Gut Microbiome and Atherosclerosis: A Mendelian Randomization Study.

Background: According to recent studies, atherosclerosis and gut microbiota are related. Nevertheless, it has been discovered that the gut microbiota varies across studies, with its function still being debated, and such relationships not proven to be causal. Thus, our study aimed to identify the key gut microbiota taxa (GM taxa) at different taxonomic levels, namely, the phylum, class, order, family, and genus, to investigate any potential causal links to atherosclerosis. Methods: We employed summary data from the MiBioGen consortium on the gut microbiota to conduct a sophisticated two-sample Mendelian randomization (MR) analysis. Pertinent information regarding atherosclerosis statistics was acquired from the FinnGen Consortium R8 publication. To assess causality, the utilized principal analytical technique was the inverse variance-weighted (IVW) method. Supplementary to IVW, additional MR methodologies were employed, including weighted median, MR-Egger, weighted methods, and simple mode. Sensitivity analyses involved the application of Cochrane's Q-test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out analysis. Results: Finally, after performing an MR study on the risk of 211 GM taxa on atherosclerosis, we discovered 20 nominal links and one strong causal link. Firmicutes (phylum ID: 1672) (odds ratio (OR) = 0.852 (0.763, 0.950), p = 0.004) continued to be connected with a lower incidence of coronary atherosclerosis, even after Bonferroni correction. Conclusions: Based on the discovered data, it was established that the phylum Firmicutes exhibits a causal relationship with a reduced occurrence of coronary atherosclerosis. This investigation could potentially provide novel insights into therapeutic objectives for atherosclerosis by focusing on the gut microbiota.

Reducing Cardiovascular Disease-An Alternative Approach.

PURPOSE: Statin drugs are effective at reducing cardiovascular events, but adherence to statin therapy remains a problem for patients and their physicians. We review a paper estimating the economic costs of poor adherence to statin drugs. METHODS: The authors examined two large databases (Medicare and Market Scan databases) including 230,000 patients with hospitalization for myocardial infarction between 2018 and 2019 to determine how many patients were not adhering to guideline-recommended anti-hyperlipidemic medications. They have also calculated the potential consequences of patients who are not adhering to the recommended therapy. RESULTS: The authors estimate that if all patients were receiving guideline-directed medical therapy, then a 22% relative risk reduction would occur in the 3-year period following discharge from the initial cardiovascular event. These findings are consistent with prior reports. This editorial discusses rationale and strategies clinicians can use to improve patients' compliance with recommendations for lipid-lowering therapy. CONCLUSION: The authors conclude that better compliance with guideline-directed lipid therapy after a cardiovascular event would lead to a large reduction in second events. Increased efforts by clinicians to improve adherence to statin therapy are warranted.

Predictive value of the neutrophil percentage-to-albumin ratio for coronary atherosclerosis severity in patients with CKD.

BACKGROUND: The neutrophil percentage-to-albumin ratio (NPAR), which is defined as the percentage of neutrophils divided by the concentration of albumin, is a cost-effective and readily available biomarker of inflammation. This study aimed to evaluate the association between the NPAR and the severity of coronary atherosclerosis in patients with chronic kidney disease (CKD). METHODS: A total of 280 CKD patients who underwent coronary angiography were retrospectively enrolled in this study. The severity of coronary atherosclerosis was evaluated using the Gensini score (GS). Patients were divided into low-, medium- and high-NPAR groups according to the tertiles of the NPAR values. Logistic regression analysis was conducted to analyze the relationship between the NPAR and the GS. The cutoff points for the sensitivity and specificity of the NPAR in predicting the GS were estimated via receiver operating characteristic (ROC) analysis. RESULTS: There was a higher prevalence of coronary artery disease (CAD) among CKD patients with higher NPARs (P =0.041). More patients in the high-NPAR group had complex CAD (triple-vessel disease and/or left main coronary artery stenosis) and chronic total occlusion lesions, and more of these patients required revascularization therapy (P<0.05). Multivariate logistic regression analysis revealed a significant positive correlation between the NPAR and the severity of coronary stenosis (adjusted OR 2.68, 95% CI 1.25-5.76, p=0.012), particularly among female and older (age ≥65) patients. The ROC analysis indicated that the optimal cutoff value for the NPAR in predicting severe coronary artery stenosis (GS>60) in CKD patients was 1.91 (sensitivity 0.495, specificity 0.749), with an area under the curve (AUC) of 0.650 (95% CI 0.581-0.719, P<0.001). A subgroup analysis according to sex revealed that the NPAR exhibited stronger predictive value in female patients (AUC 0.730, 95% CI 0.643-0.817) than in male patients (AUC 0.565, 95% CI 0.460-0.670) (P<0.001), and the optimal cutoff value for the NPAR in female patients was 1.80 (sensitivity 0.667, specificity 0.705). CONCLUSIONS: Our study demonstrated that the NPAR is independently associated with the severity of coronary atherosclerosis in CKD patients, especially in female and elderly patients (≥65 years old). Moreover, the NPAR can effectively predict the severity of coronary atherosclerosis, exhibiting greater predictive value in females than in males.

