Development Of Coronary Atherosclerosis Research Articles

Coronary heart disease and tuberculosis: an unnoticed syndemia. Review of literature and management proposal.

Tuberculosis is an increasing disease that affects about one-third of the global population. In line with the rise of tuberculosis, cardiovascular disease has shown a similar trend, with ischemic coronary heart disease becoming the leading cause of death worldwide. Based on the literature, a relationship can be drawn between tuberculosis and ischemic coronary heart disease through their shared multiple risk factors and a possible pathophysiological substrate linking them. The presentation of these two conditions reported so far is varied: it has been found as the onset of acute coronary syndrome in patients with active tuberculosis, the progressive development of coronary atherosclerosis in patients with latent tuberculosis, among others. Given this possible link and the progressive increase in their incidence rates, we can assert that we are facing an unnoticed syndemic, with their concurrent management posing a challenge due to significant pharmacological interactions. The purpose of this review is to clarify this possible link, propose an approach for diagnosis, and provide a treatment algorithm for the entire spectrum of coronary disease coexisting with tuberculosis according to the current available literature.

Coronary Plaque in Athletes.

The relationship between vigorous physical activity (PA) and the development of coronary atherosclerosis has remained less explored for many years. Recently, literature data have focused on coronary atherosclerosis in athletes showing that prevalence is not trivial, that there are differences among various types of sport, and that there are some peculiar features. As a matter of fact, plaque composition in athletes seems to be characterized by calcium rather than soft components. Specific mechanisms through which vigorous PA influences coronary artery disease are not yet fully understood. However, the prevalent calcific nature of coronary plaques in athletes could be related with a trend in a lower cardiovascular event rate.

Rewiring Endothelial Sphingolipid Metabolism to Favor S1P Over Ceramide Protects From Coronary Atherosclerosis.

Growing evidence correlated changes in bioactive sphingolipids, particularly S1P (sphingosine-1-phosphate) and ceramides, with coronary artery diseases. Furthermore, specific plasma ceramide species can predict major cardiovascular events. Dysfunction of the endothelium lining lesion-prone areas plays a pivotal role in atherosclerosis. Yet, how sphingolipid metabolism and signaling change and contribute to endothelial dysfunction and atherosclerosis remain poorly understood. We used an established model of coronary atherosclerosis in mice, combined with sphingolipidomics, RNA-sequencing, flow cytometry, and immunostaining to investigate the contribution of sphingolipid metabolism and signaling to endothelial cell (EC) activation and dysfunction. We demonstrated that hemodynamic stress induced an early metabolic rewiring towards endothelial sphingolipid de novo biosynthesis, favoring S1P signaling over ceramides as a protective response. This finding is a paradigm shift from the current belief that ceramide accrual contributes to endothelial dysfunction. The enzyme SPT (serine palmitoyltransferase) commences de novo biosynthesis of sphingolipids and is inhibited by NOGO-B (reticulon-4B), an ER membrane protein. Here, we showed that NOGO-B is upregulated by hemodynamic stress in myocardial EC of ApoE-/- mice and is expressed in the endothelium lining coronary lesions in mice and humans. We demonstrated that mice lacking NOGO-B specifically in EC (Nogo-A/BECKOApoE-/-) were resistant to coronary atherosclerosis development and progression, and mortality. Fibrous cap thickness was significantly increased in Nogo-A/BECKOApoE-/- mice and correlated with reduced necrotic core and macrophage infiltration. Mechanistically, the deletion of NOGO-B in EC sustained the rewiring of sphingolipid metabolism towards S1P, imparting an atheroprotective endothelial transcriptional signature. These data demonstrated that hemodynamic stress induced a protective rewiring of sphingolipid metabolism, favoring S1P over ceramide. NOGO-B deletion sustained the rewiring of sphingolipid metabolism toward S1P protecting EC from activation under hemodynamic stress and refraining coronary atherosclerosis. These findings also set forth the foundation for sphingolipid-based therapeutics to limit atheroprogression.

