Association between oxidative stress and atrial fibrillation.
ABSTRACT: Oxidative stress (OS) may be a key mechanism underlying the development of atrial fibrillation (AF) in experimental studies, but data in humans remain limited.Systemic OS can be estimated by measurements of circulating levels of the aminothiols including glutathione, cysteine, and their oxidized products. We tested the hypothesis that the redox potentials of glutathione (EhGSH) and cysteine will be associated with prevalent and incident AF.Plasma levels of aminothiols were measured in 1439 patients undergoing coronary angiography, of whom 148 (10.3%) had a diagnosis of AF. After a median follow-up of 6.3 years, 104 of 917 patients (11.5%) developed incident AF. Multivariate logistic regression and Cox regression models were used to determine whether OS markers were independent predictors of prevalent and incident AF after adjustment for traditional risk factors, heart failure, coronary artery disease, and high-sensitivity C-reactive protein level.For each 10% increase in EhGSH, the odds of prevalent AF was 30% higher (odds ratio [OR] 1.3; 95% confidence interval [CI] 1.1-1.7; P = .02) and 90% higher (OR 1.9; 95% CI 1.3-2.7; P = .004) when the median was used as a cutoff. The EhGSH level above the median was more predictive of chronic AF (OR 4.0; 95% CI 1.3-12.9; P = .01) than of paroxysmal AF (OR 1.7; 95% CI 1.1-2.7; P = .03). Each 10% increase in EhGSH level was associated with a 40% increase in the risk of incident AF (hazard ratio 1.4; 95% CI 1.1-1.7; P = .01).Increased OS measured by the redox potentials of glutathione is associated with prevalent and incident AF. Therapies that modulate OS need to be investigated to treat and prevent AF.
Project description:Atrial fibrillation (AF) is likely secondary to multiple different pathophysiological mechanisms that are increasingly but incompletely understood. Motivated by the hypothesis that 3 previously described electrocardiographic predictors of AF identify distinct AF mechanisms, we sought to determine if these electrocardiographic findings independently predict incident disease. Among Cardiovascular Health Study participants without prevalent AF, we determined whether left anterior fascicular block (LAFB), a prolonged QTC, and atrial premature complexes (APCs) each predicted AF after adjusting for each other. We then calculated the attributable risk in the exposed for each electrocardiographic marker. LAFB and QTC intervals were assessed on baseline 12-lead electrocardiogram (n = 4,696). APC count was determined using 24-hour Holter recordings obtained in a random subsample (n = 1,234). After adjusting for potential confounders and each electrocardiographic marker, LAFB (hazard ratio [HR] 2.1, 95% confidence interval [CI] 1.1 to 3.9, p = 0.023), a prolonged QTC (HR 2.5, 95% CI 1.4 to 4.3, p = 0.002), and every doubling of APC count (HR 1.2, 95% CI 1.1 to 1.3, p <0.001) each remained independently predictive of incident AF. The attributable risk of AF in the exposed was 35% (95% CI 13% to 52%) for LAFB, 25% (95% CI 0.6% to 44%) for a prolonged QTC, and 34% (95% CI 26% to 42%) for APCs. In conclusion, in a community-based cohort, 3 previously established electrocardiogram-derived AF predictors were each independently associated with incident AF, suggesting that they may represent distinct mechanisms underlying the disease.
Project description:Background:Little is known about the cardiovascular risks of incident atrial fibrillation/flutter (AF) in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD). Methods:We studied older US patients who newly initiated HD for ESRD (2006-11) and who had not previously been diagnosed with AF, stroke, myocardial infarction (MI) or hip fracture. We used Cox regression with AF as a time-varying covariate, adjusted for socio-demographic characteristics and comorbidities to estimate hazard ratios [HRs (95% confidence intervals)] for the events of ischemic stroke, MI and death. Hip fracture served as a negative control outcome. Results:We identified 85 377 older patients (mean age: 76.5 years) who initiated HD; of these, 14.3% were subsequently diagnosed with AF (14.9% thereof as primary diagnosis) and 49.8% died during follow-up. Incident AF was associated with nine times higher adjusted mortality during the first 30 days [9.2 (8.8-9.6)], 5-fold higher mortality between 31 and 90 days [4.6 (4.3-4.8)] and double the mortality beyond 90 days from first AF diagnosis [2.2 (2.1-2.3)]. Incident AF was similarly associated with higher adjusted risk of ischemic stroke: 2.1 (1.6-2.7) during the first 30 days, 2.5 (2.0-3.0) between 31 and 90 days and 1.5 (1.3-1.7) beyond 90 days. Similar findings were obtained for MI. However, the risk of hip fracture was only marginally increased following AF diagnosis [≤30 days: 1.1 (0.7-1.6); 31-90 days: 1.4 (1.0-1.8); >90 days: 1.2 (1.1-1.4)]. All associations were attenuated and the association with hip fracture was null when incident AF was defined by a primary diagnosis code. Conclusions:AF was strongly associated with increased risks of ischemic stroke, MI and death, with risks highest soon after AF diagnosis but extending beyond 90 days.