Predictive Value of CFIm25 Expression in Peripheral Blood Monocytes for Coronary Atherosclerosis.

Background: Cleavage factor Im25 (CFIm25) regulates cell function by affecting mRNA editing processes and plays diverse roles in various diseases. Studies have found that peripheral blood monocytes are valuable in diagnosing and prognosing coronary atherosclerosis. However, no studies have examined the predictive value of CFIm25 expression in peripheral blood monocytes for coronary atherosclerosis. Methods and Results: We collected the coronary angiography results of 267 patients and calculated the Gensini score to evaluate their degree of coronary atherosclerosis. We isolated peripheral blood monocytes and detected CFIm25 RNA expression. Based on their Gensini score, we divided the patients into negative (0, n = 46), mild lesion (≤ 8, n = 71), moderate lesion (8-23, n = 76), and severe lesion (≥ 23, n = 74) groups. Results showed that CFIm25 expression correlated negatively with the Gensini score and the number of involved coronary vessels. Univariate and multivariate binary logistic regression analyses showed that CFIm25 expression in peripheral blood monocytes was a protective factor for severe lesions, ≥ 50% stenosis, and three-vessel lesions. The areas under the receiver operating characteristic curve of CFIm25 expression for predicting lesions, severe lesions, ≥50% stenosis, and three-vessel lesions were 0.743, 0.735, 0.791, and 0.736, respectively. Conclusions: CFIm25 expression in peripheral blood monocytes correlates negatively with the degree of coronary atherosclerosis and helps predict the severity and number of coronary artery lesions.

Prognostic value of mitral annular calcification in coronary atherosclerotic disease assessed by coronary computed tomographic angiography.

Background: There is a lack of evidence on the link between mitral annular calcification (MAC) and coronary atherosclerotic diseases. The present investigation was undertaken to detect the clinical and prognostic value of MAC in coronary atherosclerotic diseases in patients who underwent coronary computed tomographic (CT) angiography. Materials and Methods: Two hundred and five individuals with MAC and without it (n = 85 and 120, respectively) were included in the present cross-sectional study. Coronary artery disease-reporting and data system (CAD-RADS) at coronary CT angiography was used to define the severity of coronary atherosclerotic diseases. Patients were classified into no or non-significant CAD (CAD-RADS 0-2) and significant CAD (CAD-RADS 3-5) according to the severity of coronary atherosclerotic diseases. The association of MAC with two mentioned groups (no or non-significant CAD and significant CAD) was assessed using the Chi-squared test and logistic regression in crude and adjusted models. Results: Patients with MAC were significantly older (69.34 ± 8.20 vs. 60.64 ± 11.42, P < 0.001), had lower glomerular infiltration rate (69.67 ± 20.92 vs. 78.00 ± 20.23, P = 0.005), and higher coronary artery calcification score (352.87 ± 495.85 vs. 200.55 ± 426.13, P = 0.05) in comparison to those without MAC. However, the significant difference between the two groups regarding coronary artery calcification score disappeared after adjustment for confounders (P = 0.14). In addition, a statistically significant positive link between MAC and significant CAD was observed (odds ratio [OR] [95% confidence interval (CI)]: 1.96 [1.04-3.71], P = 0.04). Nevertheless, the association became statistically insignificant after adjustment for confounders (OR [95% CI]: 1.60 [0.78-3.28], P = 0.2). Conclusion: The findings of the study revealed that MAC has no independent prognostic value in coronary atherosclerotic diseases evaluated by coronary CT angiography.

Small LDL subfractions are associated with coronary atherosclerosis despite no differences in conventional lipids.

