scholarly journals Mendelian Randomization analyses reveal a causal effect of thyroid function on stroke via atrial fibrillation

2019 ◽  
Author(s):  
Eirini Marouli ◽  
Aleksander Kus ◽  
M. Fabiola Del Greco ◽  
Layal Chaker ◽  
Robin Peeters ◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Thyroid Function ◽  
Mendelian Randomization ◽  
Normal Range ◽  
Standard Deviation Increase ◽  
Hashimoto’S Disease ◽  
Increased Risk ◽  
Hashimoto's Disease ◽  
Cad Risk

AbstractBackgroundSeveral observational studies suggest that variations in thyroid function, even within the normal range, are a risk factor for cardiovascular diseases, but it remains to be determined if these associations are causal or not. This study investigates whether the relationship between variation in normal range thyroid function, as well as hypothyroidism and hyperthyroidism, and the risk of stroke and Coronary Artery Disease (CAD) are causal and via which pathways these relations are mediated.Methods and FindingsWe performed Mendelian Randomization (MR) analyses for stroke and CAD using genetic instruments associated with TSH and FT4 levels respectively within either the normal range, hypothyroidism or hyperthyroidism. In detected associations, the potential mediatory role of known stroke and CAD risk factors was also examined. A one standard deviation increase in TSH was associated with a 5% decrease in the risk of stroke (OR=0.95, 95% CI= 0.91 to 0.99). Multivariable MR analyses indicated that this effect is mediated through atrial fibrillation (AF). Hashimoto’s Disease (HD) was associated with a 7% increased risk of CAD (OR=1.07, 95% CI= 1.01 to 1.13). The effect of Hashimoto’s Disease (HD) on CAD risk appears to be mediated via body mass index (BMI).ConclusionsThese results provide important new insights into the causal relationships and mediating pathways between thyroid function, stroke and CAD. Specifically, we identify normal range TSH levels and HD as potential modifiable risk factors for stroke and CAD, respectively.

scholarly journals Thyroid Function Affects the Risk of Stroke via Atrial Fibrillation: A Mendelian Randomization Study

2020 ◽  
Vol 105 (8) ◽  
pp. 2634-2641 ◽  
Author(s):  
Eirini Marouli ◽  
Aleksander Kus ◽  
Fabiola Del Greco M ◽  
Layal Chaker ◽  
Robin Peeters ◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Thyroid Function ◽  
Hashimoto’S Thyroiditis ◽  
Mendelian Randomization ◽  
Hashimoto's Thyroiditis ◽  
Normal Range ◽  
Standard Deviation Increase ◽  
Increased Risk ◽  
Cad Risk

Abstract Context Observational studies suggest that variations in normal range thyroid function are associated with cardiovascular diseases. However, it remains to be determined whether these associations are causal or not. Objective To test whether genetically determined variation in normal range thyroid function is causally associated with the risk of stroke and coronary artery disease (CAD) and investigate via which pathways these relations may be mediated. Design, Setting, and Participants Mendelian randomization analyses for stroke and CAD using genetic instruments associated with normal range thyrotropin (TSH) and free thyroxine levels or Hashimoto’s thyroiditis and Graves’ disease. The potential mediating role of known stroke and CAD risk factors was examined. Publicly available summary statistics data were used. Main Outcome Measures Stroke or CAD risk per genetically predicted increase in TSH or FT4 levels. Results A 1 standard deviation increase in TSH was associated with a 5% decrease in the risk of stroke (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.91-0.99; P = 0.008). Multivariable MR analyses indicated that this effect is mainly mediated via atrial fibrillation. MR analyses did not show a causal association between normal range thyroid function and CAD. Secondary analyses showed a causal relationship between Hashimoto’s thyroiditis and a 7% increased risk of CAD (OR, 1.07; 95% CI, 1.01-1.13; P = 0.026), which was mainly mediated via body mass index. Conclusion These results provide important new insights into the causal relationships and mediating pathways between thyroid function, stroke, and CAD. We identify variation in normal range thyroid function and Hashimoto’s thyroiditis as risk factors for stroke and CAD, respectively.

scholarly journals Prevalence, Epidemiological Characteristics, and Pharmacotherapy of Coronary Artery Disease among Patients with Atrial Fibrillation: Data from Jo-Fib Study

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
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Antiplatelet Agents ◽  
Retrospective Case ◽  
Increased Risk ◽  
Artery Disease ◽  
Epidemiological Characteristics ◽  
Cad Risk

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.

scholarly journals Greater cardiorespiratory fitness reduces incidence of atrial fibrillation: a meta-analysis

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
C Verdicchio ◽  
A Elliott ◽  
R Mahajan ◽  
D Linz ◽  
D Lau ◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Risk Factor ◽  
Cardiorespiratory Fitness ◽  
Meta Analysis ◽  
Exercise Stress ◽  
Inverse Association ◽  
Exercise Interventions ◽  
Increased Risk ◽  
Statistical Heterogeneity

