Relation of interleukin-6, C-reactive protein, and the prothrombotic state to transesophageal echocardiographic findings in atrial fibrillation

Atrial fibrillation (AF) is a major cause of morbidity and mortality from stroke due to thromboembolism from the fibrillating left atrium, including its appendage. We hypothesized that indexes of inflammation (as indicated by C-reactive protein and interleukin-6) and indexes of the prothrombotic state in AF that represent platelet activation (soluble P-selectin levels), endothelial damage or dysfunction (von Willebrand factor), coagulation (tissue factor and fibrinogen), and hemorrheology (plasma viscosity and hematocrit) would be related to the presence of thromboembolic predictors on transesophageal echocardiography in patients with long-term AF. To test this hypothesis, we recruited 37 patients with long-term AF who were receiving warfarin therapy with an international normalized ratio of > or =2.0 for > or =3 weeks before transesophageal echocardiography. Twenty-two patients had dense spontaneous echo contrast (SEC) visible in the left atrium or left atrial appendage, 10 had complex atheromatous plaque in the descending aorta, 11 had peak left atrial appendage velocities < or =0.2 m/s, and 3 had thrombus visible in the left atrial appendage. Twenty-eight patients had > or =1 transesophageal echocardiographic (TEE) risk factor for thromboembolism. Plasma levels of C-reactive protein (p = 0.03) and soluble P-selectin (p = 0.04) and hematocrit (p = 0.004) were higher among patients with AF with dense SEC than among those without. No significant associations were found for other TEE risk factors. Hematocrit was the only variable significantly associated with the presence of > or =1 TEE risk factor among patients with AF (p = 0.007) and the only independent associate of dense SEC after multivariate analysis (relative risk 1.4, 95% confidence interval 1.1 to 1.6) per 1% increase in hematocrit (p = 0.003, r(2) = 0.22). Although hematocrit was the only independent associate of dense SEC and > or =1 TEE risk factor, significant associations between dense SEC and the 2 indexes, C-reactive protein and soluble P-selectin, may indicate that mechanisms other than stasis are present with dense SEC. These observations support an "inflammatory hypothesis" in the pathogenesis of SEC that may have implications for thrombogenesis in AF.     

C反应蛋白与心房颤动的关系

目的探讨C反应蛋白(CRP)作为系统炎症因子在心房颤动发生和发展中的作用。方法入选98例患者将其分为正常对照组(n=34)、阵发性房颤组(n=31)和持续房颤组(n=33),比较各组C反应蛋白水平。结果心房颤动组CRP水平[(1.85±0.44)mg/d]比正常对照组的水平[(0.41±0.13)mg/d]高,P<0.01;在心房颤动组中持续房颤组血清中CRP[(2.02±0.54)mg/d]高于阵发性房颤组[(1.55±0.40)mg/d],P<0.01,阵发性房颤组[(2.02±0.54)mg/d]高于正常对照组(0.41±0.13)mg/dl,P<0.01。并且不同原因引起的房颤CRP不同,冠心病最高,其次为高血压,心肌病最低。结论CRP在心房颤动患者中明显升高,说明炎症状态在心房颤动的发生和持续中起一定作用。     

C反应蛋白与心房颤动的关系

目的探讨C反应蛋白(CRP)作为系统炎症因子在心房颤动发生和发展中的作用。方法入选98例患者将其分为正常对照组(n=34),阵发性心房颤动组(n=31)和持续性心房颤动组(n=33),比较各组CRP水平。结果心房颤动组CRP水平(18.5±4.4)mg/L比正常对照组(4.1±1.3)mg/L高,P<0.01;在心房颤动组中持续性心房颤动组血清中CRP(20.2±5.4)mg/L高于阵发性心房颤动组(15.5±4.0)mg/L,P<0.01;阵发性心房颤动组(20.2±5.4)mg/L高于正常对照组(4.1±1.3)mg/L,P<0.01。不同原因引起的心房颤动CRP不同,冠心病最高,其次为高血压,心肌病最低。结论CRP在心房颤动患者明显升高,其代表的炎症状态在心房颤动的发生和持续中起一定作用。     

Prognostic significance of raised plasma levels of interleukin-6 and C-reactive protein in atrial fibrillation

Background

Atrial fibrillation (AF) is a risk factor for stroke and death. Inflammation has been associated with AF, but the prognostic significance of inflammatory mediators, such as interleukin-6 (IL-6) and C-reactive protein (CRP), among patients with AF is unknown. We hypothesized that increased plasma levels of IL-6 and CRP, as indexes of an inflammatory state, would be associated with an increased risk of stroke and death among patients with AF.