Project description:BACKGROUND:Atrial fibrillation (AF) is associated with increased all-cause mortality in the general population. However, the impact of AF on the in-hospital outcomes of acute myocarditis (AM) patients is not well characterized. METHODS:Patients (age ≥ 18 years) with a primary diagnosis of AM in the National Inpatient Sample from 2007 to 2014 were included, using the ICD-9-CM diagnostic codes. We compared the in-hospital outcomes between the AF group and propensity score-matched control group without AF. RESULTS:AF was reported in 602 (9%) of the AM patients. Compared to those without AF, AM patients with AF experienced higher in-hospital mortality (odds ratio [OR] 1.7, 95% confidence interval [CI] 1.1-2.7, P = 0.02). AF was associated with higher risk of cardiogenic shock (OR 1.9, 95% CI 1.3-2.8, P < 0.001), cardiac tamponade (OR 5.6, 95% CI 1.2-25.3, P = 0.002) and acute kidney injury (OR 1.6, 95% CI 1.1-2.1, P = 0.02). Furthermore, patients with AF were more likely to have non-routine hospital discharge (31.6% vs 38.4% P = 0.02), longer length of stay and higher cost of hospitalization. CONCLUSIONS:AF was associated with increased risk of in-hospital mortality and complications in patients admitted to the hospital with acute myocarditis.
Project description:BACKGROUND:Little is known about how incident atrial fibrillation (AF) affects the clinical outcomes in chronic kidney disease (CKD) patients and whether there is a different influence between pre-existing and incident AF. METHODS:Incident CKD patients from 2000 to 2013 were retrieved from the National Health Insurance Research Database (NHIRD) of Taiwan and they were classified as non-AF (n = 15,251), prevalent AF (n = 612), and incident AF (n = 588). The outcomes of interest were end-stage renal disease (ESRD) requiring dialysis, all-cause mortality, cardiovascular (CV) mortality, acute myocardial infarction (AMI), stroke or systemic thromboembolism. RESULTS:Compared with CKD patients without AF, those with prevalent or incident AF were associated with higher adjusted rates of ESRD (hazard ratio (HR), 1.40; 95% confidence interval (CI), 1.32-1.48; HR, 2.91; 95% CI, 2.74-3.09, respectively), stroke or systemic thromboembolism (HR, 1.89; 95% CI, 1.77-2.03; HR, 1.67; 95% CI, 1.54-1.81, respectively), AMI (HR, 1.24; 95% CI, 1.09-1.41; HR, 1.99; 95% CI, 1.75-2.27, respectively), all-cause mortality (HR, 1.64; 95% CI, 1.56-1.72; HR, 2.17; 95% CI, 2.06-2.29, respectively), and CV mortality (HR, 2.95; 95% CI, 2.62-3.32; HR, 4.61; 95% CI, 4.09-5.20, respectively). Intriguingly, CKD patients with prevalent AF were associated with lower adjusted rates of ESRD, AMI, all-cause mortality, and CV mortality compared with those with incident AF. CONCLUSION:Both incident and prevalent AF were independently associated with greater risks of AMI, all-cause mortality, CV mortality, ESRD, and stroke or systemic thromboembolism. Our findings are novel in that, compared with prevalent AF, incident AF possessed an even higher risk of some clinical consequences, including ESRD, all-cause mortality, CV mortality, and AMI.
Project description:The effects of white matter hyperintensity volume and subclinical brain infarcts on the risk of incident stroke, its ischemic subtypes, and mortality require further study in diverse samples.Stroke-free participants in the Northern Manhattan Study underwent magnetic resonance imaging (N=1287; mean age 71±9 years, 60% women, 15% non-Hispanic white, 17% non-Hispanic black, 68% Hispanic) and were followed for a median of 8 years (interquartile range: 6-9 years). Cox models estimated proportional hazards of incident stroke of all types, ischemic stroke (and its subtypes), and mortality and stratified by race/ethnicity. In total 72 participants (6%) had incident strokes and 244 died (19%). In fully adjusted models, those with larger white matter hyperintensity volume had greater risk of all stroke types (hazard ratio [HR]: 1.4; 95% CI, 1.1-1.9), ischemic stroke (HR: 1.3; 95% CI, 1.0-1.8), and cryptogenic stroke (HR: 2.2; 95% CI, 1.1-4.4). White and black but not Hispanic participants had increased stroke risk (P<0.05 for heterogeneity for all and ischemic stroke). Those with subclinical brain infarct had greater risk for all stroke types (HR: 1.9; 95% CI, 1.1-3.3), ischemic stroke (HR: 2.2; 95% CI, 1.3-3.8), lacunar (HR: 4.0; 95% CI, 1.3-12.3), and cryptogenic stroke (HR: 3.6; 95% CI, 1.0-12.7), without significant heterogeneity across race/ethnic groups. Greater white matter hyperintensity volume increased both vascular (HR: 1.3; 95% CI, 1.1-1.7) and nonvascular (HR: 1.2; 95% CI, 1.0-1.5) mortality among Hispanic and white but not black participants (P=0.040 for heterogeneity). Subclinical brain infarct was associated with increased vascular mortality among Hispanic participants only (HR: 2.9; 95% CI, 1.4-5.8).In this urban US sample, subclinical cerebrovascular lesions increased the risk of clinical stroke and vascular mortality and varied by race/ethnicity and lesion type.
