Biochemical predictors of cardiac rhythm at 1 year follow-up in patients with non-valvular atrial fibrillation

C-reactive protein (CRP) is increased in patients with atrial fibrillation (AF) and it might predict the lack of sinus rhythm maintenance in the long term follow-up. Scarce data have been reported relating endothelial dysfunction and/or haemostatic or platelet markers to sinus rhythm maintenance in AF patients. We aimed to determine whether some biochemical markers including soluble thrombomodulin (sTM), soluble P-selectin, thrombin–antithrombin (TAT) complex and CRP levels could predict sinus rhythm maintenance at 1 year follow-up in non-valvular AF patients. 130 patients (70 males, mean age 67 ± 13 years) with newly diagnosed AF naïve of antithrombotic or antiplatelet therapy were studied. Baseline CRP, P-selectin, sTM and TAT levels were compared to those of 20 matched-healthy subjects in sinus rhythm. AF patients had significantly higher plasma CRP (10.5 ± 2.2 vs 3.25 ± 0.3 mg/l, p = 0.001), P-selectin (219 ± 141 vs 126 ng/ml, p = 0.01), and TAT (54 ± 237 vs 2.7 ± 3.3 ng/l, p = 0.001) levels compared with controls. Soluble TM levels, although higher than controls, did not reach statistical significance. Multivariate regression analyses showed that elevated CRP (OR = 4.8, p = 0.02) and sTM (OR = 1.05, p = 0.04) were the only two predictors of lack of sinus rhythm at 1 year follow-up. An altered inflammatory, haemostatic, endothelial and platelet environment exists in newly diagnosed AF patients. CRP and sTM levels might be used as biochemical markers to predict the status of cardiac rhythm at 1 year follow-up in some AF patients.     

Role of homocysteine for thromboembolic complication in patients with non-valvular atrial fibrilation.

Thromboembolism is the most important complication in patients with atrial fibrilation (AF). Homocysteine is a toxic amino acid that has been recently accepted as a risk factor for atherosclerosis and stroke. The aim of the present study is to show whether there is a relation between hyperhomocysteinemia and thromboembolic complications in patients with non-valvular AF. We admitted 38 patients with non-valvular AF. The patients were divided into two groups: group A (n = 20; mean age, 75.7 +/- 10.4 years; three males/17 females), and group B (n = 18; mean age, 68.0 +/- 10.6 years; 11 males/seven females). While group A consisted of the patients with AF and stroke, group B was composed of the patients with AF but without stroke. The patients having sinus rhythm (15 subjects) were used as the reference group to obtain the cut-off value. Homocysteine was measured by the immunoassay method. The means of the homocysteine levels were 12.4 +/- 3.3 micromol/l in group A, 8.3 +/- 2.3 micromol/l in group B and 9.3 +/- 1.8 micromol/l in the reference group. The cut-off value was 10.6 micromol/l. Group A had a statistically higher homocysteine level than not only group B, but also the reference group (P < 0.05). While 60% of group A (n = 12) had the elevated homocysteine level, the rate was only 22% for group B (n = 4). In conclusion, hyperhomocysteinemia may be one of the explanations for the increased rate of thromboembolic complications in older patients with AF.     

C-reactive protein and paroxysmal atrial fibrillation: evidence of the implication of an inflammatory process in paroxysmal atrial fibrillation.

BACKGROUND: Detection of inflammation is best achieved by measurements of C-reactive protein (CRP).We investigated whether inflammation might promote the development of paroxysmal atrial fibrillation (PAF), and whether high levels of CRP are associated with an increased risk of PAF. METHODS: We assessed the levels of CRP and other risk factors in patients with PAF of recent onset (<24 h), compared with age and sex matched controls with the same risk factors who had normal sinus rhythm. Patients with thyrotoxicosis, mitral stenosis, pulmonary emboli or pericarditis were excluded. Fifty patients with PAF and 50 control subjects were finally included. All patients received amiodarone (2.7 g over 24 hours). RESULTS: Conversion to normal sinus rhythm was achieved within 24 h in 40 patients. CRP levels were higher (P<0.001) in the PAF group (median = 0.80, min = 0.00, max = 5.90 mg/dl) compared with controls (median = 0.04, min = 0.00, max = 0.48 mg/dl). In the PAF group CRP levels were higher (P<0.001) for patients who failed to be cardioverted (median = 2.12, min = 0.80, max = 5.90 mg/dl) compared to cardiovertors. Nevertheless, CRP levels in patients who underwent successful cardioversion (median = 0.50, min = 0.00, max = 2.53 mg/dl) were higher compared with controls (P<0.001). Finally, CRP was higher in non-cardiovertors vs. control group, p<0.001. After multivariate adjustment left atrial size (OR, 4.4) and CRP levels (OR, 3.3) were significantly associated with successful cardioversion to sinus rhythm. CONCLUSION: These results suggest that CRP has a strong association with PAF and support the hypothesis that CRP is a potent determinant of successful cardioversion of PAF in sinus rhythm.     

