Extent Of Coronary Atherosclerosis Research Articles

Coronary atherosclerosis among symptomatic patients with zero coronary artery calcium score in computed tomography coronary angiography

BackgroundComputed tomographic coronary angiography has been recognized as a reliable imaging modality with excellent negative predictive value and a good negative likelihood ratio to exclude coronary artery disease in stable, symptomatic patients with intermediate or high risk. 1) Coronary calcium scoring has been extensively shown to be an invaluable tool to exclude the presence of coronary artery disease in low-risk patients. 2) Our aim was to identify the presence and extent of coronary atherosclerosis in computed tomographic coronary angiography in stable symptomatic patients with a zero Coronary Calcium score. ResultsThree hundred and eighty-three (383) consecutive patients aged ≥ 18 years fulfilling the criteria were enrolled as of January 1, 2021; 165 (43.1%) were male and 218 (56.9%) were female, with a mean age of 57.8 ± 4.9 years and a zero coronary artery calcium score. Two hundred and twenty-six (226) (59.0%) were hypertensive, followed by 125 (32.6%) who were smokers, and 117 (30.5%) who were diabetic. The frequency of atherosclerotic plaque in coronary arteries was 34 (8.9%), with 16 (47.1%) being male and 18 (52.9%) being female. The mean age of patients with atherosclerosis was 54.9 ± 3.3 years; among them, 13 (38.2%) were between the ages of 45 and 54, and 10 (29.4%) were between the ages of 55 and 64. Nineteen (19) (55.9%) were hypertensive, followed by 10 (29.4%) with dyslipidemia. Twenty-three (23) (67.6%) had non-obstructive plaque, and 11 (32.3%) had obstructive plaque. In the subgroup of patients with non-obstructive plaque, 13 (56.5%) were hypertensive, 8 (34.8%) were diabetic, and 16 (69.6%) had single vessel disease, while among patients with obstructive plaque, 6 (54.5%) were hypertensive, 5 (45.5%) were smokers, and all of them had single vessel disease. The most affected artery was the left anterior descending artery. ConclusionAs the frequency of atherosclerotic plaque in patients with a zero coronary calcium score is relatively high, computed tomographic coronary angiography is indicated in stable, symptomatic patients with a lower likelihood of coronary artery disease.

Triglyceride glucose index and triglyceride HDL ratio as predictors of coronary artery stenosis in diabetic and non-diabetic patients

Background and aimThe current study investigated the association between triglyceride-glucose index (TyG) and triglyceride/HDL-C indices and coronary atherosclerosis extent in diabetic and non-diabetic patients. Methods and resultsIn this case-control study, 1538 individuals were classified into two groups: diabetic and non-diabetic subjects. Each group was further grouped as follows: (1) angiography+ (2) angiography–and (3) subjects without a history of cardiovascular diseases. The TyG and TG/HDL-C indices were compared between the subgroups of the diabetic (n = 407) and non-diabetic (n = 1131) groups. In both diabetic and non-diabetic patients, there was no significant association in TG/HDL-C; and diabetic subjects, angiography+ and angiography-groups had significantly higher TyG (p < 0.05). A high TyG index was associated with a higher risk of angiography+ (OR: 1.883 (1.410–2.514)). ConclusionsThe TyG index, but not the TG/HDL-C, was an independent marker for predicting the severity of coronary stenosis in non-diabetic patients.

Association of periodontitis and tooth loss with extent of coronary atherosclerosis in patients with type 2 diabetes mellitus.

The objective was to investigate the association of periodontitis and tooth loss with extent of diabetic coronary atherosclerosis. 272 patients who were hospitalized at Shanghai East hospital and underwent a coronary artery calcium (CAC) CT scan were enrolled in this study. Individuals were grouped based on their CAC scores into a normal-to-mild coronary atherosclerosis (AS) group (0 ≤ score ≤ 100, n=184) and a moderate-to-severe group (score≥101, n=88). Periodontitis parameters and number of missing teeth were evaluated for every patient. The severity of periodontitis was categorized as mild, moderate, or severe. The taxonomic composition of the microbiota was determined using full-length 16S ribosomal RNA gene sequencing. Salivary inflammatory factors were tested by ELISA. Clinical attachment loss (CAL) (P =0.05) and the number of teeth lost (P = 0.016) were significantly higher in the moderate-to-severe coronary AS group, with these differences being more obvious in younger patients and patients with short-duration diabetes. Multivariate logistic regression analysis revealed that CAL (OR = 1.231, 95% CI = 1.066-1.214, P = 0.047) and having 10-19 missing teeth (OR = 1.604, 95% CI = 1.393-6.555, P = 0.05) were strongly associated with the presence of moderate-to-severe coronary AS. Salivary IL-6 and TNF-α levels, as well as levels of Porphyromonas gingivalis and Neisseria mucosa, were significantly elevated in the moderate-to-severe coronary AS group. It was found that both tooth loss and CAL were related to the extent of diabetic coronary AS. Saliva inflammatory factors and oral bacteremia may be new biomarkers for moderate-to-severe coronary AS.

