Lower Risk Of Coronary Artery Disease Research Articles

Dietary Strategies to Reduce Atherosclerosis and Heart Attack Risk

The article delves into the significance of incorporating omega-3 fatty acids, antioxidants, and fiber-rich foods into one's diet, all of which have been associated with a lower risk of atherosclerosis and heart attacks.

Impact of loss-of-function in angiopoietin-like 4 on the human phenome

BackgroundCarriers of the E40K loss-of-function variant in Angiopoietin-like 4 (ANGPTL4), have lower plasma triglyceride levels as well as lower rates of coronary artery disease (CAD) and type 2 diabetes (T2D). These genetic data suggest ANGPTL4 inhibition as a potential therapeutic target for cardiometabolic diseases. However, it is unknown whether the association between E40K and human diseases is due to linkage disequilibrium confounding. The broader impact of genetic ANGPTL4 inhibition is also unknown, raising uncertainties about the safety and validity of this target. MethodsTo assess the impact of ANGPLT4 inhibition, we evaluated whether E40K and other loss-of-function variants in ANGPTL4 influenced a wide range of health markers and diseases using 29 publicly available genome-wide association meta-analyses of cardiometabolic traits and diseases, as well as 1589 diseases assessed in electronic health records within FinnGen (n = 309,154). To determine whether these relationships were likely causal, and not driven by other correlated variants, we used the Bayesian fine mapping algorithm CoPheScan. ResultsThe CoPheScan posterior probability of E40K being the causal variant for triglyceride levels was 99.99 %, validating the E40K to proxy lifelong lower activity of ANGPTL4. The E40K variant was associated with lower risk of CAD (odds ratio [OR] = 0.84, 95 % CI = 0.81 to 0.87, p=3.6e-21) and T2D (OR = 0.91, 95 % CI = 0.87 to 0.95, p=2.8e-05) in GWAS meta-analyses, with results replicated in FinnGen. These significant results were also replicated using other rare loss-of-function variants identified through whole exome sequencing in 488,278 participants of the UK Biobank. Using a Mendelian randomization study design, the E40K variant effect on cardiometabolic diseases was concordant with lipoprotein lipase enhancement (r = 0.82), but not hepatic lipase enhancement (r = −0.10), suggesting that ANGPTL4 effects on cardiometabolic diseases are potentially mainly mediated through lipoprotein lipase. After correction for multiple testing, the E40K variant did not significantly increase the risk of any of the 1589 diseases tested in FinnGen. ConclusionsANGPTL4 inhibition may represent a potentially safe and effective target for cardiometabolic diseases prevention or treatment.

Haptoglobin Phenotype and Intensive Glycemic Control for Coronary Artery Disease Risk Reduction in People With Type 2 Diabetes: The ADVANCE Study.

Intensive glycemic control reduced coronary artery disease (CAD) events among the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study participants with the haptoglobin (Hp)2-2 phenotype but not in participants without the Hp2-2 phenotype. It is unknown whether and how these results translate across different demographic/clinical characteristics and treatment strategies. Haptoglobin phenotype was measured in available samples from the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) biomarker case-cohort study. Weighted multivariable-adjusted Cox regression models were used to evaluate the association between intensive glycemic control (HbA1c target of ≤6.5%) versus standard therapy (based on local guidelines) and major CAD events among participants with (n = 1,327) and without (n = 2,077) the Hp2-2 phenotype separately and within prespecified stratifications by sex, race, previous cardiovascular disease (CVD), diabetes duration, and HDL-cholesterol. While the hazard ratios (HRs) were in the hypothesized differing directions, compared with standard therapy, intensive glycemic control was not significantly associated with risk of CAD events among participants without (1.04, 95% CI 0.82-1.32) or with (0.84, 0.63-1.14, Pinteraction = 0.27) the Hp2-2 phenotype overall. Intensive therapy was associated with lower CAD risk among participants with the Hp2-2 phenotype who had no previous CVD (0.47, 0.29-0.76, Pinteraction = 0.01). Our findings suggest that intensive glycemic control contributes to the prevention of major CAD events among ADVANCE participants with the Hp2-2 phenotype and no previous CVD and are in alignment with our hypothesis that intensive glycemic control may be beneficial in a subset of people with the Hp2-2 phenotype.

