Coronary Artery Disease Cases Research Articles

Atherogenic index of plasma (AIP): a novel predictive indicator for the coronary artery disease in postmenopausal women

BackgroundDyslipidemia is one of the most important factors for coronary artery disease (CAD). Atherogenic index of plasma (AIP) is a novel indicator involved in dyslipidemia. However, the relation between AIP and CAD in postmenopausal women remains unclear. We hypotheses that AIP is a strong predictive indicator of CAD in postmenopausal women.MethodsA propensity score matching case–control study including 348 postmenopausal CAD cases and 348 controls was conducted in the present study.ResultsCompared with controls, CAD patients had higher levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (APOB), but lower high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-1 (APOA-1). The values of nontraditional lipid profiles, including non-HDL-C, TC/HDL-C, LDL-C/HDL-C, non-HDL-C/HDL-C (atherogenic index, AI), TC∗TG∗LDL/HDL-C (lipoprotein combine index, LCI), log(TG/HDL-C) (atherogenic index of plasma, AIP) and APOB/APOA-1 were all significantly higher in the CAD patients. The results of Pearson correlation analyses showed AIP was positively and significantly correlated with TC (r = 0.092, P < 0.001), TG (r = 0.775, P = 0.015), APOB (r = 0.140, P < 0.001), non-HDL-C (r = 0.295, P < 0.001), TC/HDL-C (r = 0.626, P < 0.001), LDL-C/HDL-C (r = 0.469, P < 0.001), AI (r = 0.626, P < 0.001), LCI (r = 0.665, P < 0.001), APOB/APOA-1(r = 0.290, P < 0.001) and was negatively correlated with APOA-1 (r = − 0.278, P < 0.001) and HDL-C (r = − 0.665, P < 0.001). In the multivariate logistic regression analysis, AIP was an independent predictor of CAD. After adjusting for the traditional clinical prognostic factors including diabetes and hypertension, we found AIP could be an independent risk factor for CAD (odds ratio [OR], 3.290; 95% confidence interval [CI], 1.842–5.877, P < 0.001). After adjusting for multiple clinical factors include diabetes, hypertension, smoking, heart ratio, fasting blood glucose, we found AIP also could a powerful risk factor, OR = 3.619, 95%CI (2.003–6.538), P < 0.001.ConclusionThe present study indicated that AIP might be a strong marker for predicting the risk of CAD in postmenopausal women.

Correlation of epicardial fat quantification with severity of coronary artery disease: A study in Indian population

ObjectiveWe studied the correlation of quantified epicardial fat with severity of coronary artery disease in patients [suspected cases of coronary artery disease (CAD)] referred for computed tomography (CT) coronary angiography and established cutoffs for epicardial fat volume (EFV) for the presence of CAD and obstructive CAD. MethodsA prospective cum retrospective cross-sectional observational study was carried out on 950 Indian subjects (suspected cases of CAD) who were referred for coronary CT in the year 2013–2016. EFV was quantified using semiautomatic technique on multidetector coronary CT angiography. The presence of atherosclerotic plaques and degree of stenosis was assessed on coronary CT angiography scans. The correlation between quantified EFV and degree of stenosis was assessed. Multivariate analysis was also performed. ResultsA higher quantity of epicardial fat is found in patients with increasing severity of coronary artery stenosis. The EFV cutoff for the presence of CAD and obstructive CAD are 49.75 and 67.69 mL with area under the curve, sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of 0.68, 81%, 45.9%,58.24%, 72.2%, and 62.84% and 0.709, 64.9%, 66.4%, 35.84%, 86.55%, and 66%, respectively. EFV correlates with age, weight, and body mass index (BMI). Multivariate analysis revealed EFV to be an independent risk factor for the presence of CAD. ConclusionsHigher quantities of EFV are found in patients with greater degree of coronary artery stenosis. EFV correlates with age, weight, and BMI. EFV is an independent risk factor for CAD.

Genetic Regulation of the Thymic Stromal Lymphopoietin (TSLP)/TSLP Receptor (TSLPR) Gene Expression and Influence of Epistatic Interactions Between IL-33 and the TSLP/TSLPR Axis on Risk of Coronary Artery Disease.

