Glycolysis Metabolites and Risk of Atrial Fibrillation and Heart Failure in the PREDIMED Trial

The increased prevalence of atrial fibrillation (AF) and heart failure (HF) highlights the need to better understand the mechanisms underlying these cardiovascular diseases (CVDs). In the present study, we aimed to evaluate the association between glycolysis-related metabolites and the risk of AF and HF in a Mediterranean population at high risk of CVD. We used two case–control studies nested within the PREDIMED trial. A total of 512 incident AF cases matched to 734 controls, and 334 incident HF cases matched to 508 controls, were included. Plasma metabolites were quantified by using hydrophilic interaction liquid chromatography coupled with high-resolution negative ion mode MS detection. Conditional logistic regression analyses were performed. The results showed no association between baseline plasma glycolysis intermediates and other related metabolites with AF. Only phosphoglycerate was associated with a higher risk of HF (OR for 1 SD increase: 1.28; 95% CI: 1.06, 1.53). The present findings do not support a role of the glycolysis pathway in the pathogenesis of AF. However, the increased risk of HF associated with phosphoglycerate requires further studies.

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Choline Metabolism and Risk of Atrial Fibrillation and Heart Failure in the PREDIMED Study

Clinical Chemistry ◽

10.1093/clinchem/hvaa224 ◽

2020 ◽

Author(s):

Christopher Papandreou ◽

Mònica Bulló ◽

Pablo Hernández-Alonso ◽

Miguel Ruiz-Canela ◽

Jun Li ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Multiple Testing ◽

Conditional Logistic Regression ◽

Case Control Studies ◽

Logistic Regression Models ◽

Liquid Chromatography Tandem Mass ◽

Nested Case Control ◽

Incident Cases ◽

Predimed Study

Abstract Background Few studies have examined the associations of trimethylamine-N-oxide (TMAO) and its precursors (choline, betaine, dimethylglycine, and L-carnitine) with the risk of atrial fibrillation (AF) and heart failure (HF). This study sought to investigate these associations. Methods Prospective associations of these metabolites with incident AF and HF were examined among participants at high cardiovascular risk in the PREDIMED study (PREvención con DIeta MEDiterránea) after follow-up for about 10 years. Two nested case-control studies were conducted, including 509 AF incident cases matched to 618 controls and 326 HF incident cases matched to 426 controls. Plasma levels of TMAO and its precursors were semi-quantitatively profiled with liquid chromatography tandem mass spectrometry. Odds ratios were estimated with multivariable conditional logistic regression models. Results After adjustment for classical risk factors and accounting for multiple testing, participants in the highest quartile vs. the lowest quartile of baseline choline and betaine levels had a higher risk of AF [OR (95% CI): 1.85 (1.30–2.63) and 1.57 (1.09–2.24), respectively]. The corresponding OR for AF for extreme quartiles of dimethylglycine was 1.39 (0.99–1.96). One SD increase in log-transformed dimethylglycine was positively associated with AF risk (OR, 1.17; 1.03–1.33). The corresponding ORs for HF for extreme quartiles of choline, betaine, and dimethylglycine were 2.51 (1.57–4.03), 1.65 (1.00–2.71) and 1.65 (1.04–2.61), respectively. TMAO and L-carnitine levels were not associated with AF or HF. Conclusions Our findings support the role of the choline metabolic pathway in the pathogenesis of AF and HF.

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Urea Cycle Metabolites and Atrial Fibrillation or Heart Failure Risk: Two Case-Control Studies in the PREDIMED Trial

Current Developments in Nutrition ◽

10.1093/cdn/nzab033_018 ◽

2021 ◽

Vol 5 (Supplement_2) ◽

pp. 18-18

Author(s):

Leticia Goni ◽

Cristina Razquin ◽

Estefania Toledo ◽

Marta Guasch-Ferre ◽

Clary B. Clish ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Dietary Intervention ◽