Lipoprotein subfractions currently represent a new source of cardiovascular disease (CVD) risk markers that may provide more information than conventional lipid measures. We aimed to investigate whether lipoprotein subfractions are associated with coronary atherosclerosis in patients without prior known CVD. Fasting serum samples from 60 patients with suspected coronary artery disease (CAD) were collected before coronary angiography and analyzed by nuclear magnetic resonance (NMR) spectroscopy. The severity of coronary atherosclerosis was quantified by the Gensini score (≤20.5 = nonsignificant coronary atherosclerosis, 20.6-30.0 = intermediate coronary atherosclerosis, ≥30.1 = significant CAD). Differences in lipoprotein subfractions between the three Gensini groups were assessed by two-way ANOVA, adjusted for statin use. Despite no differences in conventional lipid measures between the three Gensini groups, patients with significant CAD had higher apolipoprotein-B/apolipoprotein-A1 ratio, 30% more small and dense low-density lipoprotein 5 (LDL-5) particles, and increased levels of cholesterol, triglycerides, and phospholipids within LDL-5 compared with patients with nonsignificant coronary atherosclerosis and intermediate coronary atherosclerosis (P ≤ 0.001). In addition, the low-density lipoprotein (LDL) cholesterol/high-density lipoprotein cholesterol ratio, and triglyceride levels of LDL 4 were significantly increased in patients with significant CAD compared with patients with nonsignificant coronary atherosclerosis. In conclusion, small and dense lipoprotein subfractions were associated with coronary atherosclerosis in patients without prior CVD. Additional studies are needed to explore whether lipoprotein subfractions may represent biomarkers offering a clinically meaningful improvement in the risk prediction of CAD.

2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: The executive summary of the American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions coronary artery revascularization guideline provides the top 10 items readers should know about the guideline. In the full guideline, the recommendations replace the 2011 coronary artery bypass graft surgery guideline and the 2011 and 2015 percutaneous coronary intervention guidelines. This summary offers a patient-centric approach to guide clinicians in the treatment of patients with significant coronary artery disease undergoing coronary revascularization, as well as the supporting documentation to encourage their use. METHODS: A comprehensive literature search was conducted from May 2019 to September 2019, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, CINHL Complete, and other relevant databases. Additional relevant studies, published through May 2021, were also considered. Structure: Recommendations from the earlier percutaneous coronary intervention and coronary artery bypass graft surgery guidelines have been updated with new evidence to guide clinicians in caring for patients undergoing coronary revascularization. This summary includes recommendations, tables, and figures from the full guideline that relate to the top 10 take-home messages. The reader is referred to the full guideline for graphical flow charts, supportive text, and tables with additional details about the rationale for and implementation of each recommendation, and the evidence tables detailing the data considered in the development of this guideline.

Sex Differences in Subclinical Atherosclerosis and Systemic Immune Activation/Inflammation Among People With Human Immunodeficiency Virus in the United States.

BACKGROUND: Among people with HIV (PWH), sex differences in presentations of atherosclerotic cardiovascular disease (ASCVD) may be influenced by differences in coronary plaque parameters, immune/inflammatory biomarkers, or relationships therein. METHODS: REPRIEVE, a primary ASCVD prevention trial, enrolled antiretroviral therapy (ART)-treated PWH. At entry, a subset of US participants underwent coronary computed tomography angiography (CTA) and immune phenotyping (n = 755 CTA; n = 725 CTA + immune). We characterized sex differences in coronary plaque and immune/inflammatory biomarkers and compared immune-plaque relationships by sex. Unless noted otherwise, analyses adjust for ASCVD risk score. RESULTS: The primary analysis cohort included 631 males and 124 females. ASCVD risk was higher among males (median: 4.9% vs 2.1%), while obesity rates were higher among females (48% vs 21%). Prevalence of any plaque and of plaque with either ≥1 visible noncalcified portion or vulnerable features (NC/V-P) was lower among females overall and controlling for relevant risk factors (RR [95% CI] for any plaque: .67 [.50, .92]; RR for NC/V-P: .71 [.51, 1.00] [adjusted for ASCVD risk score and body mass index]). Females showed higher levels of IL-6, hs-CRP, and D-dimer and lower levels of Lp-PLA2 (P < .001 for all). Higher levels of Lp-PLA2, MCP-1, and oxLDL were associated with higher plaque (P < .02) and NC/V-P prevalence, with no differences by sex. Among females but not males, D-dimer was associated with higher prevalence of NC/V-P (interaction P = .055). CONCLUSIONS: Among US PWH, females had a lower prevalence of plaque and NC/V-P, as well as differences in key immune/inflammatory biomarkers. Immune-plaque relationships differed by sex for D-dimer but not other tested parameters. Clinical Trial Registration. ClinicalTrials.gov; identifier: NCT0234429 (date of initial registration: 22 January 2015).

Biomarkers and cardiovascular events in patients with stable coronary disease in the ISCHEMIA Trials.

