Atrial Fibrillation Odds Ratio Research Articles

Abstract 17950: Atrial Fibrillation Impacts Mortality, Length of Stay, Resources Utilization and Need for Endotracheal Intubation in Patients Who Were Submitted to C-section or Natural Delivery: A Nationwide Analysis 2016-2020

Background: Atrial fibrillation (AF) is rare during pregnancy but the data on its impact during delivery is scaring. In this study, we aim to analyze the impact of AF in patients who underwent delivery via Cesarean section (CS), natural spontaneous delivery (NSD) or instrumental delivery (ID). Methods: We obtained the data from the National Inpatient Sample from 2016-2020. Our primary outcome was in-hospital mortality. Secondary outcomes included length of stay, total hospital charges and respiratory failure requiring intubation. Primary and secondary outcomes were adjusted to variables that had a p-value<0.2 for that outcome. Results were considered statistically significant if p-value <0.05. Results: There were 17,785,980 deliveries who underwent CS, NSD or ID. Of this, 6,000 patients had the secondary diagnosis of atrial fibrillation. The population had a mean age of 29.13 years. (See table 1) Patient with AF had almost twenty times more change of dying compared to those without AF odds ratio (OR) 19.12, 95% Confidence interval (CI) 4.33 - 84.45, p<0.001. Furthermore, AF cohort stayed for one and a half day longer Coefficient 1.55, CI 1.16 - 1.94, p<0.001, had a higher hospital charge Coefficient 19294.05, CI 14658.17 - 23929.93 and had a higher rate of respiratory complications requiring intubation OR 15.86, CI 7.83 - 32.15, p<0.001. (See table 2) Conclusion: Atrial fibrillation has a substantial negative impact in inpatient outcomes on pregnant patients during delivery. Further research is needed to explore these disparities in maternal care.

Clinical risk factors associated with ventricular fibrillation during first ST-elevation myocardial infarction

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union’s Horizon 2020 research and innovation programme under acronym ESCAPE-NET, registered under grant agreement No 733381 Introduction Sudden cardiac death (SCD) remains a major public health issue. Most cases in the general population are caused by ischemic heart disease, and often occur in patients without known ischemic heart disease. The assessment of risk factors may point to novel causal pathways or new targets for intervention and risk prediction of SCD. Objective The aim of this study was to evaluate the effect of family history of sudden death, prior history of atrial fibrillation (AF), and anterior infarct location on ECG on the development of ventricular fibrillation (VF) during first ST-elevation myocardial infarction (STEMI). Methods We performed individual participant data meta-analyses of three European case-control studies including first STEMI patients (aged 18-80 years) with VF (cases) and without VF (controls) before revascularization (GEVAMI, AGNES, and PREDESTINATION). Analyses were done using fixed-effect, inverse variance weighted meta-analysis and multivariable logistic regression. Potential confounding variables were identified using causal diagrams and missing data were handled with multiple imputation for each cohort separately. Results We included 1664 cases and 2497 controls (median age (IQR) = 59 (51-67) years, 20% females) in the analyses. After adjusting for potential confounding, we found an independent and additive association between the three exposures and VF (see picture): for family history of sudden death odds ratio (OR) 1.59 (95% confidence interval: 1.37-1.85), for AF OR 2.41 (1.49-3.89), and for anterior myocardial infarction OR 1.50 (1.32-1.71). Further investigation indicated increased effect of family history with multiple sudden deaths in the family, a stronger effect of AF on VF developing within the first minutes of symptoms, and the effect of anterior infarctions being modified by enzymatically determined infarct size. The three risk factors showed an additive effect: with one factor present OR 1.59 (1.38-1.84), two factors OR 2.41 (1.95-2.99), and all three factors OR 5.49 (1.43-21.1). Complete case analysis gave similar results for all analyses. Conclusions Family history of sudden death, history of AF, and anterior infarct location with significant interaction with enzymatic infarct size were all independently and additively associated with an increased risk of VF in patients with a first STEMI.

