Use of Sodium-Glucose Cotransporter-2 Inhibitors and Angiotensin Receptor-Neprilysin Inhibitors in Patients With Atrial Fibrillation and Heart Failure From 2021 to 2022: An Analysis of Real-World Data.

BACKGROUND: Contemporary use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and angiotensin receptor-neprilysin inhibitors (ARNi) in patients with atrial fibrillation (AF) and heart failure (HF) has not been described. METHODS AND RESULTS: We analyzed the MarketScan databases for the period January 1, 2021 to July 30, 2022. Validated algorithms were used to identify patients with AF and HF, and to classify patients into HF with reduced ejection fraction (HFrEF) or HF with preserved ejection fraction (HFpEF). We assessed the prevalence of SGLT2i and ARNi use overall and by HF type. Additionally, we explored correlates of lower use, including demographics and comorbidities. The study population included 60 927 patients (mean age, 75 years; 43% women) diagnosed with AF and HF (85% with HFpEF, 15% with HFrEF). Prevalence of ARNi use was 11% overall (30% in HFrEF, 8% in HFpEF), whereas the corresponding figure was 6% for SGLT2i (13% in HFrEF, 5% in HFpEF). Use of both medications increased over the study period: ARNi from 9% to 12% (22%-29% in HFrEF, 6%-8% in HFpEF), and SGLT2i from 3% to 9% (6%-16% in HFrEF, 2%-7% in HFpEF). Female sex, older age, and specific comorbidities were associated with lower use of these 2 medication types overall and by HF type. CONCLUSIONS: Use of ARNi and SGLT2i in patients with AF and HF is suboptimal, particularly among women and older individuals, though use is increasing. These results underscore the need for understanding reasons for these disparities and developing interventions to improve adoption of evidence-based therapies among patients with comorbid AF and HF.

Associations of Alcohol Consumption With Left Atrial Morphology and Function in a Population at High Cardiovascular Risk.

BACKGROUND: Excessive alcohol consumption has been associated with increased risk of atrial fibrillation, although the underlying mechanisms remain unclear. An enlarged left atrium and impaired left atrial function may lead to atrial fibrillation. The association of alcohol consumption with structural and functional left atrial measures, however, has received limited attention. METHODS AND RESULTS: We studied 503 participants from the PREDIMED-Plus (Prevención con Dieta Mediterránea) trial, a randomized trial testing intensive weight loss intervention with an energy-reduced Mediterranean diet and physical activity promotion in preventing cardiovascular disease in adults with metabolic syndrome. Participants underwent transthoracic echocardiography at baseline, year 3, and year 5 of the study. Outcomes of interest included volume index and reservoir, conduit, and contractile strains of the left atrium. Alcohol consumption was calculated through food frequency questionnaires and presented as drinks consumed per day. Multiple linear regression and mixed models estimated the association of alcohol consumption with left atrial measurements at baseline and through follow-up. Cross-sectionally, higher alcohol consumption (per 1 drink/day increases) was associated with larger left atrial volume (0.65 mL/m2 [95% CI, 0.18-1.11]) and lower left atrial reservoir and contractile strain (-0.44% [95% CI, -0.87 to -0.01]; and -0.44% [95% CI, -0.75 to -0.14]). Baseline alcohol consumption was not associated with changes in left atrial measurements, but increases in alcohol consumption (per 1 drink/day increase) during follow-up were associated with left atrial enlargement (0.71 mL/m2 [95% CI, 0.17-1.26]). CONCLUSIONS: In a population at high cardiovascular risk, increased alcohol consumption was associated with left atrial enlargement and worsening atrial function. REGISTRATION: URL: http://www.controlled-trials.com; Unique identifier: ISRCTN89898870.

