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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.)

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 and Aims: Our study examined the trends of cardiovascular health metrics in individuals with coronary heart disease (CHD) and their associations with all-cause and cardiovascular disease mortality in the US., Methods and Results: The cohort study was conducted based on the National Health and Nutrition Examination Survey 1999-2018 and their linked mortality files (through 2019). Baseline CHD was defined as a composite of self-reported doctor-diagnosed coronary heart disease, myocardial infarction, and angina pectoris. Cardiovascular health metrics were assessed according to the American Heart Association recommendations. Long-term all-cause and cardiovascular disease mortality were the primary outcomes. Survey-adjusted Cox regression models were used to estimate hazard ratios and corresponding 95% confidence intervals for the associations between cardiovascular health metrics and all-cause and cardiovascular disease mortality. The prevalence of one or fewer ideal cardiovascular health metrics increased from 14.15% to 22.79% (P < 0.001) in CHD, while the prevalence of more than four ideal cardiovascular health metrics decreased from 21.65% to 15.70 % (P < 0.001) from 1999 to 2018, respectively. Compared with CHD participants with one or fewer ideal cardiovascular health metrics, those with four or more ideal cardiovascular health metrics had a 35% lower risk (hazard ratio, 0.65; 95% confidence interval: 0.51, 0.82) and a 44% lower risk (0.56; 0.38, 0.84) in all-cause and cardiovascular disease mortality, respectively., Conclusion: Substantial declines were noted in ideal cardiovascular health metrics in US adults with CHD. A higher number of cardiovascular health metrics was associated with lower all-cause and cardiovascular disease mortality in them., Competing Interests: Conflict of interest None declared., (Copyright © 2024 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.)

Aims: To evaluate the correlation between left atrial stiffness index (LASI) and left ventricular diastolic function in patients with coronary heart disease (CHD) by Autostrain LA technique., Methods: This was a retrospective analysis that included a total of 82 CHD patients who had suitable image quality for left atrial strain measurement. According to the 2016 ASE/EACVI guidelines for the echocardiographic assessment of diastolic dysfunction, the patients were divided into three groups: normal left ventricular diastolic function group (n = 26), indeterminate left ventricular diastolic function (n = 36), and left ventricular diastolic dysfunction (LVDD) (n = 20). The left atrial conduit strain (LAScd), Left atrial contractile strain (LASct), left atrial reservoir strain (LASr) and its derived parameters, including LASI and left atrial filling index (LAFI), were compared among the three groups. Furthermore, we conduct a correlation analysis between LASI and left ventricular diastolic function in patients with CHD., Results: LASr and LAScd in normal group were higher than those in indeterminate group, LASr and LAScd in indeterminate group were higher than those in LVDD group, LASI in normal group was lower than that in indeterminate group, and LASI in indeterminate group was lower than that in LVDD group (P < 0.001). LASct in both normal and indeterminate groups was higher than that in LVDD group (P < 0.05). The LAFI of normal group was lower than that of indeterminate group and LVDD group (P < 0.001). LASI was positively correlated with E/e'(r = 0.822) (P < 0.001). LASr and E/e' were negatively correlated (r = -0.637) (P < 0.001)., Conclusion: LASI is closely related to the changes of left ventricular diastolic function in CHD patients., (© 2024. The Author(s).)

Background: Social determinants of health (SDoH) are associated with cardiovascular risk factors and outcomes; however, they are absent from risk prediction models. We aimed to assess if the addition of SDoH improves the predictive ability of the MESA (Multi-Ethnic Study of Atherosclerosis) Risk Score., Methods and Results: This was a community-based prospective population cohort study that enrolled 6286 men and women, ages 45-84 years, who were free of clinical coronary heart disease (CHD) at baseline. Data from 10-year follow-up were examined for CHD events, defined as myocardial infarction, fatal CHD, resuscitated cardiac arrest, and revascularization in cases of anginal symptoms. Participants included 53% women with average age of 62 years. When adjusting for traditional cardiovascular risk factors, SDoH, and coronary artery calcium, economic strain, specifically low family income, was associated with a greater risk of CHD events (hazard ratio [HR], 1.42 [95% CI, 1.17-1.71], P value<0.001). Area under the curve of risk prediction with SDoH was 0.822, compared with 0.816 without SDoH. The calibration slope was 0.860 with SDoH and 0.878 in the original model., Conclusions: Significant associations were found between economic/financial SDoH and CHD risk factors and outcomes. Incorporation of SDoH into the MESA Risk Score did not improve predictive ability of the model. Our findings do not support the incorporation of SDoH into current risk prediction algorithms.

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.)

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.)

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.

Introduction: The cost of secondary prevention of coronary heart disease (CHD) is continuing to increase, with a substantial portion of this acceleration being driven by the expense of confirmatory diagnostic testing. Conceivably, newly developed precision epigenetic technologies could drive down these costs. However, at the current time, their impact on overall expense for CHD care is poorly understood. We hypothesized that the use of a newly developed, highly sensitive, and specific epigenetic test, PrecisionCHD, could decrease the costs of secondary prevention., Methods: To test this hypothesis, we constructed a budget impact analysis using a cost calculation model that examined the effects of substituting PrecisionCHD for conventional CHD diagnostic tests on the expenses of the initial evaluation and first year of care of stable CHD using a 1-year time horizon with no discounting., Results: The model projected that for a commercial insurer with one million members, full adoption of PrecisionCHD as the primary method of initial CHD assessment would save approximately $113.6 million dollars in the initial year., Conclusion: These analyses support the use of precision epigenetic methods as part of the initial diagnosis and care of stable CHD and can meaningfully reduce cost. Real-world pilots to test the reliability of these analyses are indicated., (© 2024. The Author(s).)

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).)

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.

Background: The triglyceride glucose-body mass index (TyG-BMI) is recognized as a reliable surrogate for evaluating insulin resistance and an effective predictor of cardiovascular disease. However, the link between TyG-BMI index and adverse outcomes in heart failure (HF) patients remains unclear. This study examines the correlation of the TyG-BMI index with long-term adverse outcomes in HF patients with coronary heart disease (CHD)., Methods: This single-center, prospective cohort study included 823 HF patients with CHD. The TyG-BMI index was calculated as follows: ln [fasting triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2] × BMI. To explore the association between the TyG-BMI index and the occurrences of all-cause mortality and HF rehospitalization, we utilized multivariate Cox regression models and restricted cubic splines with threshold analysis., Results: Over a follow-up period of 9.4 years, 425 patients died, and 484 were rehospitalized due to HF. Threshold analysis revealed a significant reverse "J"-shaped relationship between the TyG-BMI index and all-cause mortality, indicating a decreased risk of all-cause mortality with higher TyG-BMI index values below 240.0 (adjusted model: HR 0.90, 95% CI 0.86-0.93; Log-likelihood ratio p = 0.003). A distinct "U"-shaped nonlinear relationship was observed with HF rehospitalization, with the inflection point at 228.56 (adjusted model: below: HR 0.95, 95% CI 0.91-0.98; above: HR 1.08, 95% CI 1.03-1.13; Log-likelihood ratio p < 0.001)., Conclusions: This study reveals a nonlinear association between the TyG-BMI index and both all-cause mortality and HF rehospitalization in HF patients with CHD, positioning the TyG-BMI index as a significant prognostic marker in this population., (© 2024. The Author(s).)

