Risks of cardiovascular events and effects of routine blood pressure lowering among patients with type 2 diabetes and atrial fibrillation: results of the ADVANCE study. Dogma Disputed: Can Aggressively Lowering Blood Pressure in Hypertensive Patients with Coronary Artery Disease Be Dangerous? Atrial Fibrillation and Isolated Systolic Hypertension: The Systolic Hypertension in the Elderly Program and Systolic Hypertension in the Elderly Program-Extension Study Risk factors for stroke in patients with nonrheumatic atrial fibrillation: a case-control study. Comparison of the Effects of Antihypertensive Agents on Central Blood Pressure and Arterial Stiffness in Isolated Systolic Hypertension Apparent effect on blood pressure is only partly responsible for the risk reduction due to antihypertensive treatments. Effect of various antihypertensive drugs on plasma fibrinogen levels in patients with essential hypertension. Assessment of three schemes for stratifying stroke risk in patients with nonvalvular atrial fibrillation. Adjunctive renal sympathetic denervation to modify hypertension as upstream therapy in the treatment of atrial fibrillation (H-FIB) study: clinical background and study design. An evaluation of the strategy of maintenance of sinus rhythm by antiarrhythmic drug therapy after ablation and pacing therapy in patients with paroxysmal atrial fibrillation. Antiarrhythmic drug therapy and cardiac mortality in atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators. Transesophageal echocardiographic correlates of thromboembolism in high-risk patients with nonvalvular atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators Committee on Echocardiography. Response to Antihypertensive Therapy in Older Patients With Sustained and Nonsustained Systolic Hypertension The design and rationale of a multicenter clinical trial comparing two strategies for control of systolic blood pressure: The Systolic Blood Pressure Intervention Trial (SPRINT) A randomized clinical trial of early invasive intervention for atrial fibrillation (EARLY-AF) - methods and rationale. Factors associated with ischemic stroke during aspirin therapy in atrial fibrillation: analysis of 2012 participants in the SPAF I-III clinical trials. The Stroke Prevention in Atrial Fibrillation (SPAF) Investigators. Positive pressure therapy in patients with cardiac arrhythmias and obstructive sleep apnea.
AIMS The aim of this study was to investigate serious clinical outcomes associated with atrial fibrillation ( AF ) and the effects of routine blood pressure lowering on such outcomes in the presence or absence of AF , among individuals with type 2 diabetes . METHODS AND RESULTS About 11 140 patients with type 2 diabetes ( 7.6 % of whom had AF at baseline ) were r and omized to a fixed combination of perindopril and indapamide or placebo in the Action in Diabetes and Vascular Disease : preterAx and diamicroN-MR Controlled Evaluation ( ADVANCE ) study . We compared total mortality and cardiovascular disease outcomes and effects of r and omized treatment for 4.3 years on such outcomes between patients with and without AF at baseline . After multiple adjustments , AF was associated with a 61 % ( 95 % confidence interval 31 - 96 , P < 0.0001 ) greater risk of all-cause mortality and comparable higher risks of cardiovascular death , stroke , and heart failure ( all P < 0.001 ) . Routine treatment with a fixed combination of perindopril and indapamide produced similar relative , but greater absolute , risk reductions for all-cause and cardiovascular mortalities in patients with AF , compared with those without AF . The number of patients needed to be treated with perindopril-indapamide for 5 years to prevent one cardiovascular death was 42 for patients with AF and 120 for patients without AF at baseline . CONCLUSION Atrial fibrillation is relatively common in type 2 diabetes and is associated with substantially increased risks of death and cardiovascular events in patients with type 2 diabetes . This arrhythmia identifies individuals who are likely to obtain greater absolute benefits from blood pressure-lowering treatment . Atrial fibrillation in diabetic patients should be regarded as a marker of particularly adverse outcome and prompt aggressive management of all risk factors Context Experts debate the consequences of excessive lowering of diastolic pressure in patients with hypertension and coronary artery disease . Contribution This report is a secondary analysis of data from a large trial of 2 antihypertensive drug regimens in patients with known coronary artery disease . The authors found a J-shaped relationship between diastolic blood pressure and all-cause death and myocardial infa rct ion , with the increased risk occurring at diastolic blood pressures below 70 to 80 mm Hg , that is , the lower the diastolic pressure , the higher the risk . Caution s The study examined associations between blood pressure and outcomes ; it could not prove that the antihypertensive therapy that lowered diastolic pressure too much caused the adverse outcomes . The Editors For 2 decades , the hypertension literature has been haunted by the phenomenon of a paradoxical increase in morbidity and mortality with an excessive decrease in blood pressure ( J-curve ) . Indeed , several reports have shown that low diastolic pressure is associated with an increased risk for coronary heart disease and related mortality in older adults and in patients taking antihypertensive medications ( 1 - 13 ) . After doing a review and meta- analysis of pertinent studies , Farnett and colleagues ( 14 ) concluded that although there was no consistent J-shaped relationship between stroke and systolic or diastolic pressure , there was a consistent J-shaped relationship for cardiac events and diastolic pressure . These authors stated that this dichotomy in the relationship between diastolic pressure and target organ disease may leave a clinician with the uncomfortable choice of whether to prevent stroke or renal disease at the expense of coronary heart disease . These findings were at variance with the generally accepted dogma formulated by the sixth report of the Joint National Committee on Prevention , Detection , Evaluation , and Treatment of High Blood Pressure ( JNC VI ) ( 15 ) , which stated