Traditional Risk Factors For Atherosclerosis Research Articles

Traditional Cardiovascular Risk Factors and Coronary Microvascular Disease in Women and Men- A Single Center Study.

Introduction Coronary microvascular disease (CMD) is common in patients with and without obstructive epicardial coronary artery disease (CAD). Risk factors for the development of CMD have not been fully elucidated, and data regarding sex associated differences in traditional cardiovascular risk factors for obstructive CAD in patients with CMD are lacking. Methods In this single center, prospective registry, we enrolled patients with non-obstructive CAD undergoing clinically indicated invasive assessment of coronary microvascular function between November 2019 and March 2023. Associations between coronary microvascular dysfunction, traditional cardiovascular risk factors, and sex were assessed using univariate and multivariate regression models. Results Overall, 245 patients with non-obstructive CAD were included in the analysis (62.9% female; median age 68 (interquartile range [IQR]: 59,75). Microvascular dysfunction was diagnosed in 141 patients (57.5%). The prevalence of microvascular dysfunction was similar in women and men (59.0% vs. 57.0%; p=0.77). No association was found between traditional risk factors for coronary atherosclerosis and CMD regardless of whether CMD was structural or functional. In women, but not in men, older age and the presence of previous ischemic heart disease were associated with lower coronary flow reserve (CFR) (β=-0.29; p<0.01 and β=-0.15; p=0.05, respectively) and lower resistive reserve ratio (RRR) (β=-0.28; p<0.01 and β=-0.17; p=0.04, respectively). Conclusion For the entire population, no association was found between coronary microvascular dysfunction and traditional risk factors for coronary atherosclerosis. In women only, older age and previous ischemic heart disease were associated with coronary microvascular dysfunction. Larger studies are needed to elucidate risk factors for CMD.

E012 Burden and risk factors for cardiovascular involvement in connective tissue disease

Abstract Background/Aims Connective tissue diseases (CTD) are associated with several cardiovascular manifestations. Cardiovascular diseases (CVD) are significant cause of morbidity and premature death. The pathogenesis of CVD in CTD patients is incompletely understood and likely multifactorial. Traditional risk factors for atherosclerosis are common among patients with CTD as well as metabolic syndrome. Furthermore, diabetes, dyslipidaemia, hypertension, and obesity may all be exacerbated by connective tissue disease itself or treatment with glucocorticoids. The aim of this study was to assess the burden of CVD and the risk factors for the development of cardiovascular disease in patients with CTD. Methods This was a retrospective study from a single centre. We reviewed clinical records of CTD patients as determined by treating rheumatologist. This CTD cohort included patients with systemic lupus erythematosus (SLE), myositis, systemic sclerosis, Sjogren’s syndrome, mixed and undifferentiated connective tissue diseases. Data on demographic, clinical, laboratory parameters, cardiac investigations, treatment and outcome were collected from electronic patient records. CVD and traditional risk factors were defined using standard criteria. Results A total of 298 patients with CTD were included in the analysis. Mean age of the cohort was 61±17.7 years and majority were females (n = 240, 80.5%). Of the 298 patients, 64 had CVD (21.5%). Most common CVD was ischaemic heart disease (17 patients) followed by hypertension (12), arrhythmia (9), pulmonary arterial hypertension (7), valvular diseases (5), pericardial disease (3), cardiomyopathy (3), myocarditis (2), thromboembolism (3), aortic dissection (2) and coronary spasm (1). Patient with CTD who had CVD were older (72.5±12.2 years) compared to CTD patients who did not develop CVD (non-CVD group, 57.7±17.6 years). The duration of CTD was shorter in patients with CVD (88.9±41.7 months), compared to 106±84.3 months in non-CVD group. The risk factors such as smoking, diabetes and dyslipidaemia was higher in the CVD group. Comparing CVD vs non-CVD patients respectively, systolic BP (147.1±23.0 vs 133.6±18.3mmHg), diastolic BP (83.2 ± 16.3 vs 78.2 ± 11.2mmHg) and serum uric acid (321.8±97.4 vs 292±83.9mg/dL) values were higher and statistically significant (p < 0.05) in CVD group. Patients with CVD had longer exposure to steroids (50%) compared to non-CVD patients (31.6%). They required high dose steroids (9.4% vs 5.6% in non-CVD patients). Current and previous DMARD use was also higher in patients who had CVD (51.6% vs 44.9%). Conclusion This study has demonstrated high burden of cardiovascular disease in CTD patients. Traditional risk factors were more prevalent in the CVD group. DMARD’s and steroid use was also higher in the CVD group. Screening for cardiovascular diseases and disease control in CTD patients is paramount for better outcomes. Further analysis will be carried out for risk factors and relevant outcomes. Disclosure K.K. Garg: None. S. Sampath: None. A. Erinjogunola: None. B. Ting: None. H. Noori: None. G.M. Koduri: None.

Atherosclerosis evaluation and cardiovascular risk estimation using coronary computed tomography angiography.