Glycemic variability assessed using continuous glucose monitoring in individuals without diabetes and associations with cardiometabolic risk markers: A systematic review and meta-analysis

Continuous glucose monitoring (CGM) provides data on short-term glycemic variability (GV). GV is associated with adverse outcomes in individuals with diabetes. Whether GV is associated with cardiometabolic risk in individuals without diabetes is unclear. We systematically reviewed the literature to assess whether GV is associated with cardiometabolic risk markers or outcomes in individuals without diabetes. Searches were performed in PubMed/Medline, Embase and Cochrane from inception through April 2022. Two researchers were involved in study selection, data extraction and quality assessment. Studies evaluating GV using CGM for ≥24h were included. Studies in populations with acute and/or critical illness were excluded. Both narrative synthesis and meta-analyzes were performed, depending on outcome. Seventy-one studies were included; the majority were cross-sectional. Multiple measures of GV are higher in individuals with compared to without prediabetes and GV appears to be inversely associated with beta cell function. In contrast, GV is not clearly associated with insulin sensitivity, fatty liver disease, adiposity, blood lipids, blood pressure or oxidative stress. However, GV may be positively associated with the degree of atherosclerosis and cardiovascular events in individuals with coronary disease. GV is elevated in prediabetes, potentially related to beta cell dysfunction, but less clearly associated with obesity or traditional risk factors. GV is associated with coronary atherosclerosis development and may predict cardiovascular events and type 2 diabetes. Prospective studies are warranted, investigating the predictive power of GV in relation to incident disease. GV may be an important risk measure also in individuals without diabetes.

Sex differences in coronary atherosclerosis during the pre- and postmenopausal period: The Tampere Sudden Death Study

Background and aimsWomen are believed to be protected from coronary heart disease (CHD) by the effects of estrogen but detailed studies on the vessel wall level are missing. We aimed to measure sex differences in atherosclerosis during the premenopausal and postmenopausal periods directly at the coronary arteries. MethodsWe analyzed statistics for sex differences in CHD mortality in Finland in 2020. Coronary atherosclerosis was measured using computer-assisted morphometry in 10-year age groups of 185 white Caucasian women and 515 men from the Tampere Sudden Death Study. ResultsCHD mortality was rare in both women and men before 50 years of age. After 50 years of age, male mortality increased rapidly, with women reaching equal levels in the oldest age groups. In the autopsy series, there were no differences in fatty streak, fibrotic or calcified plaque areas, nor in the plaque area or stenosis percentage in coronary arteries between premenopausal women and men in the same age group. The plaque area remained 25 % smaller in both coronaries in postmenopausal women aged 51–70 years compared to men. In the oldest postmenopausal group (≥70 years), plaque area reached the level of men. In the postmenopausal period, coronary stenosis in the left anterior descending (LAD) artery remained lower among women. ConclusionWe did not detect any major sex-difference in coronary atherosclerosis in the premenopausal period when women are considered to be protected from CHD. However, in line with CHD mortality statistics, postmenopausal women showed a slower speed of coronary atherosclerosis development compared to men.

Unlocking the mysteries of VLDL: exploring its production, intracellular trafficking, and metabolism as therapeutic targets

Reducing circulating lipid levels is the centerpiece of strategies for preventing and treating atherosclerotic cardiovascular disease (ASCVD). Despite many available lipid-lowering medications, a substantial residual cardiovascular risk remains. Current clinical guidelines focus on plasma levels of low-density lipoprotein (LDL). Recent attention has been given to very low-density lipoprotein (VLDL), the precursor to LDL, and its role in the development of coronary atherosclerosis. Preclinical investigations have revealed that interventions targeting VLDL production or promoting VLDL metabolism, independent of the LDL receptor, can potentially decrease cholesterol levels and provide therapeutic benefits. Currently, methods, such as mipomersen, lomitapide, and ANGPTL3 inhibitors, are used to reduce plasma cholesterol and triglyceride levels by regulating the lipidation, secretion, and metabolism of VLDL. Targeting VLDL represents an avenue for new lipid-lowering strategies. Interventions aimed at reducing VLDL production or enhancing VLDL metabolism, independent of the LDL receptor, hold promise for lowering cholesterol levels and providing therapeutic benefits beyond LDL in the management of ASCVD.