Methods

We undertook a pilot study to determine dates of stroke or death occurring among 77 AF cases, with stored plasma samples having initially been obtained during attendance at our specialist AF clinic between 1993 and 1995. Plasma IL-6 and CRP were measured by ELISA and a high-sensitivity latex particle turbidimetric assay, respectively.

Results

Patients were followed up for a median duration of 2305 days (interquartile range, 1692 to 2592) [equivalent to 6.3 (4.6 to 7.1) years]. During this period, there were 8 (10%) strokes, 22 (29%) deaths, and 28 (36%) patients who had stroke or death. Prior stroke and high (above median) IL-6 levels were independent predictors of stroke. Age was the only independent predictor of death. High (above median) IL-6 levels remained a significant predictor of stroke or death, even after adjustment for age (hazard ratio, 2.91; 95% CI, 1.20 to 6.51; P = .007), and was the only independent predictor of stroke or death. Trends toward increased risk with high plasma CRP did not reach statistical significance (P = .06 for stroke or death).

Conclusions

In this pilot study, high plasma IL-6 levels were an independent predictor of stroke and the composite end point of stroke or death, suggesting that inflammation in AF may predict a poor prognosis.     

Relation of elevated C-reactive protein and interleukin-6 levels to left atrial size and duration of episodes in patients with atrial fibrillation

Previous studies have demonstrated inflammation to be a risk factor in patients with atrial fibrillation (AF). In this prospective study of 90 patients with persistent and permanent AF and 46 controls, we found increased C-reactive protein (CRP) and interleukin-6 levels in patients with AF compared with controls (p <0.001). Multivariate analysis revealed CRP to be an independent predictor of AF (p = 0.01). Left atrial diameter was positively related to CRP and interleukin-6 (p <0.001, R = 0.37; p <0.001, R = 0.46, respectively) and negatively related to left ventricular function. Interleukin-6 levels were positively related to AF duration before cardioversion (p = 0.02). Elevation of CRP and interleukin-6 suggest a role of inflammation in AF, and the relation of CRP and interleukin-6 to left atrial size and AF duration before cardioversion indicates that inflammation may participate in the process of atrial remodeling.     

非瓣膜性心房颤动患者心外膜脂肪组织与血栓前状态的相关性研究

目的探讨心外膜脂肪组织(EAT)体积与非瓣膜性心房颤动(简称房颤)患者血栓形成前状态的关系。方法 2012年1月至2014年1月期间住院行房颤导管射频消融治疗的非瓣膜性房颤患者90例,记录基线资料及伴发疾病,测定红细胞比积、血小板平均体积、D-二聚体和纤维蛋白原(FIB)等凝血状态指标,并进行CHA2DS2-VASc评分和超声心动图检查,同时测量总EAT体积(EAT-total)及左房周EAT体积(EAT-LA)。统计分析EAT-total、EAT-LA与血凝状态指标之间的相关性。根据CHA2DS2-VASc评分结果将研究对象分为高危组和中低危组,比较两组间各指标间的差异,并分析EAT-total、EAT-LA与CHA2DS2-VASc评分间的相关性。结果高危组EAT-total为(111.1±34.2)cm3,EAT-LA为(29.3±7.7)cm3;中低危组EAT-total为(92.8±33.9)cm3,EAT-LA为(24.0±9.2)cm3,EAT-total和EAT-LA在两组间差异显著(P0.05)。相关性分析显示,EAT-total和EAT-LA与CHA2DS2-VASc评分间呈正相关。进一步分析提示EAT-total和EAT-LA与D-二聚体和FIB正相关,多因素分析示两者与D-二聚体和FIB水平均存在独立联系。结论房颤患者EAT可能参与了房颤时血栓前状态的形成,其体积大小可能是房颤患者发生血栓栓塞的独立风险预报因子。     