Clinical risk scores based on traditional risk factors of atherosclerosis correlate imprecisely to an individual's complex pathophysiological predisposition to atherosclerosis and provide limited accuracy for predicting major adverse cardiovascular events (MACE). Over the past two decades, computed tomography scanners and techniques for coronary computed tomography angiography (CCTA) analysis have substantially improved, enabling more precise atherosclerotic plaque quantification and characterization. The accuracy of CCTA for quantifying stenosis and atherosclerosis has been validated in numerous multicentre studies and has shown consistent incremental prognostic value for MACE over the clinical risk spectrum in different populations. Serial CCTA studies have advanced our understanding of vascular biology and atherosclerotic disease progression. The direct disease visualization of CCTA has the potential to be used synergistically with indirect markers of risk to significantly improve prevention of MACE, pending large-scale randomized evaluation.

Abstract P264: HDL-C Variability and Peripheral Artery Disease

Background: Growing evidence has recognized the clinical implications of lipid variability in relation to cardiovascular disease and adverse outcomes. However, data on the association between lipid variability and the risk of incident peripheral artery disease (PAD) remain scarce compared to other manifestations like coronary artery disease and stroke. Methods: We conducted a study using data from the Chang Gung Research Database in Taiwan. A total of 93,948 patients diagnosed with hyperlipidemia between 2007 and 2013 who had at least one lipid measurement annually for four consecutive years were included in this study. Lipid levels, including total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglycerides, as well as their visit-to-visit variability (average real variability, ARV), were calculated over the four-year period. Patients were followed up until December 31, 2019, for the development of incident PAD. Results: During a mean follow-up of 5.9 years, 2,735 (2.5%) of the patients had incident PAD. The mean levels of the four lipids were all significantly associated with the development of incident PAD. However, only HDL-C ARV showed a significant association with an increased risk of incident PAD, independent of traditional risk factors for atherosclerosis and lipid-lowering therapy (adjusted hazard ratio: 1.13; 95% confidence interval: 1.004-1.27 for the comparison between patients in the highest and lowest quartile of HDL-C ARV; P for trend = 0.002). A sensitivity analysis using the variability independent of the mean as the HDL-C variability index confirmed this association. The study result was consistent across all subgroups analyzed. Conclusions: In this multi-institutional database analysis, visit-to-visit variability in HDL-C was significantly associated with the risk of incident PAD, independent of traditional risk factors for atherosclerosis, mean lipid levels, and the use of lipid-lowering therapy. Absolute levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides were all significantly associated with the development of incident PAD. Visit-to-visit variability in HDL-C was significantly linked to the risk of incident PAD, irrespective of traditional atherosclerosis risk factors, mean lipid levels, and lipid-lowering therapy use.

Serum immunoglobulin M is associated with the severity of coronary artery disease in adults.

The purpose of this study was to investigate the relationship between serum immunoglobulin M (IgM) and the severity of coronary artery disease in Chinese patients who underwent coronary angiography. A total of 2,045 patients who underwent coronary angiography (CAG) from March 2017 to March 2020 at Beijing Hospital were included in this study. Serum IgM concentration and biochemical indicators were measured before coronary angiography (CAG). The triquartile IgM levels at baseline in the population were analysed. Spearman rank correlation was used to analyse the association between IgM and traditional risk factors for coronary artery disease (CAD). CAD patients were divided into subgroups by affected area, number of affected vessels, and Gensini score to analyse the relationship between IgM and CAD severity. Multivariable logistic regression analysis was used to evaluate the association between IgM and CAD severity. Serum IgM levels were significantly lower in the CAD group (63.5 mg/dL) than in the non-coronary artery disease (NCAD) group (72.3 mg/dL) (P < 0.001). Serum IgM levels were significantly associated with sex. Serum IgM levels were positively correlated with traditional CAD risk factors such as TG, TC and LDL-C (P < 0.05), and negatively associated with the number of obstructed vessels, the number of affected areas, and Gensini scores. After adjusting for age, sex, smoking status, hypertension, dyslipidaemia, diabetes, stroke, and statin use history, a high IgM level was independently negatively associated with the severity of CAD expressed by the Gensini score. We determined that serum IgM was independently negatively associated with the severity of CAD diagnosed by angiography in Chinese adults.

Polygenic Risk Score Associates With Atherosclerotic Plaque Characteristics at Autopsy.