Background: Premature coronary heart disease (CHD) is a major cause of death in women. We aimed to characterize biomarker profiles of women who developed CHD before and after age 65 years., Methods: In the Women's Health Study (median follow-up 21.5 years), women were grouped by age and timing of incident CHD: baseline age <65 years with premature CHD by age 65 years (25 042 women; 447 events) and baseline age ≥65 years with nonpremature CHD (2982 women; 351 events). Associations of 44 baseline plasma biomarkers measured using standard assays and a nuclear magnetic resonance (NMR)-metabolomics assay were analyzed using Cox models adjusted for clinical risk factors., Results: Twelve biomarkers showed associations only with premature CHD and included lipoprotein(a), which was associated with premature CHD [adjusted hazard ratio (HR) per SD: 1.29 (95% CI 1.17-1.42)] but not with nonpremature CHD [1.09(0.98-1.22)](Pinteraction = 0.02). NMR-measured lipoprotein insulin resistance was associated with the highest risk of premature CHD [1.92 (1.52-2.42)] but was not associated with nonpremature CHD (Pinteraction <0.001). Eleven biomarkers showed stronger associations with premature vs nonpremature CHD, including apolipoprotein B. Nine NMR biomarkers showed no association with premature or nonpremature CHD, whereas 12 biomarkers showed similar significant associations with premature and nonpremature CHD, respectively, including low-density lipoprotein (LDL) cholesterol [1.30(1.20-1.45) and 1.22(1.10-1.35)] and C-reactive protein [1.34(1.19-1.50) and 1.25(1.08-1.44)]., Conclusions: In women, a profile of 12 biomarkers was selectively associated with premature CHD, driven by lipoprotein(a) and insulin-resistant atherogenic dyslipoproteinemia. This has implications for the development of biomarker panels to screen for premature CHD., (© Association for Diagnostics & Laboratory Medicine 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The number of older adults age ≥75 with chronic coronary disease (CCD) continues to rise. CCD is a major contributor to morbidity, mortality, and disability in older adults. Older adults are underrepresented in randomized controlled trials of CCD, which limits generalizability to older adults living with multiple chronic conditions and geriatric syndromes. This review discusses the presentation of CCD in older adults, reviews the guideline-directed medical and invasive therapies, and recommends a patient-centric approach to making treatment decisions., Competing Interests: Disclosure Drs E.S. Fishman and A.P. Ambrosini report no disclosures. A.A. Damluji: Dr A.A. Damluji receives research funding from the Pepper Scholars Program of the Johns Hopkins University Claude D. Pepper Older Americans Independence Center, United States funded by the National Institute on Aging P30-AG021334 and receives mentored patient-oriented research career development award from the National Heart, Lung, and Blood Institute, United States K23-HL153771 to 01. M.G. Nanna: Dr M.G. Nanna reports current research support from the American College of Cardiology Foundation, United States supported by the George F. and Ann Harris Bellows Foundation, the Patient-Centered Outcomes Research Institute, United States (PCORI), the Yale Claude D. Pepper Older Americans Independence Center (P30AG021342), and the National Institute on Aging/National Institutes of Health from R03AG074067 (GEMSSTAR award). Consulting from Heartflow, Inc, Merck., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Aims: Coronary heart disease (CHD) is a condition that carries a high risk of mortality and is associated with aging. CHD is characterized by the chronic inflammatory response of the coronary intima. Recent studies have shown that the methylation level of blood mononuclear cell DNA is closely associated with adverse events in CHD, but the roles and mechanisms of DNA methylation in CHD remain elusive., Methods and Results: In this study, the DNA methylation status within the epigenome of human coronary tissue in the sudden coronary death (SCD) group and control (CON) group of coronary heart disease was analyzed using the Illumina® Infinium Methylation EPIC BeadChip (850 K chip), resulting in the identification of a total of 2553 differentially methylated genes (DMGs). The differentially methylated genes were then subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and significant differential DNA methylation was found. Among the differentially hypomethylated genes were GAL-8, LTF, and RFPL3, while the highly methylated genes were TMEM9B, ANK3, and C6orF48. These genes were mainly enriched in 10 significantly enriched pathways, such as cell adhesion junctions, among which the differentially methylated gene GAL-8 was involved in inflammatory pathway signaling. For functional analysis of GAL-8, we first examined the differences in GAL-8 promoter methylation levels among different subgroups of human coronary tissue in the CON, CHD, and SCD groups using pyrophosphate sequencing. The results revealed reduced GAL-8 promoter methylation levels in the SCD group, while the difference between the CHD and CON groups was not statistically significant (P > 0.05). The reduced GAL-8 promoter methylation level was associated with upregulated GAL-8 expression, which led to increased expression of the inflammatory markers TNF-α, IL-1β, MCP-1, MIP-2, MMP-2, and MMP-9. This enhanced inflammatory response contributed to the accumulation of foam cells, thickening of the intima of human coronary arteries, and increased luminal stenosis, which promoted the occurrence of sudden coronary death. Next, we found that GAL-8 promoter methylation levels in PBMC were consistent with human coronary tissue. The unstable angina group (UAP) had significantly lower GAL-8 promoter methylation levels than stable angina (SAP) and healthy controls (CON) (P < 0.05), and there was a significant correlation between reduced GAL-8 promoter methylation levels and risk factors for coronary heart disease. These findings highlight the association between decreased GAL-8 promoter methylation and the presence of coronary heart disease risk factors. ROC curve analysis suggests that methylation of the GAL 8 promoter region is an independent risk factor for CHD. In conclusion, our study confirmed differential expression of GAL-8, LTF, MUC4D, TMEM9B, MYOM2, and ANK3 genes due to DNA methylation in the SCD group. We also established the consistency of GAL-8 promoter methylation alterations between human coronary tissue and patient peripheral blood monocytes. The decreased methylation level of the GAL-8 promoter may be related to the increased expression of GAL-8 and the coronary risk factors., Conclusions: Accordingly, we hypothesized that reduced levels of GAL-8 promoter methylation may be an independent risk factor for adverse events in coronary heart disease., Competing Interests: Declaration of competing interest Bing Xia, Yanlin Lu, Jingwei Liang contributed equally to this work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Inflammatory illnesses, such as periodontitis and atherosclerotic coronary heart disease (ASCHD), trigger the production of pro-inflammatory mediators. The aim of this study was to assess the accuracy of using salivary interleukin-1β (IL-1β), interleukin-18 (IL-18), and gasdermin D (GSDMD) in discerning patients with periodontitis with and without ASCHD from healthy individuals, and to assess their correlation with clinical periodontal parameters and low-density lipoprotein (LDL) levels. The study involved 120 participants: 30 were healthy subjects (control group, C), 30 had generalized periodontitis (group P), 30 had ASCHD and clinically healthy periodontium (group AS-C), and 30 had ASCHD and generalized periodontitis (group AS-P). Saliva and blood samples were collected, and periodontal characteristics such as plaque index, bleeding on probing, probing pocket depth, and clinical attachment loss were examined. IL-1β, IL-18, and GSDMD levels from saliva were determined using ELISA. LDL levels were determined from the blood samples. Groups P, AS-C, and AS-P had higher levels of salivary IL-1β, IL-18, and GSDMD than group C. The receiver operating characteristic (ROC) curves of all biomarkers showed high diagnostic accuracy, with a significant positive correlation with the clinical parameters and LDL levels. The observed correlations between the studied pro-inflammatory mediators and disease severity suggest that these biomarkers could serve as indicators of disease progression in conditions such as periodontitis and ASCHD., Competing Interests: The authors declare no conflict of interest., (© 2024 by the authors.)

MicroRNA-33b (miR-33b) affected various biological pathways in regulating cholesterol homeostasis which may link to the pathogenesis of atherosclerotic lesions. However, whether this marker is associated with the presence and severity of coronary heart disease (CHD) is undetermined. We aim to explore the diagnostic value of circulating miR-33b level in the presence and severity of CHD. Altogether 320 patients were enrolled, including 240 patients diagnosed with CHD while 80 were classified as controls after CAG examination. Circulating miR-33b level was analyzed in all subjects, the Gensini score was calculated to assess the severity of stenotic lesions. The association between miR-33b and the presence and severity of CHD was analyzed, and the diagnostic potential of miR-33b of CHD was performed by the receiver operating characteristic (ROC) analysis. The CHD group had higher miR-33b levels ( p  < 0.001), and the miR-33b content significantly elevated following an increasing Gensini score ( p for trend < 0.001). After adjustments for potential risk factors, such as several blood lipid markers, miR-33b remained a significant determinant for CHD ( p  < 0.001). ROC analysis disclosed that the AUC was 0.931. The optimal cutoff value of miR-33b was with a sensitivity of 81.3% and a specificity of 98.7% in differentiating CHD. It can prognosticate that the higher level of miR-33b was linked to increased severity of disease in CHD patients. Thus, the application of this marker might assist in the diagnosis and classification of CHD patients. Nevertheless, additional studies with larger sample sizes will be required to verify these results.

Nocturnal blood pressure and nighttime dipping patterns are associated with the occurrence of cardiovascular events. However, there is few research on whether riser pattern is associated with the poor prognosis of patients with coronary heart disease (CHD) and hypertension independent of nighttime systolic blood pressure (SBP). This prospective and observational clinical study included 568 hospitalized patients with CHD and hypertension. All patients underwent 24-h ambulatory blood pressure (BP) monitoring during their hospitalization. Multivariate adjusted Cox proportional hazard models were utilized to examine the associations of nocturnal blood pressure and dipping status with primary endpoint events. Additionally, Harrell's C-statistics were employed to compare the discriminative ability of each model. During the 1-year follow-up period, 64 (11.3%) primary endpoint events were recorded, including 55 (9.7%) atherosclerotic cardiovascular disease (ASCVD) events. After adjusting for demographic and clinical risk variables, nighttime SBP was significantly related to the risk of incident primary endpoint events [per 20 mm Hg increase: hazard ratio (HR) = 1.775, 95% confidence interval (CI) 1.256-2.507]. The riser pattern group exhibited a significantly higher risk for primary endpoint events compared to the dipper pattern group, even after adjusting for office SBP (HR: 2.687, 95% CI: 1.015-7.110, p = .047). Furthermore, the addition of nighttime SBP or dipping status to the base model yielded statistically significant increments in C-statistic values (p = .036 and p = .007). However, adding both nighttime SBP and dipping status did not significantly enhance the model's performance in predicting the risk of primary endpoint events and ASCVD events according to the C-index (p = .053 and p = .054), which meant that the riser pattern group did not exhibit a significantly higher risk for primary endpoint events compared to the dipper pattern group after adjusting for nighttime SBP. In conclusion, nocturnal SBP and riser pattern demonstrated an association with adverse prognosis in patients with CHD and hypertension. Notably, nocturnal SBP proved to be a more reliable predictor than dipping status., (© 2024 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