IMPORTANCE: Biomarkers may improve prediction of cardiovascular events for patients with stable coronary artery disease (CAD), but their importance in addition to clinical tests of inducible ischemia and CAD severity is unknown. OBJECTIVES: To evaluate the prognostic value of multiple biomarkers in stable outpatients with obstructive CAD and moderate or severe inducible ischemia. DESIGN AND SETTING: The ISCHEMIA and ISCHEMIA CKD trials randomized 5,956 participants with CAD to invasive or conservative management from July 2012 to January 2018; 1,064 participated in the biorepository. MAIN OUTCOME MEASURES: Primary outcome was cardiovascular death, myocardial infarction (MI), or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. Secondary outcome was cardiovascular death or MI. Improvements in prediction were assessed by cause-specific hazard ratios (HR) and area under the receiver operating characteristics curve (AUC) for an interquartile increase in each biomarker, controlling for other biomarkers, in a base clinical model of risk factors, left ventricular ejection fraction (LVEF) and ischemia severity. Secondary analyses were performed among patients in whom core-lab confirmed severity of CAD was ascertained by computed cardiac tomographic angiography (CCTA). EXPOSURES: Baseline levels of interleukin-6 (IL-6), high sensitivity troponin T (hsTnT), growth differentiation factor 15 (GDF-15), N-terminal pro-B-type natriuretic peptide (NT-proBNP), lipoprotein a (Lp[a]), high sensitivity C-reactive protein (hsCRP), Cystatin C, soluble CD 40 ligand (sCD40L), myeloperoxidase (MPO), and matrix metalloproteinase 3 (MMP3). RESULTS: Among 757 biorepository participants, median (IQR) follow-up was 3 (2-5) years, age was 67 (61-72) years, and 144 (19%) were female; 508 had severity of CAD by CCTA available. In an adjusted multimarker model with hsTnT, GDF-15, NT-proBNP and sCD40L, the adjusted HR for the primary outcome per interquartile increase in each biomarker was 1.58 (95% CI 1.22, 2.205), 1.60 (95% CI 1.16, 2.20), 1.61 (95% 1.22, 2.14), and 1.46 (95% 1.12, 1.90), respectively. The adjusted multimarker model also improved prediction compared with the clinical model, increasing the AUC from 0.710 to 0.792 (P < .01) and 0.714 to 0.783 (P < .01) for the primary and secondary outcomes, respectively. Similar findings were observed after adjusting for core-lab confirmed atherosclerosis severity. CONCLUSIONS AND RELEVANCE: Among ISCHEMIA biorepository participants, biomarkers of myocyte injury/distension, inflammation, and platelet activity improved cardiovascular event prediction in addition to risk factors, LVEF, and assessments of ischemia and atherosclerosis severity. These biomarkers may improve risk stratification for patients with stable CAD.

ATP-binding cassette G1 membrane transporter-mediated cholesterol efflux capacity influences coronary atherosclerosis and cardiovascular risk in Rheumatoid Arthritis.

OBJECTIVES: Cholesterol efflux capacity (CEC) measures the ability of high-density lipoprotein (HDL) to remove cholesterol from macrophages and reduce the lipid content of atherosclerotic plaques. CEC inversely associated with cardiovascular risk beyond HDL-cholesterol levels. CEC through the ATP-binding-cassette G1 (ABCG1) membrane transporter is impaired in rheumatoid arthritis (RA). We evaluated associations of ABCG1-CEC with coronary atherosclerosis, plaque progression and cardiovascular risk in RA. METHODS: Coronary atherosclerosis (noncalcified, partially, fully-calcified, low-attenuation plaque) was assessed with computed tomography angiography in 140 patients and reevaluated in 99 after 6.9 ± 0.3 years. Cardiovascular events including acute coronary syndromes, stroke, cardiovascular death, claudication, revascularization and hospitalized heart failure were recorded. ABCG1-CEC was measured in Chinese hamster ovary cells as percentage of effluxed over total intracellular cholesterol. RESULTS: ABCG1-CEC inversely associated with extensive atherosclerosis (≥5 plaques) (adjusted odds ratio 0.50 [95% CI 0.28-0.88]), numbers of partially-calcified (rate ratio [RR] 0.71 [0.53-0.94]) and low-attenuation plaques (RR 0.63 [0.43-0.91] per standard deviation increment). Higher ABCG1-CEC predicted fewer new partially-calcified plaques in patients with lower baseline and time-averaged CRP and fewer new noncalcified and calcified plaques in those receiving higher mean prednisone dose. ABCG1-CEC inversely associated with events in patients with but not without noncalcified plaques, with

The triglyceride-glucose index is associated with atherosclerosis in patients with symptomatic coronary artery disease, regardless of diabetes mellitus and hyperlipidaemia.