Interleukin-6, endothelial activation and thrombogenesis in chronic atrial fibrillation.

BACKGROUND: A prothrombotic or hypercoagulable state has been described in AF, which could increase the risk of thromboembolism. As inflammation has been related to thrombogenesis and endothelial activation, we hypothesised that the prothrombotic state in AF (as assessed by an index of thrombogenesis, prothrombin fragment 1+2 [F1+2]) and endothelial activation (soluble E-selectin (sEsel)) could be related to an index of inflammation (interleukin-6 (IL-6)). PATIENTS AND METHODS: We studied 191 consecutive patients (98 male; mean age 72.3+/-9.2 years) with chronic non-rheumatic AF who were not on anticoagulant therapy. Plasma IL-6, sEsel and F1+2 were measured by ELISA. Research indices were compared to 74 controls in sinus rhythm matched for age and sex. In 43 patients with AF, the effects of introducing anticoagulation (INR 2.0-3.0) were also studied. RESULTS: Patients with AF had elevated levels of F1+2 (p<0.001) and IL-6 (p=0.045), but not sEsel. There was no significant correlation between F1+2 and IL-6. In multivariate analysis, only F1+2 levels were independently associated with the presence of AF (p=0.001). After oral anticoagulation, plasma levels of F1+2 and sEsel were significantly decreased (both p<0.01). CONCLUSION: High levels of IL-6 in AF suggest an inflammatory state, which appears to be more related to clinical variables of the patients, rather than to the presence of AF per se. There was no association of inflammation with endothelial activation (sEsel) or the presence of abnormal thrombogenesis (high F1+2 levels) in AF. Moreover, no changes in IL-6 levels were found despite the reduction of the other markers by oral anticoagulant therapy.     

Relationship between inflammatory markers and clinical patterns of atrial fibrillation in patients with congestive heart failure

BACKGROUND: Occurence of atrial fibrillation (AF) adversely affects left atrial size and cardiac function. This arrhythmia is also associated with an increase of plasma CRP and fibrinogen concentration. It is not clear whether elevated levels of inflammatory markers in patients with congestive heart failure (CHF) are associated with AF, clinical symptoms or adverse cardiac remodelling. AIM: To investigate the association between levels of inflammatory markers and selected clinical and echocardiographic parameters as well as used treatment in the population of CHF patients with various forms of AF. METHODS: The cross-sectional study included 99 patients with CHF divided into 3 groups. Group I included patients with sinus rhythm. Group II consisted of patients admitted to hospital with AF and discharged with sinus rhythm (the category of paroxysmal and persistent AF). Group III comprised patients with permanent AF. In all patients plasma CRP and fibrinogen concentrations were measured and echocardiographic examination was carried out. Left atrial dimension (LA), ejection fraction (LVEF) and right ventricular systolic pressure (RVSP) were assessed. RESULTS: Mean CRP concentration in group III (5.83+/-5.36 mg/l) was significantly higher than in group I (p=0.001) and group II (p=0.033). In the group with permanent AF mean fibrinogen concentration was elevated to a higher level (391.0+/-77.3 mg/dl) than in group II (p=0.007) and group I (p=0.099). Mean LA and RV dimensions and RVSP in group III were significantly higher than in group I and group II. Multivariable analysis revealed that plasma CRP concentration was significantly associated with the presence of arterial hypertension (p <0.001) and LA enlargement (p=0.007). A significant association between fibrinogen level and CRP level (p=0.038), presence of permanent AF (p=0.045) and metabolic syndrome (p <0.05) was found. Values of ln CRP were significantly correlated with LA diameter (r=0.24; p=0.015). CONCLUSIONS: Increased plasma CRP level in patients with CHF were significantly associated with arterial hypertension and LA enlargement. Permanent form of AF and CRP level have been shown to be significantly associated with increased plasma fibrinogen concentration in the course of CHF.     

