title: Usefulness of Serum Carboxy-Terminal Propeptide of Procollagen Type I in Assessment of the Cardioreparative Ability of Antihypertensive Treatment in Hypertensive Patients Association of Pravastatin and Left Ventricular Mass in Hypercholesterolemic Patients: Role of 8-Iso-Prostaglandin F2&agr; Formation Randomized Trial of Atorvastatin for Reduction of Postoperative Atrial Fibrillation in Patients Undergoing Cardiac Surgery: Results of the ARMYDA-3 (Atorvastatin for Reduction of MYocardial Dysrhythmia After cardiac surgery) Study Cholesterol reduction rapidly improves endothelial function after acute coronary syndromes. The RECIFE (reduction of cholesterol in ischemia and function of the endothelium) trial. Dyslipidemia and an Unfavorable Fatty Acid Profile Predict Left Ventricular Hypertrophy 20 Years Later Ascorbate Attenuates Atrial Pacing-Induced Peroxynitrite Formation and Electrical Remodeling and Decreases the Incidence of Postoperative Atrial Fibrillation The HMG-CoA reductase inhibitor atorvastatin prevents atrial fibrillation by inhibiting inflammation in a canine sterile pericarditis model. Effect of Low-Density Lipoprotein Cholesterol on Angiotensin II Sensitivity: A Randomized Trial With Fluvastatin Relation of an exaggerated rise in white blood cells after coronary bypass or cardiac valve surgery to development of atrial fibrillation postoperatively. Predictors of atrial fibrillation after coronary artery surgery. Current trends and impact on hospital resources. N-3 Fatty acids for the prevention of atrial fibrillation after coronary artery bypass surgery: a randomized, controlled trial. High sensitivity C-reactive protein: a novel predictor for recurrence of atrial fibrillation after successful cardioversion. Efficacy of nonsteroidal anti-inflammatory medications for prevention of atrial fibrillation following coronary artery bypass graft surgery. Effects of pravastatin on ventricular
  remodeling by activation of myocardial
  KATP channels in infarcted rats: role of
  70-kDa S6 kinase Relationship between C-reactive protein concentrations during glucocorticoid therapy and recurrent atrial fibrillation. The −174G/C Interleukin-6 Polymorphism Influences Postoperative Interleukin-6 Levels and Postoperative Atrial Fibrillation. Is Atrial Fibrillation an Inflammatory Complication? Effect of C-reactive protein reduction on paroxysmal atrial fibrillation. Radiofrequency catheter ablation of the atria reduces inducibility and duration of atrial fibrillation in dogs. Statin use is associated with a reduction in atrial fibrillation after noncardiac thoracic surgery independent of C-reactive protein. Usefulness of statin drugs in protecting against atrial fibrillation in patients with coronary artery disease. Analysis of pravastatin to prevent recurrence of atrial fibrillation after electrical cardioversion. Are lipid-lowering drugs also antiarrhythmic drugs? An analysis of the Antiarrhythmics versus Implantable Defibrillators (AVID) trial. Effect of atorvastatin on the recurrence rates of atrial fibrillation after electrical cardioversion. Comparison of effectiveness of carvedilol versus metoprolol or atenolol for atrial fibrillation appearing after coronary artery bypass grafting or cardiac valve operation. Effects of atorvastatin on systemic inflammatory response after coronary bypass surgery C-reactive protein and atrial fibrillation: "evidence for the presence of inflammation in the perpetuation of the arrhythmia".
abstract: Background —We investigated whether serum concentration of carboxy-terminal propeptide of procollagen type I ( PIP ) , a marker of collagen type I synthesis , can be used to assess the ability of antihypertensive treatment to regress myocardial fibrosis in hypertensive patients . Methods and Results —The study was performed in 37 patients with essential hypertension and hypertensive heart disease . After r and omization , 21 patients were assigned to losartan and 16 patients to amlodipine treatment . At baseline and after 12 months , right septal endomyocardial biopsies were performed to quantify collagen volume fraction ( CVF ) on picrosirius red – stained sections with an automated image- analysis system . Serum PIP was measured by specific radioimmunoassay . Nineteen patients in the losartan group and 11 in the amlodipine group finished the study . Time-course changes in blood pressure during treatment were similar in the 2 groups of patients . In losartan-treated patients , CVF decreased from 5.65±2.03 % to 3.96±1.46 % ( P < 0.01 ) and PIP from 127±30 to 99±26 & mgr;g/L ( P < 0.01 ) . Neither CVF or PIP changed significantly in amlodipine-treated patients . CVF was directly correlated with PIP ( r = 0.44 , P < 0.001 ) in all hypertensives before and after treatment . Conclusions —These findings suggest that the ability of antihypertensive treatment to regress fibrosis in hypertensives with biopsy-proven myocardial fibrosis is independent of its antihypertensive efficacy . Our data also suggest that blockade of the angiotensin II type 1 receptor is associated with inhibition of collagen type I synthesis and regression of myocardial fibrosis in hypertensives . Thus , determination of serum PIP may be useful to assess the cardioreparative properties of antihypertensive treatment in hypertensives Epidemiologic