Reduced apelin levels in lone atrial fibrillation.

AIMS: Apelin is an endogenous peptide hormone that appears to have a physiological role in counter-regulation of the angiotensin and vasopressin systems. This peptide has been reported to be down-regulated in subjects with acute heart failure, but has not been studied in other cardiovascular conditions. We studied apelin levels in 73 subjects with lone atrial fibrillation (AF). METHODS AND RESULTS: Study subjects had electrocardiographic evidence of paroxysmal or chronic AF and a structurally normal heart on echocardiography. Subjects were excluded if they had a history of coronary artery disease, rheumatic heart disease, cardiomyopathy, significant valvular disease, hyperthyroidism, or antecedent hypertension. Controls were recruited from a healthy outpatient population. Plasma apelin levels were determined using a commercially available immunoassay. Seventy-three subjects with lone AF and 73 healthy controls were enrolled and studied. Mean levels of apelin were significantly lower in subjects with lone AF when compared with controls (307 vs. 648 pg/mL, P<0.00005). CONCLUSION: Reduced apelin levels were observed in this homogenous population of lone AF subjects and may represent an underlying diathesis predisposing to this common arrhythmia.     

Discordant atrial natriuretic peptide and brain natriuretic peptide levels in lone atrial fibrillation

OBJECTIVES: We sought to characterize natriuretic peptide levels in a cohort of rigorously characterized subjects with lone atrial fibrillation (AF). BACKGROUND: Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are sensitive biomarkers of cardiac contractile dysfunction. Both peptides have been reported to be elevated in cohorts with AF, but previous studies have included subjects with underlying structural heart disease. We studied these hormones in 150 subjects with lone AF. METHODS: Study subjects had electrocardiographic evidence of at least one episode of AF and a structurally normal heart on echocardiography. Subjects were excluded if they had a history of a myocardial infarction, rheumatic heart disease, cardiomyopathy, significant valvular disease, hyperthyroidism, or hypertension that preceded the onset of AF. Control subjects were obtained from a healthy outpatient primary care population. Plasma pro-ANP and N-terminal pro-BNP (nt-pro-BNP) levels were determined using commercially available immunoassays. RESULTS: A total of 150 serial subjects with lone AF were enrolled and studied, the majority during normal sinus rhythm. Median levels of nt-pro-BNP were significantly elevated in subjects with lone AF as compared with control subjects (166 vs. 133 fmol/ml, p=0.0003). There was no significant difference in pro-ANP levels between subjects with lone AF and control subjects (1,730 vs. 1,625 fmol/ml, p=0.90). CONCLUSIONS: Discordant natriuretic peptide levels were observed in this homogeneous population of subjects with lone AF. This biomarker pattern, which is present even in sinus rhythm, may represent an underlying subclinical predisposition to this common arrhythmia.     

Soluble E-selectin, von Willebrand factor, soluble thrombomodulin, and total body nitrate/nitrite product as indices of endothelial damage/dysfunction in paroxysmal, persistent, and permanent atrial fibrillation

BACKGROUND: Atrial fibrillation (AF) is associated with a prothrombotic state, which is related to endothelial damage/dysfunction. Plasma levels of soluble E-selectin (sE-sel), von Willebrand factor (vWf), and soluble thrombomodulin (sTM) have been used as indexes of endothelial activation, damage/dysfunction, and endothelial damage, respectively. Nitric oxide is also made by a healthy endothelium, and a total body nitrate/nitrite product (NOx) is used as a measure of endothelial nitric oxide production. We hypothesized that the levels of these markers of endothelial function would be abnormal in patients with paroxysmal, persistent, and permanent AF. METHODS: We studied 145 AF patients (paroxysmal AF, 35 patients; permanent AF, 50 patients; persistent AF, 60 patients) and 35 patients with "lone" AF. Plasma levels of sE-sel, vWf, and sTM (measured by enzyme-linked immunosorbent assay) and NOx (measured by a colorimetric assay based on the Griess reaction) were compared to 40 age-matched healthy control subjects in sinus rhythm. RESULTS: Patients with AF had significantly higher plasma levels of vWf (p < 0.001) and sE-sel (p = 0.005) compared with control subjects, but sTM and NOx levels were not significantly different. Levels did not differ significantly among the clinical subgroups of patients with paroxysmal, persistent, and permanent AF. Patients with lone AF had significantly higher vWF levels (p = 0.003) and significantly lower sTM levels (p = 0.0361) compared to control subjects, but sE-sel and NOx levels were not significantly different. There were no significant differences in the AF study population in vWF, sE-sel or sTM levels after 4 weeks of warfarin treatment. CONCLUSION: Endothelial perturbation exists in all clinical subgroups of patients with AF, including those with lone AF, which may contribute to the prothrombotic state seen in these patients.     