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

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

Genetically predicted lifestyle factors, socioeconomic status and risk of coronary artery disease in individuals with diabetes: a Mendelian randomization study.

This study explores the causal links between genetically predicted lifestyle factors, socioeconomic status, and coronary artery disease (CAD) risk in individuals with diabetes using a bidirectional Mendelian-randomization approach. This study explored the potential causal relationships of lifestyle factors and socioeconomic status with the risk of CAD in diabetes patients by a bidirectional, two-sample Mendelian-randomization (MR) analysis. Genetically predicted smoking initiation (p = 0.005, 95% CI: 1.08-1.55) and insomnia (p = 0.001, 95% CI: 1.06-1.29) were associated with a higher risk of CAD in individuals with diabetes, whereas educational attainment (p = 0.0001, 95% CI: 0.47-0.78) was associated with a lower risk of CAD. The lifetime smoking index (p = 0.016, 95% CI: 1.12-3.03) was suggestively associated with a higher risk of CAD, while household income before taxes (p = 0.048, 95% CI: 0.41-1.00) was suggestively associated with a lower risk of CAD. In addition, we observed a suggestive negative association between the genetically predicted risk of CAD and the lifetime smoking index (p = 0.016, 95% CI: 0.98-0.99) and a significant causal relationship between the risk of CAD and household income before taxes (p = 0.006, 95% CI: 0.97-0.99). The results of this study provide evidence that smoking initiation, lifetime smoking index and insomnia are associated with an increased risk of CAD in individuals with diabetes, educational attainment and household income before taxes are associated with a reduced risk of CAD in individuals with diabetes, and the possible role of lifetime smoking index and household income before taxes on the risk of CAD in individuals with diabetes. It provides an opportunity for the prevention and management of CAD in individuals with diabetes.

Association of the polymorphisms of the cholesteryl ester transfer protein gene with coronary artery disease: a meta-analysis.

This meta-analysis aimed to assess the association of the polymorphisms of cholesterol ester transfer protein (CETP) rs708272 (G>A), rs5882 (G>A), rs1800775 (C>A), rs4783961 (G>A), rs247616 (C>T), rs5883 (C>T), rs1800776 (C>A), and rs1532624 (C>A) with coronary artery disease (CAD) and the related underlying mechanisms. A comprehensive search was performed using five databases such as PubMed, EMBASE, Web of Science, Cochrane Library and Scopus to obtain the appropriate articles. The quality of the included studies was assessed by the Newcastle-Ottawa Scale. The statistical analysis of the data was performed using STATA 17.0 software. The association between CETP gene polymorphisms and risk of CAD was estimated using the pooled odds ratio (OR) and 95% confidence interval (95% CI). The association of CETP gene polymorphisms with lipids and with CETP levels was assessed using the pooled standardized mean difference and corresponding 95% CI. P < 0.05 was considered statistically significant. A total of 70 case-control studies with 30,619 cases and 31,836 controls from 46 articles were included. The results showed the CETP rs708272 polymorphism was significantly associated with a reduced risk of CAD under the allele model (OR = 0.846, P < 0.001), the dominant model (OR = 0.838, P < 0.001) and the recessive model (OR = 0.758, P < 0.001). AA genotype and GA genotype corresponded to higher high-density lipoprotein cholesterol (HDL-C) concentrations in the blood compared with GG genotype across the studied groups (all P < 0.05). The CETP rs5882 and rs1800775 polymorphisms were not significantly associated with CAD under the allele model (P = 0.802, P = 0.392), the dominant model (P = 0.556, P = 0.183) and the recessive model (P = 0.429, P = 0.551). Similarly, the other mentioned gene polymorphisms were not significantly associated with CAD under the three genetic models. The CETP rs708272 polymorphism shows a significant association with CAD, and the carriers of the allele A are associated with a lower risk of CAD and higher HDL-C concentrations in the blood compared to the non-carriers. The CETP rs5882, rs1800775, rs4783961, rs247616, rs5883, rs1800776, and rs1532624 are not significantly associated with CAD. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023432865, identifier: CRD42023432865.

