Lithium Receipt and Risk of Dementia in Older Veterans With Bipolar Disorder in the VA Health System

Abstract Older adults with bipolar disorder are at increased risk of developing dementia. The literature suggests lithium treatment may reduce the incidence of dementia. This study sought to inform clinical practice in the Veterans Affairs (VA) health system by estimating the effect of past year lithium receipt on dementia incidence among Veterans with bipolar disorder. Divalproex receipt was used as a comparison. Using VA medical records, 121,094 Veterans aged 50 and older with a diagnosis of bipolar disorder but no dementia diagnosis were identified in fiscal years 2005-2019. Follow-up continued until dementia diagnosis, 36 months from the index date, death, or the end of fiscal year 2020, whichever came first. 4347 (3.6%) were diagnosed with dementia during follow-up. Time-varying indicators of receipt of lithium and divalproex in the prior 365 days were calculated for each day, categorized as 301-365, 61-300, 1-60, or 0 days of receipt. Unadjusted Cox proportional hazards regression analyses indicated reduced dementia incidence with 301-365 (HR=0.86, 95% Confidence Interval [95%CI] 0.75-0.99) and 61-300 (HR=0.75, 95%CI 0.65-0.87) days of lithium receipt, compared to 0 days. For divalproex, 301-365 (HR=1.34, 95%CI 1.23-1.47) and 61-300 (HR=1.13, 95%CI 1.03-1.23) days of receipt were each associated with increased dementia incidence. Lithium effects were not statistically significant after adjusting for age, sex, race, ethnicity, medical comorbidities, and antidepressant, antipsychotic, and anxiolytic medication receipt. Divalproex effects remained statistically significant. Past year divalproex, but not lithium, receipt was significantly associated with dementia incidence among VA patients with bipolar disorder when adjusting for demographics and medical comorbidities.

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Kleine Levin syndrome is associated with birth difficulties and genetic variants in the TRANK1 gene loci

10.1101/2021.01.08.20249006 ◽

2021 ◽

Author(s):

Aditya Ambati ◽

Ryan Hillary ◽

Smaranda Leu-Semenescu ◽

Hanna M. Ollila ◽

Ling Lin ◽

...

Keyword(s):

Bipolar Disorder ◽

Genome Wide Association Study ◽

Lithium Treatment ◽

Gene Region ◽

Risk Scores ◽

Nucleotide Polymorphisms ◽

Genetic Associations ◽

Genome Wide ◽

Increased Risk

AbstractKleine-Levin Syndrome (KLS) is a rare disorder characterized by severe episodic hypersomnia, with cognitive impairment accompanied by apathy or disinhibition. Pathophysiology is unknown, although imaging studies indicate decreased activity in hypothalamic/thalamic areas during episodes. Familial occurrence is increased, and risk is associated with reports of a difficult birth. We conducted a worldwide case-control genome wide association study in 673 KLS cases collected over 14 years, and ethnically matched 15,341 control individuals. We found a strong genome-wide significant association (OR=1.48,rs71947865,p=8.6×10−9) with 20 single nucleotide polymorphisms encompassing a 35kb region located in the 3’ region of TRANK1 gene, previously associated with bipolar disorder and schizophrenia. Strikingly, KLS cases with TRANK1 rs71947865 variant had significantly increased reports of a difficult birth. As perinatal outcomes have dramatically improved over the last 40 years, we further stratified our sample by birth years and found that recent cases had a significantly reduced TRANK1 rs71947865 association. While theTRANK1 rs71947865 association did not replicate in the entire follow-up sample of 171 KLS cases, the TRANK1 rs71947865 was significantly associated with KLS in the subset follow-up sample of 59 KLS cases who reported birth difficulties (OR=1.54;p=0.01). Genetic liability of KLS as explained by polygenic risk scores was increased (pseudo r2=0.15;p<2.0×10−22 at p=0.5 threshold) in the follow-up sample. Pathway analysis of genetic associations identified enrichment of circadian regulation pathway genes in KLS cases. Our results suggest links between KLS, behavioral rhythmicity, and bipolar disorder, and indicates that the TRANK1 polymorphisms in conjunction with reported birth difficulties may predispose to KLS.Significance StatementGenetic markers in TRANK1 gene and its vicinity have been weakly associated with bipolar disorder and schizophrenia (10% increased risk). We found that the same polymorphisms are associated with Kleine-Levin Syndrome (50% increased risk), a rare sleep disorder characterized by recurrent episodes of severe hypersomnia and cognitive abnormalities. Response to lithium treatment are suggestive of a pathophysiological overlap between KLS and bipolar disorder. The study also shows that variants in the TRANK1 gene region may predispose to KLS when patients have had a difficult birth, suggesting that TRANK1 gene region modulate newborns’ response to brain injury, with consequences for mental and neurological health in adulthood. Another possibility may be that the polymorphism impact birth and KLS.