that the relationship between pressure and risk was strong , continuous , independent , predictive and etiologically significant . Within the past decade , the phenomenon of a J-curve has been studied in several large trials of normotensive and hypertensive patients ( 16 - 30 ) . Not surprisingly , arguments regarding whether a J-curve could be clinical ly significant have become somewhat contentious . That is , some rely on evidence that on-treatment diastolic pressure below 70 mm Hg does not increase risk for cardiovascular disease and thus deny an impairment of vital organ perfusion within the usual values achievable by antihypertensive treatment . Others , however , consider the J-curve a more real possibility , particularly for the heart . In contrast to other organs , the heart is perfused mostly during diastole and thus could be more vulnerable to diastolic pressure reduction . If a J-curve did exist , it should be most evident in patients with limited coronary perfusion , in other words , in those with manifest coronary artery disease ( CAD ) . Optimal blood pressure in patients with hypertension and CAD remains controversial because few r and omized clinical trials have been done in this population ( 31 , 32 ) . The International Verapamil-Tr and olapril Study ( INVEST ) ( 33 ) , a r and omized trial , evaluated more than 22000 patients with CAD and hypertension . This patient profile , together with unprecedented levels of blood pressure control , provided a unique opportunity to critically investigate the hypothesis that the risk for CAD would increase with an excessive decrease in diastolic pressure . Methods Study Design and Intervention The INVEST design , methods , and principal results have been previously published ( 33 ) . The trial used an open design with blinded end point assessment . In brief , clinical ly stable patients with CAD and hypertension were r and omly assigned to a verapamil sustained-releasebased or atenolol-based strategy .  Patients with previous myocardial infa rct ion ( MI ) within 3 months of enrollment or class IV or V congestive heart failure were excluded .  Blood pressure goals were based on JNC VI ( systolic pressure < 140 mm Hg and diastolic pressure < 90 mm Hg or systolic pressure < 130 mm Hg and diastolic pressure < 85 mm Hg in patients with diabetes or renal impairment ) ( 15 ) . The addition of tr and olapril or hydrochlorothiazide was recommended when necessary to achieve blood pressure goals . Tr and olapril was also recommended for patients with heart failure , diabetes , or renal impairment . Documented CAD was defined as any of the following : remote ( 3 months before enrollment ) confirmed MI , coronary angiography showing more than 50 % narrowing of at least 1 major coronary artery , diagnosis of classic angina pectoris , or concordant abnormalities on 2 different signals ( electrocardiography , echocardiography , or radionuclide scans ) from stress test findings concordant for ischemia ( for example , ST-segment depression or perfusion defects on radionuclide scanning or wall-motion abnormalities on echocardiography or radionuclide scanning ) . Patient Monitoring and Follow-up Protocol visits were scheduled every 6 weeks for the first 6 months and then biannually until 2 years after the last patient was enrolled . Patients were assessed for response to treatment , symptoms , treatment adherence , and adverse effects at each visit and at the end of the study as detailed elsewhere ( 33 ) . Patient follow-up was complete when we received a final assessment form through the online data system or a death report . The Internet-based electronic data collection method used in INVEST did not accept the entry until all required fields were complete . Blood pressure  was measured by using a st and ard mercury sphygmomanometer with an appropriately sized cuff applied to the upper nondominant arm at heart level . By auscultation at the brachial artery , systolic pressure was recorded at the first Korotkoff sound and diastolic pressure was recorded at the disappearance of the fifth Korotkoff sound . Blood pressure was measured twice , at least 2 minutes apart , and the measurements were averaged . Study Outcomes The primary outcome was the first occurrence of all-cause death , nonfatal MI , or nonfatal stroke by intention-to-treat analysis . The MI and stroke definitions are detailed elsewhere ( 34 ) . These 3 components individually were the main secondary outcomes . For this analysis , additional outcomes included fatal and nonfatal MI , fatal and nonfatal stroke , and average on-treatment blood pressure before outcome or censoring . Ascertainment and blinded adjudication of outcomes were described previously ( 32 ) . Follow-up data were available for 22008 ( 97.5 % ) patients . Statistical Analysis The main conclusions of INVEST were that the 2 treatment strategies were equivalent with respect to the primary outcome , main secondary outcomes , and on-treatment systolic and diastolic pressures . Thus , data for all enrolled patients were combined and included in these analyses following the intention-to-treat principle . A P value of 0.05 or less was considered statistically significant . Patients without a primary outcome event were censored at their latest follow-up visit . Average follow-up systolic and diastolic pressures were calculated for each patient by using all post-baseline results , up to the date of primary outcome or censoring . The baseline value was substituted for patients with no post-baseline data ( n= 1154 ) . In this exploratory analysis , the proportions of patients were pooled by 10 mm Hg strata of average follow-up systolic pressure , and the distribution of primary outcome event rate was evaluated to determine whether the relationship was linear . A similar presentation was prepared for diastolic pressure . Because the frequency distributions seemed consistent with a quadratic curve , a quadratic Cox proportional hazards model was formed for the time to primary outcome for each blood pressure variable , with factors for blood pressure and blood pressure squared . Similarly , the relationship between each 10 mm Hg stratum of average systolic pressure and diastolic pressure and all-cause death , fatal and nonfatal MI , and fatal and nonfatal stroke was