The association between novel ST2, BNP, atrial fibrillation and heart failure

Abstract Background/Introduction ST2, a novel marker of fibrosis has been proposed as a novel biomarker for heart failure. There is paucity of data suggesting its association with Atrial Fibrillation (AF), in particular, with regards to the its independent effect after adjustment for clinical factors and traditional biomarkers such as BNP. There is increasing evidence that inflammation and fibrosis are important players in the pathogenesis of AF, the most common arrhythmia that is associated with considerable morbidity. Purpose We sought to examine the association of ST2 with AF and its possible incremental value in combination with traditional biomarkers already used in routine clinical practice such as BNP. Methods Unselected patients presenting to a Cardiology service who had BNP for clinical reasons, concomitantly had ST2 sent. These patients included those with heart failure, acute coronary syndromes and AF, as well as patients attending cardioversion and cardiac catheterisation. The association between ST2, BNP and clinical factors was examined. ST2 was examined in tertiles as its distribution was highly skewed. Raised BNP was defined as usual (≥100 pg/ml). Results Of the 619 patients, the mean age was 69 years and 66% were male. The prevalence of co-morbidities were: Coronary heart disease - CHD (41%), Atrial Fibrillation – AF (30%), Heart Failure - HF (20%), Chronic Kidney Disease – CKD (23%). The mean eGFR was 68 ml/h and the mean LV ejection fraction was 55%. Both ST2 and BNP levels were significantly higher in patients with heart failure, CKD and AF. Mean levels of ST2 were (in ng/ml): HF vs no HF (65 vs. 38, p=0.0001) and in CKD vs. no CKD (49 vs. 41, p=0.001), CAD vs no CAD (43 vs. 42, p=0.3). Mean levels of BNP were (in pg/ml): HF vs no HF (579 vs. 131, p=0.0001), CKD vs. no CKD (379 vs. 173, p=0.0001), CAD vs. no CAD (239 vs. 206, p=0.5). In patients with AF, levels of both ST2 and BNP were higher, as were their mean ages and prevalence of co-morbidities (see Table 1). Both ST2 and BNP correlated with AF (Pearson r=0.2, p<0.0001 for ST2 and r=0.5, p<0.0001 for BNP). There was also a graded association of ST2 with AF (15%, 33% and 40% across tertiles of ST2, p=0.0001). Both ST2 and raised BNP were significant associated with AF in both univariable and multi-variable regression models, and remained independent predictors when adjusted for HF, CHD, LV EF and eGFR (Table 2, Model 2 – Relative risk ratio of AF with ST2 across tertiles 1.5, p0.005, and Odds ratio of AF with raised BNP 7.4, p<0.001). However, ST2 loses significance when BNP is added to the model in combination (Table 2 – Model 3). Conclusions Both ST2 and BNP are independent predictors of AF even after adjustment for heart failure and other clinical factors. When ST2 is used in combination with BNP, raised BNP appears to be a stronger predictor of AF than ST2. Funding Acknowledgement Type of funding sources: None.

Risk factors for and impact of poststroke pneumonia in patients with acute ischemic stroke.

Poststroke pneumonia (PSP) is a common complication of stroke and an important cause of death following stroke. However, the treatment of PSP remains inadequate due to severe impairment to the respiratory system by PSP. Thus, it is crucial to focus on preventing PSP to improve the prognosis of patients with stroke.This prospective single-center Cohort study aimed to investigate the risk factors for pulmonary infection following an ischemic stroke and identify whether PSP significantly influences the prognosis of patients after stroke.Altogether, 451 patients who were treated for acute ischemic stroke in the First Affiliated Hospital of Chongqing Medical University in China between April 2017 and April 2018 were enrolled. Clinical data from the patients from admission to 3 months after discharge were collected. PSP was the primary outcome and poor prognosis or death at 3 months following discharge was the secondary outcome observed in this study. We performed logistic regression analyses to identify the risk factors for PSP and test an association between pneumonia and poor prognosis or death after stroke.Our findings revealed the following risk factors for PSP: atrial fibrillation odds ratio (OR) = 2.884, 95% confidence intervals (CI) = 1.316–6.322), being bedridden (OR = 2.797, 95%CI = 1.322–5.921), subject to an invasive procedure (OR = 12.838, 95%CI = 6.296–26.178), massive cerebral infarction (OR = 3.994, 95%CI = 1.496–10.666), and dysphagia (OR = 2.441, 95%CI = 1.114–5.351). Pneumonia was a risk factor for poor prognosis (OR = 2.967, 95%CI = 1.273–6.915) and death (OR = 5.493, 95%CI = 1.825–16.53) after stroke.Hence, since pneumonia increases the risk of poor prognosis and death following acute ischemic stroke, preventing, and managing the risk factors for PSP may improve the prognosis and reduce the mortality after stroke.

