Identification of 15 novel risk loci for coronary artery disease and genetic risk of recurrent events, atrial fibrillation and heart failure.
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ABSTRACT:
SUBMITTER: Verweij N
PROVIDER: S-EPMC5459820 | biostudies-literature | 2017 Jun
REPOSITORIES: biostudies-literature
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Identification of 15 novel risk loci for coronary artery disease and genetic risk of recurrent events, atrial fibrillation and heart failure.
Verweij Niek N Eppinga Ruben N RN Hagemeijer Yanick Y van der Harst Pim P
Scientific reports 20170605 1
Coronary artery disease (CAD) is the major cause of morbidity and mortality in the world. Identification of novel genetic determinants may provide new opportunities for developing innovative strategies to predict, prevent and treat CAD. Therefore, we meta-analyzed independent genetic variants passing P <× 10<sup>-5</sup> in CARDIoGRAMplusC4D with novel data made available by UK Biobank. Of the 161 genetic variants studied, 71 reached genome wide significance (p < 5 × 10<sup>-8</sup>) including 1 ...[more]
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Project description:Background Perioperative atrial fibrillation (POAF) is common in patients undergoing cardiac surgery. Conflicting evidence exists whether patients with POAF after cardiac surgery have an increased long-term risk of stroke and other adverse events. Methods and Results We prospectively followed for up to 5 years 4624 patients without prior atrial fibrillation who underwent coronary artery bypass grafting in an international study. POAF was defined as atrial fibrillation that occurred during the initial hospitalization for surgery, lasted for ≥5 minutes, and required treatment. Outcomes assessed were a composite of death, nonfatal myocardial infarction or nonfatal stroke, and its individual components. Median age was 67 years, and 778 (16.8%) had an episode of POAF. The incidence of the composite outcome was 6.84 and 4.10 per 100 patient-years in patients with and without POAF, and the incidence of stroke was 0.75 versus 0.45, respectively. The adjusted hazard ratios (aHRs) were 1.36 (95% CI, 1.16-1.59) for the composite outcome; 1.33 (95% CI, 1.10-1.61) for death; 1.58 (95% CI, 1.23-2.02) for myocardial infarction, and 1.27 (95% CI, 0.81-2.00) for stroke. In a landmark analysis excluding events of the initial hospital admission, the aHRs were 1.26 (95% CI, 1.03-1.54) for the composite outcome, 1.28 (95% CI, 1.03-1.59) for death, 1.70 (95% CI, 0.86-3.36) for myocardial infarction, and 1.07 (95% CI, 0.59-1.93) for stroke. At hospital discharge, 10.7% and 1.4% of patients with and without POAF received oral anticoagulation, respectively. Conclusions Patients with POAF after cardiac surgery had an increased long-term risk of adverse outcomes, mainly death and myocardial infarction. The risk of stroke was low and not increased in patients with POAF. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00463294.
| S-EPMC8477852 | biostudies-literature
Project description:Background The CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes, previous stroke or TIA [transient ischemic attack], vascular disease, age 65 to 74 years, sex category female; 2 indicates 2 points, otherwise 1 point) scoring system is recommended to guide decisions on oral anticoagulation therapy for stroke prevention in patients with nonsurgery atrial fibrillation. A score ≥1 in men and ≥2 in women, corresponding to an annual stroke risk exceeding 1%, warrants long-term oral anticoagulation provided the bleeding risk is acceptable. However, in patients with new-onset postoperative atrial fibrillation, the optimal risk stratification method is unknown. The aim of this study was therefore to evaluate the CHA2DS2-VASc scoring system for estimating the 1-year ischemic stroke risk in patients with new-onset postoperative atrial fibrillation after coronary artery bypass grafting. Methods and Results All patients with new-onset postoperative atrial fibrillation and without oral anticoagulation after first-time isolated coronary artery bypass grafting performed in Sweden during 2007 to 2017 were eligible for this registry-based observational cohort study. The 1-year ischemic stroke rate at each step of the CHA2DS2-VASc score was estimated using a Kaplan-Meier estimator. Of the 6368 patients included (mean age, 69.9 years; 81% men), >97% were treated with antiplatelet drugs. There were 147 ischemic strokes during the first year of follow-up. The ischemic stroke rate at 1 year was 0.3%, 0.7%, and 1.5% in patients with CHA2DS2-VASc scores of 1, 2, and 3, respectively, and ≥2.3% in patients with a score ≥4. A sensitivity analysis, with the inclusion of patients on anticoagulants, was performed and supported the primary results. Conclusions Patients with new-onset atrial fibrillation after coronary artery bypass grafting and a CHA2DS2-VASc score <3 have such a low 1-year risk for ischemic stroke that oral anticoagulation therapy should probably be avoided.
