High Risk For CAD Research Articles

Fellow Quality Improvement Project: Identification of High Risk CAD Patients and Referral to Newly Established Lipid Clinic, What are the Clinical Implications?

Fellow Quality Improvement Project: Identification of High Risk CAD Patients and Referral to Newly Established Lipid Clinic, What are the Clinical Implications?

Which risk factor best predicts coronary artery disease using artificial neural network method?

BackgroundCoronary artery disease (CAD) is recognized as the leading cause of death worldwide. This study analyses CAD risk factors using an artificial neural network (ANN) to predict CAD.MethodsThe research data were obtained from a multi-center study, namely the Iran-premature coronary artery disease (I-PAD). The current study used the medical records of 415 patients with CAD hospitalized in Razi Hospital, Birjand, Iran, between May 2016 and June 2019. A total of 43 variables that affect CAD were selected, and the relevant data was extracted. Once the data were cleaned and normalized, they were imported into SPSS (V26) for analysis. The present study used the ANN technique.ResultsThe study revealed that 48% of the study population had a history of CAD, including 9.4% with premature CAD and 38.8% with CAD. The variables of age, sex, occupation, smoking, opium use, pesticide exposure, anxiety, sexual activity, and high fasting blood sugar were found to be significantly different among the three groups of CAD, premature CAD, and non-CAD individuals. The neural network achieved success with five hidden fitted layers and an accuracy of 81% in non-CAD diagnosis, 79% in premature diagnosis, and 78% in CAD diagnosis. Anxiety, acceptance, eduction and gender were the four most important factors in the ANN model.ConclusionsThe current study shows that anxiety is a high-prevalence risk factor for CAD in the hospitalized population. There is a need to implement measures to increase awareness about the psychological factors that can be managed in individuals at high risk for future CAD.

Kruppel benzeri faktör 2 polimorfizmlerinin koroner arter hastalığı riski ile ilişkisi

Purpose: Coronary artery disease is defined as complications that develop in proportion to the prevalence of ischemia due to occlusion of the coronary arteries and the resulting cell death. The development of atherosclerosis is significantly influenced by endothelial cell dysfunction. Kruppel-like factor 2, a transcription factor, has been shown to regulate critical biological events in endothelial biology, such as vascular tone, migration, proliferation, vasoreactivity, and angiogenesis. In our study, it was aimed to clarify the relationship between coronary artery disease and Kruppel-like factor 2 protein levels and C1239A polymorphisms.
 Materials and Methods: 191 individuals who underwent coronary angiography at Mersin University Faculty of Medicine, Department of Cardiology, Health, Research and Application Center were included in the study. Measurements of serum fasting blood glucose, HDL cholesterol, total cholesterol, and triglyceride levels were performed on the AU5800 (Beckman Coulter, United States) autoanalyzer. Serum LDL levels were calculated using the Friedwald equation. Serum Kruppel-like factor 2 protein levels were measured by sandwich enzyme-linked immunoassay method on the Multiskan GO (Thermo Scientific, Finland) device. Kruppel-like factor 2 C1239A variations were detected on the Applied Biosystem VIIA™ 7 Real-Time PCR (Life Technologies Co., United States) device by TaqMan® single nucleotide polymorphism (SNP) genotyping method.
 Results: Men had a 3.8-fold higher risk of CAD than women. (Odd’s ratio 3.83, 95% Confidence interval 1.98-7.39; p

Abstract P408: Association Between South Asian Ethnicity and Clinical Characteristics of Patients Undergoing Cardiac Catheterization

