Incidence Of Coronary Artery Disease Research Articles

Integration of polygenic and gut metagenomic risk prediction for common diseases

Multiomics has shown promise in noninvasive risk profiling and early detection of various common diseases. In the present study, in a prospective population-based cohort with ~18 years of e-health record follow-up, we investigated the incremental and combined value of genomic and gut metagenomic risk assessment compared with conventional risk factors for predicting incident coronary artery disease (CAD), type 2 diabetes (T2D), Alzheimer disease and prostate cancer. We found that polygenic risk scores (PRSs) improved prediction over conventional risk factors for all diseases. Gut microbiome scores improved predictive capacity over baseline age for CAD, T2D and prostate cancer. Integrated risk models of PRSs, gut microbiome scores and conventional risk factors achieved the highest predictive performance for all diseases studied compared with models based on conventional risk factors alone. The present study demonstrates that integrated PRSs and gut metagenomic risk models improve the predictive value over conventional risk factors for common chronic diseases.

Correlation of Coronary Artery Disease in Patients with Peripheral Artery Disease: Cross-Sectional Study

Background Peripheral Artery Disease (PAD) and Coronary Artery Disease (CAD) represent two facets of atherosclerotic cardiovascular disease, significantly impacting global health. Despite their high morbidity and mortality rates, the epidemiological and clinical nexus between PAD and CAD remains underexplored. Understanding the interrelation of these conditions is paramount for optimizing diagnostic and therapeutic strategies. Objective This study aimed to delineate the incidence and clinical correlation of CAD in patients diagnosed with PAD, thereby providing insights into the epidemiological characteristics and enhancing the clinical management of these conditions. Methods A cross-sectional analysis was conducted at Afridi Medical Complex's departments of vascular surgery and cardiology from 2021 to 2023. One hundred PAD patients referred for peripheral angiography were enrolled. Demographic data, Ankle Brachial Index (ABI) readings, ejection fraction percentages, and the presence of multivessel disease were evaluated. Statistical analyses were performed using SPSS version 25, focusing on mean, median, range, and significance levels to elucidate the prevalence of CAD among PAD patients. Results The study revealed a median age of 58 years among participants, with a significant male predominance (84%). ABI analysis showed that 74% and 108% of patients had mild and moderate PAD severity, respectively. The incidence of CAD in the PAD population was 56%, with angiographic assessments indicating single, double, and triple vessel disease in 23.21%, 39.29%, and 37.5% of patients, respectively. Notably, diabetes and dyslipidemia were prominent predictors of CAD presence in PAD patients. Conclusion The high prevalence of CAD in PAD patients underscores the critical need for comprehensive cardiovascular risk assessment and suggests the potential benefit of routine coronary angiography in symptomatic PAD cases, particularly among those with diabetes and dyslipidemia. This study reinforces the intertwined nature of PAD and CAD, advocating for an integrated approach to the diagnosis and management of these atherosclerotic conditions.

Abstract MP34: Association of Biological Age Acceleration With Incident Type 2 Diabetes and Coronary Artery Disease

Introduction: Biological age (BA), compared to chronological age, offers a more accurate reflection of aging status and prediction of cardiometabolic disease mortality. Genetics play an important role in the pathogenesis of type 2 diabetes (T2D) and coronary artery disease (CAD). However, the associations of BA acceleration with incident T2D and CAD as well as how the interactions between genetic risk and BA acceleration implicate in the development of these two diseases remain unclear. Hypothesis: We hypothesized that BA acceleration was significantly associated with incident T2D and CAD. We further hypothesized that there were significant interactions between BA acceleration and genetic risk in relation to risk of T2D and CAD. Methods: This prospective cohort study utilized data from the UK Biobank. BA was quantified by KDM-BA and PhenoAge, two composite measures derived from blood chemistry and physical examination data. T2D and CAD were diagnosed using self-reported medical history, medication, and hospital inpatient records. Multivariable Cox proportional hazard models were employed to estimate the associations of BA acceleration with incident T2D and CAD. A polygenic risk score (PRS) for T2D or CAD divided into tertiles was used to assess the interactions between BA acceleration (divided into quartiles) and genetic risk with regards to the development of T2D and CAD. Derived estimates were hazard ratios (HRs) and their 95% confidence intervals (CIs) per one standard deviation increment in each of the two BA measures. Results: This study analyzed 271,855 participants without T2D and 267,293 participants without CAD at baseline. Over a median follow-up time of 14.6 and 14.5 years, 9,562 incident T2D events and 18,509 incident CAD events occurred, respectively. Individuals with greater BA acceleration were at increased risk of T2D (HR for KDM-BA: 1.42, [95% CI: 1.39-1.46]; HR for PhenoAge: 1.23, [95% CI: 1.20-1.25]). Similarly, BA acceleration was significantly associated with a higher risk of CAD (HR for KDM-BA: 1.22, [95% CI: 1.20-1.25]; HR for PhenoAge: 1.12, [95% CI: 1.10-1.14]). People with greater genetic risk and BA acceleration had higher risks of T2D and CAD (P for interaction < 0.002). Compared with participants with the lowest level of PRS and BA acceleration, those with the highest level of PRS and BA acceleration had a higher risk of developing T2D (HR for KDM-BA: 7.03, [95% CI: 6.16-8.02]; HR for PhenoAge: 6.39, [95% CI: 5.38-7.58]) and CAD (HR for KDM-BA: 2.83, [95% CI: 2.62-3.06]; HR for PhenoAge: 2.27, [95% CI: 2.09-2.46]). Conclusions: BA acceleration was significantly associated higher risks of T2D and CAD, especially among individuals with a high genetic predisposition to T2D and CAD.