studies have shown that hypercholesterolemia is associated with increased left ventricular ( LV ) mass . Free radicals have been shown to be increased in hyperlipidemic patients . This study sought to determine whether pravastatin administration can affect LV mass in patients with untreated total cholesterol ≥240 mg/dl by reducing 8-iso-prostagl and in F2&agr ; concentrations , a reliable marker of oxidant injury . Fifty patients were r and omly assigned to one of two groups , one with ( n = 25 ) and one without ( n = 25 ) treatment with pravastatin ( 10 or 20 mg/d ) . A group of normolipidemic control subjects was used for comparison . Echocardiograms were performed at baseline and after 6 months of therapy . Hyperlipidemic patients showed significant increases in LV mass index at baseline compared with the normolipidemic control group ( 125 ± 8 vs. 107 ± 5 g/m2 , p < 0.0001 ) . Pravastatin treatment significantly reduced plasma total and low-density lipoprotein cholesterol levels , as well as increased high-density lipoprotein cholesterol . After 6 months of therapy with pravastatin , the magnitude of LV mass regression correlated with the magnitude of inhibition of free radical formation assessed by 8-iso-prostagl and in F2&agr ; formation ( r = 0.67 , p = 0.002 ) . Multivariate analysis revealed that regression of LV mass was significantly correlated only with the changes in 8-iso-prostagl and in F2&agr ; ( p < 0.0001 , adjusted R2 = 0.83 ) . These findings demonstrated for the first time that in addition to its primary anti-lipidemia , pravastatin may have an additional effect of reducing LV mass – independent lipid-lowering effects , possibly through attenuation of free radical formation Background — Atrial fibrillation ( AF ) after cardiac surgery is associated with increased risk of complications , length of stay , and cost of care . Observational evidence suggests that patients who have undergone previous statin therapy have a lower incidence of postoperative AF . We tested this observation in a r and omized , controlled trial . Methods and Results — Two hundred patients undergoing elective cardiac surgery with cardiopulmonary bypass , without previous statin treatment or history of AF , were enrolled . Patients were r and omized to atorvastatin ( 40 mg/d , n=101 ) or placebo  ( n=99 ) starting 7 days before operation . The primary end point was incidence of postoperative AF ; secondary end points were length of stay , 30-day major adverse cardiac and cerebrovascular events , and postoperative C-reactive protein ( CRP ) variations . Atorvastatin significantly reduced the incidence of AF versus placebo ( 35 % versus 57 % , P=0.003 ) . Accordingly , length of stay was longer in the placebo versus atorvastatin arm ( 6.9±1.4 versus 6.3±1.2 days , P=0.001 ) . Peak CRP levels were lower in patients without AF ( P=0.01 ) , irrespective of r and omization assignment . Multivariable analysis showed that atorvastatin treatment conferred a 61 % reduction in risk of AF ( odds ratio 0.39 , 95 % confidence interval 0.18 to 0.85 , P=0.017 ) , whereas high postoperative CRP levels were associated with increased risk ( odds ratio 2.0 , 95 % confidence interval 1.2 to 7.0 , P=0.01 ) . The incidence of major adverse cardiac and cerebrovascular events at 30 days was similar in the 2 arms . Conclusions — Treatment with atorvastatin 40 mg/d , initiated 7 days before surgery , significantly reduces the incidence of postoperative AF after elective cardiac surgery with cardiopulmonary bypass and shortens hospital stay . These results may influence practice patterns with regard to adjuvant pharmacological therapy before cardiac surgery BACKGROUND Cholesterol lowering reduces coronary events . One mechanism could be improvement of endothelial function . In line with this hypothesis , this study investigates whether cholesterol reduction can result in rapid improvement of endothelial function  after acute coronary syndromes . METHODS AND RESULTS Patients with acute myocardial infa rct ion or unstable angina and total cholesterol levels at admission > /=5.2 mmol/L or LDL > /=3.4 mmol/L were r and omized to placebo ( n=30 ) or pravastatin 40 mg daily ( n=30 ) for 6 weeks . Brachial ultrasound was used to measure endothelium-dependent flow-mediated dilatation ( FMD ) and response to endothelium-independent nitroglycerin . Changes in the levels of markers of platelet activation , coagulation factors , and plasma endothelin levels were also assessed . Total and LDL cholesterol levels were similar at admission and before r and omization in both groups . With pravastatin , but not with placebo , they decreased by 23 % ( P<0.05 ) and 33 % ( P<0.01 ) , respectively . FMD was unchanged with placebo , 5.43+/-0.74 % ( mean+/-SEM ) to 5.84+/-0.81 % , but increased with pravastatin , 4.93+/-0.81 % to 7.0+/-0.79 % ( P=0.02 ) , representing a 42 % relative increase . Responses to nitroglycerin were similar during the time course of the study in the 2 groups . Markers of platelet activity , coagulation factors , and endothelin levels were not affected by pravastatin . CONCLUSIONS Cholesterol reduction with pravastatin initiated early after acute coronary syndromes rapidly improves endothelial function after 6 weeks of therapy Background —Left ventricular hypertrophy ( LVH ) is a common risk factor for cardiovascular mortality . Causes other than hypertension have not previously been investigated longitudinally . The aim of the present study was to determine hemodynamic , metabolic , and psychosocial predictors at 50 years of age for the prevalence of echocardiographic LVH and geometric subtypes at age 70 by use of a large sample of men from the general population followed up for 20 years . Methods and Results —In 1970 to 1973 , all men born from 1920 to 1924 and residing in Uppsala County , Sweden , were invited to participate in a health survey aim ed at identifying risk factors for cardiovascular disease . At a reinvestigation 20 years later , echocardiographic left ventricular mass index was determined in 475 subjects . A 1-SD increase in body mass index , systolic or diastolic blood pressure , fasting LDL/HDL cholesterol , serum triglycerides , or the serum cholesterol ester proportion of several saturated fatty acids or oleic acid at age 50 significantly increased the odds of having LVH at age 70 by 27 % to 41 % , whereas an increase in linoleic acid proportion was protective . Almost all metabolic predictors were independent of ischemic heart disease , valvular disease , and use of antihypertensive medication at age 70 . Conclusions —Dyslipidemia and indices of a low dietary intake of linoleic acid and high intake of saturated and monounsaturated fats , as well as hypertension and obesity , at age 50 predicted the prevalence of LVH 20 years later in this prospect i ve longitudinal cohort study , thereby suggesting that lipids may be important in the origin of LVH Atrial fibrillation ( AF ) , the most common chronic arrhythmia , increases the risk of stroke and is an independent predictor of mortality . Available pharmacological treatments have limited efficacy . Once initiated , AF tends to self-perpetuate , owing in part to electrophysiological remodeling in the atria ; however , the fundamental mechanisms underlying this process are still unclear . We have recently demonstrated that chronic human AF is associated with increased atrial oxidative stress and peroxynitrite formation ; we have now tested the hypothesis that these events participate in both pacing-induced atrial electrophysiological remodeling and in the occurrence of AF following  cardiac surgery . In chronically instrumented dogs , we found that rapid ( 400 min−1 ) atrial pacing was associated with attenuation of the atrial effective refractory period ( ERP ) . Treatment with ascorbate , an antioxidant and peroxynitrite decomposition catalyst , did not directly modify the ERP , but attenuated the pacing-induced atrial ERP shortening following 24 to 48 hours of pacing . Biochemical studies revealed that pacing was associated with decreased tissue ascorbate levels and increased protein nitration ( a biomarker of peroxynitrite formation ) . Oral ascorbate supplementation attenuated both of these changes . To evaluate the clinical significance of these observations , supplemental ascorbate was given to 43 patients before , and for 5 days following , cardiac bypass graft surgery . Patients receiving ascorbate had a 16.3 % incidence of postoperative AF , compared with 34.9 % in control subjects . In combination , these studies suggest that oxidative stress underlies early atrial electrophysiological remodeling and offer novel insight into the etiology and potential treatment of an enigmatic and difficult to control arrhythmia . The full text of this article is available at http://www.circresaha.org OBJECTIVE It has been recently reported that AF is associated with tissue inflammation . Statins reduce C-reactive protein ( CRP ) levels . However , the effect of statin on atrial fibrillation ( AF ) is unclear . The purpose of the present study was to evaluate the effect of statin on AF in a canine sterile pericarditis model . METHODS Sterile pericarditis was created in 20 dogs r and omly assigned to two groups : a control group ( 10 dogs ) and an atorvastatin treatment group ( 10 dogs ) . Atorvastatin was administered orally ( 2 mg/kg/day ) beginning 1 week before the operation until the end of the study . Before and 2 days after the operation , CRP levels , the duration of induced AF , the atrial effective refractory period ( AERP ) , and intra-atrial conduction time were determined . RESULTS Before the operation , there were no significant differences in any of the parameters between the two groups . On the second postoperative day , the atorvastatin group had a lower CRP level ( 7.6+/-0.5 versus 11.7+/-1.3 mg/dl , P<0.0001 ) , a shorter AF duration ( 177+/-57 versus 534+/-189 s , P<0.0001 ) , a longer AERP ( 138+/-6 versus 130+/-6 ms , P<0.01 ) , and a shorter intra-atrial conduction time ( 46+/-3 versus 51+/-5 ms , P<0.01 ) than the control group . CONCLUSIONS Atorvastatin can prevent maintenance of AF by inhibiting inflammation in the canine sterile pericarditis model . Atorvastatin may thus be a novel therapeutic agent for AF Increased angiotensin II ( Ang II ) sensitivity predisposes to hypertension and plaque instability . Raised low-density lipoprotein cholesterol ( LDL-c ) may increase Ang II sensitivity , but evidence in humans for this effect of LDL-c is limited . In 28 , healthy , nonsmoking subjects , aged 30±8 years , with familial