Abstract P640: Incident Atrial Fibrillation and Cardiovascular Risk Increases in Patients With Increased Burden of Atrial Ectopy

Introduction: Atrial fibrillation (AF) is a major risk factor for cerebral ischemia in North America. Atrial ectopy has been associated with incident AF and increased stroke risk on short-duration ECG monitoring. The objective of this study was to characterize the relationship between the burden of atrial ectopy with future AF, stroke, and cardiovascular events on prolonged ECG monitoring. Methods: A retrospective, observational study was conducted at a single centre enrolling patients >18 years old referred from TIA clinic. Data was collected from 7- and 14-day Holter monitor reports, patient charts, and cardiac investigations. The final sample included 1124 patients; a subgroup of 759 patients had echocardiograms. Univariate and multivariate logistic regression determined the odds ratio (OR) of developing the composite outcome (AF, TIA/stroke, ACS, death) or secondary outcomes (AF or TIA/stroke). Results: The population was high-risk with a mean CHA 2 DS 2 -VASc of 4.0 (±1.8); during 1-year of follow-up, the primary outcome occurred amongst 116 (10.3%) patients. Univariate analysis ORs are displayed in Table 1. There was a statistically significant relationship (p<0.001) between percentage of PACs and the composite outcome (OR 4.066), and AF (11.886) for patients with 2-5% PACs. PAC runs/day was significant if >5/day for AF (OR 5.989, p<0.01) and for the composite (OR 2.231, p<0.05). Long PAC runs (>30 beats) also had significant ORs for AF (2.849, p<0.01) and the composite (5.320, p<0.01). In the subgroup analysis, reduced ejection fraction had an OR of 2.172 (1.407-5.771) for the composite outcome, and atrial dilatation had an OR of 2.778 (1.390-5.551) for AF. Conclusions: Increased burden of atrial ectopy is associated with increased odds of developing AF and a composite of cardiovascular events. Patients with increased ectopy should be considered for further, future ECG monitoring and risk stratification with echocardiogram.

Causal effects of plasma lipids on the risk of atrial fibrillation: A multivariable mendelian randomization study

Background and aimsObservational studies have suggested that plasma lipids contribute substantially to cardiovascular disease, but “cholesterol paradox” in atrial fibrillation (AF) remains. We sought to investigate the causal effects of lipid profiles on the risk of AF. Methods and resultsTwo-sample Mendelian randomization (MR) framework was implemented to examine the causality of association. Summary estimations of genetic variants associated with low density lipoprotein (LDL)-cholesterol, high density lipoprotein (HDL)-cholesterol, total cholesterol, triglycerides, lipoprotein-a [Lp(a)], apolipoprotein A1 (ApoA 1), and apolipoprotein B (ApoB) were 81, 99, 96, 61, 30, 10, and 23 single nucleotide polymorphisms, respectively. Genetic association with AF were retrieved from a genome-wide association study that included 1,030,836 individuals. The complications for AF were predefined as cardioembolic stroke (CES) and heart failure (HF). In the multivariable MR, the odds ratios for AF per standard deviation (SD) increase were 1.030 (95% confidence interval (CI) 0.979–1.083; P = 0.257) for LDL-cholesterol, 0.986 (95% CI 0.931–1.044; P = 0.622) for HDL-cholesterol, 0.965 (95% CI 0.896–1.041; P = 0.359) for triglycerides, 1.001 (95% CI 1.000–1.003; P = 0.023) for Lp(a), 1.017 (95% CI 0.966–1.070; P = 0.518) for ApoA1, and 1.002 (95% CI 0.963–1.043; P = 0.923) for ApoB. There was no evidence that other lipid components were causally associated with AF, CES, or HF, other than for a marginal association between triglycerides and HF. ConclusionsThis MR study provides robust evidence that high Lp(a) increases the risk of AF, suggesting that interventions targeting Lp(a) may contribute to the primary prevention of AF.

P5658Incorporation of severity of left atrial enlargement in clinical risk factors improves identification of patients at risk for development of atrial fibrillation

Abstract Background Early identification of patients at risk for atrial fibrillation (AF) is desirable to prevent its development and complications. Clinical predictors have been recognized but need refinement to improve predictability. We evaluated whether severity of left atrial enlargement (LAE) added to a scoring system (CHA2DS2VASC) in an unselected non-AF population improves risk stratification for incident AF. Purpose To assess the incremental benefit of LAE severity added to CHA2DS2VASc in predicting future AF in non-AF patients. Methods From 2012–2017, consecutive adult patients with an echocardiogram and no prior AF were identified. CHA2DS2VASc was used to define baseline AF risk, and the incremental risk of AF with addition of LAE was assessed through increased LA volume index (LAVI; moderate 42–48 ml/m2, severe >48 ml/m2). To quantify improvement in risk prediction, logistic regression model was fitted and odds ratios (OR) and ROC curves obtained. Results Out of 155,597 patients with no prior AF, 13.8% developed AF over 1.5±1.3 years. OR for AF with CHA2DS2VASc was 1.68 (95% CI 1.66–1.69). With addition of moderately or severely increased LAVI to the model, OR for AF increased to 2.3 (2.2–2.5) and 3.8 (3.6–4.0), respectively. ROC analysis showed c-statistics of 0.66 with CHA2DS2VASc, 0.63 with LAVI, and 0.71 with incorporation of both (Fig). AF CHAD score Conclusion(s) In non-AF patients, predictability for future AF can be improved by using clinical factors (CHA2DS2VASc) and increased LAVI. This information may guide closer monitoring and initiation of therapies to prevent progression to AF or stroke. Acknowledgement/Funding None

