalit Health Services medical centers because of anginal syndrome during 2020-2022. The data were evaluated for demographic and clinical characteristics; LDL-C level at admission, 6 months previously, and 3 months and 6-9 months after discharge; rates of reaching LDL-C target levels; and lipid lowering treatment at admission, discharge, and 6-9 months after., Results: The cohort included 10,540 patients. One-third and three-quarters did not have lipids level measurements up to 6 months before and during hospitalization, respectively. Only one-fifth of the patients reached LDL-C values before and during admission (median LDL-C 72 mg/dl; range 53-101). Approximately half were treated with high-dose potent statins. Only 10% were treated with ezetimibe. Hospitalization did not have a clinically significant effect on short-term lipid lowering treatment or LDL-C levels., Conclusions: Gaps were noted between guidelines and clinical practice for reaching LDL-C target levels. Further education and strict policy are needed.

Background and Aims: The structure-function relationships of high-density lipoprotein (HDL) subpopulations are not well understood. Our aim was to examine the interrelationships between HDL particle proteome and HDL functionality in subjects with and without coronary heart disease (CHD)., Methods: We isolated 5 different HDL subpopulations based on charge, size, and apolipoprotein A1 (APOA1) content from the plasma of 33 overweight/obese CHD patients and 33 age-and body mass index (BMI)-matched CHD-free subjects. We measured the relative molar concentration of HDL-associated proteins by liquid chromatography tandem mass spectrometry (LC-MS/MS) and assessed particle functionality., Results: We quantified 110 proteins associated with the 5 APOA1-containing HDL subpopulations. The relative molar concentration of these proteins spanned five orders of magnitude. Only 10 proteins were present in >1% while 73 were present in <0.1% concentration. Only 6 of the 10 most abundant proteins were apolipoproteins. Interestingly, the largest (α-1) and the smallest (preβ-1) HDL particles contained the most diverse proteomes. The protein composition of each HDL subpopulation was altered in CHD cases as compared to controls with the most prominent differences in preβ-1 and α-1 particles. APOA2 concentration was positively correlated with preβ-1 particle functionality (ABCA1-CEC/mg APOA1 in preβ-1) (R 2  = 0.42, p = 0.005), while APOE concentration was inversely correlated with large-HDL particle functionality (SRBI-CEC/mg APOA1 in α-1+α-2) (R 2  = 0.18, p = 0.01)., Conclusions: The protein composition of the different HDL subpopulations was altered differentially in CHD patients. The functionality of the small and large HDL particles correlated with the protein content of APOA2 and APOE, respectively. Our data indicate that distinct particle subspecies and specific particle associated proteins provide new information about the role of HDL in CHD., 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 © 2024 Elsevier B.V. All rights reserved.)

Background and Aims: High-density lipoprotein (HDL) might lose atheroprotective functions in the presence of diabetes. We sought to examine associations of HDL cholesterol (HDL-C) and HDL particle (HDL-P) subclasses with risk of coronary heart disease (CHD) stratified by diabetes., Methods: We included 393,516 participants (20,691 diabetics and 372,825 nondiabetics) from the UK Biobank. Restricted cubic splines cooperated with Cox model were used to estimate associations of HDL with CHD., Results: During a median follow-up of 13.0 years, 3398 (16.4 %) and 24,772 (6.6 %) incident CHD events occurred among diabetics and nondiabetics, respectively. HDL-C showed inverse associations with CHD among nondiabetics, whereas U-shaped associations among diabetics. Compared to individuals with normal HDL-C (40th - 60th percentile, 1.32-1.51 mmol/L), those in the top percentile (95th, >2.16 mmol/L) had lower CHD risks among nondiabetics (Hazard Ratio, 0.79; 95 % confidence interval, 0.73-0.86), but higher risks among diabetics (1.38, 1.02-1.88). As for HDL-P, there were inverted U-shaped associations of very large HDL-P and linearly negative associations of large HDL-P with CHD among nondiabetics; however, linearly positive associations of very large HDL-P and null associations of large HDL were observed among diabetics. L-shaped associations of medium and small HDL-P were found both in diabetics and nondiabetics., Conclusions: Very high HDL-C levels were associated with lower CHD risks in nondiabetics, but higher risks in diabetics. Smaller HDL-P was negatively, whereas very large HDL-P was positively associated with CHD risk in diabetics. These data advance our knowledge about the interactions between HDL and diabetes., 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 © 2024 Elsevier B.V. All rights reserved.)

The pathophysiological link between diabetes and heightened propensity for the development of coronary heart disease (CHD) is well-established. Prevailing evidence confirms that small increases in low concentrations of high-sensitivity C reactive protein (hs-CRP) in the human body can determine the tendency of developing CHD. Additionally, glycated hemoglobin (HbA1c) is a well-recognized biomarker to evaluate diabetes progression. Given the positive correlation between diabetes and CHD, this research presents a notably unprecedented label-free electrochemical approach for the dual detection of %HbA1c regarding Total Hb and hs-CRP, facilitating early CHD prediction and cost-effective point-of-care diagnostics. Furthermore, a novel redox probe O-(4-Nitrophenylphosphoryl)choline (C 11 H 17 N 2 O 6 P) was used for the electrochemical detection of CRP, a method not documented in scientific literature before. The calibration curves demonstrate a limit of detection (LOD) of 5 mg/mL in PBS (pH 8) and 6 mg/mL in simulated blood (SB) for a linear range of 0-30 mg/mL of HbA1c. Conjointly, a LOD of 0.007 mg/mL and 0.008 mg/mL for measurement in PBS (pH 7.4) and SB are reported for a linear range of 0-0.05 mg/mL of CRP. The electrochemical systems presented could accurately quantify HbA1c and CRP in mixed samples, demonstrating reasonable specificity and practical applicability for complex biological samples., 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 © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The prognostic value of growth differentiation factor-15 (GDF-15) in predicting long-term adverse outcomes in coronary heart disease (CHD) patients remains limited. Our study examines the association between GDF-15 and adverse outcomes over an extended period in CHD patients and firstly assesses the incremental prognostic effect of incorporating GDF-15 into the Framingham risk score (FRS)-based model. This single-center prospective cohort study included 3,321 patients with CHD categorized into 2,479 acute coronary syndrome (ACS) (74.6%) and 842 non-ACS (25.4%) groups. The median age was 61.0 years (range: 53.0-70.0), and 917 (27.6%) were females. Mortality and major adverse cardiovascular events (MACEs) included cardiovascular mortality, myocardial infarction (MI), stroke, and heart failure (HF) (inclusive of HF episodes requiring outpatient treatment and/or hospital admission). Cox regression models assessed the associations between GDF-15 and the incidence of all-cause mortality and MACEs. Patients were stratified into three groups based on GDF-15 levels: the first tertile group (< 1,370 ng/L), the second tertile group (1,370-2,556 ng/L), and the third tertile group (> 2,556 ng/L). The C-index, integrated discrimination improvement (IDI), net reclassification improvement (NRI), and decision curve analysis (DCA) were used to assess incremental value. Over a median 9.4-year follow-up, 759 patients (22.9%) died, and 1,291 (38.9%) experienced MACEs. The multivariate Cox model indicated that GDF-15 was significantly associated with all-cause mortality (per ln unit increase, HR = 1.49, 95% CI: 1.36-1.64) and MACEs (per ln unit increase, HR = 1.29, 95% CI: 1.20-1.38). These associations persisted when GDF-15 was analyzed as an ordinal variable (p for trend < 0.05). Subgroup analysis of ACS and non-ACS for the components of MACEs separately showed a significant association between GDF-15 and both cardiovascular mortality and HF, but no association was observed between GDF-15 and MI /stroke in both ACS and non-ACS patients. The addition of GDF-15 to the FRS-based model enhanced the discrimination for both all-cause mortality (∆ C-index = 0.009, 95% CI: 0.005-0.014; IDI = 0.030, 95% CI: 0.015-0.047; continuous NRI = 0.631, 95% CI: 0.569-0.652) and MACEs (∆ C-index = 0.009, 95% CI: 0.006-0.012; IDI = 0.026, 95% CI: 0.009-0.042; continuous NRI = 0.593, 95% CI: 0.478-0.682). DCA suggested that incorporating GDF-15 into the FRS-based model demonstrated higher net benefits compared to FRS-based models alone (All-cause mortality: FRS-based model: area under the curve of DCA (AUDC) = 0.0903, FRS-based model + GDF-15: AUDC = 0.0908; MACEs: FRS-based model: AUDC = 0.1806, FRS-based model + GDF-15: AUDC = 0.1833). GDF-15 significantly associates with the long-term prognosis of all-cause mortality and MACEs in CHD patients and significantly improves the prognostic accuracy of the FRS-based model for both outcomes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: To examine the association of Life's Essential 8 (LE8) with the risk of recurrent cardiovascular events among patients with CHD., Methods: This prospective cohort study included 11,997 patients with CHD from the UK Biobank. The LE8 score was generated using five lifestyle factors (diet, body mass index, physical activity, smoking, and sleep) and three biological factors (blood lipids, blood glucose, and blood pressure). LE8 score ranged from 0 to 100 and was categorized into quartiles. Cox proportional hazards regression models were applied to estimate the hazard ratio (HR) and 95% CI (confidence interval)., Results: During a median follow up of 12.5 years, we documented 3366 recurrent cardiovascular events, 1068 myocardial infarction, 1829 heart failure events, 703 strokes, and 934 cardiovascular deaths. The multivariable-adjusted HR (95% CI) for the highest versus the lowest quartile of LE8 score was 0.57 (0.50, 0.65) for recurrent cardiovascular events, 0.66 (0.52, 0.83) for myocardial infarction, 0.54 (0.45, 0.67) for heart failure, 0.50 (0.36, 0.68) for stroke, and 0.46 (0.37, 0.56) for cardiovascular death. Furthermore, the population attributable fraction of the lowest to the highest quartile of LE8 score were ranged from 16.2% to 32.5% for the various cardiovascular outcomes. In addition, biomarkers including renal function and inflammation collectively explained 47.6%-87.7% of the associations between the lifestyle factors and recurrent cardiovascular events., Conclusions: Better cardiovascular health as measured by LE8 was associated with significantly lower risk of recurrent cardiovascular events among patients with CHD. Clinicians should prioritize educating patients with CHD on the importance of optimal cardiovascular health for secondary prevention. In addition, our findings indicated significant mediation effect of biomarkers involving of glycemic control, renal function, liver function, lipid profile, and systemic inflammation on the associations between overall lifestyle factors and recurrent cardiovascular events., 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 © 2024 Elsevier B.V. All rights reserved.)