The thymic stromal lymphopoietin (TSLP)/TSLP receptor (TSLPR) axis is involved in multiple inflammatory immune diseases, including coronary artery disease (CAD). To explore the causal relationship between this axis and CAD, we performed a three-stage case-control association analysis with 3,628 CAD cases and 3,776 controls using common variants in the genes TSLP, interleukin 7 receptor (IL7R), and TSLPR. Three common variants in the TSLP/TSLPR axis were significantly associated with CAD in a Chinese Han population [rs3806933T in TSLP, Padj = 4.35 × 10−5, odds ratio (OR) = 1.18; rs6897932T in IL7R, Padj = 1.13 × 10−7, OR = 1.31; g.19646A>GA in TSLPR, Padj = 2.04 × 10−6, OR = 1.20]. Reporter gene analysis demonstrated that rs3806933 and rs6897932 could influence TSLP and IL7R expression, respectively. Furthermore, the “T” allele of rs3806933 might increase plasma TSLP levels (R2 = 0.175, P < 0.01). In a stepwise procedure, the risk for CAD increased by nearly fivefold compared with the maximum effect of any single variant (Padj = 6.99 × 10−4, OR = 4.85). In addition, the epistatic interaction between TSLP and IL33 produced a nearly threefold increase in the risk of CAD in the combined model of rs3806933TT-rs7025417TT (Padj = 3.67 × 10−4, OR = 2.98). Our study illustrates that the TSLP/TSLPR axis might be involved in the pathogenesis of CAD through upregulation of mRNA or protein expression of the referenced genes and might have additive effects on the CAD risk when combined with IL-33 signaling.

Adiponectin and coronary artery disease risk: A bi-directional Mendelian randomization study

BackgroundObservational studies have found adiponectin inversely associated with cardiovascular disease thereby indicating a potential target of intervention, but genetically higher adiponectin appears unrelated to coronary artery disease (CAD). To clarify, we examined the role of genetically predicted adiponectin in CAD in a larger study and additionally examined the role of genetically predicted CAD in adiponectin using a bi-directional Mendelian randomization study. MethodsWe obtained estimates using inverse variance weighting (IVW) with multiplicative random effects, based on 21 single nucleotide polymorphism (SNPs) to predict adiponectin and 28 SNPs for CAD, using two large genome wide association studies of adiponectin (ADIPOGen Consortium (n = 39,883)) and CAD CARDIoGRAMplusC4D 1000 Genomes based GWAS (n = 60,801 CAD cases; n = 123,504 controls). Sensitivity analyses included using MR-Egger, weighted median method, and exclusion of potentially invalid (pleiotropic) SNPs. ResultsAdiponectin was inversely associated with CAD (odds ratio 0.82 per unit increase log transformed adiponectin, 95% confidence interval (CI) 0.71 to 0.94) using IVW. However, the association was null using a weighted median method or MR-Egger, or after exclusion of pleiotropic SNPs acting on obesity related traits. CAD was not associated with adiponectin (−0.011 log transformed adiponectin unit per log odds CAD, 95% CI −0.039 to 0.017), with similar findings from MR-Egger, weighted median method or exclusion of pleiotropic SNPs. ConclusionAdiponectin is unlikely a cause of CAD although we cannot completely rule out the possibility. Previous observational studies are likely driven by factors driving both adiponectin and CAD, whose elucidation might provide new insights concerning interventions for CAD.

Skipping breakfast and the risk of coronary artery disease.

Nutritional studies have indicated a critical role of dietary habits in development of cardiovascular diseases (CVD). We aimed to compare the risk of coronary artery disease (CAD) in habitual 'breakfast skippers' with those of 'habitual breakfast eaters' in Western part of India. We also planned to compare the cardiometabolic profiles of both the groups. In this prospective, case-control study of 1607 individuals; 980 were patients of CAD (cases) undergoing various cardiac interventions for revascularisation and other 627 were healthy individuals (controls) who were free from CAD. Details of demographics and classical risk factors were collected for all the participants. Subjects were categorized as 'breakfast eater' or 'breakfast skippers' according to their response to the questionnaire. Logistic regression and correlation analysis were performed to assess the independent risk of all the factors and their inter-variable association. Significantly (P < 0.05) high prevalence of classical risk factors and breakfast skipping habit was found in cases when compared with controls. Diabetes showed the highest odds ratio (7.296; 95% confidence interval (CI) 4.825-11.030; P < 0.0001) for CAD, followed by hypertension (3.756; 95% CI 2.891-4.881; P < 0.0001) and habits of smoking/tobacco/alcohol consumption (1.914; 95% CI 1.528-2.398; P < 0.0001) and breakfast skipping 1.348 (95% CI 1.076-1.689; P < 0.0001). Breakfast skipping emerged as stronger risk factor than obesity and sedentary life style in Indians and showed close association with presence of hypertension. Habitual breakfast skippers are at increased risk for development of CAD and hypertension in Western India.