No association between coffee consumption and risk of atrial fibrillation: A Mendelian randomization study

Background and aimsSome observational studies have found that habitual coffee and caffeine consumption might reduce the risk of atrial fibrillation (AF). We conducted a two-sample Mendelian randomization study to explore the potential association between coffee consumption and AF. Methods and resultsThis study was based on summary-level data from the Atrial Fibrillation Consortium, including 588 190 individuals (65 446 cases and 522 744 non-cases). Nine single-nucleotide polymorphisms associated with coffee consumption at significance level of P < 5 × 10−8 were used as instrumental variables and were obtained from a genome-wide association study that included up to 375 833 individuals.The odds ratio of AF per genetically-predicted 50% increase of coffee consumption was 0.98 (95% confidence interval, 0.88, 1.10; P = 0.80) in the standard inverse-variance weighted analysis. Results were consistent in sensitivity analyses using the weighted median and MR-Egger methods, and no directional pleiotropy (P = 0.37) was observed. Moreover, complementary analyses that separated the coffee-related single-nucleotide polymorphisms based on their association with blood levels of caffeine metabolites (lower, higher, unrelated or unknown association) revealed no association with AF. ConclusionsThis study does not support a causal association between habitual coffee consumption and risk of AF.

The prevalence of atrial fibrillation on 48-hour ambulatory electrocardiography in African Americans compared to Whites: The Atherosclerosis Risk in Communities (ARIC) study

BackgroundA lower prevalence of atrial fibrillation (AF), but paradoxically higher burden of cardiovascular disease risk factors, has been observed among African Americans compared to Whites in studies of AF identified by mostly 12-lead electrocardiograms (ECGs) and clinically. MethodsWe performed 48-hour ambulatory electrocardiography (aECG) in a biracial sample of 1,193 participants in the Atherosclerosis Risk in Communities (ARIC) (mean age = 78 years, 62% African Americans, 64% female). Atrial fibrillation was identified from aECG, study visit ECGs, and discharge codes from cohort hospitalizations. We used covariate-adjusted logistic regression to estimate prevalence odds ratios (ORs) for AF in African Americans versus Whites, with adjustment for sampling and nonresponse. ResultsAfrican Americans were more likely than Whites to have hypertension and diabetes but less likely to have coronary heart disease. The prevalence of AF detected by aECG or ARIC study ECG (adjusted for age and coronary heart disease) was lower in African Americans than Whites (2.7% vs 5.0%). White men had a higher (although not significant) AF prevalence of 7.8% compared to the other race and gender groups at 2.3%-2.8%. The adjusted OR for AF was 0.49 (0.24-0.99) comparing African Americans to Whites. Findings were similar when AF was defined to include prior AF hospitalizations (OR = 0.42, 0.25-0.72). There were no significant differences by race for asymptomatic or paroxysmal AF. ConclusionsAtrial fibrillation was less prevalent in African American than white older adults, regardless of detection method. Although overall detection of new AF cases with aECG was low, future studies should consider longer-term monitoring to characterize AF by race.

Increased Ferritin Concentration and Risk of Atrial Fibrillation and Heart Failure in Men and Women: Three Studies of the Danish General Population Including 35799 Individuals.

