ApoE e2 and aging-related outcomes in 379,000 UK Biobank participants

AbstractThe Apolipoprotein E (APOE) e4 allele is associated with reduced longevity and increased Coronary Artery Disease (CAD) and Alzheimer’s disease, with e4e4 having markedly larger effect sizes than e3e4. The e2 longevity promoting variant is less studied. We conducted a phenome-wide association study of ApoE e2e3 and e2e2 with aging phenotypes, to assess their potential as targets for anti-aging interventions. Data were from 379,000 UK Biobank participants, aged 40 to 70 years. e2e3 (n=46,535) had mostly lower lipid-related biomarker levels including reduced total and LDL-cholesterol, and lower risks of CAD (Odds Ratio=0.87, 95% CI: 0.83 to 0.90, p=4.92×10−14) and hypertension(OR=0.94, 95% CI: 0.92 to 0.97, p=7.28×10−7) versus e3e3. However, lipid changes in e2e2 (n=2,398) were more extreme, including a marked increase in triglyceride levels (0.41 Standard Deviations, 95% CI: 0.37 to 0.45, p=5.42×10−92), with no associated changes in CAD risks. There were no associations with biomarkers of kidney function. The effects of both e2e2 and e2e3 were minimal on falls, muscle mass, grip strength or frailty. In conclusion, e2e3 has protective effects on some health outcomes, but the effects of e2e2 are not similar, complicating the potential usefulness of e2 as a target for anti-aging intervention.

Download Full-text

The effect of polymorphisms (174G> C and 572C> G) on the Interleukin-6 gene in coronary artery disease: a systematic review and meta-analysis

Genes and Environment ◽

10.1186/s41021-021-00172-8 ◽

2021 ◽

Vol 43 (1) ◽

Author(s):

Nader Salari ◽

Kamran Mansouri ◽

Amin Hosseinian-Far ◽

Hooman Ghasemi ◽

Masoud Mohammadi ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Interleukin 6 ◽

Odds Ratio ◽

Meta Analysis ◽

Serum Levels ◽

Protective Effects ◽

Increased Risk ◽

Artery Disease ◽

The Relationship

Abstract Background Coronary Artery Disease (CAD) is caused by the blockage of the coronary arteries. it is argued that there has an association between the Interleukin-6 gene and the occurrence of atherosclerosis, coronary artery disease, Due to the short half-life and high variability of Interleukin-6 (IL-6), limited studies have been performed on the association of serum levels of interleukin-6 with coronary artery disease. The aim of this study is to investigate the relationship between IL-6 gene polymorphisms and coronary artery disease. Methods This study was conducted as a meta-analysis of selected articles with no lower time limit and upto March 2020. Articles related to the subject were obtained by searching several data sources,such as the SID, IranDoc, Scopus, Embase, Web of Science (ISI), PubMed, Science Direct, and Google Scholar databases. The heterogeneity of the studies was assessed using the I2 index in the Comprehensive Meta-Analysis software. Results The GG genotype of the IL-6174 G> C polymorphism with a 0.8 odds ratio tended to reduce the risk of CAD by 20%. The odds ratio of CAD in CG and GG genotypes were found to be 1.16 and 1.48 times respectively, indicating the increasing effect of these two genotypes. In the IL-6-572 C>G polymorphism, CG and GG genotypes increased the risk of CAD by 1.21 and 1.27 times respectively, and the CC genotype tended to reduce the risk of CAD by 15%, considering the odds ratio of 0.85. Conclusion This study showed a relationship between IL-6174G> C and Interleukin-6 (IL-6) 572 C>G genes and coronary artery disease. Moreover, the protective effects of GG genotype in IL-6 gene 174 G> C and CC genotype in IL-6 gene 572 C>G gene were reported. The study also confirmed that the CG and CC genotypes of the G>C IL-6174 gene have an increasing effect on coronary artery disease. Moreover, CG and GG genotypes in the IL-6 gene 572 C>G increased the risk of developing CAD. It should be noted that the increased risk of developing CAD was limited to meta-analytic studies in reported literatures.