Factors Associated With Fatigue in Persons With Atrial Fibrillation in the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia affecting over 6 million people in the U.S. Fatigue is a frequent symptom of AF, yet no underlying biological mechanisms have been identified in AF-related fatigue as in other chronic conditions such as cancer or HIV fatigue (inflammation, tissue injury). We aimed to identify biomarkers and correlates of AF-fatigue in ARIC participants. METHODS: Participants with AF from ARIC visit 5 (2011-2013) were included in the study. Multiple linear regression was used to estimate the association of high sensitivity troponin (hs-TnT), N-terminal fragment B-type natriuretic peptide (NT-proBNP) and high sensitivity C-reactive protein (hsCRP) levels with self-reported fatigue (SF-12 and PROMIS Fatigue Scale), depressive symptoms (Center for Epidemiological Studies Depression survey), and physical functioning (Short Physical Performance Battery) scores. All biomarkers underwent natural-log transformation. RESULTS: There were 446 participants (mean age: 78 y ± 5; 44% women). In adjusted analyses, NT-proBNP was associated with AF-fatigue (ß: 0.11, 95% CI: 0.03, 0.19), increased depressive symptoms (ß: 0.44, 95% CI: 0.19, 0.70), and decreased physical function (ß: -0.48, 95% CI: -0.72, -0.23). Hs-TnT was also associated with elevated AF-fatigue (ß: 0.24, 95% CI: 0.09, 0.39) along with decreased physical function (ß: -1.19, 95% CI: -1.64, -0.75). No significant associations were found with hsCRP and fatigue. CONCLUSION: Increased levels of cardiac injury biomarkers, depressive symptoms, and decreased physical function were associated with AF-fatigue. Inflammation was not associated with AF-fatigue; other physiological pathways, such as cardiac overload or myocardial injury may be more relevant in AF-fatigue.

Association of alcohol consumption with circulating biomarkers of atrial fibrillation-related pathways in a population at high cardiometabolic risk.

Background: The effect of alcohol consumption on cardiovascular health, including atrial fibrillation risk, remains controversial. Evaluating the association of alcohol consumption with circulating atrial fibrillation-related biomarkers may help better understand the relevant mechanistic underpinnings. Methods: We studied 523 participants from 3 sites for the PREDIMED-Plus study, a weight-loss randomized intervention trial in metabolically unhealthy adults. N-terminal pro-B-type natriuretic protein (NTproBNP), high sensitivity troponin-T (hsTnT), high-sensitivity C-reactive protein (hsCRP), 3-nitrotyrosine (3-NT), and procollagen type 1 carboxy-terminal propeptide (PICP) were measured in fasting serum samples at baseline and years 3 and 5 of follow-up. We calculated alcohol consumption in drinks/day (1 drink = 14 grams alcohol) with validated food frequency questionnaires at each visit. Using multiple linear regression and mixed models we estimated the association of alcohol consumption with log-transformed biomarkers at baseline and longitudinally adjusting for potential confounders. Results: Among 523 participants (mean age: 65 years, 40% female), mean alcohol consumption was 1 drink/day. Cross-sectionally, alcohol consumption was not associated with cardiac biomarker concentrations. Longitudinally, compared to non-consumers, heavy drinkers (≥4 drinks/day) had smaller increases in hsTnT (ß: -0.11, 95%CI: -0.20, -0.01)and PICP (ß: -0.15, 95%CI: -0.30, 0.01) over the 5-year follow-up. In contrast, those who increased alcohol consumption over the 5-year period experienced greater increases in hsCRP (ß: 0.42, 95%CI: 0.11, 0.73) compared to those whose drinking behavior stayed the same. Conclusion: Alcohol consumption was associated with complex changes in circulating biomarkers, including comparatively lower fibrotic and myocardial damage, but higher levels of overall inflammation over time. These results underscore the need for further research to better understand the effects of alcohol on cardiovascular health.

Use of SGLT2i and ARNi in patients with atrial fibrillation and heart failure in 2021-2022: an analysis of real-world data.