Background: The red blood cell distribution width (RDW)-to-albumin ratio (RAR) has emerged as a potentially valuable prognostic indicator in diverse medical conditions. However, the prognostic significance of RAR in intensive care unit (ICU) patients with coronary heart disease (CHD) and diabetes mellitus (DM) remains uncertain and requires further investigation., Methods: This study aims to investigate the prognostic significance of RAR in ICU patients with coexisting CHD and DM through a retrospective cohort analysis using data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database (version 2.2). The study population included patients aged 18 years or older who were diagnosed with both CHD and DM. The primary endpoint was 1-year mortality, and the secondary endpoints included 30-day mortality, 90-day mortality, hospital length of stay (LOS), and ICU LOS., Results: A total of 3416 patients, of whom 64.64% were male, were included in the study. The 30-day mortality, 90-day mortality, and 1-year mortality were 7.08%, 7.44%, and 7.49%, respectively. After adjusting for confounding factors, multivariate Cox proportional risk analysis demonstrated that high RAR levels were associated with an increased risk of 30-day mortality (HR, 1.53 [95% CI 1.17-2.07], P = 0.006), 90-day mortality (HR, 1.58 [95% CI 1.17-2.13], P = 0.003), and 1-year mortality (HR, 1.58 [95% CI 1.17-2.13], P = 0.003). Furthermore, the restricted cubic spline (RCS) model indicated a linear relationship between RAR and 1-year mortality., Conclusion: The results suggest that RAR holds potential as a valuable prognostic biomarker in ICU patients with both CHD and DM. Elevated RAR levels were found to be significantly associated with increased mortality during hospitalization, facilitating the identification of individuals at higher risk of adverse outcomes. These findings underscore the importance of incorporating RAR into risk stratification and overall management strategies for ICU patients with coexisting CHD and DM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Guan, Yan, Ouyang, Li, Liu, Zuo, Huang and Zhong.)

Familial hypercholesterolemia (FH) is the most significant inherited risk factor for coronary heart disease (CHD). Current guidelines focus on monogenic FH, but the polygenic form is more common and less understood. This study aimed to assess the clinical utility of an 8-SNP LDLC polygenic score in a central Romanian cohort. The cohort included 97 healthy controls and 125 patients with premature (P)CHD. The weighted LDLC polygenic risk score (wPRS) was analyzed for associations with relevant phenotypic traits, PCHD risk, and clinical FH diagnosis. The wPRS positively correlated with LDLC and DLCN scores, and LDLC concentrations could be predicted by wPRS. A trend of increasing LDLC and DLCN scores with wPRS deciles was observed. A +1 SD increase in wPRS was associated with a 36% higher likelihood of having LDLC > 190 mg/dL and increases in LDLC (+0.20 SD), DLCN score (+0.16 SD), and BMI (+0.15 SD), as well as a decrease in HDLC (-0.14 SD). Although wPRS did not predict PCHD across the entire spectrum of values, individuals above the 90th percentile were three times more likely to have PCHD compared to those within the 10th or 20th percentiles. Additionally, wPRS > 45th percentile identified "definite" clinical FH (DLCN score > 8) with 100% sensitivity and 45% specificity. The LDLC polygenic score correlates with key phenotypic traits, and individuals with high scores are more likely to have PCHD. Implementing this genetic tool may enhance risk prediction and patient stratification. These findings, the first of their kind in Romania, are consistent with the existing literature.

Background: Coronary heart disease (CHD) and stroke have become the leading cause of premature mortality and morbidity worldwide. Therefore, sensitive and accurate biomarkers for early detection of CHD and stroke are urgently needed for effective prevention and treatment. We aim to investigate the association between blood-based HYAL2 methylation and the risk of CHD and stroke in Chinese population., Methods: In a prospective nested case-control study comprising 171 CHD cases, 139 stroke cases, who developed the diseases after recruitment and 356 controls who remained healthy during the 2.5 years of follow-up time, the methylation level of HYAL2 in the peripheral blood was quantified using mass spectrometry, and the association was calculated by logistic regression adjusted for covariant., Results: Significant association between HYAL2 methylation in the peripheral blood and increased risk of preclinical CHD and stroke were identified [odds ratios (ORs) per - 10% methylation: 1.35-1.64, p ≤ 0.045 for HYAL2&#95;CpG&#95;1, HYAL2&#95;CpG&#95;2 and HYAL2&#95;CpG&#95;3 in CHD; ORs per - 10% methylation: 0.76-1.64, p ≤ 0.033 for HYAL2&#95;CpG&#95;2 and HYAL2&#95;CpG&#95;4 in stroke]. The association in CHD was further enhanced by female gender, younger age (< 70 years old), without the history of hypertension and cancer. The combination of four HYAL2 methylation sites showed an effective discrimination of CHD and stroke cases without hypertension from controls [area under curve (AUC) = 0.78 and 0.75, respectively]., Conclusions: This study presents a strong association of altered HYAL2 methylation in peripheral blood with preclinical CHD and stroke, providing a novel biomarker for risk assessment and early detection of cardiovascular diseases., (© 2024. The Author(s).)

Background: Cardiovascular disease (CVD) is a leading cause of global mortality. Early intervention and prevention of CVD depend on accurately predicting the risk of CVD. This study aimed to investigate the association between the TyG index and the risk of coronary heart disease (CHD), congestive heart failure (CHF), heart attack (HA), stroke, and hypertension (HTN) among patients without diabetes in the United States., Methods: In this retrospective, cross-sectional study, we used data from the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2020. We conducted several regression analysis models and calculated the sensitivity and specificity of (TyG) index for predicting the onset of CHD, CHF, HA, stroke, and HTN., Results: A total of 10,937 individuals without diabetes participated in our study. Individuals with a TyG index greater than 8.96 displayed significant increasing in various parameters, including BMI, systolic/diastolic blood pressure, total cholesterol, LDL, and Apo-B levels (p < 0.001). Almost all regression models ensured that a higher TyGI value was associated with higher odds of having CHD, CHF, HA, stroke, and HTN, which patients with a TyGI value higher than 8.96 have odds ratios of 2.24-5.58 for CHD, 1.68-4.42 for stroke, 2.45-3.77 for HA and 1.75-3.93 for HTN comparing than patients with a TyGI value lower than 8.11 (p-value < 0.05).We evaluated the predictive value of the TyG index for each endpoint, obtaining the following area under the curve (AUC) values: 54.75% for CHF (95% CI: 0.542-0.614), 52.32% for stroke (95% CI: 0.529-0.584), 55.67% for HA (95% CI: 0.595-0.646), 55.59% for HTN (95% CI: 0.574-0.597), and 50.31% for CHD (95% CI: 0.592-0.646)., Conclusion: The TyG index showed a strong correlation with cardiovascular risk factors in individuals without diabetes, however it was a poor predictor of almost studied cardiovascular diseases., (© 2024. The Author(s).)

Objective: This study aims to elucidate the association between serum levels of circular RNAs circ&#95;0001879 and circ&#95;0004104 and the occurrence of coronary microcirculation disorders along with post-PCI prognosis in individuals with stable coronary heart disease., Methods: A cohort of 92 patients diagnosed with stable coronary heart disease and subjected to PCI between June 2020 and June 2022 at our institution was assembled. Patients were categorized into an exposed group (n = 60) and a non-exposed group (n = 32), predicated on the coronary angiography-derived microcirculation resistance index (caIMR)., Results: Comparative analysis revealed significantly elevated levels of circ&#95;0001879 and circ&#95;0004104 in the serum of the exposed group compared to the non-exposed group, with statistical significance (P < 0.05). Post-PCI, both caFFR and caIMR values demonstrated a marked increase in comparison to pre-surgical measurements within both groups, with the exposed group exhibiting lower indices post-surgery relative to the non-exposed group, indicative of superior microcirculatory outcomes (P < 0.05). Furthermore, serum levels of circ&#95;0001879 and circ&#95;0004104 were inversely correlated with favorable prognosis, with lower levels observed in patients with positive outcomes (P < 0.05). The predictive accuracy for poor prognosis, as indicated by the area under the curve (AUC), was enhanced when circ&#95;0001879 and circ&#95;0004104 were considered in tandem (AUC = 0.934), surpassing the predictive power of individual assessments (Z combination vs circ&#95;0001879 = 2.439, Z combination vs circ&#95;0004104 = 2.317, P < 0.05)., Conclusion: Elevated serum levels of circ&#95;0001879 and circ&#95;0004104 are observed in stable coronary heart disease patients and are significantly associated with the presence of coronary microcirculation disorders and post-PCI prognosis, underscoring their potential as prognostic biomarkers., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The use of 3 biomarkers - cystatin-C (Cys-C), retinol-binding protein (RBP), and ischemia-modified albumin (IMA) - for the clinical classification and outcome of coronary heart disease (CHD) has not been adequately evaluated. We explored the serum levels of these 3 markers and evaluated their diagnostic and prognostic values in patients with CHD. This retrospective case-control study, conducted between June 2017 and June 2018, included 201 patients with CHD hospitalized at the Henan Provincial People's Hospital and 127 healthy individuals from Henan Provincial People's Hospital as controls. Cys-C, RBP, IMA levels, and other laboratory parameters in the 2 groups were determined, and patient outcomes were analyzed. Cys-C, RBP, and IMA levels were higher in the case group than in the control group (P < .05). Logistic regression analysis confirmed that these 3 biomarkers were independent risk factors for CHD. Each indicator has clinical significance in the diagnosis and prognosis of CHD, with RBP being the most significant. The AUC value for CHD detection using a combination of the 3 indicators was 0.783, and the sensitivity and specificity values were 78% and 74.6%, respectively. Simultaneous detection of Cys-C, RBP, and IMA could be an optimal method for early diagnosis and prognosis of CHD., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

