scholarly journals LncRNA TARID Induces Cell Proliferation Through Cell Cycle Pathway Associated With Coronary Artery Disease

2021 ◽  
Author(s):  
Zheng Cheng ◽  
Yonghong Zhang ◽  
Yang Zhuo ◽  
Jie Fan ◽  
Ying Xu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Coronary Artery Disease ◽  
Cell Proliferation ◽  
Coronary Artery ◽  
Taqman Assay ◽  
Eqtl Analysis ◽  
Left Circumflex Artery ◽  
Artery Disease ◽  
The Impact ◽  
Cad Risk

Abstract Background/Aim: Long noncoding RNA TARID (lncRNA TARID) can activate the tumor suppressor TCF21 in tumorigenesis by inducing promoter demethylation. However, the impact on lncRNA TARID and its variants of coronary artery disease (CAD) are poorly understood. Methods We performed a case-control study enrolling 949 case patients and 892 controls to assess genotype. Five variants were genotyped by TaqMan assay. 20 case patients and 20 controls were used to evaluate the expression of lncRNA TARID. The qRT-PCR and cell cycle analysis were applied to examined cell proliferation and cell distribution. Results This study indicated that rs2327433 GG genotype was associated with CAD risk adjusting for traditional risk factors (OR=2.74, 95%CI: 1.10-6.83, P=0.03). Our results analyses revealed that the genotype of rs2327433 was related to the proportion of CAD patients with left anterior descending artery disease and left circumflex artery disease (P=0.025 and P=0.025, respectively). The results showed that the minor allele frequency of rs2327433 was significantly correlated with the severity of the disease (P=0.029). The eQTL analysis showed that rs2327433 may affect the transcription factors TCF21 regulated by lncRNA TARID. We found that TARID silencing regulated the cell proliferation and altered cell cycle progression by induced upregulation of CDK1 and PCNA. Conclusions SNP rs2327433 in lncRNA TARID was associated with CAD risk and the severity of CAD in Chinese Han population. Furthermore, SNP rs2327433 may affect the expression of atherosclerosis-related transcription factor TCF21 regulated by lncRNA TARID. Finally, our study provided a new lncRNA-dictated regulatory mechanism participating in cell proliferation.

scholarly journals Polygenic Hyperlipidemias and Coronary Artery Disease Risk

2019 ◽  
Author(s):  
Pietari Ripatti ◽  
Joel T Rämö ◽  
Nina J Mars ◽  
Sanni Söderlund ◽  
Christian Benner ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Genome Wide Association Study ◽  
Disease Risk ◽  
Cumulative Exposure ◽  
Risk Scores ◽  
Lipid Levels ◽  
Artery Disease ◽  
The Impact ◽  
Cad Risk

AbstractBackgroundHyperlipidemia is a highly heritable risk factor for coronary artery disease (CAD). Monogenic familial hypercholesterolemia associates with higher increase in CAD risk than expected from a single LDL-C measurement, likely due to lifelong cumulative exposure to high LDL-C. It remains unclear to what extent a high polygenic load of LDL-C or TG-increasing variants associates with increased CAD risk.Methods and ResultsWe derived polygenic risk scores (PRS) with ∼6M variants for LDL-C and TG with weights from a UK biobank-based genome-wide association study with ∼500K samples. We evaluated the impact of polygenic hypercholesterolemia and hypertriglyceridemia to lipid levels in 27 039 individuals from the FINRISK cohort, and to CAD risk in 135 300 individuals (13 695 CAD cases) from the FinnGen project.In FINRISK, LDL-C ranged from 2.83 (95% CI 2.79-2.89) to 3.80 (3.72-3.88) and TG from 0.99 (0.95-1.01) to 1.52 (1.48-1.58) mmol/l between the lowest and highest 5% of the respective PRS distributions. The corresponding CAD prevalences ranged from 8.2% to 12.7% for the LDL-C PRS and from 8.2% to 12.1% for the TG PRS in FinnGen. Furthermore, CAD risk was 1.36-fold higher (OR, 95% CI 1.24-1.49) for the LDL-C PRS and 1.31-fold higher (1.20-1.44) for the TG PRS for those with the PRS >95th percentile vs those without. These estimates were only slightly attenuated when adjusting for a CAD PRS (OR 1.26 [95% CI 1.15-1.39] for LDL-C and 1.21 [1.10-1.32] for TG PRS).ConclusionsThe CAD risk associated with a high polygenic load for lipid-increasing variants was proportional to their impact on lipid levels and mostly independent of a CAD PRS. In contrast with a PRS for CAD, the lipid PRSs point to known and directly modifiable risk factors providing more direct guidance for clinical translation.