Detection of monosodium urate depositions and atherosclerotic plaques in the cardiovascular system by dual-energy computed tomography

AimThe study aimed to explore the relationship between urate deposition and surrounding atherosclerotic plaques, and to confirm the contribution of urate deposition to the development of coronary atherosclerosis. Methods and resultsThe present study employed Dual-energy CT (DECT) material separation technology through calcium score scan to access the presence of MSU crystal deposition in coronary atherosclerotic plaques in patients with clinically suspected coronary heart diseases undergoing DECT. DECT showed that among 872 patients, 441 had plaques in coronary arteries; the incidence of plaque was 50.6 %. The patients were divided in the atherosclerotic plaque vs. non-plaque groups. There were significant differences in age, sex, blood pressure, blood glucose, serum creatinine, and history of gout and hyperuricemia between the plaque and non-plaque groups (all P < 0.05). Among the patients with coronary plaques, there were 348 patients (78.9 %) with simple atherosclerotic plaque (AP), 8 (1.8 %) with simple urate depositions (UD), and 85 (19.3 %) with urate depositions and atherosclerotic plaques (UDAP). The multivariable analysis showed that urate deposition was independently associated with plaques after adjustment for age, sex, blood pressure, blood glucose, serum creatinine, history of gout, and history of hyperuricemia (OR = 13.69, 95%CI: 7.53–22.95, P = 0.035). UPAP patients had significantly higher coronary calcium scores than AP patients [210.1 (625.2) AU vs 58.2 (182.5) AU, P < 0.001] Urate deposition (16.7 mm3) positively correlated with plaque calcification (73.8 mm³) in UPAP patients (r = 0.325, P < 0.001). ConclusionPatients with gout or a history of hyperuricemia were more likely to exhibit UDAP. Urate deposition was independently associated with plaques.

Role of dysregulated macrophage subpopulation ratios and functional changes in the development of coronary atherosclerosis.

Coronary heart disease is one of the most significant risk factors affecting human health worldwide. Its pathogenesis is intricate, with atherosclerosis being widely regarded as the leading cause. Aberrant lipid metabolism in macrophages is recognized as one of the triggering factors in atherosclerosis development. To investigate the role of macrophages in the formation of coronary artery atherosclerosis, we utilized single-cell data from wild-type mice obtained from the aortic roots and ascending aortas after long-term high-fat diet feeding, as deposited in GSE131776. Seurat software was employed to refine the single-cell data in terms of scale and cell types, facilitating the identification of differentially expressed genes. Through the application of differential expression genes, we conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analyses at 0, 8 and 16 weeks, aiming to uncover pathways with the most pronounced functional alterations as the high-fat diet progressed. The AddModuleScore function was employed to score the expression of these pathways across different cell types. Subsequently, macrophages were isolated and further subdivided into subtypes, followed by an investigation into intercellular communication within these subtypes. Subsequent to this, we induced THP-1 cells to generate foam cells, validating critical genes identified in prior studies. The results revealed that macrophages underwent the most substantial functional changes as the high-fat diet progressed. Furthermore, two clusters were identified as potentially playing pivotal roles in macrophage functional regulation during high-fat diet progression. Additionally, macrophage subtypes displayed intricate functionalities, with mutual functional counterbalances observed among these subtypes. The proportions of macrophage subtypes and the modulation of anti-inflammatory and pro-inflammatory functions played significant roles in the development of coronary artery atherosclerosis.