It aimed to explore the correlation of Glu504Lys locus mutation of aldehyde dehydrogenase-2 (ALDH2) with coronary heart disease (CHD) based on gold magnetic nanoparticles (GMNPs) chromatography and amplification refractory mutation system-PCR (ARMS-PCR). 120 CHD patients admitted to the cardiovascular Department of Wenling First People's Hospital affiliated to Wenzhou Medical University from December 2020 to December 2021 were selected as Case group and 80 non-CHD patients admitted during the same period were selected as Ctrl group. The venous blood and indexes of Total Cholesterol (TC), Triglyceride (TG), Low Density Lipoprotein Cholesterol (LDL-C), High Density Lipoprotein Cholesterol (HDL-C), and Fasting Blood Glucose (FBS) were collected. The ARMS-PCR GMNPs chromatography based on ARMS-PCR and immunochromatography assay was adopted to detect gene polymorphism of ALDH2. Correlation between ALDH2 gene polymorphism and risk factors of CHD was analyzed via logistic regression. In contrast to Ctrl group, the genotypes of GG, GA, and AA in Case group were evidently different (P < 0.05), and the frequency of A allelic gene was obviously increased (P < 0.05). Under the dominant model, frequency of GA + AA genotype in Case group was remarkably higher in contrast to Ctrl group (P < 0.05). Under the recessive model, there was no obvious difference in genotype frequency between two groups. In contrast to Ctrl group, TC, LDL-C, and FBS in Case group were notably increased (P < 0.05), while HDL-C was notably decreased (P < 0.05). The distribution frequency of abnormal LDL-C, HDL-C, and FBS in Case group was notably higher in contrast to Ctrl group (P < 0.05). LDL-C and FBS had no obvious effect on the genotypes and frequency distribution of alleles in CHD patients. However, the frequency distribution of genotypes of GA and AA and A allelic gene in patients with abnormal HDL-C was notably lower in contrast to those with normal HDL-C (P < 0.05). Logistic regression analysis showed that abnormal HDC-C with A allelic gene were independent risk factors for CHD (P = 0.001, OR = 1.934). The gene polymorphism of Glu504Lys locus of ALDH2 was closely related to the pathogenesis of CHD, A allelic gene may be a susceptibility gene for CHD, and patients with abnormal HDC-C and carried A allelic gene had relatively higher incidence of CHD., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The aim of this study was to comprehensively assess the causal relationship between the overall genetic effect of circulating ApoE levels and panvascular lesions using newer genome-wide association data and two-sample bidirectional Mendelian randomization (MR) analysis. Two-way MR using single-nucleotide polymorphisms of circulating ApoE as instrumental variables was performed using the highest-priority Genome-wide association study (GWAS) data, with factor-adjusted and data-corrected statistics, to estimate causal associations between circulating ApoE levels and 10 pan-vascular diseases in > 500,000 UK Biobank participants, > 400,000 participants of Finnish ancestry, and numerous participants in a consortium of predominantly European ancestry. Meta-analysis was conducted to assess positive results. After correcting for statistical results, elevated circulating ApoE levels were shown to have a significant protective effect against Cerebral ischemia (CI) [IVW odds ratio (OR) 0.888, 95% Confidence Interval (CI): 0.823-0.958, p = 2.3 × 10 -3 ], Coronary heart disease [IVW OR 0.950,95% CI: 0.924-0.976, p = 2.0 × 10 -4 ] had a significant protective effect and potentially suggestive protective causality against Angina pectoris [IVW odds ratio (OR) 0.961, 95%CI: 0.931-0.991, p = 1.1 × 10 -2 ]. There was a potential causal effect for increased risk of Heart failure (HF) [IVW ratio (OR) 1.040, 95%CI: 1.006-1.060, p = 1.8 × 10 -2 ]. (Bonferroni threshold p < 0.0026, P FDR  < 0.05) Reverse MR analysis did not reveal significant evidence of a causal effect of PVD on changes in circulating ApoE levels. Meta-analysis increases reliability of results. Elevated circulating ApoE levels were particularly associated with an increased risk of heart failure. Elevated ApoE levels reduce the risk of cerebral ischemia, coronary heart disease, and angina pectoris, reflecting a protective effect. The possible pathophysiological role of circulating ApoE levels in the development of panvascular disease is emphasized., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Investigating the correlation between blood cadmium levels, platelet characteristics, and susceptibility to coronary heart disease (CHD). Utilized NHANES 2005-2018 data with covariates such as age, sex, race, marital status, and socio-economic status. Blood cadmium served as the independent variable, while platelet count (PC) and mean platelet volume (MPV) were dependent variables. The average age of the participants was 68.77 ± 11.03 years, and 67.4% of them were male. The mean values for WBC, MPV, PC, and blood cadmium were 7.53 ± 3.36 × 10 3 cells/µL, 11.33 ± 0.27fL, 57.61 ± 5.34 × 10 3 cells/µL, and 2.58 ± 0.61 µg/L, respectively. Adjusting for other variables revealed increased MPV and PC with rising blood cadmium levels in cardiac patients, indicating a higher risk of CHD in those with elevated blood cadmium. The average age of the participants was 68.77 ± 11.03 years, and 67.4% of them were male. The mean values for WBC, MPV, PC, and blood cadmium were 7.53 ± 3.36 × 10 3 cells/µL, 11.33 ± 0.27fL, 57.61 ± 5.34 × 10 3 cells/µL, and 2.58 ± 0.61 µg/L, respectively. Adjusting for other variables revealed increased MPV and PC with rising blood cadmium levels in cardiac patients, indicating a higher risk of CHD in those with elevated blood cadmium. This study enhances understanding of how cadmium impacts platelet characteristics, contributing to increased CHD risk, providing insights for primary prevention strategies., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Telomere Length (TL), a marker of cellular aging, holds promise as a biomarker to elucidate the molecular mechanism of diabetes. This study aimed to investigate whether shorter telomeres are associated with a higher risk of type 2 diabetes mellitus (T2DM) incidence in patients with coronary heart disease; and to determine whether the most suitable dietary patterns, particularly a Mediterranean diet or a low-fat diet, can mitigate the development of diabetes in these patients after a follow-up period of five years., Methods: The CORonary Diet Intervention with Olive oil and cardiovascular PREVention study (CORDIOPREV study) was a single-centre, randomised clinical trial done at the Reina Sofia University Hospital in Córdoba, Spain. Patients with established coronary heart disease (aged 20-75 years) were randomly assigned in a 1:1 ratio by the Andalusian School of Public Health to receive two healthy diets. Clinical investigators were masked to treatment assignment; participants were not. Quantitative-PCR was used to assess TL measurements., Findings: 1002 patients (59.5 ± 8.7 years and 82.5% men) were enrolled into Mediterranean diet (n = 502) or a low-fat diet (n = 500) groups. In this analysis, we included all 462 patients who did not have T2DM at baseline. Among them, 107 patients developed T2DM after a median of 60 months. Cox regression analyses showed that patients at risk of short telomeres (TL < percentile 20th) are more likely to experience T2DM than those at no risk of short telomeres (HR 1.65, p-value 0.023). In terms of diet, patients at high risk of short telomeres had a higher risk of T2DM incidence after consuming a low-fat diet compared to patients at no risk of short telomeres (HR 2.43, 95CI% 1.26 to 4.69, p-value 0.008), while no differences were observed in the Mediterranean diet group., Conclusion: Patients with shorter TL presented a higher risk of developing T2DM. This association could be mitigated with a specific dietary pattern, in our case a Mediterranean diet, to prevent T2DM in patients with coronary heart disease., Trial Registration: Clinicaltrials.gov number NCT00924937., (© 2024. The Author(s).)

The clinical data of coronary heart disease(CHD) patients treated in the First Affiliated Hospital of Guangzhou University of Chinese Medicine and Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine from January 2022 to March 2023 were retrospectively collected. This study involved the descriptive analysis of demographic characteristics, clinical symptoms, and tongue and pulse features. The χ~2 test was conducted to analyze the distribution of syndrome elements and their combinations at diffe-rent stages of CHD, so as to reveal the clinical characteristics and syndrome patterns at various pathological stages of CHD. This study extracted 28 symptom entries, 10 tongue manifestation entries, and 7 pulse manifestation entries, summarized the 5 main disease locations of the heart, lung, liver, spleen, and kidney, and the 8 main disease natures of blood stasis, phlegm turbidity, Qi stagnation, heat(fire), fluid retention, Qi deficiency, Yin deficiency, and Yang deficiency and 8 combinations of disease natures. The χ~2 test showed significant differences in the distribution of syndrome elements including the lung, liver, spleen, kidney, blood stasis, heat(fire), Qi stagnation, heat syndrome, water retention, Qi deficiency, Yin deficiency, and Yang deficiency between different disease stages. Specifically, the liver, blood stasis, heat(fire), and Qi stagnation accounted for the highest proportion during unstable stage, and the lung, spleen, kidney, water retention, Qi deficiency, Yin deficiency, and Yang deficiency accounted for the highest proportion at the end stage. The distribution of Qi deficiency varied in the different time periods after percutaneous coronary intervention(PCI). As shown by the χ~2 test of the syndrome elements combination, the distribution of single disease location, multiple disease locations, single disease nature, double disease natures, multiple natures, excess syndrome, and mixture of deficiency and excess varied significantly at different stages of CHD. Specifically, single disease location, single disease nature, and excess syndrome accounted for the highest proportion during the stable stage, and double disease natures accounted for the highest proportion during the unstable stage. Multiple disease locations, multiple disease natures, and mixture of deficiency and excess accounted for the highest proportion during the end stage. In conclusion, phlegm turbidity and blood stasis were equally serious during the stable stage, and a pathological mechanism caused by blood stasis and toxin existed during the unstable stage. The overall Qi deficiency worsened after PCI, and the end stage was accompanied by the Yin and Yang damage and the aggravation of water retention. There were significant differences in the distribution of clinical characteristics and syndrome elements at different stages of CHD. The pathological process of CHD witnessed the growth and decline of deficiency and excess and the combination of phlegm turbidity and blood stasis, which constituted the basic pathogenesis.