evaluated . For the time to primary outcome , a second model was fitted , adjusting for the following baseline covariates : age ( 10-year increments ) , sex , race and ethnicity ( white , Asian , black , Hispanic , multiracial , or other ) , previous MI , heart failure ( classes I to III ) , body mass index in increments of 5 kg/m2 , U.S. residency , renal impairment , peripheral vascular disease , left ventricular hypertrophy , smoking history , coronary revascularization , dyslipidemia , stroke or transient ischemic attack , angina pectoris , arrhythmia , diabetes , cancer , aspirin use , and average systolic pressure or diastolic pressure and systolic pressure squared or diastolic pressure squared . To identify clinical ly relevant interactions between the J-shaped curve and baseline diastolic pressure , demographic characteristics , and comorbid conditions for the primary outcome , a 2-step procedure was used . First , baseline covariates were tested individually by adding the variable and 2 interaction terms ( variablediastolic pressure and variable[diastolic pressure squared ] ) to the Cox proportional hazards model . Variables included were age older than 70 years , sex , previous MI , heart failure ( classes I to III ) , previous stroke or transient ischemic attack , diabetes , cancer , renal impairment , hypercholesterolemia , peripheral vascular disease , smoking history , U.S. residency , body mass index greater than 29 kg/m2 ( mean baseline body mass index ) , and diastolic pressure greater than 86 mm Hg ( mean baseline diastolic pressure ) . The change in log likelihood was used to assess the significance of simultaneously adding the 2 interaction terms . The second step in identifying clinical ly relevant interactions between the J-shaped curve and baseline covariates was to plot the hazard ratios for the primary outcome versus diastolic pressure in the We performed a post hoc analysis of the Systolic Hypertension in the Elderly Program data base to assess the incidence of atrial fibrillation in the elderly hypertensive population , its influence on cardiovascular events , and whether antihypertensive treatment can prevent its onset . The Systolic Hypertension in the Elderly Program was a double-blind placebo-controlled trial in 4736 subjects with isolated systolic hypertension aged ≥60 years . Atrial fibrillation was an exclusion criterion from the trial . Participants were r and omly assigned to stepped care treatment with chlorthalidone and atenolol ( n=2365 ) or placebo ( n=2371 ) . The occurrence of atrial fibrillation and cardiovascular events over 4.7 years as well as the determination of cause of death at 4.7 and 14.3 years were followed . Ninety-eight subjects ( 2.06 % ) developed atrial fibrillation over 4.7 years mean follow-up , without significant difference between treated and placebo groups . Atrial fibrillation increased the risk for : total cardiovascular events ( RR 1.69 ; 95 % CI 1.21 to 2.36 ) , rapid death ( RR 3.29 ; 95 % CI 1.08 to 10.00 ) , total ( RR 5.10 ; 95 % CI 3.12 to 8.37 ) and nonfatal left ventricular failure ( RR 5.31 ; 95 % CI 3.09 to 9.13 ) . All-cause and total cardiovascular death were significantly increased in the atrial fibrillation group at 4.7 years ( HR 3.44 ; 95 % CI 2.18 to 5.42 ; HR 2.39 ; 95 % CI 1.05 to 5.43 ) and 14.3 years follow-up ( HR 2.33 ; 95 % CI 1.83 to 2.98 ; HR 2.21 ; 95 % CI 1.54 to 3.17 ) . Atrial fibrillation increased the risk for total cardiovascular events , rapid death , and left ventricular failure . All-cause mortality and total cardiovascular mortality were significantly increased in hypertensives with atrial fibrillation at 4.7 and 14.3 years follow-up PURPOSE R and omized controlled trials have demonstrated that anticoagulant therapy is very effective at preventing stroke among patients with nonrheumatic atrial fibrillation . However , these trials have reported too few strokes for powerful risk factor analysis . Observational studies may provide additional information . The purpose of this study was to identify risk factors in a larger number of patients with stroke and nonrheumatic atrial fibrillation , using case-control methodology . PATIENTS AND METHODS We identified all patients discharged from one hospital over an 8-year period who met our case definition of nonrheumatic atrial fibrillation and ischemic stroke ( n = 134 ) , and compared them with contemporaneous control subjects who were discharged with nonrheumatic atrial fibrillation without stroke ( n = 131 ) . RESULTS Cases and controls were similar in terms of duration of atrial fibrillation ; proportion with paroxysmal atrial fibrillation ; percentage with a past medical history of angina , myocardial infa rct ion , congestive heart failure , diabetes , or smoking ; and mean left atrial size . In contrast , cases were significantly older than controls ( 78.5 versus 74.8 years , p = 0.002 ) and more likely to have a history of hypertension ( 55 % versus 38 % , p = 0.0093 ) . The relative odds for stroke was 1.91 for patients with hypertension , 1.73 for patients older than 75 years , and 3.26 for patients with both factors . CONCLUSIONS Our analysis suggests that age and hypertension should be considered when deciding upon long-term anticoagulant therapy to prevent stroke in patients with nonrheumatic atrial fibrillation Isolated systolic hypertension is an important risk factor for cardiovascular disease and results primarily from elastic artery stiffening . Although various drug therapies are used to lower peripheral blood pressure ( BP ) in patients with isolated systolic hypertension , the effects of the 4 major classes of antihypertensive agents on central BP , pulse pressure ( PP ) amplification , and arterial stiffness in this condition are not clear . Fifty-nine patients over the age of 60 years with untreated isolated systolic hypertension ( systolic BP ≥140 mm Hg and diastolic BP ≤90 mm Hg ) were r and omly assigned to receive 1 of the following 4 antihypertensive agents : perindopril , atenolol , lercanidipine , or bendrofluazide  . BP was measured using a mercury sphygmomanometer , and augmentation index and carotid-femoral ( aortic ) pulse wave velocity were measured at baseline , after 2 weeks of placebo therapy , and at the end of 10 weeks of active therapy . Peripheral systolic BP and peripheral PP were reduced similarly after treatment with all 4 classes of drug . However , central PP was only reduced significantly by perindopril , lercanidipine , and bendrofluazide , whereas atenolol had no effect . Lercanidipine reduced the augmentation index , whereas atenolol increased it . Aortic pulse wave velocity was not changed by any of the drugs . In summary , despite similar reductions in peripheral systolic and PPs with the 4 classes of drug , changes in central pressure and augmentation index varied . Because central PP and increased wave reflections are considered important risk factors in patients with isolated systolic hypertension , the choice of therapy may be influenced by these findings in the future The mechanism of risk reduction obtained by blood pressure-lowering pharmacological treatment remains unclear . We explored the amount of risk reduction attributable to the apparent effect of antihypertensive medicines on blood pressure by using the capture approach . Five r and omized , placebo or nil controlled trials with a total of 28,997 subjects and 1,935 cardiovascular fatal or non-fatal events from the INDANA data base met the eligibility criteria . Computations were performed on the original individual records using multiple Cox 's proportional hazard regression models design ed for meeting the assumed treatment mode of action and comparing relevant assumptions . For coronary event , the results are inconclusive essentially because the risk reduction is mild . However , for stroke the risk reduction adjusted for baseline risk factors is 34 % ( P<0.0001 ) . The part explained by the effect of treatment on systolic blood pressure is 49 % of this reduction , with 95 % confidence interval not including 100 % . This result suggests that the apparent effect on blood pressure is not the only cause of stroke risk reduction in hypertensive subjects su bmi tted to an antihypertensive medicine In recent years , substantial evidence has accumulated to unambiguously implicate high plasma fibrinogen levels as a major cardiovascular risk factor . An open prospect i ve and r and omised pilot study was therefore undertaken in mild to moderate hypertensives to evaluate the effect of various antihypertensive drugs viz enalapril , felodipine and prazosin on the blood pressure and plasma fibrinogen levels . The systolic and diastolic blood pressures were determined at 0 , 4 and 8 weeks whereas plasma fibrinogen assays were done at baseline and at the end of the 8th week of treatment in all the drug-treated groups . It was observed that although all the three drugs effectively controlled blood pressure , only enalapril significantly reduced plasma fibrinogen levels . Due to this additional effect , enalapril has potential to control two major cardiovascular risk factors -- hypertension and high plasma fibrinogen levels -- simultaneously PURPOSE The risk of ischemic stroke varies widely among patients with nonvalvular atrial fibrillation , influencing the choice of prophylactic antithrombotic therapy . We assessed three schemes for stroke risk stratification in these patients who were treated with aspirin and who did not have prior cerebral ischemia . SUBJECTS AND METHODS Criteria from three schemes of risk stratification were applied to a longitudinally observed cohort of patients with atrial fibrillation who did not have prior cerebral ischemia and who were treated with aspirin alone or aspirin combined with low , ineffective doses of warfarin in a multicenter clinical trial . The ability of the schemes to identify patients at high ( > /=6 % ) , low ( < /=2 % ) , and intermediate annual risks of ischemic stroke was assessed . RESULTS During a mean follow-up of 1.8 years , 48 ischemic strokes occurred among 1,073 patients with atrial fibrillation who were taking aspirin ( rate = 2.5 per 100 person-years ) . Each of the three schemes predicted stroke and disabling stroke , and successfully identified patients at low risk ( observed stroke rates of 0.3 to 1.1 per 100 person-years ) , although the fractions of the cohort that were categorized as low risk varied from 14 % to 45 % . The observed rates of ischemic stroke among patients categorized as high risk ranged from 3.5 to 7.2 per 100 person-years among the stratification schemes . Two schemes considered all patients > 75 years old as high risk ( observed stroke rate 4.2 per 100 person-years ) , while the remaining scheme classified one third of patients in this age group as low risk ( observed stroke rate 0.6 per 100 person-years ) . CONCLUSIONS When tested in a large cohort of patients with atrial fibrillation who were treated with aspirin  , available risk-stratification schemes successfully identified patients with low rates of ischemic stroke , but less consistently identified high-risk patients BACKGROUND Hypertension is the most important risk factor directly attributable to the high prevalence of atrial fibrillation ( AF ) , and is one of the few modifiable risk factors for AF . Activation and overactivity of the sympathetic nervous system ( SNS ) have been implicated in the pathogenesis of both essential hypertension and AF . Catheter-based renal sympathetic denervation ( RSDN ) appears to be an effective adjunctive treatment for refractory hypertension , and may be beneficial in other conditions characterized by SNS overactivity , such as left ventricular hypertrophy and atrial arrhythmias . OBJECTIVE The H-FIB study is a multicenter prospect i ve , double-blind , r and omized ( 1:1 ) controlled trial . The primary efficacy endpoint is antiarrhythmic drug-free freedom from AF recurrence through 12 months . METHODS Patients with a history of significant hypertension who are receiving treatment with at least one antihypertensive agent who are planned for a first time ablation for symptomatic paroxysmal or persistent AF will be r and omized to either AF ablation alone ( control group ) or AF ablation + RSDN ( study group ) . CONCLUSIONS H-FIB is a multicenter , r and omized trial that will test the hypothesis that adjunctive renal sympathetic denervation , at the time of AF ablation , will increase the freedom from recurrent AF AIMS Permanent atrial fibrillation develops in many patients after ablation and pacing therapy .  