Atrial Fibrillation In Older Adults Research Articles

Cognitive impairment and treatment strategy for atrial fibrillation in older adults: The SAGE-AF study.

Cognitive impairment is strongly associated with atrial fibrillation (AF). Rate and rhythm control are the two treatment strategies for AF and the effect of treatment strategy on risk of cognitive decline and frailty is not well established. We sought to determine how treatment strategy affects geriatric-centered outcomes. The Systematic Assessment of Geriatric Elements-AF (SAGE-AF) was a prospective, observational, cohort study. Older adults with AF were prospectively enrolled between 2016 and 2018 and followed longitudinally for 2 years. In a non-randomized fashion, participants were grouped by rate or rhythm control treatment strategy based on clinical treatment at enrollment. Baseline characteristics were compared. Longitudinal binary mixed models were used to compare treatment strategy with respect to change in cognitive function and frailty status. Cognitive function and frailty status were assessed with the Montreal Cognitive Assessment Battery and Fried frailty phenotype tools. 972 participants (mean age = 75, SD = 6.8; 49% female, 87% non-Hispanic white) completed baseline examination and 2-year follow-up. 408 (42%) were treated with rate control and 564 (58%) with rhythm control. The patient characteristics of the two groups were different at baseline. Participants in the rate control group were older, more likely to have persistent AF, prior stroke, be treated with warfarin and have baseline cognitive impairment. After adjusting for baseline differences, participants treated with rate control were 1.5 times more likely to be cognitively impaired over 2 years (adjusted OR: 1.47, 95% CI:1.12, 1.98) and had a greater decline in cognitive function (adjusted estimate: -0.59 (0.23), p < 0.01) in comparison to rhythm control. Frailty did not vary between the treatment strategies. Among those who had 2-year follow-up in non-randomized observational cohort, the decision to rate control AF in older adults was associated with increased odds of decline in cognitive function but not frailty.

Assessment and Management of Atrial Fibrillation in Older Adults with Frailty.

Atrial fibrillation (AF) is a major driver of morbidity and mortality among older adults with frailty. Moreover, frailty is highly prevalent in older adults with AF. Understanding and addressing the needs of frail older adults with AF is imperative to guide clinicians caring for older adults. In this review, we summarize current evidence to support the assessment and management of older adults with AF and frailty, incorporating numerous recent landmark trials and studies in the context of the 2023 US AF guideline.

Left Atrial Strain and Incident Atrial Fibrillation in Older Adults

Atrial fibrillation (AF) is frequent in older adults and associated with left atrial (LA) dysfunction. LA strain (LAε) and LA strain rate (LASR) may detect subclinical LA disease. We investigated whether reduced LAε and LASR predict new-onset AF in older adults without history of AF or stroke. LAε and LASR were assessed by speckle-tracking echocardiography in 824 participants from the community-based Cardiovascular Abnormalities and Brain Lesions study. Positive longitudinal LAε and LASR during ventricular systole, LASR during early ventricular diastole, and LASR during LA contraction were measured. Cause-specific hazards regression modelevaluated the association of LAε and LASR with incident AF, adjusting for pertinent covariates. The mean age was 71.1 ± 9.2 years (313 men, 511 women). During a mean follow-up of 10.9years, new-onset AF occurred in 105 participants (12.7%). Lower LAε and LASR at baseline were observed in patients with new-onset AF (all p <0.01). In multivariable analysis, positive longitudinal LAε (adjusted hazard ratio [HR] per SD decrease 2.05, confidence interval [CI] 1.24 to 3.36) and LASR during LA contraction (HR per SD increase 2.24, CI 1.37 to 3.65) remained associated with new-onset AF, independently of LA volumes and left ventricular function. Along with positive longitudinal LAε, reduced LASR during ventricular systole predicted AF in participants with LA volume below the median value (HR 2.54, CI 1.10 to 6.09), whereas reduced LASR during LA contraction predicted AF in participants with larger LA (HR 2.35, CI 1.31 to 4.23). In conclusion, reduced positive longitudinal LAε and LASR predict new-onset AF in older adults regardless of LA size and may improve AF risk stratification.

