Incident atrial fibrillation and mortality in older adults with heart failure

We studied 944 hospitalized heart failure patients 65 years and older to examine the impact of incident atrial fibrillation on mortality. Patients were categorized into four groups based on past medical history and admission electrocardiogram: (1) no (neither past nor current), (2) incident (newly diagnosed), (3) past and (4) chronic (past and current) atrial fibrillation. The primary outcome was 4-year all-cause mortality. Bivariate and multivariable Cox proportion hazards analyses were used to determine risk of all-cause mortality. In the multivariable model, we adjusted for various demographic and clinical covariates. Compared with patients who never had atrial fibrillation, those with incident atrial fibrillation had a 57% higher risk of death (unadjusted hazard ratio, 1.57; 95% confidence interval, 1.22-2.03). After adjustment for other covariates the association remained unchanged (adjusted hazard ratio, 1.41; 95% confidence interval, 1.08-1.83). Past or chronic atrial fibrillation was not associated with increased risk of death.     

Cardiovascular and Stroke Risk in Japanese Hemodialysis Patients With Atrial Fibrillation

Atrial fibrillation is one of the most common arrhythmias in hemodialysis patients. We evaluated its clinical outcomes among hemodialysis patients with atrial fibrillation in Japan. Using data derived from the Japanese Dialysis Outcomes and Practice Patterns Study, we analyzed backgrounds and outcomes among hemodialysis patients with and without atrial fibrillation in Japan. Among 7002 hemodialysis patients, the prevalence of atrial fibrillation was 5.7% and the incidence was 0.2 per 100 patient‐years. Atrial fibrillation was independently associated with all‐cause mortality (hazard ratio, 1.32; 95% confidence interval, 1.02–1.71) and cardiovascular events (hazard ratio, 1.39; 95% confidence interval, 1.15–1.68), but not with stroke events (hazard ratio, 0.77; 95% confidence interval, 0.55–1.06) after adjustment for other variables. We conclude that patients with atrial fibrillation experienced higher mortality and more cardiovascular events than did patients without atrial fibrillation, although the risk of stroke was lower than expected.     

Outcomes and safety of antithrombotic treatment in patients aged 80 years or older with nonvalvular atrial fibrillation

Our aim was to evaluate the effectiveness of oral anticoagulation (OAC) in patients aged ≥80 years with nonvalvular atrial fibrillation in daily clinical practice. From February 1, 2000 to June 30, 2009, we enrolled all patients aged ≥80 years with nonvalvular atrial fibrillation attended at 2 outpatient cardiology clinics of a tertiary care university hospital. The patients received antithrombotic treatment according to the recommendations from scientific societies and were prospectively followed, with major events (i.e., all-cause death, stroke, transient ischemic attack, peripheral embolism, severe bleeding) analyzed according to the treatment group (OAC vs no OAC). Of 269 patients included in the present study (87 men, mean age 83 ± 3 years), 164 received OAC (61%). After 2.8 ± 1.9 years of follow-up, the raw rates (per 100 patient-years) of embolic events (1.52% vs 8.30%, p <0.0001) and mortality (6.67% vs 10.94%, p = 0.04) were lower for patients receiving OAC, with a nonsignificant greater rate of severe bleeding (3.03% vs 1.25%, p = 0.14). The probability of survival free of major embolic or hemorrhagic events at the mean follow-up was greater for patients receiving OAC (82.27% vs 66.10%, p = 0.004). After adjustment for age, gender, coronary heart disease, and embolic risk, evaluated using the CHADS(2) score (congestive heart failure, 1 point; hypertension [blood pressure consistently >140/90 mm Hg or hypertension medication], 1 point; age ≥75 years, 1 point; diabetes mellitus, 1 point; previous stroke or transient ischemic attack, 2 points), only OAC was an independent predictor of embolic events (hazard ratio 0.17, 95% confidence interval 0.07 to 0.41, p <0.001). The CHADS(2) score (hazard ratio 1.32, 95% confidence interval 1.01 to 1.73, p = 0.04) and OAC (hazard ratio 0.52, 95% confidence interval 0.31 to 0.88, p = 0.01) were independent predictors of mortality. In conclusion, OAC according to the scientific societies' recommendations is effective and safe in daily clinical practice, even in patients aged ≥80 years.     

