Extracranial Systemic Embolic Events in Patients With Nonvalvular Atrial Fibrillation: Incidence, Risk Factors, and Outcomes.

BACKGROUND: Nonvalvular atrial fibrillation is a major cause of thromboembolic events. In comparison with atrial fibrillation-related stroke, extracranial systemic embolic events (SEEs) remain poorly defined. METHODS AND RESULTS: All suspected SEEs reported among 37 973 participants of 4 large contemporary randomized clinical trials of anticoagulation in atrial fibrillation were independently readjudicated for clinical and objective evidence of sudden loss of perfusion of a limb or organ. Over 91 746 patient-years of follow-up, 221 SEEs occurred in 219 subjects. The SEE incidence was 0.24 of 100 and stroke incidence was 1.92 of 100 patient-years. In comparison with patients with stroke, those with SEE were more often female (56% versus 47%; P=0.01) and had comparable mean age (73.1±8.5 versus 73.5±8.8 years; P=0.57) and mean CHADS2 scores (2.4±1.3 versus 2.5±1.2; P=0.33). SEEs more frequently involved the lower extremity (58%) than visceral-mesenteric (31%) or upper extremity (10%). SEE-related care involved clinic assessment alone in 5%, 30% were hospitalized without procedures, 60% underwent endovascular or surgical intervention, and 5% underwent amputation. Within 30 days, 54% of patients recovered fully, 20% survived with deficits, and 25% died. Thirty-day mortality was greater after visceral-mesenteric than lower- or upper-extremity SEE (55%, 17%, and 9%, respectively, P≤0.0001). The relative risk of death throughout follow-up was 4.33 (95% confidence interval, 3.29-5.70) after SEE versus 6.79 (95% confidence interval, 6.22-7.41) after stroke in comparison with patients without either event. CONCLUSIONS: SEE constituted 11.5% of clinically recognized thromboembolic events in patients with atrial fibrillation and was associated with high morbidity and mortality. SEE mortality was comparable to that of ischemic stroke and varied by anatomic site.

Carotid Atherosclerosis and Stroke in Atrial Fibrillation: The Atherosclerosis Risk in Communities Study.

BACKGROUND AND PURPOSE: Whether consideration of carotid intima-media thickness (cIMT) and carotid plaque would improve risk prediction of ischemic stroke in persons with atrial fibrillation (AF) is unknown. The purpose of this study was to assess the improvement in risk prediction of stroke by adding cIMT and carotid plaque to the CHA2DS2-VASc (variables age, heart failure, hypertension, diabetes mellitus, myocardial infarction, and peripheral arterial disease) score. METHODS: We included participants from the Atherosclerosis Risk in Communities (ARIC) study (mean age, 63 years) who developed AF within 5 years after carotid measurement, were not on warfarin, and had no prior stroke at AF diagnosis. AF was ascertained from study ECGs and diagnosis codes, and stroke was physician adjudicated. Multivariable Cox models were used to assess association between carotid indices and ischemic stroke. Improvement in 10-year risk prediction of stroke was assessed by the C-statistic, net reclassification improvement, and relative integrated discrimination improvement. RESULTS: There were 81 (11.2%) stroke events that occurred among 724 participants with AF during a mean follow-up of 8.5 years. Increased cIMT and presence of carotid plaque were significantly associated with increased stroke risk. The addition of cIMT+plaque to the CHA2DS2-VASc score marginally increased the C-statistic (95% confidence interval) from 0.685 (0.623-0.747) to 0.698 (0.638-0.759). The net reclassification improvement and integrated discrimination improvement for cIMT+plaque were 0.091 (95% confidence interval, 0.012-0.170) and 0.101 (95% confidence interval, 0.002-0.226), respectively. CONCLUSIONS: Increased cIMT and presence of carotid plaque are associated with increased risk of ischemic stroke in individuals with AF. Furthermore, they may improve risk prediction of stroke, over and above the CHA2DS2-VASc score.

Development of administrative data algorithms to identify patients with critical limb ischemia.