Cardiovascular Significance and Genetics of Epicardial and Pericardial Adiposity

Epicardial and pericardial adipose tissue (EPAT) has been associated with cardiovascular diseases such as atrial fibrillation or flutter (AF) and coronary artery disease (CAD), but studies have been limited in sample size or drawn from selected populations. It has been suggested that the association between EPAT and cardiovascular disease could be mediated by local or paracrine effects. To evaluate the association of EPAT with prevalent and incident cardiovascular disease and to elucidate the genetic basis of EPAT in a large population cohort. A deep learning model was trained to quantify EPAT area from 4-chamber magnetic resonance images using semantic segmentation. Cross-sectional and prospective cardiovascular disease associations were evaluated, controlling for sex and age. Prospective associations were additionally controlled for abdominal visceral adipose tissue (VAT) volumes. A genome-wide association study was performed, and a polygenic score (PGS) for EPAT was examined in independent FinnGen cohort study participants. Data analyses were conducted from March 2022 to December 2023. The primary exposures were magnetic resonance imaging-derived continuous measurements of epicardial and pericardial adipose tissue area and visceral adipose tissue volume. Prevalent and incident CAD, AF, heart failure (HF), stroke, and type 2 diabetes (T2D). After exclusions, this study included 44 475 participants (mean [SD] age, 64.1 [7.7] years; 22 972 female [51.7%]) from the UK Biobank. Cross-sectional and prospective cardiovascular disease associations were evaluated for a mean (SD) of 3.2 (1.5) years of follow-up. Prospective associations were additionally controlled for abdominal VAT volumes for 38 527 participants. A PGS for EPAT was examined in 453 733 independent FinnGen cohort study participants. EPAT was positively associated with male sex (β = +0.78 SD in EPAT; P < 3 × 10-324), age (Pearson r = 0.15; P = 9.3 × 10-229), body mass index (Pearson r = 0.47; P < 3 × 10-324), and VAT (Pearson r = 0.72; P < 3 × 10-324). EPAT was more elevated in prevalent HF (β = +0.46 SD units) and T2D (β = +0.56) than in CAD (β = +0.23) or AF (β = +0.18). EPAT was associated with incident HF (hazard ratio [HR], 1.29 per +1 SD in EPAT; 95% CI, 1.17-1.43), T2D (HR, 1.63; 95% CI, 1.51-1.76), and CAD (HR, 1.19; 95% CI, 1.11-1.28). However, the associations were no longer significant when controlling for VAT. Seven genetic loci were identified for EPAT, implicating transcriptional regulators of adipocyte morphology and brown adipogenesis (EBF1, EBF2, and CEBPA) and regulators of visceral adiposity (WARS2 and TRIB2). The EPAT PGS was associated with T2D (odds ratio [OR], 1.06; 95% CI, 1.05-1.07; P =3.6 × 10-44), HF (OR, 1.05; 95% CI, 1.04-1.06; P =4.8 × 10-15), CAD (OR, 1.04; 95% CI, 1.03-1.05; P =1.4 × 10-17), AF (OR, 1.04; 95% CI, 1.03-1.06; P =7.6 × 10-12), and stroke in FinnGen (OR, 1.02; 95% CI, 1.01-1.03; P =3.5 × 10-3) per 1 SD in PGS. Results of this cohort study suggest that epicardial and pericardial adiposity was associated with incident cardiovascular diseases, but this may largely reflect a metabolically unhealthy adiposity phenotype similar to abdominal visceral adiposity.