Chronic kidney disease and CHADS(2) score independently predict cardiovascular events and mortality in patients with nonvalvular atrial fibrillation

Chronic kidney disease is a risk factor for cardiovascular events, but how it relates to the prognosis associated with clinical risk factors for thromboembolism in patients with nonvalvular atrial fibrillation (AF) is not well known. Estimated glomerular filtration rate (eGFR), score for congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and stroke/transient ischemic attack (CHADS(2)), and clinical outcomes of cardiovascular events were determined in 387 patients with nonvalvular AF (mean age 66 years, 289 men, mean follow-up 5.6 ± 3.2 years). Decreased eGFR (<60 ml/min/1.73 m(2)) combined with CHADS(2) score ≥2 was associated with higher all-cause (12.9% vs 1.4% per year, hazard ratio [HR] 6.9, p <0.001) and cardiovascular (6.5% vs 0.2% per year, HR 29.7, p <0.001) mortalities compared to preserved eGFR (≥60 ml/min/1.73 m(2)) combined with CHADS(2) score <2. This was also true for rates of cardiac events (cardiac death, nonfatal myocardial infarction, or hospitalization for worsening of heart failure, 10.4% vs 1.3% per year, HR 8.9, p <0.001), ischemic stroke (3.6% vs 0.2% per year, HR 11.0, p <0.001), and cardiovascular events (cardiac events and ischemic stroke, 13.6% vs 1.5% per year, HR 8.3, p <0.001). On multivariate analysis, CHADS(2) score ≥2, decreased eGFR, and male gender independently predicted all-cause mortality. In conclusion, combined eGFR and CHADS(2) score could be an independent powerful predictor of cardiovascular events and mortality in patients with nonvalvular AF. Long-term mortality, cardiac events, and stroke risk were >8 times higher when decreased eGFR (<60 ml/min/1.73 m(2)) was present with higher CHADS(2) score (≥2).     

Predictive value of the CHA2DS2-VASc score in atrial fibrillation patients at high risk for stroke despite oral anticoagulation

Introduction and objectives

The risk of stroke in atrial fibrillation is heterogeneous and depends upon underlying clinical conditions included in current risk stratification schemes. Recently, the CHA₂DS₂-VASc score has been included in guidelines to be more inclusive of common stroke risk factors seen in everyday clinical practice, and useful in defining “truly low risk” subjects. We aimed to assess the usefulness of CHA₂DS₂-VASc score to give us an additional prognostic perspective for adverse events and mortality among “real world” anticoagulated patients with atrial fibrillation who are often elderly with many comorbidities.

Methods

Consecutive outpatients with permanent/paroxysmal nonvalvular atrial fibrillation with CHA₂DS₂-VASc≥2 and stabilized oral anticoagulation (international normalized ratio 2.0-3.0) for at least the preceding 6 months were recruited. Patients with CHA₂DS₂-VASc≥2 were selected. Adverse cardiovascular events including stroke, acute coronary syndrome, or heart failure; major bleeds; and mortality were recorded during more than 2.5-year-follow-up.

Results

Of 933 patients (93.5%) assessed, 432 were males, median age 76 (71-81) years. After a follow-up of 946 (782-1068) days, 109 patients (11.7%) had adverse cardiovascular events, 80 patients (8.6%) had major bleeds, 101 patients (10.8%) died, and 230 (24.6%) had major adverse events (composite end-point). Increasing CHA₂DS₂-VASc score by 1 point had a significant impact on the occurrence of cardiovascular events (hazard ratio=1.27; 95% confidence interval, 1.13-1.44; P<.001), mortality (hazard ratio=1.36; 95% confidence interval, 1.19-1.54; P<.001); and major adverse events (hazard ratio=1.23; 95% confidence interval, 1.13-1.34; P<.001). CHA₂DS₂-VASc score was not associated with major bleeding episodes.

Conclusions

Among high risk atrial fibrillation patients on oral anticoagulation, CHA₂DS₂-VASc successfully predicts cardiovascular events and mortality, but not major bleeds.Full English text available from:www.revespcardiol.org     

High-sensitivity C-reactive protein, lipoprotein-associated phospholipase A2, and outcome after ischemic stroke