Background: Studies on the relationship between insulin resistance (IR) surrogates and long-term all-cause mortality in patients with coronary heart disease (CHD) and hypertension are lacking. This study aimed to explore the relationship between different IR surrogates and all-cause mortality and identify valuable predictors of survival status in this population., Methods: The data came from the National Health and Nutrition Examination Survey (NHANES 2001-2018) and National Death Index (NDI). Multivariate Cox regression and restricted cubic splines (RCS) were performed to evaluate the relationship between homeostatic model assessment of IR (HOMA-IR), triglyceride glucose index (TyG index), triglyceride glucose-body mass index (TyG-BMI index) and all-cause mortality. The recursive algorithm was conducted to calculate inflection points when segmenting effects were found. Then, segmented Kaplan-Meier analysis, LogRank tests, and multivariable Cox regression were carried out. Receiver operating characteristic (ROC) and calibration curves were drawn to evaluate the differentiation and accuracy of IR surrogates in predicting the all-cause mortality. Stratified analysis and interaction tests were conducted according to age, gender, diabetes, cancer, hypoglycemic and lipid-lowering drug use., Results: 1126 participants were included in the study. During the median follow-up of 76 months, 455 participants died. RCS showed that HOMA-IR had a segmented effect on all-cause mortality. 3.59 was a statistically significant inflection point. When the HOMA-IR was less than 3.59, it was negatively associated with all-cause mortality [HR = 0.87,95%CI (0.78, 0.97)]. Conversely, when the HOMA-IR was greater than 3.59, it was positively associated with all-cause mortality [HR = 1.03,95%CI (1.00, 1.05)]. ROC and calibration curves indicated that HOMA-IR was a reliable predictor of survival status (area under curve = 0,812). No interactions between HOMA-IR and stratified variables were found., Conclusion: The relationship between HOMA-IR and all-cause mortality was U-shaped in patients with CHD and hypertension. HOMA-IR was a reliable predictor of all-cause mortality in this population., (© 2024. The Author(s).)

Aims: The extent to which the contribution of pregnancy loss to cardiovascular diseases (CVDs) can be explained by metabolic disorders is poorly elucidated but holds insights for reducing long-term cardiovascular risk. The aim of this study is to investigate the mediating effects of hypertension, diabetes mellitus (DM), and lipoprotein metabolism disorders on the association of miscarriage and stillbirth with coronary heart disease (CHD), stroke, heart failure, atrial fibrillation, and composite outcomes., Methods and Results: A total of 163 283 ever-gravid women (age 55.3 ± 7.9 years) from the UK Biobank cohort without established metabolic disorders and CVDs were included and followed from 2007 to 2010 baseline until December 2020. Causal mediation analyses were used to estimate the proportion mediated. Hypertension mediated 11.1% (95% confidence interval, 3.7-18.5%) of the association between a history of miscarriage and incident CHD. Approximately, 9.5% (4.1-14.8%) of the effect of recurrent miscarriages on incident CHD was via hypertension, 8.4% (2.5-14.3%) of the effect was via lipoprotein metabolism disorders, 1.7% (0.5-2.9%) of the effect was via DM, and 10.7% (0.2-21.1%) of the effect of recurrent miscarriages on incident stroke was via hypertension. Hypertension mediated the largest proportion of effect for the atherosclerotic cardiovascular event (15.5% for a history of miscarriage and 9.4% for recurrent miscarriages), followed by lipoprotein metabolism disorders and DM., Conclusion: Hypertension, DM, and lipoprotein metabolism disorders mediated the association between miscarriage and various cardiovascular outcomes in later life. In particular, hypertension mediated a large proportion of the relationship between miscarriage and atherosclerotic CVD., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The purpose of this study was to look at any connections that could exist between neutrophil-lymphocyte ratio and coronary heart disease. We performed a cross-sectional research of 13732 participants in the National Health and Nutrition Examination Survey who were 40 or older. Multivariate logistic regression models investigated the relationship between neutrophil-to-lymphocyte ratio levels and coronary heart disease risk. To investigate potential nonlinear connections, smoothed curve fitting was used. When a nonlinear relationship was discovered, the inflexion point was determined using a recursive method. After controlling for relevant confounders, neutrophil-to-lymphocyte ratio was independently linked to a higher risk of coronary heart disease (OR = 1.74, 95% CI:1.30-2.33, P = 0.0002). Subgroup analyses showed statistically significant positive associations between neutrophil-to-lymphocyte ratio and coronary heart disease risk in women (OR = 1.25, 95% CI:1.09-1.43), participants 60 years of age and older (OR = 1.09, 95% CI:1.00-1.19), smoking status for every day or not at all (OR = 1.23, 95% CI:1.00-1.52; OR = 1.09, 95% CI:1.00-1.19), alcohol use status for moderate alcohol use (OR = 1.11, 95% CI:1.00-1.22), body mass index >30 kg/m2 (OR = 1.42, 95% CI:1.10-1.82), hypertensive (OR = 1.11, 95% CI:1.02-1.22), and individuals without diabetes (OR = 1.17, 95% CI:1.06-1.31). A positive correlation between neutrophil-to-lymphocyte ratio levels and coronary heart disease risk was also seen by smoothing curve fitting, with an inflexion point of 1.08 that was statistically significant (P<0.05). Our research shows elevated neutrophil-to-lymphocyte ratio levels are linked to a higher risk of coronary heart disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang 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: Dyslipidemia is an independent risk factor for coronary heart disease (CHD). Standard lipid panel cannot capture the complexity of the blood lipidome (ie, all molecular lipids in the blood). To date, very few large-scale epidemiological studies have assessed the full spectrum of the blood lipidome on risk of CHD, especially in a longitudinal setting., Methods and Results: Using an untargeted liquid chromatography-mass spectrometry, we repeatedly measured 1542 lipid species from 1835 unique American Indian participants who attended 2 clinical visits (≈5.5 years apart) and followed up to 17.8 years in the Strong Heart Family Study (SHFS). We first identified baseline lipid species associated with risk of CHD, followed by replication in a European population. The model adjusted for age, sex, body mass index, smoking, hypertension, diabetes, low-density lipoprotein cholesterol, estimated glomerular filtration rate, education, and physical activity at baseline. We then examined the longitudinal association between changes in lipid species and changes in cardiovascular risk factors during follow-up. Multiple testing was controlled by the false discovery rate. We found that baseline levels of multiple lipid species (eg, phosphatidylcholines, phosphatidylethanolamines, and ceramides) were associated with the risk of CHD and improved the prediction accuracy over conventional risk factors in American Indian people. Some identified lipids in American Indian people were replicated in European people. Longitudinal changes in multiple lipid species (eg, acylcarnitines, phosphatidylcholines, and triacylglycerols) were associated with changes in cardiovascular risk factors., Conclusions: Baseline plasma lipids and their longitudinal changes over time are associated with risk of CHD. These findings provide novel insights into the role of dyslipidemia in CHD.

Background: Coronary heart disease (CHD) is a major global health concern, especially among individuals with type 2 diabetes (T2D). Given the crucial role of proteins in various biological processes, this study aimed to elucidate the aetiological role and predictive performance of protein biomarkers on incident CHD in individuals with and without T2D., Methods: The discovery cohort included 1492 participants from the Cooperative Health Research in the Region of Augsburg (KORA) S4 study with 147 incident CHD cases (45 vs. 102 cases in the group with T2D and without T2D, respectively) during 15.6 years of follow-up. The validation cohort included 888 participants from the KORA-Age1 study with 70 incident CHD cases (19 vs. 51 cases in the group with T2D and without T2D, respectively) during 6.9 years of follow-up. We measured 233 plasma proteins related to cardiovascular disease and inflammation using proximity extension assay technology. Associations of proteins with incident CHD were assessed using Cox regression and Mendelian randomization (MR) analysis. Predictive models were developed using priority-Lasso and were evaluated on top of Framingham risk score variables using the C-index, category-free net reclassification index (cfNRI), and relative integrated discrimination improvement (IDI)., Results: We identified two proteins associated with incident CHD in individuals with and 29 in those without baseline T2D, respectively. Six of these proteins are novel candidates for incident CHD. MR suggested a potential causal role for hepatocyte growth factor in CHD development. The developed four-protein-enriched model for individuals with baseline T2D (ΔC-index: 0.017; cfNRI: 0.253; IDI: 0.051) and the 12-protein-enriched model for individuals without baseline T2D (ΔC-index: 0.054; cfNRI: 0.462; IDI: 0.024) consistently improved CHD prediction in the discovery cohort, while in the validation cohort, significant improvements were only observed for selected performance measures (with T2D: cfNRI: 0.633; without T2D: ΔC-index: 0.038; cfNRI: 0.465)., Conclusions: This study identified novel protein biomarkers associated with incident CHD in individuals with and without T2D and reaffirmed previously reported protein candidates. These findings enhance our understanding of CHD pathophysiology and provide potential targets for prevention and treatment., (© 2024. The Author(s).)