hypercholesterolemia , we determined the difference in infusion rate of Ang II and norepinephrine required to increase systolic blood pressure by 20 mm Hg ( Pd-20 ) after 4 weeks of placebo and fluvastatin 80 mg daily in a r and omized , double-blind , placebo-controlled , crossover study . Before infusions were started , fasting blood sample s were taken to measure lipids . After 4 weeks of placebo  , the mean LDL-c concentration was 6.3±1.4 mmol/L. The average decrease of LDL-c was 1.7±0.7 mmol/L after 4 weeks of fluvastatin ( P<0.001 ) . The mean Pd-20 for Ang II increased by 1.28 ng/kg per minute ( 95 % CI , 2.05 to 0.50 ; P=0.002 ) on fluvastatin , corresponding with a 26 % decrease in Ang II sensitivity . Ang II sensitivity , however , remained increased compared with normocholesterolemic controls . The Pd-20 values for norepinephrine were unaffected by fluvastatin . The present study in healthy , young subjects with isolated hypercholesterolemia shows an increased sensitivity to Ang II that partly can be restored by LDL-c – lowering therapy . These findings indicate that LDL-c levels directly influence Ang II sensitivity This study investigated the correlation between an elevated white blood cell ( WBC ) count as a marker of inflammation and the development of  atrial fibrillation ( AF ) after cardiac surgery .  WBC counts  were prospect ively followed in 181 consecutive patients who underwent coronary bypass or cardiac valve surgery  to determine if a baseline or postoperative WBC count elevation is an independent predictor of postoperative AF BACKGROUND  Atrial fibrillation ( AF ) after coronary artery bypass surgery ( CABG ) is the most common sustained arrhythmia . Its pathophysiology is unclear , and its prevention and management remain suboptimal . The aim of this prospect i ve study was to determine the current incidence of AF , identify its clinical predictors , and examine its impact on re source utilization . METHODS AND RESULTS Over a 12-month period ending July 31 , 1994 , a  CABG procedure was performed on 570 consecutive patients ( age range , 32 to 87 years ; median age , 67 years ; 232 [ 41 % ] were > or = 70 years ; 175 [ 31 % ] were women ; 173 [ 30 % ] were diabetics ; 364 [ 65 % ] required nonelective surgery ; 86 [ 15 % ] had had a prior CABG ; and 86 [ 15 % ] had had prior percutaneous transluminal coronary angioplasty ) .  AF occurred in 189 patients ( 33 % ) . The median age for patients with AF was 71 years compared with 66 for patients without ( P = .0001 ) . Multivariate logistic regression analysis ( odds ratio , + /- 95 % CI , P value ) was used to identify the following independent predictors of postoperative AF : increasing age ( age 70 to 80 years [ OR = 2 ; CI , 1.3 to 3 ; P = .002 ] , age > 80 years [ OR = 3 ; CI , 1.6 to 5.8 ; P = .0007 ] ) , male gender ( OR = 1.7 ; CI , 1.1 to 2.7 ; P = .01 ) , hypertension ( OR = 1.6 ; CI , 1.0 to 2.3 ; P = .03 ) , need for an intraoperative intraaortic balloon pump ( OR = 3.5 ; CI , 1.2 to 10.9 ; P = .03 ) , postoperative pneumonia ( OR = 3.9 ; CI , 1.3 to 11.5 ; P = .01 ) , ventilation for > 24 hours ( OR = 2 ; CI , 1.3 to 3.2 ; P = .003 ) , and return to the intensive care unit ( OR = 3.2 ; CI , 1.1 to 8.8 ; P = .03 ) . The mean length of hospital stay after surgery was 15.3 + /- 28.6 days for patients with AF compared with 9.3 + /- 19.6 days for patients without AF ( P = .001 ) . The adjusted length of hospital stay attributable to AF was 4.9 days , corresponding to > or = $ 10 055 in hospital charges . CONCLUSIONS AF remains the most common complication after CABG and consequently is a drain on hospital re sources . Concerted efforts to reduce the incidence of AF and the associated increased length of stay would result in substantial cost saving and decrease patient morbidity OBJECTIVES The aim of this study was to assess the efficacy of preoperative and postoperative treatment with n-3 polyunsaturated fatty acids ( PUFAs ) in preventing the occurrence of  atrial fibrillation ( AF ) after coronary artery bypass graft surgery ( CABG ) . BACKGROUND Postoperative AF is a common complication of CABG . There is growing clinical evidence that PUFAs have cardiac antiarrhythmic effects . METHODS A total of 160 patients were prospect ively r and omized to a control group ( 81 patients , 13 female , 64.9 + /- 9.1 years ) or PUFAs 2 g/day ( 79 patients , 11 female , 66.2 + /- 8.0 years ) for at least 5 days before elective CABG and until the day of discharge from the hospital . The primary end point was the development of AF in the postoperative period . The secondary end point was the hospital length of stay after surgery . All end points were independently adjudicated by two cardiologists blinded to treatment assignment . RESULTS The clinical and surgical characteristics of the patients in the two groups were similar . Postoperative AF developed in 27 patients of the control group ( 33.3 % ) and in 12 patients of the PUFA group ( 15.2 % ) ( p = 0.013 ) . There was no significant difference in the incidence of nonfatal postoperative complications , and postoperative mortality was similar in the PUFA-treated patients ( 1.3 % ) versus controls ( 2.5 % ) . After CABG , the PUFA patients were hospitalized for significantly fewer days than controls ( 7.3 + /- 2.1 days vs. 8.2 + /- 2.6 days , p = 0.017 ) . CONCLUSIONS This study first demonstrates that PUFA administration during hospitalization in patients undergoing CABG substantially reduced the incidence of postoperative AF ( 54.4 % ) and was associated with a shorter hospital stay OBJECTIVES We sought to test the hypothesis that C-reactive protein ( CRP ) can predict the recurrence of atrial fibrillation ( AF ) after successful electrical cardioversion ( CV ) . BACKGROUND In patients with AF , CRP levels are predictive of immediate failure of CV . METHODS We prospect ively measured high-sensitivity CRP in 67 patients with AF or atrial flutter who underwent successful electrical CV .  