Characteristic of Clinical Likelihood Chronic Coronary Syndrome patients with Significant Coronary Lesion in RSUP dr. Mohammad Hoesin Palembang

Chronic coronary syndrome (CCS) is a pathological process characterized by atherosclerotic plaque accumulation in the epicardial arteries, whether obstructive or non-obstructive. Significant Coronary artery disease (CAD) is defined by invasive coronary angiography as &gt;50% stenosis of the left main stem, &gt;70% stenosis in a major coronary vessel, or 30% to 70% stenosis with fractional flow reserve ?0.8. This study aimed to identify the characteristics of clinical likelihood CCS patients with site of significant coronary lesion based on pre-test probability (PTP) from demographic characteristics; risk factors; laboratory and echocardiography findings. This is a retrospective cohort study. We reviewed 60 medical records of clinical likelihood chronic coronary syndrome patients with positive inducible ischemia area from dobutamine stress echocardiography and significant CAD lesion from coronary angiography. The incidence of significant CAD in this population was 56.1%. There was a significant relationship between age &gt; 65 years with the incidence of significant LAD lesion (23.3%, p = 0.019); significant LCx lesion (20%, p = 0.043). There was a significant relationship between PTP score ? 16% with significant LAD lesion (55.0%, p = 0.001); significant LCx lesion (45.0%, p = 0.031); and significant RCA lesion (40.0%, p = 0.050). Patients with age &gt; 65 years have a higher incidence of significant LAD and LCx lesions. Patients with pre-test probability score ? 16% have a higher incidence of significant lesions across coronary branches, predominantly in the LAD.

Single Cell High Dimensional Analysis of Human Peripheral Blood Mononuclear Cells Reveals Unique Intermediate Monocyte Subsets Associated with Sex Differences in Coronary Artery Disease.

Monocytes are associated with human cardiovascular disease progression. Monocytes are segregated into three major subsets: classical (cMo), intermediate (iMo), and nonclassical (nMo). Recent studies have identified heterogeneity within each of these main monocyte classes, yet the extent to which these subsets contribute to heart disease progression is not known. Peripheral blood mononuclear cells (PBMC) were obtained from 61 human subjects within the Coronary Assessment of Virginia (CAVA) Cohort. Coronary atherosclerosis severity was quantified using the Gensini Score (GS). We employed high-dimensional single-cell transcriptome and protein methods to define how human monocytes differ in subjects with low to severe coronary artery disease. We analyzed 487 immune-related genes and 49 surface proteins at the single-cell level using Antibody-Seq (Ab-Seq). We identified six subsets of myeloid cells (cMo, iMo, nMo, plasmacytoid DC, classical DC, and DC3) at the single-cell level based on surface proteins, and we associated these subsets with coronary artery disease (CAD) incidence based on Gensini score (GS) in each subject. Only frequencies of iMo were associated with high CAD (GS > 32), adj.p = 0.024. Spearman correlation analysis with GS from each subject revealed a positive correlation with iMo frequencies (r = 0.314, p = 0.014) and further showed a robust sex-dependent positive correlation in female subjects (r = 0.663, p = 0.004). cMo frequencies did not correlate with CAD severity. Key gene pathways differed in iMo among low and high CAD subjects and between males and females. Further single-cell analysis of iMo revealed three iMo subsets in human PBMC, distinguished by the expression of HLA-DR, CXCR3, and CD206. We found that the frequency of immunoregulatory iMo_HLA-DR+CXCR3+CD206+ was associated with CAD severity (adj.p = 0.006). The immunoregulatory iMo subset positively correlated with GS in both females (r = 0.660, p = 0.004) and males (r = 0.315, p = 0.037). Cell interaction analyses identified strong interactions of iMo with CD4+ effector/memory T cells and Tregs from the same subjects. This study shows the importance of iMo in CAD progression and suggests that iMo may have important functional roles in modulating CAD risk, particularly among females.

Genetic effects of inflammatory cytokines on coronary artery disease and myocardial infarction and the mediating roles of lipid traits.

Chronic inflammation has been connected by epidemiological evidence to coronary artery disease (CAD) along with myocardial infarction (MI). Nevertheless, it is still unclear whether reverse causality or confounders account for these connections. Our objectives are to examine the causality between inflammatory cytokines and CAD/MI as well as the potential mediating influence of lipid characteristics. We acquired instrumental variables through genome-wide association studies meta-analyses of 41 inflammatory cytokines (8293 individuals). Genetic associations with CAD (122 733 cases and 424 528 controls), MI (~61 505 cases and 577 716 controls) and five candidate lipid mediators were obtained from the corresponding genome-wide association studies. A two-step, two-sample Mendelian randomization analysis was applied, followed with comprehensive sensitivity analyses. Genetically determined growth regulated oncogene-α was causally linked to a decreased incidence of CAD [odds ratio (OR), 0.97; 95% confidence interval (CI), 0.95-0.99; P = .007] and MI (OR, 0.95; 95% CI, 0.92-0.98; P = .002). There is suggestive evidence indicating a causal impact of macrophage inflammatory protein-1β upon CAD (OR, 1.04; 95% CI, 1.01-1.07; P = .010) and MI (OR, 1.07; 95% CI, 1.02-1.11; P = .002). Furthermore, we discovered suggestive causal connections between tumor necrosis factor-related apoptosis-inducing ligand and CAD (OR, 0.97; 95% CI, 0.95-1.00; P = .020). Two-step Mendelian randomization analysis revealed that triglycerides partially mediate the effect of growth regulated oncogene-α on CAD (proportion-mediated: 13.28%) and MI (8.05%). We provided novel genetic evidence supporting the causality of inflammatory cytokines on CAD/MI and elucidate the mediating effect of triglycerides in the causal pathways linking inflammatory cytokines and CAD/MI.