BACKGROUND: Inflammatory markers have been associated with ischemic stroke risk and prognosis after cardiac events. Their relationship to prognosis after stroke is unsettled. METHODS: A population-based study of stroke risk factors in 467 patients with first ischemic stroke was undertaken to determine whether levels of high-sensitivity C-reactive protein (hs-CRP) and lipoprotein-associated phospholipase A(2) (Lp-PLA2) predict risk of stroke recurrence, other vascular events, and death. RESULTS: Levels of Lp-PLA2 and hs-CRP were weakly correlated (r = 0.09; P = .045). High-sensitivity CRP, but not Lp-PLA2, was associated with stroke severity. After adjusting for age, sex, race and ethnicity, history of coronary artery disease, diabetes mellitus, hypertension, hyperlipidemia, atrial fibrillation, smoking, and hs-CRP level, compared with the lowest quartile of Lp-PLA2, those in the highest quartile had an increased risk of recurrent stroke (adjusted hazard ratio, 2.08; 95% confidence interval, 1.04-4.18) and of the combined outcome of recurrent stroke, MI, or vascular death (adjusted hazard ratio, 1.86; 95% confidence interval, 1.01-3.42). After adjusting for confounders, hs-CRP was not associated with risk of recurrent stroke or recurrent stroke, myocardial infarction, or vascular death but was associated with risk of death (adjusted hazard ratio, 2.11; 95% confidence interval, 1.18-3.75). CONCLUSIONS: Inflammatory markers are associated with prognosis after first ischemic stroke and may offer complementary information. Lipoprotein-associated phospholipase A(2) may be a stronger predictor of recurrent stroke risk. Levels of hs-CRP, an acute-phase reactant, increase with stroke severity and may be associated with mortality to a greater degree than recurrence.     

Clinical and echocardiographic markers of mortality risk in patients with atrial fibrillation

Atrial fibrillation (AF) is independently associated with increases in cardiovascular and all-cause mortality. Although cardiovascular co-morbidities predict stroke risk in AF, their relation with mortality has not been well described. To identify clinical and echocardiographic markers of mortality in patients with AF, 524 patients with AF underwent transesophageal echocardiography from August 2000 to March 2005. Clinical risk factors for systemic thromboembolism were determined for each patient. A CHADS2 (congestive heart failure, hypertension, age>75 years, diabetes, and previous stroke or transient ischemic attack) score ranging from 0 to 6 was calculated for each patient. Transesophageal echocardiographic reports were reviewed for the presence of left atrial spontaneous echocardiographic contrast, left atrial thrombus, the left ventricular ejection fraction, aortic arch atheroma, and the presence and severity of mitral regurgitation. Mortality data were obtained from the Social Security Death Master File. Univariate and multivariate models were structured to assess which variables predicted mortality. In a multivariate model, a history of heart failure, age>75 years, the absence of systemic anticoagulation with warfarin, the presence of left atrial spontaneous echocardiographic contrast, and greater than moderate mitral regurgitation were independent predictors of mortality. Increasing CHADS2 score was also an independent predictor of mortality. A CHADS2 score of 5 or 6 was associated with a >50-fold increase in mortality compared with patients with CHADS2 scores of 0. In conclusion, a history of heart failure, age>or=75 years, the absence of chronic oral anticoagulation, a CHADS2 score>0, and greater than moderate mitral regurgitation are independent predictors of mortality in patients with AF.     

A population-based study of the long-term risks associated with atrial fibrillation: 20-year follow-up of the Renfrew/Paisley study

PURPOSE: To describe the effect of atrial fibrillation on long-term morbidity and mortality. SUBJECTS AND METHODS: The Renfrew/Paisley Study surveyed 7052 men and 8354 women aged 45-64 years between 1972 and 1976. All hospitalizations and deaths occurring during the subsequent 20 years were analyzed by the presence or absence of atrial fibrillation at baseline. Lone atrial fibrillation was defined in the absence of other cardiovascular signs or symptoms. Cox proportional hazards models were used to adjust for age and cardiovascular conditions. RESULTS: After 20 years, 42 (89%) of the 47 women with atrial fibrillation had a cardiovascular event (death or hospitalization), compared with 2276 (27%) of the 8307 women without this arrhythmia. Among men, 35 (66%) of 53 with atrial fibrillation had an event, compared with 3151 (45%) of 6999 without atrial fibrillation. In women, atrial fibrillation was an independent predictor of cardiovascular events (rate ratio [RR] = 3.0; 95% confidence interval [CI]: 2.1-4.2), fatal or nonfatal strokes (RR = 3.2; 95% CI: 1.0-5.0), and heart failure (RR = 3.4; 95% CI: 1.9-6.2). The rate ratios among men were 1.8 (95% CI: 1.3-2.5) for cardiovascular events, 2.5 (95% CI: 1.3-4.8) for strokes, and 3.4 (95% CI: 1.7-6.8) for heart failure. Atrial fibrillation was an independent predictor of all-cause mortality in women (RR = 2.2; 95% CI: 1.5-3.2) and men (RR = 1.5; 95% CI: 1.2-2.2). However, lone atrial fibrillation (which occurred in 15 subjects) was not associated with a statistically significant increase in either cardiovascular events (RR = 1.5; 95% CI: 0.6-3.6) or mortality (RR = 1.8; 95% CI: 0.9-3.8). CONCLUSIONS: Atrial fibrillation is associated with an increased long-term risk of stroke, heart failure, and all-cause mortality, especially in women.     