| S-EPMC9238552 | biostudies-literature
Project description:ImportanceNew-onset postoperative atrial fibrillation (POAF) is a common complication of coronary artery bypass graft (CABG) surgery. However, the long-term risk of thromboembolism in patients who develop POAF after CABG surgery remains unknown. In addition, information on stroke prophylaxis in this setting is lacking.ObjectiveTo examine stroke prophylaxis and the long-term risk of thromboembolism in patients with new-onset POAF after first-time isolated CABG surgery compared with patients with nonsurgical, nonvalvular atrial fibrillation (NVAF).Design, setting, and participantsThis cohort study used data from a clinical cardiac surgery database and Danish nationwide registries to identify patients undergoing first-time isolated CABG surgery who developed new-onset POAF from January 1, 2000, through June 30, 2015. These patients were matched by age, sex, CHA2DS2-VASc score, and year of diagnosis to patients with nonsurgical NVAF in a 1 to 4 ratio. Data analysis was completed from February 2017 to January 2018.Main outcomes and measuresThe proportion of patients initiating oral anticoagulation therapy within 30 days and the rates of thromboembolism.ResultsA total of 2108 patients who developed POAF after CABG surgery were matched with 8432 patients with NVAF. In the full population of 10 540 patients, the median (interquartile range) age was 69.2 (63.7-74.7) years; 8675 patients (82.3%) were men. Oral anticoagulation therapy was initiated within 30 days postdischarge in 175 patients with POAF (8.4%) and 3549 patients with NVAF (42.9%). The risk of thromboembolism was lower in the POAF group than in the NVAF group (18.3 vs 29.7 events per 1000 person-years; adjusted hazard ratio [HR], 0.67; 95% CI, 0.55-0.81; P < .001). Anticoagulation therapy during follow-up was associated with a lower risk of thromboembolic events in both patients with POAF (adjusted HR, 0.55; 95% CI, 0.32-0.95; P = .03) and NVAF (adjusted HR, 0.59; 95% CI, 0.51-0.68; P < .001) compared with patients who did not receive any anticoagulation therapy. Further, the risk of thromboembolism was not significantly higher in patients with POAF compared with those who did not develop POAF after CABG surgery (adjusted HR, 1.11; 95% CI, 0.94-1.32; P < .24).Conclusions and relevanceNew-onset POAF in patients who had undergone CABG surgery was associated with a lower long-term thromboembolic risk than that of patients who had NVAF. These data do not support the notion that new-onset POAF should be regarded as equivalent to primary NVAF in terms of long-term thromboembolic risk.
| S-EPMC5875315 | biostudies-literature
Project description:Background The clinical significance of fibrillatory wave on electrocardiography during atrial fibrillation (AF) is poorly understood. The aim of the current study was to explore the association of fine fibrillatory wave with heart failure (HF) in AF. Methods and Results The current study enrolled 2442 patients with AF whose baseline ECG during AF rhythm was available from a community-based prospective survey, the Fushimi AF Registry. The impact of fine fibrillatory wave, defined as the amplitude of fibrillatory waves <0.1 mV, on the primary composite HF end point (a composite of hospitalization attributable to HF or cardiac death) was examined. Fine fibrillatory wave was observed in 589 patients (24.1%). Patients with fine fibrillatory wave were older, and had a higher prevalence of sustained AF, preexisting HF, and larger left atrial diameter than those with coarse fibrillatory wave. During the median follow-up duration of 5.9 years, the cumulative incidence of the primary composite HF end point was significantly higher in patients with fine fibrillatory wave than in those with coarse fibrillatory wave (5.3% versus 3.6% per patient-year, log-rank P<0.001). The higher risk associated with fine fibrillatory wave was consistent even for individual components of the primary composite HF end point. On multivariable analysis, fine fibrillatory wave became an independent predictor for the primary composite HF end point (hazard ratio, 1.31; 95% CI, 1.07-1.61; P=0.01). Conclusions Compared with coarse fibrillatory wave, fine fibrillatory wave was more prevalent in patients with a larger left atrial diameter or those with sustained AF and was independently associated with a higher risk of HF events. Registration URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000005834.