Contribution of Lipoprotein(a) to polygenic risk of coronary artery disease: A prospective UK Biobank analysis

Abstract Background Lipoprotein(a) (Lp[a]) is a highly atherogenic lipoprotein subfraction that may contribute to polygenic risk of coronary artery disease (CAD), but the extent of this contribution is unknown. Purpose Our objective was to estimate the contribution of Lp(a) to polygenic risk of CAD and to evaluate the respective contributions of Lp(a) and a CAD polygenic risk score (PRS) to CAD. Methods 372,385 UK Biobank participants of European ancestry free of CAD at baseline were included. Plasma Lp(a) levels were measured and a CAD-PRS was calculated using LDpred2. Over the median follow-up of 12.6 years, 13,538 participants had incident CAD (myocardial infarction, coronary artery bypass grafting or coronary angioplasty). Results The LPA region contribution to the CAD-PRS-mediated CAD risk was modest (6.5%). Lp(a) levels significantly increased the predictive performance of a CAD-PRS including age and sex in Cox regression (C-statistic 0.751 versus 0.746, difference = 0.005 (95% CI, 0.004-0.006). Compared to participants in the top CAD-PRS quintile with Lp(a) levels ≥125 nmol/L (CAD event rate 6.6%), the hazard ratio for incident CAD in participants in the bottom CAD-PRS quintile with Lp(a) levels &amp;lt;25 nmol/L was 0.18 (95% CI, 0.17-0.20, p=6.41e-241, CAD event rate 2.0%). Conclusions Compared to individuals with a high genetic risk of CAD (high CAD-PRS and high Lp(a) levels), those with a low genetic risk had an 82% lower CAD risk. These results highlight a substantial contribution of genetic risk factors to CAD and that accurate estimation of genetic risk of CAD should consider blood levels of Lp(a).

Contribution of Lipoprotein(a) to Polygenic Risk Prediction of Coronary Artery Disease: A Prospective UK Biobank Analysis.

Lp(a) (lipoprotein[a]) is a highly atherogenic lipoprotein subfraction that may contribute to polygenic risk of coronary artery disease (CAD), but the extent of this contribution is unknown. Our objective was to estimate the contribution of Lp(a) to polygenic risk of CAD and to evaluate the respective contributions of Lp(a) and a CAD polygenic risk score (PRS) to CAD. A total of 372 385 UK Biobank participants of European ancestry free of CAD at baseline were included. Plasma Lp(a) levels were measured and a CAD-PRS was calculated using the LDpred2 algorithm. Over the median follow-up of 12.6 years, 13 538 participants had incident CAD (myocardial infarction, coronary artery bypass grafting, or coronary angioplasty). The LPA region contribution to the CAD-PRS-mediated CAD risk was modest (7.2% [95% CI, 6.1-8.3]). Lp(a) levels significantly increased the predictive performance of a CAD-PRS including age and sex in Cox regression (C statistic 0.751 versus 0.746, difference, 0.005 [95% CI, 0.004-0.006]). Compared with participants in the bottom CAD-PRS quintile with Lp(a) levels <25 nmol/L (CAD event rate, 1.4%), the hazard ratio for incident CAD in participants in the top CAD-PRS quintile with Lp(a) levels ≥125 nmol/L was 5.45 (95% CI, 4.93-6.03; P=9.35×10-242, CAD event rate 6.6%). Compared with individuals with a low genetic risk of CAD (low CAD-PRS and low Lp[a] levels), those with a high genetic risk (high CAD-PRS and high Lp[a] levels) had a 5-fold higher CAD risk. These results highlight a substantial contribution of genetic risk factors to CAD and that accurate estimation of genetic risk of CAD may need to consider blood levels of Lp(a).

Healthy lifestyle, lipoprotein (a) levels and the risk of coronary artery disease.