Intensive lifestyle intervention in type 2 diabetes and risk of incident coronary artery disease for the common haptoglobin phenotypes: the Look AHEAD study

BackgroundIntensive glycemic control reduced coronary artery disease (CAD) events among the Action to Control Cardiovascular Disease Risk in Diabetes (ACCORD) participants with the haptoglobin (Hp) 2-2 phenotype only. It remains unknown whether Hp phenotype modifies the effect of an intensive lifestyle intervention (ILI) on CAD in type 2 diabetes.MethodsHaptoglobin phenotype was measured in 4542 samples from the Action for Health in Diabetes (Look AHEAD) study. Cox regression models assessed the effect of ILI (focused on weight loss from caloric restriction and physical activity) versus diabetes support and education (DSE) on CAD events in each phenotype group, and within pre-specified subgroups including race/ethnicity, sex, history of cardiovascular disease, diabetes medication use, and diabetes duration.Results1590 (35%) participants had the Hp2-2 phenotype. The ILI did not lower glycated hemoglobin (%HbA1c) to < 6.5% in either phenotype, with a peak significant difference between treatment arms of 0.5% [non-Hp2-2] and 0.6% [Hp2-2]. The cumulative CAD incidence was 13.4% and 13.8% in the DSE arm and 12.2% and 13.6% in the ILI arm for non-Hp2-2 and Hp2-2 groups, respectively. Compared to DSE, the ILI was not associated with CAD among participants without (HR = 0.95, 95% CI 0.78–1.17) or with (0.89, 0.68–1.19) the Hp2-2 phenotype (p-interaction between Hp phenotype and ILI = 0.58). After Bonferroni correction, there were no significant results among any subgroups.ConclusionsHp phenotype did not modify the effect of the weight loss ILI on risk of CAD in Look AHEAD, potentially because it did not substantially impact glycemic control among participants with or without the Hp2-2 phenotype. Further research is needed to determine if these results are conclusive.

Long noncoding RNAs MEG3, TUG1, and hsa-miR-21-3p are potential diagnostic biomarkers for coronary artery disease

Peripheral blood biomarkers are of particular importance to diagnose certain diseases including coronary artery disease (CAD) due to their non-invasiveness. Investigating the expression of noncoding RNAs (ncRNAs) paves the way to early disease diagnosis, prognosis, and treatment. Consequently, in this research, we aimed to investigate a panel of ncRNAs as potential biomarkers in patients with coronary artery disease. Two different groups have been designed (control and CAD). All participants were subjected to interviews and clinical examinations. Peripheral blood samples were collected, and plasma was extracted. At the same time, target ncRNAs have been selected based on literature review and bioinformatic analysis, and later they underwent investigation using quantitative real-time PCR. The selected panel encompassed the long non-coding RNAs (lncRNAs) MEG3, TUG1, and SRA1, and one related microRNA (miRNA): hsa-miR-21-3p. We observed statistically significant upregulation in MEG3, TUG1, and hsa-miR21-3p in CAD patients compared to control participants (p-value 0.01). Nevertheless, SRA1 exhibited downregulation with no statistical significance (p-value 0.05). All ncRNAs under study displayed a significantly strong correlation with disease incidence, age, and smoking. Network construction revealed a strong relationship between MEG3 and TUG1. ROC analysis indicated high potentiality for hsa-miR-21-3p to be a promising biomarker for CAD. Moreover, MEG3 and TUG1 displayed distinguished diagnostic discrimination but less than hsa-miR-21-3p, all of them exhibited strong statistical significance differences between CAD and control groups. Conclusively, this research pinpointed that MEG3, TUG1, and hsa-miR-21-3p are potential biomarkers of CAD incidence and diagnosis.