Relation of C-reactive protein to the first onset and the recurrence rate in lone atrial fibrillation

The presence of systemic inflammation determined by elevations in high-sensitivity C-reactive protein (hs-CRP) has been associated with persistence of atrial fibrillation (AF). The influence of inflammation markers, such as hs-CRP, on the recurrences of lone AF, however, has not been clarified. We tested the hypothesis of whether, in patients with a first paroxysmal episode of lone AF, the hs-CRP levels were elevated, and whether elevated hs-CRP could predict the recurrence rate of lone AF in patients without antiarrhythmic drugs. Using a case-control study design, the hs-CRP levels in 125 patients with a documented symptomatic first paroxysmal episode of lone AF was compared with the hs-CRP levels in 65 control patients. hs-CRP levels are presented as median values with the interquartile range (25th to 75th percentiles). The hazard ratio compared the 75th percentile of hs-CRP with the 25th percentile. In the arrhythmia group, hs-CRP was higher than in the control patients (median 0.23 mg/dl, interquartile range 0.12 to 0.49, vs 0.087 mg/dl, interquartile range 0.058 to 0.098, p <0.001). After adjusting for baseline characteristics, including, age, gender, and baseline blood pressure, hs-CRP remained a significant predictor of recurrent AF (hazard ratio 1.15, 95% confidence interval 1.04 to 1.24, p = 0.002) at 2 years of follow-up. In conclusion, this study is the first to document that the first paroxysmal episode of lone AF is associated with elevated hs-CRP levels, suggesting that hs-CRP may be a marker for inflammatory states that may promote the initiation of lone AF. These pathways may represent a novel mechanism by which structural changes resulting from inflammation could induce lone AF. The elevated hs-CRP levels could also predict the recurrence rate of lone AF in patients without antiarrhythmic drugs.     

Rare Variants in GJA5 Are Associated With Early-Onset Lone Atrial Fibrillation

Background

Genetic factors are believed to be important in early-onset lone atrial fibrillation (AF). The gene GJA5 encodes the gap-junction protein Cx40, which together with Cx43 is responsible for the electrical coupling of the atrial cardiomyocytes. The regulatory single nucleotide polymorphism rs10465885 in GJA5 was recently associated with early-onset lone AF (< 60 years) and was also found to be strongly associated with Cx40 messenger RNA levels. We hypothesized that this gene would have a strong effect in patients with a more selected phenotype, and that the findings regarding rs10465885 could be replicated in this group.

Methods

The coding region and flanking intron sequences of GJA5 were resequenced in 342 patients with onset of lone AF before the age of 50 (mean age at onset 34 ± 9 years), and in 216 controls. The single nucleotide polymorphism rs10465885 was genotyped in 342 patients and 534 control subjects and odds ratios were calculated for different genetic models.

Results

Genotyping of rs10465885 showed that the patients with early-onset lone AF were more likely to carry the A allele compared with controls (odds ratio = 1.30; P = 0.011). When resequencing GJA5, we identified the mutation A96S, previously associated with lone AF, which was not present in our control subjects or in any publicly available database or the National Heart, Lung, and Blood Institute Exome Variant Server (NHLBI EVS; 10,758 alleles).

Conclusions

We show a highly significant association between the A allele of rs10465885 and onset of lone AF before age 50. This opposes a previous study, wherein the G allele was found to be associated with AF, and makes it impossible to exclude that the associations are coincidental.     

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.     