scholarly journals Polygenic Hyperlipidemias and Coronary Artery Disease Risk

2020 ◽  
Vol 13 (2) ◽  
Author(s):  
Pietari Ripatti ◽  
Joel T. Rämö ◽  
Nina J. Mars ◽  
Yu Fu ◽  
Jake Lin ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Odds Ratio ◽  
Genome Wide Association Study ◽  
Disease Risk ◽  
Risk Scores ◽  
Lipid Levels ◽  
Artery Disease ◽  
The Impact ◽  
Cad Risk

Background: Hyperlipidemia is a highly heritable risk factor for coronary artery disease (CAD). While monogenic familial hypercholesterolemia associates with severely increased CAD risk, it remains less clear to what extent a high polygenic load of a large number of LDL (low-density lipoprotein) cholesterol (LDL-C) or triglyceride (TG)-increasing variants associates with increased CAD risk. Methods: We derived polygenic risk scores (PRSs) with ≈6M variants separately for LDL-C and TG with weights from a UK Biobank–based genome-wide association study with ≈324K samples. We evaluated the impact of polygenic hypercholesterolemia and hypertriglyceridemia to lipid levels in 27 039 individuals from the National FINRISK Study (FINRISK) cohort and to CAD risk in 135 638 individuals (13 753 CAD cases) from the FinnGen project (FinnGen). Results: In FINRISK, median LDL-C was 3.39 (95% CI, 3.38–3.40) mmol/L, and it ranged from 2.87 (95% CI, 2.82–2.94) to 3.78 (95% CI, 3.71–3.83) mmol/L between the lowest and highest 5% of the LDL-C PRS distribution. Median TG was 1.19 (95% CI, 1.18–1.20) mmol/L, ranging from 0.97 (95% CI, 0.94–1.00) to 1.55 (95% CI, 1.48–1.61) mmol/L with the TG PRS. In FinnGen, comparing the highest 5% of the PRS to the lowest 95%, CAD odds ratio was 1.36 (95% CI, 1.24–1.49) for the LDL-C PRS and 1.31 (95% CI, 1.19–1.43) for the TG PRS. These estimates were only slightly attenuated when adjusting for a CAD PRS (odds ratio, 1.26 [95% CI, 1.16–1.38] for LDL-C and 1.24 [95% CI, 1.13–1.36] for TG PRS). Conclusions: The CAD risk associated with a high polygenic load for lipid-increasing variants was proportional to their impact on lipid levels and partially overlapping with a CAD PRS. In contrast with a PRS for CAD, the lipid PRSs point to known and directly modifiable risk factors providing additional guidance for clinical translation.

scholarly journals Validation of genome-wide polygenic risk scores for coronary artery disease in French Canadians

2019 ◽  
Author(s):  
Florian Wünnemann ◽  
Ken Sin Lo ◽  
Alexandra Langford-Avelar ◽  
David Busseuil ◽  
Marie-Pierre Dubé ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Risk Scores ◽  
French Canadian ◽  
French Canadians ◽  
Polygenic Risk ◽  
Genome Wide ◽  
Artery Disease ◽  
The Impact ◽  
Cad Risk

AbstractCoronary artery disease (CAD) represents one of the leading causes of morbidity and mortality worldwide. Given the healthcare risks and societal impacts associated with CAD, their clinical management would benefit from improved prevention and prediction tools. Polygenic risk scores (PRS) based on an individual’s genome sequence are emerging as potentially powerful biomarkers to predict the risk to develop CAD. Two recently derived genome-wide PRS have shown high specificity and sensitivity to identify CAD cases in European-ancestry participants from the UK Biobank. However, validation of the PRS predictive power and transferability in other populations is now required to support their clinical utility. We calculated both PRS (GPSCAD and metaGRSCAD) in French-Canadian individuals from three cohorts totaling 3639 prevalent CAD cases and 7382 controls, and tested their power to predict prevalent, incident and recurrent CAD. We also estimated the impact of the founder French-Canadian familial hypercholesterolemia deletion (LDLR delta > 15kb deletion) on CAD risk in one of these cohorts and used this estimate to calibrate the impact of the PRS. Our results confirm the ability of both PRS to predict prevalent CAD comparable to the original reports (area under the curve (AUC) = 0.72-0.84). Furthermore, the PRS identified about 6-7% of individuals at CAD risk similar to carriers of the LDLR delta > 15kb mutation, consistent with previous estimates. However, the PRS did not perform as well in predicting incident (AUC= 0.56 - 0.60) or recurrent (AUC= 0.56 - 0.60) CAD. This result suggests that additional work is warranted to better understand how ascertainment biases and study design impact PRS for CAD. Collectively, our results confirm that novel, genome-wide PRS are able to predict CAD in French-Canadians; with further improvements, this is likely to pave the way towards more targeted strategies to predict and prevent CAD-related adverse events.