Objective: To evaluate utilization of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and angiotensin receptor neprilysin inhibitors (ARNi) in patients with atrial fibrillation (AF) and heart failure (HF). Methods: We analyzed the MarketScan databases for the period 1/1/2021 to 6/30/2022. Validated algorithms were used to identify patients with AF and HF, and to classify patients into HF with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF). We assessed the prevalence of SGLT2i and ARNi use overall and by HF type. Additionally, we explored correlates of lower utilization, including demographics and comorbidities. Results: The study population included 60,927 patients (mean age 75, 43% female) diagnosed with AF and HF (85% with HFpEF, 15% with HFrEF). Prevalence of ARNi use was 11% overall (30% in HFrEF, 8% in HFpEF), while the corresponding figure was 6% for SGLT2i (13% in HFrEF, 5% in HFpEF). Use of both medications increased over the study period: ARNi from 9% to 12% (from 22% to 29% in HFrEF, from 6% to 8% in HFpEF), and SGLT2i from 3% to 9% (from 6% to 16% in HFrEF, from 2% to 7% in HFpEF). Female sex, older age, and specific comorbidities were associated with lower utilization of these two medication types overall and by HF type. Conclusion: Use of ARNi and SGLT2i in patients with AF and HF is suboptimal, particularly among females and older individuals, though utilization is increasing. These results underscore the need for understanding reasons for these disparities and developing interventions to improve adoption of evidence-based therapies among patients with comorbid AF and HF.

Association of socioeconomic status with arterial stiffness in older African American and White adults: The ARIC study cohort.

Objective: To examine the cross-sectional associations of individual measures of SES-educational attainment and household income-and the joint effects of SES with PWV, as well as the SES-race interaction, in a cohort of older African American and White adults. Methods: Data from the Atherosclerosis Risk in Communities (ARIC) Study were used to evaluate the cross-sectional associations of individual and joint SES [education and income] and carotid femoral pulse wave velocity (cfPWV), a subclinical marker of arterial stiffness, and the interaction of SES and race using adjusted multivariable linear regression models in a cohort of 3342 men and women aged 67-89 years free of CVD in 2011-2013. Results: Participants were 64% female, 23% African American, mean cfPWV (12.3±3.5-African American and 11.6±3.9-White participants). Post-graduate education compared to less than high school was significantly associated with lower cfPWV (less stiffness) in African American (ß = -1.28 m/s; 95% CI, -1.97, -0.59) but not in White (ß = -0.69 m/s; 95% CI, -1.39, 0.01) participants. Income ≥$50K as compared to <$25K, was associated with lower cfPWV both in African American (ß = -0.82 m/s; 95% CI, -1.42, -0.22) and White (ß = -0.76 m/s; 95% CI, -1.19, -0.32) participants. The interaction of race and individual measures of SES on cfPWV in African American and White adults were not statistically significant (p-value >0.10). Conclusions: Higher SES was cross-sectionally associated with lower arterial stiffness in this cohort; the data did not support differences by race. Prospective studies of SES and cfPWV are needed to efficiently compare larger racially and regionally diverse populations with a wider range of socioeconomic profiles to better identify subgroup CVD risk.

Associations of Atrial Fibrillation with Mild Cognitive Impairment and Dementia: An Investigation Using SPRINT Research Materials.

BACKGROUND: Atrial fibrillation (AF) is linked to increased risk of dementia and cognitive decline, but whether AF and its ascertainment methods affect cognition in patients with hypertension has received less attention. METHODS: We studied 8469 participants with elevated systolic blood pressure who were free of stroke and diabetes at baseline enrolled in the Systolic Blood Pressure Intervention Trial. AF was ascertained using three approaches: self-report of AF, AF from a safety event, and study electrocardiogram-determined (ECG) AF. Mild cognitive impairment (MCI) and probable dementia (PD) were ascertained from in-person assessments or telephone interviews from the participant or an informant. We used Cox proportional hazard models to estimate hazard ratios for the association of AF (all three sources) with outcomes of MCI, PD, and a composite MCI/PD outcome. RESULTS: During a mean follow-up of 4.6 years, 974 (12%) participants had AF (prevalent or incident), 634 were diagnosed with MCI, and 316 with PD. When comparing those with AF (from any source) to those without, no differences were detected in the risk of MCI or PD. Comparison between AF sources found ECG-AF to be associated with an elevated risk of MCI/PD (hazard ratio (HR) 1.59, 95% confidence interval (95%CI) 1.06, 2.38). Neither AF ascertained through safety events nor self-reported AF were associated with MCI or PD. CONCLUSION: The association of AF with incidence of MCI/PD differed by method of AF ascertainment. Case definition of AF and quantification of AF burden are important factors in studies evaluating the link between AF and cognitive dysfunction.