Download Full-text

Associations of observational and genetically determined caffeine intake with coronary artery disease and diabetes

European Heart Journal ◽

10.1093/ehjci/ehaa946.1493 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

A Said ◽

Y.J Van De Vegte ◽

N Verweij ◽

P Van Der Harst

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Mendelian Randomization ◽

Cox Regression ◽

Caffeine Intake ◽

Uk Biobank ◽

Genome Wide ◽

Artery Disease ◽

Genetically Determined

Abstract Background Caffeine is the most widely consumed psychostimulant and is associated with lower risk of coronary artery disease (CAD) and type 2 diabetes (T2D). However, whether these associations are causal remains unknown. Objectives This study aimed to identify genetic variants associated with caffeine intake, and to investigate possible causal links between genetically determined caffeine intake and CAD or T2D. Additionally, we aimed to replicate previous observational findings between caffeine intake and CAD or T2D. Methods Genome wide associated studies (GWAS) were performed on caffeine intake from coffee, tea or both in 407,072 UK Biobank participants. Identified variants were used in a two-sample Mendelian randomization (MR) approach to investigate evidence for causal links between caffeine intake and CAD in CARDIoGRAMplusC4D (60,801 cases; 123,504 controls) or T2D in DIAGRAM (26,676 cases; 132,532 controls). Observational associations were tested within UK Biobank using Cox regression analyses. Results Moderate observational caffeine intakes from coffee or tea were associated with lower risks of CAD or T2D compared to no or high intake, with the lowest risks at intakes of 120–180 mg/day from coffee for CAD (HR=0.77 [95% CI: 0.73–0.82; P<1e-16]), and 300–360 mg/day for T2D (HR=0.76 [95% CI: 0.67–0.86]; P=1.57e-5). GWAS identified 51 novel genetic loci associated with caffeine intake, enriched for central nervous system genes. In contrast to observational analyses, MR analyses in CARDIoGRAMplusC4D and DIAGRAM yielded no evidence for causal links between caffeine intake and the development of CAD or T2D. Conclusions MR analyses indicate caffeine intake might not protect against CAD or T2D, despite protective associations in observational analyses. Manhattan_plot_CaffeineIntake Funding Acknowledgement Type of funding source: None

Download Full-text

Prospective Analysis after Coronary-artery Bypass Grafting: Platelet GP IIIa Polymorphism (HPA-1b /PlA2) Is a Risk Factor for Bypass Occlusion, Myocardial Infarction, and Death

Thrombosis and Haemostasis ◽

10.1055/s-0037-1613827 ◽

2000 ◽

Vol 83 (03) ◽

pp. 404-407 ◽

Cited By ~ 43

Author(s):

Michael Klein ◽

Hans Dauben ◽

Christiane Moser ◽

Emmeran Gams ◽

Rüdiger Scharf ◽

...

Keyword(s):

Myocardial Infarction ◽

Coronary Artery Disease ◽

Risk Factor ◽

Coronary Artery ◽

Odds Ratio ◽

Bypass Surgery ◽

Artery Bypass ◽

Bypass Grafting ◽

Hereditary Risk ◽

Artery Disease

SummaryRecently, we have demonstrated that human platelet antigen 1b (HPA-1b or PlA2) is a hereditary risk factor for platelet thrombogenicity leading to premature myocardial infarction in preexisting coronary artery disease. However, HPA-1b does not represent a risk factor for coronary artery disease itself. The aim of our present study was to evaluate the role of HPA-1b on the outcome in patients after coronaryartery bypass surgery. We prospectively determined the HPA-1 genotype in 261 consecutive patients prior to saphenous-vein coronaryartery bypass grafting. The patients were followed for one year. Among patients with bypass occlusion, myocardial infarction, or death more than 30 days after surgery, the prevalence of HPA-1b was significantly higher than among patients without postoperative complications (60 percent, 6/10, vs. 24 percent, 58/241, p <0.05, odds ratio 4.7). Using a stepwise logistic regression analysis with the variables HPA1b, age, sex, body mass index, smoking (pack-years), hypertension, diabetes, cholesterol and triglyceride concentration, only HPA-1b had a significant association with bypass occlusion, myocardial infarction, or death after bypass surgery (p = 0.019, odds ratio 4.7). This study shows that HPA-1b is a hereditary risk factor for bypass occlusion, myocardial infarction, or death in patients after coronary-artery bypass surgery.