Polygenic risk scores (PRSs) for coronary artery disease (CAD) potentially improve cardiovascular risk prediction. However, their relationship with histopathologic features of CAD has never been examined systematically. From 4327 subjects referred to CVPath by the State of Maryland Office Chief Medical Examiner for sudden death between 1994 and 2015, 2455 cases were randomly selected for genotyping. We generated PRS from 291 known CAD risk loci. Detailed histopathologic examination of the coronary arteries was performed in all subjects. The primary study outcome measurements were histopathologic plaque features determining severity of atherosclerosis, including %stenosis, calcification, thin-cap fibroatheromas, and thrombotic CAD. After exclusion of cases with insufficient DNA sample quality or with missing data, 954 cases (mean age, 48.8±14.7 years; 75.7% men) remained in the final study cohort. Subjects in the highest PRS quintile exhibited more severe atherosclerosis compared with subjects in the lowest quintile, with greater %stenosis (80.3%±27.0% versus 50.4%±38.7%; adjusted P<0.001) and a higher frequency of calcification (69.6% versus 35.8%; adjusted P=0.004) and thin-cap fibroatheroma (26.7% versus 9.5%; adjusted P=0.007). Even after adjustment for traditional CAD risk factors, subjects within the highest PRS quintile had higher odds of severe atherosclerosis (ie, ≥75% stenosis; adjusted odds ratio, 3.77 [95% CI, 2.10-6.78]; P<0.001) and plaque rupture (adjusted odds ratio, 4.05 [95% CI, 2.26-7.24]; P<0.001). Moreover, subjects within the highest quintile had higher odds of CAD-associated cause of death, especially among those aged ≤50 years (adjusted odds ratio, 4.08 [95% CI, 2.01-8.30]; P<0.001). No statistically significant associations were observed with plaque erosion after adjusting for covariates. This is the first autopsy study investigating associations between PRS and atherosclerosis severity at the histopathologic level in subjects with sudden death. Our pathological analysis suggests PRS correlates with plaque burden and features of advanced atherosclerosis and may be useful as a method for CAD risk stratification, especially in younger subjects.

Infection with Helicobacter pylori may predispose to atherosclerosis: role of inflammation and thickening of intima-media of carotid arteries.

Atherosclerosis is a major instigator of cardiovascular disease (CVD) and a main cause of global morbidity and mortality. The high prevalence of CVD calls for urgent attention to possible preventive measures in order to curb its incidence. Traditional risk factors of atherosclerosis, like age, smoking, diabetes mellitus, dyslipidemia, hypertension and chronic inflammation, are under extensive investigation. However, these only account for around 50% of the etiology of atherosclerosis, mandating a search for different or overlooked risk factors. In this regard, chronic infections, by Helicobacter pylori for instance, are a primary candidate. H. pylori colonizes the gut and contributes to several gastrointestinal diseases, but, recently, the potential involvement of this bacterium in extra-gastric diseases including CVD has been under the spotlight. Indeed, H. pylori infection appears to stimulate foam cell formation as well as chronic immune responses that could upregulate key inflammatory mediators including cytokines, C-reactive protein, and lipoproteins. These factors are involved in the thickening of intima-media of carotid arteries (CIMT), a hallmark of atherosclerosis. Interestingly, H. pylori infection was found to increase (CIMT), which along with other evidence, could implicate H. pylori in the pathogenesis of atherosclerosis. Nevertheless, the involvement of H. pylori in CVD and atherosclerosis remains controversial as several studies report no connection between H. pylori and atherosclerosis. This review examines and critically discusses the evidence that argues for a potential role of this bacterium in atherogenesis. However, additional basic and clinical research studies are warranted to convincingly establish the association between H. pylori and atherosclerosis.

The FCGR2A Is Associated with the Presence of Atherosclerotic Plaques in the Carotid Arteries-A Case-Control Study.

Atherosclerotic plaques in carotid arteries (APCA) are a prevalent condition with severe potential complications. Studies continuously search for innovative biomarkers for APCA, including those participating in cellular metabolic processes, cell adhesion, immune response, and complement activation. This study aimed to assess the relationship between APCA presence and a broad range of cardiometabolic biomarkers in the general population. The study group consisted of consecutive participants of the population study Bialystok PLUS. The proximity extension assay (PEA) technique from the Olink Laboratory (Uppsala, Sweden) was used to measure the levels of 92 cardiometabolic biomarkers. The study comprised 693 participants (mean age 48.78 ± 15.27 years, 43.4% males, N = 301). APCA was identified in 46.2% of the participants (N = 320). Of the 92 biomarkers that were investigated, 54 were found to be significantly linked to the diagnosis of APCA. After adjusting for the traditional risk factors for atherosclerosis in multivariate analysis, the only biomarker that remained significantly associated with APCA was FCGR2A. In the general population, the prevalence of APCA is very high. A range of biomarkers are linked with APCA. Nonetheless, the majority of these associations are explained by traditional risk factors for atherosclerosis. The only biomarker that was independently associated with APCA was the FCGR2A.