Abstract Funding Acknowledgements Type of funding sources: None. Introduction  Atrial Fibrillation (AF) is the most common sustained cardiac arrhythmia affecting 1-2% of the global population, with the prevalence of AF increasing dramatically over the past two decades. Although low levels of cardiorespiratory fitness (CRF) and physical activity are predictive of cardiovascular disease onset and mortality, only recently has this emerged as a potential risk factor for AF. Purpose The aim of this meta-analysis was therefore to quantify the relationship between CRF, measured by a symptom limited exercise stress test, and incident AF. We hypothesised that there would be an inverse relationship between CRF and the incidence of AF. Methods The systematic literature review was conducted using PUBMED, MEDLINE and EMBASE databases, with seven studies meeting the inclusion criteria. A random-effects meta-analysis was then used to compare the multivariate risk estimates of the lowest CRF group from each cohort with the group of the highest CRF. Results Data from 206,925 individuals (55.8% males) was used for analysis with a mean age of 55 ± 2.5 years and a mean follow-up period of 10.3 ± 5 years. The total number of AF events across the studies was 19,913. The overall pooled risk of AF in the high-CRF group versus the low-CRF group showed a significant lower risk of incident AF in those with high-CRF (OR: 0.52, 95% CI, 0.44-0.605, p &lt; 0.001). There was evidence of statistical heterogeneity between the studies (I2 = 81%, p &lt; 0.001). AF incidence rates demonstrated an overall decline in rates across the CRF quartiles from low to high. The mean incidence rate for low-CRF was 21 ± 13.4 compared to 6.9 ± 0.7 per 1000 person-years for the high CRF group (p = 0.03). Conclusion There is an inverse association between a lower CRF and an increased risk of AF, with a higher level of CRF protective against AF. This study highlights that low-CRF may be an additional risk factor for AF along with already other established lifestyle-based risk factors such as obesity and hypertension. Exercise interventions should be promoted as a primary prevention strategy in those at risk of developing AF with known risk factors. Future studies are warranted to identify the mechanism(s) through which improved CRF confers a reduction in AF incidence. Abstract Figure. AF risk between high and low-CRF

Abstract MP74: Long Term Risk-Factor Profiles for Chronic Kidney Disease in the Framingham Heart Study

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Gearoid M McMahon ◽  
Sarah R Preis ◽  
Shih-Jen Hwang ◽  
Caroline S Fox
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Risk Factor ◽  
Kidney Disease ◽  
Framingham Heart Study ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Standard Deviation Increase ◽  
Heart Study ◽  
Increased Risk

Background: Chronic Kidney Disease (CKD) is an important public health issue and is associated with an increased risk of cardiovascular disease. Risk factors for CKD are well established, but most are typically assessed at or near the time of CKD diagnosis. Our hypothesis was that risk factors for CKD are present earlier in the course of the disease. We compared the prevalence of risk factors between CKD cases and controls at time points up to 30 years prior to CKD diagnosis. Methods: Participants were drawn from the Framingham Heart Study Offspring cohort. CKD was defined as an estimated glomerular filtration rate of ≤60ml/min/1.73m2. Incident CKD cases occurring at examination cycles 6, 7, and 8 were age- and sex-matched 1:2 to controls. Risk factors including systolic blood pressure (SBP), hypertension, lipids, diabetes, smoking status, body mass index (BMI) and dipstick proteinuria were measured at the time of CKD diagnosis and 10, 20 and 30 years prior. Logistic regression models, adjusted for age, sex, and time period, were constructed to compare risk factor profiles at each time point between cases and controls Results: During follow-up, 441 new cases of CKD were identified and these were matched to 882 controls (mean age 69.2 years, 52.4% women). Up to 30 years prior to CKD diagnosis, those who ultimately developed CKD were more likely to have hypertension (OR 1.74, CI 1.21-2.49), be obese (OR 1.74, CI 1.15-2.63) and have higher triglycerides (OR 1.43, CI 1.12-1.84, p=0.005 per 1 standard deviation increase). Each 10mmHg increase in SBP was associated with an OR of 1.22 for future CKD (95% CI 1.10-1.35) Additionally, cases were more likely to have diabetes (OR 2.90, CI 1.59-5.29) and be on antihypertensive therapy (OR 1.65, CI 1.14-2.40, p=0.009) up to 20 years prior to diagnosis. Increasing HDLc was associated with a lower risk of CKD (OR 0.84, CI 0.81-0.97 per 10mg/dl). Conclusions: As many as 30 years prior to diagnosis, risk factors for CKD are identifiable. In particular, modifiable risk factors such as obesity, hypertension and dyslipidemia are present early in the course of the disease. These findings demonstrate the importance of early identification of risk factors in patients at risk of CKD through a life-course approach.