Excessive dietary sodium intake augments long-term risk of atrial fibrillation in older adults with hyperglycemia: A community-based prospective cohort study

AimStudies investigating the association between sodium intake and new-onset atrial fibrillation (AF) have come to controversial results. This study aimed to assess the effect of excessive sodium intake on new-onset AF in individuals with hyperglycemia. MethodsBetween April 2007 and November 2011, 2841 community-dwelling individuals aged 60 years and older were recruited from the Shandong area, China. Dietary sodium intake was estimated using 24-hour urine collection within seven consecutive days. Fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) were assessed. New-onset AF was diagnosed using ICD-10 with codes I48 (I48.0 – I48.9) during follow-up. ResultsThe findings were that excessive sodium intake significantly and independently increased the risk of new-onset AF in older adults with hyperglycemia: hazard ratio (HR) 1.525 [95% confidence interval 1.147;2.029] adjusted P = 0.004. The risk of new-onset AF increased by 29.3% (HR 1.293 [1.108;1.509] adjusted P = 0.001) with a one-standard deviation increase in sodium intake. Excessive sodium intake synergistically interacted with hyperglycemia on the increased risk of new-onset AF (HR 1.599 [1.342;1.905] adjusted P < 0.001 for FPG and HR 1.516 [1.271;1.808] adjusted P < 0.001 for HbA1c). ConclusionOur findings indicate that excessive sodium intake independently enhances the risk of new-onset AF among patients with hyperglycemia. A sodium-restricted diet may perhaps result in a multiplier effect on reducing the risk of new-onset AF.

Addressing the challenging yet vital task of managing atrial fibrillation in older adults to prevent heart failure

Addressing the challenging yet vital task of managing atrial fibrillation in older adults to prevent heart failure

880-P: Effects of Sodium–Glucose Cotransporter-2 Inhibitors on the Risk of Atrial Fibrillation in Older Adults with Type 2 Diabetes

Clinical evidence suggested a protective effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on the risk of atrial fibrillation (AF) in type 2 diabetes (T2D) patients, but the results were mixed. We aimed to compare the risk of AF in SGLT2i users compared to dipeptidyl peptidase-4 inhibitors (DPP4i) users and determine the effect in different subgroups. Using a 15% random sample of 2017-2018 Medicare claims data, we identified individuals with T2D, no preexisting AF, and initiated SGLT2i or DPP4i. The index date was defined as the date of the first filled prescription of SGLT2i or DPP4i. The outcome was the first incident of diagnosed AF. Inverse probability treatment weighted Cox regression models were used for analyses. Of the 97,660 eligible individuals (age 71.2±9.8 years, 54.6% women), 1.01% (n=989) had incident AF over a median follow-up of 361 days. The crude incidence rate was 8.39 (95% CI: 6.67-9.99) and 11.70 (95% CI: 10.9-12.55) per 1000 person-years in the SGLT2i group and DPP4i group, respectively. SGLT2i was associated with a significantly lower risk of incident AF (HR 0.72 [95% CI 0.56-0.89]) than DPP4i. The risk reduction of incident AF was more pronounced in Hispanic individuals and subgroups with existing cardiovascular (CV) and renal conditions. (Figure) Use of SGLT2i was associated with a lower risk of AF in individuals with T2D. Disclosure Y.Li: None. Y.Guo: None. S.Kimmel: Consultant; GlaxoSmithKline plc., Other Relationship; Janssen Research &amp; Development, LLC. J.Bian: None. D.Schatz: Advisory Panel; Medtronic, Avotres Inc., QuLab Medical Ltd., Kriya Therapeutics. J.Guo: Consultant; Pfizer Inc., Research Support; PhRMA Foundation, NIH - National Institutes of Health.

Estimates of the global, regional, and national burden of atrial fibrillation in older adults from 1990 to 2019: insights from the Global Burden of Disease study 2019.