Clinical case of a 29 weeks pregnant patient with ST-segment elevation myocardial infarction

HighlightsThis clinical case describes the management of a 29 weeks pregnant patient with myocardial infarction. The material will be useful for cardiologists, physicians, obstetricians and gynecologists, and endovascular surgeons. AbstractUnavoidable drastic changes in lifestyle due childbirth are pushing women to postpone it to an older age, thus increasing the risk of coronary artery disease (CAD) in pregnant women. This can be a problem not only for patients, but also for specialists. Currently there are 3-6 cases of acute coronary syndrome (ACS) per 100 thousand pregnancies, meaning such cases occur rarely in real clinical practice. Discomfort in the chest area does not directly indicate cardiac problem, so women do not visit cardiologist right away, and thus ACS remains undiagnosed. Besides traditional risk factors for CAD (age, dyslipidemia, smoking, physical inactivity), there are some additional obstetric factors: preeclampsia, thrombophilia and postpartum bleeding. About 40% of patients have myocardial infarction in the third trimester. Atherosclerosis is the most common cause of ACS, with coronary artery spasms, coronary artery dissection and thrombosis following behind. Currently the maternal mortality due to MI has decreased from 20% to 5% due to introduction of the percutaneous coronary intervention (PCI) into the treatment of ACS. There are not enough data on the use of thrombolytics and other medicine in the treatment of CAD, because pharmacological therapy can be dangerous in the early pregnancy at the peak of organogenesis. Moreover, PCI should be used with caution due to harmful effects of radiation on the pregnant woman and the fetus. The main task in later stages of pregnancy is to balance out the risk of stent thrombosis upon discontinuing double antiplatelet therapy and bleeding during childbirth and in the postpartum period. This article describes a clinical case of a 29 weeks pregnant patient with myocardial infarction.

Gene polymorphism in IL17A and gene-gene interaction in the IL23R/IL17A axis are associated with susceptibility to coronary artery disease

AimsStudies have confirmed that the IL-23R/IL-17A axis plays an important role in the development of autoimmune and inflammatory diseases. However, its role in coronary artery disease (CAD) remains unclear. Here, we conducted a large sample case-control study to investigate the association between the IL23R/IL17A axis and CAD in the Chinese Han population. MethodsTwo SNPs, rs2275913: G>A (IL17A) and rs6682925: T>C (IL23R), were genotyped in 3042 CAD cases and 3216 controls using the high-resolution melt technology (HRM). Logistic regression analyses were used to adjust the traditional risk factors for CAD and perform the gene interaction analyses. Multiple linear regression analyses were used to study the relationships between the selected SNPs and the levels of serum lipids. In addition, meta-analysis also was performed for the association between rs6682925 and rs2275913 with CAD in different popolations. ResultsOur case-control and meta-analysis for single SNPs demonstrated that the frequencies of the alleles and the distribution of the genotypes had no significant differences in CAD cases compared with controls. In the stratified analysis, we observed that the frequency of the IL17A rs2275913-A allele was more epidemic in early-onset CAD than in the controls (Padj = 0.005, OR = 1.209, 95% CI: 1.059–1.382), and the minor allele C of rs6682925 was associated with a decreased level of serum total cholesterol under a recessive model (Padj = 0.011). We demonstrated a significant interaction between rs6682925 and rs2275913 and CAD in the Chinese Han population. Four genotypes (CTGG, CCAA, CCAG, CCGG) were significantly associated with CAD (Padj = 2.94 × 10−4, OR = 0.619, 95% CI: 0.478–0.803; Padj = 0.01, OR = 1.808, 95% CI: 1.152–1.869; Padj = 6 × 10−6, OR = 2.179, 95% CI: 1.558–3.049; Padj = 0.001, OR = 1.883, 95% CI: 1.282–2.762, respectively). ConclusionOur study found no single SNP of rs2275913 in IL17A and rs6682925 in IL23R was associated with CAD in the Chinese population, but the interaction of them were significantly associated with CAD susceptibility, highlighting the key role of the IL-23R/IL-17A axis in the development of CAD. In addition, we also found rs2275913 was associated with early-onset CAD and rs6682925 was associated with total cholesterol levels, which will contribute to the clinical stratified management of this common disease.

Opium consumption and long-term outcomes of CABG surgery in patients without modifiable risk factors.

The question about the significance of opium consumption as a coronary artery disease (CAD) risk factor still remains open. The present study aimed to evaluate the association between opium consumption and long term outcomes of coronary artery bypass grafting (CABG) in patients without standard modifiable CAD risk factors (SMuRFs; hypertension, diabetes, dyslipidemia, and smoking). In this registry-based design, we included 23,688 patients with CAD who underwent isolated CABG between January 2006 to December 2016. Outcomes were compared in two groups; with and without SMuRF. The main outcomes were all-cause mortality, fatal and nonfatal cerebrovascular events (MACCE). Inverse probability weighting (IPW) adjusted Cox's proportional hazards (PH) model was used to evaluate the effect of opium on post-op outcomes. During 133,593 person-years of follow-up, opium consumption was associated with increased risk of mortality in both patients with and without SMuRFs (weighted Hazard Ratio (HR)s: 1.248 [1.009, 1.574] and 1.410 [1.008, 2.038], respectively). There was no association between opium consumption and fatal and non-fatal MACCE in patients without SMuRF (HR = 1.027 [0.762-1.383], HR 0.700 [0.438-1.118]). Opium consumption was associated with earlier age of CABG in both groups; 2.77 (1.68, 3.85) years in SMuRF-less and 1.70 (1.11, 2.38) years in patients with SMuRFs. Opium users not only undergo CABG at younger ages but also have a higher rate of mortality regardless of the presence of traditional CAD risk factors. Conversely, the risk of MACCE is only higher in patients with at least one modifiable CAD risk factor.