Abstract 47: Atrial Fibrillation is Associated With Increased Risk of Incident Venous Thromboembolism: The Atherosclerosis Risk in Communities Study

Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Pamela L Lutsey ◽  
Faye L Norby ◽  
Alvaro Alonso ◽  
Mary Cushman ◽  
Lin Y Chen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Venous Thromboembolism ◽  
Incidence Rate ◽  
Case Reports ◽  
Time Dependent ◽  
Atherosclerosis Risk In Communities ◽  
Increased Risk ◽  
Atherosclerosis Risk ◽  
Shared Risk

Background: It is well-established that atrial fibrillation (AF) is associated with thrombus formation in the left atrium, which can lead to ischemic stroke. Case reports, autopsies, and transesophageal echo data have indicated that clot formation also occurs in the right atrium (i.e. right-side intracardiac thrombosis) of AF patients, which could lead to pulmonary embolism (PE). However, it is unclear whether this occurrence is common. Objective: Test the hypotheses that individuals with incident AF are at elevated risk of developing venous thromboembolism (VTE), and that the association will be stronger for those presenting with PE alone versus PE and deep vein thrombosis (DVT) or DVT alone. Methods: A total of 15,205 Atherosclerosis Risk in Communities (ARIC) study participants, aged 45-64 years, were followed from baseline (1987-1989) to 2011 for incidence of AF and VTE (median follow-up 19.8 years). Incident AF and VTE events were identified via active surveillance and defined by relevant hospital discharge ICD codes. VTE events were validated by medical record review. Multivariable-adjusted Cox proportional hazards regression models were used, with AF modeled as a time-dependent covariate. We also evaluated separately risk of PE without evidence of DVT, DVT without PE, and events presenting with both PE and DVT. Results: At baseline participants were on average 54 years old, 55% female and 26% black. In the absence of AF there were 678 VTE events, for an incidence rate of 2.6 per 1000 person-years. After an AF diagnosis there were 77 events, with an incidence rate of 7.1 per 1000 person-years. In multivariable-adjusted models, having AF (versus no AF) was associated with a greater risk of incident VTE; the HR (95% CI) was 2.10 (1.65-2.68) after adjustment for demographics, 1.82 (1.42-2.32) additionally accounting for numerous AF and VTE risk factors, and 1.97 (1.53-2.53) after further adjusting for time-dependent anticoagulant use. When we restricted to PE events without evidence of DVT there were 188 events in total, of which 19 occurred following a diagnosis of AF. The HR for AF (versus no AF) was 1.53 (0.92-2.56) in fully adjusted models. For DVT alone there were 384 events in total, of which 48 occurred after AF diagnosis; the HR for AF was 2.43 (1.77-3.33). Among the 116 events presenting with both DVT and PE, 10 occurred after AF diagnosis, and the HR for AF was 1.36 (0.67-2.75). Conclusions: Diagnosis with AF was associated with a nearly 2-fold increased risk of incident VTE. The association was not stronger when isolated to those with PE without DVT, suggesting that higher risk of VTE among AF patients may be due to either the coagulation abnormalities that accompany AF, or shared risk factors that were not fully accounted for in this analysis.

scholarly journals Prevalence and impact of frailty in patients with atrial fibrillation: a systematic review and meta-analysis

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
M Proietti ◽  
G.F Romiti ◽  
V Raparelli ◽  
I Diemberger ◽  
G Boriani ◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Systematic Review ◽  
Meta Analysis ◽  
Frailty Index ◽  
Prevalence Odds Ratio ◽  
Frail Patients ◽  
Pooled Prevalence ◽  
Increased Risk ◽  
Inconsistency Index