Project description:OBJECTIVE:To describe the relationship between circulating resistin levels and cardiovascular diseases (CVD) and all-cause death in a multi-ethnic cohort. METHODS AND RESULTS:We studied 1913 participants from the Multi-Ethnic Study of Atherosclerosis with measurements of plasma resistin levels. Absolute proportions experiencing new-onset atrial fibrillation (AF), atherosclerotic CVD (myocardial infarction, angina, resuscitated cardiac arrest, stroke), heart failure (HF), and all-cause death were calculated for each quartile of resistin. We used adjusted Cox proportional regression modeling resistin as a continuous variable per standard deviation of log-transformed resistin and secondarily as a categorical variable using resistin quartiles. Results were stratified by sex and race/ethnicity. The mean age of the population was 64.5 ± 10 years with half being female and a median resistin concentration of 15.1 ng/mL (11.9-19.1). Mean follow-up time was 7.2 ± 1.8 years. There was a graded increase in the occurrence of all outcomes across increasing quartiles of resistin. Modeled as a continuous variable, after adjustment for anthropomorphic measures, traditional risk factors, markers of inflammation, and other adipokines, significant associations were noted for HF (HR 1.4, CI 1.0-2.0), hard and all CVD (HR 1.3, 1.1-1.7 and 1.3, 1.1-1.6, respectively), and CHD (HR 1.31, 1.0-1.6), but not for AF or death. Significant interaction terms were noted between resistin and race, with Hispanic race/ethnicity showing the strongest relationship between resistin and outcomes. CONCLUSIONS:In an ethnically diverse population without known CVD at baseline, there was a strong, independent association between higher resistin levels and incident CVD, CHD and HF.
Project description:Atrial fibrillation (AF) is the most common sustained arrhythmia in the elderly, and shares several risk factors with diastolic dysfunction, including hypertension and advanced age. The purpose of this study is to examine diastolic dysfunction as a risk for incident AF.We examined the association of echocardiographic parameters of diastolic function with the incidence of AF in 4480 participants enrolled in the Cardiovascular Health Study, an ongoing cohort of community-dwelling older adults from four US communities. Participants underwent baseline echocardiography in 1989-1990 and were followed for incident AF on routine follow-up and hospitalizations. After 50 941 person-years of follow-up (median follow-up time 12.1 years), 1219 participants developed AF. In multivariable-adjusted age-stratified Cox models, diastolic echocardiographic parameters were significantly associated with the risk of incident AF. The most significant parameters were the Doppler peak E-wave velocity and left atrial diameter, which demonstrated a positive nonlinear association [HR 1.5 (CI 1.3-1.9) and HR 1.7 (CI 1.4-2.1) for highest vs. lowest quintile, respectively], and Doppler A-wave velocity time integral, which displayed a U-shaped relationship with the risk of AF [HR 0.7 (CI 0.6-0.9) for middle vs. lowest quintile]. Each diastolic parameter displayed a significant association with adjusted NT-proBNP levels, although the nature of the association did not entirely parallel the risk of AF. Further cluster analysis revealed unique patterns of diastolic function that may identify patients at risk for AF.In a community-based population of older adults, echocardiographic measures of diastolic function are significantly associated with an increased risk of AF.