Administrative data have been used to identify patients with various diseases, yet no prior study has determined the utility of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)-based codes to identify CLI patients. CLI cases (n=126), adjudicated by a vascular specialist, were carefully defined and enrolled in a hospital registry. Controls were frequency matched to cases on age, sex and admission date in a 2:1 ratio. ICD-9-CM codes for all patients were extracted. Algorithms were developed using frequency distributions of these codes, risk factors and procedures prevalent in CLI. The sensitivity for each algorithm was calculated and applied within the hospital system to identify CLI patients not included in the registry. Sensitivity ranged from 0.29 to 0.92. An algorithm based on diagnosis and procedure codes exhibited the best overall performance (sensitivity of 0.92). Each algorithm had differing CLI identification characteristics based on patient location. Administrative data can be used to identify CLI patients within a health system. The algorithms, developed from these data, can serve as a tool to facilitate clinical care, research, quality improvement, and population surveillance.

Cardiovascular risk factor screening satisfaction in the Heart of New Ulm Project.

OBJECTIVE: Community-based cardiovascular disease (CVD) risk factor screening programs have been used successfully in rural health improvement initiatives. However, little is known about what consumers like or dislike about them, which is a barrier to the design of future process improvements. The objective of this study was to examine the degree to which health risks and participant characteristics predicted screening satisfaction. DESIGN: This study utilized a cross-sectional survey design. SETTING: Data was collected as part of the broader Heart of New Ulm Project, which is a community-based CVD prevention demonstration project based in rural Minnesota. PARTICIPANTS: There were 126 randomly invited individuals from the CVD risk factor screenings, with 118 individuals who agreed to participate and had complete data available for analyses. METHODS: A multivariate logistic regression analysis was used to examine the association between demographics, lifestyle, and biometric risk factors and screening satisfaction. RESULTS: Twenty percent of respondents indicated some level of dissatisfaction with the screening process. Satisfied participants were more likely to be female (OR=4.15), not have an optimal lifestyle (OR=3.47), and have an intention to improve their lifestyle habits (OR=3.26). Age, education, and CVD risk level were not significant predictors in the final model. CONCLUSION: Satisfaction was high in this screening program, with healthy males being least satisfied with their experience. This has implications for the design of future intervention efforts, as they may require specific programmatic features and more specialized, targeted marketing strategies to attract a broad spectrum of participants likely to benefit.

Association of Atrial Fibrillation With Incidence of Extracranial Systemic Embolic Events: The ARIC Study.

Background Atrial fibrillation (AF) increases the risk of stroke and extracranial systemic embolic events (SEEs), but little is known about the magnitude of the association of AF with SEE. Methods and Results This analysis included 14 941 participants of the ARIC (Atherosclerosis Risk in Communities) study (mean age, 54.2±5.8, 55% women, 74% White) without AF at baseline (1987-1989) followed through 2017. AF was identified from study ECGs, hospital discharges, and death certificates, while SEEs were ascertained from hospital discharges. CHA2DS2-VASc was calculated at the time of AF diagnosis. Cox regression was used to estimate associations of incident AF with SEE risk in the entire cohort, and between CHA2DS2-VASc score and SEE risk in those with AF. Among eligible participants, 3114 participants developed AF and 270 had an SEE (59 events in AF). Incident AF was associated with increased risk of SEE (hazard ratio [HR], 3.58; 95% CI, 2.57-5.00), after adjusting for covariates. The association of incident AF with SEE was stronger in women (HR, 5.26; 95% CI, 3.28-8.44) than in men (HR, 2.68; 95% CI, 1.66-4.32). In those with AF, higher CHA2DS2-VASc score was associated with increased SEE risk (HR per 1-point increase, 1.24; 95% CI, 1.05-1.47). Conclusions AF is associated with more than a tripling of the risk of SEE, with a stronger association in women than in men. CHA2DS2-VASc is associated with SEE risk in AF patients, highlighting the value of the score to predict adverse outcomes and guide treatment decisions in people with AF.

Association of Peripheral Artery Disease With Incident Atrial Fibrillation: The ARIC (Atherosclerosis Risk in Communities) Study.