Atrial fibrill ation (AF) is a predominant public health concern in older adults. Therefore, this study aimed to explore the global, regional, and national burden of AF in older adults aged 60-89 between 1990 and 2019. The morbidity, mortality, disability-adjusted life years (DALYs), and age-standardized rates of AF were refined from the Global Burden of Diseases study 2019. The epidemiological characteristics were assessed based on numerical values, age-standardized rates per 100,000 person-years, and estimated annual percentage changes (EAPC). Globally, a total of 33.31 million AF cases, 219.4 thousand deaths, and 65.80 million DALYs were documented in 2019. There were no appreciable changes in EAPC from 1990 to 2019. The disease burden of AF differed significantly across different territories and countries. At the national level, China exhibited the highest number of incident cases [818,493 (562,871-1,128,695)], deaths [39,970 (33,722-46,387)], and DALYs [1,383,674 (1,047,540-1,802,516)]. At the global level, high body mass index (BMI) and high systolic blood pressure (SBP) were two predominant risk factors contributing to the proportion of AF-related deaths. AF in older adults remains a major public health concern worldwide. The burden of AF varies widely at both national and regional levels. From 1990 to 2019, the cases of incidences, deaths, and DALYs have shown a global increase. The ASIR, ASMR, and ASDR have declined in the high-moderate and high SDI regions; however, the burden of AF increased promptly in the lower SDI regions. Special attention should be paid to the main risk factors for high-risk individuals with AF, which can help control systolic blood pressure and body mass index within normal limits. Over all, it is necessary to illustrate the features of the global AF burden and develop more effective and targeted prevention and treatment strategies.

A Smartwatch System for Continuous Monitoring of Atrial Fibrillation in Older Adults After Stroke or Transient Ischemic Attack: Application Design Study.

The prevalence of atrial fibrillation (AF) increases with age and can lead to stroke. Therefore, older adults may benefit the most from AF screening. However, older adult populations tend to lag more than younger groups in the adoption of, and comfort with, the use of mobile health (mHealth) apps. Furthermore, although mobile apps that can detect AF are available to the public, most are designed for intermittent AF detection and for younger users. No app designed for long-term AF monitoring has released detailed system design specifications that can handle large data collections, especially in this age group. This study aimed to design an innovative smartwatch-based AF monitoring mHealth solution in collaboration with older adult participants and clinicians. The Pulsewatch system is designed to link smartwatches and smartphone apps, a website for data verification, and user data organization on a cloud server. The smartwatch in the Pulsewatch system is designed to continuously monitor the pulse rate with embedded AF detection algorithms, and the smartphone in the Pulsewatch system is designed to serve as the data-transferring hub to the cloud storage server. We implemented the Pulsewatch system based on the functionality that patients and caregivers recommended. The user interfaces of the smartwatch and smartphone apps were specifically designed for older adults at risk for AF. We improved our Pulsewatch system based on feedback from focus groups consisting of patients with stroke and clinicians. The Pulsewatch system was used by the intervention group for up to 6 weeks in the 2 phases of our randomized clinical trial. At the conclusion of phase 1, 90 trial participants who had used the Pulsewatch app and smartwatch for 14 days completed a System Usability Scale to assess the usability of the Pulsewatch system; of 88 participants, 56 (64%) endorsed that the smartwatch app is "easy to use." For phases 1 and 2 of the study, we collected 9224.4 hours of smartwatch recordings from the participants. The longest recording streak in phase 2 was 21 days of consecutive recordings out of the 30 days of data collection. This is one of the first studies to provide a detailed design for a smartphone-smartwatch dyad for ambulatory AF monitoring. In this paper, we report on the system's usability and opportunities to increase the acceptability of mHealth solutions among older patients with cognitive impairment. ClinicalTrials.gov NCT03761394; https://www.clinicaltrials.gov/ct2/show/NCT03761394. RR2-10.1016/j.cvdhj.2021.07.002.