Moderately increased plasma ferritin, as a biomarker of iron overload, has been associated with higher rates of cardiovascular death and heart failure. However, the association of moderately increased plasma ferritin with risk of atrial fibrillation in the general population is unknown. We examined the association of plasma ferritin concentrations with risk of atrial fibrillation and heart failure in metaanalyses of 35799 men and women from 3 studies of the Danish general population: the Copenhagen City Heart Study, the Danish General Suburban Population Study, and the Copenhagen General Population Study. Multivariable adjusted fixed effects odds ratios for atrial fibrillation were 1.23 (95% CI, 1.05-1.44; P = 0.005) in men for ferritin concentration ≥300 μg/L vs <300 μg/L, 1.13 (95% CI, 0.93-1.38; P = 0.22) in women for ≥200 μg/L vs <200 μg/L, and 1.19 (95% CI, 1.06-1.35; P = 0.005) in both sexes combined (P sex interaction = 0.52). Corresponding fixed effects odds ratios for heart failure were 1.16 (95% CI, 0.98-1.37; P = 0.08) in men, 0.86 (95% CI, 0.67-1.10; P = 0.23) in women, and 1.05 (95% CI, 0.91-1.21; P = 0.45) in both sexes combined (P sex interaction = 0.05). Multivariable adjusted fixed effects odds ratio for atrial fibrillation per step increase in ferritin concentrations was 1.13 (95% CI, 1.06-1.21; P trend = 0.0005) in both sexes combined (P sex interaction = 0.59); the corresponding value for heart failure was 1.03 (95% CI, 0.95-1.11; P trend = 0.47) (P sex interaction = 0.08). In sensitivity analyses, there was no evidence of U-shaped relationships between plasma ferritin concentrations and risk of atrial fibrillation or heart failure in men or women. Increased ferritin concentration is associated with increased risk of atrial fibrillation in the general population.

THE PROGNOSIS OF DEVELOPMENT OF THE PAROXYSM OF ATRIAL FIBRILLATION IN PATIENTS WITH POST-INFARCTION CARDIOSCLEROSIS

Aim . Create an algorithm predicting the risk of development of paroxysmal atrial fibrillation in patients with coronary heart disease on the background of post-infarction cardiosclerosis (PICS). Material and Methods. There was conducted the deep analysis of a number of laboratory and functional indicators (indicators of peroxidation of proteins, lipids, antioxidant protection and skin microcirculation) at 85 patients with atrial fibrillation (AF). All patients were divided into 4 groups: patients with paroxysmal and chronic AF without PICS (27 people), patients with paroxysmal and chronic AF with PICS (12), patients with permanent AF without PICS (26) and patients with permanent form of AF with PICS (20). Results. There was created the mathematical model to predict the development of atrial fibrillation in patients with PICS with calculation of the odds ratio of atrial fibrillation. Methods of correlation and factor analysis revealed the greatest value for the prognosis of paroxysmal atrial fibrillation in patients with PICS two factors: the total level of deep oxidation products of protein and an indicator of microcirculation by laser Doppler flowmetry. The diagnostic sensitivity of the developed prognostic model was 86%, specificity of the test – 94%, the diagnostic efficiency of the test – 90%. Conclusion. The study has been proven clinical diagnostic and prognostic value of a comprehensive study of indicators of oxidation-reduction reactions, and the microcirculation indices in combination with standard laboratory and instrumental investigations in patients with AF. The developed mathematical model allows to predict the development of atrial fibrillation in patients with PICS.

Breed predisposition and heritability of atrial fibrillation in the Standardbred horse: A retrospective case–control study

ObjectivesTo assess evidence for genetic contributions to atrial fibrillation (AF) in the Standardbred horse. AnimalsEquine referrals to the Ontario Veterinary College Health Sciences Centre (OVCHSC) for 1985–2009, and age and gait matched breed registry controls. MethodsBreeds presenting ≥5 times annually were tabulated (admission year and diagnosis; total 40,039; AF 396; no AF 39,643), and breed and year effects examined. Heritability and inbreeding coefficients were determined for Standardbred AF cases and racing contemporaries, and odds ratios for AF were calculated for frequently occurring sires. ResultsYear and breed effects on diagnosis were highly significant (Chi-Square 212.85, p < 0.0001, and 304.25, p < 0.0001, respectively). Year effect on diagnosis by breed was significant from 1997, and due to Standardbred admissions each year. Quarterhorses were significantly less likely to present with AF (OR 0.0578–0.6048), Standardbreds were more likely (OR 4.3874–10.9006). Heritability of AF on the underlying scale (h2u) was estimated at 29.6 ± 3.9% and on the observed binomial scale (h2o), at 9.6%. For horses born in 1994 or later, h2u was 31.1 ± 4.3% and h2o, 10.1%. Of 22 first generation sires appearing ≥10 times in the case/control file, seven pacing and one trotting sire produced affected horses more frequently than expected (OR 2.66–66.32). Inbreeding was not a factor. ConclusionsThere is genetic liability to AF in Standardbred horses, likely due to more than single genes with simple Mendelian inheritance. Genomic studies are required.

The 894G Allele of the Endothelial Nitric Oxide Synthase 3 (eNOS) is Associated with Atrial Fibrillation in Chronic Systolic Heart Failure.