A STUDY OF CLINICAL PRESENTATION AND RISK FACTORS FOR ACUTE MYOCARDIAL INFARCTION IN PATIENTS BELOW 40 YEARS AT A TERTIARY CARE CENTRE

INTRODUCTION: Coronary Artery Disease (CAD) in young Indians, which accounts for 12-16% of cases in people below 45 years old and contributes to 50% of CAD-related deaths in those below 50 years. Traditional risk factors for CAD as hypertension and smoking explain most cases of CAD, but 15-20% have no identifiable risk factors. Recent studies show elevated Lp(a) and hyperhomocysteinemia play a role in MI and that measuring Apo B and Apo A1 is better than measuring LDL-C and HDL-C. The true prevalence of CAD in the young is understated and this study aims to determine the association of newly identified and traditional risk factors with premature onset of CAD in those 40 years or younger.Method: This was a prospective, observational study conducted in the department of general medicine at Jhalawar Medical College on 50 patients who had suffered an acute myocardial infarction.A comprehensive evaluation was performed using a pre-test proforma that included a detailed clinical history, physical examination, electrocardiography, biochemical analysis, and an echocardiographic evaluation.Results: The majority of patients (60%) were in the age range of 35-40 years,with the youngest being 19 years old.88% of the patients were male and the mean age for female patients was 36.17 years and for males, it was 34.02 years.The most common symptom in young patients was chest pain (90%),followed by sweating (52%) and breathlessness (30%).The most common risk factor for MI was tobacco abuse (86%), followed by a positive family history of CAD (16%) and a high BMI (8%).The majority of patients (72%) had multiple risk factors for AMI,24% had a single risk factor,and 4% had none.The homocysteine level was above normal in 42% of patients, with 2% having a high risk. Conclusion: Our study highlights the importance of addressing risk factors for better patient outcomes in the case of Acute Myocardial Infarction (AMI).To address the high prevalence of cigarette smoking in young adults,preventive educational programs and smoking cessation clinics need to be established.Medical personnel should prioritize educating the youth on diabetes and cholesterol management

Genetic Analysis Reveals Different Mechanisms of IL-5 Involved in the Development of CAD in a Chinese Han Population.

Coronary artery disease (CAD) is a complex disease and the leading cause of death worldwide. It is caused by genetic and environmental factors or their interactions. Candidate gene association studies are an important genetic strategy for the study of complex diseases, and multiple variants of inflammatory cytokines have been found to be associated with CAD using this method. Interleukin-5 (IL-5) is an important inflammatory immune response factor that plays a role in a various inflammatory disease. Clinical tests and animal experiments indicated that IL-5 is involved in CAD development, but the exact mechanisms are unclear. This study investigated the genetic relationship between the single nucleotide polymorphisms (SNPs) in IL5 and CAD. Based on the Chinese Han population, we collected 1,824 patients with CAD and 1,920 control subjects and performed a two-stage case-control association analysis for three SNPs in IL5 (rs2057687, rs78546665, and rs2069812) using the high resolution melt (HRM) technology. Logistic regression analyses were applied to adjust for traditional risk factors for CAD and to perform haplotype and gene interaction analyses. Multiple linear regression analyses were used to study relationships between the selected SNPs and serum lipid levels. In this study, two-stage case-control association analysis revealed that the allele and genotype frequency distributions of the three IL5 SNPs were not statistically significant between the case and control groups. In addition, none of the IL5 haplotypes were associated with CAD. Further stratified analyses were conducted by sex, age, hypertension, and disease status, respectively, and the results revealed that the rs2057687 and rs2069812 of IL5 were associated with CAD in the male group (p adj = 0.025, OR, 0.77 (95% CI, 0.62-0.97); p adj = 0.016, OR, 0.82 (95% CI, 0.70-0.97), respectively); the rs2057687 and rs78546665 of IL5 were associated with late-onset CAD (p adj = 0.039, OR, 0.78 (95% CI, 0.62-0.99); p adj = 0.036, OR, 1.46 (95% CI, 1.02-1.53), respectively); the rs2069812 of IL5 was associated with CAD in the hypertension group (p adj = 0.036, OR, 0.84 (95% CI, 0.71-0.99)); and none of the SNPs in IL5 were associated with different CAD states (anatomical CAD and clinical CAD). In addition, the association between SNPs and the serum lipid levels indicated that rs78546665 was positively correlated with triglyceride levels (p = 0.012). Finally, SNP-SNP interaction analyses revealed that interactions of rs2057687 and rs2069812 were associated with CAD (p adj = 0.046, OR, 0.77 (95% CI, 0.13-4.68)). This study suggested that the common variants of IL5 might play a role in CAD by affecting the risk factors for CAD and through SNP-SNP interactions, which provides a new target for specific treatment of CAD patients and a theoretical basis for personalized medicine.