Mortality Associated with the Number of Diseased Vessels and Therapeutic Strategies for Coronary Artery Disease: Long-Term Follow-Up

Background: The number of coronary arteries affected by atherosclerosis is believed to impact the prognosis of coronary artery disease, resulting in a higher incidence of cardiac events. However, conclusive results on the relationship between the extent of coronary atherosclerosis and outcomes are lacking. Methods: This retrospective, single-center, observational cohort study included patients with stable coronary artery disease and preserved ventricular function who had the option of any of the three therapeutic strategies (medicine, angioplasty, or surgery) included in the MASS-Trials database. Patients were stratified according to the number of diseased arteries forming single-vessel, double-vessel, and triple-vessel disease groups. The atherosclerotic burden was assessed using the SYNTAX Score. Each group was eligible for any of the three therapeutic strategies. The primary endpoint was overall mortality. Secondary endpoints included the combination of all-cause death, nonfatal myocardial infarction, and additional coronary interventions. Results: Between May 1998 and June 2009, 2,000 patients who met the inclusion criteria in the MASS-Trial database were included. The study enrolled 1,855 patients. Of these, 224(12%) had single-vessel disease (SVD), 536(29%) had double-vessel disease (2VD), and 1,095(59%) had triple-vessel disease (3VD). The entire follow-up of our sample was 5 years. Overall mortality for SVD, 2VD, and 3VD was 9(4%), 33(6.3%), and 43(3.9%), respectively (P=0.054). Pairwise comparison of mortality at 5-year follow-up showed no significant differences between SVD x 2VD, SVD x 3VD, and 2VD x 3VD (hazard ratio [HR] 1.41, 95% CI: 0.81-2.44). The secondary endpoints (combination of overall mortality, nonfatal infarction, and additional revascularization) also revealed no significant differences (P=0.2). Conclusions: Overall mortality was similar regardless of the number of diseased arteries and the degree of arterial involvement. These data suggest that optimized medical treatment as an initial strategy is safe and has a similar rate of events in any applied therapeutic option.

Coronary Atherosclerosis Across the Glycemic Spectrum Among Asymptomatic Adults: The Miami Heart Study at Baptist Health South Florida.

The contemporary burden and characteristics of coronary atherosclerosis, assessed using coronary computed tomography angiography (CCTA), is unknown among asymptomatic adults with diabetes and prediabetes in the United States. The pooled cohort equations and coronary artery calcium (CAC) score stratify atherosclerotic cardiovascular disease risk, but their association with CCTA findings across glycemic categories is not well established. Asymptomatic adults without atherosclerotic cardiovascular disease enrolled in the Miami Heart Study were included. Participants underwent CAC and CCTA testing and were classified into glycemic categories. Prevalence of coronary atherosclerosis (any plaque, noncalcified plaque, plaque with ≥1 high-risk feature, maximal stenosis ≥50%) assessed by CCTA was described across glycemic categories and further stratified by pooled cohort equations-estimated atherosclerotic cardiovascular disease risk and CAC score. Adjusted logistic regression was used to evaluate the associations between glycemic categories and coronary outcomes. Among 2352 participants (49.5% women), the prevalence of euglycemia, prediabetes, and diabetes was 63%, 30%, and 7%, respectively. Coronary plaque was more commonly present across worsening glycemic categories (euglycemia, 43%; prediabetes, 58%; diabetes, 69%), and similar pattern was observed for other coronary outcomes. In adjusted analyses, compared with euglycemia, prediabetes and diabetes were each associated with higher odds of any coronary plaque (OR, 1.30 [95% CI, 1.05-1.60] and 1.75 [1.17-2.61], respectively), noncalcified plaque (OR, 1.47 [1.19-1.81] and 1.99 [1.38-2.87], respectively), and plaque with ≥1 high-risk feature (OR, 1.65 [1.14-2.39] and 2.53 [1.48-4.33], respectively). Diabetes was associated with stenosis ≥50% (OR, 3.01 [1.79-5.08]; reference=euglycemia). Among participants with diabetes and estimated atherosclerotic cardiovascular disease risk <5%, 46% had coronary plaque and 10% had stenosis ≥50%. Among participants with diabetes and CAC=0, 30% had coronary plaque and 3% had stenosis ≥50%. Among asymptomatic adults, worse glycemic status is associated with higher prevalence and extent of coronary atherosclerosis, high-risk plaque, and stenosis. In diabetes, CAC was more closely associated with CCTA findings and informative in a larger population than the pooled cohort equations.

Highlights of Cardiovascular Disease Prevention Studies Presented at the 2023 American College of Cardiology Conference.