BACKGROUND: Although peripheral artery disease as defined by ankle-brachial index (ABI) is associated with incident atrial fibrillation (AF), questions remain about the risk of AF in borderline ABI (>0.90 to <1.0) or noncompressible arteries (>1.4). We evaluated the association of borderline ABI and ABI >1.4 in the ARIC (Atherosclerosis Risk in Communities) study, a population-based prospective cohort study. METHODS AND RESULTS: We included 14 794 participants (age, 54.2±5.8 years, 55% women, 26% blacks) with ABI measured at the baseline (1987-1989) and without AF. AF was identified from hospital records, death certificates, and ECGs. Using Cox proportional hazards, we evaluated the association between ABI and AF. During a median follow-up of 23.3 years, there were 2288 AF cases. After adjustment for cardiovascular risk factors, hazard ratio (HR) (95% confidence interval) for AF among individuals with ABI <1.0 compared with ABI 1.0 to 1.4, was 1.13 (1.01-1.27). ABI >1.4 was not associated with increased AF risk. ABI ≤0.9 and borderline ABI were associated with a higher risk of AF compared with ABI 1.0 to 1.4. Demographics-adjusted HRs (95% confidence interval) were 1.43 (1.17-1.75) and 1.32 (1.16-1.50), respectively. However, the associations of ABI ≤0.9 and borderline ABI with AF were attenuated after adjusting for cardiovascular risk factors (HR [95% confidence interval], 1.10 [0.90-1.34] and 1.14 [1.00-1.30]), respectively. CONCLUSIONS: Peripheral artery disease indicated by low ABI, including borderline ABI, is a weak risk factor for AF. ABI >1.4 is not associated with an increased AF risk. The relationship between peripheral artery disease and AF appears to be mostly explained by traditional atherosclerotic risk factors.

Early Access to the Cardiac Catheterization Laboratory for Patients Resuscitated From Cardiac Arrest Due to a Shockable Rhythm: The Minnesota Resuscitation Consortium Twin Cities Unified Protocol.

BACKGROUND: In 2013 the Minnesota Resuscitation Consortium developed an organized approach for the management of patients resuscitated from shockable rhythms to gain early access to the cardiac catheterization laboratory (CCL) in the metro area of Minneapolis-St. Paul. METHODS AND RESULTS: Eleven hospitals with 24/7 percutaneous coronary intervention capabilities agreed to provide early (within 6 hours of arrival at the Emergency Department) access to the CCL with the intention to perform coronary revascularization for outpatients who were successfully resuscitated from ventricular fibrillation/ventricular tachycardia arrest. Other inclusion criteria were age >18 and <76 and presumed cardiac etiology. Patients with other rhythms, known do not resuscitate/do not intubate, noncardiac etiology, significant bleeding, and terminal disease were excluded. The primary outcome was survival to hospital discharge with favorable neurological outcome. Patients (315 out of 331) who were resuscitated from VT/VF and transferred alive to the Emergency Department had complete medical records. Of those, 231 (73.3%) were taken to the CCL per the Minnesota Resuscitation Consortium protocol while 84 (26.6%) were not taken to the CCL (protocol deviations). Overall, 197 (63%) patients survived to hospital discharge with good neurological outcome (cerebral performance category of 1 or 2). Of the patients who followed the Minnesota Resuscitation Consortium protocol, 121 (52%) underwent percutaneous coronary intervention, and 15 (7%) underwent coronary artery bypass graft. In this group, 151 (65%) survived with good neurological outcome, whereas in the group that did not follow the Minnesota Resuscitation Consortium protocol, 46 (55%) survived with good neurological outcome (adjusted odds ratio: 1.99; [1.07-3.72], P=0.03). CONCLUSIONS: Early access to the CCL after cardiac arrest due to a shockable rhythm in a selected group of patients is feasible in a large metropolitan area in the United States and is associated with a 65% survival rate to hospital discharge with a good neurological outcome.