RESULTS At one-month follow-up , 22 patients ( 33 % ) had recurrence of their arrhythmia . Arrhythmia recurrence was associated with significantly higher pre-CV  CRP levels ( odds ratio [ OR ] 1.84 ; 95 % confidence interval [ CI ] 1.14 to 2.98 ; p = 0.013 ) even after adjusting for age ( OR 2.22 ; 95 % CI 1.25 to 3.93 ; p = 0.006 ) , for gender ( OR 1.89 ; 95 % CI 1.16 to 3.09 ; p = 0.011 ) , or duration of arrhythmia ( OR 1.86 ; 95 % CI 1.13 to 3.07 ; p = 0.015 ) . On multivariate analysis , CRP was the only independent predictor of arrhythmia recurrence ( OR 2.19 ; 95 % CI 1.05 to 4.55 ; p = 0.036 ) . CONCLUSIONS Our data suggest that high levels of CRP are associated with an increased risk of recurrence of AF within one month . These data support the hypothesis that anti-inflammatory interventions may help in maintenance of normal sinus rhythm after CV . These data also may have implication s for the identification of patients who are most likely to experience substantial benefit from CV therapy for AF This study was design ed to test whether nonsteroidal anti-inflammatory medications could reduce the frequency of atrial fibrillation  after coronary artery bypass graft surgery . The study was design ed as an open-label , r and omized trial . Patients undergoing first-time coronary artery bypass graft surgery were considered eligible . Patients with a history of atrial fibrillation , serum creatinine > 2.0 mg/dL , on antiarrhythmic treatment , and those undergoing concomitant valvular surgery were excluded . The study was conducted in a single , university-affiliated community hospital . The research ers ' role in the study was restricted to r and omizing the patients and collecting data . The primary clinical care team made all decisions regarding patient care . One hundred patients were r and omized to two groups : one received 30 mg ketorolac intravenously every 6 hours until able to take oral medications , at which point the patients were switched to 600 mg ibuprofen orally three times a day ; the other group received conventional treatment . The primary end point of the study was incidence of atrial fibrillation in the immediate postoperative period . Atrial fibrillation occurred in 14 patients ( 28.6 % ) in the conventional treatment group vs. five patients ( 9.8 % ) in the ibuprofen group ( p<0.017 ) . Nonsteroidal anti-inflammatory medications were relatively safe and effective in significantly reducing the incidence of atrial fibrillation after coronary artery bypass graft surgery Abstract Reactive cardiomyocyte hypertrophy after myocardial infa rct ion is an important risk factor for arrhythmias . Myocardial ATP-sensitive potassium ( KATP ) channels have been implicated in attenuating cardiac hypertrophy by inhibition of 70-kDa S6 kinase . We investigated the effect of pravastatin on ventricular hypertrophy during remodeling after myocardial infa rct ion and whether the attenuated hypertrophic effect was via activation of myocardial KATP channels . Twenty-four hours after ligation of the anterior descending artery , male Wistar rats were r and omized to either vehicle , nicor and il ( an agonist of KATP channels ) , pravastatin , glibenclamide ( an antagonist of KATP channels ) , or a combination of nicor and il and glibenclamide or pravastatin and glibenclamide for 4 weeks . Infa rct size and mortality were similar among the infa rct ed groups . Cardiomyocyte sizes isolated by enzymatic dissociation after infa rct ion significantly increased at the border zone in vehicle-treated infa rct ed rats compared with sham-operated rats . Rats in the nicor and il- and pravastatin-treated groups significantly attenuated cardiomyocyte hypertrophy , as compared with the vehicle-treated group . Arrhythmic scores during programmed stimulation mirrored those of cardiomyocyte hypertrophy . Increased 70-kDa S6 kinase mRNA expression in cardiac remodeling was confirmed by reverse transcription-polymerase chain reaction , consistent with the results of immunohistochemistry and Western blot for the phosphorylation of 70-kDa S6 kinase .  