To summarize selected late-breaking science on cardiovascular (CV) disease prevention presented at the 2023 American College of Cardiology (ACC) conference. The CLEAR outcomes randomized control trial (RCT) compared bempedoic acid to placebo in patients at high-risk of cardiovascular disease (CVD) or prevalent CVD and statin intolerance for CV outcomes. The YELLOW III was a single-arm study that evaluated the effect of Evolocumab on coronary plaque characteristics in patients with stable coronary artery disease (CAD). A cohort evaluated the association between a self-reported low-carbohydrate high-fat (ketogenic) diet and serum lipid levels as compared to a standard diet. The LOADSTAR trial compared CV outcomes with targeted low-density lipoprotein cholesterol (LDL-C) approach vs. high-intensity statin in patients with CAD. The PCDS statin cluster randomized trial compared the effectiveness of an electronic reminder to the clinician on a high-intensity statin use among patients with a history of ASCVD as compared to no reminder. A prospective cohort study compared the extent of coronary atherosclerosis among lifelong endurance athletes and healthy non-athletes. A causal artificial intelligence study combined polygenic risk scores with data from large CV prevention RCTs to guide systolic blood pressure and LDL-C reduction targets to reach average CV risk. The ACCESS trial evaluated the impact of eliminating copayment for low-income older adults in Canada with chronic CV diseases on composite CV outcomes. A pooled analysis of 3 large RCTs evaluated the association between residual inflammatory risk and CV outcomes, as compared to residual elevated cholesterol risk in patients receiving statin therapy. A Phase 2B RCT compared the efficacy of an oral PCSK9i, MK-0616, in reducing LDL-C as compared to a placebo. The late-breaking clinical science presented at the 2023 conference of the ACC paves the way for an evidence-based alternative to statin therapy and provides data on several common clinical scenarios encountered in daily practice.

Extent of coronary atherosclerosis is associated with deterioration of left ventricular global longitudinal strain in patients with preserved ejection fraction undergoing coronary computed tomography angiography.

This study aimed to investigate the association between the extent and severity of coronary atherosclerosis, epicardial adipose tissue (EAT) accumulation, and left ventricular (LV) global longitudinal strain (GLS) in patients with preserved LV ejection fraction (LVEF) and without LV regional wall motion abnormalities. This study included 169 preserved LVEF patients without LV wall motion abnormalities who underwent coronary computed tomography (CT) angiography for the assessment of suspected coronary artery disease (CAD). The segment stenosis score (SSS) and segment involvement score (SIS) were calculated to evaluate CAD extent. The EAT volume was defined as CT attenuation values ranging from -250 to -30 HU within the pericardial sac. LVGLS was measured using echocardiography to assess subclinical LV dysfunction. All patients had preserved LVEF of≥50%, and the mean LVGLS was -18.7% (-20.5% to -16.9%). Mean SSS and SIS were 2.0 (0-5) and 4.0 (0-36), respectively, while mean EAT volume was 116.1mL (22.9-282.5mL). Multivariate analysis using linear regression model demonstrated that LVEF (β, -17.0; 95% CI, -20.9--13.1), LV mass index (β, 0.03; 95% CI, 0.01-0.06), and EAT volume (β, 0.010; 95% CI, 0.0020-0.0195) were independently associated with LVGLS; however, obstructive CAD was not. The multivariate models demonstrated that SSS (Î, 0.12; 95% CI, 0.05-0.18) and SIS (Î, 0.27; 95% CI, 0.10-0.44) were correlated with deterioration of LVGLS, independent of other parameters. This study demonstrates that EAT volume and CAD extent are associated with the deterioration of LVGLS in this population.

Invasive aortic pulse pressure is linked to cardiac allograft vasculopathy after heart transplantation

BackgroundPulse pressure (PP) has been linked to an increased risk of extent of coronary atherosclerosis and cardiovascular events. This study aimed to investigate the contribution of aortic PP on cardiac allograft vasculopathy (CAV) progression, and cardiovascular events after heart transplantation (HTx). MethodsA total of 330 HTx patients (mean age 49 ± 25 years, 70.0% male) undergoing routine serial coronary intravascular ultrasound (IVUS) studies and had invasive aortic PP were enrolled. The median time from HTx to first IVUS was 13.6 months. CAV progression was assessed by IVUS as the changes (Δ) in plaque volume divided by the segment length (PV/SL), adjusted for the time between IVUS (median, 3.99 years; interquartile range, 1.99–7.20 years), and was defined as ΔPV/SL ≥0.50 mm3/mm/year. Major adverse cardiovascular event (MACE) was defined as any incidence of mortality, myocardial infarction, coronary revascularization, heart failure hospitalization, or re-transplantation. ResultsRecipient age, recipient sex, and renal dysfunction were independent determinant of high aortic PP (≥ 50 mmHg). High aortic PP was an independent determinant of CAV progression [odds ratio, 1.72; 95% confidence interval (CI), 1.01–2.93; p = 0.045]. Both high aortic PP (HR 1.46, 95% CI 1.01–2.11, p = 0.044) and high baseline CAV grade on angiogram (≥1, HR 1.50, 95% CI 1.03–2.21, p = 0.037) were independently associated with MACEs over 12 years. ConclusionIn post-HTx patients, high aortic PP was significantly associated with plaque progression. Both aortic PP and CAV grade are independently associated with MACE during long-term follow-up. These findings suggest that arterial stiffness and CAV can be important predictors of MACEs.

