Association between triglyceride glucose-body mass index and long-term adverse outcomes of heart failure patients with coronary heart disease.

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.

[Retrospective cross-sectional survey of clinical characteristics and syndrome elements distribution at different stages of coronary heart disease].

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.

Circulating microRNA-33b levels are associated with the presence and severity of coronary heart disease.

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.

Closing the sex gap in cardiovascular mortality by achieving both horizontal and vertical equity.

Addressing sex differences and disparities in coronary heart disease (CHD) involves achieving both horizontal and vertical equity in healthcare. Horizontal equity in the context of CHD means that both men and women with comparable health statuses should have equal access to diagnosis, treatment, and management of CHD. To achieve this, it is crucial to promote awareness among the general public about the signs and symptoms of CHD in both sexes, so that both women and men may seek timely medical attention. Women often face inequity in the treatment of cardiovascular disease. Current guidelines do not differ based on sex, but their applications based on gender do differ. Vertical equity means tailoring healthcare to allow equitable care for all. Steps towards achieving this include developing treatment protocols and guidelines that consider the unique aspects of CHD in women. It also requires implementing guidelines equally, when there is not sex difference rather than inequities in application of guideline directed care.

Plasma Biomarker Profiles for Premature and Nonpremature Coronary Heart Disease in Women.

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.

Chronic Coronary Disease in Older Adults.

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.

Association between nocturnal blood pressure phenotype and adverse cardiovascular prognosis in patients with coronary heart disease and hypertension.

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.

Telomere length as biomarker of nutritional therapy for prevention of type 2 diabetes mellitus development in patients with coronary heart disease: CORDIOPREV randomised controlled trial.

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.

Genetically Predicted Apolipoprotein E Levels with the Risk of Panvascular Diseases: A Mendelian Randomization Study.

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, PFDR < 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.

Correlation Between Blood Cadmium Levels and Platelet Characteristics, As Well As Their Impact on Susceptibility to Coronary Heart Disease: Findings from NHANES 2005-2018 Data.

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 × 103 cells/µL, 11.33 ± 0.27fL, 57.61 ± 5.34 × 103 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 × 103 cells/µL, 11.33 ± 0.27fL, 57.61 ± 5.34 × 103 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.

Association of plasma proteomics with incident coronary heart disease in individuals with and without type 2 diabetes: results from the population-based KORA study.

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.

Association between different insulin resistance surrogates and all-cause mortality in patients with coronary heart disease and hypertension: NHANES longitudinal cohort study.

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.

Coronary heart disease classification using deep learning approach with feature selection for improved accuracy.

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.

The neutrophil-to-lymphocyte ratio is associated with coronary heart disease risk in adults: A population-based study.

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.

Association of GAL-8 promoter methylation levels with coronary plaque inflammation.

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-1ß, 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.

Longitudinal Lipidomic Signature of Coronary Heart Disease in American Indian People.

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.

Central Sleep Apnea in Patients With Coronary Heart Disease Taking P2Y12 Inhibitors.

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.

Coronary heart disease prediction based on hybrid deep learning.

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.