Nicor and il-induced effects were abolished by administering glibenclamide . Similarly , the beneficial effects of pravastatin were abolished by administering glibenclamide , implicating KATP channels as the relevant target . Activation of KATP channels by pravastatin administration can attenuate ventricular remodeling through a S6 kinase-dependent pathway after infa rct ion 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 ( exp and ed 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 exp and ed 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 exp and ed 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 Background —It has been suggested that inflammation can have a role in the development of atrial arrhythmias after cardiac surgery and that a genetic predisposition to develop postoperative complications exists . This study was conceived to verify if a potential genetic modulator of the systemic inflammatory reaction to cardiopulmonary bypass ( the −174 G/C polymorphism of the promoter of the Interleukin-6 gene ) has a role in the pathogenesis of postoperative atrial fibrillation ( AF ) . Patients and Results —In 110 primary isolated coronary artery bypass patients the −174G/C Interleukin-6 promoter gene variant was determined . Interleukin-6 , fibrinogen and C-reactive protein plasma levels were determined preoperatively , 24 , 48 , and 72 hours after surgery and at discharge . Heart rate and rhythm were continuously monitored for the first 36 to 48 hours ; daily 12-lead electrocardiograms were performed thereafter until discharge . GG , CT , and CC genotypes were found in 62 , 38 , and 10 patients , respectively . Multivariate analysis ( which included genotype , age , sex , and classical risk factors for AF ) identified the GG genotype as the only independent predictor of postoperative AF . The latter occurred in 33.9 % of GG versus 10.4 % of non-GG patients ( hazard ratio 3.25 , 95%CI 1.23 to 8.62 ) . AF patients  had higher blood levels of Interleukin-6 and fibrinogen after surgery ( P < 0.001 for difference between the area under the curve ) . Conclusion —The −174G/C Interleukin-6 promoter gene variant appears to modulate the inflammatory response to surgery and to influence the development of postoperative AF . These data suggest an inflammatory component of postoperative atrial arrhythmias and a genetic predisposition to this complication BACKGROUND C-reactive protein ( CRP ) lowering is associated with a reduction in recurrent and permanent atrial fibrillation . This study sought to determine whether CRP lowering also results in a reduction of paroxysmal atrial fibrillation ( PAF ) during daily life . METHODS AND RESULTS We enrolled 80 patients with proven PAF , CRP between 0.8 and 13 mg/L , and at least 1 episode of PAF on ambulatory electrocardiographic monitoring . Forty patients were r and omized to placebo ( placebo group ) and 40 to atorvastatin ( treatment group ) .  Plasma  CRP levels and ambulatory monitoring were repeated after 4 to 6 months of therapy . The 2 groups were comparable with respect to baseline characteristics , number of episodes of PAF , and baseline plasma CRP levels . The treatment group had lower median CRP levels at study end and experienced a significant reduction in the number of episodes of PAF compared with the placebo group . Paroxysmal atrial fibrillation was completely resolved in 26 ( 65 % ) of 40 patients in the treatment group versus 4 ( 10 % ) of 40 in the placebo group . The treatment group exhibited a highly significant reduction in PAF ( P < .001 ) . By logistic regression , treatment with atorvastatin was an independent predictor of PAF resolution . CONCLUSIONS C-reactive protein lowering with atorvastatin appears to be effective in eliminating PAF during daily life in a significant proportion of patients BACKGROUND The purpose of this study was to prevent induction of sustained atrial fibrillation ( AF ) by radiofrequency catheter ablation ( RFCA ) of the atria in an open-chest canine model . METHODS AND RESULTS In dogs r and omized to acute studies , RFCA of the atria was performed after reproducible induction of sustained AF ( lasting > 30 minutes ) with burst stimulation or premature atrial pacing and perpetuation by low level cervical vagal stimulation or IV infusion of methacholine . Additionally , in four dogs , the long-term effectiveness of RFCA was assessed 7 to 21 days after ablation . Continuous discrete transmural lesions were produced with radiofrequency energy pulses ( 20 to 40 W for 60 seconds ) delivered to five atrial epicardial sites and endovascularly to the coronary sinus wall . RFCA electrically isolated regions of the atria that became dissociated from the nonisolated parts . Atrial RFCA markedly attenuated vagally induced shortening of effective refractory period ( ERP ) at both isolated and nonisolated test sites located in the left and right atria ( P < .001 , n = 5 ) . RFCA rendered noninducible sustained AF maintained by cervical vagal stimulation . The dose-response curve relating the dose of methacholine required to maintain AF was shifted down and to the right . AF was only inducible with high doses of methacholine . Atrial RFCA reduced the maximal sinus rate and prolonged the corrected sinus-node recovery time ( P < .001 , n = 6 ) . However , RFCA did not affect atrial contractile function , AV-nodal ERP , or AV-nodal or His-Purkinje conduction times . In dogs in the chronic group , normal sinus rhythm and normal AV conduction were preserved and AF was only inducible with a high dose of methacholine . No atrial perforations result ed . CONCLUSIONS RFCA in open-chest dogs produces partial vagal denervation and reduces the inducibility of AF STUDY OBJECTIVES The level of C-reactive protein ( CRP ) has been shown to be elevated in patients with atrial fibrillation/flutter ( AF ) unrelated to surgery , and statins are known to lower the CRP level . To determine whether an elevated CRP level predisposes the patient to postoperative AF and whether statin use is associated with a reduced AF incidence , we studied a consecutive group of patients who were at risk for AF after undergoing thoracic surgery ( age , > or = 60 years ) . DESIGN AND SETTING A prospect i ve study in a tertiary care cancer center of 131 patients ( mean [ + /- SD ] age , 73 + /- 6 years ) who had undergone major lung or esophageal resection .  