scholarly journals Unique and Varied Contributions of Traditional CVD Risk Factors: A Systematic Literature Review of CAD Risk Factors in China

2013 ◽  
Vol 7 ◽  
pp. CMC.S10225 ◽  
Author(s):  
Joanne Foody ◽  
Yong Huo ◽  
Linong Ji ◽  
Dong Zhao ◽  
Dylan Boyd ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Real World ◽  
Odds Ratio ◽  
Lipid Levels ◽  
Artery Disease ◽  
The Impact ◽  
Cad Risk

This study is the first systematic review of risk factors for stroke in China and supports the importance of current public health initiatives to manage the risk factors appropriately to reduce risk of stroke in high risk patients. Additionally, this study has been co-authored by prominent Chinese and US physicians and researchers with expertise in cardiovascular disease, neurologic disorders, epidemiology, and real world data. While there have been several systematic reviews of real world associations of risk factors for coronary artery disease, none focus specifically on the population of China, where there is growing evidence that such risk factors are poorly treated or uncontrolled, especially in rural areas. Background To better understand the impact of traditional cardiovascular risk factors on risk of coronary artery disease (CAD) in China, a systematic review of all Chinese observational studies published in either English or Chinese in MEDLINE and EMBASE over the last 5 years was performed and the association between any of 5 traditional risk factors (ie, hypertension, diabetes, elevated lipid levels, obesity, and smoking) and the risk of CAD was studied. Methods and Results The study found a consistent relationship between lipid levels and CAD. Higher low-density lipoprotein cholesterol values were associated with greater risk of CAD, with an odds ratio as high as 3.31. Other factors found to be significant contributors to the risk of CAD included hypertension (crude odds ratio range of 1.40-5.11), diabetes (1.50-5.97), and smoking (1.37-5.19). An association between obesity and CAD in China was observed, but the evidence supporting this was considered weak due to the paucity of studies found as part of this review. Conclusions This review provides a systematic summary of CAD risk factors in China and demonstrates the important differences that exist in CAD risk factors between countries and regions. Approaches to reduce CAD globally must take into account the unique risk factors that drive CAD in each country and region as is demonstrated by these findings.

scholarly journals Convergence of biomarkers and risk factor trait loci of coronary artery disease at 3p21.31 and HLA region

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Majid Nikpay ◽  
Ruth McPherson
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Protein Level ◽  
Human Leukocyte ◽  
Trait Loci ◽  
Artery Disease ◽  
Associated Risk Factors ◽  
The Impact ◽  
Cad Risk

AbstractHere we seek to identify molecular biomarkers that mediate the effect of risk factors on coronary artery disease (CAD). We perform a SNP-based multiomics data analysis to find biomarkers (probes) causally associated with the risk of CAD within known genomic loci for its risk factors. We identify 78 biomarkers, the majority (64%) of which are methylation probes. We detect the convergence of several CNS and lifestyle trait loci and their biomarkers at the 3p21.31 and human leukocyte antigen (HLA) regions. The 3p21.31 locus was the most populated region in the convergence of biomarkers and risk factors. In this region, we noted as the BSN gene becomes methylated the level of stomatin (STOM) in blood increases and this contributes to higher risk of CAD. In the HLA locus, we identify several methylation biomarkers associated with various CAD risk factors. SNPs in the CFB gene display a trans-regulatory impact on the GRIA4 protein level. A methylation site upstream of the APOE gene is associated with a higher protein level of S100A13 which in turn leads to higher LDL-C and greater CAD risk. We find UHRF1BP1 and ILRUN mediate the effect of obesity on CAD whereas methylation sites within NOS3 and CKM mediate the effect of their associated-risk factors on CAD. This study provides further insight into the biology of CAD and identifies a list of biomarkers that mediate the impact of risk factors on CAD. A SNP-based initiative can unite data from various fields of omics into a single network of knowledge.

scholarly journals The Impact of War-Related Stress on Coronary Artery Disease Severity in War Survivors: A SYNTAX Study