BACKGROUND: Diabetes and hyperlipidaemia are both risk factors for coronary artery disease, and both are associated with a high triglyceride-glucose index (TyG index). The TyG index has been presented as a marker of insulin resistance (IR). Its utility in predicting and detecting cardiovascular disease has been reported. However, few studies have found it to be a helpful marker of atherosclerosis in patients with symptomatic coronary artery disease (CAD). The purpose of this study was to demonstrate that the TyG index can serve as a valuable marker for predicting coronary and carotid atherosclerosis in symptomatic CAD patients, regardless of diabetes mellitus and hyperlipidaemia. METHODS: This study included 1516 patients with symptomatic CAD who underwent both coronary artery angiography and carotid Doppler ultrasound in the Department of Cardiology at Tianjin Union Medical Center from January 2016 to December 2022. The TyG index was determined using the Ln formula. The population was further grouped and analysed according to the presence or absence of diabetes and hyperlipidaemia. The Gensini score and carotid intima-media thickness were calculated or measured, and the patients were divided into four groups according to TyG index quartile to examine the relationship between the TyG index and coronary or carotid artery lesions in symptomatic CAD patients. RESULTS: In symptomatic CAD patients, the TyG index showed a significant positive correlation with both coronary lesions and carotid plaques. After adjusting for sex, age, smoking, BMI, hypertension, diabetes, and the use of antilipemic and antidiabetic agents, the risk of developing coronary lesions and carotid plaques increased across the baseline TyG index. Compared with the lowest quartile of the TyG index, the highest quartile (quartile 4) was associated with a greater incidence of coronary heart disease [OR = 2.55 (95% CI 1.61, 4.03)] and carotid atherosclerotic plaque [OR = 2.31 (95% CI 1.27, 4.20)] (P < 0.05). Furthermore, when compared to the fasting blood glucose (FBG) or triglyceride (TG) level, the TyG index had a greater area under the ROC curve for predicting coronary lesions and carotid plaques. The subgroup analysis demonstrated the TyG index to be an equally effective predictor of coronary and carotid artery disease, regardless of diabetes and hyperlipidaemia. CONCLUSION: The TyG index is a useful marker for predicting coronary and carotid atherosclerosis in patients with symptomatic CAD, regardless of diabetes mellitus and hyperlipidaemia. The TyG index is of higher value for the identification of both coronary and carotid atherosclerotic plaques than the FBG or TG level alone.

SR-B1-/-ApoE-R61h/h Mice Mimic Human Coronary Heart Disease.

Cardiovascular diseases are the leading cause of death in the modern world. Atherosclerosis underlies the majority of these pathologies and may result in sudden life-threatening events such as myocardial infarction or stroke. Current concepts consider a rupture (resp. erosion) of "unstable/vulnerable" atherosclerotic plaques as a primary cause leading to thrombus formation and subsequent occlusion of the artery lumen finally triggering an acute clinical event. We and others described SR-B1-/-ApoE-R61h/h mice mimicking clinical coronary heart disease in all major aspects: from coronary atherosclerosis through vulnerable plaque ruptures leading to thrombus formation/coronary artery occlusion, finally resulting in myocardial infarction/ischemia. SR-B1-/-ApoE-R61h/h mouse provides a valuable model to study vulnerable/occlusive plaques, to evaluate bioactive compounds as well as new anti-inflammatory and "anti-rupture" drugs, and to test new technologies in experimental cardiovascular medicine. This review summarizes and discuss our knowledge about SR-B1-/-ApoE-R61h/h mouse model based on recent publications and experimental observations from the lab.

Liraglutide treatment is associated with progression of coronary artery fibrous plaque: a prospective 1-year follow-up study in asymptomatic patients with type 2 diabetes.

OBJECTIVE: The objective of this study was to assess the association between clinically indicated liraglutide treatment and coronary artery plaque progression during 1-year follow-up in asymptomatic diabetes. METHODS: Patients were divided into a group receiving liraglutide (Lira+) and a group not receiving liraglutide (Lira-). Coronary computed tomography angiography (CCTA) was performed to assess total atheroma volume (TAV) and subtypes of plaque volumes (dense calcium, fibrous, fibrous-fatty, and necrotic core plaque) and the plaque progression during one year follow-up. RESULTS: Fifty-five patients (27%) receiving liraglutide and 149 (73%) how did not were included. Changes in TAV during 1-year of follow-up were similar in the two groups (38 ± 180 (Lira+) vs. -1 ± 160 mm3 (Lira-), P = 0.13). A greater increase in fibrous plaque volume was seen in the Lira + vs. the Lira- group (34 ± 129 vs. -2 ± 101 mm3, P = 0.04). Changes over 1-year in the other plaque subtypes were similar in the two groups. Treatment duration of liraglutide was not associated with changes in TAV. CONCLUSION: In patients with T2D without known prior coronary artery disease, liraglutide treatment was associated with a significant increase in coronary artery fibrous plaque volume during 1-year follow-up.

