scholarly journals Cardiac Risk Factors for Stroke: A Comprehensive Mendelian Randomization Study

Stroke ◽  
2021 ◽  
Author(s):  
Simon Frerich ◽  
Rainer Malik ◽  
Marios K. Georgakis ◽  
Moritz F. Sinner ◽  
Steven J. Kittner ◽  
...  

Background and Purpose: Observational studies suggest an association of stroke with cardiac traits beyond atrial fibrillation, the leading source of cardioembolism. However, controversy remains regarding a causal role of these traits in stroke pathogenesis. Here, we leveraged genetic data to systematically assess associations between cardiac traits and stroke risk using a Mendelian Randomization framework. Methods: We studied 66 cardiac traits including cardiovascular diseases, magnetic resonance imaging–derived cardiac imaging, echocardiographic imaging, and electrocardiographic measures, as well as blood biomarkers in a 2-sample Mendelian Randomization approach. Genetic predisposition to each trait was explored for associations with risk of stroke and stroke subtypes in data from the MEGASTROKE consortium (40 585 cases/406 111 controls). Using multivariable Mendelian Randomization, we adjusted for potential pleiotropic or mediating effects relating to atrial fibrillation, coronary artery disease, and systolic blood pressure. Results: As expected, we observed strong independent associations between genetic predisposition to atrial fibrillation and cardioembolic stroke and between genetic predisposition to coronary artery disease as a proxy for atherosclerosis and large-artery stroke. Our data-driven analyses further indicated associations of genetic predisposition to both heart failure and lower resting heart rate with stroke. However, these associations were explained by atrial fibrillation, coronary artery disease, and systolic blood pressure in multivariable analyses. Genetically predicted P-wave terminal force in V1, an electrocardiographic marker for atrial cardiopathy, was inversely associated with large-artery stroke. Conclusions: Available genetic data do not support substantial effects of cardiac traits on the risk of stroke beyond known clinical risk factors. Our findings highlight the need to carefully control for confounding and other potential biases in studies examining candidate cardiac risk factors for stroke.

2020 ◽  
Author(s):  
Michael G. Levin ◽  
Derek Klarin ◽  
Themistocles L. Assimes ◽  
Matthew S. Freiberg ◽  
Erik Ingelsson ◽  
...  

ABSTRACTImportanceSmoking is associated with atherosclerotic cardiovascular disease, but the relative contribution to each subtype (coronary artery disease [CAD], peripheral artery disease [PAD], and large-artery stroke) remains less well understood.ObjectiveTo determine the effect of smoking on risk of coronary artery disease, peripheral artery disease, and large-artery stroke.DesignMendelian randomization study using summary statistics from genome-wide associations of smoking (up to 462,690 individuals), coronary artery disease (up to 60,801 cases, 123,504 controls), peripheral artery disease (up to 24,009 cases, 150,983 controls), and large-artery stroke (up to 4,373 cases, 406,111 controls)SettingPopulation-based study of primarily European-ancestry individualsParticipantsParticipants in genome-wide association studies of smoking, coronary artery disease, peripheral artery disease, and stroke.ExposuresGenetic liability to smoking defined by lifetime smoking index: an integrated measure of smoking status, age at initiation, age at cessation, number of cigarettes smoked per day, and declining effect of smoking on health outcomes).Main Outcome MeasureRisk of coronary artery disease, peripheral artery disease, and large-artery stroke.ResultsGenetic liability to smoking was associated with increased risk of PAD (OR 2.13; 95% CI 1.78-2.56; P = 3.6 × 10−16), CAD (OR 1.48; 95% CI 1.25-1.75; P = 4.4 × 10−6), and stroke (OR 1.4; 95% CI 1.02-1.92; P = 0.036). Risk of PAD in smokers was greater than risk of large-artery stroke (pdifference = 0.025) or CAD (pdifference = 0.0041). The effect of smoking on ASCVD remained independent from the effects of smoking on traditional cardiovascular risk factors.Conclusions and RelevanceGenetic liability to smoking is a strong, causal risk factor for CAD, PAD, and stroke, although the effect of smoking is strongest for PAD. The effect of smoking is independent of traditional cardiovascular risk factors.


