Coronary Artery Disease Cases Research Articles

Cardiovascular risk factors and major recurrent coronary events: A genetic liability study in patients with coronary artery disease in the UK Biobank

Background and aimsMendelian randomization confirmed multiple risk factors for primary events of coronary artery disease (CAD), but no such studies have been performed on recurrent major coronary events despite interesting insights derived from other designs. We examined the associations between genetically-influenced classical cardiovascular risk factors and the risk of recurrent major coronary events in a cohort of CAD patients. MethodsWe included all first-time CAD cases (defined as angina pectoris, chronic ischemic heart disease or acute myocardial infarction) of European ancestry from the UK Biobank. Cases were followed till the end of follow-up, death or when they developed a recurrent major coronary event (chronic ischemic heart disease or acute myocardial infarction). Standardized weighted genetic risk scores were calculated for body mass index (BMI), systolic blood pressure, LDL cholesterol and triglycerides. ResultsFrom a total of 22,949 CAD patients (mean age at first diagnosis 59.8 (SD 7.3) years, 71.1% men), 12,539 (54.6%) reported a recurrent major coronary event within a period of maximum 17.8 years. One standard deviation higher genetically-determined LDL cholesterol was associated with a higher risk of a recurrent major coronary event (odds ratio: 1.08 [95% confidence interval: 1.05, 1.11]). No associations were observed for genetically-influenced BMI (1.00 [0.98, 1.03]), systolic blood pressure (1.01 [0.98, 1.03]) and triglycerides (1.02 [0.995, 1.05]). ConclusionsDespite the use risk-reducing medications following a first coronary event, this study provided genetic evidence that, of the classical risk factors, mainly high LDL cholesterol was associated with a higher risk of developing recurrent major coronary events.

Minimal improvement in coronary artery disease risk prediction in Chinese population using polygenic risk scores: evidence from the China Kadoorie Biobank.

Several studies have reported that polygenic risk scores (PRSs) can enhance risk prediction of coronary artery disease (CAD) in European populations. However, research on this topic is far from sufficient in non-European countries, including China. We aimed to evaluate the potential of PRS for predicting CAD for primary prevention in the Chinese population. Participants with genome-wide genotypic data from the China Kadoorie Biobank were divided into training ( n = 28,490) and testing sets ( n = 72,150). Ten previously developed PRSs were evaluated, and new ones were developed using clumping and thresholding or LDpred method. The PRS showing the strongest association with CAD in the training set was selected to further evaluate its effects on improving the traditional CAD risk-prediction model in the testing set. Genetic risk was computed by summing the product of the weights and allele dosages across genome-wide single-nucleotide polymorphisms. Prediction of the 10-year first CAD events was assessed using hazard ratios (HRs) and measures of model discrimination, calibration, and net reclassification improvement (NRI). Hard CAD (nonfatal I21-I23 and fatal I20-I25) and soft CAD (all fatal or nonfatal I20-I25) were analyzed separately. In the testing set, 1214 hard and 7201 soft CAD cases were documented during a mean follow-up of 11.2 years. The HR per standard deviation of the optimal PRS was 1.26 (95% CI:1.19-1.33) for hard CAD. Based on a traditional CAD risk prediction model containing only non-laboratory-based information, the addition of PRS for hard CAD increased Harrell's C index by 0.001 (-0.001 to 0.003) in women and 0.003 (0.001 to 0.005) in men. Among the different high-risk thresholds ranging from 1% to 10%, the highest categorical NRI was 3.2% (95% CI: 0.4-6.0%) at a high-risk threshold of 10.0% in women. The association of the PRS with soft CAD was much weaker than with hard CAD, leading to minimal or no improvement in the soft CAD model. In this Chinese population sample, the current PRSs minimally changed risk discrimination and offered little improvement in risk stratification for soft CAD. Therefore, this may not be suitable for promoting genetic screening in the general Chinese population to improve CAD risk prediction.

Prevalence of familial hypercholesterolemia and its association with coronary artery disease: A Chinese cohort study.