Differential association of high-sensitive cardiac Troponin T and Troponin I with coronary atherosclerotic burden, inducible ischemia and long-term prognosis in patients with chronic coronary syndrome

Abstract Background High-sensitivity (hs) assays for the measurement of cardiac troponin T (cTnT) and cardiac troponin I (cTnI) are now used widely for the diagnosis of myocardial infarction. However, it is also increasingly apparent that troponin concentrations well below the thresholds used in acute coronary syndromes may provide diagnostic and prognostic information also for patients with chronic coronary syndromes (CCS). Purpose This study is aimed at evaluating the association of hs-cTnT and hs-cTnI with clinical/molecular profiles, measures of myocardial ischemia and coronary artery disease (CAD), and their potential role as predictors of adverse cardiovascular events in a population of patients with CCS. Methods Hs-cTnT and hs-cTnI were measured in 365 patients with CCS (mean age 61±8, 217 males) as part of the multicenter Evaluation of Integrated Cardiac Imaging (EVINCI) European study. Patients were characterized for clinical and molecular profile and underwent stress imaging to detect myocardial ischemia and coronary computed tomographic angiography (CTA) to assess the presence of CAD. An individual coronary CTA score was calculated combining extent, severity, composition, and location of plaques. All patients entered a clinical follow-up (1600±369 days). The composite cardiovascular outcome measure included all-cause mortality, non-fatal myocardial infarction, and hospitalization for unstable angina or heart failure. Clinical, molecular, and imaging parameters were used in a multivariate step-wise analysis to identify those associated with hs-cTnT and hs-cTnI. The possible role of troponins as independent predictors of adverse cardiovascular events was evaluated by Kaplan-Meier and Cox analysis. Results The median values (IQR) of hs-cTnT and of hs-cTnI were 6.4 (4.9) ng/L and 4.4 (10.3) ng/L, respectively. In a multivariate model, age, gender, diabetes, NT-proBNP, and CTA score were independently associated with plasma hs-cTnT; triglycerides, HDL-cholesterol, and ischemia were independently associated with hs-cTnI (Table 1); interleukin-6 was associated with both troponins. At Kaplan-Meier analysis, event-free survival was significantly worse in patients with levels higher than the median values of both hs-cnT and hs-cTnI (Figure 1A, B). At Cox analysis, after correction for age, gender, and risk factors (EUROscore), only high hs-cTnI remained an independent predictor of cardiovascular events (hs-cTnT: HR 2.17, 95% CI, 0.87–5.41, P=ns; hs-cTnI: HR 2.65, 95% CI, 1.09–6.44, P=0.031). Conclusion In patients with CCS, the presence and extent of coronary atherosclerosis is related with circulating levels of hs-cTnT, while the presence of ischemia is related with circulating levels of hs-cTnI, suggesting different mechanisms of release. Only high levels of hs-cTnI were independent predictors of cardiovascular events. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Grant from the European Union FP7-CPFP506-2007 (Evaluation ofIntegrated Cardiac Imaging for the Detection and Characterisation of Ischemic Heart Disease).

The relationship of platelet to lymphocyte ratio with the presence and extent of coronary atherosclerosis detected by coronary computed tomography angiography

Objectives: Platelet-lymphocyte ratio (PLR) combines the predictive risk of platelet and lymphocyte counts into a single risk index. PLR has been studied as a predictive marker in a variety of cardiovascular diseases. However, our understanding of the link between PLR and coronary artery disease (CAD) remains limited. The present study aimed to evaluate the relationship between PLR and intensity of coronary atherosclerosis in patients with suspected CAD. Methods: In this retrospective study, we included 221 patients undergoing dual-source 64-slice coronary computed tomography angiography (CCTA). Total and different types of leukocyte counts were measured with an automatic blood counter. Based on a modified version of the American Heart Association's categorisation, the coronary artery tree was divided into 16 segments. To assess the extent of coronary atherosclerosis, the number of affected coronary segments was counted. Coronary artery plaques were classified into three categories: (1) calcified plaque, (2) non-calcified plaque, and (3) mixed plaque. Results: After multivariable backward stepwise regression analysis, PLR remained as an independent predictor for both the presence and extent of coronary atherosclerosis (OR=2.38, 95% CI: 1.27-4.47 and OR=1.66, 95% CI: 1.10-2.51, respectively). There was no significant relationship between PLR and plaque morphology. Conclusions: Higher PLR was associated with the intensity of coronary atherosclerosis detected by CCTA. Further research is necessary to determine the optimal approach to using PLR in medical practice.

Assessment of Clinical Features in HIV-Infected Patients with Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention in China.