Background: We sought to describe differences in the characteristics of coronary interventions in U.S. South Asians (SA), an ethnicity at high risk for CAD, as compared to other races/ethnicities in New Jersey. Methods: In this single-center, retrospective cohort study of 8,850 patients from 2019-2021 undergoing coronary interventions (elective or acute), SAs were identified by 2 expert adjudicators. We used multivariable linear regression to estimate differences in mean age of coronary intervention by race/ethnicity (SA, non-Hispanic White [NHW], non-Hispanic Black [NHB], Hispanic, Other Asian, Other/unspecified). Among a subset of 7,288 patients, we used logistic regression to estimate odds of premature CAD (age<50y for overall cohort, <45y for male, <55y for female) and odds of multi-vessel disease (MVD; >2 vessels with ≥70% stenosis), adjusted for confounders (Table). Results: Among 8,850 patients (mean age 68y; 34% female; 5,011 [58%] NHW, 1,054 [12%] SA), 8.6% had premature CAD, 38% had acute coronary syndrome, and 20% had MVD. SA males, on average, were 5.1y younger and SA females were 3.9y younger, than NHW (male: SA, 63y [SD,12], 67[11] for NHW; female: SA, 67[11], NHW, 70[12]. p<0.001). Compared to NHW, SAs had 4.0x higher odds (male: 4.6x, female: 2.1x), NHB had 2.6x higher odds (M: 2.7x, F: 2.3x), other Asians had 2.1x higher odds (M: 2.3x, F: 1.3x), and Hispanics had 4.5x higher odds (M: 5.4x, F: 2.5x) of premature CAD (Table). SAs also had 47% higher odds of MVD than NHW (male: 45%, female: 47%), while NHB and Hispanics had 46% and 24% lower odds, respectively (Table). Findings were similar when restricting the cohort to patients requiring acute intervention (SA vs. NHW; OR [95% CI]. premature CAD, 3.73[2.44,5.71]; MVD, 1.54[1.12,2.11]). Conclusion: Independent of CAD risk factors, NJ SA males and females undergoing coronary intervention have more than 4 times and 2 times the likelihood of premature CAD, respectively, and more than 1.4 times the likelihood of multi-vessel disease compared to NHW.

Coronary artery calcium score in people living with HIV. Results from the French CAC study

Abstract Background People living with HIV (PLWH) have a higher risk of CAD. Whether coronary artery calcification (CAC) score could better stratify the CV risk remains debated in this middle age population. Purpose We conducted the French CAC score study to compare the CAC score between PLHIV and HIV− subjects at intermediate risk. Methods 689 subjects (257 PLHIV and 432 HIV−) were consecutively addressed for CV risk evaluation including CAC score assessment in 2 centers between 2013 and 2019. Subjects were included if they were 18 years'old or older, had no known cardiovascular disease and had a CAC score along with cardiometabolic assessment. Results The mean age of the cohort was 59.3 years ± 10.7 and predominantly male (54%). PLHIV were younger (55.8 years ± 9.1 vs 61.3±11.3, p<0.004), with a lower rate of diabetics (18% vs 26%, p=0.009) and lower levels of total cholesterol, LDLc, and HDLc (2.0 mmol/l vs, 2.2 mmol/l; 1.2 mmol/L vs 1.3 mmol/L; and 1.2 mmol/L vs 1.4 mol/L respectively, all p<0.001). The prevalence of hypertension, dyslipidemia and obesity was similar between PLHIV and the HIV− group (40%, 43% and 21%, respectively). No differences were observed in CV therapies prescribed including antihypertensive drugs and statins between PLHIV and the HIV− group (39% vs 37%, p=0.54 and 46% vs 39%, p=0.065). In contrast, PLHIV had higher rate of triglycerides (1.4 mmol/L vs 1.2 mmol/L, p=0.01), higher rate of active smoking (28% vs 14%, p<0.001), CRP level (4.0 mg/L vs 2.9 mg/L, p<0.001) along with higher black ethnicity representation (17% vs 5%;, p<0.001). 96% of PLHIV were under antiretroviral therapy at the time of enrollment with 88% who had been exposed to protease inhibitors. In subjects who had carotid and/or limb ultrasound evaluation (67% and 45% respectively in PLHIV and HIV), no increased rate of arterial stenosis >50% was found (13% vs 8%, p=0.16). Concerning, CV risk estimation using 10-year ASCVD and HEART scores, we observed that the median ASCVD score was similar between PLHIV and HIV− group (10.7% vs 9.8, p=0.15) but that PLHIV had a higher HEART score (3.0% vs 2.0%, p<0.001). The repartition between the ASCVD or HEART scores classes between the 2 groups was similar with 80% of the cohort classified as low or intermediate CV risk with the ASCVD score and 88% at intermediate or borderline CV risk with the HEART score. However, no statistically significant differences was found between the 2 groups regarding the prevalence of CAC = 0 (41% vs 44%, p=0.52) and the median CAC score (7.7 vs 8.2, p=0.81). Conclusion In this cohort of subjects at intermediate CV risk according to CV risk scores estimation (ASCVD or HEART scores), PLHIV had a similar prevalence of CAC = 0 and median CAC scores as compared to HIV− subjects despite a younger age (6 years). Longitudinal follow up will explore whether this similar CAC score evaluation will be translated into higher CV events. Funding Acknowledgement Type of funding sources: None.