To explore the effects of Du Meridian moxibustion combined with ear acupuncture on clinical symptoms and serum neurotransmitters in patients with coronary heart disease and insomnia. This study is a retrospective study. From June 2021 to May 2023, 116 patients with coronary heart disease and insomnia treated at our hospital were selected as subjects. They were divided into 2 groups according to the treatment. The control group received treatment with alprazolam, while the experimental group received Du Meridian moxibustion combined with ear acupuncture in addition to alprazolam treatment. The efficacy of the 2 groups was compared, and the levels of cardiac function indicators, serum melatonin, leptin, and neurotransmitters were measured. The total effectiveness rate in the experimental group was 93.10% (with a cure rate of 36.21%, a significant improvement rate of 41.38%, and an effective rate of 15.52%), which was significantly higher than the 79.31% in the control group (with a cure rate of 24.14%, a significant improvement rate of 32.76%, and an effective rate of 22.41%) (P < .05). Both groups exhibited an increase in left ventricular ejection fraction, stroke volume, and cardiac output after treatment compared to before treatment. Additionally, left ventricular end-systolic diameter decreased after treatment compared to before treatment, but the cardiac function was compared between the 2 groups after treatment (P > .05). In both groups, serum melatonin and serotonin (5-HT) levels increased after treatment compared to before treatment, while serum leptin, dopamine, and glutamate levels decreased after treatment compared to before treatment. Furthermore, the experimental group had higher serum melatonin, 5-HT, and gamma-aminobutyric acid levels compared to the control group, and lower serum leptin, dopamine, and glutamate levels compared to the control group (P < .05). The serum traditional Chinese medicine syndrome score and Pittsburgh sleep quality index score of the 2 groups decreased after treatment, and the experimental group was lower than the conventional group (P < .05). The combination of Du Meridian acupuncture with ear acupuncture in the treatment of insomnia in coronary heart disease can regulate the expression of serum melatonin, leptin, and neurotransmitters, alleviate symptoms, and improve therapeutic efficacy., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Hyperuricemia, characterized by elevated serum uric acid levels, has garnered significant attention in cardiovascular research due to its potential association with coronary heart disease (CHD). While some studies suggest hyperuricemia as a risk factor of CHD, others present conflicting findings. A systematic review and dose-response meta-analysis is warranted to comprehensively summarize the previous studies and determine the association between hyperuricemia and CHD, thereby supporting clinical practice and future studies in this field., Methods: In this study, we will comprehensively search Medline, EMBase, Cochrane Central, ICTRP, and ClinicalTrials.gov, from inception to December 31, 2024. Prospective or retrospective cohort studies and case-control studies investigating the association between hyperuricemia and CHD will be included. Two independent reviewers will conduct study selection, data extraction, and risk of bias assessment. The primary outcome will be the pooled relative risk of CHD associated with hyperuricemia by using random-effect model. Dose-response meta-analysis will be performed with linear and non-linear model to explore the the magnitude and direction of the association between serum uric acid levels and CHD risk. Subgroup analyses will be conducted based on uric acid test approaches and corresponding cut-off values and human races. Sensitivity analyses will assess the robustness of the results with leave-one-out method, while publication bias will be evaluated using funnel plots, Egger's test, and Begg's test. We will further use GRADE to evaluate the quality of the evidences provided by our systematic review., Expected Results: From this systematic review and dose-response meta-analysis, we hope out findings will provide reliable conclusion and data support on the association between hyperuricemia and CHD. The transparent and replicable methodologies outlined in this protocol contribute to advancing understanding of hyperuricemia as a potentially modifiable risk factor for CHD, thus supporting evidence-based strategies for cardiovascular disease management., Conclusions: This protocol describes a rigorous plan to systematically review and analyze the quantitative association between hyperuricemia and CHD risk. In a word, we will help further clinical practice and scientific studies in this field., Trial Registration: This protocol was registered in PROSPERO CRD42024538553., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright: © 2024 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: To date, no studies have investigated the correlation between the neutrophil-to-lymphocyte ratio (NLR) and the long-term risk of mortality in individuals with both coronary heart disease (CHD) and hypertension. This study aims to evaluate the association between NLR and all-cause and cardiovascular mortality among this patient population., Methods: National Death Index (NDI) and National Health and Nutrition Examination Survey (NHANES 2001-2018) were the data sources. A nonlinear association between the NLR and mortality risk was shown by restricted cubic spline (RCS) analysis. Using a weighted Cox proportional hazards model, we quantitatively evaluated the effect of NLR on mortality risk.The capacity of NLR to forecast survival was assessed by evaluating time-dependent receiver operating characteristic (ROC) curves. A mediating influence analysis was conducted to assess the influence of NLR on mortality through eGFR as a mediator., Results: The study involved a total of 2136 individuals. During the median follow-up interval of 76.0 months, 801 deaths were recorded. The RCS analysis showed NLR and mortality risk to have a nonlinear relationship. Two groups were established based on the participants' NLR levels: a group with high NLR (NLR > 2.65) and a group with low NLR (NLR < 2.65). After adjusting for potential confounding factors, the Cox proportional hazards model revealed that participants with an increased NLR faced a significantly higher risk of cardiovascular mortality. (HR 1.58, 95% CI 1.33-1.82, p < 0.0001) and all-cause mortality (HR 1.46, 95% CI 1.30-1.62, p < 0.0001). An analysis of interactions and data stratification corroborated the validity of our findings. eGFR was identified as a partial mediator in the association between NLR and mortality rates, contributing 12.17% and 9.66% of the variance in all-cause and cardiovascular mortality, respectively. The predictive performance for cardiovascular mortality was quantified using ROC curves, with respective AUC values of 0.67, 0.65, and 0.64 for predictions over 3, 5, and 10 years. The AUC values for all-cause mortality were 0.66, 0.64, and 0.63 for the same time frames., Conclusion: For patients with CHD and hypertension, an elevated NLR serves as an independent prognostic indicator for both all-cause and cardiovascular mortality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Song, Chen, Yu and Zhu.)