Objectives We aimed to compare coronary risk factors, burden of coronary artery disease (CAD), and 1-year prognosis of people living with HIV (PLWH) and HIV-negative controls who underwent percutaneous coronary intervention (PCI) for acute coronary syndromes (ACSs). Background Cardiovascular disease is drawing more and more attention in PLWH since effective antiretroviral therapy (ART) has been available. Clinical characteristics and outcomes of PLWH undergoing PCI for ACS in China remain unknown. Methods We compared demographic characteristics, angiographic features, and 1-year outcomes of 48 PLWH versus 48 HIV-negative controls matched for age (±2 years), sex, diabetes mellitus, and year of PCI (±2 years) in Beijing Ditan Hospital, Capital Medical University from January 2008 to November 2020. Results In PLWH (mean age: 53.6 ± 10.6 years, 95.8% male, and 79.2% on ART), high-density lipoprotein cholesterol was lower than in HIV-negative controls; however, the statin use was more common, the incidence of hypertension was lower, and low-density lipoprotein cholesterol, and the body mass index were significantly lower than in controls. Two groups had a similar extent of coronary atherosclerosis as measured by the presence of multivessel diseases and the median Gensini score; however, lesions of PLWH were longer and were more likely to locate at the proximal segment of the coronary artery. In addition, the risk of major adverse cardiac and cerebrovascular events at 1 year was similar in both groups. Conclusion PLWH undergoing PCI displayed similar CAD burden and 1-year prognosis compared with HIV-negative patients. Early detection of cardiovascular risk factors and appropriate secondary prevention of CAD in PLWH might alleviate the risk of severe adverse cardiovascular events.

A Novel Integrated Biomarker for Evaluation of Risk and Severity of Coronary Atherosclerosis, and Its Validation

Objective: To assess the feasibility of a combination of biochemical and imaging parameters for estimation of risk and severity of coronary atherosclerosis (CA), and to verify the created integrated biomarker (i-BIO) on independent cohort. Methods: Two cohorts of patients admitted to the hospital for coronary angiography and ultrasound carotid dopplerography were enrolled into the study (n = 205 and n = 216, respectively). The extent of CA was assessed by Gensini Score (GS). Results: According to GS, participants were distributed as follows: atherosclerosis-free (GS = 0), CA of any stage (GS > 0), subclinical CA (GS < 35), severe CA (GS ≥ 35). Based on the analysis of mathematical models, including biochemical and imaging parameters, we selected and combined the most significant variables as i-BIO. The ability of i-BIO to detect the presence and severity of CA was estimated using ROC-analysis with cut-off points determination. Risk of any CA (GS > 0) at i-BIO > 4 was 7.3 times higher than in those with i-BIO ≤ 4; risk of severe CA (GS ≥ 35) at i-BIO ≥ 9 was 3.1 times higher than at i-BIO < 9. Results on the tested cohort confirmed these findings. Conclusions: The i-BIO > 4 detected CA (GS > 0) with sensitivity of 87.9%, i-BIO ≥ 9 excluded patients without severe CA (GS < 35), specificity 79.8%. Validation of i-BIO confirmed the feasibility of i-BIO > 4 to separate patients with any CA with sensitivity 76.2%, and of i-BIO ≥ 9 to exclude atherosclerosis-free subjects with specificity of 84.0%.

Cumulative exposure amount of PM2.5 in the ambient air is associated with coronary atherosclerosis - Serial coronary CT angiography study

BackgroundWe investigated the change of coronary atherosclerosis with long-term exposure to fine particulate matter of aerodynamic diameter <2.5 ​μm (PM2.5) using coronary computed tomography angiography (CCTA). MethodsSubjects undergoing serial CCTAs between January 2007 and December 2017 (n ​= ​3,127) were analyzed. Each individual's cumulative amount of PM2.5 exposure between the two CCTAs was evaluated by Kriging interpolation and zonal analysis, considering the time interval between the two CCTAs. The main outcome was progression of coronary artery calcium (CAC) with additional semiquantitative analysis on the changes in the severity and composition of atherosclerotic plaques. ResultsThe CAC scores increased by 30.8 Agatston units per-year under a median PM2.5 concentration 24.9 ​μg/m3 and tended to increase with the cumulative amount of PM2.5 exposure (r ​= ​0.321, p ​<0.001). The CAC progressed in 1,361 (43.5%) subjects during a median 53 months follow-up. The cumulative amount of PM2.5 exposure was independently associated with CAC progression (adjusted OR 1.09, p ​<0.001). By random forest analysis, the relative impact of cumulative amount of PM2.5 exposure on CAC progression was higher than that of traditional cardiovascular risk factors and the average concentration of PM2.5. The extent of coronary atherosclerosis and newly developed calcified plaque on follow-up were also significantly associated with the cumulative amount of PM2.5 exposure. ConclusionsCumulative exposure to air pollution is associated with the progression of diffuse coronary calcification, the importance of which may be more significant than other traditional cardiovascular risk factors. Further investigations into the causality between PM2.5 and coronary atherosclerosis are warranted to improve global cardiovascular health.