老年高血压并存心房颤动患者左心房内径和血栓前状态研究

目的 探讨老年高血压并存心房颤动(房颤)患者左心房内径(LAD)的变化及其与血栓前状态各指标的相关性. 方法 高血压患者105例,其中65例并存房颤(房颤组),40例无房颤(非房颤组),30例健康体检无高血压和房颤为对照组.用M型心脏超声测定LAD,同时检测其纤维蛋白原(Fg)、D-二聚体(D-Dimer)、血浆假性血友病因子(wvF)及红细胞压积(HCT),并进行比较.再将房颤患者分为阵发性房颤组和持续性房颤组,比较其LAD、Fg、D-Dimer、vwF、HCT.然后以LAD为因变量,Fg、D-Dimer、vwF、HCT为白变量,进行直线相关分析. 结果 房颤组与对照组和非房颤组比较,LAD为(43.56±6.72)mm与(31.63±4.32)mm和(36.28±5.83)mm(均P＜0.05),Fg为(4.24±0.59)g/L与(2.80±0.46)g/L和(3.09±0.49) g/L(均P＜0.05),D-Dimer为(0.43+0.13) mg/L与(0.18±0.08) mg/L和(0.28±0.10) mg/L(均P＜0.05);房颤组vwF、HCT分别为(290.44±29.02)％、0.46±0.07,与对照组(84.15±20.26)％、0.34±0.03比较,差异有统计学意义(均P＜0.05).非房颤组与对照组比较,LAD、D-Dimer差异有统计学意义(P＜0.05).持续房颤组与阵发房颤组比较,LAD、Fg、D-Dimer、vwF、HCT差异有统计学意义(均P＜0.05),LAD与Fg(r=0.683)、D-Dimer(r=0.735)、vwF(r=0.763)、HCT(r=0.759)呈正相关(均P＜0.01). 结论 LAD增大为房颤发生的危险因素,房颤患者存在血栓前状态,且LAD越大,血栓风险越大.     

Correlation between left atrial size, prothrombotic state and markers of endothelial dysfunction in patients with lone chronic nonrheumatic atrial fibrillation

Atrial fibrillation is associated with a prothrombotic state and endothelial dysfunction. To understand whether the prothrombotic state was correlated with endothelial dysfunction and whether the latter was related to atrial dimension (endocardial damage), we studied systemic hemocoagulative activity and markers of endothelial dysfunction in 45 patients with chronic nonrheumatic atrial fibrillation and in 35 controls. We assessed fibrinogen, antithrombin III, protein C, markers of platelet activation (platelet factor 4 and beta-thromboglobulin) as markers of fibrinolysis, and D-dimer, tissue plasminogen activator, plasminogen activator inhibitor, von Willebrand's factor and soluble thrombomodulin as endothelial dysfunction. Plasma fibrinogen (P<0. 005), platelet factor 4 (P<0.001), thromboglobulin (P<0.001), D-dimer (P<0.03), tissue plasminogen activator (P<0.006), plasminogen activator inhibitor (P<0.04) and both von Willebrand's factor (P<0.0001) and soluble thrombomodulin (P<0.03) were significantly higher in the patients than in the controls. Positive significant linear correlations were found between fibrinogen and markers of endothelial dysfunction and left atrial volume and fibrinogen or markers of endothelial dysfunction. These findings confirm that chronic nonrheumatic atrial fibrillation is associated with a prothrombotic state but also suggest that there is a correlation between endothelial dysfunction, coagulation factors and left atrial dimension.     

风湿性二尖瓣狭窄伴心房颤动患者血栓前状态的研究

目的 :观察风湿性二尖瓣狭窄伴心房颤动 (房颤 )的血栓前状态。方法 :使用酶联免疫法和凝固法测量 2 4例风湿性心脏病 (风心病 )伴窦性心律患者 (窦律组 )、2 5例风心病伴房颤患者 (房颤组 )和 2 0例对照者 (对照组 )的外周血浆因子Ⅷ相关抗原 (VWFAg)、血小板α颗粒膜蛋白 14 0 (GMP 14 0 )、D 二聚体 (D dimer)和纤维蛋白原 (Fg)的水平变化 ,进行统计学分析。 结果 :与对照组比 ,窦律组血浆VWFAg、D dimer和Fg水平均显著升高(P <0 .0 5 ) ,而血浆GMP 14 0水平无显著性改变 (P >0 .0 5 ) ;房颤组血浆GMP 14 0、D dimer和Fg水平也明显升高 (P <0 .0 5 )。房颤组与窦律组相比血浆GMP 14 0、VWFAg、D dimer水平更高 (P <0 .0 5 ) ,而Fg水平在二者之间无明显变化 (P >0 .0 5 )。结论 :风湿性二尖瓣狭窄伴房颤患者外周血存在血栓前状态。     

Relationship between C-reactive protein concentrations during glucocorticoid therapy and recurrent atrial fibrillation.