Machine learning algorithm-based risk prediction model of coronary artery disease.

In view of high mortality associated with coronary artery disease (CAD), development of an early predicting tool will be beneficial in reducing the burden of the disease. The database comprising demographic, conventional, folate/xenobiotic genetic risk factors of 648 subjects (364 cases of CAD and 284 healthy controls) was used as the basis to develop CAD risk and percentage stenosis prediction models using ensemble machine learning algorithms (EMLA), multifactor dimensionality reduction (MDR) and recursive partitioning (RP). The EMLA model showed better performance than other models in disease (89.3%) and stenosis prediction (82.5%). This model depicted hypertension and alcohol intake as the key predictors of CAD risk followed by cSHMT C1420T, GCPII C1561T, diabetes, GSTT1, CYP1A1 m2, TYMs 5'-UTR 28bp tandem repeat and MTRR A66G. MDR and RP models are in agreement in projecting increasing age, hypertension and cSHMTC1420T as the key determinants interacting in modulating CAD risk. Receiver operating characteristic curves exhibited clinical utility of the developed models in the following order: EMLA (C = 0.96) > RP (C = 0.83) > MDR (C = 0.80). The stenosis prediction model showed that xenobiotic pathway genetic variants i.e. CYP1A1 m2 and GSTT1 are the key determinants of percentage of stenosis. Diabetes, diet, alcohol intake, hypertension and MTRR A66G are the other determinants of stenosis. These eleven variables contribute towards 82.5% stenosis. To conclude, the EMLA model exhibited higher predictability both in terms of disease prediction and stenosis prediction. This can be attributed to higher number of iterations in EMLA model that can increase the prediction accuracy.

EBF1 gene polymorphism and its interaction with smoking and drinking on the risk of coronary artery disease for Chinese patients.

Objective: Early B-cell factor 1 (EBF1) is a transcription factor that is expressed in early B-cells, adipocytes, and olfactory neurons, and is essential for the maturation of early B lymphocytes. The present study analyzes the influence of EBF1 gene polymorphism and its interaction with smoking and drinking on the risk of coronary artery disease (CAD). Methods: In the present study, 243 CAD cases were enrolled as the CAD group and 215 non-CAD patients as the control group by case–control study. We analyzed their genotypes of the rs987401919, rs36071027, and rs1056065671 loci of the EBF1 gene by Sanger sequencing and detected their content of HDL-C, LDL-C, and TG. Results: The C allele at the rs987401919 and rs36071027 loci of EBF1 was found to be the risk factor for CAD (Odds ratio, OR = 1.233; 95% confidence interval, CI: 1.039–1.421; P=0.017; OR = 1.487; 95% CI: 1.015–1.823; P=0.042). The interaction between single nucleotide polymorphisms (SNP) of the rs987401919 and rs36071027 loci and smoking and drinking were distinctly associated with the incidence of CAD (P<0.05). The content of systolic blood pressure (SBP), diastolic blood pressure (DBP), HDL-C, LDL-C, and TG was distinctly changed after gene mutation at the rs987401919 and rs36071027 loci (P<0.05). Conclusion: The results of the present study show that the mutation (CT+TT) at the rs987401919 and rs36071027 loci of EBF1 and its interaction with smoking and drinking are risk factors for CAD, and that the mechanism may be related to the changes in blood pressure and blood lipid content.