Abstract Background Frailty is a clinical syndrome characterized by a reduced physiologic function, increased vulnerability to stressors, and an increased risk of adverse outcomes. Patients with Atrial Fibrillation (AF) are often burdened with a high number of comorbidities and prone to frailty. The prevalence of frailty, its management and association with major outcomes in patients with AF are still unclear. Purpose To estimate the pooled prevalence of frailty in patients with AF, as well as its association with AF-related risk factors and comorbidities, oral anticoagulants (OAC) prescription, and major outcomes. Methods We systematically searched PubMed and EMBASE, from inception to 31st January 2021, for studies reporting the prevalence of frailty (irrespective of the tool used for assessment). Pooled prevalence, odds ratio (OR), and 95% Confidence Intervals (CI) were computed using random-effect models; heterogeneity was assessed through the inconsistency index (I2). This study was registered in PROSPERO: CRD42021235854. Results A total of 1,116 studies were retrieved from the literature search, and 31 were finally included in the systematic review (n=842,521 patients). The frailty pooled prevalence was 39.6% (95% CI=29.2%-51.0%, I2=100%; Figure 1). Significant subgroup differences were observed according to geographical location (higher prevalence found in European-based cohorts; p=0.003) and type of tool used for the assessment (higher prevalence in studies using the Clinical Frailty Scale and Tilburg Frailty Index tools; p&lt;0.001). Meta-regressions showed that study-level mean age and prevalence of hypertension, diabetes, and history of stroke were directly associated with frailty prevalence. Frailty was significantly associated with a 29% reduced probability of OAC prescription in observational studies (OR=0.71, 95% CI=0.62–0.81). Frail patients with AF were at higher risk of all-cause death (OR=4.12, 95% CI=3.15–5.41), ischemic stroke (OR=1.55, 95% CI=1.01–2.38), and bleeding (OR=1.55, 95% CI=1.12–2.14), compared to non-frail patients with AF. Conclusions In this systematic review and meta-analysis analysis, the prevalence of frailty was high in patients with AF, and associated with study-level mean age and prevalence of several stroke risk factors. Frailty may influence the management of patients, and worsening the prognosis for all major AF-related outcomes. FUNDunding Acknowledgement Type of funding sources: None. Prevalence of Frailty among AF patients

scholarly journals Evaluating the effects of alcohol and tobacco use on cardiovascular disease using multivariable Mendelian randomization

2019 ◽  
Author(s):  
Daniel B. Rosoff ◽  
George Davey Smith ◽  
Nehal Mehta ◽  
Toni-Kim Clarke ◽  
Falk W. Lohoff
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Alcohol Use ◽  
Tobacco Use ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Density Lipoprotein ◽  
Genome Wide Association Studies ◽  
Cvd Risk ◽  
Increased Risk

ABSTRACTAlcohol and tobacco use, two major modifiable risk factors for cardiovascular disease (CVD), are often consumed together. Using large publicly available genome-wide association studies (results from > 940,000 participants), we conducted two-sample multivariable Mendelian randomization (MR) to simultaneously assess the independent effects of alcohol and tobacco use on CVD risk factors and events. We found genetic instruments associated with increased alcohol use, controlling for tobacco use, associated with increased high-density-lipoprotein-cholesterol (HDL-C), decreased triglycerides, but not with coronary heart disease (CHD), myocardial infarction (MI), nor stroke; and instruments for increased tobacco use, controlling for alcohol use, associated with decreased HDL-C, increased triglycerides, and increased risk of CHD and MI. Exploratory analysis found associations with HDL-C, LDL-C, and intermediate-density-lipoprotein metabolites. Consistency of results across complementary methods accommodating different MR assumptions strengthened causal inference, providing strong genetic evidence for the causal effects of modifiable lifestyle risk factors on CVD risk.

scholarly journals Metabolic and lifestyle factors in relation to senile cataract: a Mendelian randomization study

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Shuai Yuan ◽  
Alicja Wolk ◽  
Susanna C. Larsson
Keyword(s):  
Standard Deviation ◽  
Odds Ratio ◽  
Mendelian Randomization ◽  
Coffee Consumption ◽  
Smoking Initiation ◽  
Lifestyle Factors ◽  
Senile Cataract ◽  
Nucleotide Polymorphisms ◽  
Standard Deviation Increase ◽  
Increased Risk

AbstractWe conducted a Mendelian randomization study to determine the associations of body mass index (BMI), type 2 diabetes (T2D), systolic blood pressure (SBP), coffee and alcohol consumption and smoking initiation with senile cataract. Independent single nucleotide polymorphisms associated with the metabolic and lifestyle factors at the p < 5 × 10–8 were selected as instrument variables. Summary-level data for senile cataract were obtained from the FinnGen consortium (20,157 cases and 154,905 non-cases) and UK Biobank study (6332 cases and 354,862 non-cases). Higher genetically predicted BMI and SBP and genetic predisposition to T2D and smoking initiation were associated with an increased risk of senile cataract. The combined odds ratios were 1.19 (95% confidence interval (CI) 1.09–1.29; p < 0.001) per one standard deviation increase in BMI (~ 4.8 kg/m2), 1.13 (95% CI 1.04–1.23; p = 0.004) per 10 mmHg increase in SBP, 1.06 (95% CI 1.03–1.09; p < 0.001) per one unit increase in log-transformed odds ratio of T2D, and 1.19 (95% CI 1.10–1.29; p < 0.001) per one standard deviation increase in prevalence of smoking initiation. Genetically predicted coffee consumption showed a suggestive association with senile cataract (odds ratio per 50% increase, 1.18, 95% CI 1.00–1.40; p = 0.050). This study suggests causal roles of obesity, T2D, SBP and smoking in senile cataract.

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