Medicina ◽  
2021 ◽  
Vol 57 (6) ◽  
pp. 605
Author(s):  
Hanna K. Al-Makhamreh ◽  
Mohammed Q. Al-Sabbagh ◽  
Ala’ E. Shaban ◽  
Abdelrahman F. Obiedat ◽  
Ayman J. Hammoudeh

Background and Objectives: Patients with AF are at increased risk for Coronary Artery Disease (CAD) owing to their shared etiologies and risk factors. This study aimed to assess the prevalence, cardiovascular risk factors, and used medications of CAD in AF patients. Materials and Methods: This retrospective, case-control study utilized data from the Jordanian Atrial Fibrillation (Jo-Fib) registry. Investigators collected clinical features, history of co-existing comorbidities, CHA2DS2-VASc, and HAS BLED scores for all AF patients aged >18 visiting 19 hospitals and 30 outpatient cardiology clinics. A multivariable binary logistic regression was used to asses for factors associated with higher odds of having CAD. Results: Out of 2000 patients with AF, 227 (11.35%) had CAD. Compared to the rest of the sample, those with CAD had significantly higher prevalence of hypertension (82.38%; p < 0.01), hypercholesterolemia (66.52%, p < 0.01), diabetes (56.83%, p < 0.01), and smoking (18.06%, p = 0.04). Patients with AF and CAD had higher use of anticoagulants/antiplatelet agents combination (p < 0.01) compared to the rest of the sample. Females had lower CAD risk than males (OR = 0.35, 95% CI: 0.24–0.50). AF Patients with dyslipidemia (OR = 2.5, 95% CI: 1.8–3.4), smoking (OR = 1.7, 95% CI: 1.1–2.6), higher CHA2DS2-VASc score (OR = 1.5, 95% CI: 1.4–1.7), and asymptomatic AF (OR = 1.9, 95% CI: 1.3–2.6) had higher risk for CAD. Conclusions: Owing to the increased prevalence of CAD in patients with AF, better control of cardiac risk factors is recommended for this special group. Future studies should investigate such interesting relationships to stratify CAD risk in AF patients. We believe that this study adds valuable information regarding the prevalence, epidemiological characteristics, and pharmacotherapy of CAD in patients with AF.


2021 ◽  
Author(s):  
Daniel Hui ◽  
Christopher S. Thom ◽  
Kimberly Lorenz ◽  
Scott M. Damrauer ◽  
Themistocles L. Assimes ◽  
...  

An inverse correlation between stature and risk of coronary artery disease (CAD) has been observed in several epidemiologic studies, and recent Mendelian randomization (MR) experiments have suggested evidence that this association may be causal. However, the extent to which the effect estimated by MR can be explained by established cardiovascular risk factors is unclear, with a recent report suggesting that lung function traits could fully explain the height-CAD effect. To clarify this relationship, we utilized the largest set of genetic instruments for human stature to date, comprising >2,000 genetic variants for height and CAD. In univariable analysis, we confirmed that a one standard deviation decrease in height (~6.5 cm) was associated with a 12.0% increase in the risk of CAD, consistent with previous reports. In multivariable analysis accounting for effects from up to 12 established risk factors, we observed a >3-fold attenuation in the causal effect of height on CAD susceptibility (3.7%, p = 2.1x10-2). We observed minimal effects of lung function traits on CAD risk in our analyses, indicating that these traits are unlikely to explain the residual association between height and CAD risk. In sum, these results suggest that height does not add meaningful clinical impact on CAD risk prediction beyond established risk factors.


Author(s):  
K. I. Shakhgeldyan ◽  
V. Y. Rublev ◽  
B. I. Geltser ◽  
B. O. Shcheglov ◽  
V. G. Shirobokov ◽  
...  