Biomarkers of Vascular Inflammation for Cardiovascular Risk Prognostication: A Meta-Analysis

ObjectivesThe purpose of this study was to systematically explore the added value of biomarkers of vascular inflammation for cardiovascular prognostication on top of clinical risk factors. BackgroundMeasurement of biomarkers of vascular inflammation is advocated for the risk stratification for coronary heart disease (CHD). MethodsWe systematically explored published reports in MEDLINE for cohort studies on the prognostic value of common biomarkers of vascular inflammation in stable patients without known CHD. These included common circulating inflammatory biomarkers (ie, C-reactive protein, interleukin-6 and tumor necrosis factor-a, arterial positron emission tomography/computed tomography and coronary computed tomography angiography–derived biomarkers of vascular inflammation, including anatomical high-risk plaque features and perivascular fat imaging. The main endpoint was the difference in c-index (Δ[c-index]) with the use of inflammatory biomarkers for major adverse cardiovascular events (MACEs) and mortality. We calculated I2 to test heterogeneity. This study is registered with PROSPERO (CRD42020181158). ResultsA total of 104,826 relevant studies were screened and a final of 39 independent studies (175,778 individuals) were included in the quantitative synthesis. Biomarkers of vascular inflammation provided added prognostic value for the composite endpoint and for MACEs only (pooled estimate for Δ[c-index]% 2.9, 95% CI: 1.7-4.1 and 3.1, 95% CI: 1.8-4.5, respectively). Coronary computed tomography angiography–related biomarkers were associated with the highest added prognostic value for MACEs: high-risk plaques 5.8%, 95% CI: 0.6 to 11.0, and perivascular adipose tissue (on top of coronary atherosclerosis extent and high-risk plaques): 8.2%, 95% CI: 4.0 to 12.5). In meta-regression analysis, the prognostic value of inflammatory biomarkers was independent of other confounders including study size, length of follow-up, population event incidence, the performance of the baseline model, and the level of statistical adjustment. Limitations in the published literature include the lack of reporting of other metrics of improvement of risk stratification, the net clinical benefit, or the cost-effectiveness of such biomarkers in clinical practice. ConclusionsThe use of biomarkers of vascular inflammation enhances risk discrimination for cardiovascular events.

The role of soluble leptin receptor in the pathogenesis of coronary heart disease

Introduction. The participation of soluble leptin receptor (SLR) in the formation of hyperleptinemia and leptin resistance in patients with coronary artery disease (CAD) in combination with obesity is discussed. Aim. Study of the role of SLR in the pathogenesis of ischemic heart disease. Materials and methods. A cohort study of 744 patients was performed: 465 patients with CAD (56 years old, Q1=44; Q3=62), 270 patients without CAD (52 years old, Q1=44; Q3=56). Methods: EchoCG, heart computed tomography, coronary angiography. In the blood serum, the lipids, glucose, creatinine, uric acid, and c-reactive protein were assessed using a highly sensitive method (HF-CRP). Concentrations of SLR, leptin (LN), adiponectin (total and high molecular weight), fatty acid binding protein-4 (FABP-4) tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), serum insulin were determined by enzyme immunoassay. Results. The level of SLR in blood serum in men and women with CAD is lower than in men without CAD (p &lt;0.001). In CAD patients, obesity was associated with a low SLR level in the blood serum and a high free LN index. At a serum SLR concentration of &lt;7.5ng/ml in men with CAD, the incidence of obesity was higher simultaneously with signs of visceral obesity of the heart, the presence of atherosclerotic plaques in the common carotid arteries, high glycaemic levels, insulin, IL-6, and LN in serum, serum LN/adiponectin ratio and a high HOMA-IR index. Diabetes mellitus, visceral obesity, high levels of hs-CRP, TNF-α, FABP-4, serum insulin, and HOMA-IR index were more often detected in women with coronary artery disease with SLR &lt;10.2 ng/ml. In men and women with CAD, there were no differences in SLR concentration depending on the extent of coronary atherosclerosis. Conclusion. An increase in the free LN index indicates the disruption of connections in the leptin-receptor system and reflects the mechanisms of compensation for overcoming the resistance of peripheral tissues to leptin, which is confirmed by a noticeable negative relationship between the levels of SLR and leptin in the serum of men with coronary artery disease. A low concentration of SLR in patients with CAD is associated with obesity, pro-atherogenic and pro-inflammatory markers of cardiovascular diseases.

Прогресування фіброзу печінки у хворих на стабільну ішемічну хворобу серця на тлі неалкогольної жирової хвороби печінки