Cardiometabolic co-morbidities, diabetes (DM), hypertension (HTN), and obesity contribute to cardiovascular disease. Circulating biomarkers facilitate prognostication for patients with cardiovascular disease. We explored the relation between cardiometabolic co-morbidity burden in patients with chronic coronary disease and biomarkers of myocardial stretch, injury, inflammation, and platelet activity. We analyzed participants from the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trials biorepository with plasma biomarkers (N-terminal probrain natriuretic peptide, high-sensitivity cardiac troponin T, high-sensitivity C-reactive protein, interleukin-6, soluble CD40 ligand, and growth differentiation factor-15) and clinical risk factors (hemoglobin A1c [HbA1c], systolic blood pressure [SBP], and body mass index [BMI]) at baseline. We defined cardiometabolic co-morbidities as DM, HTN, and obesity at baseline. Co-morbidity burden is characterized by the number and severity of co-morbidities. Controlled co-morbidities were defined as HbA1c <7% for those with DM, SBP <130 mm Hg for those with HTN, and BMI <30 kg/m 2 . Severely uncontrolled was defined as HbA1c ≥8%, SBP ≥160 mm Hg, and BMI ≥35 kg/m 2 . We performed linear regression analyses to examine the association between co-morbidity burden and log-transformed biomarker levels, adjusting for age, gender, estimated glomerular filtration rate controlled for hemodialysis, and left ventricular ejection fraction. A total of 752 participants (mean age 66 years, 19% women, 84% White) were included in this analysis. Self-reported Black race, current smokers, history of myocardial infarction, and heart failure had a greater cardiometabolic co-morbidity burden. The presence of ≥1 severely uncontrolled co-morbidity was associated with significantly higher baseline levels of high-sensitivity cardiac troponin T, high-sensitivity C-reactive protein, interleukin-6, and growth differentiation factor-15 than participants with no co-morbidities. In conclusion, increasing cardiometabolic co-morbidity burden in patients with chronic coronary disease is associated with higher levels of circulating biomarkers of myocardial injury and inflammation., Competing Interests: Declaration of competing interest Dr. Bangalore reports grants from National Heart, Lung, and Blood Institute during the conduct of the study; grants and personal fees from Abbott Vascular; personal fees from Biotronik, Pfizer, Amgen, and Reata outside the submitted work. Dr. Mavromatis reports grants from National Heart, Lung, and Blood Institute (NHLBI); grants from NHLBI (CV Inflammation Reduction Trial and GMCSF in PAD-3 Trial), grants from CSL Behring, St Jude's Medical, Medtronic, DalCor Pharmaceuticals, AstraZeneca, Novartis, Regeneron, and Member of American College of Cardiology and Society of Cardiovascular Angiography and Interventions. Dr. Newby reports grants from the National Institutes of Health/NHLBI, AstraZeneca Healthcare Foundation, Boehringer Ingelheim (Ingelheim, Germany), CSL, and Medtronic. Dr. Reynolds reports grants from NHLBI, during the conduct of the study, she receives support from Abbott Vascular (donation of optical coherence tomography catheters for an unrelated research study), Biotelemetry Inc. (donation of telemetry monitors for an unrelated research study), and Siemens. Dr. Hochman is principal investigators for the ISCHEMIA trial for which, in addition to support by National Heart, Lung, and Blood Institute grant, devices and medications were provided by Abbott Vascular; Medtronic, Inc.; Abbott Laboratories (formerly St. Jude Medical, Inc.); Royal Philips NV (formerly Volcano Corporation); Arbor Pharmaceuticals, LLC; AstraZeneca Pharmaceuticals, LP (Wilmington, Delaware); Merck Sharp & Dohme Corp.; Omron Healthcare, Inc, Sunovion Pharmaceuticals, Inc. Espero BioPharma; and Amgen, Inc; and financial donations from Arbor Pharmaceuticals LLC and AstraZeneca Pharmaceuticals LP. Dr. Hochman is also the PI for ISCHEMIA-EXTEND. Drs. Anthopolos, Maron, Newman, and Berger reports grants from the NHLBI during the conduct of the study. The remaining authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Sodium is crucial for maintaining cardiovascular health, especially in relation to heart failure. The impact of baseline serum sodium concentrations on the outcomes of newly diagnosed coronary heart disease (CHD) without heart failure remains unclear. This prospective cohort study included 681 patients who were newly diagnosed with CHD. Cox proportional hazards models and restricted cubic spline (RCS) analysis were used to assess the relationship between serum sodium concentrations and major adverse cardiovascular events. The improvement in traditional prediction models by the addition of serum sodium concentrations was assessed using changes in the C-statistic, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). During a median follow-up of 51.04 months (IQR: 40.88-53.80 months), 131 events were recorded. Multivariate Cox proportional hazards models showed that the L2 group (136-138.9 mmol/L) had the highest MACE risk. Compared to L2, the hazard ratios (HRs) and 95% confidence intervals (CIs) for the L1 (130-135.9 mmol/L), L3 (139-140.9 mmol/L), L4 (141-142.9 mmol/L), and L5 (143-147.0 mmol/L) groups were 0.31 (0.14-0.70, P = 0.005), 0.48 (030-0.78, P = 0.003), 0.56 (0.34-0.92, P = 0.022), and 0.37 (0.22-0.64, P < 0.001), respectively. Including serum sodium concentrations in the prediction model significantly improved the C-statistic from 0.647 to 0.679 (P = 0.022), with an NRI of 0.338 (P < 0.001) and an IDI of 0.026 (P < 0.001). RCS analysis showed a nonlinear relationship: within the 130-138 mmol/L sodium range, MACE risk gradually increased with higher sodium levels (HR 1.39, 95% CI 1.09-1.76, P = 0.008); whereas within the 138-147 mmol/L range, the risk gradually decreased (HR 0.88, 95% CI 0.80-0.98, P = 0.014). Baseline serum sodium concentrations are significantly associated with long-term cardiovascular risk in newly diagnosed CHD patients, showing an inverted U-shaped relationship, whereas low serum sodium may be specifically linked to higher risks of death and nonfatal myocardial infarction. Further research is needed to explore the impact of long-term changes in serum sodium concentrations on disease prognosis., (© 2024. The Author(s).)

Background: The incidence of coronary heart disease (CHD) in youth is rapidly increasing but difficultly recognized in the early stage., Methods and Results: In this retrospective study, 194 CHD patients under the age of 45 who previously experienced chest pain symptoms and 170 non-CHD patients were included and demographic data were collected. Systemic inflammation index (SII) and systemic inflammation response index (SIRI) were increased in young CHD patients (p < 001). Spearman's correlation analysis showed that both SII and SIRI were negatively correlated with HDL and positively correlated with hypertension, Gensini score, and hsTnI. Logistic regression analysis indicated that SII and SIRI were independently associated with the presence of CHD in youth with chest pain symptoms. The area under the ROC curve (AUC) of the SII model for young CHD patients was 0.805 (0.728-0.869), and the sensitivity and specificity were 0.65 and 0.823, respectively. Meanwhile, the AUC for the SIRI model was 0.812 (0.739-0.872), and the sensitivity and specificity were 0.673 and 0.8022. The calibration curves of both SII and SIRI models are in good agreement with the actual curves. And the decision curves of both models indicated their clinical practicality., Conclusion: SII and SIRI are independent risk factors for CHD in young adults, which can quickly and effectively identify CHD patients among young adults who have previously experienced chest pain symptoms., (© 2024 The Author(s). Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Background: Metabolomics may reveal novel biomarkers for coronary heart disease (CHD). We aimed to identify circulating metabolites and construct a metabolite risk score (MRS) associated with incident CHD among racially and geographically diverse populations., Methods: Untargeted metabolomics was conducted using baseline plasma samples from 900 incident CHD cases and 900 age-/sex-/race-matched controls (300 pairs of Black Americans, White Americans, and Chinese adults, respectively), which detected 927 metabolites with known identities among ≥80% of samples. After quality control, 896 case-control pairs remained and were randomly divided into discovery (70%) and validation (30%) sets within each race. In the discovery set, conditional logistic regression and least absolute shrinkage and selection operator over 100 subsamples were applied to identify metabolites robustly associated with CHD risk and construct the MRS. The MRS-CHD association was evaluated using conditional logistic regression and the C-index. Mediation analysis was performed to examine if MRS mediated associations between conventional risk factors and incident CHD. The results from the validation set were presented as the main findings., Results: Twenty-four metabolites selected in ≥90% of subsamples comprised the MRS, which was significantly associated with incident CHD (odds ratio per 1 SD, 2.21 [95% CI, 1.62-3.00] after adjusting for sociodemographics, lifestyles, family history, and metabolic health status). MRS could distinguish incident CHD cases from matched controls (C-index, 0.69 [95% CI, 0.63-0.74]) and improve CHD risk prediction when adding to conventional risk factors (C-index, 0.71 [95% CI, 0.65-0.76] versus 0.67 [95% CI, 0.61-0.73]; P <0.001). The odds ratios and C-index were similar across subgroups defined by race, sex, socioeconomic status, lifestyles, metabolic health, family history, and follow-up duration. The MRS mediated large portions (46.0%-74.2%) of the associations for body mass index, smoking, diabetes, hypertension, and dyslipidemia with incident CHD., Conclusions: In a diverse study sample, we identified 24 circulating metabolites that, when combined into an MRS, were robustly associated with incident CHD and modestly improved CHD risk prediction beyond conventional risk factors., Competing Interests: None.

Objective: To investigate the factors influencing accelerated aging in patients with type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD)., Methods: A total of 216 patients diagnosed with T2DM and CHD between August 2019 and August 2023 at Xuzhou Central Hospital were selected. Patients were divided into an aging group and a non-aging group, based on the positive or negative values of phenotypic age acceleration (PhenoAgeAccel). Logistic regression analysis was conducted. Variables that had a univariate analysis P < 0.05 were included in the multivariate analysis to identify factors influencing aging in patients with T2DM and CHD, and the area under the curve of the model was reported., Results: This study included 216 patients, with 89 in the accelerated aging group, and 127 in the non-accelerated aging group. The average age of patients was 70.40 (95% CI: 69.10-71.69) years, with 137 males (63.4%). Compared with the non-accelerated aging group, patients in the accelerated aging group were older, with a higher proportion of males, and a higher prevalence of hypertension, stable angina pectoris, and unstable angina pectoris. Multivariate Logistic regression analysis indicated that the absolute value of neutrophils (NEUT#), urea (UREA), adenosine deaminase (ADA), and the triglyceride-glucose index (TyG) were risk factors for accelerated aging, while cholinesterase (CHE) was a protective factor. For each unit increase in NEUT#, UREA, ADA, and TyG, the risk of aging increased by 64%, 48%, 10%, and 789%, respectively. The overall area under the receiver operating characteristic (ROC) curve of the model in the training set was 0.894, with a 95% confidence interval (CI) of 0.851-0.938., Conclusion: NEUT#, CHE, UREA, ADA, and TyG are predictors of accelerated aging in patients with T2DM and CHD, with the model showing favorable overall predictive performance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Huang, Liu, Chen, Chen and Wang.)