Familial hypercholesterolemia (FH) is underrecognized, and its association with coronary artery disease (CAD) remains limited, especially in China. We aimed to investigate the prevalence of FH and its relationship with CAD in a large Chinese cohort. FH was defined using the Make Early Diagnosis to Prevent Early Death (MEDPED) criteria. The crude and age-sex standardized prevalence of FH were calculated based on surveys of the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) project during 2007-2008. The associations of FH with incident CAD and its major subtypes were estimated with the cohort-stratified multivariate Cox proportional hazard models based on the data from the baseline to the last follow-up (2018-2020). Among 98,885 included participants, 190 participants were defined as FH. Crude and age-sex standardized prevalence and 95% confidence interval (CI) of FH were 0.19% (0.17%-0.22%) and 0.13% (0.10%-0.16%), respectively. The prevalence varied across age groups and peaked in the group of 60-<70 years (0.28%), and the peak prevalence (0.18%) in males was earlier, yet lower than the peak crude prevalence in females (0.41%). During a mean follow-up of 10.7 years, 2493 cases of incident CAD were identified. After multivariate adjustment, FH patients had a 2.03-fold greater risk of developing CAD compared to non-FH participants. The prevalence of FH was estimated to be 0.19% in the participants, and it was associated with an elevated risk of incident CAD. Our study suggests that early screening of FH has certain public health significance for the prevention of CAD.

Validation of a Case Definition to Identify Patients Diagnosed With Cardiovascular Disease in Canadian Primary Care Practices

BackgroundCardiovascular disease (CVD) is a leading cause of death globally. This study validates a primary care-based electronic medical record case definition for CVD. MethodsThis retrospective, cross-sectional study explores electronic medical record data from 1574 primary care providers participating in the Canadian Primary Care Sentinel Surveillance Network. A reference standard was created by reviewing medical records of a subset of patients in this network (n = 2017) for coronary artery disease (CAD), cerebrovascular disease (CeVD), and peripheral vascular disease (PVD). Together, these data produced a CVD reference. We applied validated case definitions to an active patient population (≥ 1 visit between January 1, 2018 and December 31, 2019) to estimate prevalence using the exact binomial test (N = 689,301). Descriptive statistics, χ2 tests, and t tests characterized patients with vs without CVD. ResultsThe optimal CVD Case Definition 2 had a sensitivity of 68.5% (95% Confidence Interval [CI]: 61.6%-74.8%), a specificity of 97.8% (95% CI: 97.0%-98.4%), a positive predictive value of 77.7% (95% CI: 71.6%-82.7%), and a negative predictive value of 96.5% (95% CI: 95.8%-97.1%). Included in this CVD definition was a strong CAD case definition with sensitivity of 91.6% (95% CI: 84.6%-96.1%), specificity of 98.3% (95% CI: 97.6%-98.8%), a PPV of 74.8% (95% CI: 67.8%-80.7%), and an NPV of 99.5% (95% CI: 99.1%-99.7%). This CVD definition also included CeVD and PVD case definitions with low sensitivity (77.6% and 36.6%) but high specificity (98.6% and 99.0%). The estimated prevalence of CVD among primary care patients is 11.2% (95% CI, 11.1%-11.3%; n = 77,064); the majority had CAD (6.4%). ConclusionsThis study validated a definition of CVD and its component parts—CAD, CeVD, and PVD. Understanding the prevalence and disease burden for patients with CVD within primary care settings can improve prevention and disease management.