Introduction. Postoperative atrial fibrillation (POAF) is one of the most common complications of coronary artery bypass grafting (CABG) and occurs in 25–65% of patients.Aim. The study aimed to assess the predictive potential of preoperative risk factors for POAF in patients with coronary artery disease (CAD) after CABG based on machine learning (ML) methods.Material and Methods. An observational retrospective study was carried out based on data from 866 electronic case histories of CAD patients with a median age of 63 years and a 95% confidence interval [63; 64], who underwent isolated CABG on cardiopulmonary bypass. Patients were assigned to two groups: group 1 comprised 147 (18%) patients with newly registered atrial fibrillation (AF) paroxysms; group 2 included 648 (81.3%) patients without cardiac arrhythmia. The preoperative clinical and functional status was assessed using 100 factors. We used statistical analysis methods (Chi-square, Fisher, Mann – Whitney, and univariate logistic regression (LR) tests) and ML tests (multivariate LR and stochastic gradient boosting (SGB)) for data processing and analysis. The models’ accuracy was assessed by three quality metrics: area under the ROC-curve (AUC), sensitivity, and specificity. The cross-validation procedure was performed at least 1000 times on randomly selected data.Results. The processing and analysis of preoperative patient status indicators using ML methods allowed to identify 10 predictors that were linearly and nonlinearly related to the development of POAF. The most significant predictors were the anteroposterior dimension of the left atrium, tricuspid valve insufficiency, ejection fraction <40%, duration of the P–R interval, and chronic heart failure of functional class III–IV. The accuracy of the best predictive multifactorial model of LR was 0.61 in AUC, 0.49 in specificity, and 0.72 in sensitivity. The values of similar quality metrics for the best model based on SGB were 0.64, 0.6, and 0.68, respectively.Conclusion. The use of SGB made it possible to verify the nonlinearly related predictors of POAF. The prospects for further research on this problem require the use of modern medical care methods that allow taking into account the individual characteristics of patients when developing predictive models.


Circulation ◽  
2021 ◽  
Author(s):  
Tiffany M. Powell-Wiley ◽  
Paul Poirier ◽  
Lora E. Burke ◽  
Jean-Pierre Després ◽  
Penny Gordon-Larsen ◽  
...  

The global obesity epidemic is well established, with increases in obesity prevalence for most countries since the 1980s. Obesity contributes directly to incident cardiovascular risk factors, including dyslipidemia, type 2 diabetes, hypertension, and sleep disorders. Obesity also leads to the development of cardiovascular disease and cardiovascular disease mortality independently of other cardiovascular risk factors. More recent data highlight abdominal obesity, as determined by waist circumference, as a cardiovascular disease risk marker that is independent of body mass index. There have also been significant advances in imaging modalities for characterizing body composition, including visceral adiposity. Studies that quantify fat depots, including ectopic fat, support excess visceral adiposity as an independent indicator of poor cardiovascular outcomes. Lifestyle modification and subsequent weight loss improve both metabolic syndrome and associated systemic inflammation and endothelial dysfunction. However, clinical trials of medical weight loss have not demonstrated a reduction in coronary artery disease rates. In contrast, prospective studies comparing patients undergoing bariatric surgery with nonsurgical patients with obesity have shown reduced coronary artery disease risk with surgery. In this statement, we summarize the impact of obesity on the diagnosis, clinical management, and outcomes of atherosclerotic cardiovascular disease, heart failure, and arrhythmias, especially sudden cardiac death and atrial fibrillation. In particular, we examine the influence of obesity on noninvasive and invasive diagnostic procedures for coronary artery disease. Moreover, we review the impact of obesity on cardiac function and outcomes related to heart failure with reduced and preserved ejection fraction. Finally, we describe the effects of lifestyle and surgical weight loss interventions on outcomes related to coronary artery disease, heart failure, and atrial fibrillation.


Sign in / Sign up

Export Citation Format

Share Document