RNA-sequencing reveals significant differences in the inflammatory response of iPSC-derived endothelial cells from ACS patients and healthy controls

Abstract Background Coronary artery disease (CAD) and cardiovascular diseases (CVD) in general still represent the leading cause of death worldwide. As a multifactorial disease entity, genetic predisposition and lifestyle strongly impact disease development and progression. Here, induced pluripotent stem cells (iPSC) are an ideal tool to differentiate (epi-)genetic from lifestyle disease risk modulation and identify the underlying molecular mechanisms. Aim This study aims to determine differences in iPSC-derived endothelial cell (iPSC-EC) characteristics and functionality between healthy donors and high-risk CAD patients. Methods IPSC from participants with similar lifestyle but different disease status (healthy >65 y/o, n=5, acute coronary syndrome (ACS) <65y/o, n=6) were differentiated into iPSC-EC. Cells were exposed to inflammatory stimulation with tumour necrosis factor alpha (TNF-a) followed by bulk RNA-seq. Monocyte (THP-1) recruitment was assessed under protective and atherogenic flow conditions. Mitotic age was calculated based on DNA-methylation via Hannum estimate (1) for each donor at the iPSC and iPSC-EC (passage 4) stage. Results ACS-iPSC-EC had significantly higher upregulation of E-selectin upon TNF-a stimulation on mRNA level (ACS: 532.1-fold±48.7 vs healthy: 322.3-fold±55.7 with p=0.02). Similarly, ICAM1 protein upregulation was higher in ACS-iPSC-EC compared to healthy iPSC-EC as determined by flow cytometry (ACS: 1.4-fold±0.01 vs healthy: 1.1-fold±0.0007; p<0.001). ACS-iPSC-EC recruited significantly more THP-1 per view field under protective (high shear stress, laminar) flow conditions (ACS: 78.4±20.7 vs healthy: 33.25±12.3 with p=0.04) compared to healthy iPSC-EC. While both groups recruited significantly more THP-1 under atherogenic than protective conditions (ACS: 302±38.9 with p=0.0055 vs healthy: 340±70.4 with p=0.0005), there was no difference between the donor groups (p=0.43). Analysis of bulk RNA-seq data showed significant differences in TNF-a-induced transcriptome changes. Gene set enrichment analysis identified differences in signalling pathways related to leukocyte and lymphocyte-mediated immunity, adaptive immune response, cytokine activity, and many more as shown in Figure 1 (p.adj ≤1e-10). IPSC of both groups had a negative calculated mitotic age (in years) which significantly increased after endothelial differentiation and four population doublings (ACS-iPSC: −14.1±0.7 vs ACS-EC: −0.1±1.1, p<0.0001 and healthy-iPSC: −13.7±0.8 vs healthy-EC: 2.5±1.5, p=0.0001). Conclusion The higher rate of basal THP-1 recruitment and upregulation of adhesion molecules on mRNA and protein level and the distinct transcriptome changes suggest intrinsic differences between patient and healthy iPSC-EC both in the basal state and in inflammatory response. Furthermore, this demonstrates iPSC as a viable in vitro model also for polygenetic diseases such as CAD. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): German Cardiac Society, Research Scholarship

Transient ischemic dilation or transient RV visualization in patients with normal SPECT stress myocardial perfusion imaging: Correlation with CT coronary artery calcium scoring and coronary angiography

BackgroundAncillary findings on MPI, such as transient ischemic dilation (TID) and transient right ventricular visualization (TRV), are recognized as markers of extensive CAD and predictive of adverse outcomes. They usually occur in association with stress-induced regional MPI abnormalities. However, the clinical significance of these ancillary markers in the presence of normal stress MPI is incompletely understood. MethodsFrom a cohort of 564 consecutive patients referred for clinical SPECT stress MPI, 44 patients had normal stress SPECT MPI and either TID (n = 28) or TRV (n = 16). These imaging findings were correlated with CT coronary calcium (CAC), CT coronary angiography (CTA), and invasive coronary angiography (ICA) in patients with severe CAC ≥ 1000 HU. TID and TRV were quantified as stress/rest ratios. Severe CAD was defined as > 70% luminal stenosis on CTA or ICA. ResultsThe median TID ratio was 1.23, with a range of 1.13–1.48; the median TRV ratio was 1.30, with a range of 1.20–1.48. Of 44 patients with TID or TRV, only 9 patients (20.5%) had severe obstructive > 70% CAD by angiography (6 of 28 patients (21.5%) with TID and 3 of 16 patients (19%) with TRV). Severe multi-vessel CAD occurred in only 2 of 44 patients (4.5%). In contrast, of 9 patients with CAC > 1000 HU, 6 (67%) had severe obstructive CAD. ConclusionIn patients with normal stress SPECT MPI and TID or TRV, the incidence of severe obstructive CAD was relatively low and predominantly single-vessel CAD. These findings do not support the concept that TID or TRV with normal stress MPI is predictive of high-risk CAD.