Relationship between C-reactive protein level and early recurrence of atrial fibrillation after electrical cardioversion

INTRODUCTION AND OBJECTIVES: Atrial remodeling is responsible for the early recurrence of atrial fibrillation (AF) after cardioversion. Recently, it has been shown that the C-reactive protein (CRP) level is elevated in patients with AF, indicating that inflammation may play a role in the pathogenesis of this arrhythmia. We postulated that a high CRP level would predict early recurrence of AF after electrical cardioversion. PATIENTS AND METHOD: Forty-two patients with persistent AF, but without known heart disease, who underwent elective electrical cardioversion were investigated. The CRP level was measured immediately before cardioversion. The study population comprised the 37 patients in whom sinus rhythm was restored. RESULTS: After a follow-up period of 30 days, 16 patients (43%) had recurrence of AF; the other 21 (57%) remained in sinus rhythm. The mean CRP level was significantly higher in patients with AF recurrence (6.3 [3.3] mg/L vs 2.4 [2.1] mg/L, P=.0001). On dividing patients according to whether their CRP level was < or =3 mg/L or >3 mg/L, it was observed that only 33% of those in sinus rhythm had a level >3 mg/L compared with 81% of those with AF recurrence (P=.004). Patients with a CRP level >3 mg/L had a significant increase in the 1-month risk of AF recurrence (RR=3.7; 95% CI, 1.3-10.8). There was no association between CRP level and left atrial diameter (P =.50) or AF duration (P=.458). CONCLUSIONS: A high CRP level is associated with early recurrence of AF after electrical cardioversion, suggesting that inflammation could play a role in atrial remodeling.     

炎症在老年性心房颤动中的作用

目的探讨炎症在老年性心房颤动（AF）、心房重构的发生及持续中的作用。方法选择88例老年患者,其中持续性房颤组30例,阵发性房颤组30例,窦性心律组28例。所有入选患者进行心脏超声心动图检查,并检测患者外周血高敏C-反应蛋白（hs—CRP）、血管紧张素转换酶（ACE）水平。结果外周血hs—CRP、ACE水平持续性房颤组为（8．9±2．6）mg／ml、（89．7±11．3）U／L,阵发性房颤组为（4．7±2．3）mg／ml、（39．6±10．6）U／L,窦性心律组为（1．9±0．7）mg／ml、（36．8±10．5）U／L。持续性房颤组外周血ACE、hs—CRP水平高于阵发性房颤组和窦性心律组（P〈0．05）,阵发性房颤组外周血hs—CRP水平高于窦性心律组（P〈0．05）,阵发性房颤组ACE水平与窦性心律组相比差异无统计学意义（P〉0．05）。结论外周血hs—CRP、ACE水平增高与心房颤动的发生和持续可能相关。     

Relationship between inflammation and atrial fibrillation in patients with isolated rheumatic mitral stenosis

BACKGROUND AND AIM OF THE STUDY: Atrial fibrillation (AF) is the most common arrhythmia in patients with rheumatic mitral stenosis (MS), with an increased risk of mortality and morbidity. Although recent data have suggested that the inflammatory process is associated with non-valvular AF, the relationship between inflammation and AF occurrence in MS patients remains unknown. The study aim was to determine whether plasma levels of high-sensitivity C-reactive protein (hs-CRP), as a marker of inflammation, are elevated in patients with isolated rheumatic MS and AF compared to patients with MS but without AF. METHODS: The study population comprised 89 patients with isolated rheumatic MS (57 patients in sinus rhythm and 32 in AF) and 35 healthy controls. Patients with MS were categorized into subgroups in terms of their mitral valve area (MVA). Mean transmitral diastolic gradients and pulmonary artery pressure were monitored, and morphologic features of the mitral valve classified using an echocardiographic scoring system. Plasma levels of hs-CRP were monitored in all patients and control subjects, using a commercially available analytical kit. RESULTS: Patients with AF were shown to have significantly higher plasma levels of hs-CRP compared to those in sinus rhythm and controls (p < 0.001). In general, patients with AF were older (p < 0.001) and had a larger left atrial diameter (LAD) (p < 0.001). Plasma levels of hs-CRP were associated with LAD only in the AF group (rho = 0.437; p = 0.012). Multivariate logistic regression analysis revealed a significant independent relationship between AF and hs-CRP plasma level (odds ratio (OR) 3.57; 95% confidence interval (CI) 1.2-10.5; p = 0.021), age (OR 1.08; 95% CI 1.03-1.14; p = 0.003), and LAD (OR 1.2; 95% CI 1.02-1.4; p = 0.023). CONCLUSION: The study results indicated that hs-CRP plasma levels are associated with the presence of AF in patients with MS. This finding may have important implications for the development of new therapeutic and preventive approaches of AF in the setting of MS.     