Project description:Prior studies suggested an association between bisphosphonates and atrial fibrillation/flutter (AF) in women. This relationship in men, including those with sleep-disordered breathing (SDB), remains unclear. This study evaluated the relationship between bisphosphonate use and prevalent (nocturnal) and incident (clinically relevant) AF in a population of community-dwelling older men.A total of 2,911 male participants (mean age, 76 years) of the prospective observational Osteoporotic Fractures in Men Study sleep cohort with overnight in-home polysomnography (PSG) constituted the analytic cohort. Nocturnal AF from ECGs during PSG and incident AF events were centrally adjudicated. The association of bisphosphonate use and AF was examined using multivariable-adjusted logistic regression for prevalent AF and Cox proportional hazards regression for incident AF.A total of 123 (4.2%) men were current bisphosphonate users. Prevalent nocturnal AF was present in 138 participants (4.6%). After multivariable adjustment, there was a significant association between current bisphosphonate use and prevalent AF (OR, 2.33; 95% CI, 1.13-4.79). In the subset of men with moderate to severe SDB, this association was even more pronounced (OR, 3.22; 95% CI, 1.29-8.03). However, the multivariable-adjusted relationship between bisphosphonate use and incident AF did not reach statistical significance (adjusted hazard ratio, 1.53; 95% CI, 0.96-2.45).These results support an association between bisphosphonate use and prevalent nocturnal AF in community-dwelling older men. The data further suggest that those with moderate to severe SDB may be a particularly vulnerable group susceptible to bisphosphonate-related AF. Similar associations were not seen for bisphosphonate use and clinically relevant incident AF.
Project description:Background and Purpose- Atrial fibrillation (AF) is associated with dementia independent of clinical stroke. The mechanisms underlying this association remain unclear. In a community-based cohort, the ARIC study (Atherosclerosis Risk in Communities), we evaluated (1) the longitudinal association of incident AF and (2) the cross-sectional association of prevalent AF with brain magnetic resonance imaging (MRI) abnormalities. Methods- The longitudinal analysis included 963 participants (mean age, 73±4.4 years; 62% women; 51% black) without prevalent stroke or AF who underwent a brain MRI in 1993 to 1995 and a second MRI in 2004 to 2006 (mean, 10.6±0.8 years). Outcomes included subclinical cerebral infarctions, sulcal size, ventricular size, and, for the cross-sectional analysis, white matter hyperintensity volume and total brain volume. Results- In the longitudinal analysis, 29 (3.0%) participants developed AF after the first brain MRI. Those who developed AF had higher odds of increase in subclinical cerebral infarctions (odds ratio [OR], 3.08; 95% CI, 1.39-6.83), worsening sulcal grade (OR, 3.56; 95% CI, 1.04-12.2), and worsening ventricular grade (OR, 9.34; 95% CI, 1.24-70.2). In cross-sectional analysis, of 969 participants, 35 (3.6%) had prevalent AF at the time of the 2004 to 2006 MRI scan. Those with AF had greater odds of higher sulcal (OR, 3.9; 95% CI, 1.7-9.1) and ventricular grade (OR, 2.4; 95% CI, 1.0-5.7) after multivariable adjustment and no difference in white matter hyperintensity or total brain volume. Conclusions- AF is independently associated with increase in subclinical cerebral infarction and worsening sulcal and ventricular grade-morphological changes associated with aging and dementia. More research is needed to define the mechanisms underlying AF-related neurodegeneration.
Project description:BACKGROUND:Atrial fibrillation (AF)-related symptoms and physical performance are relied upon to guide therapeutic management of patients with AF. We sought to understand whether AF predisposes to or is a result of physical disability and poor subjective health in the community. METHODS:We studied relations between physical disability (Rosow-Breslau Functional Health Scale), subjective health (self-report) and incident AF, and the converse, in the Framingham Heart Study. RESULTS:In 3,609 participants (age 73 ± 8 years, 59% women), a subset of 861 participants (24%) had prevalent physical disability at baseline. During 5.8 ± 1.8 years of follow-up, 555 participants (10-year age- and sex-adjusted incidence rate 13%) developed incident AF. Prevalent physical disability was related to incident AF (multivariable-adjusted hazard ratio 1.25, 95% CI 1.02-1.54, P = .03). In 3,525 participants, prevalent poor subjective health (n = 333) also was related to incident AF (n = 552, multivariable-adjusted hazard ratio 1.31, 95% CI 1.00-1.70, P = .048). Conversely, in 2,080 participants (age 69 ± 6 years, 55% women), interim AF (n = 106) was associated with newly reported physical disability (n = 573) at a follow-up examination (multivariable-adjusted odds ratio 1.58, 95% CI 1.08-2.31, P = .01). In 1,954 participants, interim AF (n = 96) likewise was related to newly reported poor subjective health (n = 224, multivariable-adjusted odds ratio 1.83, 95% CI 1.10-3.02, P = .02). CONCLUSIONS:Physical disability and poor subjective health were related to incident AF in a community-based cohort. Conversely, interim AF was related to newly reported physical disability and poor subjective health. Because AF guidelines incorporate symptoms, it is essential to clarify the temporality and mechanisms linking physical disability, subjective health, and AF.