Association of Sodium-Glucose Cotransporter-2 Inhibitors With Incident Atrial Fibrillation in Older Adults With Type 2 Diabetes

Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) have demonstrated many cardiovascular and kidney function benefits for patients with type 2 diabetes (T2D). However, the results of SGLT-2i use in primary prevention of atrial fibrillation (AF) were inconsistent in clinical trials, and incident AF was not a prespecified end point. To examine incident AF with initiation of an SGLT-2i compared with initiation of a dipeptidyl peptidase-4 inhibitor (DPP-4i) or a glucagonlike peptide-1 receptor agonist (GLP-1RA) among older adults (aged ≥66 years) with T2D in routine clinical practice. A population-based new-user cohort study included older adults with T2D who had no history of AF and were enrolled in Medicare fee-for-service from April 1, 2013, to December 31, 2018. Data analysis was performed from June 28 to December 1, 2021. To control for potential confounding, new users of SGLT-2i were 1:1 propensity score (PS)-matched to new users of DPP-4is or GLP-1RAs in 2 pairwise comparisons based on 138 baseline covariates. The primary outcome was incident AF, defined as an inpatient diagnosis code for AF. Hazard ratios (HRs) and rate differences (RDs) per 1000 person-years, with their 95% CIs, were estimated in the PS-matched groups. New users of SGLT-2is were 1:1 PS-matched to new users of a DPP-4i (n = 74 868) or GLP-1RA (n = 80 475). Overall, the mean (SD) age of study participants was 72 (5) years, and 165 984 were women (53.4%). The risk of incident AF was lower in the SGLT-2i group than the matched DPP-4i group (HR, 0.82; 95% CI, 0.76 to 0.89; RD, -3.7; 95% CI, -5.2 to -2.2 per 1000 person-years) or the matched GLP-1RA group (HR, 0.90; 95% CI, 0.83 to 0.98; RD, -1.8; 95% CI, -3.2 to -0.3 per 1000 person-years). Results were consistent across several sensitivity and subgroup analyses. The findings of this study suggest that the initiation of an SGLT-2i was associated with a reduced risk of incident AF compared with a DPP-4i or GLP-1RA. The results may be helpful when weighing the potential risks and benefits of various glucose level-lowering agents in older adults with T2D.

Cognitive impairment, age, quality of life, and treatment strategy for atrial fibrillation in older adults: The SAGE-AF study.

Atrial fibrillation (AF) treatment includes anticoagulation for high stroke risk individuals and either rate or rhythm control strategies. We aimed to investigate the impact of age, geriatric factors, and medical comorbidities on choice of rhythm versus rate control strategy in older adults. Patients with AF aged ≥65 years with CHA2 DS2 VASc score ≥2 and eligible for anticoagulation were recruited for the Systematic Assessment of Geriatric Elements-AF (SAGE-AF) prospective cohort study. An interview that included measures of HRQoL, cognitive function, vision, hearing, and frailty was performed. The association between these elements and AF treatment strategy was examined by multivariable logistic regression models. One thousand two hundred forty-four participants (mean age 76 years; 49% female; 85% non-Hispanic white) were enrolled. Rate and rhythm control were used in 534 and 710 participants, respectively. Compared to participants <75 years, those ≥75 were more likely to be treated with a rate control strategy (age 75-84 adjusted odds ratio [aOR] 1.37 [95% CI 0.99, 1.88]; age 85+ aOR=2.05, 95% CI 1.30, 3.21). Those treated with a rate control strategy were more likely to have cognitive impairment (aOR=1.50, 95% CI 1.13, 1.99), and peripheral vascular disease (PVD) (aOR=1.82, 95% CI 1.22, 2.72) but less likely to have visual impairment (aOR 0.73 [0.55, 0.98]), congestive heart failure (CHF; aOR 0.68 [0.49, 0.94]) or receive anticoagulation (aOR 0.53, 95% CI 0.36, 0.78). Older age, cognitive impairment, and PVD were associated with use of rate control strategy. Visual impairment, CHF, and anticoagulation use were associated with a rhythm control strategy. There was no difference in HRQoL between the rate and rhythm control groups. This study suggests that certain geriatric elements may be associated with AF treatment strategies. Further study is needed to evaluate how these decisions affect outcomes.