Urea Cycle ◽

Conditional Logistic Regression ◽

Virgin Olive Oil ◽

Case Control ◽

Control Group ◽

Ratio Test ◽

Case Control Studies

Abstract Objectives To prospectively analyze the associations between urea cycle metabolites and incident atrial fibrillation (AF) or heart failure (HF), and to evaluate the effect of a Mediterranean diet (MD) intervention on such associations. Methods We designed two nested case-control studies within the PREDIMED trial, a randomized controlled trial aimed to evaluate the effect of two MD interventions, supplemented with either extra virgin olive oil (EVOO) or nuts, on cardiovascular disease (CVD). Fasting blood samples were collected at baseline and urea cycle metabolites (arginine, citrulline, and ornithine) and methylarginines (asymmetric dimethylarginine/symmetric dimethylarginine ratio (ADMA/SDMA ratio)) were determined using liquid chromatography tandem mass spectrometry. We used conditional logistic regression models, adjusted for potential confounders, to analyze the associations between the metabolites and incident AF or HF. Potential interactions between metabolites and intervention (MD groups vs control group) were tested with the likelihood ratio test. Results The study population comprised a total of 1241 participants (509 cases) for AF case-control and 824 participants (326 cases) for HF case-control. Arginine was inversely associated with incident AF (OR per SD 0.83, 95% CI 0.73; 0.94) and HF (OR per SD 0.82, 95% CI 0.69; 0.97). Whereas ADMA/SDMA ratio was positively associated with AF (OR per SD 1.19, 95% CI 1.02; 1.41) but not with HF risk. A statistically significant interaction (P = 0.044) was found between arginine and intervention on HF risk. The lower risk of HF associated with arginine was only observed in participants of the MD groups (EVOO + nuts). Conclusions The results of the present study suggest that urea cycle metabolites, arginine and ADMA/SDMA ratio specifically, could be involved in AF and HF pathophysiology. Moreover, the dietary intervention may modify the association between arginine and HF. Funding Sources National Institutes of Health (NIH), Spanish Government Official Agency for funding biomedical research-Instituto de Salud Carlos III (ISCIII) and CIBEROBN

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Incidence of atrial fibrillation, ischaemic heart disease and heart failure in patients with diabetes

Cardiovascular Diabetology ◽

10.1186/s12933-021-01313-7 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Amy Groenewegen ◽

Victor W. Zwartkruis ◽

Betül Cekic ◽

Rudolf. A. de Boer ◽

Michiel Rienstra ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Heart Disease ◽

Ischaemic Heart Disease ◽

Incidence Rate ◽

Diabetes Status ◽

Increased Risk ◽

Patients With Diabetes ◽

Rate Ratios ◽

Age And Sex

Abstract Background Diabetes has strongly been linked to atrial fibrillation, ischaemic heart disease and heart failure. The epidemiology of these cardiovascular diseases is changing, however, due to changes in prevalence of obesity-related conditions and preventive measures. Recent population studies on incidence of atrial fibrillation, ischaemic heart disease and heart failure in patients with diabetes are needed. Methods A dynamic longitudinal cohort study was performed using primary care databases of the Julius General Practitioners’ Network. Diabetes status was determined at baseline (1 January 2014 or upon entering the cohort) and participants were followed-up for atrial fibrillation, ischaemic heart disease and heart failure until 1 February 2019. Age and sex-specific incidence and incidence rate ratios were calculated. Results Mean follow-up was 4.2 years, 12,168 patients were included in the diabetes group, and 130,143 individuals in the background group. Incidence rate ratios, adjusted for age and sex, were 1.17 (95% confidence interval 1.06–1.30) for atrial fibrillation, 1.66 (1.55–1.83) for ischaemic heart disease, and 2.36 (2.10–2.64) for heart failure. Overall, incidence rate ratios were highest in the younger age categories, converging thereafter. Conclusion There is a clear association between diabetes and incidence of the major chronic progressive heart diseases, notably with heart failure with a more than twice increased risk.

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Prognostic value of atrial fibrillation in patients with heart failure and different left ventricular ejection fraction: results of the multicenter RIF-CHF register

Russian Journal of Cardiology ◽

10.15829/1560-4071-2021-4200 ◽

2021 ◽

Vol 26 (1) ◽

pp. 4200

Author(s):

I. V. Zhirov ◽

N. V. Safronova ◽

Yu. F. Osmolovskaya ◽

S. N. Тereschenko

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Ejection Fraction ◽

Cardiovascular Mortality ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Ventricular Ejection Fraction ◽