Мета: оцінити жорсткість печінки у хворих на стабільну ішемічну хворобу серця (ІХС) на тлі неалкогольної жирової хвороби печінки (НАЖХП) залежно від вираженості коронарного атеросклерозу. Матеріали і методи. Обстежено 220 хворих на стабільну ІХС, поєднану з НАЖХП. Серед них були виділені пацієнти з неалкогольним жировим гепатозом (НАЖГ) та неалкогольним стеатогепатитом (НАСГ). Контрольну групу становили 20 практично здорових осіб. Усім хворим проведено загальноклінічне обстеження, електрокардіографію, коронарографію, еластографію, оцінку функціонального стану печінки. Результати. Аналіз отриманих результатів виявив підвищення жорсткості печінки в усіх групах хворих порівняно з контролем. Зокрема, у хворих із НАЖГ швидкість зсувної хвилі вірогідно перевищувала показник здорових осіб у всіх групах хворих. За умов НАСГ показник жорсткості паренхіми печінки більше ніж вдвічі перевищував рівень контрольної групи. Встановлено вірогідну відмінність стану паренхіми печінки залежно від стадії НАЖХП. Аналіз стадійності фібротичних змін печінки виявив певні закономірності залежно від прогресування НАЖХП. Зокрема, стадія F1 фіброзу печінки мала місце у більше ніж половини хворих групи ІА (р &lt; 0,05). У хворих групи ІБ на фоні НАСГ близько у 60 % осіб спостерігали стадію F2 фіброзу (р &lt; 0,05), а у 25 % пацієнтів — стадію F3. У хворих ІІ групи стадійність фіброзу суттєво не відрізнялась від пацієнтів І групи. Найбільш прогностично несприятливий перебіг НАЖХП виявлено у ІІІ групі. Зокрема, у 34,8 % осіб групи ІІІА спостерігали стадію F2 фіброзу, у випадку НАСГ у понад 70 % хворих групи ІІІБ виявляли значні фібротичні зміни паренхіми печінки стадії F3 (р &lt; 0,05). Більше того, понад 13 % пацієнтів групи ІІІБ мали стадію F4 фіброзу. Висновки. Перебіг НАЖХП у хворих на стабільну ІХС характеризується підвищенням жорсткості паренхіми печінки, що вірогідно залежить від стадії НАЖХП та є більш вираженою на тлі НАСГ. Прогресування фіброзу печінки у хворих із НАЖХП, що поєднана зі стабільною ІХС, залежить від вираженості коронарного атеросклерозу та є найбільш прогностично несприятливим у хворих із перенесеним гострим коронарним синдромом та вираженими рубцевими змінами міокарда.

Sexual Dysfunction and the Impact of Beta-Blockers in Young Males With Coronary Artery Disease.

Objective: We aimed to assess the association of erectile dysfunction (ED) with the extent of coronary atherosclerosis, and to examine whether revascularization and medication use have an impact on ED status in patients with early onset of coronary artery disease (EOCAD).Methods: International Index of Erectile Function (IIEF-5) was used to evaluate sexual function in 296 male patients with EOCAD (age, 39.9 ± 4.8 years), and 354 male controls (age, 40.6 ± 4.4 years). The extent of coronary atherosclerosis was measured by Gensini score. Endothelial function was evaluated by two vasomotor indexes including endothelin-1 (ET-1) and nitric oxide (NO) by ELISA.Results: ED was more frequent (57.8 vs. 31.1%, P < 0.001) and serious (IIEF-5 score:17.7 ± 6.0 vs. 21.6 ± 5.0, P < 0.001) among EOCAD patients than that among controls. IIEF-5 score was negatively correlated with Gensini score (r = −0.383, P < 0.001). The adjusted odds ratio (OR) for the presence of ED (EOCAD vs. controls) was 1.88 [95% confidential interval (CI), 1.12-3.18]. However, ET-1 and NO attenuated the association between ED and EOCAD (adjusted OR: 1.54, 95% CI: 0.84-2.80). IIEF-5 score increased after coronary revascularization in patients not on beta-blockers (18.71 ± 4.84 vs. 17.59 ± 6.05, P < 0.001) as compared with baseline, while stayed unchanged in the subgroup using beta-blockers (17.82 ± 5.12 vs. 17.70 ± 5.98, P = 0.09).Conclusions: ED was common in patients with EOCAD, and associated with the severity of coronary atherosclerosis. Endothelial dysfunction may be a pathophysiologic mechanism underlying both ED and EOCAD. Coronary revascularization confers a benefit in ED amelioration, while this effect did not appear in patients using beta-blocker.

Fibrinogen and a Triad of Thrombosis, Inflammation, and the Renin-Angiotensin System in Premature Coronary Artery Disease in Women: A New Insight into Sex-Related Differences in the Pathogenesis of the Disease.

Coronary artery disease (CAD) is the leading cause of morbidity and mortality in women worldwide. Its social impact in the case of premature CAD is particularly devastating. Many differences in the presentation of the disease in women as compared to men, including atypical symptoms, microvascular involvement, and differences in pathology of plaque formation or progression, make CAD diagnosis in women a challenge. The contribution of different risk factors, such as smoking, diabetes, hyperlipidemia, or obesity, may vary between women and men. Certain pathological pathways may have different sex-related magnitudes on CAD formation and progression. In spite of the already known differences, we lack sufficiently powered studies, both clinical and experimental, that assess the multipathogenic differences in CAD formation and progression related to sex in different age periods. A growing quantity of data that are presented in this article suggest that thrombosis with fibrinogen is of more concern in the case of premature CAD in women than are other coagulation factors, such as factors VII and VIII, tissue-type plasminogen activator, and plasminogen inhibitor-1. The rise in fibrinogen levels in inflammation is mainly affected by interleukin-6 (IL-6). The renin–angiotensin (RA) system affects the inflammatory process by increasing the IL-6 level. Unlike in men, in young women, the hypertensive arm of the RA system is naturally downregulated by estrogens. At the same time, estrogens promote the fibrinolytic path of the RA system. In young women, the promoted fibrinolytic process upregulates IL-6 release from leukocytes via fibrin degradation products. Moreover, fibrinogen, whose higher levels are observed in women, increases IL-6 synthesis and exacerbates inflammation, contributing to CAD. Therefore, the synergistic interplay between thrombosis, inflammation, and the RA system appears to have a more significant influence on the underlying CAD atherosclerotic plaque formation in young women than in men. This issue is further discussed in this review. Fibrinogen is the biomolecule that is central to these three pathways. In this review, fibrinogen is shown as the biomolecule that possesses a different impact on CAD formation, progression, and destabilization in women to that observed in men, being more pathogenic in women at the early stages of the disease than in men. Fibrinogen is a three-chain glycoprotein involved in thrombosis. Although the role of thrombosis is of great magnitude in acute coronary events, fibrinogen also induces atherosclerosis formation by accumulating in the arterial wall and enabling low-density lipoprotein cholesterol aggregation. Its level rises during inflammation and is associated with most cardiovascular risk factors, particularly smoking and diabetes. It was noted that fibrinogen levels were higher in women than in men as well as in the case of premature CAD in women. The causes of this phenomenon are not well understood. The higher fibrinogen levels were found to be associated with a greater extent of coronary atherosclerosis in women with CAD but not in men. Moreover, the lysability of a fibrin clot, which is dependent on fibrinogen properties, was reduced in women with subclinical CAD compared to men at the same stage of the disease, as well as in comparison to women without coronary artery atherosclerosis. These findings suggest that the magnitude of the pathological pathways contributing to premature CAD differs in women and men, and they are discussed in this review. While many gaps in both experimental and clinical studies on sex-related differences in premature CAD exist, further studies on pathological pathways are needed.