Coronary artery disease incidence, risk factors, awareness, and medication utilization in a 10-year cohort study

BackgroundThere is a substantial disparity in coronary artery disease (CAD) burden between Iran and other nations that place a strong emphasis on the assessment of CAD risk factors and individuals’ awareness and ability to control them.MethodsTwo thousand participants of a community-based Iranian population aged 20–74 years were investigated with a mean follow-up of 9.9 years (range: 7.6 to 12.2). An analysis of Cox regression was conducted to determine the association between CAD development and classic risk factors such as age, sex, smoking, physical activity, education, obesity, dyslipidemia, hypertension, and diabetes mellitus. Furthermore, we computed the population attributable fraction for these risk factors.ResultsAfter a follow-up period of nearly 10 years, 225 CAD events were reported, constituting 14.5% of the overall incidence. Nighty three percent of participants had more than one risk factor. Age was the most predictive risk factor, with a hazard ratio (HR) and confidence interval (CI) of 5.56 (3.87–7.97, p < 0.001) in men older than 45 and females older than 55 compared to lower ages. In comparison to females, males had an HR of 1.45 (CI: 1.11–1.90, p value = 0.006) for developing CAD. Nearly 80% of the patients had dyslipidemia, with a hazard ratio of 2.19 (CI: 1.40–3.44, p = 0.01). Among the participants, 28.9% had hypertension, and 52% had prehypertension, which had HRs of 4.1 (2.4–7.2, p < 0.001) and 2.4 (1.4–4.2, p < 0.001), respectively. Diabetes, with a prevalence of 17%, had an HR of 2.63 (CI: 2 -3.47, p < 0.001), but prediabetes was not significantly associated with CAD. Awareness of diabetes, dyslipidemia, and hypertension was 81%, 27.9%, and 48.1%, respectively. Regarding medication usage, the corresponding percentages were 51% for diabetes, 13.2% for dyslipidemia, and 41% for hypertension.ConclusionsCompared to previous studies in Iran and neighboring countries, the current study found a higher incidence of CAD, more prevalent risk factors, and a lower awareness and ability to control these risk factors. Thus, an effective preventive strategy is needed to reduce the CAD burden in Iran.

Validation of genetic risk scores for coronary artery disease, developed on European population samples, in Russian population

Aim. To evaluate the information content of genetic risk scores (GRSs) for coronary artery disease (CAD), previously developed on European populations, in representatives of the Russian population.Material and methods. The work involved 1685 people from the ESSE-Ivanovo epidemiological study. CAD was verified in 3,1% of individuals. The coronary composite endpoint was assessed annually during 8-year follow-up. Next generation sequencing was performed using a targeted panel. Logistic regression analysis and area under the ROC curve (AUC) were used. Age, sex, and smoking status were taken into account in the multivariate model.Results. Of the 16 GRSs included in the analysis, only 2 GRSs demonstrated significance in the univariate analysis of association with CAD (highest AUC — 0,577). In a multivariate model, with an increase by 1 standard deviation (SD) for the 6 studied GRSs, a significant association with CAD was obtained — the odds ratio varied in the range of 1,31-1,47. The two GRSs demonstrated significant differences in the incidence of CAD between the groups corresponding to the upper and lower quintiles. Forty-five endpoints were registered. The risk ratio for the end point with an increase in GRS by 1 SD, taking into account cofactors, exceeded statistical significance for the 9 analyzed GRS and was in the range of 1,36-1,54.Conclusion. For the first time in Russia, 16 CAD GRSs, previously developed on European samples, was validated. The results were reproduced only for a few of the studied CAD SGRs.

Sex differences in the associations of HDL particle concentration and cholesterol efflux capacity with incident coronary artery disease in type 1 diabetes: The RETRO HDLc cohort study

In type 1 diabetes, women lose their relative protection (compared to men) against coronary artery disease (CAD), while high-density lipoprotein cholesterol (HDL-C) is less strongly associated with lower CAD risk in women. We aimed to assess whether sex differences in the HDL particle concentration (HDL-P) and cholesterol efflux capacity (CEC) association with CAD may explain these findings. HDL-P (calibrated differential ion mobility analysis) and total and ATP binding cassette transporter A1 (ABCA1)-specific CEC were quantified among 279 men and 271 women with type 1 diabetes (baseline mean age 27·8 years; diabetes duration, 19·6 years). Clinical CAD was defined as CAD death, myocardial infarction and/or coronary revascularization. Women had higher large HDL-P levels and marginally lower concentrations of small HDL-P and ABCA1-specific CEC than men. No sex differences were observed in extra-small HDL-P, medium HDL-P and total CEC. During a median follow-up of 26 years, 37·6 % of men and 35·8 % of women developed CAD (p = 0·72). In multivariable Cox models stratified by sex (pTotal HDL-P x sex interaction=0·01), HDL-P was negatively associated with CAD incidence in both sexes. However, associations were stronger in men, particularly for extra-small HDL-P (hazard ratio (HR)men=0·11, 95 % confidence interval (CI): 0·04-0·30; HRwomen=0·68, 95 % CI: 0·28-1·66; pinteraction=0·001). CEC did not independently predict CAD in either sex. Despite few absolute differences in HDL-P concentrations by sex, the HDL-P - CAD association was weaker in women, particularly for extra-small HDL-P, suggesting that HDL-P may be less efficient in providing atheroprotection in women and perhaps explaining the lack of a sex difference in CAD in type 1 diabetes.