Lipoprotein (a) [Lp(a)] is associated with coronary artery disease (CAD). However, the role of healthy lifestyle against the risk of CAD with consideration of high Lp(a) levels remains unclear. This study examined 4512 participants who underwent serum Lp(a) level assessment at Kanazawa University Hospital from 2008 to March 2016. Their lifestyle habits were examined based on four questionnaires regarding dietary pattern, exercise habits, smoking status and body weight. Logistic regression analyses were performed to identify the association between healthy lifestyle and CAD independent of Lp(a) levels. The Lp(a) levels were significantly associated with CAD (odds ratio [OR]: 1.12, 95% confidence interval [CI]: 1.08-1.17, p = 1.3 × 10-7 per 10 mg/dL). Under these circumstances, the lifestyle risk score was also significantly associated with CAD (OR: 1.24, 95% CI: 1.12-1.36, p = 2.4 × 10-8 ). Compared with patients with a favourable lifestyle who have Lp(a) levels of <30 mg/dL, those with an intermediate or unfavourable lifestyle were at higher risk for CAD (OR: 1.11, 95% CI: 1.02-1.20, p = 0.003 and OR: 1.40, 95% CI: 1.16-1.54, p = 3.6 × 10-5 , respectively). Further, patients with a favourable, intermediate or unfavourable lifestyle who have Lp(a) levels of ≥30 mg/dL were at high risk for CAD (OR: 1.21, 95% CI: 1.08-1.34, p = 0.0014; OR: 1.31, 95% CI: 1.14-1.48, p = 1.2 × 10-4 ; and OR: 1.81, 95% CI: 1.44-2.18, p = 2.2 × 10-7 , respectively). Healthy lifestyle was associated with a lower risk of CAD regardless of Lp(a) levels.

Coronary Artery Disease Risk Prediction in Patients With Severe Aortic Stenosis: Development and Validation of the Aortic Stenosis-Coronary Artery Disease (AS-CAD) Score

Patients at a low risk of coronary artery disease (CAD) could be triaged to noninvasive coronary computed tomography angiogram instead of invasive coronary angiography, reducing health care costs and patient morbidity. Therefore, we aimed to develop a CAD risk prediction score to identify those who underwent transcatheter aortic valve implantation (TAVI) at a low risk of CAD. We enrolled 1,782 patients who underwent TAVI and randomized the patients to the derivation or validation cohort 2:1. The aortic stenosis-CAD (AS-CAD) score was developed using logistic regression, followed by separation into low- (score 0 to 5), intermediate- (6 to 10), or high-risk (>11) categories. The AS-CAD was validated initially through the k-fold cross-validation, followed by a separately held validation cohort. The average age of the cohort was 82 ± 7years, and 41% (730 of 1,782) were female; 35% (630) had CAD. The male sex, previous percutaneous coronary intervention, stroke, peripheral arterial disease, diabetes, smoking status, left ventricular ejection fraction <50%, and right ventricular systolic pressure >35mm Hg were all associated with an increased risk of CAD and were included in the final AS-CAD model (all p <0.03). Within the validation cohort, the AS-CAD score stratified those into low, intermediate, and high risk of CAD (p <0.001). Discrimination was good within the internal validation cohort, with a c-statistic of 0.79 (95% confidence interval 0.74 to 0.84), with similar power obtained using k-fold cross-validation (c-statistic 0.74 [95% confidence interval 0.70 to 0.77]). In conclusion, The AS-CAD score robustly identified those at a low risk of CAD in patients with severe AS. The use of AS-CAD in practice could avoid potential complications of invasive coronary angiogram by triaging low-risk patients to noninvasive coronary assessment using existing computed tomography data.

Intake of Low Glycaemic Index Foods but Not Probiotics Is Associated with Atherosclerosis Risk in Women with Polycystic Ovary Syndrome.

A total of 127 women were divided into two groups: AIP over 0.11 (highAIP) and AIP ≤ 0.11 (lowAIP). The KomPAN® questionnaire was used to measure food frequency intake; pro-healthy, non-healthy, low glycaemic and probiotic dietary indexes were calculated based on daily food consumption. Body composition was measured by air displacement plethysmography (BodPod). AIP was calculated as a logarithm of triglycerides and high-density lipoproteins from plasma. The highAIP group was 63% less likely to consume low glycaemic index foods three or more times a day than the lowAIP group. The HighAIP group was also 62% less likely to consume buckwheat, oats, whole-grain pasta or coarse-ground grains at least a few times a week. Pro-healthy foods tended to be less frequently consumed by the highAIP group, when adjusted for BMI and age. Women with PCOS at high risk of atherosclerosis consumed less low glycaemic index foods than women with a low risk of atherosclerosis. Intake of high-fibre, low glycaemic index foods could prevent atherosclerosis in women with PCOS; however, the effect of probiotic food intake remains unclear.