Download Full-text

Gánh nặng xơ vữa động mạch cảnh ở người mắc bệnh động mạch vành sớm

Journal of Clinical Medicine- Hue Central Hospital ◽

10.38103/jcmhch.2021.71.9 ◽

2021 ◽

Author(s):

Thanh Huong Truong

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Carotid Stenosis ◽

Odds Ratio ◽

Carotid Atherosclerosis ◽

Multivariate Logistic Regression Analysis ◽

Lipoprotein Cholesterol ◽

Premature Coronary Artery Disease ◽

Viet Nam ◽

Artery Disease

TÓM TẮT Đặt vấn đề: Dữ liệu xơ vữa động mạch (ĐM) cảnh ở người mắc bệnh động mạch vành sớm (BĐMVS) còn hạn chế tại Việt Nam. Do đó, nghiên cứu này nhằm mục tiêu xác định tỉ lệ xơ vữa ĐM cảnh và các yếu tố liên quan đến tình trạng này ở người mắc BĐMVS tại Việt Nam. Đối tượng, phương pháp nghiên cứu: Đây là nghiên cứu mô tả với 94 người mắc BĐMVS được siêu âm ĐM cảnh. Kết quả: Tình trạng hẹp ĐM cảnh không ý nghĩa và có ý nghĩa quan sát thấy ở 16 (17.0%) và 4 bệnh nhân (4.3%), tương ứng. Phân tích hồi quy logistic đa biến thấy nồng độ lipoprotein cholesterol tỷ trọng thấp (LDL-C) trong máu liên quan độc lập với hẹp ĐM cảnh có ý nghĩa (Odds Ratio = 1.504). Kết luận: Tại Việt Nam, người mắc BĐMVS có tỉ lệ cao bị hẹp ĐM cảnh. Sàng lọc hẹp ĐM cảnh nên được thực hiện cho nhóm bệnh nhân này, đặc biệt là khi có kèm tăng LDL-máu. Từ khoá: Xơ vữa, hẹp động mạch cảnh, bệnh động mạch vành, sớm ABSTRACT BURDEN OF CAROTID ATHEROSCLEROSIS IN PATIENTS WITH PREMATURE CORONARY ARTERY DISEASE Background: Data about carotid atherosclerosis in patients with premature coronary artery disease (PCAD) is still limited in Vietnam. Therefore, this study aims to investigate the prevalence of carotid atherosclerosis in patients with PCAD and factors related to carotid stenosis in these patients in Vietnam. Methods: This is a cross-sectional study that enrolled 94 patients with PCAD. All of patients were screened carotid atherosclerosis using ultrasonography. Results: Non-significant andsignificant carotid stenosiswere observed in 16 patients (17.0%) and 4 patients (4.3%), respectively. Multivariate logistic regression analysis showed that serum low density lipoprotein cholesterol (LDL-C) level was independently related to the presence of carotid stenosis with Odds ratio as 1.504. Conclusions: Prevalence of carotid stenosis is high in patients with PCAD in Vietnam. Screening of carotid stenosis should be recommended in these patients, especially in whom with elevated LDL-C. Key words: Atherosclerosis, carotid stenosis,coronary artery disease, premature.

Download Full-text

Rare, Damaging DNA Variants in CORIN and Risk of Coronary Artery Disease: Insights From Functional Genomics and Large-Scale Sequencing Analyses

Circulation Genomic and Precision Medicine ◽

10.1161/circgen.121.003399 ◽

2021 ◽

Author(s):

Minxian Wang ◽

Vivian S. Lee-Kim ◽

Deepak S. Atri ◽

Nadine H. Elowe ◽

John Yu ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Association Analysis ◽

Rare Variant ◽

Odds Ratio ◽

Large Scale ◽

Missense Mutations ◽

Rare Variant Association ◽

Missense Variants ◽

Artery Disease

Background: Corin is a protease expressed in cardiomyocytes that plays a key role in salt handling and intravascular volume homeostasis via activation of natriuretic peptides. It is unknown if Corin loss-of-function (LOF) is causally associated with risk of coronary artery disease (CAD). Methods: We analyzed all coding CORIN variants in an Italian case-control study of CAD. We functionally tested all 64 rare missense mutations in Western Blot and Mass Spectroscopy assays for proatrial natriuretic peptide cleavage. An expanded rare variant association analysis for Corin LOF mutations was conducted in whole exome sequencing data from 37 799 CAD cases and 212 184 controls. Results: We observed LOF variants in CORIN in 8 of 1803 (0.4%) CAD cases versus 0 of 1725 controls ( P , 0.007). Of 64 rare missense variants profiled, 21 (33%) demonstrated <30% of wild-type activity and were deemed damaging in the 2 functional assays for Corin activity. In a rare variant association study that aggregated rare LOF and functionally validated damaging missense variants from the Italian study, we observed no association with CAD—21 of 1803 CAD cases versus 12 of 1725 controls with adjusted odds ratio of 1.61 ([95% CI, 0.79–3.29]; P =0.17). In the expanded sequencing dataset, there was no relationship between rare LOF variants with CAD was also observed (odds ratio, 1.15 [95% CI, 0.89–1.49]; P =0.30). Consistent with the genetic analysis, we observed no relationship between circulating Corin concentrations with incident CAD events among 4744 participants of a prospective cohort study—sex-stratified hazard ratio per SD increment of 0.96 ([95% CI, 0.87–1.07], P =0.48). Conclusions: Functional testing of missense mutations improved the accuracy of rare variant association analysis. Despite compelling pathophysiology and a preliminary observation suggesting association, we observed no relationship between rare damaging variants in CORIN or circulating Corin concentrations with risk of CAD.