Association of physical activity with the incidence of atrial fibrillation in persons > 65 years old: the Atherosclerosis Risk in Communities (ARIC) study.

AIMS: To evaluate the association of physical activity (PA) with atrial fibrillation (AF) incidence in an elderly population. METHODS: We studied 5166 participants of the Atherosclerosis Risk in Communities cohort examined in 2011-2013 free of AF. Self-reported PA was evaluated with a validated questionnaire. Weekly minutes of leisure-time moderate to vigorous physical activity (MVPA) were calculated and categorized using the 2018 Physical Activity Guidelines for Americans (no activity [0 min/week], low [> 0- < 150 min/week], adequate [150- < 300 min/week], high [≥ 300 min/week]). Incident AF through 2019 was ascertained from hospital discharges and death certificates. Cox models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for AF by levels of physical activity adjusting for potential confounders. RESULTS: The mean (SD) age for the sample was 75 (5) years (59% female, 22% Black). During a mean (SD) follow-up time of 6.3 (2.0) years, 703 AF events were identified. The association of MVPA with AF incidence showed a U-shaped relationship. Compared to those not engaging in MVPA, individuals with low MVPA had a 23% lower hazard of AF (HR = 0.77; 95% CI 0.61, 0.96), while those with adequate MVPA had a 14% lower hazard (HR 0.86; 95% CI 0.69, 1.06). High levels of MVPA were not associated with AF risk (HR 0.97; 95% CI 0.78, 1.20). CONCLUSION: This study suggests that being involved in low to moderate levels of MVPA is associated with lower AF risk, with no evidence of increased risk of AF in those with higher levels of MVPA.

Risk Factors for Dementia in Patients With Atrial Fibrillation.

Although dementia and atrial fibrillation (AF) are common in older adults, risk factors for dementia have not been sufficiently characterized in patients with AF. We studied 621,773 patients with AF without dementia at the time of AF diagnosis who were enrolled in the MarketScan Commercial and Medicare Supplemental databases from 2007 to 2015. Dementia incidence and presence of predictors at the time of AF diagnosis (cardiometabolic conditions, mental and neurologic disorders, and other chronic conditions) were based on International Classification of Diseases, Ninth Revision, Clinical Modification codes in outpatient and inpatient claims, whereas medication usage was based on outpatient pharmacy claims. A frailty score was calculated using a previously established algorithm. The associations between the predictors of interest and dementia were assessed with multivariable Cox models. Patients had a mean age of 68 years (SD 14 years) and 41% were women. During a mean follow-up of 2.0 years, there were 16,073 cases of dementia. The strongest predictors of dementia were frailty (hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.40 to 1.45, per 1-SD increase in the score), cognitive impairment (HR 1.50, 95% CI 1.36 to 1.65), mood disorders (HR 1.49, 95% CI 1.32 to 1.70), schizophrenia (HR 1.86, 95% CI 1.75 to 1.98), and substance abuse (HR 1.58, 95% CI 1.39 to 1.80). Among cardiometabolic conditions, only stroke (HR 1.17, 95% CI 1.13 to 1.22) and diabetes mellitus (HR 1.14, 95% CI 1.11 to 1.18) were associated with small increases in dementia risk after adjusting for demographics, frailty, co-morbidities, and medications. We have identified several risk factors for dementia in patients with AF.

Epidemiology of atrial fibrillation in the All of Us Research Program.

BACKGROUND: The prevalence, incidence and risk factors of atrial fibrillation (AF) in a large, geographically and ethnically diverse cohort in the United States have not been fully described. METHODS: We analyzed data from 173,099 participants of the All of Us Research Program recruited in the period 2017-2019, with 92,318 of them having electronic health records (EHR) data available, and 35,483 having completed a medical history survey. Presence of AF at baseline was identified from self-report and EHR records. Incident AF was obtained from EHR. Demographic, anthropometric and clinical risk factors were obtained from questionnaires, baseline physical measurements and EHR. RESULTS: At enrollment, mean age was 52 years old (range 18-89). Females and males accounted for 61% and 39% respectively. Non-Hispanic Whites accounted for 67% of participants, with non-Hispanic Blacks, non-Hispanic Asians and Hispanics accounting for 26%, 4% and 3% of participants, respectively. Among 92,318 participants with available EHR data, 3,885 (4.2%) had AF at the time of study enrollment, while the corresponding figure among 35,483 with medical history data was 2,084 (5.9%). During a median follow-up of 16 months, 354 new cases of AF were identified among 88,433 eligible participants. Individuals who were older, male, non-Hispanic white, had higher body mass index, or a prior history of heart failure or coronary heart disease had higher prevalence and incidence of AF. CONCLUSION: The epidemiology of AF in the All of Us Research Program is similar to that reported in smaller studies with careful phenotyping, highlighting the value of this new resource for the study of AF and, potentially, other cardiovascular diseases.