Natriuretic peptides in patients with atrial fibrillation and advanced chronic heart failure: determinants and prognostic value of (NT-)ANP and (NT-pro)BNP.

AIMS: To study the determinants of natriuretic peptides in advanced chronic heart failure (CHF) patients with and without atrial fibrillation (AF) and to evaluate the prognostic value of natriuretic peptides in AF compared with sinus rhythm patients with advanced CHF. METHODS AND RESULTS: The study group comprised 354 advanced CHF patients [all New York Heart Association (NYHA) III/IV], including 76 AF patients. AF patients were older (70+/-7 vs. 67+/-8; P=0.01), and non-ischaemic CHF was more common (42 vs. 19%; P=0.002) than in sinus rhythm patients, but left-ventricular ejection fraction was comparable (0.23+/-0.08 vs. 0.24+/-0.07; P=ns). At baseline, (NT-)ANP and NT-proBNP levels were significantly higher in AF patients, compared with those in sinus rhythm. By multivariate regression analysis, AF was identified as independent determinant of (NT-)ANP, but not of (NT-pro)BNP levels. After a mean follow-up of 3.2+/-0.9 (range 0.4-5.4) years, cardiovascular mortality was comparable (55 vs. 47%; P=ns). In both groups, AF and sinus rhythm, NT-proBNP [AF: adjusted HR 5.8 (1.3-25.4), P=0.02; sinus rhythm: adjusted HR 3.1 (1.7-5.7), P<0.001] was an independent risk indicator of cardiovascular mortality. CONCLUSION: In advanced CHF patients, AF affects (NT-)ANP levels, but not (NT-pro)BNP levels. NT-proBNP is an independent determinant of prognosis in advanced CHF, irrespective of the rhythm, AF, or sinus rhythm.     

Activation of generalised inflammatory reaction following electrical cardioversion

BACKGROUND: Restoration of sinus rhythm in patients with atrial fibrillation (AF) is associated with an increased risk of thrombo-embolic complications due to delayed return of the left atrial and left atrial appendage systolic function. Direct current cardioversion (DC), used for AF termination, may cause myocardial injury and subsequent activation of inflammatory response. A C-reactive protein (CRP) is a non-specific marker of inflammation. AIM: To examine the effects of external DC of AF or atrial flutter (AFlut) on inflammatory processes. METHODS: The study group consisted of 35 patients (20 females and 15 males, mean age 67.9+/-9.7 years, range 46-83 years) with paroxysmal or persistent AF/AFlut who underwent elective DC. CRP plasma concentration was measured before and 24 hours after DC. RESULTS: The mean total DC energy was 431.2 J. CRP plasma concentration increased significantly following DC - from 3.9+/-3.4 ng/ml before DC to 7.2+/-6.7 ng/ml after DC (p<0.0001). CRP level correlated with body mass index (r=0.34, p<0.05), however, this correlation became non-significant after inclusion of the presence of diabetes into the statistical model. There was also a positive correlation between CRP values before and after DC (r=0.72, p<0.0001). No correlation between CRP and gender, total power of DC nor the number of DC shocks was detected. CONCLUSIONS: External DC of AF/Aflut causes activation of inflammatory processes measured as a significant increase in the CRP plasma concentration.     