Background: Coronary heart disease (CHD) is a common cardiovascular disease that is associated with altered gut microbiota. Enteroviruses, an essential component of the gut microbiome, may play an important role in disease progression. However, the relationship between enteroviruses and CHD remains unclear. The development of high-throughput sequencing technologies has facilitated research on the interconnections between viruses and disease-related metabolites., Methods and Results: Mice were fed a high-fat diet (CHD group) or chow diet (Sham group) for 12 weeks, and ligation of the left anterior descending coronary artery was performed at the end of week 8. After 4 weeks, all animals were euthanised. Subsequently, the animals were evaluated for basic haemato-biochemical parameters and cardiac function, and aorta staining was performed. Based on enteroviral metagenomics and serum UPLC-MS/MS metabolomics analyses, we evaluated the association between enteroviral groups and serum metabolites of CHD mouse model. A high-fat diet and coronary ligation enabled the establishment of the CHD mouse model. Notably, the enterovirus spectrum of the sham group was significantly different from that of the CHD group, with 24 viral communities of different family and species classification, such as Tsarbombavirus, Mingyongvirus, Claudivirus, and Firehammervirus, exhibiting significant differences. In addition, 731 Differential metabolites were detected in the serum of both groups of mice. Correlation network analysis revealed a close relationship between various metabolites related to lipid metabolism and different viruses, including Tsarbombavirus, Mingyongvirus, Claudivirus, and Firehammervirus., Conclusions: An animal model of CHD, characterised by lipid disturbance and myocardial ischaemia, was established using a high-fat diet and ligation of the left anterior descending branch of the coronary artery. Tsarbombavirus, Firehammervirus, Mingyongvirus, and Claudivirus were associated with metabolites in the lipid metabolism pathway. The results indicate that Tsarbombavirus may be the main genus interacting with CHD-related metabolites in mice. Conclusively, the findings of our study provide novel insights into the potential relationship enterovirus groups and metabolites associated with CHD., (© 2024. The Author(s).)

Background: Conventional low-density lipoprotein cholesterol (LDL-C) quantification includes cholesterol attributable to lipoprotein(a) (Lp(a)-C) due to their overlapping densities., Objectives: The purposes of this study were to compare the association between LDL-C and LDL-C corrected for Lp(a)-C (LDL Lp(a)corr ) with incident coronary heart disease (CHD) in the general population and to investigate whether concomitant Lp(a) values influence the association of LDL-C or apolipoprotein B (apoB) with coronary events., Methods: Among 68,748 CHD-free subjects at baseline LDL Lp(a)corr was calculated as "LDL-C-Lp(a)-C," where Lp(a)-C was 30% or 17.3% of total Lp(a) mass. Fine and Gray competing risk-adjusted models were applied for the association between the outcome incident CHD and: 1) LDL-C and LDL Lp(a)corr in the total sample; and 2) LDL-C and apoB after stratification by Lp(a) mass (≥/<90th percentile)., Results: Similar risk estimates for incident CHD were found for LDL-C and LDL-C Lp(a)corr30 or LDL-C Lp(a)corr17.3 (subdistribution HR with 95% CI) were 2.73 (95% CI: 2.34-3.20) vs 2.51 (95% CI: 2.15-2.93) vs 2.64 (95% CI: 2.26-3.10), respectively (top vs bottom fifth; fully adjusted models). Categorization by Lp(a) mass resulted in higher subdistribution HRs for uncorrected LDL-C and incident CHD at Lp(a) ≥90th percentile (4.38 [95% CI: 2.08-9.22]) vs 2.60 [95% CI: 2.21-3.07]) at Lp(a) <90th percentile (top vs bottom fifth; P interaction 0.39). In contrast, apoB risk estimates were lower in subjects with higher Lp(a) mass (2.43 [95% CI: 1.34-4.40]) than in Lp(a) <90th percentile (3.34 [95% CI: 2.78-4.01]) (P interaction 0.49)., Conclusions: Correction of LDL-C for its Lp(a)-C content provided no meaningful information on CHD-risk estimation at the population level. Simple categorization of Lp(a) mass (≥/<90th percentile) influenced the association between LDL-C or apoB with future CHD mostly at higher Lp(a) levels., Competing Interests: Funding Support and Author Disclosures The BiomarCaRE Project is funded by the European Union Seventh Framework Programme Collaborative Project (FP7/2007–2013) under grant agreement no. HEALTHF2-2011–278913. The MORGAM Project has received funding from European Union projects MORGAM (Biomed, BMH4-CT98-3183), GenomEUtwin (Fifth Framework Programme FP5, QLG2-CT-2002-01254), BiomarCaRE (FP7, HEALTH-F2-2011-278913), European Network for Genetic and Genomic Epidemiology (ENGAGE) (FP7, HEALTH-F4-2007-201413), Consortium on Health and Ageing: Network of cohorts in Europe and the United States (CHANCES) (FP7, HEALTH-F3-2010-242244), euCanSHare (Horizon 2020, No. 825903), Digital, Risk-Based Screening for Atrial Fibrillation in the European Community project - European Union (AFFECT-EU) (Horizon 2020, no. 847770), and Medical Research Council, London (G0601463, no. 80983: Biomarkers in the MORGAM Populations). This funding has supported central coordination, workshops, and part of the activities of the MORGAM Data Centre, the MORGAM Laboratories, and the MORGAM Participating Centres; MORGAM Participating Centres are funded by regional and national governments, research councils, charities, and other local sources. Dr Schnabel has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 648131), German Ministry of Research and Education (BMBF 01ZX1408A), and German Center for Cardiovascular Research (DZHK e.V.; grant no. 81Z1710103); and has received personal fees from BMS/Pfizer. Dr Kee has received funding from the National Institute of Health Research United Kingdom. Dr Salomaa was supported by the Finnish Foundation for Cardiovascular Research and the Juho Vainio Foundation; and has received grants from Bayer AG. Dr Zeller was supported by the German Center of Cardiovascular Research (DZHK e.V.; DZHK, 81Z0710102). Dr Blankenberg has received a grant from Abbott Diagnostics during the conduct of the study; has received grants and personal fees from Abbott Diagnostics, Bayer, SIEMENS, and Thermo Fisher; has received grants from Singulex; and has received personal fees from AstraZeneca, AMGEN, Medtronic, Pfizer, Roche, Siemens Diagnostic, and Novartis. Dr Söderberg has been supported by the Swedish Heart-Lung Foundation (20140799, 20120631, and 20100635), the County Council of Västerbotten (ALF, VLL- RV-967561, RV-841381548791), and Umeå University; and has received grants and personal fees from Actelion Ltd. All funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Outside the scope of the present work, Dr Arnold has received consulting fees and grant support from Novartis. Dr Brunner has received grant supports from Daiichi-Sankyo, Novartis, Pfizer, and Sanofi; has received nonfinancial support from Abbott, ASAHI INTECC, and Inari Medical; and has received personal fees from Amgen and Novartis. Dr Bay is supported by a grant from the German Heart Foundation (grant no. S/06/23). Dr Koenig has received consulting fees and lecture fees from AstraZeneca, Novartis, and Amgen; has received consulting fees from Pfizer, The Medicines Company, DalCor Pharmaceuticals, Kowa, Corvidia Therapeutics, Esperion, Genentech, OMEICOS, Novo Nordisk, LIB Therapeutics, TenSixteen Bio, New Amsterdam Pharma, and Daiichi-Sankyo; has received lecture fees from Berlin-Chemie, Bristol Myers Squibb, and Sanofi; and has received grant support and provision of reagents from Singulex, Abbott, Roche Diagnostics, and Dr Beckmann Pharma. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: This study aimed to explore the association between the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and the risk and severity of CHD among NAFLD patients., Methods: This retrospective study included 278 patients with NAFLD and chest pain. The TG/HDL-C ratio was calculated and coronary angiography performed. All individuals were divided into NAFLD + CHD and NAFLD groups. The severity of coronary artery stenosis is quantified using the Gensini score based on angiographic results. In NAFLD patients, the association between the TG/HDL-C ratio and the risk and severity of CHD was explored., Results: CHD was detected in 139 of 278 patients. Compared to NAFLD group, multivariate logistic regression showed that TG/HDL-C ratio was a risk factor for CHD among NAFLD patients after adjustment for confounding factors with the odds ratio (OR 1.791, 95% CI 1.344-2.386, P<0.001). Further analysis using multivariate logistic regression based on tertiles revealed that, after adjusting for confounding factors, compared to the T1 group, the risk of CHD in the T2 group was 2.17-fold higher (OR, 2.17; 95% CI, 1.07-4.38; P = 0.031). Similarly, the risk of CHD in the T3 group increased by 2.84-fold (OR, 2.84; 95% CI, 1.36-5.94; P = 0.005). The multifactor linear regression analysis showed each 1-unit increase in TG/HDL-C ratio in the NAFLD + CHD group was associated with a 7.75-point increase in Gensini score (β=7.75, 95% CI 5.35-10.15, P<0.001)., Conclusion: The TG/HDL-C ratio was positively correlated with CHD risk and reflected coronary atherosclerosis severity in NAFLD patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cheng, Yi, Chen, Wei, Su, Chen, Lin, Gu, Li, Xu, Liu and Li.)