FREQUENCY OF SIGNIFICANT CORONARY ARTERY DISEASE IN CASES WITH ST SEGMENT DEPRESSION DURING RECOVERY PHASE OF EXERCISE

Coronary Artery Disease (CAD) imposes physical, social, and economic burden. It is amongst the leading causes of mortality and morbidity. Exercise-induced ST segment depression is considered reliable ECG finding for the diagnosis of obstructive coronary atherosclerosis. Exercise testing has an excellent safety record. The aim of the study is to determine the frequency of significant coronary artery disease in cases with ST-segment depression during recovery phase of exercise tolerance test. This descriptive case series was carried out at the Department of Cardiology, Rehmatul-Lil-Alamin Institute of Cardiology, Lahore, from 11-01-2021 to 10-07-2021. A total of 89 patients were taken in this study. Conventional coronary angiography via femoral or radial route was performed. Lesions were quantified by QCA technique in addition to visual assessment. Significant CAD was labelled as per operational definition. Patients ranged between 30-70 years of age with mean age of 51.8±10.8 years. There were 56 males (62.9%) while remaining 33 (37.1%) were females. History of diabetes mellitus was reported in 31 patients (34.8%), hypertension in 38 patients (42.7%) and smoking 51 (57.3%). Family history of CAD found in 46 patients (51.7%). Hyperlipidemia reported in 38 patients (42.7%). Significant CAD was observed in 76 patients (85.4%). Stratification for age, gender, diabetes mellitus, hypertension and smoking were carried out and found no association with significant CAD. In conclusion, 85.4% frequency rate of significant coronary artery disease in cases with ST segment depression during recovery phase of exercise tolerance test was observed. Thus, careful evaluation of ST segment depression occurring in recovery phase may add significantly to the clinical information derived from the results of ETT.

Causal association between sleep traits and the risk of coronary artery disease in patients with diabetes.

The association between sleep traits and coronary artery disease (CAD) in patients with diabetes has been reported in previous observational studies. However, whether these potential relationships are causal remains unclear. We aim to assess the causal relationship between sleep traits and CAD in diabetic. Genetic instrumental variables associated with five sleep-related traits (insomnia, sleep duration, ease of getting up, morningness and snoring) were extracted from corresponding genome-wide association studies (GWAS). The associations of genetic variants with CAD were based on 15,666 individuals with diabetes (3,968 CAD cases and 11,696 controls). The primary analysis was derived using the inverse variance weighting method. Further sensitivity analysis was conducted to confirm the robustness and consistency of the main results. Genetic liability to insomnia was significantly related to the increased risk of CAD in individuals with diabetes [odds ratio (OR): 1.163; 95% CI: 1.072-1.254; p = 0.001]. Suggestive evidence was found for the borderline associations between both sleep duration (OR: 0.629; 95% CI: 0.380-1.042, p = 0.072) and snoring (OR: 1.010, 95% CI: 1.000-1.020, p = 0.050) with CAD risk. However, no consistent evidence was found for the association between ease of getting up and morningness with the risk of CAD in diabetic. Similar results can be verified in most sensitivity analyses. We provide consistent evidence for the causal effect of insomnia on the increased risk of CAD in individuals with diabetes. The management of sleep health should be emphasized to prevent CAD in diabetic patients.

Coronary computed tomography angiography assessment of relationship between right coronary artery-aorta angle and the development of coronary artery disease.

Whilst a correlation has been established between wide left main coronary artery bifurcation [left anterior descending-left circumflex (LAD-LCx)] angle (>80°) and the development of coronary artery disease (CAD), this retrospective, causal-comparative pilot study aimed to explore whether a relationship exists between right coronary artery (RCA)-aorta angle and CAD. Thirty normal cases were identified via radiology reports and selected as the control group with coronary computed tomography angiography (CCTA) scans performed on a 320-slice computed tomography (CT) scanner. Thirty CAD cases were selected with invasive coronary angiography performed to confirm the degree of stenosis, and CCTA performed on dual source and 320-slice CT scanners. An independent sample t-test was used to compare the differences in coronary angles between the normal and CAD group, and analysis of variance (ANOVA) was used to assess for significant differences between coronary angles in normal and CAD subgroups. Coronary angle measurements were conducted by two independent assessors with high intraclass correlation (r=0.971-0.998, P<0.001). RCA-aorta angle measurements were significantly larger in the normal group [87.47°, 95% confidence interval (CI): 79.31° to 95.78°] compared to the CAD group (76.82°, 95% CI: 67.82° to 85.61°, P=0.05). No significant difference was found between RCA-aorta angle and degree of coronary stenosis (P=0.75). This study suggests a relationship between narrow RCA-aorta angle and CAD.

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.

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

Preliminary Feasibility of Stress Myocardial Elastography for the Detection of Coronary Artery Disease.