High sensitivity C-reactive protein: a predictor for recurrence of atrial fibrillation after successful cardioversion

Atrial fibrillation (AF) is often associated, more or less indirectly, with an inflammatory acute or chronic process. So it is probable that the inflammation could contribute to the genesis and the perpetuation of this dysrhythmia. Phlogistic test indexes in patients (pts) with AF will be positive and have prognostic significance in patients treated with electrical cardioversion with restoration of a sinus rhythm. We evaluated 106 pts affected by AF of recent onset without known cardiovascular disease. We measured the plasma concentration of C-reactive protein (CRP) through a high sensibility method, in addition to routine blood samples. We perfomed an ECG 1 week and a Holter ECG monitoring 1 and 6 months after the electrical cardioversion. The CRP values were high (5.8 ± 10.7 U/L), with values above the normal range in 60 pts. After electrical cardioversion, we obtained restoration of sinus rhythm in all the patients. One week after cardioversion, 85 pts (80%) were in sinus rhythm, while after 6 months 60 pts (56%) maintained a sinus rhythm. In total 46 (43%) patients had a recurrence of atrial fibrillation within 6 months, and 41 of these 46 patients (89%) had elevated values of CRP (P < 0.001 with respect to the patients who maintained a sinus rhythm). 18/21 patients (86%) with an AF relapse in the first week and 23/25 patients (92%) with AF recurrences at 6 months later had elevated values of CRP. The patients with AF may have elevated values of CRP, and the assessment of this increase may be predictive of early relapses of AF after electrical cardioversion.     

Transient atrial fibrillation complicating acute inferior myocardial infarction: implications for future risk of ischemic stroke

BACKGROUND: Atrial fibrillation (AF) that occurs as a frequent complication of myocardial infarction (MI) is associated with a poor clinical outcome. It nonetheless remains uncertain whether AF that occurs transiently during MI is associated with a subsequent increased risk of the development of AF and ischemic stroke. METHODS: We retrospectively studied the impact of transient AF on the long-term risk of the occurrence of AF, ischemic stroke, and mortality in 431 consecutive patients (mean [+/- SEM] age, 64 +/- 1 years; 75% men). All patients had experienced an acute inferior ST-segment-elevation MI and had preserved left ventricular ejection fraction (LVEF) [> 45%]. RESULTS: All patients were in sinus rhythm on hospital admission, and transient AF was observed in 59 patients (13.7%) during their hospitalization for MI. On hospital discharge, all patients were in sinus rhythm and had been prescribed antiplatelet agents alone as antithrombotic therapy. Patients in whom transient AF developed during MI were older (mean age, 70 +/- 1.4 vs 64 +/- 0.7 years, respectively; p < 0.01) and more likely to be women (37% vs 23%, respectively; p < 0.02) compared with those without AF. At 1-year follow-up, the incidence of AF (22.0% vs 1.3%, respectively; p < 0.01) and ischemic stroke (10.2% vs 1.8%, respectively; p < 0.01) was higher in patients with transient AF than in those without transient AF. The total mortality rate was nonetheless similar (5.6% vs 6.8%, respectively; p = 0.73); Cox regression analysis demonstrated that age > 65 years and transient AF during MI were independent predictors of the subsequent occurrence of AF and the development of ischemic stroke. CONCLUSION: Transient AF complicating acute inferior MI is associated with an increased future risk of AF occurrence and ischemic stroke in patients with preserved LVEF, despite the use of antiplatelet therapy.     

缺血性心力衰竭患者心房颤动与血清尿酸水平的关联性

目的 探讨缺血性心力衰竭（HF）患者心房颤动（AF）与血清尿酸（SUA）水平的关联性。方法 连续性收集于2012年10月~2014年10月就诊于佛山市中医院的缺血性HF患者363例,根据心电图或者病史记录将患者分为AF组和无AF组,比较两组间基线特征及SUA与AF的相关性。结果 363例患者中,共有78例患者患有AF,285例患者为正常窦性心律。与无AF患者相比,AF患者的SUA水平显著提高〔(64±21) vs.(57±19) mg/L,P<0.01〕。同时,AF组患者的年龄更大〔(71±8) vs.(66±11)岁,P<0.01〕。此外,AF患者的超声心动图指标,包括左室射血分数、左房内径、左心室舒张末期内径以及左心室舒张末期容积,同样显著高于窦性心律正常的患者。多因素回归分析显示,校正相关影响因素后,SUA水平仍为AF的独立相关因素(OR=1.27,95% CI,1.06-1.52,P≤0.01)。结论 SUA水平是缺血性HF患者AF的独立相关因素。     

Elevated preprocedural high-sensitivity C-reactive protein levels are associated with neointimal hyperplasia and restenosis development after successful coronary artery stenting.