Atrial fibrillation (AF) in patients with heart failure signals poor prognosis. The endothelial nitric oxide synthase (eNOS) enzyme is a key player in the counterregulation of oxidative stress, which is related in part to AF pathogenesis. The purpose of this study was to investigate a possible clinical association in heart failure patients between the presence of exon 7 G894T eNOS polymorphism, known to result in the Glu298Asp protein variant, and the occurrence of AF. We analyzed the DNA of 344 patients with chronic systolic heart failure for exon 7 G894T eNOS polymorphism, using PCR. Odds ratios for AF were calculated for the homo- and heterozygous G-allele G894T variants relative to the TT variant. Of the 344 patients, 204 (59%) were homozygous for the G allele, 122 (36%) were heterozygous (GT), and 18 (5%) were homozygous for the T allele. AF episodes were documented in 73 patients (36%) with the GG genotype, in 35 (29%) with GT, and in 2 (11%) with TT. The odds ratio for AF, based on the presence of at least one G allele in the eNOS 894 gene, was 3.96 (95% confidence interval, 1.17‒13.56, p=0.04). Having two G alleles increased the odds ratio to 4.5 (95% confidence interval, 1.0‒20.0, p=0.02). Patients with systolic heart failure demonstrate strong correlation between AF and the presence of a G allele in the exon 7 G894T eNOS genotype. These findings support the importance of eNOS polymorphism in the pathogenesis of AF in heart failure patients.

Does Elevated C-Reactive Protein Increase Atrial Fibrillation Risk?: A Mendelian Randomization of 47,000 Individuals From the General Population

The purpose of this study was to test whether the association of C-reactive protein (CRP) with increased risk of atrial fibrillation is a robust and perhaps even causal association. Elevated levels of CRP previously have been associated with increased risk of atrial fibrillation. We studied 10,276 individuals from the prospective Copenhagen City Heart Study, including 771 individuals who had atrial fibrillation during follow-up, and another 36,600 persons from the cross-sectional Copenhagen General Population Study, including 1,340 cases with atrial fibrillation. Individuals were genotyped for 4 CRP gene polymorphisms and had high-sensitivity CRP levels measured. A CRP level in the upper versus lower quintile associated with a 2.19-fold (95% confidence interval [CI]: 1.54- to 3.10-fold) increased risk of atrial fibrillation. Risk estimates attenuated slightly after multifactorial adjustment to 1.77 (95% CI: 1.22 to 2.55), and after additional adjustment for heart failure and plasma fibrinogen level to 1.47 (95% CI: 1.02 to 2.13) and 1.63 (95% CI: 1.21 to 2.20), respectively. Genotype combinations of the 4 CRP polymorphisms associated with up to a 63% increase in plasma CRP levels (p < 0.001), but not with increased risk of atrial fibrillation. The estimated causal odds ratio for atrial fibrillation by instrumental variable analysis for a doubling in genetically elevated CRP levels was lower than the odds ratio for atrial fibrillation observed for a doubling in plasma CRP on logistic regression (0.94 [95% CI: 0.70 to 1.27] vs. 1.36 [95% CI: 1.30 to 1.44]; p < 0.001). Elevated plasma CRP robustly associated with increased risk of atrial fibrillation; however, genetically elevated CRP levels did not. This suggests that elevated plasma CRP per se does not increase atrial fibrillation risk.

The Single Nucleotide Polymorphisms of Kir3.4 Gene and Their Correlation with Lone Paroxysmal Atrial Fibrillation in Chinese Han Population

Acetylcholine induced inwardly rectifying current (I(KACh)) is a heteromultimeric complex formed by Kir3.1 and Kir3.4 subunits and plays important roles in the development of atrial fibrillation (AF). AF is a common disorder among Chinese, the frequency of AF is about 0.61%, and in patients with strokes it is 12.1%. We hypothesise that lone paroxysmal AF genetic variation in Kir3.4 may predispose the atria to fibrillation in the Chinese population. We recruited 186 patients with lone paroxysmal AF, and 210 matched controls by age (49.61+/-8.04 years), sex, smoking habit, and left atrial dimension in Zhejiang Province, China. Genotype of Kir3.4 was determined with polymerase chain reaction (PCR) and direct sequencing. The SPSS statistical software was used for chi(2) test. LD and haplotypes were calculated using SHESIS software package. Three synonymous known single nucleotide polymorphisms (SNPs) in Kir3.4 were genotyped, including C171T (rs6590357), G810T (rs7118824) and C834T (rs7118833). We found low levels of linkage disequilibrium (LD) between C171T and G810T (D'=0.272), complete LD between SNPs G810T and C834T (D'=1) in AF patients and controls. The case-control analysis revealed that the frequency of genotype and allele in three SNPs are significantly different between lone paroxysmal AF patients than in control subjects. The odds ratio (OR) for AF 171T and 810T alleles were 1.546 (95% CI 1.015-2.355) and 1.520 (95% CI 1.012-2.284), respectively, when compared with patients without Kir3.4T alleles in these two loci. The OR for AF in patients with C-T genotype were 13.364 (95% CI 5.710-31.278) and 37.135 (95% CI 9.050-152.381) when comparing patients with T-G genotype. Our findings suggest that C171T and G810T SNPs in Kir3.4 gene might be risk factors for lone paroxysmal AF in Chinese population.