孤立性心房颤动患者血浆血小板α颗粒膜蛋白-140和血栓素B_2及6-酮-前列腺素F_(1α)浓度变化的研究

目的研究孤立性心房颤动(房颤)患者血小板功能改变,探讨房颤引起血栓前状态的原因。方法用放射免疫分析法对21例孤立性阵发性房颤(A组)、28例孤立性持续性房颤(B组)患者分别于房颤发作及终止后1周测定外周静脉血浆血小板а颗粒膜蛋白-140(GMP-140)、血栓素B2(TXB2)、6-酮-前列腺素F1α(6-K-PGF1α)浓度,并与27例风湿性心脏病二尖瓣狭窄伴持续性房颤(C组)、32例阵发性室上性心动过速患者(D组)及与20例健康体检者(对照组)相比较。结果A、B组患者房颤发作时及C组患者GMP-140、TXB2和TXB2/6-K-PGF1α比A组患者房颤终止后1周和D组及对照组明显上升。A组患者血浆GMP-140、TXB2浓度及TXB2/6-K-PGF1α与房颤发作时间呈正相关,而与患者年龄、性别及左心房内径等临床参数无关。结论无论是器质性心脏病房颤还是孤立性房颤,无论是阵发性房颤还是持续性房颤都存在血小板的激活和血管内皮细胞功能损伤。     

Inflammatory activation in an unselected population of subjects with atrial fibrillation: links with structural heart disease, atrial remodeling and recent onset

Previous studies investigated circulating levels of C-reactive protein (CRP) mostly in subjects with paroxysmal atrial fibrillation (AF) and lone AF (LAF). We, therefore, aimed to investigate circulating levels of CRP in patients with new onset AF with particular regards to AF duration, even in the presence of structural heart disease (SHD). CRP levels were evaluated in 96 consecutive patients with new onset AF (50 with LAF and 46 with SHD, 41 with paroxysmal AF (PAF) (<7 days) and 55 persistent AF (>7 days). Patients with AF had higher CRP levels than controls (4.8 ± 6.99 vs. 1.59 ± 1.32 mg/L; p < 0.001). AF patients with SHD had higher CRP levels than LAF patients (7.08 ± 9.19 vs. 2.63 ± 2.47 mg/L; p < 0.01) and control subjects (vs. 1.59 ± 1.32 mg/L; p < 0.001): CRP levels in LAF patients were higher than in controls (p < 0.01). CRP levels were significantly increased in subjects with paroxysmal AF (6.67 ± 9.44 mg/L) with respect to those with persistent AF (3.54 ± 4.44 mg/L, p < 0.05) and controls (1.59 ± 1.32 mg/L, p < 0.001 vs. paroxysmal AF, p < 0.01 vs. persistent AF). Differences related to the presence of LAF and SHD remained significant even after multivariable regression analysis. CRP concentrations significantly correlated with left atrial size(r 0.23, p < 0.05). Increased CRP levels are detectable in patients with AF, proportional to atrial remodeling, recent onset of dysrhythmia and SHD.     

Associations of big endothelin-1 and C-reactive protein in atrial fibrillation

Background Atrial fibrillation (AF) is associated with inflammation and endothelial dysfunction. However, the association between inflammation (as indexed by high-sensitivity C-reactive protein, hs-CRP) and endothelial function [as indexed by big endothelin-1 (ET-1)] in AF patients remains unclear. Methods We enrolled 128 patients with lone AF, among which 83 had paroxysmal AF, and 45 had persistent AF. Eighty-two age- and gender-matched controls of paroxysmal supraventricular tachycardia without AF history were evaluated. Plasma hs-CRP, big ET-1 levels and other clinical characteristics were compared among the groups. Results Patients with persistent AF had higher hs-CRP concentrations than those with paroxysmal AF (P < 0.05), both groups had higher hs-CRP level than controls (P < 0.05). Patients with persistent AF had higher big ET-1 level than those with paroxysmal AF, although the difference did not reach the statistical significance (P > 0.05), and both groups had higher big ET-1 levels than controls (P < 0.05). Multiple regression analyses revealed hs-CRP as an independent determinant of AF (P < 0.001). Further adjusted for big ET-1, both big ET-1 and hs-CRP were independent predictors for AF (P < 0.001), but the odds ratio for hs-CRP in predicting AF attenuated from 8.043 to 3.241. There was a positive relation between hs-CRP level and big ET-1 level in paroxysmal AF patients (r = 0.563, P < 0.05), however, the relationship in persistent AF patients was poor (r = 0.094, P < 0.05). Conclusions Both plasma hs-CRP and big ET-1 levels are elevated in lone AF patients, and are associated with AF. In paroxysmal lone AF patients, there were significant positive correlations between plasma hs-CRP level and big ET-1 level.     