High-sensitivity CRP and interleukin (IL)-6 levels were measured before surgery , on arrival at the postanesthesia care unit , and on the first morning after surgery . Continuous telemetry was used for 72 to 96 h to detect AF . RESULTS AF occurred in 38 of 131 patients ( 29 % ) at a median time after surgery of 3 days . Although CRP and IL-6 levels increased significantly ( p < 0.001 ) in response to surgery , patients with or without AF did not differ in perioperative values . In a stepwise logistic regression , statin use was associated with a threefold decrease in the odds of developing AF ( odds ratio [ OR ] , 0.26 ; 95 % confidence interval [ CI ] , 0.08 to 0.82 ; p = 0.022 ) and a greater PR interval ( OR , 1.11 per 5-ms increments ; 95 % CI , 1.01 to 1.22 ; p = 0.027 ) predicted an increase in the risk of AF . CONCLUSIONS The preoperative use of statins was associated with a protective effect against postoperative AF independent of CRP levels . In contrast to AF in the general population , early markers of inflammation did not predict the postoperative occurrence of AF Atrial  fibrillation ( AF ) is prevalent in the elderly , in patients with hypertension , and in patients with coronary artery disease ( CAD ) . We hypothesized that statin therapy might be effective in preventing AF in patients with CAD and examined this hypothesis in a sample of patients with chronic stable CAD without AF , followed prospect ively at a large outpatient cardiology practice . The association between statin use and the risk of developing AF was examined univariately and then with adjustment for potential confounding factors . Four hundred forty-nine men and women between the ages of 40 and 87 years were followed for an average of 5 years . Fifty-two patients ( 12 % ) developed AF during follow-up . Statin therapy was used by 59 % of the patients during the study period and was associated with a significantly reduced risk of developing AF ( crude odds ratio , 0.48 , 95 % confidence interval 0.28 to 0.83 ) . This association remained significant after adjustment for potential confounders , including age , hypertension , left ventricular systolic function , occurrence of heart failure or acute ischemic events , and baseline cholesterol and changes in cholesterol levels ( adjusted odds ratio 0.37 , 95 % confidence interval 0.18 to 0.76 ) . Use of  statins in patients with chronic stable CAD appears to be protective against AF . The underlying mechanism for this effect is unknown but appears to be independent of the reduction in serum cholesterol levels To test the hypothesis that a statin could reduce the recurrence rate of atrial fibrillation after electrical cardioversion ( EC ) , we performed an open , controlled multicenter study . Patients ( n = 114 ) who had atrial fibrillation > 48 hours and who were scheduled for EC were r and omized to receive 40 mg of pravastatin once daily for 3 weeks before and 6 weeks after EC or no drug in addition to st and ard therapy . Pravastatin did not reduce the recurrence rate of atrial fibrillation after EC OBJECTIVES This study sought to evaluate the antiarrhythmic effects of lipid-lowering drug therapy as assessed by ventricular tachyarrhythmia ( ventricular tachycardia [VT]/ventricular fibrillation [ VF ] ) recurrences recorded by an implantable cardioverter defibrillator ( ICD ) in patients with atherosclerotic heart disease ( ASHD ) . BACKGROUND R and omized trials of lipid-lowering drugs suggest reduction of sudden death ( SD ) in patients with ASHD . Because SD is usually secondary to VT/VF , this observation suggests that lipid-lowering therapy has antiarrhythmic effects . METHODS The probability of VT/VF recurrence in patients with ASHD treated with an ICD in the Antiarrhythmics Versus Implantable Defibrillators ( AVID ) trial who did not receive lipid-lowering drug therapy ( n = 279 ) was compared with that in patients who received early and consistent lipid-lowering therapy ( n = 83 ) . In addition , all-cause mortality and cardiac mortality of all patients in the AVID trial with ASHD who did not receive lipid-lowering therapy ( n = 564 ) were compared with that of those who received early and consistent lipid-lowering therapy  ( n = 149 ) . RESULTS Using multivariate analyses , lipid-lowering therapy was associated with a reduction in the relative hazard for VT/VF recurrence of 0.40 ( 95 % confidence interval [ CI ] 0.15 to 0.58 ) ( adjusted p = 0.003 ) in the ICD subgroup . Lipid-lowering therapy was also associated with a reduction in the relative hazard for all-cause mortality of 0.36 ( 95 % CI 0.15 to 0.68 ) ( adjusted p = 0.03 ) and a reduction in the relative hazard for cardiac mortality of 0.39 ( 95 % CI 0.16 to 0.78 ) ( adjusted p = 0.04 ) in the larger study population . CONCLUSIONS