177-OR: Sodium–Glucose Cotransporter-2 Inhibitors and the Risk of Incident Atrial Fibrillation in Older Adults with Type 2 Diabetes

The role of SGLT-2i in the primary prevention of atrial fibrillation (AF) remains unclear from clinical trials. We assessed the association of SGLT-2i use and incident AF in routine clinical practice. Using Medicare claims data 2013-2018, we identified patients with type 2 diabetes (T2D) and aged ≥66 years with no AF history (i.e., no diagnosis, procedure or medication codes suggestive of underlying AF at baseline) initiating an SGLT-2i or a comparator (a DPP-4i or a GLP-1RA) , in two pairwise comparisons (74,868 and 80,475 1:1 propensity score-matched pairs, respectively) . The primary outcome was AF hospitalization. Secondary outcomes were AF diagnosis in any care setting and AF treated with medications. We calculated hazard ratios (HRs) and rate differences (RDs, per 1000 patient-year) , in the matched groups, well-balanced across 138 baseline covariates. Over a median follow-up of approximately 6 months, the risk of AF hospitalization was lower in the SGLT-2i group than the DPP-4i group (HR, 0.82 [95%CI, 0.76-0.89]; RD, -3.7 [95%CI, -5.2, -2.2]) or the GLP-1RA group (HR, 0.90 [95%CI, 0.83-0.98]; RD, -1.8 [95%CI, -3.2, -0.3]) (Table) . Findings for secondary outcomes were consistent with the primary outcome. In routine care, SGLT-2i use was associated with a reduction in the risk of incident AF, compared to DPP-4i or GLP-1RA among older patients with T2D. Disclosure M.Zhuo: None. J.M.Paik: None. D.J.Wexler: Other Relationship; Elsevier, Novo Nordisk, UpToDate. B.M.Everett: Consultant; Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc., Lilly, Provention Bio, Inc., UpToDate, Other Relationship; American Heart Association, Research Support; Novo Nordisk. E.D'andrea: None. R.Glynn: None. S.C.Kim: Research Support; AbbVie Inc., Bristol-Myers Squibb Company, Pfizer Inc., Roche Pharmaceuticals. E.Patorno: Research Support; Boehringer Ingelheim International GmbH, National Institutes of Health, Patient-Centered Outcomes Research Institute.

Screening for Atrial Fibrillation in Older Adults at Primary Care Visits: VITAL-AF Randomized Controlled Trial.

Undiagnosed atrial fibrillation (AF) may cause preventable strokes. Guidelines differ regarding AF screening recommendations. We tested whether point-of-care screening with a handheld single-lead ECG at primary care practice visits increases diagnoses of AF. We randomized 16 primary care clinics 1:1 to AF screening using a handheld single-lead ECG (AliveCor KardiaMobile) during vital sign assessments, or usual care. Patients included were ages ≥65 years. Screening results were provided to primary care clinicians at the encounter. All confirmatory diagnostic testing and treatment decisions were made by the primary care clinician. New AF diagnoses during the 1-year follow-up were ascertained electronically and manually adjudicated. Proportions and incidence rates were calculated. Effect heterogeneity was assessed. Of 30 715 patients without prevalent AF (n=15 393 screening [91% screened], n=15 322 control), 1.72% of individuals in the screening group had new AF diagnosed at 1 year versus 1.59% in the control group (risk difference, 0.13% [95% CI, -0.16 to 0.42]; P=0.38). In prespecified subgroup analyses, new AF diagnoses in the screening and control groups were greater among those aged ≥85 years (5.56% versus 3.76%, respectively; risk difference, 1.80% [95% CI, 0.18 to 3.30]). The difference in newly diagnosed AF between the screening period and the previous year was marginally greater in the screening versus control group (0.32% versus -0.12%; risk difference, 0.43% [95% CI, -0.01 to 0.84]). The proportion of individuals with newly diagnosed AF who were initiated on oral anticoagulants was not different in the screening (n=194, 73.5%) and control (n=172, 70.8%) arms (risk difference, 2.7% [95% CI, -5.5 to 10.4]). Screening for AF using a single-lead ECG at primary care visits did not affect new AF diagnoses among all individuals aged 65 years or older compared with usual care. URL: https://www. gov; Unique identifier: NCT03515057.

Atrial fibrillation in older adults with cancer.