Machine Learning Algorithm to Predict Obstructive Coronary Artery Disease: Insights from the CorLipid Trial.

Developing risk assessment tools for CAD prediction remains challenging nowadays. We developed an ML predictive algorithm based on metabolic and clinical data for determining the severity of CAD, as assessed via the SYNTAX score. Analytical methods were developed to determine serum blood levels of specific ceramides, acyl-carnitines, fatty acids, and proteins such as galectin-3, adiponectin, and APOB/APOA1 ratio. Patients were grouped into: obstructive CAD (SS > 0) and non-obstructive CAD (SS = 0). A risk prediction algorithm (boosted ensemble algorithm XGBoost) was developed by combining clinical characteristics with established and novel biomarkers to identify patients at high risk for complex CAD. The study population comprised 958 patients (CorLipid trial (NCT04580173)), with no prior CAD, who underwent coronary angiography. Of them, 533 (55.6%) suffered ACS, 170 (17.7%) presented with NSTEMI, 222 (23.2%) with STEMI, and 141 (14.7%) with unstable angina. Of the total sample, 681 (71%) had obstructive CAD. The algorithm dataset was 73 biochemical parameters and metabolic biomarkers as well as anthropometric and medical history variables. The performance of the XGBoost algorithm had an AUC value of 0.725 (95% CI: 0.691–0.759). Thus, a ML model incorporating clinical features in addition to certain metabolic features can estimate the pre-test likelihood of obstructive CAD.

Identification of protective biologic factors in patients with high cardiovascular risk, but normal coronary arteries (NormCorn).

Endothelial progenitor cells (EPCs) have an important role in repair following vascular injury. Telomere length has been shown to be correlated with genome stability and overall cell health. We hypothesized that both EPCs and telomere size are related to protective mechanisms against coronary artery disease. Our aim was to evaluate the level and function of circulating EPCs and telomere length in patients with multiple cardiovascular risk factors and anatomically normal coronary arteries vs. matched controls. We included 24 patients, with coronary CTA demonstrating normal coronaries and a high risk of CAD of >10% by ASCVD risk estimator. Control groups included 17 patients with similar cardiovascular profiles but with established CAD and a group of 20 healthy volunteers. Circulating EPCs levels were assessed by flow cytometry for expression of vascular endothelial growth factor receptor 2, CD34 and CD133. The capacity of the cells to form colony forming units (CFUs) was quantified after 1 week of culture. Telomere length was determined by the southern blotting technique. Patients with high risk for CVD and normal coronaries had augmented EPCs function, compared with the CAD group (1.1 vs. 0.22 CFU/f; P = 0.04) and longer telomeres compared with the CAD group (10.7 kb vs. 2.8 kb P = 0.015). These patients displayed a similar profile to the healthy group. Patients with a high risk for CAD, but normal coronary arteries have EPCs function and telomere length which resemble healthy volunteers, and augmented compared with patients with established CAD, which could serve as a protective mechanism against atherosclerosis development in these high-risk patients.

Machine Learning Coronary Artery Disease Prediction Based on Imaging and Non-Imaging Data.

The prediction of obstructive atherosclerotic disease has significant clinical meaning for the decision making. In this study, a machine learning predictive model based on gradient boosting classifier is presented, aiming to identify the patients of high CAD risk and those of low CAD risk. The machine learning methodology includes five steps: the preprocessing of the input data, the class imbalance handling applying the Easy Ensemble algorithm, the recursive feature elimination technique implementation, the implementation of gradient boosting classifier, and finally the model evaluation, while the fine tuning of the presented model was implemented through a randomized search optimization of the model’s hyper-parameters over an internal 3-fold cross-validation. In total, 187 participants with suspicion of CAD previously underwent CTCA during EVINCI and ARTreat clinical studies and were prospectively included to undergo follow-up CTCA. The predictive model was trained using imaging data (geometrical and blood flow based) and non-imaging data. The overall predictive accuracy of the model was 0.81, using both imaging and non-imaging data. The innovative aspect of the proposed study is the combination of imaging-based data with the typical CAD risk factors to provide an integrated CAD risk-predictive model.