Association of an ADRB3 Variant with Coronary Artery Disease Within the Chinese Han Population: Construction of a Predictive Nomogram Model

Objective: Coronary artery disease (CAD) is a the most common type of heart disease, and is associated with the highest mortality rate. The role of the β3-adrenergic receptor gene (ADRB3) in energy homeostasis and lipolysis suggests that it may be associated with obesity, insulin resistance, diabetes, and hypertension. Herein, we sought to examine the relationship between CAD and variants of the ADRB3 gene in individuals with Han and Uygur ethnicities in China. Methods: All 1022 participants were genotyped for two ADRB3 single nucleotide polymorphisms (SNPs; rs1892818 and rs9693898) using real-time polymerase chain reaction (TaqMan). Uygur (259 CAD patients, 161 control group) and Han (308 CAD patients, 294 control group) were included in two case-control studies. We subsequently developed a predictive model using ADRB3 genetic variation and clinical variables to predict risk of CAD. Results: The rs1892818 CT genotype (8.5% vs 3.9%, p = 0.019) and T allele (4.3% vs 1.9%, p = 0.021) were more frequently detected in the control subjects compared to CAD patients of the Han population but not in the Uygur population. The rs9693898 was not associated with CAD in either ethnic population. Logistic regression analysis further demonstrated that carriers of the rs1892818 CT genotype had a lower risk of CAD than did those with the CC genotype (CT vs CC, p = 0.044, odds ratio [OR] = 0.441, 95% confidence interval [CI]: 0.199-0.976). Using this data, we constructed a predictive nomogram model for CAD with an area under the curve (95% CI) of 0.722 (0.682, 0.761). Conclusions: Our results suggest that rs1892818 is associated with CAD in the Han population and that the CT genotype of rs1892818 may serve as a protective factor for CAD in Han individuals. The proposed nomograms can be used for the prediction of CAD in this population.

Neither Trimethylamine-N-Oxide nor Trimethyllysine Is Associated with Atherosclerosis: A Cross-Sectional Study in Older Japanese Adults.

Recent evidence suggests that trimethylamine-N-oxide (TMAO), a metabolite of L-carnitine and choline, is linked to atherosclerosis and cardiovascular diseases. As TMAO content is very high in fish, we raised the following question: why do Japanese people, who consume lots of fish, show a low risk of atherosclerosis? To address this question, we investigated the effects of TMAO and other L-carnitine-related metabolites on carotid intima-media thickness (IMT). Participants were recruited from a small island and a mountainous region. Plasma L-carnitine, γ-butyrobetaine (γBB), TMAO, trimethyllysine (TML), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) levels were measured using liquid or gas chromatography-mass spectrometry. Plasma L-carnitine concentration was higher in men than in women. TMAO and TML were significantly higher in the residents of the island than in the mountainous people. In multiple linear regression analyses in all participants, TML showed a significant inverse association with max-IMT and plaque score (PS), whereas TMAO did not show any associations. In women, L-carnitine was positively associated with max-IMT and PS. TMAO was correlated with both EPA and DHA levels, implying that fish is a major dietary source of TMAO in Japanese people. Our study found that plasma TMAO was not an apparent risk factor for atherosclerosis in elderly Japanese people, whereas a low level of TML might be a potential risk. L-carnitine may be a marker for atherosclerosis in women.