2021 ◽  
Vol 18 (6) ◽  
pp. 3233
Author(s):  
Hanna Al-Makhamreh ◽  
Dana Alkhulaifat ◽  
Abdallah Al-Ani ◽  
Baraa Mafrachi ◽  
Aseel Saadeh ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
University Hospital ◽  
Syntax Score ◽  
Syrian Refugee ◽  
War Survivors ◽  
Artery Disease ◽  
The Impact ◽  
Cad Risk

Background: Due to the strong relationship between stress and heart disease, particularly acute myocardial infarction (MI), this study investigated the complexity of coronary artery disease (CAD) among Syrian refugee patients referred to Jordan University Hospital and its relation to war-related stressors. Methods: This is a retrospective study that utilized the SYNTAX I score in order to evaluate all Syrian refugees that underwent coronary artery catheterization at Jordan University Hospital during the period between May of 2014 and December of 2017. Results: There was a significant association between war-related stressors and high SYNTAX score (SX score), thus indicating a higher complexity of CAD in Syrian war survivors with higher stress scores. The strongest war-related correlation was observed with crossing green-lines, in which Syrian refugee patients who had crossed such lines had significantly higher SYNTAX scores. Regression analysis demonstrated that war stressors were positive predictors of increased SYNTAX scores even when adjusted for conventional CAD risk factors. Surprisingly, none of the CAD risk factors were significantly associated with SYNTAX score. Conclusion: Our findings suggest that exposure to multiple war-related stressors may increase the complexity and severity of CAD in Syrian war survivors. Thus, special attention, efforts, and resources should be allocated to screen for such vulnerable patients in order to provide them with the appropriate healthcare.

The Impact of Smoking on Cardiovascular Outcomes and Comorbidities in Statin-treated Patients with Coronary Artery Disease: A Post hoc Analysis of the GREACE Study

2013 ◽  
Vol 11 (5) ◽  
pp. 779-784 ◽  
Author(s):  
Vasilios G. Athyros ◽  
Konstantinos Tziomalos ◽  
Niki Katsiki ◽  
Thomas D. Gossios ◽  
Olga Giouleme ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Cardiovascular Outcomes ◽  
Post Hoc Analysis ◽  
Artery Disease ◽  
Post Hoc ◽  
The Impact

scholarly journals Impact of Coronary CT angiography in combination with CAD-RADS on the management of coronary artery disease patients

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
F Andre ◽  
S Seitz ◽  
P Fortner ◽  
R Sokiranski ◽  
F Gueckel ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Risk Stratification ◽  
Coronary Ct Angiography ◽  
Patient Management ◽  
Male Gender ◽  
Coronary Ct ◽  
History Of ◽  
Artery Disease ◽  
The Impact

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Siemens Healthineers Introduction Coronary CT angiography (CCTA) plays an increasing role in the detection and risk stratification of patients with coronary artery disease (CAD). The Coronary Artery Disease – Reporting and Data System (CAD-RADS) allows for standardized classification of CCTA results and, thus, may improve patient management. Purpose Aim of this study was to assess the impact of CCTA in combination with CAD-RADS on patient management and to identify the impact of cardiovascular risk factors (CVRF) on CAD severity. Methods CCTA was performed on a third-generation dual-source CT scanner in patients, who were referred to a radiology centre by their attending physicians. In a total of 4801 patients, CVRF were derived from medical reports and anamnesis. Results The study population consisted of 4770 patients (62.0 (54.0-69.0) years, 2841 males) with CAD (CAD-RADS 1-5), while 31 patients showed no CAD and were excluded from further analyses. Age, male gender and the number of CVRF were associated with more severe CAD stages (all p < 0.001). 3040 patients (63.7 %) showed minimal or mild CAD requiring optimization of CVRF i.e. medical therapy but no further assessment at his time. A group of 266 patients (5.6 %) had a severe CAD defined as CAD-RADS 4B/5. In the multivariate regression analysis, age, male gender, history of smoking, diabetes mellitus and hyperlipidaemia were significant predictors for severe CAD, whereas arterial hypertension and family history of CAD did not reach significance. Of note, a subgroup of 28 patients (10.5 %) with a severe CAD (68.5 (65.5-70.0) years, 26 males, both p = n.s.) had no CVRF. Conclusions CCTA in combination with the CAD-RADS allowed for effective risk stratification of CAD patients. The majority of the patients showed non-obstructive CAD and, thus, could be treated conservatively without the need for further CAD assessment. CVRF out of arterial hypertension and family history had an impact on CAD severity reflected in higher CAD-RADs gradings. Of note, a relevant fraction of patients with CAD did not have any CVRF and, thus, may not be covered by risk stratification models. CAD-RADS n Age (years) Males (%) 1 1453 56.0 (50.0-62.0) 623 (42.9 %) 2 1587 62.0 (55.0-69.0) 918 (57.8 %) 3 1067 66.0 (59.0-71.0) 749 (70.2 %) 4A 397 66.0 (59.0-72.0) 317 (79.8 %) 4B 162 67.0 (61.0-74.0) 139 (85.8 %) 5 104 66.0 (58.5.0-77.0) 95 (91.3 %)

scholarly journals Impact of established cardiovascular disease on 10-year death after coronary revascularization for complex coronary artery disease