Reduced Ejection Fraction ◽

Number Of Patients ◽

Increased Risk

Heart failure (HF) and atrial fibrillation (AF) are the most common cardiovascular conditions in clinical practice and frequently coexist. The number of patients with HF and AF is increasing every year.Aim. To analyze the effect of clinical course and management of HF and AF on the outcomes.Material and methods. The data of 1,003 patients from the first Russian register of patients with HF and AF (RIF-CHF) were analyzed. The endpoints included hospitalization due to decompensated HF, cardiovascular mortality, thromboembolic events, and major bleeding. Predictors of unfavorable outcomes were analyzed separately for patients with HF with preserved ejection fraction (AF+HFpEF), mid-range ejection fraction (AF+HFmrEF), and reduced ejection fraction (AF+HFrEF).Results. Among all patients with HF, 39% had HFpEF, 15% — HFmrEF, and 46% — HFrEF. A total of 57,2% of patients were rehospitalized due to decompensated HF within one year. Hospitalization risk was the highest for HFmrEF patients (66%, p=0,017). Reduced ejection fraction was associated with the increased risk of cardiovascular mortality (15,5% vs 5,4% in other groups, p<0,001) but not ischemic stroke (2,4% vs 3%, p=0,776). Patients with HFpEF had lower risk to achieve the composite endpoint (stroke+MI+cardiovascular death) as compared to patients with HFmrEF and HFrEF (12,7% vs 22% and 25,5%, p<0,001). Regression logistic analysis revealed that factors such as demographic characteristics, disease severity, and selected therapy had different effects on the risk of unfavorable outcomes depending on ejection fraction group.Conclusion. Each group of patients with different ejection fractions is characterized by its own pattern of factors associated with unfavorable outcomes. The demographic and clinical characteristics of patients with mid-range ejection fraction demonstrate that these patients need to be studied as a separate cohort.

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Abstract 12427: Racial Disparities in Hospitalization for Atrial Fibrillation: The Nationwide Inpatient Sample 2001-09

Circulation ◽

10.1161/circ.130.suppl_2.12427 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Gene F Kwan ◽

Danielle M Enserro ◽

Allan J Walkey ◽

Renda S Wiener ◽

Emelia J Benjamin ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Racial Differences ◽

Nationwide Inpatient Sample ◽

The United States ◽

Census Bureau ◽

Outcome Data ◽

Hospitalization Rates ◽

Increased Risk ◽

Modifiable Factors

Introduction: Racial differences in atrial fibrillation (AF) prevalence and disparities in treatment are well established; however, racial differences in outcomes among patients hospitalized with AF are less clear. We assessed racial differences in complications related to AF in a representative sample of AF hospitalization in the United States. Methods: We identified adults (≥ 40 years) with a principal diagnosis of AF and length of stay (LOS) among survivors of 1-30 days using weighted national estimates from the Nationwide Inpatient Sample. We excluded patients undergoing cardiac surgery or with missing covariates. Annual AF hospitalization rates by race were calculated using the total US population obtained from the US Census Bureau. We used multivariable regression models (covariates listed in Table) to examine associations of race with heart failure and hospital mortality among patients admitted with AF. Results: 2,244,036 AF hospitalizations (85% White, 6.7% Black, 5.0% Hispanic and 1.4% Asian/Pacific Islander) were analyzed from 2001-09. Hospitalization and outcome data by year are summarized in the table. Across all studied years, Blacks had lower AF hospitalization rates than Whites. Yet in all study years, mean LOS was longer for Blacks (range 4.2-4.6 days) than Whites (range 3.4-3.6 days). Blacks consistently had increased risk of in-hospital heart failure (Odds Ratio [OR] ranged from 1.5 [1.4, 1.7] to 1.7 [1.6, 1.9] across years) and death (OR, 1.5 [1.1, 2.1] to 2.3 [1.7, 3.0]) compared with Whites after adjustment for comorbidities. Conclusions: Although Blacks have lower incidence of hospitalizations for AF, they experience higher risk of heart failure, longer LOS, and greater mortality compared with Whites hospitalized with AF. Further public health investigation is warranted to examine the causes for disparities in outcomes among Blacks with AF and identify modifiable factors that may improve outcomes of Blacks with AF.

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Abstract P369: Polypharmacy, Adverse Outcomes, and Treatment Effectiveness in Elderly Patients With Atrial Fibrillation

Circulation ◽

10.1161/circ.141.suppl_1.p369 ◽

2020 ◽

Vol 141 (Suppl_1) ◽

Cited By ~ 1

Author(s):

Aniqa Alam ◽

Nemin Chen ◽

Pamela L Lutsey ◽

Richard MacLehose ◽

J'Neka Claxton ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Ischemic Stroke ◽