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Elevated plasma growth and differentiation factor 15 predicts incident anemia in older adults aged 60 years and older

The Journals of Gerontology Series A ◽

10.1093/gerona/glaa324 ◽

2020 ◽

Author(s):

Yuko Yamaguchi ◽

Marta Zampino ◽

Toshiko Tanaka ◽

Stefania Bandinelli ◽

Yusuke Osawa ◽

...

Keyword(s):

Older Adults ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Differentiation Factor ◽

Hazards Model ◽

Increased Risk ◽

The Relationship

Abstract Background Anemia is common in older adults and associated with greater morbidity and mortality. The causes of anemia in older adults have not been completely characterized. Although elevated circulating growth and differentiation factor 15 (GDF-15) has been associated with anemia in older adults, it is not known whether elevated GDF-15 predicts the development of anemia. Methods We examined the relationship between plasma GDF-15 concentrations at baseline in 708 non-anemic adults, aged 60 years and older, with incident anemia during 15 years of follow-up among participants in the Invecchiare in Chianti (InCHIANTI) Study. Results During follow-up, 179 (25.3%) participants developed anemia. The proportion of participants who developed anemia from the lowest to highest quartile of plasma GDF-15 was 12.9%, 20.1%, 21.2%, and 45.8%, respectively. Adults in the highest quartile of plasma GDF-15 had an increased risk of developing anemia (Hazards Ratio 1.15, 95% Confidence Interval 1.09, 1.21, P<.0001) compared to those in the lower three quartiles in a multivariable Cox proportional hazards model adjusting for age, sex, serum iron, soluble transferrin receptor, ferritin, vitamin B12, congestive heart failure, diabetes mellitus, and cancer. Conclusions Circulating GDF-15 is an independent predictor for the development of anemia in older adults.

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Sex-Specific Associations between Blood Pressure and Risk of Atrial Fibrillation Subtypes in the Tromsø Study

Journal of Clinical Medicine ◽

10.3390/jcm10071514 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1514

Author(s):

Hilde Espnes ◽

Jocasta Ball ◽

Maja-Lisa Løchen ◽

Tom Wilsgaard ◽

Inger Njølstad ◽

...

Keyword(s):

Atrial Fibrillation ◽

Blood Pressure ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Pressure Management ◽

Reference Models ◽

Proportional Hazards Regression ◽

Hazard Ratios ◽

Increased Risk

The aim of this study was to explore sex-specific associations between systolic blood pressure (SBP), hypertension, and the risk of incident atrial fibrillation (AF) subtypes, including paroxysmal, persistent, and permanent AF, in a general population. A total of 13,137 women and 11,667 men who participated in the fourth survey of the Tromsø Study (1994–1995) were followed up for incident AF until the end of 2016. Cox proportional hazards regression analysis was conducted using fractional polynomials for SBP to provide sex- and AF-subtype-specific hazard ratios (HRs) for SBP. An SBP of 120 mmHg was used as the reference. Models were adjusted for other cardiovascular risk factors. Over a mean follow-up of 17.6 ± 6.6 years, incident AF occurred in 914 (7.0%) women (501 with paroxysmal/persistent AF and 413 with permanent AF) and 1104 (9.5%) men (606 with paroxysmal/persistent AF and 498 with permanent AF). In women, an SBP of 180 mmHg was associated with an HR of 2.10 (95% confidence interval [CI] 1.60–2.76) for paroxysmal/persistent AF and an HR of 1.80 (95% CI 1.33–2.44) for permanent AF. In men, an SBP of 180 mmHg was associated with an HR of 1.90 (95% CI 1.46–2.46) for paroxysmal/persistent AF, while there was no association with the risk of permanent AF. In conclusion, increasing SBP was associated with an increased risk of both paroxysmal/persistent AF and permanent AF in women, but only paroxysmal/persistent AF in men. Our findings highlight the importance of sex-specific risk stratification and optimizing blood pressure management for the prevention of AF subtypes in clinical practice.