Download Full-text

Revascularization versus Medical Management of Coronary Artery Disease in Prerenal Transplant Patients: A Meta-Analysis

Cardiorenal Medicine ◽

10.1159/000487763 ◽

2018 ◽

Vol 8 (3) ◽

pp. 192-198

Author(s):

Haroon Kamran ◽

Eric Kupferstein ◽

Navneet Sharma ◽

Gagandeep Singh ◽

James R. Sowers ◽

...

Keyword(s):

Coronary Artery Disease ◽

Renal Transplantation ◽

Coronary Artery ◽

Medical Management ◽

Odds Ratio ◽

Patient Population ◽

Fixed Effects ◽

Coronary Revascularization ◽

Meta Analysis ◽

Artery Disease

Introduction: End-stage renal disease requiring renal transplantation comprises a growing patient population at risk for cardiovascular disease (CVD) morbidity and mortality in large part due to accelerated atherosclerosis. Consequently, these patients are at even higher risk of major surgical CVD mortality. A paucity of research has addressed the posttransplantation CVD outcomes related to different treatment strategies in this patient population and therefore, there are no specific preoperative guidelines regarding management of coronary artery disease in this high-risk population undergoing renal transplantation. Objective: Through meta-analysis we compare coronary revascularization to medical management prior to renal transplantation in patients who are found to have significant obstructive coronary artery disease. Results: A total of 6 studies were deemed suitable out of 777 articles reviewed. This included 260 patients who received medical management and 338 who received coronary revascularization. There were 36 events in the revascularization and 57 events in the medical management group. One study only reported hazard ratios but no CVD outcomes. Comprehensive Meta-Analysis software was used to calculate pooled odds ratio with 95% confidence intervals (CI) for the fixed effects. The data is presented as forest plots. The pooled odds ratio with 95% CI for the fixed effects was 1.415 (95% CI 0.885–2.263), p = 0.147, indicating that there is no difference in CVD outcomes between pretransplant treatment strategy. This observation suggests that the CVD outcomes posttransplantation are not affected when optimal medical therapy is used instead of coronary revascularization.

Download Full-text

Genetic variants of PEAR1 and ischemic clinical outcomes in coronary artery disease patients: a systematic review and meta-analysis

Pharmacogenomics ◽

10.2217/pgs-2021-0022 ◽

2021 ◽

Author(s):

Xinyi Zhang ◽

Sicong Li ◽

Yuxuan Zhao ◽

Ningjia Tang ◽

Tong Jia ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Clinical Outcomes ◽

Odds Ratio ◽

Meta Analysis ◽

Electronic Database ◽

Artery Disease ◽

Relationship Of ◽

The Relationship ◽

Ischemic Events

Aim: The aim of this study was to assess the association between PEAR1 polymorphisms and ischemic clinical outcomes. Materials & methods: We searched the electronic database for articles on the relationship of PEAR1 SNPs and ischemic events in patients with coronary artery disease (CAD) up to October 2020. Results: A total of 9914 patients with CAD from six studies focusing on 12 SNPs of PEAR1 were included in this study. The A allele of rs12041331 were associated with ischemic events (odds ratio: 1.40; 95% CI: 1.04–1.88; p = 0.03). The AA homozygotes of rs2768759 was related to a higher risk of ischemic events than carriers of the C allele (odds ratio: 2.08; 95% CI: 1.09–3.97; p = 0.03). Conclusion: PEAR1 rs12041331 and rs2768759 are significantly associated with ischemic events in patients with CAD.