Elderly Patients ◽

Rate Control ◽

Treatment Effectiveness ◽

Adverse Outcomes ◽

Pharmacy Claims ◽

Increased Risk ◽

The Impact

Background: Polypharmacy is highly prevalent in elderly individuals with chronic conditions, including atrial fibrillation (AF). The impact of polypharmacy on adverse outcomes and on treatment effectiveness in elderly AF patients remains unaddressed. Methods: We studied 338,810 AF patients ≥75 years of age with 1,761,660 active prescriptions [mean (SD), 5.1 (3.8) per patient] enrolled in the MarketScan Medicare Supplemental database in 2007-2015. Polypharmacy was defined as ≥5 active prescriptions at AF diagnosis based on outpatient pharmacy claims. AF treatments (oral anticoagulation, rhythm and rate control) and cardiovascular endpoints (ischemic stroke, bleeding, heart failure) were defined based on inpatient, outpatient and pharmacy claims. Multivariable Cox models were used to estimate associations of polypharmacy with cardiovascular endpoints and the interaction between polypharmacy and AF treatments in relation to cardiovascular endpoints. Results: Prevalence of polypharmacy was 52% (176,007 of 338,810). Patients with polypharmacy had increased risk of major bleeding [hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.12, 1.20] and heart failure (HR 1.33, 95%CI 1.29, 1.36), but not of ischemic stroke (HR 0.96, 95%CI 0.92, 1.00), compared to those not with polypharmacy (Table). Polypharmacy status did not consistently modify the effectiveness of oral anticoagulants. However, rhythm control (vs. rate control) was more effective in preventing heart failure hospitalization in patients not with polypharmacy (HR 0.87, 95%CI 0.76, 0.99) than among those with polypharmacy (HR 0.98, 95%CI 0.91, 1.07, p for interaction = 0.02). Conclusion: Polypharmacy is frequent among elderly patients with AF, associated with adverse outcomes, and potentially affecting the effectiveness of AF treatments. Optimizing management of polypharmacy in elderly AF patients may lead to improved outcomes.

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Risk of osteoporosis and fragility fractures in asthma due to oral and inhaled corticosteroids: two population-based nested case-control studies

Thorax ◽

10.1136/thoraxjnl-2020-215664 ◽

2020 ◽

Vol 76 (1) ◽

pp. 21-28 ◽

Cited By ~ 1

Author(s):

Christos V Chalitsios ◽

Dominick E Shaw ◽

Tricia M McKeever

Keyword(s):

Cumulative Dose ◽

Inhaled Corticosteroids ◽

Conditional Logistic Regression ◽

Fragility Fractures ◽

Case Control ◽

Practice Research ◽

Clinical Practice Research Datalink ◽

Case Control Studies ◽

Increased Risk ◽

Nested Case Control

BackgroundInhaled (ICS) and oral (OCS) corticosteroids are used widely in asthma; however, the risk of osteoporosis and fragility fracture (FF) due to corticosteroids in asthma is not well-established.MethodsWe conducted two nested case-control studies using linked data from the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) databases. Using an asthma cohort, we separately identified patients with osteoporosis or FF and gender-, age- and practice-matched controls. Conditional logistic regression was used to determine the association between ICS and OCS exposure, and the risk of osteoporosis or FF. The prevalence of patients receiving at least one bisphosphonate was also calculated.ResultsThere was a dose–response relationship between both cumulative dose and number of OCS/ICS prescriptions within the previous year, and risk of osteoporosis or FF. After adjusting for confounders, people receiving more OCS prescriptions (≥9 vs 0) had a 4.50 (95% CI 3.21 to 6.11) and 2.16 (95% CI 1.56 to 3.32) increased risk of osteoporosis and FF, respectively. For ICS (≥11 vs 0) the ORs were 1.60 (95% CI 1.22 to 2.10) and 1.31 (95% CI 1.02 to 1.68). The cumulative dose had a similar impact, with those receiving more OCS or ICS being at greater risk. The prevalence of patients taking ≥9 OCS and at least one bisphosphonate prescription was just 50.6% and 48.4% for osteoporosis and FF, respectively.ConclusionsThe findings suggest that exposure to OCS or ICS is an independent risk factors for bone health in patients with asthma. Steroid administration at the lowest possible level to maintain asthma control is recommended.

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Frailty and Anticoagulant Therapy in Patients Aged 65 Years or Older with Atrial Fibrillation

Cardiovascular Innovations and Applications ◽

10.15212/cvia.2019.0562 ◽

2020 ◽

Vol 4 (3) ◽

pp. 153-161

Author(s):

Jiapeng Liu ◽

Xin Du ◽

Mengmeng Li ◽

Zhaoxu Jia ◽

Shangxin Lu ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Anticoagulant Therapy ◽