We compared a strategy that initially allowed patients to remain in atrial fibrillation with a strategy that initially attempted to restore and maintain sinus rhythm . METHODS AND RESULTS In this multicentre r and omized controlled trial , 68 patients affected by severely symptomatic paroxysmal atrial fibrillation were assigned , after successful atrioventricular junction ablation and pacing treatment  , to antiarrhythmic drug therapy with amiodarone , propafenone , flecainide or sotalol and were compared with 69 patients assigned , after successful AV junction ablation and pacing treatment , to no antiarrhythmic drug therapy . The patients were followed-up for 12 to 24 months ( mean 16+/-4 ) . The drug arm patients had a 57 % reduction in the risk of developing permanent atrial fibrillation ( 21 % vs 37 % , P=0.02 ) . Evaluation after 12 months revealed similar quality of life scores and echocardiographic parameters in the two groups , but the drug arm patients had more episodes of heart failure and hospitalizations ( P=0.05 ) . The outcome was similar between the 40 patients who developed permanent atrial fibrillation and the 97 who did not . CONCLUSION Conventional antiarrhythmic therapy reduces the risk of development of permanent atrial fibrillation after ablation and pacing therapy . The present data do not support the concept that the development of permanent atrial fibrillation is related to an adverse outcome when a perfect control of heart rate is obtained by ablation and pacing BACKGROUND AND OBJECTIVES The relation between cardiac mortality and antiarrhythmic drug administration has not been fully determined . This relation was analyzed in 1,330 patients enrolled in the Stroke Prevention in Atrial Fibrillation Study , a r and omized clinical trial comparing warfarin , aspirin and placebo for the prevention of ischemic stroke or systemic embolism in patients with nonvalvular atrial fibrillation . METHODS Patients who received antiarrhythmic drug therapy for atrial fibrillation in this study were compared with patients not receiving antiarrhythmic agents . The relative risk of cardiac mortality , including arrhythmic death , in patients receiving antiarrhythmic drug therapy  was determined and adjusted for other cardiac risk factors . RESULTS In patients receiving antiarrhythmic drug therapy , cardiac mortality was increased 2.5-fold ( p = 0.006 , 95 % confidence interval [ CI ] 1.3 to 4.9 ) and arrhythmic death was increased 2.6-fold ( p = 0.02 , 95 % CI 1.2 to 5.6 ) . Among patients with a history of congestive heart failure , those given antiarrhythmic medications had a relative risk of cardiac death of 4.7 ( p less than 0.001 , 95 % CI 1.9 to 11.6 ) compared with that of patients not so treated ; the relative risk of arrhythmic death in the treated group was 3.7 ( p = 0.01 , 95 % CI 1.3 to 10.4 ) . Patients without a history of congestive heart failure had no increased risk of cardiac mortality ( relative risk 0.70 , 95 % CI 0.2 to 3.1 ) during antiarrhythmic drug therapy . After exclusion of 23 patients with documented ventricular arrhythmias and adjustment for other variables predictive of cardiac death , patients receiving antiarrhythmic drugs were not at increased risk of cardiac death or arrhythmic death . However , in patients with a history of heart failure who received antiarrhythmic drug therapy , the relative risk of cardiac death was 3.3 ( p = 0.05 , 95 % CI 0.99 to 11.1 ) and that of arrhythmic death was 5.8 ( p = 0.009 , 95 % CI 1.5 to 21.7 ) compared with the risk in patients not taking antiarrhythmic medications . CONCLUSIONS Although antiarrhythmic drug therapy was not r and omly determined in this trial , the data suggest that in patients with atrial fibrillation and a history of congestive heart failure , the risk of such therapy may outweigh the potential benefit of maintaining sinus rhythm The risk for ischemic stroke in patients with atrial fibrillation is related to underlying structural heart disease [ 1 - 3 ] . Although most strokes are believed to arise from embolism of left atrial thrombi [ 4 , 5 ] , other mechanisms may contribute . Transesophageal echocardiography ( TEE ) provides a unique diagnostic window for evaluating the left atrium , left atrial appendage , and thoracic aorta , but the manner in which specific TEE findings in patients with atrial fibrillation correlate with thromboembolic risk and response to therapy has not been fully established [ 6 - 13 ] . We performed TEE in patients with nonvalvular atrial fibrillation who were at high intrinsic risk for thromboembolism and were participating in the Stroke Prevention in Atrial Fibrillation ( SPAF-III ) study , a r and omized clinical trial . In that study , adjusted-dose warfarin ( target international normalized ratio [ INR ] , 2 to 3 ) was compared with combination therapy consisting of low-intensity warfarin ( INR , 1.2 to 1.5 ) plus aspirin , 325 mg/d . The trial was stopped after an interim analysis indicated that the efficacy of adjusted-dose warfarin therapy was superior to that of combination therapy . Low anticoagulation intensity in the combination therapy group yielded high stroke rates that were similar to those expected during treatment with aspirin alone [ 14 , 15 ] . In the current analysis , we 1 ) correlate TEE observations among patients with atrial fibrillation at high risk for thromboembolism with rate of subsequent stroke and 2 ) compare treatment responses . Methods Patients Patients were recruited from the SPAF-III multicenter trial , which was design ed to compare two antithrombotic medication regimens for prevention of ischemic stroke and systemic embolism ( primary events ) . The study , whose design is described else-where in detail [ 14 ] , involved patients with nonvalvular atrial fibrillation who were stratified for risk on the basis of clinical and transthoracic echocardiographic criteria derived from previous analyses [ 15 ] . Women older than 75 years of age and patients of any age and either sex with systolic hypertension ( systolic blood pressure > 160 mm Hg ) , previous thromboembolism , or impaired left ventricular function ( M-mode echocardiographic fractional shortening of 0.25 or recent clinical congestive heart failure ) were r and omly assigned to receive adjusted-dose