BACKGROUND: Recent data indicate that an elevated serum level of high-sensitivity C-reactive protein (hs-CRP) predicts the risk of recurrent coronary events, and that statin therapy decreases the risk of coronary events. This study assessed the relationship between the pre-procedural hs-CRP level and in-stent neointimal hyperplasia (NIH) after stenting and the effects of statins on the relationship between restenosis after stenting and the serum hs-CRP levels of patients with coronary artery disease. METHODS AND RESULTS: This study included 100 patients who underwent stent implantation for angiographically significant stenosis. Patients were divided into a normal C-reactive protein (CRP) group (<0.5 mg/dl, n=59) and elevated CRP group (>or=0.5 mg/dl, n=41). All patients underwent angiographic and intravascular ultrasound follow-up at 6 months. The baseline CRP level was 0.29+/-0.08 mg/dl in the normal CRP group and 2.90+/-2.31 mg/dl in the elevated CRP group. The NIH cross-sectional area (CSA) in the minimal lumen CSA at follow-up was significantly larger in the elevated CRP group compared with the normal CRP group (1.9+/-1.3 mm2 vs 3.0+/-1.5 mm2, p=0.001). A significant positive correlation was found between pre-interventional CRP level and NIH area (r=0.52, p<0.001). In patients with normal CRP, an association between statin therapy and restenosis was not observed. However, when the analysis was confined to patients with elevated CRP, statin therapy significantly reduced the restenosis rate (20% vs 37.5%, p=0.031). In the normal CRP group, the intra-stent neointimal area at 6 months was not different between the non-statin and statin groups (2.2+/-1.4 mm2 vs 1.8+/-1.1 mm2). However, in the elevated CRP group, statin therapy significantly decreased the neointimal area at 6-month follow-up (3.6+/-1.7 mm2 vs 2.4+/-1.3 mm2, p<0.001). CONCLUSION: Measuring the pre-interventional hs-CRP level may help predict the development of restenosis after stenting and statin therapy will significantly reduce the restenosis rate in patients with an elevated hs-CRP.     

C反应蛋白对心房颤动药物复律后复发的远期预测价值

目的研究基线C反应蛋白(CRP)水平与心房颤动(简称房颤)药物复律后远期复发之间的关系。方法 71例持续性房颤患者使用胺碘酮复律,并且接受胺碘酮维持窦性节律的治疗,复律成功43例。根据基线CRP水平将复律成功的43例分为2组(0~4 mg/L组、≥4 mg/L组)。随访观察3年后,了解基线CRP水平与房颤复发间的关系。结果随访期内,有32(74.7%)例房颤复发。CRP 0~4 mg/L组,有12(12/21,57.1%)例房颤复发,CRP水平≥4 mg/L组有20例(20/22,90.9%)房颤复发,两组比较差异有显著性(P0.05)。Cox相关分析表明CRP基线水平与房颤复发相关(风险比6.09;95%可信区间3.15~12.60)。结论在预测房颤药物复律后房颤复发上,基线CRP水平可能有预测价值。     

Effect of Physical Exercise on Platelet Activity and the von-Willebrand-Factor in Patients with Persistent Lone Atrial Fibrillation