Associations of Serum Magnesium with Brain Morphology and Subclinical Cerebrovascular Disease: The Atherosclerosis Risk in Communities-Neurocognitive Study.

Circulating magnesium has been associated with a lower risk of dementia, but the physiologic effects by which magnesium may prevent neurological insults remain unclear. We studied 1466 individuals (mean age 76.2 ± 5.3, 28.8% black, 60.1% female) free of prevalent stroke, with measured serum magnesium and with available MRI scans obtained in 2011-2013, participating in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS). Cross-sectional differences in frontal, temporal, parietal, and occipital lobe volume, along with deep grey matter, total brain, and white matter hyperintensity volume across serum magnesium (categorized into quintiles and per standard deviation increases) were assessed using multiple linear regression. We also examined associations of magnesium with the prevalence of cortical, subcortical, and lacunar infarcts using multiple logistic regression. After adjusting for demographics, biomarkers, medications, and cardiometabolic risk factors, higher circulating magnesium was associated with greater total brain volume and frontal, temporal, and parietal lobe volumes (volumes 0.14 to 0.19 standard deviations higher comparing Q5 to Q1). Elevated magnesium was also associated with lower odds of subcortical infarcts (OR (95%CI): 0.44 (0.25, 0.77) comparing Q5 to Q1) and lacunar infarcts (OR (95%CI): 0.40 (0.22, 0.71) comparing Q5 to Q1). Elevated serum magnesium was cross-sectionally associated with greater brain volumes and lower odds of subclinical cerebrovascular disease, suggesting beneficial effects on pathways related to neurodegeneration and cerebrovascular damage. Further exploration through prospective analyses is needed to assess increasing circulating magnesium as a potential neuroprotective intervention.

Association of heart failure subtypes and atrial fibrillation: Data from the Atherosclerosis Risk in Communities (ARIC) study.

AIMS: To determine the prevalence and incidence of AF among HF subtypes in a biracial community-based cohort. METHODS: We studied 6496 participants in the Atherosclerosis Risk in Community study (mean age, 75.8 ± 5.3, 59% women, 23% black) who attended the 2011-2013 visit. HF was identified from physician adjudicated diagnosis, hospital discharges, and self-report. HF subtypes were based on echocardiography. A left ventricular ejection fraction <40% represents HF with reduced ejection fraction (HFrEF), 40%-49% for HF with midrange ejection fraction (HFmEF), and ≥ 50% for HF with preserved ejection fraction (HFpEF). AF was ascertained through 2017 from study electrocardiograms, hospital discharges, and death certificates. Confounder-adjusted logistic regression and Cox models were used to estimate associations of HF subtype with prevalent and incident AF. RESULTS: Among eligible participants, 393 had HF (HFpEF = 232, HFmEF = 41, HFrEF = 35 and unclassified HF = 85) and 735 had AF. Compared to those without HF, all HF subtypes were more likely to have prevalent AF [odds ratio (95% confidence interval (CI)) 7.4 (5.6-9.9) for HFpEF, 8.1 (4.3-15.3) for HFmEF, 10.0 (5.0-20.2) for HFrEF, 8.8 (5.6-14.0) for unclassified HF]. Among participants without AF at baseline (n = 5761), 610 of them developed AF. Prevalent HF was associated with increased risk of AF [hazard ratio (95%CI) 2.3 (1.6-3.2) for HFpEF, 5.0 (2.7-9.3) for HFmEF, 3.5 (1.7-7.6) for HFrEF, 1.9 (0.9-3.7) for unclassified HF]. CONCLUSION: AF and HF frequently co-occur, with small differences by HF subtype, underscoring the importance of understanding the interplay of these two epidemics and evaluating shared preventive and therapeutic strategies.