Machine-learning diet quality score and risk of cardiovascular disease

&lt;i&gt;Objectives&lt;/i&gt;: Various diet scores have been established to measure overall diet quality, especially for the prevention of cardiovascular disease (CVD). Diet scores constructed by utilizing modern machine learning techniques may contain independent information and can provide better dietary recommendations in combination with the existing diet scores. &lt;i&gt;Methods&lt;/i&gt;: We proposed a novel machine-learning diet quality score (DQS) and examined the performance of DQS in combination with the Healthy Eating Index-2015 (HEI2015), Mediterranean Diet Score (MED), Alternative Healthy Eating Index-2010 (AHEI) and Dietary Approaches to Stop Hypertension score (DASH score). The data used in this study were from the 2011–2012 to 2017–2018 cycles of the US National Health and Nutrition Examination Survey (NHANES). Participants aged above 20 self-reported their food intake and information on relevant covariates. We used an elastic-net penalty regression model to select important food features and used a generalized linear regression model to estimate odds ratios (ORs) and 95% CIs after controlling for age, sex, and other relevant covariates. &lt;i&gt;Results&lt;/i&gt;: A total of 16756 participants were included in the analysis. DQS was significantly associated with coronary artery disease (CAD) risk after adjusting for one of the other common diet scores. The ORs for DQS combined with the HEI2015, MED, AHEI, and DASH scores were all approximately 0.900, with &lt;i&gt;p&lt;/i&gt; values smaller than 0.05. The OR for DQS in the full score model including all other scores was 0.905 (95% CI, 0.828–0.989, &lt;i&gt;p&lt;/i&gt;=0.028). Only marginal associations were found between DQS and other CVDs after adjusting for other diet scores. &lt;i&gt;Conclusions&lt;/i&gt;: Based on data from four continuous cycles of the NHANES, higher DQS was found to be consistently associated with a lower risk of CAD. The DQS captured unique predictive information independent of the existing diet scores and thus can be used as a complementary scoring system to further improve dietary recommendations for CAD patients.

Leveraging Machine Learning Techniques to Forecast Chronic Total Occlusion before Coronary Angiography

Chronic total occlusion (CTO) remains the most challenging procedure in coronary artery disease (CAD) for interventional cardiology. Although some clinical risk factors for CAD have been identified, there is no personalized prognosis test available to confidently identify patients at high or low risk for CTO CAD. This investigation aimed to use a machine learning algorithm for clinical features from clinical routine to develop a precision medicine tool to predict CTO before CAG. Data from 1473 CAD patients were obtained, including 1105 in the training cohort and 368 in the testing cohort. The baseline clinical characteristics were collected. Univariate and multivariate logistic regression analyses were conducted to identify independent risk factors that impact the diagnosis of CTO. A CTO predicting model was established and validated based on the independent predictors using a machine learning algorithm. The area under the curve (AUC) was used to evaluate the model. The CTO prediction model was developed with the training cohort using the machine learning algorithm. Eight variables were confirmed as 'important': gender (male), neutrophil percentage (NE%), hematocrit (HCT), total cholesterol (TC), high-density lipoprotein cholesterol (HDL), ejection fraction (EF), troponin I (TnI), and N-terminal pro-B-type natriuretic peptide (NT-proBNP). The model achieved good concordance indices of 0.724 and 0.719 in the training and testing cohorts, respectively. An easy-to-use tool to predict CTO in patients with CAD was developed and validated. More research with larger cohorts are warranted to improve the prediction model, which can support clinician decisions on the early discerning CTO in CAD patients.

Abstract 13441: Transcriptomic Analysis of Endothelial Colony Forming Cells From the BioHEART-CT Study to Unravel New Biomarkers for Coronary Artery Disease