Cancer and atrial fibrillation (AF) are common co-morbid conditions in older adults. Both cancer and cancer treatment increase the risk of developing new AF which increases morbidity and mortality. Heart rate and rhythm control along with anticoagulation therapy remain the mainstay of treatment of AF in older adults with both cancer and AF. Adjustments to the treatment may be necessary because of drug interactions with concurrent chemotherapy. Cancer and old age increase the risk of both, thromboembolism and bleeding. The risk of these complications is further enhanced by concomitant cancer therapy, frailty, poor nutrition status and, coexisting geriatric syndromes. Therefore, careful attention needs to be given to the risks and benefits of using anticoagulant medications. This review focuses on the management of AF in older patients with cancer, including at the end-of-life care.

Prevalence and treatment of atrial fibrillation in older adults.

Atrial fibrillation (AF) is the most frequent cardiac arrhythmiawith an impact on morbidity and mortality found in the geriatric population. This retrospective study is the first to investigate the prevalence, treatment and comorbidities of AF in alarge cohort of older adults. Older adults with AF hospitalized between 2010 and 2018. The mean age of the 10,700 AF patients in 2018 was 83.2 ± 6.4years. The frequency of anticoagulation in older adults with AF between 2010 and 2018 was analyzed. The relationship between comorbidities and anticoagulation in 2018 was examined. Logistic regression analysis was used to identify possible predictive factors for anticoagulation. The prevalence of AF in 35,887 hospitalized older adults was 29.8% in 2018. The mean CHA2DS2VASc score was 4.4 ± 1.3 (male 3.8 ± 1.3, female 4.7 ± 1.2). From 2010 to 2018, the frequency of anticoagulation for patients with AF rose from 32.1% to 64.2%. Statistically significant differences in the examined characteristics between anticoagulated and not anticoagulated patients were found. Furthermore, there were no predictive factors for anticoagulation in multivariate logistic analysis. Hospitalized older adults have an increased prevalence of AF compared to the general population. Despite the higher risk of bleeding, older adults were more frequently anticoagulated in the observation period, preferably with direct oral anticoagulants (DOACs). Patients without anticoagulation had more diagnoses and were worse in functional tests. This study suggests that the decision to give anticoagulants to older adults should be personalized.

Abstract 14355: Metabolic Dysregulation and Incident Atrial Fibrillation in Older Adults

Introduction: Obesity and dysmetabolism are major risk factors for atrial fibrillation (AF). Fasting and post-load levels of glucose and non-esterified fatty acids (NEFA) reflect different facets of metabolic regulation, but their contributions to AF risk have not been studied simultaneously in prior studies. We assessed fasting and post-load glucose and NEFA in an older cohort to identify their independent associations with new-onset AF, and secondarily with baseline ECG parameters known to be markers of AF risk. Methods: This study focused on participants from the community-based Cardiovascular Health Study who were free of prevalent AF and had serum collected in the fasting state and after an oral glucose tolerance test. Maximal p wave duration and p wave terminal force in V1 (PTFV1) were measured from 12-lead ECG. Associations were evaluated with linear regression for ECG parameters, and Cox regression for AF. Results: The study included 1,877 participants (age 77.7±4.4). After adjustment, both fasting and post-load glucose, but not NEFA, were positively associated with higher PTFV1. When fasting and post-load glucose were entered together, only the relationship for the latter remained significant (63 μV*ms greater PTFV1 per SD increment in post-load glucose [p=0.028]). During median follow-up of 11.4 years, 717 cases of incident AF occurred. Post-load glucose, but not fasting glucose or either NEFA measure, showed an association with incident AF (adj. HR per SD=1.11 [95% CI=1.02, 1.21], p=0.017). There was significant interaction by sex (p=0.015). The positive relationship of post-load glucose with AF was observed in women (adj. HR per SD=1.21 [1.09, 1.35], p&lt;0.001), but not men (adj. HR per SD=0.97 [0.85, 1.12], p=0.714). Conclusions: Among older adults, post-load glucose, but not fasting glucose or NEFA measures, was positively associated with incident AF, with consistent findings for PTFV1 on baseline ECG. The relationship with AF appeared specific to women. Because post-load glucose is a marker of both pancreatic β-cell insufficiency and skeletal muscle decline, these findings suggest that interventions to address such tissue-organ dysfunction in older women might prevent AF in this high-risk population.