Background: As meta-inflammation is a common feature for obesity, type 2 diabetes (T2D), nonalcoholic fatty liver disease and atherosclerosis, we have proposed a new concept, metabolic inflammatory syndrome (MIS), to cluster such diseases. We aimed to characterize MIS and explore its association with coronary heart disease (CHD) among T2D inpatients in China., Methods: A total number of 8344 T2D participants were enrolled. Each component of MIS and metabolic syndrome (MS) was analyzed. Their association with the risk of CHD was assessed using a binary logistic analysis., Results: Among the T2D inpatients, the detection rate of MIS was much higher than that of MS (93.6 % vs. 53.2 %). Among all the components of MIS and MS, carotid atherosclerosis (71.9 %) was most commonly detected, which increased with aging in subgroups. Surprisingly, the most common combination of MIS was with all 4 components in T2D patients, with a constituent ratio of 30.9 %. According to the odds ratios (ORs), MIS was a better predictor of CHD than MS, especially after adjustment for age, sex, smoking, and alcohol consumption (adjusted OR for MIS: 3.083; for MS: 1.515). The presence of more components of MIS was associated with a higher detection rate of CHD (P < 0.001). Among all the components of MIS and MS, carotid atherosclerosis best predicted the risk of CHD (adjusted OR: 1.787)., Conclusions: MIS is an independent risk factor for CHD, with a bigger OR value than MS. Carotid atherosclerosis, with the highest detection rate, was the best individual predictor of CHD and thus a critical component of MIS. The concept of MIS represents the understanding of metabolic diseases from the perspective of holistic integrative medicine., Competing Interests: Declaration of Competing Interest No potential conflict of interest relevant to this study was reported., (Copyright © 2023. Published by Elsevier Ltd.)

Purpose: To quantify associations between various retinal microvascular changes and the risk of the development of coronary heart disease (CHD)., Methods: PubMed, Embase, Web of Science, and Cochrane Library databases were searched for cohort studies on the association between retinal microvascular changes and incident CHD up to July 31, 2023. The summary risk estimates were estimated using the random-effects model. Subgroup and sensitivity analyses were performed to investigate the potential source of heterogeneity., Results: The authors identified 21 studies that met the inclusion criteria of this meta-analysis through database searching. This study yielded significant associations between retinal microvascular changes, including arteriolar narrowing, venular widening, vessel occlusion, and other retinal vascular signs, and the risk of CHD, with pooled adjusted hazard ratios of 1.20 (95% confidence interval: 1.13-1.27). In sex- and age-stratified analyses, retinal microvascular changes were associated with a greater risk of developing CHD in female patients and younger adults., Conclusion: A range of retinal microvascular changes was associated with the risk of CHD, particularly in female patients and younger ages. The results of this study support the concept that retinal microvascular abnormalities may be markers for future CHD. Noninvasive retinal microvascular assessments may be helpful in screening patients with increased CHD risk.

Background: Traditional risk evaluation models have been applied to guide public health and clinical practice in various studies. However, the application of existing methods to data sets with missing and censored data, as is often the case in electronic health records, requires additional considerations. We aimed to develop and validate a predictive model that exhibits high performance with data sets that contain missing and censored data., Methods and Results: This is a retrospective cohort study of coronary heart disease at Weihai Municipal Hospital on unique patients aged 18 to 96 years between 2013 and 2021. A total of 169 692 participants formed our study population, of which 10 895 participants were diagnosed with coronary heart disease. Models were built for the risk of coronary heart disease based on demographic, laboratory, and medical history variables. All complete samples were assigned to the training set (n=110 325), whereas the remaining samples were assigned to the validation set (n=59 367). The area under the receiver operating characteristic curve value was 0.800 (95% CI, 0.794-0.805), and the C statistic was 0.796 (95% CI, 0.791-0.801) in the derivation cohort, and the corresponding values were 0.837 (95% CI, 0.821-0.853) and 0.838 (95% CI, 0.822-0.854) in the validation cohort. The calibration curve demonstrated its good calibration ability, and decision curve analysis showed its clinical usefulness., Conclusions: Our proposed risk prediction model has demonstrated significant effectiveness in handling the complexities of electronic health record data, which often involve extensive missing data and censoring. This approach may offer potential assistance in the use of electronic health records to enhance patient outcomes.

Abstract: Central sleep apnea (CSA) is common in patients with heart failure. Recent studies link ticagrelor use with CSA. We aimed to evaluate CSA prevalence in patients with coronary heart disease (CHD) and whether ticagrelor use is associated with CSA. We reviewed consecutive patients with CHD who underwent a polysomnography (PSG) test over a 5-year period from 3 sleep centers. We sampled patients who were on ticagrelor or clopidogrel during a PSG test at a 1:4 ticagrelor:clopidogrel ratio. Patients with an active opioid prescription during PSG test were excluded. Age, left ventricle (LV) dysfunction, and P2Y12 inhibitor use were included in a multivariate logistic regression. A total of 135 patients were included with 26 on ticagrelor and 109 on clopidogrel (age 64.1 ± 11.4, 32% male). High CSA burden (12%) and strict CSA (4.4%) were more common in patients on ticagrelor than in those on clopidogrel (27% vs. 8.3% and 10.0% vs. 1.8%). Ticagrelor use (vs. clopidogrel) was associated with high CSA burden (OR 3.53, 95% CI 1.04-12.9, P = 0.039) and trended toward significance for strict CSA (OR 6.32, 95% CI 1.03-51.4, P = 0.052) when adjusting for age and LV dysfunction. In an additional analysis also adjusting for history of atrial fibrillation, ticagrelor use and strict CSA became significantly associated (OR 10.0, 95% CI 1.32-117, P = 0.035). CSA was uncommon in patients with CHD undergoing sleep studies. Ticagrelor use (vs. clopidogrel) was associated with high CSA burden and trended toward significance for strict CSA., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Coronary heart disease (CHD) is one of the deadliest diseases and a risk prediction model for cardiovascular conditions is needed. Due to the huge number of features that lead to heart problems, it is often difficult for an expert to evaluate these huge features into account. So, there is a need of appropriate feature selection for the given CHD dataset. For early CHD detection, deep learning modes (DL) show promising results in the existing studies., Objective: This study aimed to develop a deep convolution neural network (CNN) model for classification with a selected number of efficient features using the LASSO (least absolute shrinkage and selection operator) technique. Also, aims to compare the model with similar studies and analyze the performance of the proposed model using accuracy measures., Methods: The CHD dataset of NHANES (National Health and Nutritional Examination Survey) was examined with 49 features using LASSO technique. This research work is an attempt to apply an improved CNN model for the classification of the CHD dataset with huge features CNN model with feature extractor consists of a fully connected layer with two convolution 1D layers, and classifier part consists of two fully connected layers with SoftMax function was trained on this dataset. Metrics like accuracy recall, specificity, and ROC were used for the evaluation of the proposed model., Results: The feature selection was performed by applying the LASSO model. The proposed CNN model achieved 99.36% accuracy, while previous studies model achieved over 80 to 92% accuracy., Conclusion: The application of the proposed CNN with the LASSO model for the classification of CHD can speed up the diagnosis of CHD and appears to be effective in predicting cardiovascular disease based on risk features.