Myocardial elastography (ME) is a cardiac strain imaging technique that has been found capable of detecting a decrease in radial strain caused by ischemia or infarction in patients with coronary artery disease (CAD) as well as in a canine model. Prior studies have focused on rest imaging, but stress testing can reveal functional deficits caused by stenoses that are asymptomatic at rest. Therefore, it has been proposed that stress ME (S-ME) improves the detection of CAD. A novel strain difference (Δε) metric is presented and investigated in a canine model of induced ischemia, as well as in a study in human patients with CAD validated by myocardial perfusion imaging. In the canine model study, flow-limiting stenosis was induced by partial ligation in n=2 canines, and stenosis was found to consistently reduce Δε in the affected myocardial regions compared with baseline, as well as compared to myocardial regions that are remote to the induced stenosis. In the clinical study, the median Δε was significantly lower (p < 0.05) in infarcted myocardial regions (-6.29%) than in those with normal perfusion (4.62%), with Δε in ischemic regions falling in between (-2.91%). The same trend was observed when considering radial strain during stress and, to a lesser degree, at rest alone. The results indicate that S-ME may be more sensitive to mild cases of CAD that are functionally asymptomatic at rest.

Smoking and coronary artery disease risk in patients with diabetes: A Mendelian randomization study.

Previous observational studies have shown an association between smoking and coronary artery disease (CAD) in patients with diabetes. Whether this association reflects causality remains unestablished. This study aimed to explore the causal effect of smoking on CAD in patients with diabetes. Genetic signatures for smoking were extracted from a large genome-wide association study (GWAS), consisted of up to 1.2 million participants. Four smoking phenotypes were included: smoking initiation, cigarettes per day, age at initiation of regular smoking, and smoking cessation. Genetic associations with CAD in patients with diabetes were extracted from another GWAS, which included 15,666 participants (3,968 CAD cases and 11,696 controls). The analyses were performed using the univariable and multivariable Mendelian randomization (MR) method. MR analysis revealed that smoking initiation was positively related to CAD risk in patients with diabetes (OR = 1.322, 95% CI = 1.114 - 1.568, P = 0.001), but this association was attenuated when adjusted for cardiovascular risk factors (OR = 1.212, 95% CI = 1.008 - 1.457, P = 0.041). Age at initiation of regular smoking was negatively related to CAD in patients with diabetes (OR = 0.214, 95% CI = 0.070 - 0.656, P = 0.007), but this association became insignificant when adjusted for cardiovascular risk factors. This study supported the effect of smoking initiation on the risk of CAD in patients with diabetes.

Prevalence, Incidence, Diagnosis and Management of Myocardial Infarction in Saudi Arabia

Cardiovascular disease (CVD) affects a third of the global population, with myocardial infarction (MI) being a severe form primarily caused by coronary artery disease (CAD). Saudi Arabia's urbanization has led to an increase in CAD cases, driven by risk factors like obesity, hypercholesterolemia, diabetes, hypertension, and dyslipidemia. Family history also plays a role, especially in younger myocardial infarction (MI) patients. Diagnostic tools include electrocardiography, cardiac biomarkers, and imaging. Telemedicine aids in remote diagnosis. Recent studies in Saudi Arabia show chest pain as a common MI symptom, with younger patients more likely to have ST-segment elevation MI. Management follows international guidelines, emphasizing early recognition, emergency medical services intervention, and reperfusion therapy. Medications, including antiplatelets and statins, are used, but gender disparities exist. Cardiac rehabilitation programs and public health initiatives contribute to post-MI care. Despite advancements, challenges like door-to-balloon time persist, requiring further improvements in MI care in Saudi Arabia.

Sex-Specific Survival Bias and Interaction Modeling in Coronary Artery Disease Risk Prediction.