Proteomics and Risk of Atrial Fibrillation in Older Adults (From the Atherosclerosis Risk in Communities [ARIC] Study)

Plasma proteomic profiling may aid in the discovery of novel biomarkers upstream of the development of atrial fibrillation (AF). We used data from the Atherosclerosis Risk in Communities study to examine the relation between large-scale proteomics and incident AF in a cohort of older-aged adults in the United States. We quantified 4,877 plasma proteins in Atherosclerosis Risk in Communities participants at visit 5 (2011-2013) using an aptamer-based proteomic profiling platform. We used Cox proportional hazards models to assess the association between protein levels and incident AF, and explored relation of selected protein biomarkers using annotated pathway analysis. Our study included 4,668 AF-free participants (mean age 75 ± 5 years; 59% female; 20% Black race) with proteomic measures. A total of 585 participants developed AF over a mean follow-up of 5.7 ± 1.7 years. After adjustment for clinical factors associated with AF, N-terminal pro-B-type natriuretic peptide (NT-proBNP) was associated with the risk of incident AF (hazard ratio, 1.82; 95% CI, 1.68 to 1.98; p, 2.91×10-45 per doubling of NT-proBNP). In addition, 36 other proteins were also significantly associated with incident AF after Bonferroni correction. We further adjusted for medication use and estimated glomerular filtration rate and found 17 proteins, including angiopoietin-2 and transgelin, that remained significantly associated with incident AF. Pathway analyses implicated the inhibition of matrix metalloproteases as the top canonical pathway in AF pathogenesis. In conclusion, using a large-scale proteomic platform, we identified both novel and established proteins associated with incident AF and explored mechanistic pathways of AF development.

Brachial Flow-Mediated Dilation and Risk of Atrial Fibrillation in Older Adults: The Cardiovascular Health Study.

BackgroundEndothelial dysfunction is associated with common risk factors for AF and has been implicated in the pathophysiology of atrial fibrillation (AF) through a variety of mechanisms. We determined the prospective association of brachial flow-mediated dilation (FMD) with incident AF among older adults.MethodsWe included 2027 Cardiovascular Health Study participants (mean age=78.3 years, male=39%, Black=17%) who underwent brachial FMD measurement at the 1997 to 1998 clinic visit. Incident AF was ascertained by study electrocardiograms, hospital discharge diagnosis coding and Medicare claims data. Cox regression models were used to examine the association between FMD and incident AF.ResultsWe identified 754 incident of AF cases (37%) over a median follow-up of 11.0 years. After adjusting for age, sex, race, height, weight, cardiovascular disease, cigarette smoking, hypertension, diabetes, kidney function, c-reactive protein, physical activity, alcohol consumption, and statins, the risk of AF did not differ according to brachial FMD response (4th vs 1st quartile hazard ratio (HR)=1.01, 95% confidence interval (CI): 0.81, 1.26; per FMD unit increment HR=1.01, 95% CI: 0.97, 1.05).ConclusionWe found no relationship between brachial FMD and the risk of developing AF in this elderly cohort. Our findings suggest that the utility of brachial FMD as a risk marker for AF in older individuals is minimal.

Office, central and ambulatory blood pressure for predicting incident atrial fibrillation in older adults.

Recently, more sophisticated blood pressure (BP) measurements, such as central and ambulatory BP (ABP), have proven to be stronger predictors of future cardiovascular disease than conventional office BP. Their predictive value for atrial fibrillation development is not established. We investigated the prognostic impact for incident atrial fibrillation of office, central and ambulatory BP measurements in a predominantly older population-based cohort. Of 1004 participants in the Cardiovascular Abnormalities and Brain Lesions (CABL) study, 769 in sinus rhythm with no history of atrial fibrillation or stroke (mean age 70.5 years) underwent ABP and arterial wave reflection analysis for central BP determination. Fine and Gray's proportional subdistribution hazards models were used to assess the association of BP parameters with incident atrial fibrillation. During 9.5 years, atrial fibrillation occurred in 83 participants. No office BP variable showed a significant association with incident atrial fibrillation. Central SBP and central pulse pressure were marginally associated with incident atrial fibrillation in multivariate analysis. Among ABP variables, 24-h SBP [adjusted hazard ratio per 10 mmHg, 1.24; 95% confidence interval (CI) 1.07--1.44; P = 0.004], daytime SBP (adjusted hazard ratio per 10 mmHg, 1.21; 95% CI 1.04--1.40; P = 0.011) and night-time SBP (adjusted hazard ratio per 10 mmHg, 1.22; 95% CI 1.07--1.39; P = 0.002) were significantly associated with incident atrial fibillation. In a predominantly older, stroke-free community-based cohort, ABP was a better independent predictor of incident atrial fibrillation than central BP, whereas office BP was inadequate for this purpose.