In patients with ASHD who have received an ICD , lipid-lowering therapy is associated with reduction in the probability of VT/VF recurrence , suggesting that part of the benefit of lipid-lowering therapy may be due to an antiarrhythmic effect To study the effect of atorvastatin on recurrence of atrial fibrillation ( AF ) after electrical cardioversion ( EC ) , 48 patients with AF lasting 48 hours who were scheduled for EC were r and omized to the atorvastatin ( group I ) and control ( group II ) groups . Six patients in group I ( 25 % ) and 2 patients in group II ( 8.3 % ) had spontaneous conversion before EC ( p > 0.05 ) . The end point was the recurrence of AF during 3 months of follow-up . Eighteen patients in group I ( 12.5 % ) and 11 patients in group II ( 45.8 % ) had recurrence ( p = 0.01 , log-rank test ) . With the Cox proportional model , the predictors of recurrence included a body mass index of 25 to 30 kg/m2 ( relative risk [ RR ] 0.07 , 95 % confidence interval [ CI ] 0.008 to 0.59 ) , body mass index > or = 30 kg/m2 ( RR 0.24 , 95 % CI 0.08 to 0.72 ) , AF duration of > or = 3 months ( RR 0.28 , 95 % CI 0.09 to 0.83 ) , diabetes mellitus ( RR 0.34 , 95 % CI 0.12 to 0.98 ) , and left atrial diameter of > or = 45 mm ( RR 0.23 , 95 % CI 0.07 to 0.74 ) . Atorvastatin was associated with a significantly reduced risk of developing AF ( unadjusted RR 0.23 , 95 % CI 0.064 to 0.82 , p = 0.024 ) . This association remained significant after adjustment for these predictors ( adjusted RR 0.19 , 95 % CI 0.052 to 0.72 , p = 0.01 ) . High-sensitivity C-reactive protein levels at baseline were not different between the 2 groups ( p = 0.92 ) . Although the high-sensitivity C-reactive protein levels decreased significantly 48 hours after EC compared with the baseline levels in group I ( 2.82 + /- 1.46 vs 2.56 + /- 1.3 mg/dl , p = 0.02 ) , no significant change occurred in group II ( 2.87 + /- 0.8 vs 2.84 + /- 0.8 mg/dl , p = 0.09 ) . In conclusion , atorvastatin decreased the recurrence rate of AF after EC A retrospective review of 115 patients who underwent cardiac surgery demonstrated a marked reduction in postoperative atrial fibrillation ( 8 % vs 32 % , p < 0.05 ) in patients who received carvedilol versus metoprolol or atenolol immediately after surgery . A prospect i ve study examining the possibility of carvedilol 's greater efficacy in preventing postoperative atrial fibrillation appears warranted Objectives : Systemic inflammatory response occurs frequently after coronary artery bypass surgery , and it is strongly correlated with the risk of postoperative morbidity and mortality . Recent studies demonstrate that treatment with statin is associated with a significant and marked decrease in inflammation-associated variables such as the C-reactive protein , cytokines , and adhesion molecules . Therefore , we investigated the effects of preoperative atorvastatin treatment on systemic inflammatory response and perioperative morbidity after cardiopulmonary bypass . Design : Double-blinded , placebo-controlled , r and omized study . Setting : University hospital . Patients : Forty patients were r and omized to treatment with atorvastatin ( 20 mg/day , group A , n = 20 ) or placebo ( group B , n = 20 ) 3 wks before surgery . Interventions : Three-week treatment by atorvastatin 20 mg/day . Measurement and Main Results : Postoperative serum levels of both interleukin-6 and interleukin-8 increased significantly over baseline , but the peak levels observed 4 hrs postoperatively were significantly lower in the atorvastatin group . In the same fashion , CD11b expression on neutrophils was significantly lower in the statin group at 4 and 24 hrs postoperatively . Finally , neutrophil-endothelial adhesion was significantly reduced in the statin patients compared with controls . The operation time , blood loss , need for inotropic support , intubation time , and length of intensive care unit or hospital stay did not differ significantly between the two groups . The systemic inflammatory response syndrome score on postoperative days 1 and 2 was comparable in both groups . Conclusions : Pretreatment with atorvastatin significantly reduces cytokine release and neutrophil adhesion to the venous endothelium in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass 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 prospect ively 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
target: Data from different observational trials have shown that treatment with statins significantly reduces the incidence of new-onset AF in the primary and secondary prevention .
  The data are insufficient to recommend the use of statins before EC .
  Finally , perioperative statin therapy may represent an important non-antiarrhythmic adjunctive therapeutic strategy for the prevention of postoperative AF
background: The aim of the present systematic review is to present an overview of the evidence linking atrial fibrillation ( AF ) , inflammation and oxidative stress , with emphasis on the potential of statins to decrease the incidence of different types of AF , including new-onset AF , after electrical cardioversion ( EC ) and after cardiac surgery .
  Observational and clinical trials have studied the impact of statin therapy on new-onset , post-EC or postoperative AF .