The role of CDKN2B in cardiovascular risk in ethnic Saudi Arabs: A validation study

BackgroundGenome-wide association studies (GWASs) have yielded a wealth of information furnishing support for the variability in genetic predisposition to disease. However, the actual impact of such findings on any particular ethnic population needs to be validated through replication studies. In the present study, we verified recent findings of a GWAS demonstrating a strong association for the cyclin-dependent kinase 4 inhibitor B (CDKN2B) genomic region with coronary artery disease (CAD)/myocardial infarction (MI) in ethnic Saudi Arabs. MethodologyWe genotyped 8 CDKN2B SNPs for cardiovascular risk in 4650 Saudi Arabs, comprising 2429 CAD cases (1860 males; 569 female) and 2221 controls (1189 male; 1032 female) by Taqman assay. ResultsFour SNPs, rs4977574_A [0.56(0.50–0.63); p < 0.0001], rs10757274_A [0.87(0.77–0.97); p = 0.014], rs10738607_A [0.89(0.80–1.00); p = 0.043] and rs1333045_T [0.54(0.48–0.61); p < 0.0001] residing on the CDKN2B gene were significantly associated with CAD following multivariate adjustments for MI, HTN and DM, while four others were weakly associated with the disease. Likewise, three SNPs, rs1412829_G [0.84(0.72–0.97); p = 0.019], rs564398_C [0.81(0.70–0.94); p = 0.006], rs4977756_G [0.87(0.76–0.99); p = 0.036] were significantly associated with MI after multivariate adjustments for CAD, HTN and DM, while the other five displayed borderline associations. ConclusionsOur findings strongly support the notion of a critical role for the CDKN2B gene locus as a cardiovascular risk in ethnic Arabs. The study also demonstrates the importance of replication studies in ascertaining the role of a genomic sequence in disease.

Genetic predictors of testosterone and their associations with cardiovascular disease and risk factors: A Mendelian randomization investigation

BackgroundTestosterone supplementation has been linked to increased cardiovascular disease risk in some observational studies. The causal role of testosterone can be investigated using a Mendelian randomization approach. Methods and resultsWe assessed genetic associations of variants in two gene regions (SHBG and JMJD1C) with several cardiovascular risk factors (lipids, adiponectin, blood pressure, anthropometric traits) plus male pattern baldness, including control outcomes and potential mediators. We assessed genetic associations with coronary artery disease (CAD) risk in the CARDIoGRAMplusC4D consortium (171,191 individuals including 60,801 cases), and associations with CAD and ischaemic stroke risk in the UK Biobank (367,643 individuals including 25,352 CAD cases and 3650 ischaemic stroke cases).Genetic predictors of increased serum testosterone were associated with lipids, blood pressure, and height. There was some evidence of an association with risk of CAD (SHBG gene region: odds ratio (OR) 0.95 per 1 unit increase in log-transformed testosterone [95% confidence interval: 0.81–1.12, p = 0.55]; JMJD1C gene region: OR 1.24 [1.01–1.51, p = 0.04]) and ischaemic stroke both overall (SHBG: OR 1.05 [0.64, 1.73, p = 0.83]; JMJD1C: OR 2.52 [1.33, 4.77, p = 0.005]) and in men. However, associations with some control outcomes were in the opposite direction to that expected. ConclusionsSex hormone-related mechanisms appear to be relevant to cardiovascular risk factors and for stroke (particularly for men). However, the extent that these findings are specifically informative about endogenous testosterone or testosterone supplementation is unclear. These findings underline a fundamental limitation for the use of Mendelian randomization where biological knowledge about the function of genetic variants is uncertain.

Serum magnesium levels and risk of coronary artery disease: Mendelian randomisation study

BackgroundObservational studies have shown that serum magnesium levels are inversely associated with risk of cardiovascular disease, but whether this association is causal is unknown. We conducted a Mendelian randomisation study to investigate whether serum magnesium levels may be causally associated with coronary artery disease (CAD).MethodsThis Mendelian randomisation analysis is based on summary-level data from the CARDIoGRAMplusC4D consortium’s 1000 Genomes-based genome-wide association meta-analysis of 48 studies with a total of 60,801 CAD cases and 123,504 non-cases. Six single-nucleotide polymorphisms associated with serum magnesium levels at genome-wide significance were used as instrumental variables.ResultsA genetic predisposition to higher serum magnesium levels was inversely associated with CAD. In conventional Mendelian randomisation analysis, the odds ratio of CAD was 0.88 (95% confidence interval [CI] 0.78 to 0.99; P = 0.03) per 0.1-mmol/L (about 1 standard deviation) increase in genetically predicted serum magnesium levels. Results were consistent in sensitivity analyses using the weighted median and heterogeneity-penalised model averaging methods, with odds ratios of 0.84 (95% CI 0.72 to 0.98; P = 0.03) and 0.83 (95% CI 0.71 to 0.96; P = 0.02), respectively.ConclusionsThis study based on genetics provides evidence that serum magnesium levels are inversely associated with risk of CAD. Randomised controlled trials elucidating whether magnesium supplementation lowers the risk of CAD, preferably in a setting at higher risk of hypomagnesaemia, are warranted.