Incidence of flow-limiting coronary artery stenoses in patients with diabetes - a coronary angiography natural history study

Abstract Background Diabetes is an established risk factor for the development of coronary atherosclerosis. We sought to assess the association between diabetes and the incidence of coronary artery atherosclerosis progression on coronary angiography. Methods Using the Swedish Coronary Angiography and Angioplasty Registry (SCAAR), we included all coronary artery segments with mild to no atherosclerosis defined as &amp;lt;50% luminal obstruction in patients undergoing a first-time coronary angiography in Sweden between 1989 and 2017. Patients with two or more vessel disease were excluded as were patients with a previous history of coronary artery disease. In patients with one vessel disease, the diseased vessel including all its branches were excluded. Patients were followed for 15 years until a clinically indicated re-angiography was done, death occurred or end of follow-up (April 2018). The primary outcome was plaque progression to flow-limiting coronary artery stenosis defined as ≥50% luminal obstruction on repeat angiography assessed using epidemiological tables, Kaplan Meier event rates, and Cox proportional hazard models. The importance of selected risk factors (smoking, hypertension, hyperlipidemia, and established coronary artery disease) was assessed. Results A total of 2 661 245 coronary segments in 248 736 patients were included in the study. Diabetes was present in 30 533 patients and 320 815 coronary artery segments. Kaplan-Meier event rates and incidence rates (IR) per 1000 segment-years were higher in patients with diabetes (5.5%, IR 2.78 [95% CI 2.70–2.85] vs. 3.0%, 1.44 [1.42–1.46]) resulting in an almost two-folded hazard ratio (HR) of plaque progression (HR 1.93 [95% CI 1.87– 2.00]). The anatomical distribution of plaque progression was similar between the two cohorts on all levels of analysis (coronary artery level, main artery and branches level, and coronary segment level artery). Diabetic patients with established coronary artery disease had a significantly higher risk of future events compared to those without clinically significant coronary artery disease. Conclusions Diabetes was associated with an almost twofold higher incidence rate of plaque progression but did not appear to alter the anatomical location of plaque development compared to the absence of diabetes. Once coronary artery disease is established, the rate of atherosclerotic events accelerates. Therefore, adopting aggressive primary prevention strategies is crucial to reduce the risk of adverse outcomes in diabetic patients.Event rates and anatomical distributionProgression of stenoses by risk factor

Dynamic changes in inflammatory responses and 3-year clinical outcomes of XINSORB scaffolds in coronary stenting

BackgroundInflammation is known to play a crucial role in the development of coronary atherosclerosis and vascular healing after stenting. This study aimed to investigate the dynamic changes in inflammatory responses between XINSORB and TIVOLI scaffolds and their correlation with 3-year clinical outcomes. MethodA total of 140 patients in the XINSORB group and 42 patients in the TIVOLI group were included in this prospective, single-center study, conducted in Shanghai tenth People's Hospital. Blood samples were collected at baseline, 24 h, 6 months, and 12 months after stent implantation to measure high sensitivity C-reactive protein (hsCRP), fibrinogen (FBG), white blood cell count (WBC), tumor necrosis factor (TNF), and interleukin-6 (IL-6). Receiver-operating characteristic curves and proportional hazards models were generated to evaluate the relationship between 24-h postoperative inflammatory indicators and 3-year patient-oriented composite endpoints (POCE). ResultThe levels of hsCRP, FBG, WBC, TNF, and IL-6 reached their peak levels 24 h after stenting and then gradually decreased to levels comparable to baseline at 6 and 12 months. During the 3-year follow-up, 11.4 % of the XINSORB cohort and 9.5 % of the TIVOLI cohort experienced POCE (P = 0.948). High levels of hsCRP and IL-6 24 h after the procedure were associated with clinical endpoints, and the combination of these two biomarkers improved the predictive ability of prognosis. ConclusionsThere were no significant differences between the changes in the concentration of inflammatory biomarkers after XINSORB stents or drug-eluting stent implantation. Reduction in postoperative inflammatory levels may decrease the occurrence of clinical outcomes. This study provides insights into the dynamic changes of inflammatory responses and their correlation with clinical outcomes, which could have implications for the management of patients undergoing coronary stenting. Trial registrationThe study has been registered on the official website of the China Clinical Trial Registry (ChiCTR1800014966).