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Association of oral contraceptives and tubal ligation with risk of early natural menopause

Human Reproduction ◽

10.1093/humrep/deab054 ◽

2021 ◽

Author(s):

C R Langton ◽

B W Whitcomb ◽

A C Purdue-Smithe ◽

L L Sievert ◽

S E Hankinson ◽

...

Keyword(s):

Oral Contraceptives ◽

Proportional Hazards ◽

Reproductive Factors ◽

Cox Proportional Hazards ◽

Tubal Ligation ◽

Health Study ◽

Early Menopause ◽

Natural Menopause ◽

Increased Risk

Abstract STUDY QUESTION What is the association of oral contraceptives (OCs) and tubal ligation (TL) with early natural menopause? SUMMARY ANSWER We did not observe an association of OC use with risk of early natural menopause; however, TL was associated with a modestly higher risk. WHAT IS KNOWN ALREADY OCs manipulate hormone levels, prevent ovulation, and may modify the rate of follicular atresia, while TL may disrupt the blood supply to the ovaries. These mechanisms may be associated with risk of early menopause, a condition associated with increased risk of cardiovascular disease and other adverse health outcomes. STUDY DESIGN, SIZE, DURATION We examined the association of OC use and TL with natural menopause before the age of 45 years in a population-based study within the prospective Nurses’ Health Study II (NHSII) cohort. Participants were followed from 1989 to 2017 and response rates were 85-90% for each cycle. PARTICIPANTS/MATERIALS, SETTING, METHODS Participants included 106 633 NHSII members who were premenopausal and aged 25-42 years at baseline. Use, duration and type of OC, and TL were measured at baseline and every 2 years. Menopause status and age were assessed every 2 years. Follow-up continued until early menopause, age 45 years, hysterectomy, oophorectomy, death, cancer diagnosis, or loss to follow-up. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CIs adjusted for lifestyle, dietary, and reproductive factors. MAIN RESULTS AND THE ROLE OF CHANCE Over 1.6 million person-years, 2579 members of the analytic cohort experienced early natural menopause. In multivariable models, the duration, timing, and type of OC use were not associated with risk of early menopause. For example, compared with women who never used OCs, those reporting 120+ months of OC use had an HR for early menopause of 1.01 (95% CI, 0.87-1.17; P for trend=0.71). TL was associated with increased risk of early menopause (HR = 1.17, 95% CI, 1.06-1.28). LIMITATIONS, REASONS FOR CAUTION Our study population is homogenous with respect to race and ethnicity. Additional evaluation of these relations in more diverse populations is important. WIDER IMPLICATIONS OF THE FINDINGS To our knowledge, this is the largest study examining the association of OC use and TL with early natural menopause to date. While TL was associated with a modest higher risk of early menopause, our findings do not support any material hazard or benefit for the use of OCs. STUDY FUNDING/COMPETING INTEREST(S) The study was sponsored by UO1CA176726 and R01HD078517 from the National Institutes of Health and Department of Health and Human Services. The work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors have no competing interests to report. TRIAL REGISTRATION NUMBER N/A

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Cognitive dispersion and ApoEe4 genotype predict dementia diagnosis in 8-year follow-up of the oldest-old

Age and Ageing ◽

10.1093/ageing/afaa232 ◽

2020 ◽

Author(s):