Lack of genetic support for shared aetiology of Coronary Artery Disease and Late-onset Alzheimer\u2019s disease

Epidemiological studies suggest a positive association between coronary artery disease (CAD) and late-onset Alzheimer’s disease (LOAD). This large-scale genetic study brings together ‘big data’ resources to examine the causal impact of genetic determinants of CAD on risk of LOAD. A two-sample Mendelian randomization approach was adopted to estimate the causal effect of CAD on risk of LOAD using summary data from 60,801 CAD cases from CARDIoGRAMplusC4D and 17,008 LOAD cases from the IGAP Consortium. Additional analyses assessed the independent relevance of genetic associations at the APOE locus for both CAD and LOAD. Higher genetically determined risk of CAD was associated with a slightly higher risk of LOAD (Odds Ratio (OR) per log-odds unit of CAD [95% CI]: 1.07 [1.01–1.15]; p = 0.027). However, after exclusion of the APOE locus, the estimate of the causal effect of CAD for LOAD was attenuated and no longer significant (OR 0.94 [0.88–1.01]; p = 0.072). This Mendelian randomization study indicates that the APOE locus is the chief determinant of shared genetic architecture between CAD and LOAD, and suggests a lack of causal relevance of CAD for risk of LOAD after exclusion of APOE.

Evaluation of the predictive value of Gensini score on determination of severity of coronary artery disease in cases with left bundle branch block

Abstract Left bundle branch block (LBBB) is one of the features which predicts severe organic heart disease. In this study, we aimed to examine the predictive role of Gensini score as marker of severity of coronary artery disease (CAD) in patients with LBBB and its relationship with other CAD risk factors and complications. We have included patients who referred to our center for selective coronary angiography with transient and or permanent LBBB on their surface electrocardiography (ECG). Cases with pacemaker rhythm and known non-CAD related causes of LBBB pattern on surface ECG were excluded from this study. Demographic variables and clinical features were studied. To determine severity of CAD, Gensini score was measured. The relationship between presence of CAD and deteriorated ejection fraction has been demonstrated by previous works, but we found no association between severity of CAD and degree of ejection fraction deterioration. This might imply to the role of non-CAD factors toward reduction of ejection fraction. In cases with hypertension in the setting of LBBB, higher Gensini scores were seen regardless of ventricular ejection fraction. Thus, earlier screening for possible CAD in cases with LBBB and hypertension seems rational. Keywords: Left bundle branch block Electrocardiography Severity of coronary artery disease Gensini score

Increased Peripheral Blood Visfatin Concentrations May Be a Risk Marker of Coronary Artery Disease: A Meta-Analysis of Observational Studies.

A comprehensive quantitative evaluation of the relationship between peripheral blood visfatin concentrations and coronary artery disease (CAD) is lacking. This study is the first attempt to quantify this relationship via a meta-analysis of published observational studies in terms of weighted mean difference (WMD). Literature retrieval, article selection, and data extraction were conducted. Heterogeneity was inspected using both subgroup and meta-regression analyses. In total, 15 articles involving 1053 CAD cases and 714 controls were included. Overall, peripheral blood visfatin concentrations were significantly higher in CAD cases than in controls (WMD: 4.72 ng/mL; 95% confidence interval [CI]: 2.97-6.47; P < .001), with significant heterogeneity and publication bias. Six studies were theoretically missing based on filled funnel plot, and considering the impact of these missing studies still detected a significant overall mean difference in visfatin (WMD: 2.82 ng/mL; 95% CI: 2.22-3.58; P < .001; number of studies: 21). Subgroup and meta-regression analyses indicated age, body mass index, race, diabetes, systolic blood pressure, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were identified as possible causes of heterogeneity. In conclusion, our findings suggest that increased peripheral blood visfatin concentrations may be a risk marker of CAD.