BACKGROUND: Little direct information is available on the effect of C-Reactive Protein (CRP) lowering on the reduction of recurrent atrial fibrillation (AF). METHODS AND RESULTS: We compared low-dose glucocorticoid therapy (16 mg methylprednisolone for 4 weeks tapered to 4 mg for 4 months) and placebo in 104 patients who had experienced persistent AF with a median concentration of CRP 1.14 mg/dL (min=0.01, max=2.58). Methylprednisolone reduced recurrent AF (primary end-point) from 50% in the placebo group to 9.6% in the glucocorticoid group and permanent AF (expanded end-point) from 29% in the placebo group to 2% in the glucocorticoid group. Survival distributions for methylprednisolone were significantly different (for both primary and expanded end-point, P < 0.001). In multivariate Cox analysis, average CRP concentrations during follow-up were significant predictors of the primary end-point, with a relative risk 6.72 (P = 0.006) and the expanded end-point, with a relative risk of 11.67 (P = 0.0006). CONCLUSIONS: CRP concentration is a risk factor for recurrent and permanent AF. Methylprednisolone successfully prevents recurrent and permanent AF.     

超敏C反应蛋白、白细胞介素-6与家兔急性心房颤动的关系及黄油干预

目的：探讨黄油干预家兔血清超敏C反应蛋白（hs—CRP）、白细胞介素-6（IL-6）水平及对急性心房颤动（房颤）的影响。方法：30只家兔随机分为正常组（72=15）、黄油组（＂=15），黄油组预先给予人造黄油灌胃4周。通过开胸植入食道调搏电极（程序刺激与Burst刺激相结合）刺激肺静脉建立家兔急性房颤模型。根据实验结果是否诱发出房颤将家兔分为房颤组与非房颤组。应用ELISA双抗体夹心方法测定血清中hs—cRP、IL-6的水平。比较房颤组与非房颤组刺激前血清中hs—CRP、IL-6的水平。比较黄油组与正常组刺激前与刺激后血清中hs—cRP、IL-6的水平，并进行统计学分析。结果：房颤组刺激前血清hs—CRP、IL-6水平均高于非房颤组（P〈0．01）。黄油组血清hs—CRP、IL-6的水平均高于正常组（P〈0．05）。黄油组的房颤诱发率均明显高于正常组（P〈0．05）。结论：刺激前血清hs—CRP、IL-6水平越高，房颤越易诱发，房颤持续时间越长。预先控制血清hs—CRP、IL-6水平升高就可能会有效抑制房颤的发生、发展。表明炎症状态可能参与了房颤的发生、发展。     

超敏C反应蛋白、白细胞介素-6与家兔急性心房颤动的关系及黄油干预

目的：探讨黄油干预家兔血清超敏C反应蛋白（hs—CRP）、白细胞介素-6（IL-6）水平及对急性心房颤动（房颤）的影响。方法：30只家兔随机分为正常组（72=15）、黄油组（＂=15），黄油组预先给予人造黄油灌胃4周。通过开胸植入食道调搏电极（程序刺激与Burst刺激相结合）刺激肺静脉建立家兔急性房颤模型。根据实验结果是否诱发出房颤将家兔分为房颤组与非房颤组。应用ELISA双抗体夹心方法测定血清中hs—cRP、IL-6的水平。比较房颤组与非房颤组刺激前血清中hs—CRP、IL-6的水平。比较黄油组与正常组刺激前与刺激后血清中hs—cRP、IL-6的水平，并进行统计学分析。结果：房颤组刺激前血清hs—CRP、IL-6水平均高于非房颤组（P〈0．01）。黄油组血清hs—CRP、IL-6的水平均高于正常组（P〈0．05）。黄油组的房颤诱发率均明显高于正常组（P〈0．05）。结论：刺激前血清hs—CRP、IL-6水平越高，房颤越易诱发，房颤持续时间越长。预先控制血清hs—CRP、IL-6水平升高就可能会有效抑制房颤的发生、发展。表明炎症状态可能参与了房颤的发生、发展。     