Unraveling the role of VLDL in the relationship between type 2 diabetes and coronary atherosclerosis: a Mendelian randomization analysis.

The causal link between Type 2 diabetes (T2D) and coronary atherosclerosis has been established through wet lab experiments; however, its analysis with Genome-wide association studies (GWAS) data remains unexplored. This study aims to validate this relationship using Mendelian randomization analysis and explore the potential mediation of VLDL in this mechanism. Employing Mendelian randomization analysis, we investigated the causal connection between T2D and coronary atherosclerosis. We utilized GWAS summary statistics from European ancestry cohorts, comprising 23,363 coronary atherosclerosis patients and 195,429 controls, along with 32,469 T2D patients and 183,185 controls. VLDL levels, linked to SNPs, were considered as a potential mediating causal factor that might contribute to coronary atherosclerosis in the presence of T2D. We employed the inverse variance weighted (IVW), Egger regression (MR-Egger), weighted median, and weighted model methods for causal effect estimation. A leave-one-out sensitivity analysis was conducted to ensure robustness. Our Mendelian randomization analysis demonstrated a genetic association between T2D and an increased coronary atherosclerosis risk, with the IVW estimate at 1.13 [95% confidence interval (CI): 1.07-1.20]. Additionally, we observed a suggestive causal link between T2D and VLDL levels, as evidenced by the IVW estimate of 1.02 (95% CI: 0.98-1.07). Further supporting lipid involvement in coronary atherosclerosis pathogenesis, the IVW-Egger estimate was 1.30 (95% CI: 1.06-1.58). In conclusion, this study highlights the autonomous contributions of T2D and VLDL levels to coronary atherosclerosis development. T2D is linked to a 13.35% elevated risk of coronary atherosclerosis, and within T2D patients, VLDL concentration rises by 2.49%. Notably, each standard deviation increase in VLDL raises the likelihood of heart disease by 29.6%. This underscores the significant role of lipid regulation, particularly VLDL, as a mediating pathway in coronary atherosclerosis progression.

Analysis of polymorphism of innate immunity receptor genes in patients with coronary atherosclerosis and in a population sample from Novosibirsk

Understanding the molecular mechanisms of atherosclerotic vascular lesions formation is necessary both for assessing the risks of cardiovascular diseases and for finding approaches to their therapy. The task remains relevant, despite the large number of studies carried out, because there are differences in the factors of genetic predisposition to atherosclerosis and its complications between different ethno-territorial groups. The aim of this study was to search for genetic variants of pattern recognition receptors associated with lipid metabolism disorders that can lead to the development of coronary atherosclerosis (CA).Material and methods. Analysis of exons and adjacent splicing sites of pattern recognition receptors genes in patients with CA (30 men), and then genotyping of a population sample from Novosibirsk (n = 1441) by real-time PCR for selected rs113706342 of the TLR1 gene and analysis of associations of its carriage with lipid metabolism were performed.Results and discussion. The frequency of the minor allele rs113706342 C of the TLR1 gene in the sample of residents of Novosibirsk was 0.0114 ± 0.0062, the carriage of this variant was associated with an increased level of low-density lipoprotein cholesterol in both women and men (p = 0.009 and p = 0.019, respectively). Women carriers of the minor allele C for rs113706342 also had a statistically significant increase in total serum cholesterol (p = 0.013) compared with TT homozygotes. To test the role of this variant in the development of CA, genotyping of an extended sample of patients is required. In one of the patients with CA, a previously undescribed single nucleotide variant chr16:3614637 G/C was found, leading to the Leu101Val substitution in the NLRC3 gene; segregation analysis is required to assess its functional significance.Conclusions. The association of rs113706342 C of the TLR1 gene with lipid metabolism disorders in the Russian population is shown.