Leukocyte Count and Coronary Artery Disease Events in People With Human Immunodeficiency Virus: A Longitudinal Study.

People with human immunodeficiency virus (HIV; PWH) have increased cardiovascular risk. Higher leukocyte count has been associated with coronary artery disease (CAD) events in the general population. It is unknown whether the leukocyte-CAD association also applies to PWH. In a case-control study nested within the Swiss HIV Cohort Study, we obtained uni- and multivariable odds ratios (OR) for CAD events, based on traditional and HIV-related CAD risk factors, leukocyte count, and confounders previously associated with leukocyte count. We included 536 cases with a first CAD event (2000-2021; median age, 56 years; 87% male; 84% with suppressed HIV RNA) and 1464 event-free controls. Cases had higher latest leukocyte count before CAD event than controls (median [interquartile range], 6495 [5300-7995] vs 5900 [4910-7200]; P < .01), but leukocytosis (>11 000/µL) was uncommon (4.3% vs 2.1%; P = .01). In the highest versus lowest leukocyte quintile at latest time point before CAD event, participants had univariable CAD-OR = 2.27 (95% confidence interval, 1.63-3.15) and multivariable adjusted CAD-OR = 1.59 (1.09-2.30). For comparison, univariable CAD-OR for dyslipidemia, diabetes, and recent abacavir exposure were 1.58 (1.29-1.93), 2.19 (1.59-3.03), and 1.73 (1.37-2.17), respectively. Smoking and, to a lesser degree, alcohol and ethnicity attenuated the leukocyte-CAD association. Leukocytes measured up to 8 years before the event were significantly associated with CAD events. PWH in Switzerland with higher leukocyte counts have an independently increased risk of CAD events, to a degree similar to traditional and HIV-related risk factors.

Hypomethylation in MTNR1B: a novel epigenetic marker for atherosclerosis profiling using stenosis radiophenotype and blood inflammatory cells

BackgroundChanges in gene-specific promoter methylation may result from aging and environmental influences. Atherosclerosis is associated with aging and environmental effects. Thus, promoter methylation profiling may be used as an epigenetic tool to evaluate the impact of aging and the environment on atherosclerosis development. However, gene-specific methylation changes are currently inadequate epigenetic markers for predicting atherosclerosis and cardiovascular disease pathogenesis.ResultsWe profiled and validated changes in gene-specific promoter methylation associated with atherosclerosis using stenosis radiophenotypes of cranial vessels and blood inflammatory cells rather than direct sampling of atherosclerotic plaques. First, we profiled gene-specific promoter methylation changes using digital restriction enzyme analysis of methylation (DREAM) sequencing in peripheral blood mononuclear cells from eight samples each of cranial vessels with and without severe-stenosis radiophenotypes. Using DREAM sequencing profiling, 11 tags were detected in the promoter regions of the ACVR1C, ADCK5, EFNA2, ENOSF1, GLS2, KNDC1, MTNR1B, PACSIN3, PAX8-AS1, TLDC1, and ZNF7 genes. Using methylation evaluation, we found that EFNA2, ENOSF1, GLS2, KNDC1, MTNR1B, PAX8-AS1, and TLDC1 showed > 5% promoter methylation in non-plaque intima, atherosclerotic vascular tissues, and buffy coats. Using logistic regression analysis, we identified hypomethylation of MTNR1B as an independent variable for the stenosis radiophenotype prediction model by combining it with traditional atherosclerosis risk factors including age, hypertension history, and increases in creatinine, lipoprotein (a), and homocysteine. We performed fivefold cross-validation of the prediction model using 384 patients with ischemic stroke (50 [13%] no-stenosis and 334 [87%] > 1 stenosis radiophenotype). For the cross-validation, the training dataset included 70% of the dataset. The prediction model showed an accuracy of 0.887, specificity to predict stenosis radiophenotype of 0.940, sensitivity to predict no-stenosis radiophenotype of 0.533, and area under receiver operating characteristic curve of 0.877 to predict stenosis radiophenotype from the test dataset including 30% of the dataset.ConclusionsWe identified and validated MTNR1B hypomethylation as an epigenetic marker to predict cranial vessel atherosclerosis using stenosis radiophenotypes and blood inflammatory cells rather than direct atherosclerotic plaque sampling.