Maintenance of Sinus Rhythm after Cardioversion of Atrial Fibrillation in Patients with Lone Atrial Fibrillation and Patients with Hypertension

Background: The success rate and prognosis of cardioversion of atrial fibrillation (AF) in patients with organic heart disease is well known. In contrast, little data exist about cardioversion success and maintenance of sinus rhythm (SR) in patients with lone AF and in patients with hypertension as the only underlying cardiovascular disease. Methods: In a prospective cardioversion registry 148 of 181 patients (81.8%) with lone AF (age 58 ± 13 years, duration of AF 7.6 ± 19 weeks) and 120 of 148 patients (81.1%) with hypertension (age 62 ± 10 years, duration of AF 6.6 ± 21 weeks) had successful cardioversion and were followed for 7.7 ± 1.9 months. Results: At follow-up, 120 patients (81.1%) with lone AF were in SR, and 18 of these patients had had repeated cardioversion during follow-up (AF total recurrence rate 31.1%). In stepwise regression analysis, the number of previous cardioversions was predictive of rhythm at follow-up (P = 0.0453). Rhythm at follow-up did not differ between patients who were or were not on antiarrhythmic drugs. At follow-up 96 patients (80%) with hypertension were in SR, and 9 of these had had repeated cardioversion during follow-up (AF total recurrence rate 27.5%). As in lone AF, the recurrence rate of AF did not differ between patients with or without antiarrhythmic drug treatment, and in multivariate regression analysis, the number of previous cardioversions was the only clinical predictor of rhythm at follow-up (P = 0.0284). Conclusions: Even in patients with such benign conditions as lone AF or hypertension as the only underlying disease, the prognosis of cardioversion in terms of maintenance of SR is poor. Future studies of rhythm control versus rate control need to include not only patients with organic heart disease but also patients with lone AF and patients with hypertension, since the long-term benefits of these two strategies remain unclear even in these subsets of patients.     

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.     

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.     

C-reactive protein and nitric oxide level in patients with white coat hypertension

Abstract Background. There are controversial results regarding the endothelial function in patients with white coat hypertension (WCH). The aim of this study was to assess endothelial function measuring nitric oxide (NO) and C-reactive protein (CRP) level in WCH and to compare those with essential hypertension (EH) and healthy subjects. Methods. The 40 newly diagnosed patients with EH, 40 patients with WCH and 40 healthy volunteers were included to study. Plasma CRP levels were measured by immunonephelometery method. Plasma NO level was also detected by using the Griess method. Results. Plasma CRP level was significantly higher in patients with EH when compared with those with WCH and healthy subjects (6.3 ± 2.1 mg/l, 2.1 ± 0.9 mg/l and 1.6 ± 1.3 mg/l, p < 0.05, respectively). However, there was no significant difference with respect to CRP level between those with WCH and healthy subjects. NO level was significantly lower in patients with EH when compared with those with WCH and healthy subjects (4.6 ± 1.1 μmol/l, 6.9 ± 1.2 μmol/l and 8.1 ± 1.5 μmol/l, p < 0.05, respectively). There was no significant difference with respect to NO level between those with WCH and healthy subjects. Plasma CRP level was positively correlated with office, daytime, night-time and 24-h blood pressure values, whereas NO level was inversely correlated with these parameters. Plasma CRP level was also inversely correlated with NO level. Conclusions. Our data suggest that CRP concentration is significantly higher and NO level is meaningfully lower in patients with essential hypertension when compared with those with WCH and controls. This may suggest that endothelial functions are preserved in patients with WCH in contrast to essential hypertension.     