Transcriptome-wide association study reveals novel susceptibility genes for coronary atherosclerosis.

Genetic risk factors substantially contributed to the development of coronary atherosclerosis. Genome-wide association study (GWAS) has identified many risk loci for coronary atherosclerosis, but the translation of these loci into therapeutic targets is limited for their location in non-coding regions. Here, we aimed to screen the potential coronary atherosclerosis pathogenic genes expressed though TWAS (transcriptome wide association study) and explore the underlying mechanism association. Four TWAS approaches (PrediXcan, JTI, UTMOST, and FUSION) were used to screen genes associated with coronary atherosclerosis. Enrichment analysis of TWAS-identified genes was applied through the Metascape website. The summary-data-based Mendelian randomization (SMR) analysis was conducted to provide the evidence of causal relationship between the candidate genes and coronary atherosclerosis. At last, the cell type-specific expression of the intersection genes was examined by using human coronary artery single-cell RNA-seq, interrogating the immune microenvironment of human coronary atherosclerotic plaque at different stages of maturity. We identified 19 genes by at least three approaches and 1 gene (NBEAL1) by four approaches. Enrichment analysis enriching the genes identified at least by two TWAS approaches, suggesting that these genes were markedly enriched in asthma and leukocyte mediated immunity reaction. Further, the summary-data-based Mendelian randomization (SMR) analysis provided the evidence of causal relationship between NBEAL1 gene and coronary atherosclerosis, confirming the protecting effects of NBEAL1 gene and coronary atherosclerosis. At last, the single cell cluster analysis demonstrated that NBEAL1 gene has differential expressions in macrophages, plasma cells and endothelial cells. Our study identified the novel genes associated with coronary atherosclerosis and suggested the potential biological function for these genes, providing insightful guidance for further biological investigation and therapeutic approaches development in atherosclerosis-related diseases.

Analysis of coronary artery lesion degree and related risk factors in patients with coronary heart disease

Background. The study of the association of risk factors and atherosclerotic burden assessed by coronary angiography is promising in terms of both understanding the pathogenesis of the disease and predicting its development. The aim of the study was to investigate the relationship between traditional risk factors and the severity of coronary atherosclerosis in patients with stable CHD.Materials and methods. Risk factors were studied in 100 patients who underwent angiography. Based on the Gensini (GS) score, participants were divided into groups: patients with moderate lesion of coronary arteries (GS = 8–39), with severe lesion (GS ≥ 40), and control group (GS = 0). To verify the association between the variables, Pearson’s chi-square test was used. The results were presented as relative risk (RR) and the confidence interval (95% CI).Results. It was found that in patients with GS score less than 40 points, statistically significant factors were hypertension (RR = 2.6; 95% CI: 1.023–10.09; р = 0.018), family history (RR = 2.94; 95% CI: 1.501–5.762; р &lt; 0.001), depression (RR = 1.81; 95% CI: 1.202–2.738; р = 0.028), In patients with GS ≥ 40, the most important factors were diabetes (RR = 1.72; 95% CI: 1.187–2.511; р = 0,017), family history (RR = 2.02; 95% CI: 1.233–3.315; р = 0.002), inactivity (RR = 1.85; 95% CI: 1.219–2.824; р = 0.005). The GS scores were significantly higher in smokers compared non-smokers (44.0 vs. 32.0; p = 0.043).Conclusion. The most significant influence on the development of coronary atherosclerosis is exerted by a family history and physical inactivity. Arterial hypertension and depression are associated with moderate coronary artery disease. Severe athero sclerosis is associated with diabetes mellitus, long smoking history, low levels of high-density lipoprotein cholesterol.