Objective: To investigate the characteristic of circulating microparticle in patients with acute myocardial infarction (AMI) and its possible mechanism of promoting coagulation., Methods: A prospective case-control study was conducted. The patients with coronary heart disease admitted to the second department of cardiology in Harbin First Hospital from June to November 2023 were enrolled, and they were grouped according to whether the patients occurred AMI or not. On the day of admission, disseminated intravascular coagulation (DIC) score was calculated. At the same time, fasting venous blood was collected, and the levels of D-dimer, fibrin degradation product (FDP) and the activities of major coagulation factors were detected. The level of circulating microparticle was determined by microparticle trapping method. The microparticle carrying tissue factor (TF + MP) level was detected by tissue factor (TF) dependent F Xa production assay. Spearman correlation method was used to analyze the correlation among the indicators., Results: A total of 52 patients with coronary heart disease were enrolled, including 26 patients in AMI group and 26 patients in non-AMI group. There was no significant difference in gender, age, body mass index (BMI), underlying diseases, smoking history, and pre-admission treatment of patients between the two groups, indicating that the baseline data of the two groups were balanced and comparable. Compared with the non-AMI group, the DIC score and D-dimer, FDP levels in the AMI group were significantly increased [DIC score: 3 (3, 4) vs. 3 (2, 3), D-dimer (mg/L): 8.80 (6.84, 15.66) vs. 2.13 (1.64, 3.86), FDP (mg/L): 30.13 (19.30, 52.54) vs. 20.00 (13.51, 28.37), all P < 0.01], indicating that the degree of coagulation activation in AMI patients was more severe. The consumption of major coagulation factors in the coagulation pathway in the AMI group was heavier than that in the non-AMI group [F II: 59.45% (49.65%, 71.25%) vs. 63.65% (49.98%, 73.22%), F V: 96.95% (73.50%, 112.78%) vs. 105.05% (73.48%, 131.48%), F VII: 42.30% (36.98%, 51.98%) vs. 53.40% (46.58%, 69.88%), F X: 60.90% (48.22%, 80.82%) vs. 73.50% (56.80%, 85.98%), F XI: 82.45% (62.90%, 99.10%) vs. 92.40% (73.90%, 114.25%), F XII: 29.90% (12.42%, 42.38%) vs. 34.65% (16.32%, 48.20%), all P < 0.05]. The circulating TF + MP level in the AMI group was significantly higher than that in the non-AMI group [nmol/L: 0.13 (0.06, 0.20) vs. 0.08 (0.04, 0.15), P < 0.05]. There was no significant difference in the level of circulating microparticle between AMI group and non-AMI group [nmol/L: 1.24 (0.71, 3.77) vs. 1.35 (0.73, 2.14), P > 0.05]. Correlation analysis showed that circulating TF + MP level in the patients with coronary heart disease was significantly positively correlated with coagulation indicator DIC score (r = 0.307, P = 0.027), D-dimer (r = 0.696, P < 0.001) and FDP (r = 0.582, P < 0.001), and there was a strong negative correlation with exogenous pathway factor F VII (r = -0.521, P < 0.001) and common pathway factor F X (r = -0.332, P = 0.016)., Conclusions: The circulating TF + MP level in AMI patients was significantly higher than that in the non-AMI patients. TF + MP may play an important role in activating the extrinsic coagulation pathway, exacerbating coagulation factor consumption, and promoting clot formation during AMI occurrence.

Background and Aim: Accumulating evidence suggests a potential link between thyroid function with hypertension. However, the research results are limited, and there is no research to explore the relationship between central and peripheral thyroid hormones (THs) sensitivity and different grades of hypertension in patients with coronary heart disease (CHD). This study aims to prove the complex interaction between thyroid system and blood pressure, and provides new ideas for the assessment of hypertension in patients with CHD., Methods and Results: Calculate parameters representing central and peripheral sensitivity to THs. Logistic regression analysis was used to analyze the relationship between central and peripheral THs sensitivity of CHD patients and different grades of hypertension, especially in different ages, sexes, blood glucose levels, smoking, and drinking statuses. Among the 34,310 participants, 19,610 (57.16 %) were diagnosed with hypertension. The risk of hypertension and TSHI (OR: 0.88; 95 % CI: 0.87-0.90; P < 0.001), TT4RI (OR: 0.998; 95 % CI: 0.998-0.999; P < 0.001), TFQI (OR: 0.63; 95 % CI: 0.60-0.67; P < 0.001), PTFQI (OR: 0.63; 95 % CI: 0.59-0.67; P < 0.001) was negatively associated. The risk of hypertension was positively associated with FT3/FT4 (OR: 1.20; 95 % CI: 1.17-1.22; P < 0.001). After stratified analysis, these associations remained significant at different ages, sexes, blood glucose levels, grades of hypertension, smoking, and drinking statuses (P < 0.001)., Conclusions: This study shows that the decrease in central THs sensitivity index and the increase in peripheral THs sensitivity index are associated with a higher risk of hypertension in CHD patients., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 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:  Lipoprotein(a), or Lp(a), has been recognized as a strong risk factor for atherosclerotic cardiovascular disease. However, the relationship between Lp(a) and bleeding remains indistinct, especially in the secondary prevention population of coronary artery disease (CAD). This investigation aimed to evaluate the association of Lp(a) with long-term bleeding among patients with CAD., Methods:  Based on a prospective multicenter cohort of patients with CAD consecutively enrolled from January 2015 to May 2019 in China, the current analysis included 16,150 participants. Thus, according to Lp(a) quintiles, all subjects were divided into five groups. The primary endpoint was bleeding at 2-year follow-up, and the secondary endpoint was major bleeding at 2-year follow-up., Results:  A total of 2,747 (17.0%) bleeding and 525 (3.3%) major bleeding were recorded during a median follow-up of 2.0 years. Kaplan-Meier survival analysis showed the highest bleeding incidence in Lp(a) quintile 1, compared with patients in Lp(a) quintiles 2 to 5 ( p  < 0.001), while the incidence of major bleeding seemed similar between the two groups. Moreover, restricted cubic spline analysis suggested that there was an L-shaped association between Lp(a) and 2-year bleeding after adjustment for potential confounding factors, whereas there was no significant association between Lp(a) and 2-year major bleeding., Conclusion:  There was an inverse and L-shaped association of Lp(a) with bleeding at 2-year follow-up in patients with CAD. More attention and effort should be made to increase the clinician awareness of Lp(a)'s role, as a novel marker for bleeding risk to better guide shared-decision making in clinical practice., Competing Interests: None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Aims/Background Coronary heart disease is a common disease in the elderly and has a complex pathogenesis, which complicates the clinical diagnostic process. Thus, enhancing the diagnostic efficiency for coronary heart disease is imperative to improve the life expectancy of the elderly. This study aimed to explore the diagnostic value of multimodal cardiovascular imaging technology coupled with biomarker detection in elderly patients with coronary heart disease. Methods The medical records of 421 patients with suspected coronary heart disease obtained from the geriatric department of the First Affiliated Hospital of Hebei North University from February 2020 to February 2023 were retrospectively analysed. After excluding 10 patients who did not meet the inclusion criteria, the remaining 411 patients were included in this study. The included subjects had undergone coronary computed tomography angiography and were divided into coronary heart disease group (n=208) and non-coronary heart disease group (n=203) according to the diagnostic results. Multimodal cardiovascular imaging (coronary computed tomography angiography and echocardiography) and detection of serum biomarkers such as small dense low-density lipoprotein, lipoprotein a, and gamma-glutamyl transferase were performed in both groups. The clinical indicators of the two groups were compared, and the combined diagnostic efficacy of multimodal cardiovascular imaging and biomarker detection was evaluated. Results Compared to the non-coronary heart disease group, the coronary heart disease group had significantly higher levels of maximum area stenosis, total plaque volume, total plaque burden and fibrotic plaque volume ( p < ..001), and lower left ventricular ejection fraction level ( p < ..001). Additionally, the coronary heart disease group exhibited higher levels of left ventricular end-diastolic volume, left ventricular end-systolic volume and stroke volume than the non-coronary heart disease group ( p < ..001), and had higher levels of small dense low-density lipoprotein, lipoprotein a and gamma-glutamyl transferase ( p < ..001). Our results demonstrated that combined diagnosis had better diagnostic efficacy than individual approaches, marked by higher area under the curve and sensitivity of the former ( p < ..001). Conclusion Multimodal cardiovascular imaging technology combined with biomarker detection can distinctly improve the accuracy of coronary heart disease diagnosis in elderly patients.

Background: Triglyceride-glucose (TyG) index is a surrogate marker of insulin resistance and metabolic abnormalities, which is closely related to the prognosis of a variety of diseases. Patients with both CHD and depression have a higher risk of major adverse cardiovascular and cerebrovascular events (MACCE) and worse outcome. TyG index may be able to predict the adverse prognosis of this special population., Methods: The retrospective cohort study involved 596 patients with both CHD and depression between June 2013 and December 2023. The primary outcome endpoint was the occurrence of MACCE, including all-cause death, stroke, MI and emergent coronary revascularization. The receiver operating characteristic (ROC) curve, Cox regression analysis, Kaplan-Meier survival analysis, and restricted cubic spline (RCS) analysis were used to assess the correlation between TyG index and MACCE risk of in patients with CHD complicated with depression., Results: With a median follow-up of 31 (15-62) months, MACCE occurred in 281(47.15%) patients. The area under the ROC curve of TyG index predicting the risk of MACCE was 0.765(0.726-0.804) ( P <0.01). Patients in the high TyG index group(69.73%) had a significantly higher risk of developing MACCE than those in the low TyG index group(23.63%) ( P <0.01). The multifactorial RCS model showed a nonlinear correlation (nonlinear P <0.01, overall P <0.01), with a critical value of 8.80 for the TyG index to predict the occurrence of MACCE. The TyG index was able to further improve the predictive accuracy of MACCE., Conclusions: TyG index is a potential predictor of the risk of MACCE in patients with CHD complicated with depression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhao, Wang, Chen, Ding, Hou, Gui, Liu, Li, Liu, Sun and Zhao.)