BACKGROUND: The risk of stroke is of great clinical importance in patients with atrial fibrillation (AF). It is not known whether physical exercise influences plasma coagulation and platelet aggregability during AF. The purpose of this study was to assess the effect of physical exercise on platelet activity, thrombin generation, and levels of von-Willebrand-factor in patients with persistent AF. METHODS: Thirteen patients with lone AF (>or=1 year) were compared with 13 matched patients in sinus rhythm. Patients with AF were anticoagulated effectively with coumarin. All patients underwent bicycle ergometry using a respiratory gas exchange technique for 20 min at one-third of the age-adjusted maximal workload. Thereafter, workload was increased until maximal exercise capacity was reached. Platelet factor-4 (PF-4), beta-thromboglobulin (beta-TG; marker for platelet activation), von-Willebrand-factor (vWF; marker for endothelial dysfunction), prothrombin fragment F1 + 2 (F1 + 2; marker for thrombin generation) and fibrinogen levels were determined throughout the study in all patients. RESULTS: Gas exchange variables, hemodynamic parameters and norepinephrine levels were comparable in the groups during moderate (45 +/- 5 W) and heavy exercise (198 +/- 38 W). In contrast to moderate exercise, PF-4 and beta-TG levels increased to 212 +/- 56% ( p < 0.05) and to 145 +/- 24% ( p < 0.05), respectively, in patients with AF during heavy exercise. In contrast, physical exercise had no significant effect on platelet activity in patients with sinus rhythm. Levels of vWF increased by delta24% ( p < 0.05) in all patients during maximal exercise, whereas F1 + 2 levels increased only in patients with sinus rhythm. CONCLUSIONS: Heavy physical activity increases platelet activity and vWF levels during AF, whereas moderate exercise has no procoagulatory effect. Coumarin therapy prevents exercise-induced thrombin generation only. Future studies are needed to prove the hypothesis that heavy physical exercise is a risk factor for thromboembolic events in patients with AF.     

Elevation of C-reactive protein in "active" coronary artery disease

Unstable angina occurs most commonly in the setting of atherosclerotic coronary artery disease (CAD), but there is little information concerning the mechanisms responsible for the transition from clinically stable to unstable coronary atherosclerotic plaque. Recently, increased focal infiltration of inflammatory cells into the adventitia of coronary arteries of patients dying suddenly from CAD and activation of circulating neutrophils in patients with unstable angina have been observed. To characterize the presence of inflammation in "active" atherosclerotic lesions, the acute phase reactant C-reactive protein (CRP) was measured in 37 patients admitted to the coronary care unit with unstable angina, 30 patients admitted to the coronary care unit with nonischemic illnesses and 32 patients with stable CAD. CRP levels were significantly elevated (normal less than 0.6 mg/dl) in 90% of the unstable angina group compared to 20% of the coronary care unit group and 13% of the stable angina group. The average CRP values were significantly different (p = 0.001) for the unstable angina group (2.2 +/- 2.9 mg/dl) compared to the coronary care (0.9 +/- 0.7 mg/dl) and stable angina (0.7 +/- 0.2 mg/dl) groups. There was a trend for unstable angina patients with ischemic ST-T-wave abnormalities to have higher CRP values (2.6 +/- 3.4) than those without electrocardiographic changes (1.3 +/- 0.9, p = 0.1). The data demonstrate increased levels of an acute phase reactant in unstable angina. These findings suggest that an inflammatory component in "active" angina may contribute to the susceptibility of these patients to vasospasm and thrombosis.     

Association between C-reactive protein and recurrence of atrial fibrillation after successful electrical cardioversion: a meta-analysis.

OBJECTIVES: We conducted a systematic review and meta-analysis of observational studies to examine the association between baseline C-reactive protein (CRP) levels and the recurrence of atrial fibrillation (AF) after successful electrical cardioversion (EC). BACKGROUND: Current evidence links AF to the inflammatory state. Inflammatory indexes such as CRP have been related to the development and persistence of AF. However, inconsistent results have been published with regard to the role of CRP in predicting sinus rhythm maintenance after successful EC. METHODS: Using PubMed, the Cochrane clinical trials database, and EMBASE, we searched for literature published June 2006 or earlier. In addition, a manual search was performed using all review articles on this topic, reference lists of papers, and abstracts from conference reports. Of the 225 initially identified studies, 7 prospective observational studies with 420 patients (229 with and 191 without AF relapse) were finally analyzed. RESULTS: Overall, baseline CRP levels were greater in patients with AF recurrence. The standardized mean difference in the CRP levels between the patients with, and those without AF was 0.35 units (95% confidence interval 0.01 to 0.69); test for overall effect z-score = 2.00 (p = 0.05). The heterogeneity test showed that there were significant differences between individual studies (p = 0.02; I(2) = 60.2%). Further analysis revealed that differences between the CRP assays possibly account for this heterogeneity. CONCLUSIONS: Our meta-analysis suggests that increased CRP levels are associated with greater risk of AF recurrence, although there was significant heterogeneity across the studies. The use of CRP levels in predicting sinus rhythm maintenance appears promising but requires further study.     