2021 ◽  
Author(s):  
Rutao Wang ◽  
Scot Garg ◽  
Chao Gao ◽  
Hideyuki Kawashima ◽  
Masafumi Ono ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Coronary Revascularization ◽  
Long Term Outcomes ◽  
Vital Status ◽  
Increased Risk ◽  
Artery Disease ◽  
The Impact

Abstract Aims To investigate the impact of established cardiovascular disease (CVD) on 10-year all-cause death following coronary revascularization in patients with complex coronary artery disease (CAD). Methods The SYNTAXES study assessed vital status out to 10 years of patients with complex CAD enrolled in the SYNTAX trial. The relative efficacy of PCI versus CABG in terms of 10-year all-cause death was assessed according to co-existing CVD. Results Established CVD status was recorded in 1771 (98.3%) patients, of whom 827 (46.7%) had established CVD. Compared to those without CVD, patients with CVD had a significantly higher risk of 10-year all-cause death (31.4% vs. 21.7%; adjusted HR: 1.40; 95% CI 1.08–1.80, p = 0.010). In patients with CVD, PCI had a non-significant numerically higher risk of 10-year all-cause death compared with CABG (35.9% vs. 27.2%; adjusted HR: 1.14; 95% CI 0.83–1.58, p = 0.412). The relative treatment effects of PCI versus CABG on 10-year all-cause death in patients with complex CAD were similar irrespective of the presence of CVD (p-interaction = 0.986). Only those patients with CVD in ≥ 2 territories had a higher risk of 10-year all-cause death (adjusted HR: 2.99, 95% CI 2.11–4.23, p < 0.001) compared to those without CVD. Conclusions The presence of CVD involving more than one territory was associated with a significantly increased risk of 10-year all-cause death, which was non-significantly higher in complex CAD patients treated with PCI compared with CABG. Acceptable long-term outcomes were observed, suggesting that patients with established CVD should not be precluded from undergoing invasive angiography or revascularization. Trial registration SYNTAX: ClinicalTrials.gov reference: NCT00114972. SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050. Graphic abstract

scholarly journals Impact of Coronary Artery Disease and Diabetes Mellitus on the Long-Term Follow-Up in Patients after Retrograde Recanalization of the Femoropopliteal Arterial Region

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Joanna Wojtasik-Bakalarz ◽  
Zoltan Ruzsa ◽  
Tomasz Rakowski ◽  
Andreas Nyerges ◽  
Krzysztof Bartuś ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Risk Of Death ◽  
Significant Difference ◽  
Long Term Follow Up ◽  
Artery Disease ◽  
The Impact

The most relevant comorbidities in patients with peripheral artery disease (PAD) are coronary artery disease (CAD) and diabetes mellitus (DM). However, data of long-term follow-up of patients with chronic total occlusion (CTO) are scarce. The aim of the study was to assess the impact of CAD and DM on long-term follow-up patients after superficial femoral artery (SFA) CTO retrograde recanalization. In this study, eighty-six patients with PAD with diagnosed CTO in the femoropopliteal region and at least one unsuccessful attempt of antegrade recanalization were enrolled in 2 clinical centers. Mean time of follow-up in all patients was 47.5 months (±40 months). Patients were divided into two groups depending on the presence of CAD (CAD group: n=45 vs. non-CAD group: n=41) and DM (DM group: n=50 vs. non-DM group: n=36). In long-term follow-up, major adverse peripheral events (MAPE) occurred in 66.6% of patients with CAD vs. 36.5% of patients without CAD and in 50% of patients with DM vs. 55% of non-DM subjects. There were no statistical differences in peripheral endpoints in both groups. However, there was a statistically significant difference in all-cause mortality: in the DM group, there were 6 deaths (12%) (P value = 0.038). To conclude, patients after retrograde recanalization, with coexisting CTO and DM, are at higher risk of death in long-term follow-up.

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