CETP inhibitors are a class of lipid-lowering drugs in development for treatment of coronary heart disease (CHD). Genetic studies in East Asian ancestry have interpreted the lack of CETP signal with low-density lipoprotein cholesterol (LDL-C) and lack of drug target Mendelian randomization (MR) effect on CHD as evidence that CETP inhibitors might not be effective in East Asian participants. Capitalizing on recent increases in sample size of East Asian genetic studies, we conducted a drug target MR analysis, scaled to a standard deviation increase in high-density lipoprotein cholesterol. Despite finding evidence for possible neutral effects of lower CETP levels on LDL-C, systolic blood pressure and pulse pressure in East Asians (interaction p-values < 1.6 × 10 -3 ), effects on cardiovascular outcomes were similarly protective in both ancestry groups. In conclusion, on-target inhibition of CETP is anticipated to decrease cardiovascular disease in individuals of both European and East Asian ancestries., (© 2024. The Author(s).)

Blood cell ratios are a standard clinical index for the assessment of inflammation. Although a large number of epidemiological investigations have shown that inflammation is a potential risk factor for the development of coronary heart disease (CHD), there is not sufficient and direct evidence to confirm the relationship between blood cell ratios and CHD. Therefore, this study aimed to elucidate the effect of blood cell ratios on the incidence of coronary heart disease. This 10-year national study included data from 24,924 participants. The independent variable was blood cell ratios, and the dependent variable was coronary heart diseases (yes or no). The relationship between blood cell ratios and coronary heart disease was verified using baseline characteristic analysis, multivariate logistic regression analysis, smoothed fitted curves, and subgroup analysis. This study found that in multiple logistic regression analysis showed significant positive correlation between monocyte counts × meutrophil counts/lymphocyte counts (SIRI) (OR = 1.495; 95% CI = 1.154-1.938), monocyte-lymphocyte ratio (MLR) (OR = 3.081; 95% CI = 1.476-6.433) and the incidence of CHD; lymphocyte-monocyte ratio (LMR) (OR = 0.928;95% CI = 0.873-0.987), monocyte-lymphocyte ratio (PLR) (OR = 0.997;95% CI = 0.994-1.000) showed negative correlation with CHD. The smoothed curve fitting shows a nonlinear relationship between SIRI, LMR, PLR, and CHD, with an inverted U-shaped curve between SIRI and CHD, an L-shaped angle between LMR and CHD, and a U-shaped curve between PLR and CHD, respectively. Their inflection points are 1.462, 3.75, and 185.714, respectively. SIRI has an inverted U-shaped curve with coronary heart disease, suggesting that low levels of SIRI increase the risk of CHD; LMR with an L-shaped curve with CHD, and PLR with a U-shaped curve with CHD, suggesting that the risk of CHD can be prevented when LMR and PLR are reduced to a certain level. This has positive implications for the prevention and treatment of CHD., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The Triglyceride glucose (TyG) index-related indicators improve risk stratification by identifying individuals prone to atherosclerosis early in life. This study aimed to examine the relation between TyG-waist circumference-to-height ratio (TyG-WHtR) and coronary heart disease., Methods: Data from four National Health and Nutrition Examination Surveys (NHANES) cycles between 2011 and 2018 were used for a cross-sectional study. The association between TyG-WHtR and coronary heart disease risk was examined using a multifactorial logistic regression model, and corresponding subgroup analyses were performed. Nonlinear correlations were analyzed using smooth curve fitting and threshold effects analysis. When nonlinear connections were discovered, appropriate inflection points were investigated using recursive methods., Results: TyG-WHtR and coronary heart disease were significantly positively correlated in the multifactorial logistic regression analysis. Subgroup analyses and interaction tests revealed that gender, age, smoking status, and cancer were not significantly associated with this correlation (P for interaction > 0.05). Furthermore, utilizing threshold effect analysis and smooth curve fitting, a nonlinear connection with an inflection point of 0.36 was observed between TyG-WHtR and coronary heart disease., Conclusions: According to this study, the American population is far more likely to have coronary heart disease if they have higher TyG-WHtR levels., (© 2024. The Author(s).)

Background and Aims: Low-density lipoprotein cholesterol (LDLc) and body mass index (BMI) are not always correlated and their relationship is probably dependent on age, indicating differential age-specific associations of these factors with health outcomes. We aim to discriminate the roles of LDLc and BMI in coronary heart disease (CHD) across different age groups., Methods: This is a prospective cohort study of 368,274 participants aged 38-73 years and free of CHD at baseline. LDLc and BMI were measured at baseline, and incident CHD was the main outcome. Cox proportional hazards model and restricted cubic spline (RCS) regression were used to estimate hazard ratio (HR) and 95% confidence interval (CI) of exposure on CHD., Results: After a mean of 12 years of follow-up, similar relationships of LDLc and BMI with CHD risk were observed in the overall population but in differential age-specific patterns. Across the age groups of <50, 50-54, 55-59, 60-64 and ≥ 65 years, the LDLc-CHD association diminished with the adjusted HRs decreasing from 1.35, 1.26, 1.19, 1.11 to 1.08; while no declining trend was found in BMI-CHD relationship with the adjusted HRs of 1.15, 1.11, 1.12, 1.13 and 1.15, respectively. The interaction and mediation between LDLc and BMI on CHD risk were more pronounced at young-age groups. LDLc-CHD but not BMI-CHD association was dependent on sex, metabolic syndrome and lipid-lowering drugs use., Conclusions: There were differential age-specific associations of LDLc and BMI with the risk of developing CHD, calling for future efforts to discriminate the age-different benefits from lipids management or weight control on the primary prevention for CHD., 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 © 2024 Elsevier B.V. All rights reserved.)

Background: Higher levels of plasma glycine are linked to a reduced risk, while increased levels of total branched-chain amino acids (tBCAAs) are associated with a higher risk of essential hypertension and coronary heart disease (CHD). As these metabolic components are interconnected, analyzing the tBCAAs/glycine ratio may help to understand their interplay in the pathogenesis of cardiovascular disease., Methods: The Cox regression approach was combined with the development of novel genetic tools for assessments of associations between plasma metabolomic data (glycine, tBCAAs, and tBCAAs/glycine ratio) from the UK Biobank and the development of hypertension and CHD. Genome-wide association study was performed on 186 523 White UK Biobank participants to identify new independent genetic instruments for the 2-sample Mendelian randomization analyses. P -gain statistic >10 identified instruments associated with tBCAAs/glycine ratio significantly stronger compared with individual amino acids. Outcomes of genome-wide association study on hypertension and CHD were derived from the UK Biobank (nonoverlapping sample), FinnGen, and CARDIoGRAMplusC4D., Results: The tBCAAs/glycine ratio was prospectively associated with a higher risk of developing hypertension and CHD (hazard ratio quintile Q5 versus Q1, 1.196 [95% CI, 1.109-1.289] and 1.226 [95% CI, 1.160-1.296], respectively). Mendelian randomization analysis demonstrated that tBCAAs/glycine ratio ( P -gain >10) was a risk factor for hypertension (meta-analyzed inverse-variance weighted causal estimate 0.45 log odds ratio/SD (95% CI, 0.26-0.64) and CHD (0.48 [95% CI, 0.29-0.67]) with an absolute effect significantly larger compared with the effect of glycine (-0.06 [95% CI, -0.1 to -0.03] and -0.08 [95% CI, -0.11 to -0.05], respectively) or tBCAAs (0.22 [95% CI, 0.09-0.34] and 0.12 [95% CI, 0.01-0.24], respectively)., Conclusions: The total BCAAs/glycine ratio is a key element of the metabolic signature contributing to hypertension and CHD, which may reflect biological pathways shared by glycine and tBCAAs., Competing Interests: Disclosures None.

Background: The blood-urea-nitrogen (BUN)-to-serum-albumin (ALB) ratio (BAR) has been identified as a novel indicator of both inflammatory and nutritional status, exhibiting a correlation with adverse cardiovascular outcomes. This study aims to investigate the potential predictive value of BAR levels at admission for the development of CIN in patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI)., Methods: Retrospective data were collected from patients who were admitted and underwent CAG or PCI between January 2018 and December 2022 at the Cardiac Medical Center of Union Hospital of Fujian Medical University, and the patients were divided into CIN and non-CIN groups. The BAR was computed by dividing the BUN count by the ALB count. Using multiple variable logistic regression, risk variables associated with the development of CIN were found., Results: A total of 156 patients developed CIN (7.78%). The development of CIN was predicted by a BAR ratio > 4.340 with a sensitivity of 84.0% and a specificity of 70.2%, according to receiver operating characteristic (ROC) analysis. BAR, female gender, diuretic use, and statin medication use were found to be independent predictors of CIN using multifactorial analysis., Conclusions: When patients are receiving CAG/PCI, BAR is a simple-to-use marker that can be used independently to predict the presence of CIN., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background and Aims: Atherosclerosis is the main cause of stroke and coronary heart disease (CHD), both leading mortality causes worldwide. Proteomics, as a high-throughput method, could provide helpful insights into the pathological mechanisms underlying atherosclerosis. In this study, we characterized the associations of plasma protein levels with CHD and with carotid intima-media thickness (CIMT), as a surrogate measure of atherosclerosis., Methods: The discovery phase included 1000 participants from the KORA F4 study, whose plasma protein levels were quantified using the aptamer-based SOMAscan proteomics platform. We evaluated the associations of plasma protein levels with CHD using logistic regression, and with CIMT using linear regression. For both outcomes we applied two models: an age-sex adjusted model, and a model additionally adjusted for body mass index, smoking status, physical activity, diabetes status, hypertension status, low density lipoprotein, high density lipoprotein, and triglyceride levels (fully-adjusted model). The replication phase included a matched case-control sample from the independent KORA F3 study, using ELISA-based measurements of galectin-4. Pathway analysis was performed with nominally associated proteins (p-value < 0.05) from the fully-adjusted model., Results: In the KORA F4 sample, after Bonferroni correction, we found CHD to be associated with five proteins using the age-sex adjusted model: galectin-4 (LGALS4), renin (REN), cathepsin H (CTSH), and coagulation factors X and Xa (F10). The fully-adjusted model yielded only the positive association of galectin-4 (OR = 1.58, 95% CI = 1.30-1.93), which was successfully replicated in the KORA F3 sample (OR = 1.40, 95% CI = 1.09-1.88). For CIMT, we found four proteins to be associated using the age-sex adjusted model namely: cytoplasmic protein NCK1 (NCK1), insulin-like growth factor-binding protein 2 (IGFBP2), growth hormone receptor (GHR), and GDNF family receptor alpha-1 (GFRA1). After assessing the fully-adjusted model, only NCK1 remained significant (β = 0.017, p-value = 1.39e-06). Upstream regulators of galectin-4 and NCK1 identified from pathway analysis were predicted to be involved in inflammation pathways., Conclusions: Our proteome-wide association study identified galectin-4 to be associated with CHD and NCK1 to be associated with CIMT. Inflammatory pathways underlying the identified associations highlight the importance of inflammation in the development and progression of CHD., (© 2024. The Author(s).)