The association between water intake and future cardiometabolic disease outcomes in the Malmö Diet and Cancer cardiovascular cohort.

The aim of this study was to explore the longitudinal association between reported baseline water intake and incidence of coronary artery disease (CAD) and type 2 diabetes in the Malmö Diet and Cancer Cohort (n = 25,369). Using cox proportional hazards models, we separately modelled the effect of plain and total (all water, including from food) water on CAD and type 2 diabetes risk, whilst adjusting for age, sex, diet collection method, season, smoking status, alcohol intake, physical activity, education level, energy intake, energy misreporting, body mass index, hypertension, lipid lowering medication, apolipoprotein A, apolipoprotein B, and dietary variables. Sensitivity analyses were run to assess validity. After adjustment, no association was found between tertiles of plain or total water intake and type 2 diabetes risk. For CAD, no association was found comparing moderate to low intake tertiles from plain or total water, however, risk of CAD increased by 12% (95% CI 1.03, 1.21) when comparing high to low intake tertiles of plain water, and by 17% (95% CI 1.07, 1.27) for high versus low tertiles of total water. Sensitivity analyses were largely in agreement. Overall, baseline water intake was not associated with future type 2 diabetes risk, whilst CAD risk was higher with higher water intakes. Our findings are discordant with prevailing literature suggesting higher water intakes should reduce cardiometabolic risk. These findings may be an artefact of limitations within the study, but future research is needed to understand if there is a causal underpinning.

Faecalibacterium prausnitzii as a potential Antiatherosclerotic microbe

BackgroundThe gut microbiota plays a crucial role in coronary artery disease (CAD) development, but limited attention has been given to the role of the microbiota in preventing this disease. This study aimed to identify key biomarkers using metagenomics and untargeted metabolomics and verify their associations with atherosclerosis.MethodsA total of 371 participants, including individuals with various CAD types and CAD-free controls, were enrolled. Subsequently, significant markers were identified in the stool samples through gut metagenomic sequencing and untargeted metabolomics. In vivo and in vitro experiments were performed to investigate the mechanisms underlying the association between these markers and atherosclerosis.ResultsFaecal omics sequencing revealed that individuals with a substantial presence of Faecalibacterium prausnitzii had the lowest incidence of CAD across diverse CAD groups and control subjects. A random forest model confirmed the significant relationship between F. prausnitzii and CAD incidence. Notably, F. prausnitzii emerged as a robust, independent CAD predictor. Furthermore, our findings indicated the potential of the gut microbiota and gut metabolites to predict CAD occurrence and progression, potentially impacting amino acid and vitamin metabolism. F. prausnitzii mitigated inflammation and exhibited an antiatherosclerotic effect on ApoE−/− mice after gavage. This effect was attributed to reduced intestinal LPS synthesis and reinforced mechanical and mucosal barriers, leading to decreased plasma LPS levels and an antiatherosclerotic outcome.ConclusionsSequencing of the samples revealed a previously unknown link between specific gut microbiota and atherosclerosis. Treatment with F. prausnitzii may help prevent CAD by inhibiting atherosclerosis.

Coronary artery lesions in Takayasu arteritis.

Takayasu arteritis (TAK) is a granulomatous inflammation of vessels of large diameter, mainly affecting the aorta and its proximal branches, which is more common in young women. The incidence of coronary artery disease in TAK is unknown and not sufficiently studied. A literature review was performed for the period 2003 to 2023 using a search of the PubMed and Scopus scientific databases. We used the following key words to search the academic journal databases: "Takayasu arteritis", "coronary angiography", "myocardial revascularization", "coronary artery disease", "angina pectoris", and "myocardial infarction". The analysis of studies showed that coronary artery lesions (CAL) in TAK are not uncommon, being identified particularly in children and young individuals. Pathology of the coronary arteries increases the morbidity and mortality of TAK patients. In TAK, the ostia and proximal segments of the coronary arteries are more frequently affected, presenting as stenosis or occlusion with the development of stable coronary artery disease, unstable coronary artery disease, acute myocardial infarction, and sudden death. The diagnosis of TAK and coronary artery pathology is often complicated due to nonspecific manifestations and frequently the absence of symptoms. The treatment of patients with TAK with CAL is challenging and requires both pharmacological therapy and interventional or surgical methods of myocardial revascularization. Takayasu arteritis is a more prevalent cause of CAL development, especially in young patients, than previously believed, and cardiovascular death due to CAL is not rare. Early diagnosis of TAK with CAL, particularly occlusion or hemodynamically significant stenosis, and the prompt initiation of appropriate treatment prevent dangerous complications, reduce mortality, and improve prognosis.