DASH Score and Subsequent Risk of Coronary Artery Disease: The Findings From Million Veteran Program.

BackgroundWhile adherence to healthful dietary patterns has been associated with a lower risk of coronary artery disease (CAD) in the general population, limited data are available among US veterans. We tested the hypothesis that adherence to Dietary Approach to Stop Hypertension (DASH) food pattern is associated with a lower risk of developing CAD among veterans.Methods and ResultsWe analyzed data on 153 802 participants of the Million Veteran Program enrolled between 2011 and 2016. Information on dietary habits was obtained using a food frequency questionnaire at enrollment. We used electronic health records to assess the development of CAD during follow‐up. Of the 153 802 veterans who provided information on diet and were free of CAD at baseline, the mean age was 64.0 (SD=11.8) years and 90.4% were men. During a mean follow‐up of 2.8 years, 5451 CAD cases occurred. The crude incidence rate of CAD was 14.0, 13.1, 12.6, 12.3, and 11.1 cases per 1000 person‐years across consecutive quintiles of Dietary Approach to Stop Hypertension score. Hazard ratios (95% confidence interval) for CAD were 1.0 (ref), 0.91 (0.84–0.99), 0.87 (0.80–0.95), 0.86 (0.79–0.94), and 0.80 (0.73–0.87) from the lowest to highest quintile of Dietary Approach to Stop Hypertension score controlling for age, sex, body mass index, race, smoking, exercise, alcohol intake, and statin use (P linear trend, <0.0001).ConclusionsOur data are consistent with an inverse association between Dietary Approach to Stop Hypertension diet score and incidence of CAD among US veterans.

IL-13 may be involved in the development of CAD via different mechanisms under different conditions in a Chinese Han population

Interleukin-13 (IL-13) has important functions in atherosclerosis, but its role in coronary artery disease (CAD) is unclear. Here, we studied the genetic role of IL-13 in CAD in a Chinese Han population using tag SNPs covering the whole IL13 gene (i.e., rs1881457, rs2069744 and rs20541) and a two-stage cohort containing 1863 CAD cases and 1841 controls. Traditional risk factors for CAD, such as age, BMI, and other factors, were used as covariates in logistic regression analysis. In the total population, we found that two haplotypes of IL13 (ATG and ATA, ordered rs1881457C-rs2069744T-rs20541A) significantly contributed to the risk of CAD with adjusted p values less than 0.05 (padj = 0.019 and padj = 0.042, respectively). In subgroup population analyses, the variant rs1881457C was found to significantly contribute to a nearly two fold increase in the risk of CAD in men (padj = 0.023, OR = 1.91, 95% CI: 1.09-3.33). The variant rs1881457C also significantly contributed to a nearly twofold risk of late-onset CAD (padj = 0.024, OR = 1.93, 95% CI: 1.09-3.42). In conclusion, IL13 might be involved in CAD via different mechanisms under different conditions in the Chinese Han population.

Hysterectomy is associated with higher risk of coronary artery disease: A nationwide retrospective cohort study in Taiwan.

Hysterectomy is a common procedure for benign pathologies of the uterus. Reduced production of estrogen following hysterectomy has been reported. Yet the association between hysterectomy and coronary artery disease (CAD) risk remains controversial. The aim of this study was to investigate the effect of hysterectomy on the risk of CAD; calculations were adjusted for traditional risk factors.This study used a 1 million patient cohort of the Taiwan National Health Insurance database and included a total of 7331 women who received hysterectomy from 2000 to 2013. We randomly selected a control group composed of 29,324 women without hysterectomy by 1:4 matching the age (exact year) with the hysterectomy group.The mean (standard deviation) age was 43.5 ± 4.0 in the hysterectomy and 43.6 ± 4.0 in the control group. A total of 1986 CAD cases developed in both groups during a median follow-up of 7 years. Significant differences were observed in CAD incidence in the hysterectomy versus control group (9.82 vs. 7.17/1000 person-years, P < .001, adjusted hazard ratio = 1.31 [95% confidence interval: 1.18–1.45]).We found a significant association between hysterectomy and CAD, even after adjustment for baseline CAD risk factors.