Effect of rate and rhythm control on left ventricular function and cardiac dimensions in patients with persistent atrial fibrillation: results from the RAte Control versus Electrical Cardioversion for Persistent Atrial Fibrillation (RACE) study.

OBJECTIVES: The purpose of this study was to evaluate left ventricular function and atrial and ventricular diameters in patients with persistent atrial fibrillation (AF) treated with rate or rhythm control. BACKGROUND: Restoration of sinus rhythm in patients with persistent AF may improve left ventricular function and reduce atrial dimensions. Adequate rate control in AF may preserve ventricular function. METHODS: In 335 patients included in the RAte Control versus Electrical Cardioversion for Persistent Atrial Fibrillation (RACE) study, echocardiography was performed at baseline and 1- and 2-year follow-up. Echocardiography was compared between patients randomized to rate control (n = 160) and rhythm control (n = 175). In the rhythm control group, echocardiography was compared between patients with AF versus sinus rhythm at study end. Multivariate analysis was performed to determine parameters related to improvement of left ventricular function and increase of atrial diameters. RESULTS: Fractional shortening improved significantly under rate and rhythm control (31 +/- 10% at baseline to 33 +/- 9% at 2 years, and from 30 +/- 10% to 34 +/- 9%; both P < .05, respectively). Under rate control, left and right atrial size increased significantly compared to baseline. Under rhythm control, only left atrial size increased. Multivariate analysis revealed that only sinus rhythm at study end was associated with an increase of fractional shortening. AF at study end, hypertension, and no use of angiotensin-converting enzyme inhibitors were independently associated with increase in atrial size. CONCLUSIONS: Routine rate control prevents deterioration of left ventricular function. Maintenance of sinus rhythm is associated with improvement of left ventricular function and reduction of atrial sizes.     

Frequency of helicobacter pylori seropositivity and C-reactive protein increase in atrial fibrillation in patients undergoing coronary angiography

Atrial fibrillation (AF) is the most common rhythm disturbance seen in clinical practice. Evidence emerged that suggested inflammation was associated with risk of AF. Helicobacter pylori causes gastric and esophageal inflammation, as well as systemic and vascular inflammation. These local and systemic inflammatory effects may increase the risk of AF. Study patients were consecutive patients who underwent angiography for suspicion of coronary artery disease. Patients' AF status was determined by a search of hospital discharge summaries for diagnostic International Classification of Diseases, Ninth Revision codes for AF, assessment of previous electrocardiograms at the index and previous admissions to LDS Hospital (Salt Lake City, Utah), and search of the electrocardiographic database of LDS Hospital. In addition to routine laboratory studies, serum was analyzed to determine H pylori serostatus and index C-reactive protein (CRP) level. A total of 943 patients with known AF status were studied. Those with AF tended to be older (70.9 +/- 9.5 vs 63.9 +/- 10.7 years; p <0.001) and had a higher prevalence of congestive heart failure (28% vs 11%; p <0.001). In addition, patients with AF were more likely to be seropositive for H pylori in comparison to the seronegative group (65% vs 55%; p = 0.049). Mean CRP was similar between those with and without AF (2.2 +/- 2.7 vs 2.3 +/- 2.4 mg/dl; p = 0.79). There was no apparent association between H pylori serostatus and CRP. Multivariate predictors of AF included age (hazard ratio [HR] 1.07 per year, 95% confidence interval [CI] 1.04 to 1.10, p <0.0001) and heart failure (HR 2.87, 95% CI 1.59 to 5.18, p <0.0001). H pylori added to the model was marginally associated with AF (HR 1.53, 95% CI 0.95 to 2.47, p = 0.08) when not accounting for age. However, younger patients (<50 years) who were H pylori seropositive had a higher relative risk of AF (8%) versus those who were seronegative (0%). In comparison, older patients seropositive for H pylori had only a modest increased risk of AF (17.5% vs 15.4%; p = 0.11). In conclusion, these data showed a general association of H pylori and AF in patients with multiple cardiovascular risk factors. The association did not persist after accounting for other risk factors. Although older age was highly associated with AF risk in this population, H pylori was additive across 3 distinct age groups, with the highest risk conveyed in the younger cohort.