Download Full-text

Abstract 13531: Coronary Artery Disease Predicts Venous Occlusion in Patients Undergoing Lead Extraction

Circulation ◽

10.1161/circ.142.suppl_3.13531 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Kris Kumar ◽

Stacey Howell ◽

Saket Sanghai ◽

George Giraud ◽

Peter Jessel ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Odds Ratio ◽

Nyha Class ◽

Vascular Occlusion ◽

Venous Occlusion ◽

Lead Extraction ◽

Lead Failure ◽

Increased Risk ◽

Artery Disease

Introduction: Pacemaker and ICD lead failure or vascular occlusion can require lead extraction. Predictors of a need for lead extraction due to venous occlusion are not well characterized. Hypothesis: Coronary artery disease (CAD) is an independent predictor of lead extraction due to venous occlusion. Methods: We performed a retrospective study of consecutive patients in a prospectively collected registry at a single center undergoing lead extraction due to either venous occlusion or lead failure from 10/2011 to 02/2020. Patients requiring lead extraction due to infection were excluded. Continuous variables are reported as mean ± standard deviation or total number reported as a percentage (%). Chi square test and logistic regression were used to estimate difference in rates and Odds Ratio. Statistically significant findings were identified with a p valve < 0.05. Results: Of 384 procedures included in the database, 131 patients met inclusion criteria for venous occlusion (17%) or lead failure (83%) (Table 1). Average age of the cohort was 55.1 ± 16.4 years and 51% were female. Baseline ejection fraction was 44.6 ± 15.5% and 19.7% of patients had NYHA class III or IV symptoms. 29.7% had a history of CAD. Average number of leads extracted was 1.3 ± 0.57 compared to 2.1 ± 0.82 leads in situ. Patients with CAD had a statistically significant increased risk for extraction as a result of venous occlusion Odds Ratio of 6.80, 95% CI 2.47-18.6, p = 0.0001. Conclusions: Identification of predictors of venous occlusion and risk stratification of these patients is an important component of procedural planning and shared decision making. CAD is a predictor of venous occlusion in patients undergoing lead extraction and should be assessed as a risk factor for complex lead management decisions. Further study is warranted to identify mechanisms by which this relationship can be used to predict need for extraction due to vascular occlusion.

Download Full-text

Abstract 162: Single Nucleotide Polymorphism of the B-Type Natriuretic Peptide Helps Predict the Presence of Significant Coronary Artery Disease

Circulation Research ◽

10.1161/res.115.suppl_1.162 ◽

2014 ◽

Vol 115 (suppl_1) ◽

Author(s):

Terry Y Li ◽

M. Y Tse ◽

Nicole M Ventura ◽

Marie-France Hetu ◽

Amer M Johri ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Coronary Angiography ◽

Natriuretic Peptide ◽

Genetic Screening ◽

Odds Ratio ◽

Single Nucleotide ◽

Artery Disease ◽

Peptide Gene ◽

Significant Disease

Early detection and diagnosis of coronary artery disease (CAD) is crucial in reducing the morbidity and mortality. The clinical standard for detecting CAD is by angiography which is associated with rare but important clinical risks. Recent studies have shown that up to 40% of patients referred for angiography do not have significant disease. This discrepancy between referral and diagnosis may be improved by the utilization of genetic screening. A single nucleotide polymorphisms (SNP) of the B-type natriuretic peptide gene (NPPB), rs198389, was previously found to be associated with several cardiovascular diseases. Our objective was to determine whether detection of genetic variation could contribute to better selection of patients referred for angiography. We hypothesized that an SNP analysis of the NPPB gene may help differentiate patients with significant disease from those with non-significant CAD. Ninety-three patients referred for coronary angiography at the Kingston General Hospital Cardiac Catheterization Lab were consented for genetic screening. Blood samples were collected during angiography procedure. Genomic DNA was isolated from leukocytes, and screened for SNPs using a real-time PCR-based TaqMan SNP Assay. We found that more males were referred for coronary angiography than females: 69% versus 31%. Two out of ten males (20%) were found to have no or minimal CAD. In contrast, 48% of females were found to have non-significant CAD. Older age (≥ 69 years) was deemed to be a significant predictor of CAD in the total recruited population (odds ratio of 3.4), but no age difference was found between healthy and diseased females. Additionally, a mutation of the B-type natriuretic peptide gene (NPPB) was found to be a significant predictor of CAD in the younger population (< 69 years), with an odds ratio of 5.9. We found a significant difference between patterns of CAD development in males and females, suggesting that different diagnostic criteria should be used depending upon gender. Moreover, younger individuals with two copies of the major allele for the NPPB SNP were more likely to develop CAD, making this SNP a potential factor in the prediction of CAD in younger population.

Download Full-text