scholarly journals High Plasma Glutamate and a Low Glutamine-to-Glutamate Ratio Are Associated with Increased Risk of Heart Failure but Not Atrial Fibrillation in the Prevención con Dieta Mediterránea (PREDIMED) Study

2020 ◽  
Vol 150 (11) ◽  
pp. 2882-2889 ◽  
Author(s):  
Christopher Papandreou ◽  
Pablo Hernández-Alonso ◽  
Mònica Bulló ◽  
Miguel Ruiz-Canela ◽  
Jun Li ◽  
...  

ABSTRACT Background Although the association between glutamate and glutamine in relation to cardiometabolic disorders has been evaluated, the role of these metabolites in the development of atrial fibrillation (AF) and heart failure (HF) remains unknown. Objectives We examined associations of glutamate, glutamine, and the glutamine-to-glutamate ratio with AF and HF incidence in a Mediterranean population at high cardiovascular disease (CVD) risk. Methods The present study used 2 nested case-control studies within the PREDIMED (Prevención con Dieta Mediterránea) study. During ∼10 y of follow-up, there were 509 AF incident cases matched to 618 controls and 326 HF incident cases matched to 426 controls. Plasma concentrations of glutamate and glutamine were semiquantitatively profiled with LC–tandem MS. ORs were estimated with multivariable conditional logistic regression models. Results In fully adjusted models, per 1-SD increment, glutamate was associated with a 29% (95% CI: 1.08, 1.54) increased risk of HF and glutamine-to-glutamate ratio with a 20% (95% CI: 0.67, 0.94) decreased risk. Glutamine-to-glutamate ratio was also inversely associated with HF risk (OR per 1-SD increment: 0.80; 95% CI: 0.67, 0.94) when comparing extreme quartiles. Higher glutamate concentrations were associated with a worse cardiometabolic risk profile, whereas a higher glutamine-to-glutamate ratio was associated with a better cardiometabolic risk profile. No associations between the concentrations of these metabolites and AF were observed. Conclusions Our findings suggest that high plasma glutamate concentrations possibly resulting from alterations in the glutamate-glutamine cycle may contribute to the development of HF in Mediterranean individuals at high CVD risk. This trial was registered at www.isrctn.com as ISRCTN35739639.

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Amy Groenewegen ◽  
Victor W. Zwartkruis ◽  
Betül Cekic ◽  
Rudolf. A. de Boer ◽  
Michiel Rienstra ◽  
...  

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.


2021 ◽  
Vol 26 (1) ◽  
pp. 4200
Author(s):  
I. V. Zhirov ◽  
N. V. Safronova ◽  
Yu. F. Osmolovskaya ◽  
S. N. Тereschenko

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.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Gene F Kwan ◽  
Danielle M Enserro ◽  
Allan J Walkey ◽  
Renda S Wiener ◽  
Emelia J Benjamin ◽  
...  

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.


Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Mariana Lazo ◽  
Lu Shen ◽  
Marc K Halushka ◽  
Brad C Astor ◽  
Casey M Rebholz ◽  
...  

Introduction: Myocardial fibrosis is a key feature of heart failure, and its mechanisms are incompletely understood. It has been postulated that advanced glycation end-products (AGEs) form an etiologic link between diabetes and its vascular complications. Binding of AGEs to the cellular receptor for AGEs (RAGE) induces a state of increased oxidative stress, inflammation and fibrosis. Circulating soluble RAGEs (sRAGE) compete with cellular RAGE for the binding of AGEs which reduces the activation of the AGE-RAGE mediated pro-inflammatory and pro-fibrotic signaling pathways. We hypothesize that low levels of sRAGE will be associated with higher risk of heart failure. Methods: We conducted a prospective analysis of a random subsample of 1,157 participants from the ARIC Study who attended visit 2 (1990-1992). We included participants without a history of heart disease or heart failure, and with measured plasma sRAGE levels. Incident heart failure was defined as death from health failure or hospitalization due to heart failure. Results: In this community-based population (mean age 63 years, 60% women, 78% white), there were 132 incident cases of heart failure during approximately 20 years of follow up. Lower levels of sRAGE were significantly and independently associated with an increased risk of heart failure (Table). Analyses stratified by diabetes status at baseline showed that the risk of heart failure among those in the lowest quartile, compared to those in the upper quartile, was consistent but stronger among persons with diabetes compared to those without diabetes with HR=5.31 (95%CI 1.05-26.76) versus HR=2.50 (95%CI, 1.22-5.13), respectively. We did not observe any significant interactions by race or obesity status. Conclusions: Lower circulating levels of sRAGE are independently associated with the development of heart failure in older adults. These results highlight the pathophysiological role of the AGE-RAGE-sRAGE axis even among persons without diabetes.


Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Aniqa Alam ◽  
Nemin Chen ◽  
Pamela L Lutsey ◽  
Richard MacLehose ◽  
J'Neka Claxton ◽  
...  

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.


2020 ◽  
Author(s):  
Christopher Papandreou ◽  
Mònica Bulló ◽  
Pablo Hernández-Alonso ◽  
Miguel Ruiz-Canela ◽  
Jun Li ◽  
...  

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.


2020 ◽  
Vol 4 (3) ◽  
pp. 153-161
Author(s):  
Jiapeng Liu ◽  
Xin Du ◽  
Mengmeng Li ◽  
Zhaoxu Jia ◽  
Shangxin Lu ◽  
...  

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.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
C Ergatoudes ◽  
P.-O Hansson ◽  
K Svardsudd ◽  
A Rosengren ◽  
E Thunstrom ◽  
...  

Abstract Background Several characteristics or conditions are associated with increased risk for heart failure (HF). In recent years we have witnessed gradually improved cardiovascular prevention and treatment. However, how the risk profile of HF has changed during the last decades remains inadequately studied. Purpose To compare risk factors for heart failure in two generations of middle-aged men from the general population born 30 years apart. Methods Two cohorts of randomly selected men born in 1913 (n=855) and in 1943 (n=798) and resident in Gothenburg, Sweden were first examined at 50 years of age in 1963 and 1993, respectively, and followed longitudinally over 21 years until age 71. Data about medical history, concomitant diseases and general health were collected by questionnaires, repeated medical examinations and review of individual medical records. The outcome was defined as hospitalization with HF as a discharge diagnosis or HF reported on the death certificate. Cox-regression analysis was used to examine the impact of baseline characteristics and time-updated atrial fibrillation (AF), ischemic heart disease (IHD) and diabetes mellitus (DM) on the outcome. Furthermore the incidence of HF overall between the two cohorts was also compared. Significance was defined as p<0.05 for all two-sided tests, except for interaction terms where p<0.10 was applied. Results During a 21-year follow up, 80 men born in 1913 (9.4%) and 36 men born in 1943 (4.6%) developed HF. Men born in 1943 had a 52% lower risk for HF (adjusted HR 0.48 95% CI 0.29–0.77 p=0.003) compared to men born in 1913. Baseline characteristics associated with higher HF risk in both cohorts were higher body mass index (BMI) and the use of antihypertensive medication. Higher heart rate was associated with an increased risk only in men born 1913 whereas higher systolic blood pressure (SBP), smoking, higher glucose levels and higher total cholesterol levels were associated with higher risk in men born 1943. Onset of AF, IHD or DM was associated with higher HF risk in both cohorts. Multivariable models using stepwise regression showed that AF, IHD, higher BMI (continuous variable), use of antihypertensive medication and higher heart rate (piecewise linear) were independent predictors for HF in men born in 1913 whereas AF, higher glucose levels, IHD and higher SBP (piecewise linear) in men born in 1943. Finally, interaction analyses showed that in comparison with those born in 1913, the relative importance as risk factors for HF among those born in 1943 has decreased for AF whereas it has increased for systolic blood pressure and cholesterol. Of note, impact of IHD as risk factor decreased numerically, and that of physical activity increased, but for both without reaching statistical significance. Cox proportional hazard analysis Conclusions The incidence of HF in middle aged men living in Gothenburg has decreased during the last decades, and in the meantime risk profile for incident HF has also changed.


Heart ◽  
2020 ◽  
Vol 106 (15) ◽  
pp. 1160-1168 ◽  
Author(s):  
Mi Kyoung Son ◽  
Jin Joo Park ◽  
Nam-Kyoo Lim ◽  
Won-Ho Kim ◽  
Dong-Ju Choi

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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