warfarin ( target INR , 2.0 to 3.0 ) or a combination of low-intensity warfarin ( 0.5 to 3.0 mg/d ; dose was initially adjusted to cause deviation of the INR to 1.2 to 1.5 and was then fixed ) and aspirin . Seventy-three percent of the patients were receiving warfarin at various dose intensities before trial entry ; these patients were equally distributed between assigned treatment groups . Antithrombotic treatment was assigned before performance of TEE and was not influenced by TEE findings . Patients were followed monthly by telephone and in clinic every 3 months , and a st and ard question naire on stroke symptoms was administered annually . All patients whose responses to the question naire suggested the occurrence of stroke were referred for clinical examination by a local affiliated neurologist who was blinded to treatment , and all events were adjudicated by a blinded event verification committee [ 14 ] . This project was design ed to supplement the SPAF-III clinical trial on the basis of the hypothesis that spontaneous echocardiographic contrast detected by TEE identifies patients at high risk for thromboembolism for whom adjusted-dose warfarin  would prove superior to  combination therapy . All participants in the parent study were encouraged , but not required , to provide separate , written informed consent for TEE after r and om assignment to antithrombotic treatment . This was done to prevent the results of TEE from influencing recruitment of patients into the trial or from altering treatment . The intended sample size of 412 TEE examinations was selected to detect an absolute difference in event rates of 3.9 % per year ( based on projected event rates of 5.4 % per year in patients with spontaneous echocardiographic contrast and 1.5 % per year in patients without contrast ) over a mean observation period of 2.5 years . Secondary objectives were to correlate clinical thromboembolic events with function of the left atrial appendage , thrombus of the left atrium and left atrial appendage , and atherosclerotic lesions in the thoracic aorta imaged by TEE . Transesophageal Echocardiography Transesophageal echocardiography was performed within 3 months of enrollment with patients under light sedation and topical anesthesia , according to specific protocol s for acquisition and interpretation [ 16 ] . Commercially available ultrasonography equipment incorporated biplane or multiplane transducers with at least 48 crystals operating at a st and ard frequency of 5 MHz with gray-scale imaging . Signal processing , log compression , and persistence values were established for each manufacturer . Images were interpreted locally , and data were entered into st and ardized forms by echocardiographers who were blinded to antithrombotic treatment assignment but not to patient demographic or clinical features . Original videotaped recordings were collected in a central echocardiographic registry for validation and quality control . To assure generalizability of the results to laboratories used in clinical practice , the analyses reported here are based on image interpretation at the local laboratories . The following features were specifically assessed : left atrial appendage size , peak ante grade ( emptying ) velocity of blood flow in the left atrial appendage , spontaneous echocardiographic contrast in the left atrium or left atrial appendage , thrombus of the left atrium or left atrial appendage , and atherosclerotic disease of the thoracic aorta . Spontaneous echocardiographic contrast was defined as a pattern of slowly swirling intracavitary echodensities imaged with gain setting s adjusted to distinguish background noise . Contrast was classified as faint when visualized intermittently during the cardiac cycle or when enhanced gain setting s were required for detection and was classified as dense when continuously present at st and ard gain . Aortic plaque was classified by location and as either simple or complex according to mobility , ulceration , pedunculation , or thickness greater than 4 mm [ 16 ] . We postulated that reduced emptying velocity from the left atrial appendage , which reflects stasis , would be associated with dense spontaneous echocardiographic contrast and thrombus formation , whereas complex aortic plaque would be a consequence of atherosclerotic vascular abnormality . We also postulated that these findings would predispose patients to ischemic stroke through separate pathogenic mechanisms . Statistical Analysis The analyses reported here were limited to variables accessible only by TEE and were hypothesized a priori to have potential predictive relations to clinical thromboembolism . Baseline comparisons between groups were done by using the chi-square test for categorical data and the Student t-test for continuous variables . The Cox proportional-hazards regression model was used to estimate the univariate relative risk associated with TEE characteristics . The primary analysis compared rates of cerebral ischemic events and systemic embolism among patients who had dense spontaneous echocardiographic contrast detected in the left atrium or left atrial appendage with rates in patients who did not have dense contrast ; the log-rank statistic was used to compare the times to events between these groups . Secondary analyses , conducted similarly , compared event rates in groups that were identified by left atrial appendage size , flow velocity , thrombus , and aortic plaque . For these comparisons , the area of the left atrial appendage was dichotomized at the upper quartile ; flow velocity was dichotomized at the lower quartile . When interaction was seen between treatment and TEE characteristics , analysis of the relation of TEE findings to events was confined to the combination therapy group and treatment effect was described separately ; when no interaction was seen , the analysis was stratified by therapy . The relative reduction in event rate associated with adjusted-dose warfarin therapy was computed as the difference between unity and the rate ratio determined by a Poisson regression model [ 17 ] . A Cox proportional-hazards regression model was fit to confirm the independence of TEE characteristics identified as univariate thromboembolic risk factors . Confidence intervals for event rates