The 10-year Atherosclerotic Cardiovascular Disease risk score is the standard approach to predict risk of incident cardiovascular events, and recently, addition of coronary artery disease (CAD) polygenic scores has been evaluated. Although age and sex strongly predict the risk of CAD, their interaction with genetic risk prediction has not been systematically examined. This study performed an extensive evaluation of age and sex effects in genetic CAD risk prediction. The population-based Norwegian HUNT2 (Trøndelag Health Study 2) cohort of 51 036 individuals was used as the primary dataset. Findings were replicated in the UK Biobank (372 410 individuals). Models for 10-year CAD risk were fitted using Cox proportional hazards, and Harrell concordance index, sensitivity, and specificity were compared. Inclusion of age and sex interactions of CAD polygenic score to the prediction models increased the C-index and sensitivity by accounting for nonadditive effects of CAD polygenic score and likely countering the observed survival bias in the baseline. The sensitivity for females was lower than males in all models including genetic information. We identified a total of 82.6% of incident CAD cases by using a 2-step approach: (1) Atherosclerotic Cardiovascular Disease risk score (74.1%) and (2) the CAD polygenic score interaction model for those in low clinical risk (additional 8.5%). These findings highlight the importance and complexity of genetic risk in predicting CAD. There is a need for modeling age- and sex-interaction terms with polygenic scores to optimize detection of individuals at high risk, those who warrant preventive interventions. Sex-specific studies are needed to understand and estimate CAD risk with genetic information.

Test-Retest Reliability and Internal Consistency of the Coronary Artery Disease Education Questionnaire Short Version in the Marathi Language.

Introduction Patient education specific to the disease must be incorporated into the management of coronary artery disease (CAD) or any other disease as the patients understand the education provided in their native language better. The brief version of the CAD education questionnaire is a valid and reliable instrument for evaluating patients' understanding of the condition.To the best of our knowledge and understanding from the literature review, no questionnaire evaluating the knowledge of CAD in the Marathi language had been found because of which this study was carried out. Methods For the process of translation and cross-cultural adaptation, the framework for self-report measureswas taken into consideration in which qualified translators translated both ways forward into the Marathi language and backward into the English language. The translators and a recording observer combined their efforts to create one synthesized version. The questionnaire was fine-tuned by the expert group to produce the final version and 30 diagnosed cases of CAD were tested with the pre-final version. The Marathi version of the questionnaire's validity and reliability were evaluated using Cohen's kappa (k) and Cronbach's alpha (α). Results Thirty individuals with CAD were recruited (mean age 68±12.36, consisting of 22 males and 08 females) to test the pre-final version, and equivalence was tested for every item by probing the participants for the understanding of the item. The Likert scale demonstrated that patients understood the purpose of each question. A total of 200 participants - 153 males population and 47 femaleswith a mean age of 66.64±5.6094 years who can read and speak in the Marathi language were consideredto assess the test-retest reliability and internal consistency who completed the questionnaire twice, with a gapof two weeks but only 188 participant's data was analyzed as twelve participants dropped out of the study because they could not report due to transportation and health-related issues. The obtained α value demonstrated satisfactory internal consistency, while the k value indicated almost perfect agreement. Conclusion The study concluded that the Marathi version of the CAD education questionnaire short version is reliable and cross-culturally adapted; therefore, it is an effective tool for evaluating the knowledge of CAD among Marathi language-speaking patients.

Impact of cardiovascular health and genetic risk on coronary artery disease in Chinese adults

ObjectiveTo examine whether adherence to ideal cardiovascular health (CVH) can mitigate the genetic risk of coronary artery disease (CAD) in non-European populations.MethodsFine and Grey’s models were used to calculate HRs...

Impact of the COVID-19 pandemic on the use of myocardial perfusion imaging for the assessment of coronary artery disease: a Brazilian experience

The COVID-19 pandemic and the lockdown period caused deep effects on healthcare, including cardiac imaging, with a possible negative influence on the evaluation of coronary artery disease (CAD). This study aimed to evaluate the impact of the COVID-19 pandemic on myocardial perfusion imaging (MPI) performance and results in a Brazilian, Nuclear Cardiology laboratory. Patients with or without known CAD who underwent MPI in three 30-day periods (pre-pandemic [mid-February to mid-March 2020], lockdown [April-May 2020], and post-lockdown [August 2020]) were studied. MPI volumes dropped from 204 pre-lockdown to 43 during lockdown (78.9% reduction), rising to 248 after lockdown. The use of pharmacologic stress increased from 36.3% to 53.5% during lockdown. The frequency of abnormal MPI tests did not differ significantly among the time intervals, as well as the frequency of myocardial ischemia. Younger age, ≥1 cardiac risk factor, and known CAD were independent predictors of the performance of MPI during the lockdown period. In conclusion, a large reduction of MPI performance occurred during lockdown, when imaging was sought mainly by younger patients, with cardiac risk factors or known CAD. There was no significant difference in the frequency of abnormal MPI or of myocardial ischemia among the periods, which might indicate missed cases of CAD during lockdown; therefore, the consequences of cardiac testing reductions should be continuously assessed.