Seguimiento clínico de una muestra contemporánea de pacientes con fibrilación auricular en tratamiento con digoxina: resultados del estudio AFBAR

Introduction and objectivesWe aimed to assess and compare the effect of digoxin on clinical outcomes in patients with atrial fibrillation vs those under beta-blockers or none of these drugs.MethodsAFBAR is a prospective registry study carried out by a team of primary care physicians (n = 777 patients). Primary endpoints were survival, survival free of admission due to any cause, and survival free of admission due to cardiovascular causes. The mean follow up was 2.9 years. Four groups were analyzed: patients receiving digoxin, beta-blockers, or digoxin plus beta-blockers, and patients receiving none of these drugs.ResultsOverall, 212 patients (27.28%) received digoxin as the only heart control strategy, 184 received beta-blockers (23.68%), 58 (7.46%) were administered both, and 323 (41.57%) received none of these drugs. Digoxin was not associated with all-cause mortality (estimated hazard ratio = 1.42; 95% confidence interval, 0.77-2.60; P = .2), admission due to any cause (estimated hazard ratio = 1.03; 95% confidence interval, 0.710-1.498; P = .8), or admission due to cardiovascular causes (estimated hazard ratio = 1.193; 95% confidence interval 0.725-1.965; P = .4). No association was found between digoxin use and all-cause mortality, admission due to any cause, or admission due to cardiovascular causes in patients without heart failure. There was no interaction between digoxin use and sex in all-cause mortality or in survival free of admission due to any cause. However, an association was found between sex and admission due to cardiovascular causes.ConclusionsDigoxin was not associated with increased all-cause mortality, survival free of admission due to any cause, or admission due to cardiovascular causes, regardless of underlying heart failure.Full English text available from: www.revespcardiol.org/en     

Prognostic usefulness of free fatty acids in patients with stable coronary heart disease

Circulating nonesterified or free fatty acids (FFAs) may contribute to the development of cardiovascular pathology and correlate with ischemia in acute cardiovascular conditions. The aim of this study was to assess whether serum levels of FFAs are associated with long-term prognosis in subjects with stable coronary heart disease. This observational prospective cohort study included 1,206 participants in 3-weeks inpatient rehabilitation programs after acute myocardial infarction, coronary syndromes, or coronary intervention at 2 rehabilitation clinics in Germany (1999 to 2000). Eight-year prognosis (time to a secondary fatal or nonfatal cardiovascular disease event including myocardial infarction and stroke [n = 153] and time to death from any cause [n = 124]) was examined according to FFA quartiles and in spline regression. FFAs were correlated with established serum markers of cardiovascular risk and strongly related to secondary cardiovascular events and all-cause mortality in age- and gender-adjusted analysis. When additionally controlling for multiple established risk factors and risk markers, the hazard ratio in the fourth versus first quartile was 1.34 (95% confidence interval 0.79 to 2.24) for secondary cardiovascular events and 1.09 (95% confidence interval 0.62 to 1.91) for all-cause mortality. Dose-response modeling suggested that very high FFAs might predict an increased risk for mortality (hazard ratio 1.98, 95% confidence interval 0.98 to 4.02, for 95th percentile vs first quartile). In conclusion, FFAs are closely correlated with cardiovascular risk markers, and in particular, very high FFA might identify patients with stable coronary heart disease with worse prognoses.     

Comparison of the impact of atrial fibrillation on the risk of stroke and cardiovascular death in women versus men (The Copenhagen City Heart Study)