Coronary artery disease (CAD) remains the leading cause of death worldwide. There are unmet needs for the diagnosis and treatment for patients with CAD, especially those without modifiable risk factors who are suspected to be at low risk for CAD. Endothelial function has predictive value for future cardiovascular events. We previously showed that endothelial colony forming cells (ECFCs) derived from the BioHEART-CT (The BioHEART Study: Assessing Patients with Suspected Cardiovascular Disease for New Biomarkers and Risk Factors) cohort can be used as a viable tool to evaluate endothelial function in patients as these cells retain the memory of their host. Here, we aimed to characterize the transcriptomic profiles of ECFCs in non-CAD and CAD patients. Based upon our previous findings on the positive correlation between mitochondrial superoxide level and the severity of CAD, we hypothesize that the transcriptomic and functional analyses of the mitochondrial pathways are dysregulated in the ECFCs in CAD patients. RNA-sequencing was performed in ECFCs cultured from the peripheral blood of 44 patients from the BioHEART-CT cohort who had computed tomography coronary angiograms scored for coronary artery calcium (CAC) and Gensini to measure CAD severity. The cohort included 45.5% women and 54.5% men with an average age of 61.6 years. Non-CAD group was determined by a Gensini score of zero, whereas CAD group was determined by a Gensini score of greater than 5. These CAD patients had median CAC score of 266.8, with significant presence of calcified and soft plaques in their coronary arteries. Transcriptomic analysis of ECFCs showed that a total of 37 genes were upregulated and 77 genes were downregulated in the CAD patients. To investigate the functional relevance of the pathways altered in the CAD cohort, dysregulation of genes was analyzed using gene set enrichment analysis. We found that the metabolic processes, those associated with mitochondrial biogenesis, were significantly altered in the ECFCs. Our approach of using RNA-sequencing to determine the gene characteristics of CAD patients and their functional relevance to disease has the potential to unravel previously un-identified genes or biomarkers that are distinct to CAD patients.

Association between the ratio of serum eicosapentaenoic acid to arachidonic acid and risk of coronary artery disease in young Chinese patients.

Long-chain (LC) omega-3 PUFAs, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may play an anti-inflammatory effect and decrease the risk of coronary artery disease (CAD). In contrast, omega-6 PUFA, mainly arachidonic acid (AA), has pro-inflammatory and pro-aggregatory effects, which may increase the risk of CAD. This study evaluated the associations between EPA, DHA, AA, and their ratios (EPA/AA and DHA/AA) with the risk of CAD in young Chinese patients. A total of 182 young patients with CAD and 143 age-matched controls were included. Traditional cardiovascular risk factors were recorded. Serum EPA, DHA and AA were measured by ultra-performance liquid chromatography-mass spectrometry. The level of AA was significantly higher, while the level of EPA was lower in the CAD group than that in the control group. There was no significant difference in DHA level in the two groups. Both the ratios of EPA/AA and DHA/AA were lower in the CAD group than that in the control. Multivariate logistic regression analysis showed that higher serum AA level was associated with the increased risk of CAD, while EPA was a protective factor for CAD. There was no significant association between DHA level and the risk of CAD. Although both higher ratios of EPA/AA [per tertile increment, adjusted odds ratios (ORs) (OR) 0.356, 95% confidence intervals (CI) 0.247-0.513] and DHA/AA (adjusted OR = 0.465, 95%CI = 0.332-0.653) were associated with a lower risk of CAD in young patients. Receiver operating characteristic (ROC) curve analysis showed that compared with AA, the diagnostic value was increased in EPA/AA, but not in DHA/AA. EPA, but not DHA may play a protective role in CAD, while AA may be associated with the increased risk of CAD in young Chinese patients. The ratio of EPA/AA can increase the predictive value for diagnosing CAD than EPA or AA alone.

Role of SPECT Myocardial Perfusion Imaging, in Assessment and Early Diagnosis of Asymptomatic Coronary Artery Disease; An Analytical Study Conducted in a Tertiary Care Hospital of Islamabad, Pakistan

Exercise Tolerance Test (ETT) and Myocardial Perfusion Imaging (MPI) are known non-invasive modalities to detect coronary artery disease (CAD). Aim of this study was to find out better modality for early detection of asymptomatic CAD. Material and Methods: 25 asymptomatic individuals with one or more cardiac risk factors were enrolled. Probability of CAD was calculated, using Framingham scoring; patients classified as low, intermediate and high-risk group. Each (n=25) underwent ETT and MPI. ETT response was categorized as normal, ischemic or equivocal. MPI results as normal, mild, moderate to severe degree defects. 18 patients had follow-up angiograms. Results: Risk stratification showed 14 patients were in intermediate group, 4 had high and 7 had low risk of CAD. In intermediate group, 6 patients had ischemic ETT changes, 10 had perfusion defects on scan and all 10 patients had ≥ 70% stenosis on coronary angiograms. In high-risk group; 2 subjects had positive ETTs, 3 had positive scans and all 3 showed significant vascular involvement on coronary angiogram. In low risk group 3 patients had positive ETT and MPS, 2 had mild vascular stenosis. Considering angiography as gold standard, we observed that MPI had sensitivity (86.66%) and specificity (90%), whereas ETT had 66.6% and 70% respectively. Positive and negative predictive values of MPI were 92.8% and 81.8 % respectively. Post-test probability of MPI was i.e. 0.72-0.88; compared to ETT which was 0.55-0.78. Conclusion: MPI is a better modality than ETT for early diagnosis of occult CAD, especially in intermediate and high risk group.