Association of White Blood Cell Count and Differential with the Incidence of Atrial Fibrillation: The Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Although inflammation is involved in the development of atrial fibrillation (AF), the association of white blood cell (WBC) count and differential with AF has not been thoroughly examined in large cohorts with extended follow-up. METHODS: We studied 14,500 men and women (25% blacks, 55% women, mean age 54) free of AF at baseline (1987-89) from the Atherosclerosis Risk in Communities (ARIC) study, a community-based cohort in the United States. Incident AF cases through 2010 were identified from study electrocardiograms, hospital discharge records and death certificates. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for AF associated with WBC count and differential. RESULTS: Over a median follow-up time of 21.5 years for the entire cohort, 1928 participants had incident AF. Higher total WBC count was associated with higher AF risk independent of AF risk factors and potential confounders (HR 1.09, 95% CI 1.04-1.15 per 1-standard deviation [SD] increase). Higher neutrophil and monocyte counts were positively associated with AF risk, while an inverse association was identified between lymphocyte count and AF (multivariable adjusted HRs 1.16, 95% CI 1.09-1.23; 1.05, 95% CI 1.00-1.11; 0.91, 95% CI 0.86-0.97 per 1-SD, respectively). No significant association was identified between eosinophils or basophils and AF. CONCLUSIONS: High total WBC, neutrophil, and monocyte counts were each associated with higher AF risk while lymphocyte count was inversely associated with AF risk. Systemic inflammation may underlie this association and requires further investigation for strategies to prevent AF.

Echocardiographic measures of cardiac structure and function are associated with risk of atrial fibrillation in blacks: the Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND: Several studies have examined the link between atrial fibrillation (AF) and various echocardiographic measures of cardiac structure and function in whites and other racial groups but not in blacks. Exploring AF risk factors in blacks is important given that the lower incidence of AF in this racial group despite higher risk factors, is not completely explained. METHODS: We examined the association of echocardiographic measures with AF incidence in 2283 blacks (64.5% women, mean age 58.8 years) free of diagnosed AF and enrolled in the Jackson cohort of Atherosclerosis Risk in Communities (ARIC) study, a prospective study of cardiovascular disease. Echocardiography was performed in 1993-1995, and incident AF was determined by electrocardiograms at a follow-up study exam, hospitalization discharge codes and death certificates through the end of 2009. Cox proportional hazards regression was used to estimate hazard ratios and 95% confidence intervals for AF associated with the echocardiographic measures, adjusting for age, sex, and known AF risk factors. RESULTS: During an average follow-up of 13.5 years, 191 (8.4%) individuals developed AF. Left ventricular (LV) internal diameter 2-D (diastole) and percent fractional shortening of LV diameter displayed a U-shaped relationship with risk of AF, while left atrial diameter displayed a J-shaped nonlinear association. LV mass index was associated positively with AF. E/A ratio <0.7 or >1.5 and ejection fraction (EF <50%) were also associated with higher AF risk. These measures improved risk stratification for AF in addition to traditional risk factors, although not significantly {C-statistic of 0.767 (0.714-0.819) vs. 0.744 (0.691-0.797)}. CONCLUSIONS: In a community-based population of blacks, echocardiographic measures of cardiac structure and function are significantly associated with an increased risk of AF.

White blood cell count, C-reactive protein, and incident heart failure in the Atherosclerosis Risk in Communities (ARIC) Study.

PURPOSE: To test the hypothesis that inflammation measured by white blood cell count (WBC) and C-reactive protein (CRP) is associated positively with incident heart failure (HF). METHODS: Using the Atherosclerosis Risk in Communities (ARIC) Study, we conducted separate Cox proportional hazards regression analyses for WBC (measured 1987-1989) and CRP (measured 1996-1998) in relation to subsequent heart failure occurrence. A total of 14,485 and 9,978 individuals were included in the WBC and CRP analyses, respectively. RESULTS: There were 1647 participants that developed HF during follow-up after WBC assessment and 613 developed HF after CRP assessment. After adjustment for demographic variables and traditional HF risk factors, the hazard ratio (95% confidence interval) for incident HF across quintiles of WBC was 1.0, 1.10 (0.9-1.34), 1.27 (1.05-1.53), 1.44 (1.19-1.74), and 1.62 (1.34-1.96), p trend < .001; hazard ratio across quintiles of CRP was 1.0, 1.03 (0.68-1.55), 0.99 (0.66-1.51), 1.40 (0.94-2.09), and 1.70 (1.14-2.53), p trend .002. Granulocytes appeared to drive the relation between WBCs and heart failure (hazard ratios across quintiles: 1.0, 0.93 [0.76-1.15], 1.26 [1.04-1.53], 1.67 [1.39-2.01], and 2.19 [1.83-2.61], p trend < .0001), whereas lymphocytes or monocytes were not related. CONCLUSIONS: Greater levels of WBC (especially granulocytes) and CRP are associated with increased risk of heart failure in middle-aged adults, independent of traditional risk factors.