The Copenhagen City Heart Study is a population-based cohort study. Using baseline data from 3 cohort examinations (1976 to 1978, 1981 to 1983, and 1991 to 1994), we analyzed the gender-specific effect of atrial fibrillation (AF) on the risk of stroke and cardiovascular death during 5 years of follow-up. Baseline data from 29,310 subjects were included. AF was documented in 276 subjects (110 women and 166 men). During a mean follow-up of 4.7 years, 635 strokes were identified, 35 of which occurred in subjects who had AF (22 women and 13 men). After adjustment for age and co-morbidity, the effect of AF on the risk of stroke was 4.6-fold greater in women (hazard ratio 7.8, 95% confidence interval 5.8 to 14.3) than in men (hazard ratio 1.7, 95% confidence interval 1.0 to 3.0). Cardiovascular death occurred in 1,122 subjects, 63 of whom had AF (28 in women and 35 in men). The independent effect of AF on cardiovascular mortality rate was 2.5-fold greater in women (hazard ratio 4.4, 95% confidence interval 2.9 to 6.5) than in men (hazard ratio 2.2, 95% confidence interval 1.6 to 3.1). Our results indicate that AF is a much more pronounced risk factor for stroke and cardiovascular death in women than in men.     

Atrial fibrillation and risk of clinical events in chronic heart failure with and without left ventricular systolic dysfunction: results from the Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) program.

OBJECTIVES: We assessed the risk of adverse cardiovascular (CV) outcomes associated with atrial fibrillation (AF) in the Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) program, which enrolled patients with chronic heart failure (CHF) and a broad range of ejection fractions (EFs). BACKGROUND: Atrial fibrillation is associated with an increased risk of adverse CV outcomes in patients with CHF and reduced EF. The risk of AF in patients with CHF and preserved left ventricular ejection fraction (PEF) is unknown. METHODS: A total of 7,599 patients with symptomatic CHF were randomized to candesartan or placebo. Patients were divided by baseline EF (< or =40% or >40%) in low or preserved EF groups. Major outcomes were cardiovascular death or hospitalization for worsening heart failure, and all-cause mortality. Median follow-up was 37.7 months. RESULTS: A total of 670 (17%) patients in the low EF group and 478 (19%) in the PEF group had AF at baseline. Atrial fibrillation predicted a high risk of cardiovascular morbidity and mortality regardless of baseline EF. Patients with AF and low EF had the highest absolute risk for adverse CV outcomes. However, AF was associated with greater relative increased risk of the major outcomes in patients with PEF than in patients with low EF: hazard ratio 1.72 (95% confidence interval [CI] 1.45 to 2.06) versus 1.29 (95% CI 1.14 to 1.46), respectively. The same was true for the risk of all-cause mortality. Candesartan was associated with similar treatment effects regardless of baseline rhythm. CONCLUSIONS: Atrial fibrillation is associated with an increased risk of CV outcomes in patients with CHF and either reduced EF or PEF. Candesartan improved outcomes similarly regardless of baseline rhythm.     

Causes of Death and Influencing Factors in Patients with Atrial Fibrillation

Background

Atrial fibrillation is associated with a higher mortality, but causes of death of atrial fibrillation patients and their specific predictors have been less well defined. We aimed to identify the causes of death among atrial fibrillation patients and secondly, clinical predictors for the different modes of deaths.

Methods

Patients diagnosed with atrial fibrillation in a four-hospital institution between 2000 and 2010 were identified. During a follow-up of 929 ± 1082 days (median 456, interquartile 10-1584), 1253 deaths were recorded (yearly rate 5.5%).

Results

Cardiovascular deaths accounted for 54% and noncardiovascular for 43%. The three main causes of death were heart failure (29%), infection (18%), and cancer (12%). Fatal stroke or fatal bleeding each accounted for 7% of all deaths. On multivariate analysis, the strongest predictors of death were permanent atrial fibrillation, heart failure (whether with decreased or with preserved ejection fraction), previous bleeding, and renal failure, which were independently associated with an increase in the risk of all-cause mortality (35%, 78%, 42%, and 79%, respectively), cardiovascular mortality (43%, 129%, 46%, and 93%, respectively), and noncardiovascular mortality (21%, 45%, 40%, and 50%, respectively). Oral anticoagulant use was independently associated with a lower risk of all-cause mortality (hazard ratio [HR] 0.62; 95% confidence interval [CI], 0.54-0.71; P <.0001), cardiovascular mortality (HR 0.60; 95% CI, 0.49-0.72; P <.0001), and noncardiovascular mortality (HR 0.60; 95% CI, 0.49-0.74; P <.0001).

Conclusions

The majority of deaths were related to a cardiovascular origin, and heart failure was the most common cause of death in atrial fibrillation patients. Despite the high risk of stroke associated with atrial fibrillation, only 7% died from stroke. Optimization of management of any underlying heart disease and associated comorbidities should be a relevant therapeutic target to reduce total mortality in atrial fibrillation patients.     