were calculated by using a Poisson regression model ; tests of significance were two-sided and were not adjusted for multiple comparisons . All analyses were done according to the intention-to-treat principle . Results Of 1044 high-risk patients with atrial fibrillation enrolled in the r and omized trial , 382 ( 37 % ) volunteered for TEE ( range , 10 % to 80 % of SPAF-III participants recruited at 18 clinical centers offering TEE ) . Salient features of these 382 patients were similar to those of the 662 participants who did not undergo transesophageal imaging ( Table 1 ) . The mean patient age was 71 years , 36 % of patients had clinical ischemic heart disease , and almost half had a history of congestive heart failure . Balanced proportions of patients were assigned to therapy with adjusted-dose warfarin ( n = 190 ) or fixed-dose warfarin and aspirin ( n = 192 ) . Time from r and om assignment of treatment to TEE was similar in the two groups ( mean , 23 days ) . The trial was stopped after a mean observation period of 1.1 years because an interim analysis indicated the lack of efficacy of the combination regimen [ 18 ] . Up to that point , 23 primary events ( all of which were ischemic strokes ) occurred in the subset of participants who had undergone TEE ( event rate , 3.1 % per year in patients assigned to adjusted-dose warfarin compared with 7.8 % per year in those assigned to combination therapy ; P = 0.04 ) . Background The goal of the present study was to assess the effect of antihypertensive therapy on clinic ( CBP ) and ambulatory ( ABP ) blood pressures , on ECG voltages , and on the incidence of stroke and cardiovascular events in older patients with sustained and nonsustained systolic hypertension . Methods and Results Patients who were ≥60 years old , with systolic CBP of 160 to 219 mm Hg and diastolic CBP of < 95 mm Hg , were r and omized into the double-blind placebo-controlled Systolic Hypertension in Europe ( Syst-Eur ) Trial . Treatment consisted of nitrendipine , with the possible addition of enalapril , hydrochlorothiazide , or both .  Patients enrolled in the Ambulatory Blood Pressure Monitoring Side Project were classified according to daytime systolic ABP into 1 of 3 subgroups : nonsustained hypertension ( < 140 mm Hg ) , mild sustained hypertension ( 140 to 159 mm Hg ) , and moderate sustained hypertension ( ≥160 mm Hg ) . At baseline , patients with nonsustained hypertension had smaller ECG voltages ( P < 0.001 ) and , during follow-up , a lower incidence of stroke ( P < 0.05 ) and of cardiovascular complications ( P = 0.01 ) than other groups . Active treatment reduced ABP and CBP in patients with sustained hypertension but only CBP in patients with nonsustained hypertension ( P < 0.001 ) . The influence of active treatment on ECG voltages ( P < 0.05 ) and on the incidence of stroke ( P < 0.05 ) and cardiovascular events ( P = 0.06 ) was more favorable than that of placebo only in patients with moderate sustained hypertension . Conclusions Patients with sustained hypertension had higher ECG voltages and rates of cardiovascular complications than did patients with nonsustained hypertension . The favorable effects of active treatment on these outcomes were only statistically significant in patients with moderate sustained hypertension Background : High blood pressure is an important public health concern because it is highly prevalent and a risk factor for adverse health outcomes , including coronary heart disease , stroke , decompensated heart failure , chronic kidney disease , and decline in cognitive function . Observational studies show a progressive increase in risk associated with blood pressure above 115/75 mm Hg . Prior research has shown that reducing elevated systolic blood pressure lowers the risk of subsequent clinical complications from cardiovascular disease . However , the optimal systolic blood pressure to reduce blood pressure – related adverse outcomes is unclear , and the benefit of treating to a level of systolic blood pressure well below 140 mm Hg has not been proven in a large , definitive clinical trial . Purpose : To describe the design considerations of the Systolic Blood Pressure Intervention Trial ( SPRINT ) and the baseline characteristics of trial participants . Methods : The Systolic Blood Pressure Intervention Trial is a multicenter , r and omized , controlled trial that compares two strategies for treating systolic blood pressure : one targets the st and ard target of < 140 mm Hg , and the other targets a more intensive target of < 120 mm Hg . Enrollment focused on volunteers of age ≥50 years ( no upper limit ) with an average baseline systolic blood pressure ≥130 mm Hg and evidence of cardiovascular disease , chronic kidney disease , 10-year Framingham cardiovascular disease risk score ≥15 % , or age ≥75 years . The Systolic Blood Pressure Intervention Trial recruitment also targeted three pre-specified subgroups : participants with chronic kidney disease ( estimated glomerular filtration rate < 60 mL/min/1.73 m2 ) , participants with a history of cardiovascular disease , and participants 75 years of age or older . The primary outcome is first the occurrence of a myocardial infa rct ion ( MI ) , acute coronary syndrome , stroke , heart failure , or cardiovascular disease death . Secondary outcomes include all-cause mortality , decline in kidney function or development of end-stage renal disease , incident dementia , decline in cognitive function , and small-vessel cerebral ischemic disease . Results : Between 8 November 2010 and 15 March 2013 , Systolic Blood Pressure Intervention Trial recruited and r and omized 9361 people at 102 clinics , including 3331 women , 2648 with chronic kidney disease , 1877 with a history of cardiovascular disease , 3962 minorities , and 2636 ≥75 years of age . Limitations : Although the overall recruitment target was met , the numbers recruited in the high-risk subgroups were lower than planned . Conclusions : The Systolic Blood Pressure Intervention Trial will provide important information on the risks and benefits of intensive blood pressure treatment targets in a diverse sample of high-risk participants , including those with prior cardiovascular disease , chronic kidney disease , and those aged ≥75 years BACKGROUND The ideal management of patients with newly diagnosed symptomatic atrial fibrillation ( AF ) remains unknown . Current practice guidelines recommend a trial of antiarrhythmic drugs ( AAD ) prior to considering an invasive ablation procedure . However , earlier ablation offers an opportunity to halt the progressive patho-anatomical changes associated with AF , as well as impart other important clinical benefits . OBJECTIVE The aim of this study is to determine the optimal initial management strategy for patients with newly diagnosed , symptomatic atrial fibrillation . METHODS / DESIGN The EARLY-AF study ( Clinical Trials.govNCT02825979 ) is a prospect i ve , open label , multicenter , r and omized trial with a blinded assessment of outcomes . A total of 298 patients will be r and omized in a 1:1 fashion to first-line AAD therapy , or first-line cryoballoon-based pulmonary vein isolation .  