Time-resolved simulation of blood flow through left anterior descending coronary artery: effect of varying extent of stenosis on hemodynamics

Background and objectivesReal-time blood flow variation is crucial for understanding the dynamic development of coronary atherosclerosis. The main objective of this study is to investigate the effect of varying extent of stenosis on the hemodynamic features in left anterior descending coronary artery.MethodsVarious Computational fluid dynamics (CFD) models were constructed with patient-specific CT image data, using actual fractional flow reserve (FFR) as boundary conditions to provide a real-time quantitative description of hemodynamic properties. The hemodynamic parameters, such as the local and instantaneous wall shear stress (WSS), oscillating shear index (OSI) and relative residence time (RRT), blood flow velocity and pressure drop during various phases of cardiac cycle were provided in detail.ResultsThere was no evident variation in hemodynamic parameters in the cases of less than 50% stenosis while there were abrupt and dramatic changes in hemodynamics when the stenosis aggravated from 60 to 70%. Furthermore, when the stenosis was beyond 70%, there existed substantial pressure difference, WSS, and blood flow velocity in the center of the stenosis. Although OSI and RRT increased along with the aggravation of stenosis, they appeared with obvious abnormalities across all cases, even in mild stenosis.ConclusionThe simulation could present a dynamic and comprehensive profile of how hemodynamic parameters vary in accordance with divergent severities of stenosis, which could serve as an effective reference for the clinicians to have a deeper insight into the pathological mechanism of coronary atherosclerosis and stenosis.

Causal relationships of excessive daytime napping with atherosclerosis and cardiovascular diseases: a Mendelian randomization study.

Previous observational studies have found conflicting evidence on the relationship between daytime napping and incident cardiovascular diseases (CVDs), but it remains unclear whether these associations present causality. This study aims to verify whether and why there is a causal relationship between these parameters, and whether there is an etiological basis. A two-sample Mendelian randomization analysis was performed using 79 single nucleotide polymorphisms associated with daytime napping. Summary-level data for coronary atherosclerosis, peripheral atherosclerosis, total CVD, and five CVD outcomes were obtained from the FinnGen study. Meta-analyses were aimed at investigating the relationships of excessive daytime napping with total CVD, coronary heart disease, myocardial infarction (MI), and stroke incidence. Subgroup, network meta-analysis (NMA) and trial sequential analysis (TSA) were also performed in this study. The inverse-variance weighted method demonstrated that a genetic predisposition to more frequent daytime napping was significantly associated with higher odds of coronary atherosclerosis (odds ratio [OR] = 1.55, 95% confidence interval [CI]: 1.11 to 2.17), MI (OR = 1.63, 95% CI: 1.06 to 2.50), and heart failure (OR = 1.80, 95%CI: 1.28 to 2.52). In NMA, an increased risk of developing CVD in people who napped for more than 60 min a day than those who did not nap was demonstrated and then supported by TSA results (summary relative risk = 1.98, 95% CI: 1.39 to 2.82). Habitual daytime napping is causally associated with an increased risk of incident CVD primarily via the development of coronary atherosclerosis. An average napping duration of more than 60 min is associated with an elevated risk of CVD in all participants.

Association between high oxidized high-density lipoprotein levels and increased pericoronary inflammation determined by coronary computed tomography angiography