Machine learning provides increasingly reliable assistance for medical experts in diagnosing coronary heart disease. This study proposes a deep learning hybrid model based coronary heart disease (CAD) prediction method, which can significantly improve the prediction accuracy compared to traditional solutions. This research scheme is based on the data of 7291 patients and proposes a hybrid model, which uses two different deep neural network models and a recurrent neural network model as the main model for training. The prediction results based on the main model training use a k-nearest neighbor model for secondary training so as to improve the accuracy of coronary heart disease prediction. The comparison between the model prediction results and the clinical diagnostic results shows that the prediction model has a prediction accuracy rate of 82.8%, a prediction precision rate of 87.08%, a prediction recall rate of 88.57%, a prediction F1-score of 87.82%, and an area under the curve value of 0.8 in the test set. Compared to single model machine learning predictions, the hybrid model has a significantly improved accuracy and has effectively solved the problem of overfitting. A deep learning based CAD prediction hybrid model that combines multiple weak models into a strong model can fully explore the complex inter-relationships between various features under limited feature values and sample size, improve the evaluation indicators of the prediction model, and provide effective auxiliary support for CAD diagnosis., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Background: Coronary heart disease (CHD) is the first cause of death globally. Hypertension is considered to be the most important independent risk factor for CHD. Early and accurate diagnosis of CHD in patients with hypertension can plays a significant role in reducing the risk and harm of hypertension combined with CHD., Objective: To propose a non-invasive method for early diagnosis of coronary heart disease according to tongue image features with the help of machine learning techniques., Methods: We collected standard tongue images and extract features by Diagnosis Analysis System (TDAS) and ResNet-50. On the basis of these tongue features, a common machine learning method is used to customize the non-invasive CHD diagnosis algorithm based on tongue image., Results: Based on feature fusion, our algorithm has good performance. The results showed that the XGBoost model with fused features had the best performance with accuracy of 0.869, the AUC of 0.957, the AUPR of 0.961, the precision of 0.926, the recall of 0.806, and the F1-score of 0.862., Conclusion: We provide a feasible, convenient, and non-invasive method for the diagnosis and large-scale screening of CHD. Tongue image information is a possible effective marker for the diagnosis of CHD.

Background: The relationship between genetically-driven liver fat and coronary heart disease (CHD) remains unclear. ApoB-containing lipoproteins are known causal factors for CHD and may explain this relationship., Methods and Results: We conducted a genome-wide association study (GWAS) in the UK Biobank to identify genetic variants associated with liver fat. We then investigated the effects that these genetic variants had on both apoB-containing lipoproteins and CHD. Using Mendelian Randomization (MR) analyses, we examined if the relationship between genetically-driven liver fat and CHD could be attributed to its effect on apoB-containing lipoproteins. We found 25 independent liver-fat associated single-nucleotide polymorphisms (SNPs) with differing effects on lipoprotein metabolism. The SNPs were classified into three groups/clusters. The first cluster (N = 3 SNPs) displayed lipoprotein-raising effects. The second cluster (N = 12 SNPs) displayed neutral effects on lipoproteins and the third cluster (N = 10 SNPs) displayed lipoprotein-lowering effects. For every 1% higher liver fat, the first cluster showed an increased risk of CHD (OR = 1.157 [95% CI: 1.108-1.208]). The second cluster showed a non-significant effect on CHD (OR = 0.988 [95% CI: 0.965-1.012], whereas the third cluster showed a protective effect of increased liver fat on CHD (OR = 0.942 [95% CI: 0.897-0.989]). When adjusting for apoB, the risk for CHD became null., Conclusions: Here, we identify 25 liver-fat associated SNPs. We find that SNPs that increase, decrease or have neutral effects on apoB-containing lipoproteins show increased, decreased or neutral effects on CHD, respectively. Therefore, the relationship between genetically-driven liver fat and CHD is mediated by the causal effect of apoB., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Blood DNA methylation was associated with coronary heart disease (CHD) risk in Caucasians. We investigated the association between DNA methylation in peripheral blood at the reported loci and CHD in the Chinese population., Methods: The integrin subunit beta 2 (ITGB2) gene was identified in 196 CHD cases and 184 controls, and its methylation level was determined by mass spectrometry. Logistic regression was used to assess the association., Results: Hypomethylation of ITGB2 was significantly associated with heart failure CHD and NYHA Ⅰ&Ⅱ CHD patients with minor to medium cardiac function impairment (ITGB2&#95;CpG&#95;11/cg08422803, OR per -10 % methylation = 1.15 and 1.16; p = 0.012 and 0.018 by Bonferroni correction, respectively). Hypomethylation of ITGB2&#95;CpG&#95;11/cg08422803 was a risk factor for CHD in people < 65 years and males (p < 0.05 after Bonferroni correction). The combination of ITGB2 methylation and conventional CHD risk factors could efficiently discriminate CHD, heart failure CHD, NYHA I&II CHD, and myocardial infarction CHD patients from controls (AUC = 0.78, 0.81, 0.80, and 0.81, respectively)., Conclusion: Blood-based ITGB2 methylation has the potential as a biomarker for CHD. The combination of ITGB2 methylation and conventional CHD risk factors may improve the risk assessment and detection of 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 © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Low birth weight is a known risk factor for adult coronary heart disease (CHD), but the additional effect of weight development during childhood and early adult life has not been studied., Methods: We included 35 659 men born 1945 to 1961 from the population-based BMI Epidemiology Study Gothenburg, with data available on birthweight, BMI in childhood (8 years), and BMI in young adulthood (20 years). Information on CHD diagnoses was retrieved from national registers. We used Cox proportional hazards regression to estimate hazard ratios and 95% CIs for the risk of early and late CHD (before and after 58.4 years of age, respectively)., Results: During follow-up, a total of 3380 cases of CHD (fatal and nonfatal) were registered. Birth weight was inversely associated with the risk of both early (hazard ratio, 0.88 per SD increase [95% CI, 0.84-0.92]) and late (hazard ratio, 0.94 per SD increase [95% CI, 0.90-0.98]) CHD, independently of BMI at 8 years and BMI change during puberty. In a model including birth weight (below or above the median) together with overweight at 8 and 20 years, only birth weight and young adult overweight, but not overweight in childhood, were significantly associated with the risk of CHD. A birth weight below the median, followed by overweight at 20 years of age was associated with a more than doubled risk of early CHD (hazard ratio, 2.29 [95% CI, 1.86-2.81]), compared with the reference (birth weight above the median and normal weight at 20 years of age). This excess risk was even more pronounced for a birthweight below 2.5 kg., Conclusions: We demonstrate that low birth weight and young adult overweight are important developmental markers of risk for adult CHD. These findings motivate a life course perspective for prevention and risk assessment of adult CHD., Competing Interests: Disclosures I. Lindh has received compensation from Gedeon Richter and Exeltis for lectures and participation in Advisory Board during the previous 3 years. The other authors report no conflicts.

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in developed countries, but its role in predicting cardiovascular disease (CVD) needs further investigation. Herein, we studied the association between NAFLD and the risk of CVD, stroke, and coronary heart disease (CHD) among Japanese people., Methods: This prospective cohort study analyzed data from 2,517 men and 3,958 women, aged 30-84 years, who were registered in the Suita Study. NAFLD was defined as Fatty Liver Index (FLI) ≥ 60. Cox proportional hazard models were applied to calculate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of incident CVD, stroke, and CHD events by baseline FLI. The results were adjusted for age, smoking, alcohol consumption, hypertension, diabetes, lipid profile, chronic kidney disease, and cardiac murmur or valvular diseases., Results: Within 16.6 years of median follow-up, 590 participants developed CVD (346 stroke events and 244 CHD events). Women with NAFLD (FLI ≥ 60) showed a higher risk of CVD and stroke: HRs (95% CIs) = 1.69 (1.16, 2.46) and 2.06 (1.31, 3.24), respectively. Besides, women in the fourth and fifth (highest) FLI quintiles showed a higher risk of CVD and stroke than those in the third (middle) quintile: HRs (95% CIs) = 1.60 (1.08, 2.36) and 1.67 (1.13, 2.45) for CVD and 1.73 (1.07, 2.79) and 1.90 (1.18, 3.05) for stroke, respectively. No corresponding associations were detected in men. NAFLD was not associated with CHD risk in either sex., Conclusions: NAFLD, diagnosed by FLI, was associated with a higher risk of CVD and stroke in Japanese women. From a preventive perspective, women with NAFLD should be targeted for CVD screenings and interventions., Competing Interests: Declaration of Competing Interest There is nothing to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aim      To study associations between the risk of severe adverse cardiovascular outcomes (SACVO) and all-cause death with psychosocial risk factors (PS RFs), such as stress, anxiety and depressive symptoms, low level of education, low income, social isolation, and type D personality, in patients with arterial hypertension (AH) and ischemic heart disease (IHD) managed in primary health care institutions in a multi-year prospective study.Material and methods  PS RFs were assessed in patients with AH or IHD, who participated in a multi-year prospective COMETA study, using the Hospital Anxiety and Depression Scale (HADS), DS-14 questionnaire, and a visual analogue scale (VAS) for assessment of stress level. Associations of PS FRs with SACVO and all-cause death after a 1.5-year follow-up were analyzed using multivariate Cox regression models.Results At 1.5 years after patients were included in the study, it was possible to obtain data for 2,538 patients (age at baseline, 66.6 ± 7.8 years, 28.1% men), 106 of whom died during that period. The incidence of SACVO was 40.0 per 1000 person-years. According to the results of multivariate regression analysis, a very high level of anxiety symptoms (HADS-A≥14) was significantly associated with SACVO (odds ratio (OR), 1.81; 95% confidence interval (CI), 1.04-3.15; p=0. 02). The composite endpoint that included all-cause death and/or SACVO was significantly associated with a high (VAS score ≥8) stress level (OR, 1.53; 95% CI, 1.00-2.33; p=0.04) and a very high (HADS-D≥14) level of depressive symptoms (OR, 2.11; 95% CI, 1.22-3.62; p=0.02). A low level of education adjusted for gender and age increased the likelihood of SACVO by 1.7 (95% CI, 1.19-2.43) times. No significant associations were found between the analyzed outcomes and type D personality or with social isolation.Conclusion      In patients with AH or IHD, the presence of high-grade stress and severe depressive symptoms increased the likelihoods of all-cause death and SACVO while a low level of education and severe anxiety symptoms were associated with SACVO. The study results showed that PS RFs for cardiovascular diseases keep the PS RF prognostic significance in the conditions of modern treatment of AH and IHD. Due to the negative impact on the prognosis, PS RFs should be taken into account when taking measures for secondary prevention of AH and IHD.