Elevated platelet microparticle levels in nonvalvular atrial fibrillation: relationship to p-selectin and antithrombotic therapy

BACKGROUND: Platelet microparticles (PMPs), are procoagulant membrane vesicles that are derived from activated platelets, the levels of which are elevated in patients with hypertension, coronary artery disease (CAD), diabetes, and stroke, all of which are conditions that lead to (and are associated with) atrial fibrillation (AF). We hypothesized the following: (1) PMP levels are elevated in patients with AF compared to levels in both healthy control subjects (ie, patients without cardiovascular diseases who are in sinus rhythm) and disease control subjects (ie, patients with hypertension, CAD, diabetes or stroke, but who are in sinus rhythm); (2) PMP levels correlate with levels of soluble P-selectin (sP-selectin) [a marker of platelet activation]; and (3) PMP levels are related to the underlying factors in patients with AF that contribute to the overall risk of stroke secondary to AF. METHODS: We performed a case-control study of 70 AF patients, 46 disease control subjects and 33 healthy control subjects. Peripheral venous levels of PMP and sP-selectin were analyzed by flow cytometry and enzyme-linked immunosorbent assay, respectively. RESULTS: Both AF patients and disease control subjects had significantly higher levels of PMPs (p < 0.001) and sP-selectin (p = 0.001) compared to healthy control subjects, but there was no difference between AF patients and disease control subjects. There was no difference in PMP levels between patients with paroxysmal and permanent AF (p = 0.581), and between those receiving therapy with aspirin and warfarin (p = 0.779). No significant correlation was observed between PMP and sP-selectin levels (p = 0.463), and the clinical characteristics that contribute to increased stroke risk in patients with AF. On stepwise multiple regression analysis in the combined cohort of AF patients plus disease control subjects, the presence/absence of AF was not an independent determinant of PMP and sP-selectin levels. CONCLUSION: There is evidence of platelet activation (ie, high PMP and sP-selectin levels) in AF patients, but this is likely to be due to underlying cardiovascular diseases rather than the arrhythmia per se.     

Meta-analysis of association between C-reactive protein and immediate success of electrical cardioversion in persistent atrial fibrillation

Current evidence links atrial fibrillation (AF) to the inflammatory state. Also, increased C-reactive protein (CRP) levels have been associated with greater risk of recurrence of AF after successful electrical cardioversion (EC). We conducted a meta-analysis of observational studies to examine the association between baseline CRP levels and the immediate success of EC in persistent AF. We searched the literature published November 2007 or earlier. In addition, a manual search was performed using all review articles on this topic, reference lists of studies, and abstracts from conference reports. Of the 342 initially identified studies, 6 prospective observational studies with a combined 366 patients (297 with successful and 69 with failed EC) were analyzed. Overall, CRP levels were greater in patients with failed EC. The standardized mean difference in the CRP levels between patients with successful and those with failed EC was -0.41 units (95% confidence intervals -0.68 to -0.14) and the Z score for overall effect was 2.98 (p=0.003). The heterogeneity test showed that there were no significant differences between the individual studies (p=0.36; I(2)=9.1%). In conclusion, our meta-analysis suggests that increased CRP levels are associated with greater risk of EC failure. CRP assessment before cardioversion may provide prognostic information regarding the success of the procedure.     

C-reactive protein and atrial fibrillation: "evidence for the presence of inflammation in the perpetuation of the arrhythmia"