Trends in Coronary Artery Disease Screening before Kidney Transplantation.

Coronary artery disease (CAD) screening in asymptomatic kidney transplant candidates is widespread but not well supported by contemporary cardiology literature. In this study we describe temporal trends in CAD screening before kidney transplant in the United States. Using the United States Renal Data System, we examined Medicare-insured adults who received a first kidney transplant from 2000 through 2015. We stratified analysis on the basis of whether the patient's comorbidity burden met guideline definitions of high risk for CAD. We examined temporal trends in nonurgent CAD tests within the year before transplant and the composite of death and nonfatal myocardial infarction in the 30 days after transplant. Of 94,832 kidney transplant recipients, 37,139 (39%) underwent at least one nonurgent CAD test in the 1 year before transplant. From 2000 to 2015, the transplant program waitlist volume had increased as transplant volume stayed constant, whereas patients in the later eras had a slightly higher comorbidity burden (older, longer dialysis vintage, and a higher prevalence of diabetes mellitus and CAD). The likelihood of CAD test in the year before transplant increased from 2000 through 2003 and remained relatively stable thereafter. When stratified by CAD risk status, test rates decreased modestly in patients who were high risk but remained constant in patients who were low risk after 2008. Death or nonfatal myocardial infarction within 30 days after transplant decreased from 3% in 2000 to 2% in 2015. Nuclear perfusion scan was the most frequent modality of testing throughout the examined time periods. CAD testing rates before kidney transplantation have remained constant from 2000 through 2015, despite widespread changes in cardiology guidelines and practice.

Abstract 12277: Concordance of High Polygenic CAD Risk Score With High Coronary Artery Calcium Score & Low Polygenic CAD Risk Score With Low Coronary Artery Calcium Score: A Real World Experience

Introduction: Genetic predisposition for CAD is well established. Polygenic risk scores are emerging as tools which attempt to quantify the genomic component of an individual’s risk for CAD. However, clinical utility for individual risk stratification is unclear. Hypothesis: 180 SNPs previously identified in Caucasian Genome Wide-Association Studies for CAD were used to construct a weighted restricted polygenic risk score (PRS; normalized range 11.18 -17.58). This study hypothesizes that high PRS (>=85th percentile) is associated with high (>400) coronary artery calcium (CAC) score, & a low PRS(< 85th percentile) is associated with low (<100) CAC. Methods: Between January 2018 and March 2020, 21,784 patients underwent CAC screening and/or PRS testing. Caucasian patients with both PRS and CAC scores were reviewed. Patients with CAC 100-400 were excluded. Fisher’s exact test for high/low PRS and high/low CAC was utilized. Results: 2,752 patients were identified to have low (<100) or high (>400) CAC; 306 (11.1%) had a high CAC (table 1). Odds ratio of high PRS associated with high CAC and low PRS associated with low CAC was 1.54 (95% CI: 1.07-2.19; p=0.017). Conclusion: Our real-world experience in a Caucasian cohort shows that high PRS is associated with a high CAC, as is a low PRS with low CAC. Concordance between PRS and CAC lends support for incorporating PRS in the clinical setting, especially for early identification of individuals at high risk for CAD. Larger, ethnically diverse studies are needed.

Abstract 13252: Is There a Gender-Specific Association Between High Coronary Artery Calcium Score and High Polygenic CAD Risk Score?

Introduction: Genetic predisposition for CAD is well established. Polygenic risk scores are emerging as tools which attempt to quantify the genomic component of an individual’s risk for CAD. However, their clinical utility for individual risk stratification is unclear. Hypothesis: 180 SNPs previously identified in Caucasian Genome Wide-Association Studies for CAD were used to construct a weighted restricted polygenic risk score (PRS; normalized range 11.18 -17.58). This study hypothesizes a gender-specific association between high PRS (>=85th percentile) and high coronary artery calcium score (CAC) score, defined as >400. Methods: Between January 2018 & March 2020, 21,784 patients underwent CAC screening and/or PRS testing. Caucasian patients with both PRS and CAC scores were identified. Fisher’s exact test was utilized to test the association between high PRS and high CAC in men and women. Results: Both PRS and CAC were available for 3,197 Caucasian patients, out of which 2,106 (65.8%) were women (figure 1: gender adjusted PRS distribution). Odds ratio of high PRS and high CAC was 1.64 (95% CI: 0.86-2.97; p >0.05) in women and 1.59 (95% CI: 0.98 - 2.53; p>0.05) in men. Conclusions: There is no statistically significant, gender-specific association between high PRS and high CAC in our Caucasian cohort. However, there is a trend suggestive of a positive correlation in women. This clinical data is the first of its kind in a real world setting on the use of PRS for CAD risk assessment. Larger, ethnically diverse studies are needed.