SPONTANEOUS THIRD-DEGREE ATRIOVENTRICULAR BLOCK IN A DIABETIC PATIENT PRESENTING AS RECURRENT SYNCOPE

Chronic, uncontrolled hyperglycemia is associated with an increased incidence of coronary artery disease, cardiac failure, diabetic nephropathy, diabetic retinopathy, and associated mortality. A 72-year-old female presented to the OPD with multiple episodes of loss of consciousness for the past 1 month. The patient also had other comorbidities such as hypertension, diabetes mellitus (DM), and hypothyroidism. On systemic examination, her blood pressure was 124/77 mmHg (supine) and 116/72 mmHg (standing), and her pulse rate was 56 beats/min. She had a loss of vibration sense in both lower limbs up to the ankle. Fundus examination showed non-proliferative diabetic retinopathy. The rest of the systemic examination was clinically normal. Her HbA1C was 8.1%, and other routine investigations were within normal limits. Electrocardiography (ECG) showed sinus bradycardia. Echocardiography showed normal ventricular function with no evidence of ischemic heart disease (IHD). 24-h Holter ECG revealed sinus bradycardia with an intraventricular conduction defect, a third-degree AV block with junctional beats, and rare supraventricular ectopics. This is a case of Type 2 DM with complete heart block (CHB) of spontaneous onset. Other causes of AV block have been ruled out, and it seems that this case of CHB is possibly due to cardiac autonomic neuropathy (CAN). Multiple factors, such as the duration of diabetes, poor glycemic control, metabolic derangements, and genetic factors, determine CAN. This case emphasizes that patients with type 2 diabetes without IHD can develop CHB spontaneously.

Associations of combined polygenic risk score and glycemic status with atrial fibrillation, coronary artery disease and ischemic stroke

BackgroundIt is unknown whether high hemoglobin A1c (HbA1c) is associated with increases in the risk of cardiovascular disease among individuals with elevated genetic susceptibility. We aimed to investigate the association between HbA1c and atrial fibrillation (AF), coronary artery disease (CAD), and ischemic stroke according to the polygenic risk score (PRS).MethodsThe UK Biobank cohort included 502,442 participants aged 40–70 years who were recruited from 22 assessment centers across the United Kingdom from 2006 to 2010. This study included 305,605 unrelated individuals with available PRS and assessed new-onset AF, CAD, and ischemic stroke. The participants were divided into tertiles based on the validated PRS for each outcome. Within each PRS tertiles, the risks of incident events associated with HbA1c levels were investigated and compared with HbA1c < 5.7% and low PRS. Data were analyzed from November 2022 to May 2023.ResultsOf 305,605 individuals, 161,605 (52.9%) were female, and the mean (SD) age was 56.6 (8.1) years. During a median follow-up of 11.9 (interquartile range 11.1–12.6) years, the incidences of AF, CAD, and ischemic stroke were 4.6, 2.9 and 1.1 per 100 person-years, respectively. Compared to individuals with HbA1c < 5.7% and low PRS, individuals with HbA1c ≥ 6.5% and high PRS had a 2.67-times higher risk for AF (hazard ratio [HR], 2.67; 95% confidence interval (CI), 2.43–2.94), 5.71-times higher risk for CAD (HR, 5.71; 95% CI, 5.14–6.33) and 2.94-times higher risk for ischemic stroke (HR, 2.94; 95% CI, 2.47–3.50). In the restricted cubic spline models, while a U-shaped trend was observed between HbA1c and the risk of AF, dose-dependent increases were observed between HbA1c and the risk of CAD and ischemic stroke regardless PRS tertile.ConclusionsOur results suggest that the nature of the dose-dependent relationship between HbA1c levels and cardiovascular disease in individuals with different PRS is outcome-specific. This adds to the evidence that PRS may play a role together with glycemic status in the development of cardiovascular disease.

Joint association of genetic risk and accelerometer-measured physical activity with incident coronary artery disease in the UK biobank cohort.