Feasibility of rotational atherectomy in patients with acute coronary syndrome: favorable in-hospital outcomes and clinical importance of complexed coronary atherosclerosis.

The feasibility of rotational atherectomy (RA) during percutaneous coronary intervention (PCI) in patients who present with acute coronary syndrome (ACS) remains fully unsettled. We retrospectively evaluated 198 consecutive patients who underwent RA during PCI from 2009 to 2020. All patients underwent intracoronary imaging (intravascular ultrasound 96.5%, optical coherence tomography 9.1%, both 5.6%) during PCI. Patients who underwent RA during PCI were divided into two groups: ACS (n = 49; unstable angina pectoris, n = 27; non-ST-elevation myocardial infarction, n = 18, and ST-elevation myocardial infarction, n = 4) and chronic coronary syndrome (CCS) (n = 149). The RA procedural success rate was comparable between in the ACS and CCS groups (93.9 vs. 89.9%, P = 0.41). No significant differences were observed in procedural complications and in-hospital death between the groups. The incidence of major adverse cardiovascular event (MACE) after 2 years was significantly higher in ACS group compared with CCS group (38.7 vs. 17.4%, log-rank P = 0.002). Multivariable Cox regression analysis identified SYNTAX score or CABG SYNTAX score > 22 (hazard ratio (HR) 2.66, 95% confidence interval (CI) 1.40-5.06, P = 0.002) and mechanical circulatory support during the procedure (HR 2.61, 95% CI 1.21-5.59, P = 0.013) as predictors of MACE at 2 years, but not ACS on index admission (HR 1.58, 95% CI 0.84-2.99, P = 0.151). RA procedure is feasible as a bail-out strategy for ACS lesions. However, more complexed coronary atherosclerosis and mechanical circulatory support during RA procedure, but no ACS lesions were associated with worse mid-term clinical outcomes.

Cytokine Profile and Concentrations of Metabolic Hormones in the Blood of Overweight Men with Coronary Arteriosclerosis.

Plasma concentrations of cytokines and metabolic hormones and their association with vulnerable atherosclerotic plaques were studied in 36 overweight men (age 40-77 years; BMI 25.0-29.9 kg/m2) with coronary atherosclerosis who underwent coronary endarterectomy. According to histological analysis, the patients were divided into two groups: with stable (17 (47.2%) men) and vulnerable (19 (52.8%) men) plaques in the coronary arteries. The plasma levels of cytokines and metabolic hormones were measured by multiplex analysis: C-peptide, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1, glucagon, IL-6, insulin, leptin, monocyte chemoattractant protein-1, and TNFα. In overweight patients with vulnerable plaques, the level of glucagon was lower by 4.17 times, GIP - by 2.47 times, and insulin - by 2.1 times. At the same time, the risk of occurrence of a vulnerable plaque increases by 5.4% with a decrease in GIP concentration by 1 pg/ml irrespectively of age, as well as by 3.1% with an increase in insulin concentration by 10 pg/ml, without achieving statistical significance when included in the age model. Overweight men with coronary atherosclerosis and vulnerable plaques have lower levels of insulin, glucagon, and GIP. The levels of GIP and insulin are inversely associated with the risk of having vulnerable atherosclerotic plaque.

Application of SF-36 Health Status Survey in Patients with Arterial Hypertension.

BACKGROUND: To estimate quality of life (QOL) in patients with arterial hypertension (AH) using SF-36 Health Status Survey. SUBJECTS AND METHODS: We included 268 patients (144 men, 124 women) with grade 1-3 AH (subgroup 1 - with coronary stenosis less than 50% (n=158), subgroup 2 - with coronary artery stenosis of 50% or more (n=110)). In the control group - 80 people (47 men, 33 women) without AH. Laboratory and instrumental methods included total cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, creatinine, electrocardiography, echocardiography, Doppler ultrasound of brachiocephalic arteries, stress echocardiography with physical exercises and coronary angiography. For QOL evaluation we used SF-36 Health Status Survey. RESULTS: According to the results of the SF-36 Health Status Survey, when assessing physical (PH) and mental (MH) among the groups, there was a significant decrease in summary points in patients of subgroup 2, in whom, according to coronary angiography, it was revealed stenosis of the carotid arteries 50% and more. Anxiety and depression predominated in men. Patients with corrected cholesterol and LDL-cholesterol levels, as well as after coronary angioplasty, were assessed for QOL with limited physical activity, but with high social functioning. CONCLUSIONS: AH, especially with hemodynamically significant atherosclerosis of the coronary arteries are the predictors for QOL worsening in cardiological patients, mostly in men. Using of the international questionnaire "SF-36 Health Status Survey" is advisable to assess the QOL in patients with cardiovascular diseases. In this sense, the interaction of a cardiologist and a psychotherapist is appropriate and justified for the most optimal management of a patient with this pathology.