Abstract 4403: Significant Single Nucleotide Polymorphism Associated with Atrial Fibrillation Located on Chromosome 4q25 in a Whole Genome Association Study and Association with Left Atrial Gene Expression

Introduction: Heritability studies of atrial fibrillation (AF) suggest a complex genetic basis for common AF. Recently a locus on chromosome 4q25 was associated with AF in a genome-wide association study (GWAS), but the mechanism by which this locus is associated with AF is unknown. Methods: To identify genetic variations associated with AF, we performed an analysis of AF as a secondary phenotype from a case-control GWAS of myocardial infarction. 210,178 autosomal SNPs of high quality were genotyped in 138 AF cases and 546 controls. Stratified score tests of the trend/additive model and general genotypic model were performed for each SNP. Genomic control and multidimensional scaling were used to control and assess population stratification. The SNP meeting genome-wide significance was genotyped in 46 left atrial appendage tissue samples for which we obtained expression levels for 22,184 transcripts. Cis expression traits within 1 megabase of the top SNP were tested for association with the SNP genotypes. Results: One SNP (rs4611994) met our per-SNP genome-wide significance thresholds (both a conservative Bonferroni threshold or a more liberal FDR-based threshold) for association with AF, which was in perfect linkage disequilibrium with the locus on chromosome 4q25 found in the deCODE genetics AF study (r 2 with SNP rs2200733=1.0). This SNP yielded an AF odds ratio of 2.28 under the additive model, with a p-value using genomic control/general genotype model of 5.0E-08, and a minor allele frequency 0.13 in controls and 0.25 in AF cases, and a genome-wide p-value of 0.046 by permutation analysis. In the 46 left atrial tissue samples, cis analysis demonstrated significant association between rs4611994 genotype and expression of LRIT3 (Leucine-rich repeat, immunoglobulin-like domain and transmembrane domain-containing protein 3) with q-value 2.22E-03 and the C isoform of PITX2 with q-value 7.50E-03. Conclusions: Our GWAS for common AF has replicated the AF-associated locus on chromosome 4q25. The genotype at this locus was correlated with cis regulation of the LRIT3 and PITX2C transcripts, suggesting these genes as candidates for mechanistic studies.

S1-3 GENETICS OF CLINICAL ATRIAL FIBRILLATION IN TAIWAN

Background: Atrial fibrillation is a complex disease. Its etiologies are diverse and genetic factors may also contribute to this disease. Human minK protein is the ?-subunit of IKs potassium channel and play important roles in cardiac cellular electrophysiology. We investigated the association between atrial fibrillation and the polymorphism of minK gene (38G or 38S) in Taiwan. Methods: We included 108 patients with atrial fibrillation and 108 controls. The case and control patients were matched regarding their age, sex, the presence of valvular heart disease and the presence of left ventricular dysfunction. The genotype of minK was determined using polymerase chain reaction and restriction fragment analysis. Results: The results showed an association between the minK38G allele and atrial fibrillation. The odds ratios for atrial fibrillation in patients bearing one or two minK38G alleles were 2.16 (95% confidence interval 0.81–5.74) and 3.58 (95% confidence interval 1.38–9.27) respectively when compared to patients without minK38G allele. In a logistic regression model, the odds ratio for atrial fibrillation was 1.80 (95% confidence interval 1.20-2.71, p<0.0046) for bearing one more minK 38G allele. Conclusions: We report the association between the minK38G allele and clinical atrial fibrillation. Our findings suggest possible genetic control on the pathogenesis of atrial fibrillation.