BACKGROUND: Atrial fibrillation (AF) is associated to a high risk of systemic embolism. The mechanisms that contribute to thrombogenesis in these patients are still poorly understood. Systemic and/or local inflammation could be involved in the process of thrombogenesis and contribute to the perpetuation of the arrhythmia. The purpose of the study was to evaluate the role of inflammation and its relation to thrombogenesis and cardiac rhythm in AF. METHODS: We prospectively studied 130 patients with newly diagnosed non-valvular AF in absence of antithrombotic therapy. Determinations of C-reactive protein (CRP) and thrombin-antithrombin complex (TAT) plasma levels, along with a transesophageal echocardiogram were performed in all the patients at admission. RESULTS: Mean age of the group was 67+/-14 years. CRP levels were significantly elevated in AF patients versus controls (matched by age, gender and cardiovascular risk factors) (1.0+/-1.8 versus 0.3+/-0.4 mg/dl, respectively, p<0.01). Baseline TAT levels were also significantly elevated in AF patients but no correlation was found between CRP and TAT. At 1-year of follow-up, mean CRP levels were still elevated in patients that remained in AF compared to those who converted to sinus rhythm (1.2+/-1.8 compared to 0.5+/-1.5 mg/dl, p=0.03). CRP was the only biochemical predictor of sinus rhythm maintenance at 1-year follow-up independently of clinical (including adjustment for risk factors and antiarrhythmic drugs), biochemical and echo parameters. CONCLUSIONS: There is evidence for the presence of inflammation in patients with non-valvular AF, which is not related to activation of the coagulation cascade. The persistence of inflammation is associated with chronic AF at 1-year follow up.     

血浆抵抗素水平与心房颤动关系的临床研究

目的：通过测定血浆抵抗素的水平,研究其在孤立性心房颤动（房颤）的发生与维持中的作用;同时分析影响其水平的相关因素及房颤的风险因素。方法研究对象为2014年6月至12月因心悸等不适就诊我院心内科的患者140例,其中试验组为房颤人群,分为孤立性房颤（60例）和房颤合并高血压（55例）;根据发病时间不同,孤立性房颤又分为阵发性与持续性房颤,各30例。正常对照组为正常人群,共25例。使用单因素方差分析比较房颤人群与正常人群血浆抵抗素水平的差异。用 Pearson 及多重线性回归法分析影响房颤患者抵抗素水平的相关因素。用 Logistic 回归分析影响房颤的风险因素。结果①超敏 C 反应蛋白（hs-CRP）及血浆抵抗素水平：所有房颤组的水平均高于对照组,其中孤立性房颤组低于房颤合并高血压组;阵发性房颤组低于持续性房颤组。② Pearson 相关分析：血浆抵抗素水平与hs-CRP 水平、左房内径大小及收缩压均呈正相关（分别为 r ＝0．530,P ＝0．000;r ＝0．265,P ＝0．004;r ＝0．364,P ＝0．000）。多重线性回归分析进一步显示收缩压（SBP）、hs-CRP 水平与血浆抵抗素的水平存在线性关系：Y ＝－2．172＋0．089 SBP ＋1．347 hs-CRP（R2＝0．307,P ＜0．05）。③ Logistic 回归分析表明血浆抵抗素水平、hs-CRP 水平均被纳入回归方程,且 OR 值均＞1。结论①血浆抵抗素水平孤立性房颤组明显高于对照组,其中又以持续性房颤组增高为著,表明抵抗素与房颤的发生、节律的维持相关。②血浆抵抗素水平与 hs-CRP 的水平呈正相关,间接表明房颤的发生可能与抵抗素具有某种炎性特质相关,提示抵抗素可引起炎症反应并和炎症介质一起参与了房颤发生、维持。③血浆抵抗素水平在房颤合并高血压患者中升高明显,且具有协同效应,提示抵抗素也许具有独立表达高血压与房颤疾病的潜质。同时本研究也证实了高血压为房颤的风险因素,可推测抵抗素通过高血压影响房颤。     

Increased inflammatory markers are associated with obesity and not with target organ damage in newly diagnosed untreated essential hypertensive patients

The aim of this study was to investigate whether inflammatory markers are associated with hypertensive end organ damage or obesity in patients with hypertension. Seventy newly diagnosed essential hypertensive patients (29 men and 41 women aged 49.6 ± 9.5 y) and 25 age-sex-matched normotensive subjects (12 men and 13 women aged 45.8 ± 7.3 y) were asked about their family history of hypertension and smoking habits, and body mass index (BMI) was recorded and blood samples were taken to measure fibrinogen, C-reactive protein (CRP), and homocysteine levels. In hypertensive patients, creatinine clearance, urinary albumin extraction, and left ventricular mass index were determined. Hypertensive patients had significantly higher BMIs and inflammatory markers when compared with normotensive healthy controls. The CRP was positively associated with BMI (P < .05), diastolic blood pressure (P < .05), fibrinogen (P < .01), urinary albumin extraction (P < .01), and left ventricular mass index (P < .05). The BMI and serum fibrinogen level were independently associated with CRP. The effect of inflammation on the development of hypertensive end organ damage may be associated with obesity, so that control of obesity may eliminate the inflammatory state in hypertensive patients and also hypertensive end organ damage.     