Cost-effectiveness of antithrombotic agents for atrial fibrillation in older adults at risk for falls: a mathematical modelling study.

Antithrombotic drugs decrease stroke risk in patients with atrial fibrillation, but they increase bleeding risk, particularly in older adults at high risk for falls. We aimed to determine the most cost-effective antithrombotic therapy in older adults with atrial fibrillation who are at high risk for falls. We conducted a mathematical modelling study from July 2019 to March 2020 based on the Ontario, Canada, health care system. We derived the base-case age, sex and fall risk distribution from a published cohort of older adults at risk for falls, and the bleeding and stroke risk parameters from an atrial fibrillation trial population. Using a probabilistic microsimulation Markov decision model, we calculated quality-adjusted life years (QALYs), total cost and incremental cost-effectiveness ratios (ICERs) for each of acetylsalicylic acid (ASA), warfarin, apixaban, dabigatran, rivaroxaban and edoxaban. Cost data were adjusted for inflation to 2018 values. The analysis used the Ontario public payer perspective with a lifetime horizon. In our model, the most cost-effective antithrombotic therapy for atrial fibrillation in older patients at risk for falls was apixaban, with an ICER of $8517 per QALY gained (5.86 QALYs at $92 056) over ASA. It was a dominant strategy over warfarin and the other antithrombotic agents. There was moderate uncertainty in cost-effectiveness ranking, with apixaban as the preferred choice in 66% of model iterations (given willingness to pay of $50 000 per QALY gained); edoxaban, 30 mg, was preferred in 31% of iterations. Sensitivity analysis across ranges of age, bleeding risk and fall risk still favoured apixaban over the other medications. From a public payer perspective, apixaban is the most cost-effective antithrombotic agent in older adults at high risk for falls. Health care funders should implement strategies to encourage use of the most cost-effective medication in this population.

Atrial Fibrillation Is Associated With Syncope and Falls in Older Adults: A Systematic Review and Meta-analysis

ObjectiveTo examine the potential association of atrial fibrillation (AF) to syncope and falls, we undertook a systematic review and meta-analysis given the increasing prevalence of AF in older adults as well as emerging data that it is a risk factor for dementia. Patients and MethodsCENTRAL, PubMed, and EMBASE databases were searched from inception to January 31, 2019, to retrieve relevant studies. Search terms consisted of MeSH, tree headings, and keywords relating patients with “AF,” “falls,” “syncope,” and “postural hypotension.” When possible; results were pooled using a random-effects model. ResultsA total of 10 studies were included, with 7 studies (36,444 patients; mean ± SD age, 72±10 years) reporting an association between AF and falls and 3 studies (6769 patients; mean ± SD age, 65±3 years) reporting an association between AF and syncope. Pooled analyses demonstrate that AF is independently associated with falls (odds ratio, 1.19; 95% CI, 1.07-1.33; P=.001) and syncope (odds ratio, 1.88; 95% CI, 1.20-2.94; P=.006). There was overall moderate bias and low-moderate heterogeneity (I2=37%; P=.11) for falls and moderate bias with low statistical heterogeneity (I2=0%; P=.44) for syncope. Persistent AF, but not paroxysmal AF, was associated with orthostatic intolerance in 1 study (4408 patients; mean ± SD age, 66±6 years). ConclusionAF is independently associated with syncope and falls in older adults. Further studies are needed to delineate mechanistic links and to guide management to improve outcomes in these patients. Trial RegistrationPROSPERO: trial identifier: CRD4201810721.