Tam Watermeyer ◽

Jantje Goerdten ◽

Boo Johansson ◽

Graciela Muniz-Terrera

Keyword(s):

Cognitive Performance ◽

Cox Regression ◽

Oldest Old ◽

Cost Effective ◽

Carrier Status ◽

Dementia Diagnosis ◽

Cognitive Domains ◽

Dementia Incidence ◽

Composite Scores

Abstract Background Cognitive dispersion, or inconsistencies in performance across cognitive domains, has been posited as a cost-effective tool to predict conversion to dementia in older adults. However, there is a dearth of studies exploring cognitive dispersion in the oldest-old (>80 years) and its relationship to dementia incidence. Objective The main aim of this study was to examine whether higher cognitive dispersion at baseline was associated with dementia incidence within an 8-year follow-up of very old adults, while controlling for established risk factors and suggested protective factors for dementia. Methods Participants (n = 468) were from the Origins of Variance in the Old-Old: Octogenarian Twins study, based on the Swedish Twin Registry. Cox regression analyses were performed to assess the association between baseline cognitive dispersion scores and dementia incidence, while controlling for sociodemographic variables, ApoEe4 carrier status, co-morbidities, zygosity and lifestyle engagement scores. An additional model included a composite of average cognitive performance. Results Cognitive dispersion and ApoEe4 were significantly associated with dementia diagnosis. These variables remained statistically significant when global cognitive performance was entered into the model. Likelihood ratio tests revealed that cognitive dispersion and cognitive composite scores entered together in the same model was superior to either predictor alone in the full model. Conclusions The study underscores the usefulness of cognitive dispersion metrics for dementia prediction in the oldest-old and highlights the influence of ApoEe4 on cognition in very late age. Our findings concur with others suggesting that health and lifestyle factors pose little impact upon cognition in very advanced age.

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Abstract P169: Health Literacy and Outcomes in Heart Failure: a Prospective Community Study

Circulation ◽

10.1161/circ.135.suppl_1.p169 ◽

2017 ◽

Vol 135 (suppl_1) ◽

Author(s):

Matteo Fabbri ◽

Kathleen Yost ◽

Lila Finney Rutten ◽

Sheila Manemann ◽

Susan Weston ◽

...

Keyword(s):

Heart Failure ◽

Health Literacy ◽

Proportional Hazards ◽

International Classification Of Diseases ◽

Cox Proportional Hazards ◽

Low Literacy ◽

Adequate Health Literacy ◽

Low Health Literacy ◽

Increased Risk

Background: Growing evidence documents the association between low health literacy and poorer health outcomes. However, less is known about the relationship between health literacy and outcomes among patients with heart failure (HF). We examined the association of health literacy with risk of hospitalization and mortality in patients with HF. Methods: Residents in an 11-county region in southeastern Minnesota with incident HF from 1/01/2013 to 3/31/2015 were identified using the International Classification of Diseases, Ninth Revision code 428 (n=3715) and prospectively surveyed to measure health literacy using established screening questions. A total of 1992 patients returned a survey (response rate 54%); 1779 patients with complete clinical data and adequate follow up were retained for analysis. Health literacy, measured as a composite on three 5-point scales, was categorized as adequate (≤ 10) or low (> 10). Cox proportional hazards regression and Andersen-Gill models were used to determine the association of health literacy with mortality and hospitalization. Results: Among 1779 patients (mean age 74, 53% male), 10% had low health literacy. After a mean follow-up of 8±4 months, 72 deaths and 600 hospitalizations occurred. Low health literacy was associated with increased mortality and hospitalizations (Figure). After adjusting for age, sex, comorbidity, education and marital status, the hazard ratio for death and hospitalization in patients with low health literacy was 2.84 (95% CI: 1.63, 4.96) and 1.43 (95% CI: 1.04, 1.96) respectively, compared to patients with adequate health literacy. Conclusions: Low health literacy is associated with increased risk of hospitalization and death among patients with HF. Health literacy is critical to the self-management demands of living with heart failure. Evaluation of health literacy in the clinical setting may guide inventions to target patients with low literacy.