Association of Genetic Instrumental Variables for Lung Function on Coronary Artery Disease Risk: A 2-Sample Mendelian Randomization Study.

Lung function, assessed by forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), is inversely associated with coronary artery disease (CAD), but these associations could be because of confounding or reversed causality. We conducted a 2-sample Mendelian randomization study, using publicly available data from relevant genome-wide association studies, to examine the role of FEV1 or FVC on CAD. We used the most recent genome-wide association studies on lung function to extract genetic instruments related to FEV1 and FVC (n=92 749). Data on the association between genetic instruments and CAD were obtained from Coronary Artery Disease Genome wide Replication and Meta-analysis plus The Coronary Artery Disease Genetics 1000 Genomes-based genome-wide association studies (60 801 CAD cases and 123 504 controls). We used inverse-variance weighting with a multiplicative random effect to estimate the genetic instrumented association of FEV1 and FVC on CAD. Sensitivity analyses included weighted median and MR-Egger methods. Each SD greater FEV1 was associated with a lower risk of CAD (odds ratio, 0.78 per SD; 95% confidence interval, 0.62-0.98) with a similar magnitude for FVC on CAD risk (odds ratio, 0.82 per SD; 95% confidence interval, 0.64-1.06). Estimates for FEV1 were similar when using MR-Egger method (odds ratio, 0.80 per SD; 95% confidence interval, 0.33-1.94) although the magnitude was smaller for weighted median method (odds ratio, 0.93 per SD; 95% confidence interval, 0.75-1.17). Estimates for FVC in the sensitivity analyses were attenuated (median) or changed direction (MR-Egger). Our study suggested an inverse relation between FEV1 and CAD, but for FVC, evidence is less clear.

Abstract P245: High Consumption of Caffeinated Tea is Associated With Increased Risk of Coronary Artery Disease but Caffeinated Coffee Consumption is Not

Introduction: Prior studies have suggested a link between diet and Coronary Artery Disease (CAD), but there have been mixed findings on the risks and benefits of coffee and tea consumption. We assessed whether there is an association and dose response between coffee and tea intake on CAD incidence among Veterans. Methods: Million Veteran Program (MVP) is a national, representative longitudinal study of Veterans for genomic and non-genomic research that combines data from self-reported surveys, electronic health records, and biospecimens. Using food frequency data collected from 2011-2017 and CAD outcomes obtained from electronic health records, we used cox proportional hazard ratios (HR) to evaluate the association of coffee or tea intake with CAD incidence among Veterans with complete data. Follow-up began at the completion of the food frequency survey. Tea and coffee were evaluated separately, with intake categorized as never or less than one cup/month, 1-3 cups/month, one cup/week, 2-4 cups/week, 5-6 cups/week, one cup/day, 2-3 cups/day, 4-5 cups/day, or 6+ cups/day. For tea, the last two categories were combined to obtain stable estimates. Multivariate models were adjusted for known CAD risk factors (age, smoking status, physical activity, and education) and other caffeine use (e.g. tea for coffee). We plan to use restricted cubic splines to assess dose-response relationships. Results: Among 139,549 participants (90.3% male, mean age 64 ± 12 years), 74.2% consumed 1+ cups of coffee a month and 53.7% consumed 1+ cups of tea a month. During a median follow up of 3.2 years, we observed 4,715 new cases of CAD. Compared to those who drank less than one cup of coffee/month, adjusted HRs (95% CI) for CAD were 1.06 (0.92-1.22) for 1-3 cups/month, 1.09 (0.91-1.29) for one cup/week, 0.96 (0.84-1.10) for 2-4 cups/week, 0.92 (0.81-1.04) for 5-6 cups/week, 0.93 (0.85-1.01) for one cup/day, 0.99 (0.91-1.07) for 2-3 cups/day, 1.05 (0.93-1.19) for 4-5 cups/day, and 1.08 (0.92-1.28) for 6+ cups/day (p-linear trend=0.24). Compared to those who drank less than one cup of caffeinated tea/month, adjusted HRs (95% CI) for CAD were 1.08 (0.99-1.17) for 1-3 cups/month, 1.11 (0.99-1.23) for one cup/week, 1.01 (0.91-1.12) for 2-4 cups/week, 1.03 (0.89-1.17) for 5-6 cups/week, 1.04 (0.93-1.17) for one cup/day, 1.12 (0.98-1.28) for 2-3 cups/day, and 1.27 (1.04-1.58) for 4+ cups/day (p-linear trend=0.14). Conclusion: While coffee intake was not associated with incidence of CAD, there was an elevated risk of CAD restricted to Veterans consuming 4+ cups of caffeinated tea per day.