Background: Screening for cardiovascular disease is currently recommended before kidney transplantation. The present study aimed to validate the proposed algorithm by the American Heart Association (AHA-2022) considering cardiovascular findings and outcomes in kidney transplant candidates, and to compare AHA-2022 with the previous recommendation (AHA-2012)., Methods and Results: We applied the 2 screening algorithms to an observational cohort of kidney transplant candidates (n=529) who were already extensively screened for coronary heart disease by referral to cardiac computed tomography between 2014 and 2019. The cohort was divided into 3 groups as per the AHA-2022 algorithm, or into 2 groups as per AHA-2012. Outcomes were degree of coronary heart disease, revascularization rate following screening, major adverse cardiovascular events, and all-cause death. Using the AHA-2022 algorithm, 69 (13%) patients were recommended for cardiology referral, 315 (60%) for cardiac screening, and 145 (27%) no further screening. More patients were recommended cardiology referral or screening compared with the AHA-2012 (73% versus 53%; P <0.0001). Patients recommended cardiology referral or cardiac screening had a higher risk of major adverse cardiovascular events (hazard ratio [HR], 5.5 [95% CI, 2.8-10.8]; and HR, 2.1 [95% CI, 1.2-3.9]) and all-cause death (HR, 12.0 [95% [CI, 4.6-31.4]; and HR, 5.3 [95% CI, 2.1-13.3]) compared with patients recommended no further screening, and were more often revascularized following initial screening (20% versus 7% versus 0.7%; P <0.001)., Conclusions: The AHA-2022 algorithm allocates more patients for cardiac referral and screening compared with AHA-2012. Furthermore, the AHA-2022 algorithm effectively discriminates between kidney transplant candidates at high, intermediate, and low risk with respect to major adverse cardiovascular events and all-cause death.

Hypertensive patients with snoring and elevated plasma homocysteine levels are common. When these factors are combined, the risk of coronary heart disease (CHD) is high. Herein, we developed and validated an easy-to-use nomogram to predict high-risk CHD in snoring hypertensive patients with elevated plasma homocysteine.Snoring patients (n = 1,962) with hyperhomocysteinemia and hypertension were divided into training (n = 1,373, 70%) and validation (n = 589, 30%) sets. We extracted CHD predictors using multivariate Cox regression analysis, then constructed a nomogram model. Internal validation using 1,000 bootstrap resampling was performed to assess the consistency and discrimination of the predictive model using the area under the receiver operating characteristic curve (AUC) and calibration plots.We constructed a nomogram model with the extracted predictors, including age, waist-height ratio, smoking, and low-density lipoprotein cholesterol levels. The AUCs of the training and validation cohorts at 80 months were 0.735 (95% CI: 0.678-0.792) and 0.646 (95% CI: 0.547-0.746), respectively. The consistency between the observed CHD survival and the probability of CHD survival in the training and validation sets was acceptable based on the calibration plots. A total of more than 151 points in the nomogram can be used in the identification of high-risk patients for CHD among snoring hypertensive patients with elevated plasma homocysteine.We developed a CHD risk prediction model for snoring hypertension patients with hyperhomocysteinemia. Our findings provide a useful clinical tool for the rapid identification of high-risk CHD at an early stage.