Relation of C-Reactive Protein and New-Onset Atrial Fibrillation in Patients With Acute Myocardial Infarction

Recent studies have implicated systemic inflammation in the genesis and maintenance of atrial fibrillation (AF). A robust inflammatory response is an integral component of the response to tissue injury during acute myocardial infarction (AMI). However, there is no information concerning the association between inflammation and AF in patients with AMI. We studied 1,209 patients admitted for AMI. C-reactive protein (CRP) was measured by a high-sensitivity assay within 12 to 24 hours after symptom onset. The relation between CRP and new-onset AF occurring during the hospital course and at 1 year was analyzed using multivariable logistic regression and Cox models, respectively. New-onset AF during hospitalization occurred in 6.5%, 10.4%, and 17.1% of patients in the first, second and third CRP tertiles, respectively (p trend <0.0001). In a multivariable logistic regression, adjusting for clinical variables and ejection fraction, compared with patients in the first CRP tertile, the odds ratios for AF were 1.5 (95% confidence interval 0.9 to 2.5, p = 0.15) and 2.0 (95% confidence interval 1.2 to 3.3, p = 0.008) in patients in the second and third CRP tertiles, respectively (p for trend = 0.007). In a Cox multivariate analysis, CRP remained an independent predictor of new-onset AF at 1 year. In conclusion, in a large cohort of patients with AMI, there was a graded positive association between increased CRP and new-onset AF. Inflammation may contribute to the development of AF in the setting of AMI.

Increasing Prevalence of Atrial Fibrillation among Patients Hospitalized with Acutely Decompensated Heart Failure

Background: Atrial fibrillation (AF) is a common precipitant of acute decompensation and subsequent hospitalization for heart failure (HF). A recent study suggests that the prevalence of AF in the general population is increasing. Objective: Define secular trends in the prevalence of AF among patients admitted with acute decompensated HF (ADHF). We also ascertained whether these trends were similar in patients with reduced (systolic HF, SHF) or preserved (diastolic HF, DHF) ejection fraction (EF). Methods: We characterized 6076 consecutive patients admitted with ADHF to Mayo Clinic hospitals in Rochester MN between January 1, 1987, and December 31, 2001. EF was measured within one month of admission in 4596 (76%) of patients. In those with EF measurement, 2167 (47%) had DHF (EF ≥ 50%). Results: In all patients admitted over the three consecutive 5-year periods the prevalence of AF increased (28%, 31% and 38% respectively, p < 0.0001). In the subset of patients who had an EF measured, the prevalence of AF increased in both SHF (23%, 27% and 36%; p < 0.0001) and DHF (38%, 39% and 45%; p = 0.012). When controlling for changes in patient characteristics (age, sex, creatinine, hemoglobin, presence of coronary disease, hypertension or diabetes) over time, the trend for increases in the prevalence of AF over the study period remained significant in all patients (Odds ratio for AF = 1.045 per year, CI 1.029–1.062, p < 0.0001) and in patients with SHF (Odds ratio for AF = 1.032 per year, CI 1.050–1.097, p < 0.0001) but not in patients with DHF (Odds ratio for AF = 1.022 per year, CI 0.999–1.045, p = 0.06). However, patients with DHF were more likely to have AF than patients with SHF (41 vs 29%, p <0.0001). Conclusion: In patients hospitalized with ADHF over a 15-year period, the prevalence of AF increased over time which may reflect the burden of AF in the community, the increasing age of hospitalized HF patients as well as changes in the natural history of HF over time. This trend is likely to compound the economic burden of HF and AF, two highly associated conditions.

Do off-pump techniques reduce the incidence of postoperative atrial fibrillation in elderly patients undergoing coronary artery bypass grafting?

Background Atrial fibrillation is the most common postoperative complication in patients undergoing coronary artery bypass grafting (CABG) with advancing age having been shown to have a significant association with its incidence. This study aims to assess whether off-pump coronary artery bypass (OPCAB) reduces the incidence of atrial fibrillation in elderly patients. Methods A meta-analysis of all observational studies reporting a comparison between the two techniques in elderly patients (> 70 years) between 1999–2003 was performed. The primary outcome of interest was the incidence of postoperative atrial fibrillation. The quality of each study was evaluated by examining three items: patient selection, matching of the off-pump and cardiopulmonary bypass patient groups, and assessment of outcome. Meta-regression analysis was undertaken to see the effects of study size and quality on the calculated odds ratio. Results Eight studies fulfilled our inclusion criteria, all of which were nonrandomized. In total the studies identified 3017 subjects, of which 764 had off-pump surgery (25%) and 2253 underwent cardiopulmonary bypass (75%). Meta-analysis showed that after off-pump surgery there was a significantly lower incidence of postoperative atrial fibrillation in these patients (odds ratio 0.70, 95% confidence interval [CI] 0.56–0.89). Meta-regression analysis including study characteristics did not show any associations affecting the calculated odds ratio of atrial fibrillation. Conclusions Our study demonstrates a reduced incidence of postoperative atrial fibrillation in an elderly population with off-pump as compared with cardiopulmonary bypass techniques. We appreciate, however, that our statistical analysis uses nonrandomized published data and that the results must be treated with caution. If this finding is confirmed by a large-scale randomized trial, it has significant implications on the operative strategy employed for this patient group.