| S-EPMC9075419 | biostudies-literature
Project description:BackgroundCoronary artery disease (CAD) and atrial fibrillation (AF) frequently coexist in clinical practice, making it challenging for the treating physician to choose anticoagulation and antiplatelet therapies. The aim of this study was to investigate antithrombotic strategies and assess related adverse outcomes in stable coronary artery disease (SCAD) and acute coronary syndrome (ACS) patients with AF when the CHA2DS2-VASc score was ≥2.MethodsWe performed a retrospective study and collected data from a computer-based patient record management system in Zhengzhou University People's Hospital in China. In total, 2978 patients with a hospital discharge diagnosis of CAD and concomitant AF who met the inclusion criteria were enrolled from January 1, 2012 to December 31, 2016, and data from 2050 patients were finally analysed. The χ2 test was used to compare the incidences of clinical endpoints between the SCAD+AF group and the ACS + AF group. Multivariable Cox regression analysis was performed to identify independent predictive factors of adverse outcomes in both groups.ResultsOral anticoagulant (OAC) monotherapy was the most common antithrombotic therapy in SCAD+AF patients (49.55%), while double antiplatelet therapy (DAPT) was the most common treatment in ACS + AF patients (54.19%) at discharge. OAC monotherapy significantly increased and the use of single antiplatelet therapy (SAPT) decreased during follow-up (34 ± 13 months) when compared to their use at discharge in the SCAD+AF group (all p < 0.001). In the ACS + AF group, the proportion of patients using DAPT decreased notably, while the proportions of patients using SAPT and dual therapy (DT) combining OAC with SAPT increased significantly during follow-up (all p < 0.001) compared to the proportions at discharge. According to multivariable Cox regression analysis, age, hypertension and prior stroke were independent risk factors for ischaemic stroke in the SCAD+AF group and ACS + AF group (all p < 0.05). OAC was an independent protective factor for ischaemic stroke in both groups (all p < 0.05). Previous bleeding independently increased the risk of haemorrhage in both groups (all p < 0.01).ConclusionsIn this study, the proportion of anticoagulant-antiplatelet combined therapy was low in ACS + AF patients with high stroke risk. In clinical practice, the awareness of anticoagulation needs to be strengthened regarding patients with CAD and AF.
| S-EPMC7339421 | biostudies-literature
Project description:BackgroundGenome-wide association studies have identified multiple loci associated with coronary artery disease and myocardial infarction, but only a few of these loci are current targets for on-market medications. To identify drugs suitable for repurposing and their targets, we created 2 unique pipelines integrating public data on 49 coronary artery disease/myocardial infarction-genome-wide association studies loci, drug-gene interactions, side effects, and chemical interactions.MethodsWe first used publicly available genome-wide association studies results on all phenotypes to predict relevant side effects, identified drug-gene interactions, and prioritized candidates for repurposing among existing drugs. Second, we prioritized gene product targets by calculating a druggability score to estimate how accessible pockets of coronary artery disease/myocardial infarction-associated gene products are, then used again the genome-wide association studies results to predict side effects, excluded loci with widespread cross-tissue expression to avoid housekeeping and genes involved in vital processes and accordingly ranked the remaining gene products.ResultsThese pipelines ultimately led to 3 suggestions for drug repurposing: pentolinium, adenosine triphosphate, and riociguat (to target CHRNB4, ACSS2, and GUCY1A3, respectively); and 3 proteins for drug development: LMOD1 (leiomodin 1), HIP1 (huntingtin-interacting protein 1), and PPP2R3A (protein phosphatase 2, regulatory subunit b-double prime, α). Most current therapies for coronary artery disease/myocardial infarction treatment were also rediscovered.ConclusionsIntegration of genomic and pharmacological data may prove beneficial for drug repurposing and development, as evidence from our pipelines suggests.
| S-EPMC6205215 | biostudies-literature
Project description:Obesity has been identified as a risk factor for postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG). However, no studies have addressed the influence of race on this association. A total of 13,594 patients undergoing first-time, isolated CABG without preoperative AF between 1992 and 2011 were included in our study. The association between body mass index and POAF was compared by race. Relative risk and 95% CIs were computed using maximum likelihood log-binomial regression. Increasing levels of body mass index were associated with higher POAF risk after CABG in black but not white patients (pinteraction = 0.0009).