A Meta-Analysis on the Global Prevalence, Risk factors and Screening of Coronary Heart Disease in Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS: Cardiovascular disease remains the leading cause of death in patients with nonalcoholic fatty liver disease (NAFLD). Studies examining the association of coronary heart disease (CHD) and NAFLD are cofounded by various cardiometabolic factors, particularly diabetes and body mass index. Hence, we seek to explore such association by investigating the global prevalence, independent risk factors, and influence of steatosis grade on manifestation of CHD among patients with NAFLD. METHODS: Two databases, Embase and Medline, were utilized to search for articles relating to NAFLD and CHD. Data including, but not limited to, continent, diagnostic methods, baseline characteristics, prevalence of CHD, CHD severity, NAFLD severity, and risk factors were extracted. RESULTS: Of the 38 articles included, 14 reported prevalence of clinical coronary artery disease (CAD) and 24 subclinical CAD. The pooled prevalence of CHD was 44.6% (95% confidence interval [CI], 36.0%-53.6%) among 67,070 patients with NAFLD with an odds ratio of 1.33 (95% CI, 1.21%-1.45%; P < .0001). The prevalence of CHD was higher in patients with moderate to severe steatosis (37.5%; 95% CI, 15.0%-67.2%) than those with mild steatosis (29.6%; 95% CI, 13.1%-54.0%). The pooled prevalence of subclinical and clinical CAD was 38.7% (95% CI, 29.8%-48.5%) and 55.4% (95% CI, 39.6%-70.1%), respectively. CONCLUSION: Steatosis was found to be related with CHD involvement, with moderate to severe steatosis related to clinical CAD. Early screening and prompt intervention for CHD in NAFLD are warranted for holistic care in NAFLD.

Application of an antibody microarray for serum protein profiling of coronary artery stenosis.

Protein expression profiling in the serum is used to identify novel biomarkers and investigate the signaling pathways in various diseases. The aim of the present study was to evaluate serum biomarkers associated with coronary artery stenosis resulting from atherosclerosis. The study included 4 groups of subjects: group A and B with and without coronary lesions, respectively, were selected from a previously reported cohort study on coronary atherosclerosis, control group C comprised of asymptomatic subjects and group D was used for independent validation of the microarray data by ELISA. Labeled serum proteins were profiled by an Explorer antibody array, which included 656 specific antibodies in two replicates (FullMoon Biosystems, USA). Cadherin-P, interleukin-5, glutathione S-transferase Mu, and neuronal nitric oxide synthase were sex-independently increased in Group A compared with those in group B. The microarray data on cadherin-P were externally validated in an independent group D using ELISA. Fibroblast growth factor-1, FGF-2, collagen II, granulocyte-macrophage colony-stimulating factor, IL-1 alpha, angiopoietin-2, granulocyte colony-stimulating factor, lymphocyte cell-specific protein tyrosine kinase, and IkappaB kinase b were increase in men in group A compared with group B. Cyclin-dependent kinase 1, DNA fragmentation factor subunit alpha DFF45/ICAD, adenovirus type 2 E1A, calponin, ADP-ribosylation factor-6, muscle-specific actin, thyroid hormone receptor alpha, and alpha-methylacyl-CoA racemase were specifically increased in women in Group A compared with group B. Alterations in the levels of specific proteins may point to the signaling pathways contributing to coronary atherosclerosis, and these proteins will be useful biomarkers for the progression of cardiovascular diseases.

Lipoprotein oxidation may underlie the paradoxical association of low cholesterol with coronary atherosclerotic risk in rheumatoid arthritis.