Clinical and echocardiographic predictors of outcomes in patients with apical hypertrophic cardiomyopathy

Apical hypertrophic cardiomyopathy (HC) is considered to have a favorable prognosis, but recent observations have suggested less benign clinical courses. We investigated the outcomes in patients with apical HC and evaluated the predictors. All 454 patients with apical HC (316 men, age 61 ± 11 years) were recruited. Major cardiovascular events (MACE) were defined as unplanned hospitalization because of heart failure, stroke, or cardiovascular mortality. The patients were divided into 2 groups: group 1 with MACE and group 2 without MACE. During the follow-up period (43 ± 20 months), the all-cause mortality rate was 9% (39 of 454), and 110 patients (25%) had MACE. The subjects in group 1 were older and a greater proportion had diabetes, hypertension, and atrial fibrillation. On the echocardiogram, the left atrial volume index (left atrial volume index 36 ± 17 vs 31 ± 12 ml/m(2)), transmitral E velocity (65 ± 17 vs 61 ± 16 cm/s), mitral annulus Ea velocity (4.5 ± 1.4 vs 5.1 ± 1.8 cm/s), Sa velocity (5.8 ± 1.4 vs 6.6 ± 1.4 cm/s), E/Ea ratio (15 ± 5 vs 13 ± 5), and right ventricular systolic pressure (31 ± 8 vs 28 ± 7 mm Hg) were significantly different between groups 1 and 2 (p <0.05 for all). The left atrial volume index (for each 1-ml/m(2) increase, hazard ratio 1.01, 95% confidence interval 1.00 to 1.03; p = 0.047), Sa velocity (hazard ratio 0.83, 95% confidence interval 0.72 to 0.96, p = 0.014), and E/Ea ratio (hazard ratio 1.04, 95% confidence interval 1.00 to 1.09, p = 0.030) were independent predictors of a poor prognosis, along with age and the presence of diabetes or hypertension. In conclusion, the clinical outcomes of patients with apical HC were less benign in older patients and in those with hypertension or diabetes. In addition, the left atrial volume index, Sa velocity, and E/Ea ratio were predicters of a poor prognosis in patients with apical HC.     

Prior History of Falls and Risk of Outcomes in Atrial Fibrillation: The Loire Valley Atrial Fibrillation Project

BackgroundPatients with nonvalvular atrial fibrillation are often denied oral anticoagulation due to falls risk. The latter is variably defined, and existing studies have not compared the associated risk of bleeding with other cardiovascular events. There are no data about outcomes in individuals with nonvalvular atrial fibrillation with a prior history of (actual) falls, rather than being “at risk of falls.” Our objective was to evaluate the risk of cardiovascular outcomes associated with prior history of falls in patients with atrial fibrillation in a contemporary “real world” cohort.MethodsPatients with nonvalvular atrial fibrillation in a 4-hospital institution between 2000 and 2010 were included. Stroke/thromboembolism event rates were calculated according to prior history of falls. Risk factors were investigated by Cox regression.ResultsAmong 7156 atrial fibrillation patients, prior history of falls/trauma was uncommon (n = 76; 1.1%). Compared with patients without history of falls, those patients were older and less likely to be on oral anticoagulation; they also had higher risk scores for stroke/thromboembolism but not for bleeding. Compared with no prior history of falls, rates of stroke/thromboembolism (P = .01) and all-cause mortality (P < .0001) were significantly higher in patients with previous falls. In multivariable analyses, prior history of falls was independently associated with stroke/thromboembolism (hazard ratio [HR] 5.19; 95% confidence interval [CI], 2.1-12.6; P < .0001), major bleeding (HR 3.32 [1.23-8.91]; P = .02), and all-cause mortality (HR 3.69; 95% CI, 1.52-8.95; P = .04), but not hemorrhagic stroke (HR 4.20; 95% CI, 0.58-30.48; P = .16) in patients on oral anticoagulation.ConclusionIn this large “real world” atrial fibrillation cohort, prior history of falls was uncommon but independently increased risk of stroke/thromboembolism, bleeding, and mortality, but not hemorrhagic stroke in the presence of anticoagulation. Prior history of (actual) falls may be a more clinically useful risk prognosticator than “being at risk of falls.”     