Diagnosing Coronary Artery Disease on the Basis of Hard Ensemble Voting Optimization.

Background and Objectives: Recently, many studies have focused on the early diagnosis of coronary artery disease (CAD), which is one of the leading causes of cardiac-associated death worldwide. The effectiveness of the most important features influencing disease diagnosis determines the performance of machine learning systems that can allow for timely and accurate treatment. We performed a Hybrid ML framework based on hard ensemble voting optimization (HEVO) to classify patients with CAD using the Z-Alizadeh Sani dataset. All categorical features were converted to numerical forms, the synthetic minority oversampling technique (SMOTE) was employed to overcome imbalanced distribution between two classes in the dataset, and then, recursive feature elimination (RFE) with random forest (RF) was used to obtain the best subset of features. Materials and Methods: After solving the biased distribution in the CAD data set using the SMOTE method and finding the high correlation features that affected the classification of CAD patients. The performance of the proposed model was evaluated using grid search optimization, and the best hyperparameters were identified for developing four applications, namely, RF, AdaBoost, gradient-boosting, and extra trees based on an HEV classifier. Results: Five fold cross-validation experiments with the HEV classifier showed excellent prediction performance results with the 10 best balanced features obtained using SMOTE and feature selection. All evaluation metrics results reached &gt; 98% with the HEV classifier, and the gradient-boosting model was the second best classification model with accuracy = 97% and F1-score = 98%. Conclusions: When compared to modern methods, the proposed method perform well in diagnosing coronary artery disease, and therefore, the proposed method can be used by medical personnel for supplementary therapy for timely, accurate, and efficient identification of CAD cases in suspected patients.

Genetic Determinants of Cardiovascular Disease: The Endothelial Nitric Oxide Synthase 3 (eNOS3), Krüppel-Like Factor-14 (KLF-14), Methylenetetrahydrofolate Reductase (MTHFR), MiRNAs27a and Their Association with the Predisposition and Susceptibility to Coronary Artery Disease.

Amplification Refractory Mutation System (ARMS) PCR was used to detect MTHFR, KLF-14, miRNA-27a and eNOS3 genotyping in CAD patients and healthy controls. About 125 CAD cases and 125 controls were enrolled in this study and statistical associations were calculated including p-value, risk ratio (RR), and odds ratio (OD). There were statistically significant differences (p &lt; 0.05) in genotype distributions of MTHFR 677 C&gt;T, KLF-14 rs972283 G&gt;A, miRNAs27a rs895819 A&gt;G and eNOS3 rs1799983 G&gt;T between CAD patients and controls. In addition, our results indicated that the MTHFR-TT genotype was associated with increased CAD susceptibility with an OR 2.75 (95%) and p &lt; 0.049, and the KLF14-AA genotype was also associated with increased CAD susceptibility with an OR of 2.24 (95%) and p &lt; 0.024. Moreover, the miRNAs27a-GG genotype protects from CAD risk with an OR = 0.31 (0.016), p = 0.016. Our results also indicated that eNOS3 -GT genotype is associated with CAD susceptibility with an OR = 2.65, and p &lt; 0.0003. The MTHFR 677C&gt;T, KLF14 rs972283 G&gt;A, miRNAs27a A&gt;G, and eNOS3 rs1799983 G&gt;T genotypes were associated with CAD susceptibility (p &lt; 0.05). These findings require verification in future large-scale population based studies before these loci are used for the prediction and identification of individuals at risk to CAD. Weight control, physical activity, and smoking cessation are very influential recommendations given by clinicians to the at risk individuals to reduce or delay the development of CAD.