Sphingolipids and physical function in the Atherosclerosis Risk in Communities (ARIC) study.

Long-chain sphingomyelins (SMs) may play an important role in the stability of myelin sheath underlying physical function. The objective of this study was to examine the cross-sectional and longitudinal associations of long-chain SMs [SM (41:1), SM (41:2), SM (43:1)] and ceramides [Cer (41:1) and Cer (43:1)] with physical function in the Atherosclerosis Risk in Communities (ARIC) study. Plasma concentrations of SM (41:1), SM (41:2), SM (43:1), Cer (41:1) and Cer (43:1) were measured in 389 ARIC participants in 2011-13. Physical function was assessed by grip strength, Short Physical Performance Battery (SPPB), 4-m walking speed at both 2011-13 and 2016-17, and the modified Rosow-Breslau questionnaire in 2016-2017. Multivariable linear and logistic regression analyses were performed, controlling for demographic and clinical confounders. In cross-sectional analyses, plasma concentrations of SM 41:1 were positively associated with SPPB score (ß-coefficients [95% confidence internal]: 0.33 [0.02, 0.63] per 1 standard deviation [SD] increase in log-transformed concentration, p value 0.04), 4-m walking speed (0.042 m/s [0.01, 0.07], p value 0.003), and negatively with self-reported disability (odds ratio = 0.73 [0.65, 0.82], p value < 0.0001). Plasma concentrations of the five metabolites examined were not significantly associated with longitudinal changes in physical function or incidence of poor mobility. In older adults, plasma concentrations of long-chain SM 41:1 were cross-sectionally positively associated with physical function.

Low Serum Magnesium is Associated with Incident Dementia in the ARIC-NCS Cohort.

Higher serum magnesium is associated with lower risk of multiple morbidities, including diabetes, stroke, and atrial fibrillation, but its potential neuroprotective properties have also been gaining traction in cognitive function and decline research. We studied 12,040 participants presumed free of dementia in the Atherosclerosis Risk in Communities (ARIC) study. Serum magnesium was measured in fasting blood samples collected in 1990-1992. Dementia status was ascertained through cognitive examinations in 2011-2013, 2016-2017, and 2018-2019, along with informant interviews and indicators of dementia-related hospitalization events and death. Participants' cognitive functioning capabilities were assessed up to five times between 1990-1992 and 2018-2019. The cognitive function of participants who did not attend follow-up study visits was imputed to account for attrition. We identified 2519 cases of dementia over a median follow-up period of 24.2 years. The lowest quintile of serum magnesium was associated with a 24% higher rate of incident dementia compared to those in the highest quintile of magnesium (HR, 1.24; 95% CI, 1.07, 1.44). No relationship was found between serum magnesium and cognitive decline in any cognitive domain. Low midlife serum magnesium is associated with increased risk of incident dementia, but does not appear to impact rates of cognitive decline.

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.

Polypharmacy, Adverse Outcomes, and Treatment Effectiveness in Patients ≥75 With Atrial Fibrillation.

Background Polypharmacy is highly prevalent in elderly people with chronic conditions, including atrial fibrillation (AF). The impact of polypharmacy on adverse outcomes and on treatment effectiveness in elderly patients with AF remains unaddressed. Methods and Results We studied 338 810 AF patients ≥75 years of age enrolled in the MarketScan Medicare Supplemental database in 2007-2015. Polypharmacy was defined as ≥5 active prescriptions at AF diagnosis (defined by the presence of International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes) based on outpatient pharmacy claims. AF treatments (oral anticoagulation, rhythm and rate control) and cardiovascular end points (ischemic stroke, bleeding, heart failure) were defined based on inpatient, outpatient, and pharmacy claims. Multivariable Cox models were used to estimate associations of polypharmacy with cardiovascular end points and the interaction between polypharmacy and AF treatments in relation to cardiovascular end points. Prevalence of polypharmacy was 52%. Patients with polypharmacy had increased risk of major bleeding (hazard ratio [HR], 1.16; 95% CI, 1.12-1.20) and heart failure (HR, 1.33; 95% CI, 1.29-1.36) but not ischemic stroke (HR, 0.96; 95% CI, 0.92-1.00), compared with those not receiving polypharmacy. Polypharmacy status did not consistently modify the effectiveness of oral anticoagulants. Rhythm control (versus rate control) was more effective in preventing heart failure hospitalization in patients not receiving polypharmacy (HR, 0.87; 95% CI, 0.76-0.99) than among those with polypharmacy (HR, 0.98; 95% CI, 0.91-1.07; P=0.02 for interaction). Conclusion Polypharmacy is common among patients ≥75 with AF, is associated with adverse outcomes, and may modify the effectiveness of AF treatments. Optimizing management of polypharmacy in AF patients ≥75 may lead to improved outcomes.