Background: The plant-based Portfolio dietary pattern includes recognized cholesterol-lowering foods (ie, plant protein, nuts, viscous fiber, phytosterols, and plant monounsaturated fats) shown to improve several cardiovascular disease (CVD) risk factors in randomized controlled trials. However, there is limited evidence on the role of long-term adherence to the diet and CVD risk. The primary objective was to examine the relationship between the Portfolio Diet Score (PDS) and the risk of total CVD, coronary heart disease (CHD), and stroke., Methods: We prospectively followed 73 924 women in the Nurses' Health Study (1984-2016), 92 346 women in the Nurses' Health Study II (1991-2017), and 43 970 men in the Health Professionals Follow-up Study (1986-2016) without CVD or cancer at baseline. Diet was assessed using validated food frequency questionnaires at baseline and every 4 years using a PDS that positively ranks plant protein (legumes), nuts and seeds, viscous fiber sources, phytosterols (mg/day), and plant monounsaturated fat sources, and negatively ranks foods high in saturated fat and cholesterol., Results: During up to 30 years of follow-up, 16 917 incident CVD cases, including 10 666 CHD cases and 6473 strokes, were documented. After multivariable adjustment for lifestyle factors and a modified Alternate Healthy Eating Index (excluding overlapping components), comparing the highest with the lowest quintile, participants with a higher PDS had a lower risk of total CVD (pooled hazard ratio [HR], 0.86 [95% CI, 0.81-0.92]; P trend <0.001), CHD (pooled HR, 0.86 [95% CI, 0.80-0.93]; P trend =0.0001), and stroke (pooled HR, 0.86 [95% CI, 0.78-0.95]; P trend =0.0003). In addition, a 25-percentile higher PDS was associated with a lower risk of total CVD (pooled HR, 0.92 [95% CI, 0.89-0.95]), CHD (pooled HR, 0.92 [95% CI, 0.88-0.95]), and stroke (pooled HR, 0.92 [95% CI, 0.87-0.96]). Results remained consistent across sensitivity and most subgroup analyses, and there was no evidence of departure from linearity for CVD, CHD, or stroke. In a subset of participants, a higher PDS was associated with a more favorable blood lipid and inflammatory profile., Conclusions: The PDS was associated with a lower risk of CVD, including CHD and stroke, and a more favorable blood lipid and inflammatory profile, in 3 large prospective cohorts., Competing Interests: Disclosures Dr Glenn has received honoraria or travel support from the Soy Nutrition Institute Global, Vinasoy, and the Academy of Nutrition and Dietetics. Dr Malik has received funding from the Canada Research Chairs Program; Connaught New Researcher Award, the Joannah & Brian Lawson Centre for Child Nutrition, and a Temerty Faculty of Medicine Pathway grant, University of Toronto; Canada Foundation for Innovation; and Ontario Research Fund; and is an advisory board member of the Canadian Institutes of Health Research Institute of Nutrition, Metabolism and Diabetes. Dr Jenkins has received research grants from Saskatchewan & Alberta Pulse Growers Associations; the Agricultural Bioproducts Innovation Program through the Pulse Research Network; the Advanced Foods and Material Network; Loblaw Companies Ltd; Unilever Canada and Netherlands; Barilla; the Almond Board of California; Agriculture and Agri-Food Canada; Pulse Canada; Kellogg’s Company Canada; Quaker Oats Canada; Procter & Gamble Technical Centre Ltd; Bayer Consumer Care, Springfield, NJ; Pepsi/Quaker; International Nut & Dried Fruit Council; Soy Foods Association of North America; the Coca-Cola Company (investigator initiated, unrestricted grant); Solae; Haine Celestial; the Sanitarium Company; Orafti; the International Tree Nut Council Nutrition Research and Education Foundation; the Peanut Institute; Soy Nutrition Institute; the Canola and Flax Councils of Canada; the Calorie Control Council; the Canadian Institutes of Health Research; the Canada Foundation for Innovation; and the Ontario Research Fund; has received in-kind supplies for trials as research support from the Almond Board of California, Walnut Council of California, the Peanut Institute, Barilla, Unilever, Unico, Primo, Loblaw Companies, Quaker (PepsiCo), Pristine Gourmet, Bunge Limited, Kellogg Canada, and WhiteWave Foods; has been on the speaker’s panel, served on the scientific advisory board, or received travel support or honoraria from Nutritional Fundamentals for Health–Nutramedica, Saint Barnabas Medical Center, The University of Chicago, 2020 China Glycemic Index International Conference, Atlantic Pain Conference, Academy of Life Long Learning, the Almond Board of California, Canadian Agriculture Policy Institute, Loblaw Companies Ltd, the Griffin Hospital (for the development of the NuVal scoring system), the Coca-Cola Company, Epicure, Danone, Diet Quality Photo Navigation, Better Therapeutics (FareWell), Verywell, True Health Initiative, Heali AI Corp, Institute of Food Technologists, Soy Nutrition Institute, Herbalife Nutrition Institute, Saskatchewan & Alberta Pulse Growers Associations, Sanitarium Company, Orafti, the International Tree Nut Council Nutrition Research and Education Foundation, the Peanut Institute, Herbalife International, Pacific Health Laboratories, Barilla, Metagenics, Bayer Consumer Care, Unilever Canada and Netherlands, Solae, Kellogg, Quaker Oats, Procter & Gamble, Abbott Laboratories, Dean Foods, the California Strawberry Commission, Haine Celestial, PepsiCo, the Alpro Foundation, Pioneer Hi-Bred International, DuPont Nutrition and Health, Spherix Consulting and WhiteWave Foods, the Advanced Foods and Material Network, the Canola and Flax Councils of Canada, Agri-Culture and Agri-Food Canada, the Canadian Agri-Food Policy Institute, Pulse Canada, the Soy Foods Association of North America, the Nutrition Foundation of Italy, Nutra-Source Diagnostics, the McDougall Program, the Toronto Knowledge Translation Group (St Michael’s Hospital), the Canadian College of Naturopathic Medicine, the Hospital for Sick Children, the Canadian Nutrition Society, the American Society of Nutrition, Arizona State University, Paolo Sorbini Foundation, and the Institute of Nutrition, Metabolism and Diabetes; received an honorarium from the US Department of Agriculture to present the 2013 W.O. Atwater Memorial Lecture; received the 2013 Award for Excellence in Research from the International Nut and Dried Fruit Council; received funding and travel support from the Canadian Society of Endocrinology and Metabolism to produce mini-cases for the Canadian Diabetes Association; and is a member of the International Carbohydrate Quality Consortium; his wife, Alexandra L. Jenkins, is a director and partner of INQUIS Clinical Research for the food industry; his daughters, Wendy Jenkins and Amy Jenkins, have published a book that promotes the use of the foods described here (The Portfolio Diet for Cardiovascular Risk Reduction); and his sister, Caroline Brydson, received funding through a grant from the St Michael’s Hospital Foundation to develop a cookbook for one of his studies. Dr Kendall has received grants or research support from the Advanced Food Materials Network, Agriculture and Agri-Food Canada, Almond Board of California, Barilla, Canadian Institutes of Health Research, Canola Council of Canada, International Nut and Dried Fruit Council, International Tree Nut Council Research and Education Foundation, Loblaw Brands Ltd, the Peanut Institute, Pulse Canada, and Unilever; has received in-kind research support from the Almond Board of California, Barilla, California Walnut Commission, Kellogg Canada, Loblaw Companies, Nutrartis, Quaker (PepsiCo), the Peanut Institute, Primo, Unico, Unilever, and WhiteWave Foods/Danone; has received travel support or honoraria from the Barilla, California Walnut Commission, Canola Council of Canada, General Mills, International Nut and Dried Fruit Council, International Pasta Organization, Lantmannen, Loblaw Brands Ltd, Nutrition Foundation of Italy, Oldways Preservation Trust, Paramount Farms, the Peanut Institute, Pulse Canada, Sun-Maid, Tate & Lyle, Unilever, and White Wave Foods/Danone; has served on the scientific advisory board for the International Tree Nut Council, International Pasta Organization, McCormick Science Institute, and Oldways Preservation Trust; is a founding member of the International Carbohydrate Quality Consortium; is chair of the Diabetes and Nutrition Study Group of the European Association for the Study of Diabetes; is on the clinical practice guidelines expert committee for nutrition therapy of the European Association for the Study of Diabetes; and is a director of glycemia consulting and the Toronto 3D Knowledge Synthesis and Clinical Trials Foundation. Dr Sievenpiper has received research support from the Canadian Foundation for Innovation, Ontario Research Fund, Province of Ontario Ministry of Research and Innovation and Science, Canadian Institutes of health Research (CIHR), Diabetes Canada, American Society for Nutrition (ASN), International Nut and Dried Fruit Council (INC) Foundation, National Honey Board (U.S. Department of Agriculture [USDA] honey “Checkoff” program), Institute for the Advancement of Food and Nutrition Sciences (IAFNS), Pulse Canada, Quaker Oats Center of Excellence, The United Soybean Board (USDA soy “Checkoff” program), The Tate and Lyle Nutritional Research Fund at the University of Toronto, The Glycemic Control and Cardiovascular Disease in Type 2 Diabetes Fund at the University of Toronto (a fund established by the Alberta Pulse Growers), The Plant Protein Fund at the University of Toronto (a fund which has received contributions from IFF), and The Nutrition Trialists Network Research Fund at the University of Toronto (a fund established by an inaugural donation from the Calorie Control Council). He has received food donations to support randomized controlled trials from the Almond Board of California, California Walnut Commission, Peanut Institute, Barilla, Unilever/Upfield, Unico/Primo, Loblaw Companies, Quaker, Kellogg Canada, Danone, Nutrartis, Soylent, and Dairy Farmers of Canada. He has received travel support, speaker fees and/or honoraria from ASN, Danone, Dairy Farmers of Canada, FoodMinds LLC, Nestlé, Abbott, General Mills, Nutrition Communications, International Food Information Council (IFIC), Calorie Control Council, International Sweeteners Association, International Glutamate Technical Committee, Arab Beverages Association, and Phynova. He has or has had ad hoc consulting arrangements with Perkins Coie LLP, Tate & Lyle, Inquis Clinical Research, and Brightseed. He is a former member of the European Fruit Juice Association Scientific Expert Panel and former member of the Soy Nutrition Institute (SNI) Scientific Advisory Committee. He is on the Clinical Practice Guidelines Expert Committees of Diabetes Canada, European Association for the study of Diabetes (EASD), Canadian Cardiovascular Society (CCS), and Obesity Canada/Canadian Association of Bariatric Physicians and Surgeons. He serves as an unpaid member of the Board of Trustees of IAFNS and formerly served as an unpaid scientific advisor for the Carbohydrates Committee of IAFNS. He is a Director at Large of the Canadian Nutrition Society (CNS), founding member of the International Carbohydrate Quality Consortium (ICQC), Executive Board Member of the Diabetes and Nutrition Study Group (DNSG) of the EASD, and Director of the Toronto 3D Knowledge Synthesis and Clinical Trials foundation. His spouse is an employee of AB InBev. The other authors have no conflicts of interests to report.

Coronary heart disease (CHD) is the leading cause of mortality worldwide. Identifying effective diagnostic markers and understanding risk factors is crucial for prevention and management. This study aimed to investigate the levels of homocysteine (Hcy) and lipoprotein-associated phospholipase A2 (Lp-PLA2) in human plasma and their roles in the diagnosis and prognosis of CHD. A retrospective study was conducted on 232 patients with CHD, divided into Acute Myocardial Infarction, unstable angina pectoris, and stable angina pectoris groups, and a control group of 75 healthy adults. Blood samples were analyzed for serum Hcy and Lp-PLA2 levels using the cycling enzyme method and ELISA method, respectively. Statistical analyses were performed to evaluate the risk factors, and diagnostic efficacy was assessed using receiver operating characteristic (ROC) curves. No significant differences in age and sex were observed between the study and control groups, whereas marked disparities in risk factors such as obesity, hypertension, diabetes, and hyperlipidemia were noted. Significant differences in serum Hcy and Lp-PLA2 levels were identified among the CHD subgroups. Univariate and multivariate logistic regression analyses revealed that Hcy, Lp-PLA2, hypertension, and hyperlipidemia were significant risk factors for CHD. The combined diagnostic Area Under the Curve (AUC) for Hcy and Lp-PLA2 was found to be higher than that when using them individually. This study identified the elevation of Hcy and Lp-PLA2 levels as independent risk factors for CHD, and their conjoint analysis significantly enhanced clinical diagnostic efficacy. These findings provide valuable insights for CHD diagnosis, treatment, and prevention, highlighting the importance of these markers in CHD management., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Coronary heart disease (CHD) is a major complication of type 2 diabetes mellitus (T2DM), which causes an adverse prognosis. There is an urgent need to explore effective biomarkers to evaluate the patients' adverse outcomes., Objective: This study aimed to identify a novel indicator for screening T2DM and T2DM-CHD and predicting adverse prognosis., Materials and Methods: The study enrolled 52 healthy individuals, 85 T2DM patients, and 97 T2DM patients combined with CHD. Serum miR-199-3p levels in all study subjects were detected with PCR, and its diagnostic significance was evaluated by receiver operating curve (ROC) analysis. The involvement of miR-199-3p in disease development was assessed by the Chi-square test, and the logistic regression analysis was performed to estimate the risk factor for major adverse cardiovascular events (MACE) in T2DM-CHD patients., Results: Significant downregulation of miR-199-3p was observed in the serum of both T2DM and T2DM-CHD patients, which discriminated patients from healthy individuals and distinguished T2DM and T2DM-CHD patients. Reduced serum miR-199-3p was associated with the increasing blood glucose, glycated hemoglobin (HbA1c), and homeostasis model assessment-insulin resistance index (HOMA-IR) of T2DM patients and the increasing triglycerides (TG), low-density lipoprotein (LDL), fibrinogen, and total cholesterol (TC) and decreasing high-density lipoprotein (HDL) of T2DM-CHD patients. miR-199-3p was also identified as a biomarker predicting the occurrence of MACE., Conclusion: Downregulated miR-199-3p could screen the onset of T2DM and its complication with CHD. Reduced serum miR-199-3p was associated with the severe development of T2DM and T2DM-CHD and predicted the adverse outcomes of T2DM-CHD patients., (© 2023. The Author(s).)