Prevalence and trends of coronary artery disease risk factors and their effect on age of diagnosis in patients with established coronary artery disease: Tehran Heart Center (2005\u20132015)

BackgroundCoronary artery disease (CAD) is a universal public health challenge, more prominently so in the low- and middle-income countries. In this study, we aimed to determine prevalence and trends of CAD risk factors in patients with documented CAD and to determine their effects on the age of CAD diagnosis.Materials and methodsWe conducted a registry-based, serial cross-sectional study using the coronary angiography data bank of the Tehran Heart Center. Adult patients who had obstructive (> 50% stenosis) CAD were included in the study. The prevalence and 11-year trends of conventional CAD risk factors were analyzed by sex and age, and their adjusted effects on the age of CAD diagnosis were calculated.ResultsFrom January 2005 to December 2015, data for 90,094 patients were included in this analysis. A total of 61,684 (68.5%) were men and 28,410 (31.5%) were women. Men were younger at diagnosis than women, with a mean age of 60.1 in men and 63.2 in women (p < 0.001), and had fewer risk factors at the time of diagnosis. Mean age at diagnosis had an overall increasing trend during the study period. Increasing trend was seen in body-mass index, hypertension prevalence, diabetes mellitus. All lipid profile components (total cholesterol, low-density lipoprotein cholesterol, triglycerides, and high-density lipoprotein cholesterol) decreased over time. Of particular interest, opium consumption was associated with 2.2 year earlier age of CAD diagnosis.ConclusionThe major results of this study (lower age of CAD diagnosis in men, lower age of diagnosis associated with most risk factors, and lower prevalence of serum lipids over time) were expected. A prominent finding of this study is confirming opium use was associated with a much younger age of CAD onset, even after adjusting for all other risk factors. In addition to recommendations for control of the traditional risk factors, spreading information about the potential adverse effect of opium use, which has only recently been associated with higher risk of CAD, may be necessary.

The GEnetic Syntax Score: a genetic risk assessment implementation tool grading the complexity of coronary artery disease\u2014rationale and design of the GESS study

BackgroundCoronary artery disease (CAD) remains one of the leading causes of mortality worldwide and is associated with multiple inherited and environmental risk factors. This study is designed to identify, design, and develop a panel of genetic markers that combined with clinical and angiographic information, will facilitate the creation of a personalized risk prediction algorithm (GEnetic Syntax Score—GESS). GESS score could be a reliable tool for predicting cardiovascular risk for future adverse events and for guiding therapeutic strategies.MethodsGESS (ClinicalTrials.gov Identifier: NCT03150680) is a prospective, non-interventional clinical study designed to enroll 1080 consecutive patients with no prior history of coronary revascularization procedure, who undergo scheduled or emergency coronary angiography in AHEPA, University General Hospital of Thessaloniki. Next generation sequencing (NGS) technology will be used to genotype specific single-nucleotide polymorphisms (SNPs) across the genome of study participants, which were identified as clinically relevant to CAD after extensive bioinformatic analysis of literature-based SNPs. Enrichment analyses of Gene Ontology-Molecular Function, Reactome Pathways and Disease Ontology terms were also performed to identify the top 15 statistically significant terms and pathways. Furthermore, the SYNTAX score will be calculated for the assessment of CAD severity of all patients based on their angiographic findings. All patients will be followed-up for one-year, in order to record any major adverse cardiovascular events.DiscussionA group of 228 SNPs was identified through bioinformatic and pharmacogenomic analysis to be involved in CAD through a wide range of pathways and was correlated with various laboratory and clinical parameters, along with the patients' response to clopidogrel and statin therapy. The annotation of these SNPs revealed 127 genes being affected by the presence of one or more SNPs. The first patient was enrolled in the study in February 2019 and enrollment is expected to be completed until June 2021. Hence, GESS is the first trial to date aspiring to develop a novel risk prediction algorithm, the GEnetic Syntax Score, able to identify patients at high risk for complex CAD based on their molecular signature profile and ultimately promote pharmacogenomics and precision medicine in routine clinical settings.Trial registration GESS trial registration: ClinicalTrials.gov Number: NCT03150680. Registered 12 May 2017- Prospectively registered, https://clinicaltrials.gov/ct2/show/NCT03150680.