Observational studies indicate that serum sex hormone-binding globulin (SHBG) levels are inversely correlated with blood lipid levels and coronary heart disease (CHD) risk. Given that dyslipidemia is an established risk factor for CHD, we aim to employ Mendelian randomization (MR) in conjunction with mediation analysis to confirm the mediating role of blood lipid levels in the association between SHBG and CHD. First, we assessed the causality between serum SHBG levels and five cardiovascular diseases using univariable MR. The results revealed causality between SHBG levels and reduced risk of CHD, myocardial infarction, as well as hypertension. Specifically, the most significant reduction was observed in CHD risk, with an odds ratio of 0.73 (95% CI 0.63-0.86) for each one-standard-deviation increase in SHBG. The summary-level data of serum SHBG levels and CHD are derived from a sex-specific genome-wide association study (GWAS) conducted by UK Biobank (sample size = 368,929) and a large-scale GWAS meta-analysis (60,801 cases and 123,504 controls), respectively. Subsequently, we further investigated the mediating role of blood lipid level in the association between SHBG and CHD. Mediation analysis clarified the mediation proportions for four mediators: high cholesterol (48%), very low-density lipoprotein cholesterol (25.1%), low-density lipoprotein cholesterol (18.5%), and triglycerides (44.3%). Summary-level data for each mediator were sourced from the UK Biobank and publicly available GWAS. The above results confirm negative causality between serum SHBG levels and the risk of CHD, myocardial infarction, and hypertension, with the causal effect on reducing CHD risk largely mediated by the improvement of blood lipid profiles., (© 2024. The Author(s).)

Long-chain n -3 polyunsaturated fatty acid (PUFA) supplementation has shown potential benefits in the prevention of coronary heart disease (CHD); however, the impact of omega-3 fatty acid levels on CHD risk remains a subject of debate. Here, we aimed to investigate the association between n -3 PUFA levels and the risk of CHD, with particular reference to the subtypes of n -3 PUFA., Methods: Prospective studies and retrospective case-control studies analyzing n -3 PUFA levels in CHD, published up to 30 July 2022, were selected. A random effects meta-analysis was used for pooled assessment, with relative risks (RRs) expressed as 95% confidence intervals (CIs) and standardized mean differences expressed as weight mean differences (WMDs). Subgroup and meta-regression analyses were conducted to assess the impact of n -3 PUFA exposure interval on the CHD subtype variables of the study., Results: We included 20 prospective studies (cohort and nested case-control) and 16 retrospective case-control studies, in which n -3 PUFAs were measured. Higher levels of n -3 PUFAs (ALA, EPA, DPA, DHA, EPA + DHA, total n -3 PUFAs) were associated with a reduced risk of CHD, with RRs (95% CI) of 0.89 (0.81, 0.98), 0.83 (0.72, 0.96); 0.80 (0.67,0.95), 0.75 (0.64, 0.87), 0.83 (0.73, 0.95), and 0.80 (0.70, 0.93), respectively, p < 0.05. CHD patients had significantly lower n -3 PUFA levels compared to healthy controls ( p < 0.05). In the subgroup analysis, a significant inverse trend was found for both fatal CHD and non-fatal CHD with n -3 PUFA (EPA + DHA) levels. Also, the link between n -3 PUFA levels in erythrocytes with total CHD was generally stronger than other lipid pools., Conclusions: n -3 PUFAs are significantly related to CHD risk, and these findings support the beneficial effects of n -3 PUFAs on CHD.

The receptor for advanced glycation endproducts (RAGE) has pro-inflammatory and pro-atherogenic effects. Low plasma levels of soluble RAGE (sRAGE), a decoy receptor for RAGE ligands, have been associated with increased risk for major adverse coronary events (MACE) in the general population. We performed a genome-wide association study to identify genetic determinants of plasma sRAGE in 4338 individuals from the cardiovascular arm of the Malmö Diet and Cancer study (MDC-CV). Further, we explored the associations between these genetic variants, incident first-time MACE and mortality in 24,640 unrelated individuals of European ancestry from the MDC cohort. The minor alleles of four single nucleotide polymorphisms (SNPs): rs2070600, rs204993, rs116653040, and rs7306778 were independently associated with lower plasma sRAGE. The minor T (vs. C) allele of rs2070600 was associated with increased risk for MACE [HR 1.13 95% CI (1.02-1.25), P = 0.016]. Neither SNP was associated with mortality. This is the largest study to demonstrate a link between a genetic sRAGE determinant and CV risk. Only rs2070600, which enhances RAGE function by inducing a Gly82Ser polymorphism in the ligand-binding domain, was associated with MACE. The lack of associations with incident MACE for the other sRAGE-lowering SNPs suggests that this functional RAGE modification is central for the observed relationship., (© 2024. The Author(s).)

Background: Comprehensive blood lipoprotein profiles and their association with incident coronary heart disease (CHD) among racially and geographically diverse populations remain understudied., Methods and Results: We conducted nested case-control studies of CHD among 3438 individuals (1719 pairs), including 1084 White Americans (542 pairs), 1244 Black Americans (622 pairs), and 1110 Chinese adults (555 pairs). We examined 36 plasma lipids, lipoproteins, and apolipoproteins, measured by nuclear magnetic resonance spectroscopy, with incident CHD among all participants and subgroups by demographics, lifestyle, and metabolic health status using conditional or unconditional logistic regression adjusted for potential confounders. Conventionally measured blood lipids, that is, total cholesterol, triglycerides, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol, were each associated with incident CHD, with odds ratios (ORs) being 1.33, 1.32, 1.24, and 0.79 per 1-SD increase among all participants. Seventeen lipoprotein biomarkers showed numerically stronger associations than conventional lipids, with ORs per 1-SD among all participants ranging from 1.35 to 1.57 and a negative OR of 0.78 (all false discovery rate <0.05), including apolipoprotein B100 to apolipoprotein A1 ratio (OR, 1.57 [95% CI, 1.45-1.7]), low-density lipoprotein-triglycerides (OR, 1.55 [95% CI, 1.43-1.69]), and apolipoprotein B (OR, 1.49 [95% CI, 1.37-1.62]). All these associations were significant and consistent across racial groups and other subgroups defined by age, sex, smoking, obesity, and metabolic health status, including individuals with normal levels of conventionally measured lipids., Conclusions: Our study highlighted several lipoprotein biomarkers, including apolipoprotein B/ apolipoprotein A1 ratio, apolipoprotein B, and low-density lipoprotein-triglycerides, strongly and consistently associated with incident CHD. Our results suggest that comprehensive lipoprotein measures may complement the standard lipid panel to inform CHD risk among diverse populations.

Aims: Associations of plasma viscosity and plasma Ig levels (a determinant of viscosity) with incident coronary heart disease (CHD) events; and with CHD, cardiovascular disease (CVD: CHD and stroke) and all-cause mortalities., Methods: Meta-analysis of plasma viscosity levels from the MONitoring of trends and determinants of CArdiovascular (MONICA)/Cooperative Health Research in the Region of Augsburg, MONICA Glasgow and Speedwell Studies; and five other published studies. Meta-analysis of IgA, IgG and IgM levels from the Augsburg, Glasgow and Speedwell studies; and one other published study., Results: Over median follow-up periods of 14-26 years, there were 2270 CHD events, and 4220 all cause deaths in 28 605 participants with baseline plasma viscosity measurements. After adjustment for major risk factors, (HRs; 95% CIs) for a 1 SD increase in viscosity were 1.14 (1.09 to 1.20) for CHD events; and 1.21 (1.17 to 1.25) for all-cause mortality. 821 CHD events and 2085 all-cause deaths occurred in 8218 participants with baseline Ig levels. For CHD events, adjusted HRs for 1 SD increases in IgA, IgG and IgM were, respectively, 0.97 (0.89 to 1.05); 0.95(0.76 to 1.17) and 0.90 (0.79 to 1.03). Corresponding adjusted HRs for all-cause mortality were 1.08 (95% CI 1.02 to 1.13), 1.03 (95% CI 0.94 to 1.14) and 1.01 (95% CI 0.96 to 1.06)., Conclusions: After risk factor adjustment, plasma viscosity was significantly associated with risks of CHD events; and with CHD, CVD and all-cause mortalities. We found no significant association of IgA, IgG or IgM levels with incident CHD events or mortality, except for a borderline association of IgA with all-cause mortality., Competing Interests: Competing interests: MW is a consultant to Amgen and Kirin. No other author declares conflicting interests., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)