Abstract 10481: The Effect of Current Smoking on Platelet Reactivity Measures by Point-of-Care Methods in Patients Treated With and Without Clopidogrel

Introduction: Smoking is associated with worse response to P2Y12 inhibitors. However, the relationship between smoking, platelet reactivity (PR) and traditional risk factors for atherosclerosis is unclear. Hypothesis: To analyze the relationship between smoking, PR and risk factors for atherosclerosis. Methods: A prospective databank of 13 research protocols was retrospectively analyzed. Among 1260 patients included in the analysis, 299 were smokers; 721 had acute coronary syndromes (521 with clopidogrel), and 539 had stable coronary artery disease (4 with clopidogrel). The association between smoking and PR analyzed by Multiplate-ADP (MPADP) and VerifyNow-PRUTest (VNPRU), inflammatory markers (leukocytes and hs-C-reactive protein), creatinine, HbA1c, total cholesterol, HDL-c, LDL-c and triglycerides, was analyzed in univariate and multivariable models. PR results were analyzed as continuous and categorical variables (bellow or above the median). Results: Unadjusted results for the comparison between smokers and non-smokers are depicted in the Table and Figure. In adjusted models, the significant associations between smoking and PR were maintained: 1) MPADP Odds-Ratio (OR)=0.984, p&lt;0.001; 2) VNPRU OR=0.996, P=0.008; 3) MPADPCAT&gt;MD OR=0.450, P&lt;0.001; 4) VNADPCAT&gt;MD OR=0.408, p&lt;0.001; 5) ADPMEDIAN&gt;MD OR=0.394, p&lt;0.001). HDL-c (negative) was the only risk factor for atherosclerosis that correlated independently with smoking in all adjusted models, with leukocytes (positive) and creatinine (negative) showing correlation in 4 of the 5 models. Conclusion: Smoking is independently associated with lower PR and HDL-c levels.

Plasma Gut Microbe-Derived Metabolites Associated with Peripheral Artery Disease and Major Adverse Cardiac Events.

Cardiovascular diseases are associated with gut dysbiosis, but the role of microbe-derived metabolites as biomarkers or modulators of cardiovascular disease are not well understood. This is a targeted metabolomics study to investigate the association of nine microbe-derived metabolites with lower extremity peripheral artery disease (PAD), a form of atherosclerosis, and major adverse cardiac events (MACE). The study cohort consists of individuals with intermittent claudication and ankle-brachial index (ABI) < 0.9 (N = 119) and controls without clinically-apparent atherosclerosis (N = 37). The primary endpoint was MACE, a composite endpoint of myocardial infarction, coronary revascularization, stroke, transient ischemic attack, or cardiac-related death. Plasma metabolite concentrations differed significantly between the PAD and control groups. After adjustment for traditional atherosclerosis risk factors, kynurenine, hippuric acid, indole-3-propionic acid (IPA), and indole-3-aldehyde (I3A) concentrations were negatively associated with PAD, whereas indoxyl sulfate and 3-hydroxyanthranilic acid were positively associated. Hippuric acid, IPA, and I3A correlated with ABI, a surrogate for atherosclerotic disease burden. Those in the highest I3A concentration quartile had significantly improved freedom from MACE during follow-up compared to those in the lowest quartile. This study identifies specific indole- and phenyl-derived species impacted by gut microbial metabolic pathways that could represent novel microbiome-related biomarkers of PAD.

Polygenic risk score associates with atherosclerosis severity at autopsy

Abstract Background Polygenic risk scores (PRS) for coronary artery disease (CAD) are emerging as a potential method to improve cardiovascular risk prediction. Questions remain about their applicability to diverse populations as well as their correlation with coronary histopathology. Purpose To assess whether high genetic risk associates with histopathologic coronary plaque morphology. Methods We assessed 122 known CAD risk loci in 954 Black and White subjects within our sudden death registry to generate a PRS. The cohort was divided into quintiles according to z-score-standardized PRS, both in a race-stratified fashion and in the pooled sample. Detailed histopathologic examination of the coronary arteries was performed in all subjects. Results Subjects in the highest PRS quintile exhibited more severe atherosclerosis compared to subjects in the lowest quintile, with greater mean cross-sectional luminal narrowing (71.5% (95% CI, 66.6%-76.5%) vs. 56.6% (95% CI, 51.1%-62.1%); adjusted p&amp;lt;0.001; Figure 1) and a higher frequency of calcification (adjusted OR 2.19; 95% CI 1.31–3.68; p=0.003) after adjustment for the first 10 principal components, age, sex, and race. Higher z-score-standardized PRS was predictive for the finding of severe atherosclerosis (i.e., ≥75% cross-sectional luminal narrowing) even after additional controlling for traditional CAD risk factors including hypertension, smoking, diabetes mellitus, and hyperlipidemia (adjusted OR 1.39; 95% CI 1.19–1.63; p&amp;lt;0.001; Figure 2). Among Black subjects, higher PRS was associated with higher odds of plaque rupture (adjusted OR 1.31; 95% CI 1.03–1.66; p=0.03) and predicted CAD-associated cause of death among subjects younger than 50 years old (adjusted OR 1.26; 95% CI 1.01–1.58; p=0.04). Conclusions This is the first autopsy study investigating associations between PRS and atherosclerotic plaque morphology at a histopathologic level. Our pathological analysis suggests PRS correlates with plaque burden and coronary artery calcification and may be useful as a method for CAD risk stratification, especially in younger subjects. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): R01 HL141425 Leducq Foundation Grant

Design, methods and baseline characteristics of the Beijing Hospital Atherosclerosis Study: a prospective dynamic cohort study.