Dual Effect of IL-6 -174 G/C Polymorphism and Promoter Methylation in the Risk of Coronary Artery Disease Among South Indians.

Inflammation plays an important role in the pathogenesis of atherosclerosis and coronary syndromes; moreover, various lines of evidence suggest that genetic factors do contribute to the risk of coronary artery disease (CAD). The proinflammatory cytokine IL-6 is a central mediator of inflammation associated with CAD. The present study is aimed to investigate the association of single nucleotide polymorphism in the promoter region of the IL-6 gene (-174 G>C) and methylation with the susceptibility of CAD. Genotyping of IL-6 -174 G/C polymorphism was performed by PCR-RFLP. Methylation-specific PCR method was used to study the IL-6 gene promoter methylation. Analysis of 470 subjects (265 CAD patients and 205 controls) showed association of the -174 G/C variant with the CAD risk in dominant model (OR 1.58, 95% CI, 1.024-2.23, P=0.04). Further, the analysis of the distribution of genotypes and alleles of -174 G>C polymorphism according to clinical features of CAD, revealed significant association of genotype and allele (OR 1.86, 95% CI 1.18-2.84 P=0.01, andOR 1.71, 95% CI 1.09-2.23 P=0.02 respectively) with diabetes, and we found no association with hypertension (OR 0.95, 95% CI 0.57-1.59, P=0.8). We also analyzed the methylation status of IL-6 promoter region between cases and controls showed significant hypo methylation in CAD subjects (OR 2.36, 95% CI 1.51-4.259, P=0.006). Additionally, GC, CC genotypes and C allele carriers show hypomethylation in CAD cases compared to controls (54.58 vs. 76.85%, 29.83 vs. 40% respectively). In conclusion, the promoter polymorphism -174 G/C is associated with CAD risk and further carriers of 'C' allele at -174 locus showed significant hypo methylation which could contribute to increased risk of CAD. The present study highlights the association of allele and genotypes with differential DNA methylation of CpG islands in the IL-6 promoter region which may affect IL-6 gene regulation.

Prediction of coronary disease incidence by biomarkers of inflammation, oxidation, and metabolism

The effect of circulating biomarkers in predicting coronary artery disease (CAD) is not fully elucidated. This study aimed to determine the relationship with CAD and the predictive capacity of nine biomarkers of inflammation (TNF-α, IL-10, IL-6, MCP-1, CRP), oxidation (GHS-Px), and metabolism (adiponectin, leptin, and insulin). This was a case-cohort study, within the REGICOR population-cohorts (North-Eastern Spain), of 105 CAD cases and 638 individuals randomly selected from a cohort of 5,404 participants aged 35–74 years (mean follow-up = 6.1 years). Biomarkers’ hazard ratio (HR)/standard deviation was estimated with Cox models adjusted for age, sex, and classical risk factors. Discrimination improvement and reclassification were analyzed with the c-index and the Net reclassification index (NRI). GHS-Px (adjusted HRs = 0.77; 95%CI:0.60–0.99), insulin (1.46; 1.08–1.98), leptin (1.40; 1.03–1.90), IL-6 (1.34; 1.03–1.74), and TNF-α (1.80; 1.26–2.57) were significantly associated with CAD incidence. In the model adjusted for all biomarkers, TNF-α (1.87;1.31–2.66) and insulin (1.59;1.16–2.19) were independently associated with CAD. This final model, compared to a model without biomarkers, showed a c-index difference of 1.3% (−0.7, 3.2) and a continuous NRI of 33.7% (2.6, 61.9). TNF-α and insulin are independently associated with CAD incidence and they improve reclassification when added to a model including classical risk factors.