Abstract 11308: Genome-Wide Polygenic Risk Scores Incoronary Artery Disease Risk Prediction: Results From the Asian Indian Diabetic Heart Study/Sikh Diabetes Study

Introduction: Polygenic risk score (PRS) has been shown to be highly effective in predicting coronary artery disease (CAD) risk in Western European populations. However, such studies on South Asians are scarce despite the fact that they account for 50% of the global burden of CAD. Hypothesis: In this study, we evaluated the predictive efficacy of PRS derived from the Asian Indian (AI) ancestry-specific score (PRS AI ) and European-derived PRS (PRS EU ). Also, we compared these with the clinical risk score (CRS). Methods: The study used 4602 participants (791 CAD cases and 3790 controls) from the Asian Indian Diabetic Heart Study/Sikh Diabetes Study. Weighted PRS was constructed using 100 significant SNPs from our Punjabi/Sikh CAD GWAS and 75 SNPs identified from the European GWAS catalog. The CRS was derived using the clinical risk factors described for the Framingham risk score. Results: Ancestry-specific PRS AI showed an enhanced efficacy of over 30% in estimating the relative risk for CAD over PRS EU . In sensitivity analysis, the area under the curve (AUC) for PRS AI and PRS EU were 0.84 and 0.72, respectively, while the AUC remained unchanged on combining the PRS (AI+EU) , i.e., 0.84. PRS AI also predicted the risk for increased waist to hip ratio (β=0.11, p=4.1x10 -13 ) in both gender, while fasting glucose levels (β=0.08, 3.0x10 -3 ) were confined to females. Conclusions: The results highlight evidence for the utility of PRS for identifying genetically predisposed high-risk individuals and attest to its broader clinical value. Also, sex differences may play a role in determining the risk for CAD, and increased fasting glucose and type 2 diabetes (T2D) are known to increase the risk of heart disease in women more than men, especially after menopause.

Polygenic risk score improves the accuracy of a clinical risk score for coronary artery disease

BackgroundThe value of polygenic risk scores (PRSs) towards improving guideline-recommended clinical risk models for coronary artery disease (CAD) prediction is controversial. Here we examine whether an integrated polygenic risk score improves the prediction of CAD beyond pooled cohort equations. MethodsAn observation study of 291,305 unrelated White British UK Biobank participants enrolled from 2006 to 2010 was conducted. A case–control sample of 9499 prevalent CAD cases and an equal number of randomly selected controls was used for tuning and integrating of the polygenic risk scores. A separate cohort of 272,307 individuals (with follow-up to 2020) was used to examine the risk prediction performance of pooled cohort equations, integrated polygenic risk score, and PRS-enhanced pooled cohort equation for incident CAD cases. The performance of each model was analyzed by discrimination and risk reclassification using a 7.5% threshold.ResultsIn the cohort of 272,307 individuals (mean age, 56.7 years) used to analyze predictive accuracy, there were 7036 incident CAD cases over a 12-year follow-up period. Model discrimination was tested for integrated polygenic risk score, pooled cohort equation, and PRS-enhanced pooled cohort equation with reported C-statistics of 0.640 (95% CI, 0.634–0.646), 0.718 (95% CI, 0.713–0.723), and 0.753 (95% CI, 0.748–0.758), respectively. Risk reclassification for the addition of the integrated polygenic risk score to the pooled cohort equation at a 7.5% risk threshold resulted in a net reclassification improvement of 0.117 (95% CI, 0.102 to 0.129) for cases and − 0.023 (95% CI, − 0.025 to − 0.022) for noncases [overall: 0.093 (95% CI, 0.08 to 0.104)]. For incident CAD cases, this represented 14.2% correctly reclassified to the higher-risk category and 2.6% incorrectly reclassified to the lower-risk category.ConclusionsAddition of the integrated polygenic risk score for CAD to the pooled cohort questions improves the predictive accuracy for incident CAD and clinical risk classification in the White British from the UK Biobank. These findings suggest that an integrated polygenic risk score may enhance CAD risk prediction and screening in the White British population.