| S-EPMC4799751 | biostudies-literature
Project description:BackgroundPostoperative atrial fibrillation (pAF) after coronary artery bypass grafting is a common complication. Whether pAF is associated with an increased risk of cerebrovascular accident (CVA) remains uncertain. We investigated the association between pAF and long-term risk of CVA by performing a post hoc analysis of 10-year outcomes of the ART (Arterial Revascularization Trial).MethodsFor the present analysis, among patients enrolled in the ART (n=3102), we excluded those who did not undergo surgery (n=25), had a history of atrial fibrillation (n=45), or had no information on the incidence of pAF (n=9). The final population consisted of 3023 patients, of whom 734 (24.3%) developed pAF with the remaining 2289 maintaining sinus rhythm. Competing risk and Cox regression analyses were used to investigate the association between pAF and the risk of CVA.ResultsAt 10 years, the cumulative incidence of CVA was 6.3% (4.6%-8.1%) versus 3.7% (2.9%-4.5%) in patients with pAF and sinus rhythm, respectively. pAF was an independent predictor of CVA at 10 years (hazard ratio, 1.53 [95% CI, 1.06-2.23]; P=0.025) even when CVAs that occurred during the index admission were excluded from the analysis (hazard ratio, 1.47 [95% 1.02-2.11]; P=0.04).ConclusionsPatients with pAF after coronary artery bypass grafting are at higher risk of CVA. These findings challenge the notion that pAF is a benign complication.
| S-EPMC7845484 | biostudies-literature
Project description:Patients with atrial fibrillation affected by an acute coronary syndrome have indications for oral anticoagulation and dual antiplatelet therapy with aspirin and a P2Y12 adenosine diphosphate receptor inhibitor after coronary artery stenting. The concurrent use of all 3 agents, termed triple oral antithrombotic therapy, significantly increases the risk of bleeding. To date, there is a lack of evidence on the proper combination and duration of anticoagulant and antiplatelet agents in patients with indications for both therapies. As such, care has been guided by expert opinion, and there is wide variation in clinician practice. In this review, the latest evidence on the risks and benefits of triple oral antithrombotic therapy in patients with atrial fibrillation after coronary artery stenting is summarized. We discuss the clinical risk scores useful in guiding the prediction of stroke, bleeding, and stent thrombosis. Additionally, we highlight where additional evidence is needed to determine the proper balance of anticoagulant and antiplatelet agents in this patient population.
| S-EPMC6649565 | biostudies-literature
Project description:Background: Several works of observational clinical research indicate that coronary artery disease (CAD) and atrial fibrillation (AF) aggravate each other. However, it is unknown whether these associations reveal independent causal processes. Objective: The present study aimed to evaluate causal associations between CAD and AF using two-sample Mendelian randomization (TSMR) analysis. Methods: Summary-level Genome-wide association study (GWAS) data for CAD were obtained from the CARDIoGRAMplusC4D consortium, including 60,801 patients and 123,504 controls. General data for AF were acquired from the largest meta-analysis, comprising of 60,620 patients with AF and 970,216 non-cases. After data harmonization, three different methods—inverse-variance weighted (IVW), MR-Egger, and weighted-median—were applied for TSMR analysis. Results: The calculated ORs (95% CIs) for AF using IVW, MR-Egger, and weighted-median analysis were 1.11 (1.05, 1.17; p-value < 0.001), 1.14 (1.00, 1.29; p-value = 0.049), and 1.13 (1.08, 1.19; p-value < 0.001), respectively; for CAD, the results were 1.01 (0.97, 1.04; p-value = 0.76), 0.95 (0.89, 1.02; p-value = 0.15), and 1.00 (0.95, 1.05; p-value = 0.97). Conclusion: This comprehensive TSMR analysis provides evidence that patients with CAD are associated with an increased risk of AF. However, no causal association was found between patients with AF and the risk of CAD. These findings benefit clinical decision-making. Early heart-rhythm monitoring should be performed in patients with CAD. The prevention and treatment of AF complications such as thrombosis may be essential to reduce the incidence of CAD in AF patients.
| S-EPMC8949548 | biostudies-literature