BackgroundThe atherosclerotic coronary artery disease (CAD) risk assessment based on conventional risk factors have only moderate performance, and residual risks still exist. Thus, we reported here a cohort study that aims to identify and validate the new biosignatures (especially the metabolomics, lifestyle biomarkers and biological age), and elucidate their predictive effect on CAD and subsequent cardiovascular events.MethodsThis prospective, single-center, cohort study commenced in March 2017 and seeks to examine patients undergoing coronary angiography (CAG) at the Beijing Hospital. Patients’ baseline demographic and medical history data are captured by questionnaires. Blood samples are taken before CAG for clinical laboratory tests and metabolomics analyses. Traditional CAD risk factors are analyzed by routine assays. CAD-related metabolites from different metabolic pathways and lifestyle biomarkers are measured by liquid chromatography-tandem mass spectrometry methods. Biological ages are calculated based on the laboratory and metabolomics data. The enrolled patients attend annual follow-up examinations for 10 years. The primary end points are the composite end points of major adverse cardiovascular events, including death from any cause, non-fatal myocardial infarction, and non-fatal stroke. Quality management and control are carried out through the entire research process, including standardized baseline and follow-up investigation, intra- and inter-run quality controls for laboratory measurements, etc.ResultsBaseline data of the enrolled 2,970 patients from 2017 to 2020 were collected and are presented in this article. Among them, there were more males (62.5%) than females, and the patients tended to be old and overweight. The percentages of diagnosed hypertension and diabetes were 67.3% and 35.2%, respectively. A total of 8.5% had a family history of premature CAD. Their lipid profiles were within the normal range, probably due to the use of statins.ConclusionsThis study has successfully initiated an investigation into the roles of new biosignatures in predicting CAD among Chinese Han patients undergoing CAG. To the best of our knowledge, this cohort is the first study systematically focusing on the association of lifestyle biomarkers and biological age with CAD risk. Findings from this study will provide biomarkers to discriminate the presence of CAD and to predict subsequent cardiovascular events.

Coronary Computed Tomography Angiography Evaluation of Plaque Morphology and Its Relationship to HDL and Total Cholesterol to HDL Ratio

<h3>Lead Author's Financial Disclosures</h3> Nothing to disclose. <h3>Study Funding</h3> None. <h3>Background/Synopsis</h3> Traditionally non-high-density lipoprotein (non-HDL) indicators have been utilized to stratify cardiovascular risk. Population studies have demonstrated an inverse relationship between HDL cholesterol levels and cardiovascular risk, however, the mechanism by which HDL exhibits its protective effect on the cardiovascular system remains unclear. <h3>Objective/Purpose</h3> To investigate the relationship between the HDL-C level and the total cholesterol to HDL (TC/HDL) ratio with coronary artery plaque burden as determined by coronary computed tomography angiography (CCTA). <h3>Methods</h3> This is a cross-sectional study evaluating the association of HDL-C and TC/HDL ratio with coronary artery plaque volumes. We identified 190 subjects who had undergone quantitative plaque analysis and had lipoprotein values available at our institution. Plaque was analyzed quantitatively utilizing semi-automated plaque analysis software (QAngio version 2.0.5). The plaque volumes are presented as total atheroma volume normalized (TAVnorm). The HDL-C level and TC/HDL ratio were analyzed as continuous variables and categorized at clinically relevant levels. Multivariate regression models adjusted for cardiovascular risk factors were used to evaluate the association of HDL-C and TC/HDL ratio with coronary plaque volumes. <h3>Results</h3> The mean (SD) age of the 190 subjects was 58.9 (+/-9.8) years, and 63% were male. After adjustment for cardiovascular risk factors, HDL- C (>40mg/dL) is inversely associated with fibrous (p=0.003), fibrous fatty (p=0.009), low attenuation plaque (LAP) (p=0.014), total non- calcified plaque (TNCP)(p=0.003), and total plaque (TP)(p=0.005) volume but not associated with dense calcified plaque (p=0.229). TC/HDL ratio (>4.0) is directly associated with LAP (p=0.024) and not associated with fibrous, fibrofatty, TNCP, dense calcified plaque and TP volume. Notably, when examined as continuous variables, increasing HDL- C level is inversely associated with fibrous plaque, TNCP and TP volume and increasing TC/HDL ratio is directly associated with increasing fibrous plaque, and fibrous fatty plaque, LAP, TNCP and TP volume, independent of other risk factors. <h3>Conclusions</h3> There is a strong association between low HDL-C and increasing TC/HDL ratio with increasing coronary plaque volumes, independent of traditional risk factors of atherosclerosis. The findings of this study suggest mechanistic evidence supporting the protective role of HDL-C in coronary artery disease. Additionally, TC/HDL ratio offers value as a secondary treatment target beyond LDL-C, which is especially beneficial in individuals with prevalent lipid discordance, such as those with diabetes and metabolic syndrome.