Clinical characteristics of persistent lone atrial fibrillation in the RACE study

In the RAte Control versus Electrical cardioversion for persistent atrial fibrillation (RACE) study, 522 patients were randomized to either rate or rhythm control therapy. Lone atrial fibrillation (AF) was present in 89 patients. Demographics, cardiovascular mortality and morbidity, and quality of life were compared between patients with lone AF and those with underlying structural heart disease. Patients with lone AF were significantly younger (65 +/- 10 vs 69 +/- 8 years) and had fewer complaints of fatigue (p = 0.01) and dyspnea (p = 0.005). With lone AF, quality-of-life scores were higher on almost all 8 Medical Outcomes Study Short-Form health survey questionnaire subscales, and comparable to healthy, age- and gender-matched controls. Mean follow-up was 2.3 +/- 0.6 years. Cardiovascular end points occurred in 9 patients with lone AF (10%), consisting of death (all bleedings) 3%, thromboembolic complications in 3%, nonfatal bleeding in 2%, and pacemaker implantation in 2%, but no heart failure and severe adverse effects due to antiarrhythmic drugs occurred. End points occurred in 95 patients (22%) with underlying diseases. Heart failure and severe adverse effects from drugs did not occur in patients with lone AF in this study. Despite the absence of demonstrable cardiovascular and cerebrovascular disease, lone AF is associated with bleeding and thromboembolism.     

Relationship of interleukin-6 and C-reactive protein to the prothrombotic state in chronic atrial fibrillation

OBJECTIVES: We sought to test the hypothesis that there is a relationship between inflammation and the prothrombotic state in atrial fibrillation (AF). BACKGROUND: Atrial fibrillation is associated with a prothrombotic or hypercoagulable state, which may contribute to an increased risk of stroke and thromboembolism. Inflammation may be involved in the pathogenesis of AF, but the role of inflammation in the pathophysiology of the prothrombotic state of AF has not been studied in detail, despite evidence of a link between inflammation and arterial atherothrombotic disorders. METHODS: We measured plasma indexes of inflammation (C-reactive protein [CRP] and interleukin-6 [IL-6]) and the prothrombotic state, including markers of platelet activation (soluble P-selectin), endothelial damage/dysfunction (von Willebrand factor), the coagulation cascade (tissue factor [TF], fibrinogen), and indexes of blood rheology (plasma viscosity, plasma fibrinogen, and hematocrit) in 106 patients with chronic AF and 41 healthy control subjects included in a cross-sectional analysis. RESULTS: Compared with controls, AF patients had higher levels of IL-6 (p = 0.034), CRP (p = 0.003), TF (p = 0.019), and plasma viscosity (p = 0.045). Plasma IL-6 levels were higher among AF patients at "high" risk of stroke (p = 0.003). After adjusting for potential confounding clinical variables (e.g., vascular disease), AF remained significantly associated with a raised logarithmic transformation (log) of TF (p = 0.04), but the relationships between AF and log IL-6, log CRP, and plasma viscosity became nonsignificant. Among AF patients, log TF (p < 0.001) and high stroke risk (p = 0.003) were independent associates of log IL-6 (adjusted r(2) = 0.443), whereas log fibrinogen (p < 0.001) and plasma viscosity (p = 0.04) were independent associates of log CRP (adjusted r(2) = 0.259). CONCLUSIONS: Increased plasma IL-6, CRP, and plasma viscosity support the case for the existence of an inflammatory state among "typical" populations with chronic AF. These indexes of inflammation are related to indexes of the prothrombotic state and may be related to the clinical variables of the patients (underlying vascular disease and co-morbidities), rather than simply to the presence of AF itself.