Association of Optimism with Cardiovascular Events and All-Cause Mortality: Systematic Review and Meta-Analysis

BackgroundThe effect of psychological health on cardiovascular disease is an underappreciated yet important area of study. Understanding the relationship between these two entities may allow for more comprehensive care of those with cardiovascular disease. The primary objective of this meta-analysis is to evaluate the relationship between optimism and risk of developing adverse events such as all-cause mortality or fatal and non-fatal cardiovascular disease in community-based populations.MethodA systematic search of electronic databases was conducted from inception through November 2021 for prospective studies evaluating optimism and adverse outcomes. Two reviewers independently selected prospective cohort studies that evaluated optimism and either all-cause mortality or cardiovascular disease and reported hazard ratios of these outcomes between optimistic and non-optimistic groups. Studies that reported odds ratio or other risk assessments were excluded. Pooled hazard ratios were calculated in random-effects meta-analyses.ResultsPooled analysis of six studies (n = 181,709) showed a pooled hazard ratio of 0.87 (95% confidence interval [CI], 0.82-0.92) for all-cause mortality among those with more optimistic mindset. Analysis of seven studies (n = 201,210) showed a pooled hazard ratio of 0.59 (95% CI, 0.37-0.93) for cardiovascular disease and pooled hazard ratio of 0.57 (95% CI, 0.07-4.56) for stroke.ConclusionsIn this pooled meta-analysis, optimism was associated with a reduced risk of all-cause mortality and of cardiovascular disease. These results suggest an important relationship between psychological health and cardiovascular disease that may serve as an area for intervention by clinicians.     

Usefulness of postexercise ankle-brachial index to predict all-cause mortality

Peripheral arterial disease predicts future cardiovascular events and all-cause mortality. Conventional methods of assessment might underestimate its true prevalence. We sought to determine whether a postexercise ankle-brachial index (ABI), not only improved peripheral arterial disease detection, but also independently predicted death. This was an observational study of consecutive patients referred for ABI measurement before and after the fixed-grade treadmill or symptom-limited exercise component to a noninvasive vascular laboratory from January 1990 to December 2000. The subjects were classified into 2 groups. Group 1 included patients with an ABI of ≥0.85 before and after exercise, and group 2 included patients with a normal ABI at rest but <0.85 after exercise. A total of 6,292 patients underwent ABI measurements with exercise during the study period. Propensity score matching of the groups was performed to minimize observational bias. Overall mortality, as determined using the United States Social Security death index, was the end point. The 10-year mortality rate of groups 1 and 2 was 32.7% and 41.2%, respectively. An abnormal postexercise ABI result independently predicted mortality (hazard ratio 1.3, 95% confidence interval 1.07 to 1.58, p = 0.008). Additional independent predictors of mortality were age, male gender, diabetes, and hypertension. After the exclusion of patients with a history of cardiovascular events, the predictive value of an abnormal postexercise ABI remained statistically significant (hazard ratio 1.67, 95% confidence interval 1.29 to 2.17, p <0.0001). In conclusion, our results have shown that the postexercise ABI is a powerful independent predictor of all-cause mortality and provides additional risk stratification beyond the ABI at rest.     

Intravenous Iron Exposure and Mortality in Patients on Hemodialysis

Background and objectives

Clinical trials assessing effects of larger cumulative iron exposure with outcomes are lacking, and observational studies have been limited by assessment of short-term exposure only and/or failure to assess cause-specific mortality. The associations between short- and long-term iron exposure on all-cause and cause-specific mortality were examined.

Design, setting, participants, & measurements

The study included 14,078 United States patients on dialysis initiating dialysis between 2003 and 2008. Intravenous iron dose accumulations over 1-, 3-, and 6-month rolling windows were related to all-cause, cardiovascular, and infection-related mortality in Cox proportional hazards models that used marginal structural modeling to control for time-dependent confounding.

Results

Patients in the 1-month model cohort (n=14,078) were followed a median of 19 months, during which there were 27.6% all-cause deaths, 13.5% cardiovascular deaths, and 3% infection-related deaths. A reduced risk of all-cause mortality with receipt of >150–350 (hazard ratio, 0.78; 95% confidence interval, 0.64 to 0.95) or >350 mg (hazard ratio, 0.79; 95% confidence interval, 0.62 to 0.99) intravenous iron compared with >0–150 mg over 1 month was observed. There was no relation of 1-month intravenous iron dose with cardiovascular or infection-related mortality and no relation of 3- or 6-month cumulative intravenous iron dose with all-cause or cardiovascular mortality. There was a nonstatistically significant increase in infection-related mortality with receipt of >1050 mg intravenous iron in 3 months (hazard ratio, 1.69; 95% confidence interval, 0.87 to 3.28) and >2100 mg in 6 months (hazard ratio, 1.59; 95% confidence interval, 0.73 to 3.46).