Protective Effects of Circulating TIMP3 on Coronary Artery Disease and Myocardial Infarction: A Mendelian Randomization Study.

Tissue inhibitor of metalloproteinase 3 (TIMP3) is a protease with high expression levels in the heart and plays an essential role in extracellular matrix turnover by maintaining equilibrium with matrix metalloproteinases. Considerable data in experimental models have demonstrated a protective role of TIMP3 in coronary artery disease (CAD) and myocardial infarction (MI). However, causality remains unexplored in population studies. Here, we sought to decipher the potential causality between TIMP3 and CAD/MI using the Mendelian randomization (MR) method. We extracted summary−level datasets for TIMP3 and CAD/MI from the genome−wide association studies performed in the KORA study and CARDIoGRAMplusC4D consortium, respectively. Seven independent SNPs were obtained as instrumental variables for TIMP3. The MR analyses were replicated using FinnGen datasets, and the main results were combined in meta−analyses. Elevated genetically predicted serum TIMP3 levels were causally associated with a lower risk of CAD [odds ratio (OR), 0.97; 95% confidence interval (CI), 0.95, 0.98; p = 5.29 × 10−5] and MI (OR, 0.96; 95% CI, 0.95, 0.98; p = 3.85 × 10−5). The association patterns persisted in the meta−analyses combining the different datasets (CAD: OR, 0.97; 95% CI, 0.96, 0.99; p = 4.37 × 10−5; MI: OR, 0.97; 95% CI, 0.96, 0.99; p = 9.96 × 10−5) and was broadly consistent across a set of complementary analyses. Evidence of heterogeneity and horizontal pleiotropy was limited for all associations considered. In conclusion, this MR study supports inverse causal associations between serum TIMP3 and the risk of CAD and MI. Strategies for raising TIMP3 levels may offer new avenues for the prevention strategies of atherosclerotic cardiovascular diseases.

Association between HBV Infection and the Prevalence of Coronary Artery Disease in the US Population.

Aims This study aims to investigate the association between HBV infection and coronary artery disease (CAD) prevalence in the US population. A nomogram was proposed to predict CAD based on HBV infection. Methods 25,749 individuals were collected from the 2001-2014 National Health and Nutrition Examination Survey. Participants with hepatitis B core antibody seropositivity were identified with HBV infection, including current and previous HBV infection status. We used adjusted logistic regression and performed sensitivity analysis to investigate the association between HBV infection and the prevalence of CAD. The effect size was evaluated by odds ratio (OR) with a 95% confidence interval (CI). Then, we created a nomogram to predict coronary artery disease. Additionally, we applied the Cox regression model to assess the association between HBV infection and all-cause mortality in those with baseline CAD. Results 1790 (6.95%) individuals were with HBV infection. In the adjusted model, individuals with HBV showed a decreased CAD risk than those without (OR, 0.81; 95% CI, 0.67-0.98). Consistently, reduced risk in self-reported angina (OR, 0.72; 95% CI, 0.52-0.98) and coronary heart disease (OR, 0.76; 95% CI, 0.58-0.98) was observed in the hepatitis B core antibody seropositivity group. The subgroup analysis showed a consistent trend in the subgroups of age (<45 or ≥45), gender (male or female), hypertension (no or yes), and diabetes (no or yes). In the testing set, the proposed predictive model showed good performance with an area under the curve of 0.85 (95% CI, 0.83-0.86). There was no significant association between HBV infection and all-cause mortality in CAD patients (adjusted P = 0.202). Conclusion Our study suggests that HBV infection was associated with lower CAD risk. The proposed nomogram showed good performance in predicting CAD. However, no significant association was observed between HBV and all-cause mortality in CAD patients.