Quantification of myocardial flow reserve using a gamma camera with solid-state cadmium-zinc-telluride detectors: Relation to angiographic coronary artery disease

BackgroundPrevious studies have suggested using gamma cameras with cadmium-zinc-telluride (CZT) detectors to quantify myocardial blood flow (MBF) and flow reserve (MFR). In this study, we aimed to evaluate the feasibility and accuracy of MFR quantification using a CZT camera compared to coronary angiography. MethodsForty-one participants referred for coronary angiography underwent a rest/stress one-day myocardial perfusion imaging protocol using a CZT gamma camera. Rest and stress dynamic phases were followed by acquisition of traditional perfusion images and time-activity curves were generated. Angiographic and perfusion results were compared to MFR. ResultsPatients with abnormal perfusion presented reduced MFR (2.01 [1.48-2.77] vs. 2.94 [2.38-3.64], P = 0.002), and reduced stress MBF. Patients with high-risk CAD had lower global MFR compared to patients without obstructive disease (1.99 [1.22-2.84] vs. 2.89 [2.22-3.58], P = 0.026). Obstructed vessels showed lower regional MFR when compared to non-obstructed (1.81 [1.19-2.67] vs. 2.75 [2.13-3.42], P < 0.001). A regional MFR of 2.2 provided a sensitivity of 63.2% and specificity of 74.1% to identify an obstructive lesion in the corresponding artery. ConclusionIn patients undergoing invasive coronary angiography for the evaluation of CAD, quantifying MBF and MFR in a CZT gamma camera is feasible and reflects underlying disease. In these patients, reduced regional MFR suggests the presence of obstructive lesion(s).

Genome-Wide Variants Associated With Longitudinal Survival Outcomes Among Individuals With Coronary Artery Disease.

ObjectiveCoronary artery disease (CAD) is an age-associated condition that greatly increases the risk of mortality. The purpose of this study was to identify gene variants associated with all-cause mortality among individuals with clinically phenotyped CAD using a genome-wide screening approach.Approach and ResultsWe performed discovery (n = 684), replication (n = 1,088), and meta-analyses (N = 1,503) for association of genomic variants with survival outcome using secondary data from White participants with CAD from two GWAS sub-studies of the Duke Catheterization Genetics Biorepository. We modeled time from catheterization to death or last follow-up (median 7.1 years, max 12 years) using Cox multivariable regression analysis. Target statistical screening thresholds were p × 10–8 for the discovery phase and Bonferroni-calculated p-values for the replication (p < 5.3 × 10–4) and meta-analysis (p < 1.6 × 10–3) phases. Genome-wide analysis of 785,945 autosomal SNPs revealed two SNPs (rs13007553 and rs587936) that had the same direction of effect across all three phases of the analysis, with suggestive p-value association in discovery and replication and significant meta-analysis association in models adjusted for clinical covariates. The rs13007553 SNP variant, LINC01250, which resides between MYTIL and EIPR1, conferred increased risk for all-cause mortality even after controlling for clinical covariates [HR 1.47, 95% CI 1.17–1.86, p(adj) = 1.07 × 10–3 (discovery), p(adj) = 0.03 (replication), p(adj) = 9.53 × 10–5 (meta-analysis)]. MYT1L is involved in neuronal differentiation. TSSC1 is involved in endosomal recycling and is implicated in breast cancer. The rs587936 variant annotated to DAB2IP was associated with increased survival time [HR 0.65, 95% CI 0.51–0.83, p(adj) = 4.79 × 10–4 (discovery), p(adj) = 0.02 (replication), p(adj) = 2.25 × 10–5 (meta-analysis)]. DAB2IP is a ras/GAP tumor suppressor gene which is highly expressed in vascular tissue. DAB2IP has multiple lines of evidence for protection against atherosclerosis.ConclusionReplicated findings identified two candidate genes for further study regarding association with survival in high-risk CAD patients: novel loci LINC01250 (rs13007553) and biologically relevant candidate DAB2IP (rs587936). These candidates did not overlap with validated longevity candidate genes. Future research could further define the role of common variants in survival outcomes for people with CAD and, ultimately, improve longitudinal outcomes for these patients.