Conclusions

Among patients on incident dialysis, receipt of ≤1050 mg intravenous iron in 3 months or 2100 mg in 6 months was not associated with all-cause, cardiovascular, or infection-related mortality. However, nonstatistically significant findings suggested the possibility of infection-related mortality with receipt of >1050 mg in 3 months or >2100 mg in 6 months. Randomized clinical trials are needed to assess the safety of exposure to greater cumulative intravenous iron doses.     

Relations between QRS|T angle, cardiac risk factors, and mortality in the third National Health and Nutrition Examination Survey (NHANES III)

On the surface electrocardiogram, an abnormally wide QRS|T angle reflects changes in the regional action potential duration profiles and in the direction of the repolarization sequence, which is thought to increase the risk of ventricular arrhythmia. We investigated the relation between an abnormal QRS|T angle and mortality in a nationally representative sample of subjects without clinically evident heart disease. We studied 7,052 participants ≥40 years old in the third National Health and Nutrition Examination Survey with 12-lead electrocardiograms. Those with self-reported or electrocardiographic evidence of a previous myocardial infarction, QRS duration of ≥120 ms, or history of heart failure were excluded. Borderline and abnormal spatial QRS|T angles were defined according to gender-specific 75th and 95th percentiles of frequency distributions. All-cause (1,093 women and 1,191 men) and cardiovascular (462 women and 455 men) mortality during the 14-year period was assessed through linkage with the National Death Index. On multivariate analyses, an abnormal spatial QRS|T angle was associated with an increased hazard ratio (HR) for cardiovascular mortality in women (HR 1.82, 95% confidence interval 1.05 to 3.14) and men (HR 2.21, 95% confidence interval 1.32 to 3.68). Also, the multivariate adjusted HR for all-cause mortality associated with an abnormal QRS|T angle was 1.30 (95% confidence interval 0.95 to 1.78) for women and 1.87 (95% confidence interval 1.29 to 2.7) for men. A borderline QRS|T angle was not associated with an increased risk of all-cause or cardiovascular mortality. In conclusion, an abnormal QRS|T angle, as measured on a 12-lead electrocardiogram, was associated with an increased risk of cardiovascular and all-cause mortality in this population-based sample without known heart disease.     

Clinical Outcomes in Asymptomatic and Symptomatic Atrial Fibrillation Presentations in GARFIELD-AF: Implications for AF Screening

BackgroundAsymptomatic atrial fibrillation is often detected incidentally. Prognosis and optimal therapy for asymptomatic compared with symptomatic atrial fibrillation is uncertain. This study compares clinical characteristics, treatment, and 2-year outcomes of asymptomatic and symptomatic atrial fibrillation presentations.MethodsGlobal Anticoagulant Registry in the Field-Atrial Fibrillation (GARFIELD-AF) is a global, prospective, observational study of newly diagnosed atrial fibrillation with ≥1 stroke risk factors (http://www.clinicaltrials.gov, unique identifier: NCT01090362). Patients were characterized by atrial fibrillation-related symptoms at presentation and the CHA₂DS₂-VASc score. Two-year follow-up recorded anticoagulation patterns (vitamin K antagonist, direct oral anticoagulants, parenteral therapy) and outcomes (stroke/systemic embolism, all-cause mortality, and bleeding).ResultsAt presentation, of 52,032 eligible patients, 25.4% were asymptomatic and 74.6% symptomatic. Asymptomatic patients were slightly older (72 vs 70 years), more often male (64.2% vs 52.9%), and more frequently initiated on anticoagulation ± antiplatelets (69.4% vs 66.0%). No difference in events (adjusted hazard ratios, 95% confidence interval) for nonhemorrhagic stroke/systemic embolism (1.19, 0.97-1.45), all-cause mortality (1.06, 0.94-1.20), or bleeding (1.02, 0.87-1.19) was observed. Anticoagulation was associated with comparable reduction in nonhemorrhagic stroke/systemic embolism (0.59, 0.43–0.82 vs 0.78, 0.65–0.93) and all-cause mortality (0.69, 0.59-0.81 vs 0.77, 0.71-0.85) in asymptomatic versus symptomatic, respectively.ConclusionsMajor outcomes do not differ between asymptomatic and symptomatic atrial fibrillation presentations and are comparably reduced by anticoagulation. Opportunistic screening-detected asymptomatic atrial fibrillation likely has the same prognosis as asymptomatic atrial fibrillation at presentation and likely responds similarly to anticoagulation thromboprophylaxis.