Impact of iron status and inflammatory indices on atherosclerotic burden of patients with helicobacter pylori infection and coronary arterial disease

Objective: Both inflammation and iron deficiency are suggested to be associated with coronary arterial diseases (CAD) and H. Pylori infection. The explanatory interaction depending on serum iron status and inflammatory biomarkers for the extent of atherosclerosis in H. Pylori infection is obscure. Therefore, we aimed to analyze the impact of iron Status and inflammatory indices on atherosclerotic burden of seropositive CAD patients with CagA (cytotoxin-associated gene A) strains of H. Pylori.&#x0D; Materials and Methods: This was an observational study of patients' undergone elective and urgent coronary angiography due to CAD. Serologic H. pylori infection status and iron status was determined in all of 293 subjects. Further seropositive patients were divided into groups to evaluate the extent of coronary atherosclerosis according to Syntax scoring system. Propensity score matching and covariate- adjusted multivariate logistic regression were used to adjust for baseline differences between study groups.&#x0D; Results: The odds ratio of positive serology for the presence of iron deficiency and acute coronary syndromes were 2.5 (95% CI (1.1-5.4); p = 0.02) and 3.0 (95% CI (1.3-7.0); p = 0.007) respectively. After controlling for diabetes mellitus, smoking, MPV, RDW and haemoglobin levels; Tsat ≤ 24.5 remained negatively associated with advanced atherosclerosis (OR:9.9, 95% CI (4.1-24.3); p &lt; 0.0001). In our matched sample, multivariable linear regression analysis showed that association of syntax score with Tsat was independent of hs-CRP (p=0.001).&#x0D; Conclusions: Irrespective of inflammatory status, transferrin saturation can be the decisive mirror indicator of advanced atherosclerosis in seropositive CAD patients with CagA strains of H. Pylori.

Relation between Baseline Coronary Atherosclerotic Status, Cardiovascular Events, and Malignancies in Type 2 Diabetics: A Long-Term Prospective Cohort Study

Introduction: Coronary artery disease and malignancy occur more frequently in patients with type 2 diabetes. They may share inflammation as a possible common pathogenetic mechanism, but it is unclear whether a clinical correlation exists between them. Methods: This prospective cohort study followed 735 asymptomatic diabetics, aged 63.4 ± 5.3 years (mean ± standard deviation) for 12.2 ± 0.6 years after baseline coronary artery calcium scoring and cardiac computed tomography angiography. We examined extent and nature of coronary atherosclerosis and incidence of clinical cardiovascular (CV) events (death or myocardial infarction) and sought a relation to incidence of malignancy and malignancy mortality. Results: Total mortality was 16.5% (121/735 patients): malignancy was cause of death in 48/121 (39.7%) of these and CV events in 44/121 (36.3%). There was no relation between extent of coronary atherosclerosis and incident malignancy (plaque volume 127 [21, 427] mm³ (median [interquartile range]) for incident malignancy versus 153 [24, 427] mm³ no malignancy, p = 0.71) or death from malignancy (plaque volume 176 [26, 646] versus 144 [22, 411] mm³, p = 0.32). There was also no relation between presence of high-risk plaque and incident malignancy (high-risk plaque in 27.1% with malignancy vs. 21.6% without, p = 0.18) or fatal malignancy (p = 0.16). Incident and fatal malignancy were not related to clinical CV events. Independent predictors of incident and fatal malignancy were age, smoking at baseline, and elevated C-reactive protein. Conclusion: This study found no relation between extent of coronary atherosclerosis or incidence of CV events and malignancy. Malignancy surpassed CV disease as the commonest long-term cause of mortality in middle-aged and older diabetics.