Associations of serum uric acid with incident dementia and cognitive decline in the ARIC-NCS cohort.

INTRODUCTION: Elevated serum uric acid (SUA) is associated with cardiovascular risk factors, which often contribute to dementia and dementia-like morbidity, yet several cross-sectional studies have shown protective associations with cognition, which would be consistent with other work showing benefits of elevated SUA through its antioxidant properties. METHODS: We studied 11,169 participants free of dementia and cardiovascular disease from the Atherosclerosis Risk in Communities (ARIC) cohort. SUA was measured in blood samples collected in 1990-92, baseline for this study (age range 47-70 years). Incident dementia was ascertained based on clinical assessments in 2011-13 and 2016-17, surveillance based on dementia screeners conducted over telephone interviews, hospitalization discharge codes, and death certificates. Cognitive function was assessed up to four times between 1990 and 92 and 2016-17. We estimated the association of SUA, categorized into quartiles, with incidence of dementia using Cox regression models adjusting for potential confounders. The association between cognitive decline and SUA was assessed using generalized estimating equations. RESULTS: Over a median follow-up period of 24.1 years, 2005 cases of dementia were identified. High baseline SUA was associated with incident dementia (HR, 1.29; 95% CI, 1.12, 1.47) when adjusted for sociodemographic variables. However, after further adjustment including cardiovascular risk factors, this relationship disappeared (HR, 1.03; 95% CI, 0.88, 1.21). Elevated baseline SUA was associated with faster cognitive decline even after further adjustment (25-year global z-score difference, -0.149; 95% CI, -0.246, -0.052). CONCLUSION: Higher levels of mid-life SUA were associated with faster cognitive decline, but not necessarily with higher risk of dementia.

Sex and racial differences in cardiovascular disease risk in patients with atrial fibrillation.

BACKGROUND: Outcomes among atrial fibrillation (AF) patients may differ according to race/ethnicity and sex due to differences in biology, the prevalence of cardiovascular risk factors, and the use and effectiveness of AF treatments. We aimed to characterize patterns of cardiovascular risk across subgroups of AF patients by sex and race/ethnicity, since doing so may provide opportunities to identify interventions. We also evaluated whether these patterns changed over time. METHODS: We utilized administrative claims data from the Optum Clinformatics® Datamart database from 2009 to 2015. Patients with AF with ≥6 months of enrollment prior to the first non-valvular AF diagnosis were included in the analysis. Final analysis utilized Cox proportional hazard models to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for cardiovascular outcomes stratified by sex and race/ethnicity. An additional analysis stratified outcomes by calendar year of AF diagnosis to evaluate changes in outcomes over time. RESULTS: In a cohort of 380,636 AF patients, women had a higher risk of ischemic stroke [HR (95% CI): 1.25 (1.19, 1.31)] and lower risk of heart failure and myocardial infarction [HR (95% CI): 0.91 (0.88, 0.94) and 0.81 (0.77, 0.86), respectively)] compared to men. Black patients had elevated risk across all endpoints compared to whites, while Hispanics and Asian Americans showed no significant differences in any outcome compared to white patients. These sex and race/ethnic differences did not change over time. CONCLUSIONS: We found sex and race/ethnic differences in risk of cardiovascular outcomes among AF patients, without evidence of improvement over time.