Patients with symptomatic treatment naïve AF will be included . Arrhythmia outcomes will be assessed by implantable cardiac monitor ( ICM ) . The primary outcome is time to first recurrence of AF , atrial flutter , or atrial tachycardia ( AF/AFL/AT ) between days 91 and 365 following AAD initiation or AF ablation . Secondary outcomes include arrhythmia burden , quality of life , and healthcare utilization . DISCUSSION The EARLY-AF study is a r and omized trial design ed to evaluate the optimal first management approach for patients with AF . We hypothesize that catheter ablation will be superior to drug therapy in prevention of AF recurrence BACKGROUND AND PURPOSE Nonvalvular atrial fibrillation ( AF ) is a strong , independent risk factor for stroke , but the absolute rate of stroke varies widely among AF patients , importantly influencing the potential benefit of antithrombotic prophylaxis . We explore factors associated with ischemic stroke in AF patients taking aspirin .  METHODS We performed multivariate logistic regression analysis of 2012 participants given aspirin alone or in combination with low , inefficacious doses of warfarin in the Stroke Prevention in Atrial Fibrillation I-III trials followed for a mean of 2.0 years , during which 130 ischemic strokes were observed . RESULTS Age ( relative risk [RR]=1.8 per decade , P<0.001 ) , female sex ( RR=1.6 , P=0.01 ) , history of hypertension ( RR=2.0 , P<0.001 ) , systolic blood pressure > 160 mm Hg ( RR=2.3 , P<0.001 ) , and prior stroke or transient ischemic attack ( RR=2.9 , P<0.001 ) were independently associated with increased stroke risk . Regular consumption of > /=14 alcohol-containing drinks per week was associated with reduced stroke risk ( adjusted RR=0.4 , P=0.04 ) . Among SPAF III participants , estrogen hormone replacement therapy was associated with a higher risk of ischemic stroke ( adjusted RR=3.2 , P=0.007 ) . With the use of these variables , a risk stratification scheme for primary prevention separated participants into those with high ( 7.1%/y , 22 % of the cohort ) , moderate ( 2.6%/y , 37 % of the cohort ) , and low ( 0.9%/y , 41 % of the cohort ) rates of stroke . Ischemic strokes in low-risk participants were less often disabling ( P<0.001 ) . CONCLUSIONS Patients with AF who have high and low rates of stroke during treatment with  aspirin can be identified . However , validation of our risk stratification scheme is necessary before it can be applied with confidence to clinical management . Postmenopausal estrogen replacement therapy and moderate alcohol consumption may additionally modify the risk of stroke in AF , but these findings require confirmation BACKGROUND Positive pressure therapy ( CPAP ) in patients with cardiac arrhythmias and obstructive sleep apnea ( OSAS ) may have favorable effects by correcting intermittent hypoxemia and sympathetic activation . OBJECTIVE To assess the effect of CPAP added to pharmacological treatment in the rate control and prevention of arrhythmias recurrence in patients with OSA . MATERIAL S AND METHODS Prospect i ve , interventional study study which included patients diagnosed with OSAS ( cardiorespiratorypolygraphy , AHI>5/hour ) , and arrhythmias ( ECG , Holter ECG ) , divided in two groups : group A ( pharmacological therapy only ) and group B ( pharmacological therapy and CPAP ) . The patients were evaluated at enrollment ( T0 ) , at 3 and 6 months ( T3 and T6 ) regarding the type , severity and recurrence of cardiac arrhythmias . RESULTS 36 patients ( 31 men ) , mean age : 63.2 ± 12 years were enroled . In group A : 7 patients with ventricular extrasystoles , 8 with permanent atrial fibrillation , 1 patient with atrial flutter and 2 patients with paroxystic supraventricular tachycardia . In group B : 8 patients with ventricular extrasystoles , 5 with permanent atrial fibrillation , 2 patients with recurrent episodes of atrial fibrillation and 3 with paroxystic supraventricular tachycardia . A positive correlation ( r : 0.74 , p < 0.001 ) between Oxygen Desaturation Index and AHI was found . At T6 , 12 patients from group B , and 18 from group A were evaluated . In group B , the mean heart rate in patients with atrial fibrillation was 69/min . , lower than in group A ( 82/min . ) , no cases with recurrent atrial fibrillation were found , and more patients with class II Lown ventricular extrasystoles passed in class I Lown , compared to group A. In group B , heart rate statistically correlated with AHI ( r : 0.53 , p < 0.005 ) . CONCLUSION In patients with OSAS , adding CPAP to pharmacological therapy has favorable effects on preventing recurrences , heart rate control in patients with atrial fibrillation and in reducing frequency and /or severity of ventricular extrasystoles
Antihypertensive therapy reduces the risk of atrial fibrillation modestly but benefits appear to be larger in patients with heart failure , with no clear evidence of benefit in patients without heart failure .
Previous suggestions of class-specific effects could not be confirmed in this more comprehensive analysis
AIMS High blood pressure is known to be associated with future risk of atrial fibrillation .
Whether such risks can be reduced with antihypertensive therapy is less clear .
We conducted a systematic review and meta- analysis of large-scale r and omized trials that have reported the effect of antihypertensive agents on atrial fibrillation .