Association of road traffic noise exposure and prevalence of coronary artery disease: A cross-sectional study in North India.

Epidemiological studies have established that noise from transportation sources exceeding the safe limits elevates the risk for cardiovascular diseases. The results however have remained heterogeneous. The present study was conducted to investigate the association between road traffic noise exposure and prevalence of coronary artery disease besides sub-group analysis was performed for identifying the most susceptible population. Traffic noise exposure was measured using the Lden metric in both continuous and categorical forms. A cross-sectional study was performed and information about sociodemographic, lifestyle, and health-related factors was collected. Noise level < 60 dB(A) representing the quiet areas was used as the reference group. Univariate and multivariate logistic regressions were performed to estimate the odds for self-reported coronary artery disease concerning road traffic noise after adjusting for confounding variables. The residents living in noisy areas were found to have a 2.25 times higher risk per 5 dB(A) increment in the noise levels (95% CI = 1.38 to 3.67). Males were at a higher risk of CAD (OR = 2.61; 95% CI = 1.84 to 3.72) as compared to females (OR = 2.07; 95% CI = 1.37–3.13). The subgroup analysis revealed that being sensitive to noise, belonging to a higher age group, reporting higher stress levels, and poor sleep quality were associated with higher risk. The study also provides evidence that exposure to noise levels greater than 60 dB(A) is associated with the prevalence of coronary artery disease in adults.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11356-021-14582-2.

Circulating Level of Monocyte Chemoattractant Protein-1 and Risk of Coronary Artery Disease: A Case-Control and Mendelian Randomization Study.

BackgroundCoronary artery disease (CAD) ranks the leading cause of death worldwide, and inflammation has been implicated in all stages of CAD and is considered to contribute to the pathophysiological basis of atherogenesis.MethodsHere, we implemented a case–control study and a two-sample Mendelian randomization (MR) study to explore the associations between CAD risk and genetic predisposition to circulating level of monocyte chemoattractant protein-1 (MCP1), the most important regulator of monocyte trafficking.ResultsIn case–control study, we found circulating level of MCP1 was significantly associated with increased risk of CAD (OR for per quartile increment: 1.33, 95% CI: 1.19–1.49, P<0.001). Further, genetically predicted higher level of MCP1 was significantly associated with higher risk of CAD (OR for 1-SD increase: 1.05, 95% CIs: 1.02–1.08, P value: 0.002) in MR analysis. Sensitivity analyses were also conducted to validate the main findings, and we also did not detect any directional pleiotropy effects using the MR Egger intercept test (P=0.831).ConclusionTo sum up, our study suggested that increased CAD risk was associated with a predisposition to higher level of MCP1. Additional insight into the contribution of MCP1 to the occurrence of CAD is still needed.

Diagnostic Yield of Coronary Angiography in Asymptomatic Orthotopic Liver Transplantation Candidates

BackgroundThe ideal cardiac risk stratification strategy for orthotopic liver transplantation (OLT) is unknown. Our institution performed coronary angiography for asymptomatic OLT candidates at high risk for CAD: ≥65 years of age, diabetic and ≥55 years of age or diagnosed ≥5 years, abnormal stress test, or at the discretion of the OLT committee. MethodsThe analysis included 301 consecutive, asymptomatic OLT candidates who underwent coronary angiography. The primary outcome was the prevalence of obstructive CAD. ResultsAt 2-year follow-up, OLT was performed in 44.9%, and 42.2% died. The prevalence of obstructive CAD, involvement of the proximal or mid LAD, and 3-vessel CAD were 10.3%, 6.6%, and 0.7%, respectively. Percutaneous and surgical revascularization were performed in 7.0% and 1.3%, respectively. Stress test was performed in 54.8%. The sensitivity and specificity of stress testing were 0% and 87.1%, respectively. The negative and positive predictive values of stress testing were 91.4% and 0%, respectively. Chest computed tomography (CT) was performed in 83.1%. Moderate or severe coronary artery calcification (CAC) was present in 47.8%. The sensitivity and specificity of moderate or severe CAC were 88.9% and 57.3%, respectively. The negative and positive predictive values of moderate or severe CAC were 97.7% and 20.2%, respectively. Multivariate analysis demonstrated that CAC was an independent predictor of obstructive CAD (HR 10.7; 95% CI 3.2–37.9; p < 0.001). ConclusionsThe prevalence of obstructive CAD in asymptomatic OLT candidates at high risk was uncommon. Alternative diagnostic strategies may be preferred to coronary angiography.