Previous research demonstrates the joint association of self-reported physical activity and genotype with coronary artery disease. However, an existing research gap is whether accelerometer-measured overall physical activity or physical activity intensity can offset genetic predisposition to coronary artery disease. This study explores the independent and joint associations of accelerometer-measured physical activity and genetic predisposition with incident coronary artery disease. Incident coronary artery disease based on hospital inpatient records and death register data serves as the outcome of this study. Polygenic risk score and overall physical activity, measured as Euclidean Norm Minus One, and intensity, measured as minutes per day of moderate-to-vigorous intensity physical activity (MVPA), are examined both linearly and by decile. The UK Biobank population-based cohort recruited over 500,000 individuals aged 40 to 69 between 2006 and 2010, with 103,712 volunteers participating in a weeklong wrist-worn accelerometer study from 2013 to 2015. Individuals of White British ancestry (n = 65,079) meeting the genotyping and accelerometer-based inclusion criteria and with no missing covariates were included in the analytic sample. In the sample of 65,079 individuals, the mean (SD) age was 62.51 (7.76) and 61% were female. During a median follow-up of 6.8 years, 1,382 cases of coronary artery disease developed. At the same genetic risk, physical activity intensity had a hazard ratio (HR) of 0.41 (95% CI: 0.29-0.60) at the 90th compared to 10th percentile, equivalent to 31.68 and 120.96 minutes of moderate-to-vigorous physical activity per day, respectively, versus an HR of 0.61 (95% CI: 0.52-0.72) for overall physical activity. The combination of high genetic risk and low physical activity intensity showed the greatest risk, with an individual at the 10th percentile of genetic risk and 90th percentile of intensity facing an HR of 0.14 (95% CI: 0.09-0.21) compared to an individual at the 90th percentile of genetic risk and 10th percentile of intensity. Physical activity, especially physical activity intensity, is associated with an attenuation of some of the risk of coronary artery disease but this pattern does not vary by genetic risk. This accelerometer-based study provides the clearest evidence to date regarding the joint influence of genetics, overall physical activity, and physical activity intensity on coronary artery disease.

Histopathological study of heart and cardiac vessels in autopsy cases from tertiary health-care center

Background: Atherosclerosis is a chronic inflammatory disease causing more morbidity and mortality in developed as well as in developing countries. Among Indians, atherosclerotic lesions occur 10–15 years earlier, and the lesions are formed in the advanced stage. It is difficult and expensive to evaluate the atherosclerotic lesions in living subjects. Atherosclerosis of cardiac vessels and myocardial infarction are the most common fatal cardiac diseases discovered in autopsies. The incidence of coronary artery diseases is increasing worldwide as well as in India, which carries a huge challenge in diagnosing the same. Aims and Objectives: The aims and objectives are to study the spectrum of histopathological findings in heart and atherosclerotic lesions in cardiac vessels in autopsy cases. Materials and Methods: This is a retrospective study done in the Department of Pathology at Government Kilpauk Medical College and Hospital over a period of 1 year (March 2022–December 2022). In this study, a total of 100 autopsy cases were taken to study the pathology of the heart and the grading of atherosclerotic lesions in cardiac vessels. Heart specimens were received from the Forensic Medicine Department. The atherosclerotic lesions of cardiac vessels were graded according to the American Heart Association (AHA) classification. Results: Among 100 cases studied during a period of 1 year, most of the cases were in the age group of 30–41 years. Male preponderance was noted when compared to females. Out of 100 cases, 79 cases had histopathological evidence of atherosclerosis, and other findings were as follows: one case of giant cell myocarditis, one case of pericarditis, and one case of adenocarcinoma of the lung extending into the coronary vessels. The most common type of atherosclerotic lesion seen was type 7 AHA, most frequently involving the aorta, followed by both coronary ostia and the left anterior descending artery. Conclusion: In this study, atherosclerotic lesions were observed very frequently in younger individuals. It is an indication for the implementation of antiatherogenic preventive measures in young populations. It highlights the importance of screening for cardiovascular risk factors at an early age.

Percutaneous coronary intervention facilities in Nigeria.

In Nigeria, the incidence of coronary artery disease has doubled over the last three decades. However, there appears to be a lack of adequate heart catheterisation facilities. A list of percutaneous coronary intervention (PCI)-capable facilities was compiled for each state in Nigeria and the federal capital territory. Population estimates for 2019 were obtained from the National Bureau of Statistics and this was utilised to calculate the number of PCI facilities per person in each state and the country. There are 12 operational PCI facilities in Nigeria, 11 of which are in the private health sector. Overall, there is one PCI facility per 16 761 272 people in Nigeria. There is a distinct lack of PCI-capable facilities in Nigeria. There needs to be an investment from the government and stakeholders in Nigeria to increase the access to PCI, given the paradigm shift from communicable to noncommunicable diseases.