BackgroundImpaired high-density lipoprotein (HDL) function is a risk factor for cardiac mortality. We aimed to investigate the association between oxidized HDL (oxHDL) and pericoronary adipose tissue (PCAT) attenuation, a novel imaging biomarker of pericoronary inflammation, by using coronary computed tomography angiography (CTA). MethodsA total of 287 outpatients with suspected coronary artery disease who had undergone both oxHDL measurement and coronary CTA were examined. PCAT attenuation values were assessed at the proximal 10–50 mm segments of the right coronary artery on coronary CTA. The presence of significant stenosis (luminal narrowing of >50 %) and high-risk plaque characteristics were also evaluated. Patients were then classified into tertiles according to their oxHDL level: low (n = 95), moderate (n = 96), and high (n = 96) groups. ResultsPCAT attenuation in the high oxHDL group was significantly higher than that in other groups after adjusting for age and apolipoprotein-A-I. Multivariate linear regression analysis revealed that oxHDL was significantly associated with PCAT attenuation in the right coronary artery (β = 3.832, p < 0.001), whereas HDL cholesterol was not. Furthermore, subgroup analyses demonstrated that the association between oxHDL and PCAT attenuation remained significant in older patients (β = 6.367, p < 0.001) and in those with hypertension (β = 4.922, p < 0.011), dyslipidemia (β = 3.264, p = 0.010), diabetes mellitus (β = 4.284, p = 0.015), and significant stenosis (β = 3.075, p = 0.021). ConclusionsHigh oxHDL levels were significantly associated with increased pericoronary inflammation, as assessed using coronary CTA. Our results may explain the association between impaired HDL function and the development of coronary atherosclerosis.

Visceral Adiposity Index Is Associated with the Increased Syntax Score in Patients with Type 2 Diabetes Mellitus.

Background: The visceral adipose tissue excess in patients with diabetes mellitus (DM) is one of the mechanisms that plays role in the development of coronary atherosclerosis. Our study aimed to investigate the relationship between visceral adiposity index (VAI), an indicator of visceral adiposity, and Syntax score (SxS), a predictor of the severity of coronary artery disease (CAD), in patients with stable angina pectoris (SAP) and type 2 DM. Methods: A total of 253 patients with SAP and type 2 DM were included in this cross-sectional study. The patients were divided into three risk groups (low risk <22, 32 ≥ intermediate risk ≥22, high risk ≥33) according to the SxS based on invasive coronary angiography. Several adiposity indexes such as body mass index, waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), body adiposity index (BAI), and lipid accumulation product index (LAPI) were calculated using relevant formulas. In addition, VAI scores for each patient were calculated. Results: There were no statistically significant differences between the low-, intermediate-, and high-risk groups for WHtR, BAI, and LAPI. WHR was found significantly lower in the low SxS group (P = 0.0038), and VAI was found significantly higher (P = 0.021) in the high SxS group. Besides, in multivariate logistic regression analysis, the VAI (odds ratio: 2.455; 95% confidence interval: 1.244-4.845; P = 0.010) was an independent predictor of high SxS. In the receiver operating characteristic curve analysis, VAI with an optimal cutoff value of 2.048 predicted the severe coronary lesion with a sensitivity of 60.8% and a specificity of 61.5%. Conclusion: This study showed that VAI was an independent predictor in estimating CAD severity in patients with SAP and type 2 DM.

Kynurenine Pathway Metabolites as Potential Clinical Biomarkers in Coronary Artery Disease.

Coronary artery disease (CAD) is one of the leading cause of mortality worldwide. Several risk factors including unhealthy lifestyle, genetic background, obesity, diabetes, hypercholesterolemia, hypertension, smoking, age, etc. contribute to the development of coronary atherosclerosis and subsequent coronary artery disease. Inflammation plays an important role in coronary artery disease development and progression. Pro-inflammatory signals promote the degradation of tryptophan via the kynurenine pathway resulting in the formation of several immunomodulatory metabolites. An unbalanced kynurenic pathway has been implicated in the pathomechanisms of various diseases including CAD. Significant improvements in detection methods in the last decades may allow simultaneous measurement of multiple metabolites of the kynurenine pathway and such a thorough analysis of the kynurenine pathway may be a valuable tool for risk stratification and determination of CAD prognosis. Nevertheless, imbalance in the activities of different branches of the kynurenine pathway may require careful interpretation. In this review, we aim to summarize clinical evidence supporting a possible use of kynurenine pathway metabolites as clinical biomarkers in various manifestations of CAD.

COVID-19 and atherosclerosis: looking beyond the acute crisis

COVID-19 and atherosclerosis: looking beyond the acute crisis