Frequency of elevation of C-reactive protein in atrial fibrillation

Inflammation has been implicated in the pathogenesis of cardiovascular diseases. C-reactive protein (CRP), a marker of systemic inflammation, predicts the risk of coronary events and stroke. Atrial fibrillation (AF) is associated with atrial structural changes that may have an inflammatory basis. We tested the hypothesis that CRP is a risk factor for AF. Subjects were those included in the database registry of the Intermountain Heart Collaborative Study from 1994 to 2001. Patients who had >or=1 electrocardiogram that demonstrated AF formed the disease group (n = 347), and those who had neither electrocardiographic nor clinical evidence for AF comprised the control group (n = 2,449). Logistic regression assessed the quartile (Q) of CRP and 13 other clinical and angiographic predictors of AF. Average age was 63 +/- 12 years, 33% were women, and 61% had advanced coronary artery disease. Patients who had AF were older (by 7 years) and more frequently had a history of heart failure than did controls (41% vs 9%). CRP was higher in patients who had AF than in controls (p <0.001). Q-CRP was a univariable predictor of AF (odds ratio 1.39/Q, 95% confidence interval 1.25 to 1.55, p <0.001). Adjusting for age and heart failure decreased the predictive value of Q-CRP to 1.20/Q (95% confidence 1.07 to 1.34, p = 0.002), whereas further adjustment for 11 other variables had little additional effect (odds ratio 1.19/Q, 95% confidence interval 1.06 to 1.33, p = 0.003). Thus, high levels of CRP independently predicted an increased risk of AF among a large, prospectively studied patient cohort that was assessed angiographically. Increased CRP is a new risk marker for AF propensity, and testing therapies that target inflammation should be considered.     

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.     

92例心房颤动患者与C-反应蛋白及其-717A>G多态性关系的分析

目的:分析92例心房颤动(房颤)患者与C-反应蛋白(CRP)及其-717A>G多态性的关系.方法:采用免疫比浊法测定92例房颤患者(房颤组)和60例对照者(对照组)的血清CRP水平,同时应用聚合酶链反应检测CRP的-717A/G的基因多态性,结合其他临床资料分析.结果:Logistic回归分析显示自然对数转换CRP(InCRP)水平(0R=7 84,P<0 01)与房颤独立相关,房颤组的水平显著高于对照组.2组-717A/G基因型的分布趋势相同,差异无统计学意义;但等位基因频数分布2组间存在显著性差异(χ2=4 38,P<0 05),G等位基因在房颤组中表现为低频率.CRP水平与-717A/G基因型无关,但AA基因型个体TC水平显著高于GA+GG型个体(P<0 05),但这种关系仅限于房颤患者.结论:血清CRP水平升高可能是房颤的独立危险因子,AA基因型在房颤组中表现为高TC水平,可能代表更高的炎症状态.     

C反应蛋白与心房颤动合并血栓的相关分析

目的 探讨C反应蛋白(CRP)与非瓣膜性心房颤动(房颤)患者左心房内血栓形成的关系。方法 按照经食道心脏超声(TEE)检查结果将非瓣膜性房颤患者154例分为：血栓组46例、非血栓组108例。检测血浆中CRP、D-二聚体的浓度及TEE检测左心房直径(LAd)、左室射血分数(LVEF)、缩短分数(FS)。将可能的相关因素进行logistic多因素回归分析。结果 血栓组患者在CRP[(5.77±6.37) mg/L比(1.73±2.39) mg/L,P=0.003]、LAd[(59.86±10.70)mm比(47.97±13.19)mm,P＜0.001]、LVEF[(58.75±8.28)％比(64.10±6.75)％,P＜0.001]与非血栓组差异有统计学意义。logistic回归发现CRP≥1.33 mg/L(OR 2.856,95％CI1.235 ～6.600,P=0.014),LAd≥54.5 mm(OR 4.236,95％ CI 1.877 ～9.562,P=0.001)是非瓣膜性房颤患者血栓形成的独立危险因素。结论 CRP升高、左心房扩大是非瓣膜性房颤患者血栓形成的独立危险因素,炎症反应可能参与心房血栓形成。