Advanced Age ◽

Elderly Adults ◽

Clinical Frailty Scale ◽

Cross Sectional ◽

Factors Associated ◽

Frailty Status ◽

Increased Risk

Background: Elderly adults with atrial fibrillation (AF) are at increased risk of frailty and thromboembolic complications. However, studies on the prevalence of frailty in AF patients and data on the relationship between frailty and the use of anticoagulants are limited.Methods: We conducted a cross-sectional study involving 500 participants. Patients aged 65 years or older were consecutively selected from the Chinese Atrial Fibrillation Registry study. The patient’s frailty status was assessed with use of the Canadian Study of Health and Aging Clinical Frailty Scale. We assessed the prevalence of and factors associated with frailty, and how frailty affects anticoagulant therapy.Results: In 500 elderly adults with AF (age 75.2±6.7 years; 51.6% female), 201 patients (40.2%) were frail. The prevalence of frailty was higher in females (P=0.002) and increased with age and CHA2DS2-VASc score (P for trend less than 0.001 for both). The factors associated with frailty were a history of heart failure (odds ratio [OR] 2.40, 95% confidence interval [CI] 1.39‐4.14), female sex (OR 2.09, 95% CI 1.27‐3.43), and advanced age (OR 1.13, 95% CI 1.09‐1.17). Frail patients were significantly less likely to have ever been prescribed anticoagulants compared with nonfrail patients (81.7 vs. 54.9%, P<0.001).Conclusions: Frailty is prevalent in elderly adults with AF, especially in females, those of advanced age, and those with heart failure. Frailty status has a significant impact on prescription of anticoagulants for high-risk AF patients.

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Impact of atrial fibrillation in patients with heart failure and reduced, mid-range or preserved ejection fraction

Heart ◽

10.1136/heartjnl-2019-316219 ◽

2020 ◽

Vol 106 (15) ◽

pp. 1160-1168 ◽

Cited By ~ 3

Author(s):

Mi Kyoung Son ◽

Jin Joo Park ◽

Nam-Kyoo Lim ◽

Won-Ho Kim ◽

Dong-Ju Choi

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Ejection Fraction ◽

Reduced Ejection Fraction ◽

Propensity Score Matching Analysis ◽

Increased Risk ◽

Multicentre Cohort Study ◽

Patients With Heart Failure ◽

Registration Number

ObjectiveTo determine the prognostic value of atrial fibrillation (AF) in patients with heart failure (HF) and preserved, mid-range or reduced ejection fraction (EF).MethodsPatients hospitalised for acute HF were enrolled in the Korean Acute Heart Failure registry, a prospective, observational, multicentre cohort study, between March 2011 and February 2014. HF types were defined as reduced EF (HFrEF, LVEF <40%), mid-range EF (HFmrEF, LVEF 40%–49%) or preserved EF (HFpEF, LVEF ≥50%).ResultsOf 5414 patients enrolled, HFrEF, HFmrEF and HFpEF were seen in 3182 (58.8%), 875 (16.2%) and 1357 (25.1%) patients, respectively. The prevalence of AF significantly increased with increasing EF (HFrEF 28.9%, HFmrEF 39.8%, HFpEF 45.2%; p for trend <0.001). During follow-up (median, 4.03 years; IQR, 1.39–5.58 years), 2806 (51.8%) patients died. The adjusted HR of AF for all-cause death was 1.06 (0.93–1.21) in the HFrEF, 1.10 (0.87–1.39) in the HFmrEF and 1.22 (1.02–1.46) in the HFpEF groups. The HR for the composite of all-cause death or readmission was 0.97 (0.87–1.07), 1.14 (0.93–1.38) and 1.03 (0.88–1.19) in the HFrEF, HFmrEF and HFpEF groups, respectively, and the HR for stroke was 1.53 (1.03–2.29), 1.04 (0.57–1.91) and 1.90 (1.13–3.20), respectively. Similar results were observed after propensity score matching analysis.ConclusionsAF was more common with increasing EF. AF was seen to be associated with increased mortality only in patients with HFpEF and was associated with an increased risk of stroke in patients with HFrEF or HFpEF.Trial registration numberNCT01389843

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Atrial fibrillation ablation in heart failure: What do we know? What can we do?

EP Europace ◽

10.1093/europace/euaa217 ◽

2020 ◽

Author(s):

Andrea Chiocchini ◽

Maria Terricabras ◽

Atul Verma

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Catheter Ablation ◽

Ejection Fraction ◽

Potential Benefit ◽

Randomized Trials ◽

Specific Patient ◽

Reduced Ejection Fraction ◽

Increased Risk ◽

Maintain Sinus Rhythm

Abstract Atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF) are two conditions that frequently impact reciprocally on each other. Patients with HFrEF have an increased risk of stroke, hospitalization and mortality after they develop AF and vice versa, AF causing deterioration of the ejection fraction is also associated to increased mortality. Catheter ablation has emerged as an effective alternative to antiarrhythmic drug treatment to maintain sinus rhythm and some randomized trials have shown a potential benefit in terms of mortality and hospitalization. This review discusses the available evidence regarding catheter ablation treatment in this specific patient group.

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