OBJECTIVE: To compare coronary plaque burden, proatherogenic cytokines, oxidized low-density lipoprotein (oxLDL), anti-oxLDL antibodies, lipoprotein(a)-cholesterol, and their relationships in patients with rheumatoid arthritis with low-density lipoprotein cholesterol (LDL-C)<1.8 mmol/L versus ≥1.8 mmol/L. Also, to study differences in inflammation and proprotein convertase subtilisin/kexin type-9 (PCSK9), which impacts LDL clearance, in patients with low versus high LDL-C. METHODS: Computed tomography angiography evaluated coronary plaque (noncalcified, partially calcified, fully calcified, and high-risk plaque) in 150 patients from a single-center observational cohort. Ox-LDL, anti-oxLDL IgG, lipoprotein(a)-cholesterol, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-6, tumor necrosis factor-α (TNF-α) and PCSK9 were measured. Analyses adjusted for Framingham general cardiovascular risk score, statin use, and high-density lipoprotein cholesterol. RESULTS: Patients with LDL-C<1.8 mmol/L versus ≥1.8 mmol/L demonstrated: 1) higher likelihood of per-segment plaque (adjusted-OR = 1.67 [95%CI = 1.10-2.55], p = 0.017) and high-risk plaque presence (adjusted-OR 2.78 [95%CI = 1.06-7.29], p = 0.038); 2) greater anti-oxLDL titers (p = 0.020), which positively associated with TNF-α and likelihood of noncalcified, partially calcified and high-risk plaque presence only in patients with LDL-C<1.8 mmol/L (all p-for-interaction≤0.046); 3) increased lipoprotein(a)-cholesterol content (10.33% [8.11-12.54] versus 6.68% [6.10-7.25], p < 0.001), which positively associated with oxLDL (p < 0.001) and anti-oxLDL (p = 0.036); 4) higher interleukin-6 and PCSK9. No differences in CRP, ESR, or oxLDL were observed. CONCLUSION: RA patients with LDL-C<1.8 mmol/L had more coronary plaque, higher anti-oxLDL titers and anti-oxLDL associated with plaque only in this group. It is possible the observed paradoxical association of low LDL-C with greater atherosclerosis may be related to higher production of the oxidation-prone lipoprotein(a)-cholesterol and anti-oxLDL antibodies, resulting in increased vascular LDL uptake and plaque formation.

Unsupervised machine learning based on clinical factors for the detection of coronary artery atherosclerosis in type 2 diabetes mellitus.

BACKGROUND: Coronary atherosclerosis can lead to serious cardiovascular events. In type 2 diabetes (T2DM) patients, the effects of clinical factors on coronary atherosclerosis have not been fully elucidated. We used a clustering method to distinguish the population heterogeneity of T2DM and the differences in coronary atherosclerosis evaluated on coronary computed tomography angiography (CCTA) among groups and to facilitate clinical management. METHODS: Clinical data from 1157 T2DM patients with coronary atherosclerosis who underwent CCTA in our hospital from January 2018 to September 2021 were retrospectively collected. The coronary artery segment plaque type and stenosis, the number of involved vessels, the segment involvement score (SIS) and the segment stenosis score (SSS) were evaluated and calculated. Unsupervised clustering analysis based on clinical information was used (cluster 1: n = 463; cluster 2: n = 341; cluster 3: n = 353). The association of coronary plaque characteristics with cluster groups was evaluated. RESULTS: The clinical data among the three groups were different in several aspects: (1) Cluster 1 had the least male patients (41.7%), the lowest proportion of patients with smoking (0%) or alcohol history (0.9%), and the lowest level of serum creatinine (74.46 ± 22.18 µmol/L); (2) Cluster 2 had the shortest duration of diabetes (7.90 ± 8.20 years) and was less likely to be treated with diabetes (42.2%) or statins (17.6%) and (3) Cluster 3 was the youngest (65.89 ± 10.15 years old) and had the highest proportion of male patients (96.6%), the highest proportion of patients with smoking (91.2%) and alcohol (59.8%) history, the highest level of eGFR (83.81 ± 19.06 ml/min/1.73m2), and the lowest level of HDL-C (1.07 ± 0.28 mmol/L). The CCTA characteristics varied with different clusters: (1) Cluster 1 had the largest number of segments with calcified plaques (2.43 ± 2.46) and the least number of segments with mixed plaques (2.24 ± 2.59) and obstructive stenosis (0.98 ± 2.00); (2) Cluster 1 had the lowest proportion of patients with mixed plaques (68%) and obstructive stenosis (32.2%); (3) Cluster 3 had more segments with noncalcified plaques than cluster 1 (0.63 ± 1.02 vs 0.40 ± 0.78, P < 0.05) and the highest proportion of patients with noncalcified plaques (39.9%) and (4) There was no significant difference in the extent of coronary plaques among the three clusters. CONCLUSIONS: The unsupervised clustering method could address T2DM patients with heterogeneous clinical indicators and identify groups with different types of coronary plaque and degrees of coronary stenosis. This method has the potential for patient stratification, which is essential for the clinical management of T2DM patients with coronary atherosclerosis.