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Diet Inflammatory Index and Dementia Incidence: A Population-Based Study

Neurology ◽

10.1212/wnl.0000000000012973 ◽

2021 ◽

pp. 10.1212/WNL.0000000000012973

Author(s):

Sokratis Charisis ◽

Eva Ntanasi ◽

Mary Yannakoulia ◽

Costas A Anastasiou ◽

Mary H Kosmidis ◽

...

Keyword(s):

Proportional Hazards ◽

Population Based ◽

Cox Proportional Hazards ◽

Community Dwelling ◽

Dietary Interventions ◽

Clinical Criteria ◽

Inflammatory Index ◽

Incident Dementia ◽

Dementia Incidence ◽

Increased Risk

Background and objectives:Aging is characterized by a functional shift of the immune system towards a proinflammatory phenotype. This derangement has been associated with cognitive decline and has been implicated in the pathogenesis of dementia. Diet can modulate systemic inflammation; thus, it may be a valuable tool to counteract the associated risks for cognitive impairment and dementia. The present study aimed to explore the associations between the inflammatory potential of diet, assessed using an easily applicable, population-based, biomarker-validated diet inflammatory index (DII), and the risk for dementia in community-dwelling older adults.Methods:Individuals from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) were included in the present cohort study. Participants were recruited through random population sampling, and were followed for a mean of 3.05 (SD=0.85) years. Dementia diagnosis was based on standard clinical criteria. Those with baseline dementia and/or missing cognitive follow-up data were excluded from the analyses. The inflammatory potential of diet was assessed through a DII score which considers literature-derived associations of 45 food parameters with levels of pro- and anti-inflammatory cytokines in the blood; higher values indicated a more pro-inflammatory diet. Consumption frequencies were derived from a detailed food frequency questionnaire, and were standardized to representative dietary intake normative data from 11 different countries. Analysis of dementia incidence as a function of baseline DII scores was performed by Cox proportional hazards models.Results:Analyses included 1059 individuals (mean age=73.1 years; 40.3% males; mean education=8.2 years), 62 of whom developed incident dementia. Each additional unit of DII was associated with a 21% increase in the risk for dementia incidence [HR=1.21 (1.03 – 1.42); p=0.023]. Compared to participants in the lowest DII tertile, participants in the highest one (maximal pro-inflammatory diet potential) were 3 [(1.2 – 7.3); p=0.014] times more likely to develop incident dementia. The test for trend was also significant, indicating a potential dose-response relationship (p=0.014).Conclusions:In the present study, higher DII scores (indicating greater pro-inflammatory diet potential) were associated with an increased risk for incident dementia. These findings might avail the development of primary dementia preventive strategies through tailored and precise dietary interventions.

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Association of poor sleep burden in middle age and older adults with risk for delirium during hospitalization

The Journals of Gerontology Series A ◽

10.1093/gerona/glab272 ◽

2021 ◽

Author(s):

Ma Cherrysse Ulsa ◽

Xi Zheng ◽

Peng Li ◽

Arlen Gaba ◽

Patricia M Wong ◽

...

Keyword(s):

Sleep Disturbances ◽

Proportional Hazards ◽

Time Lag ◽

Cox Proportional Hazards ◽

Poor Sleep ◽

Cardiovascular Risks ◽

Cox Proportional Hazards Models ◽

Increased Risk ◽

The Uk

Abstract Background Delirium is a distressing neurocognitive disorder recently linked to sleep disturbances. However, the longitudinal relationship between sleep and delirium remains unclear. This study assessed the associations of poor sleep burden, and its trajectory, with delirium risk during hospitalization. Methods 321,818 participants from the UK Biobank (mean age 58±8y[SD]; range 37-74y) reported (2006-2010) sleep traits (sleep duration, excessive daytime sleepiness, insomnia-type complaints, napping, and chronotype–a closely-related circadian measure for sleep timing), aggregated into a sleep burden score (0-9). New-onset delirium (n=4,775) was obtained from hospitalization records during 12y median follow-up. 42,291 (mean age 64±8; range 44-83y) had repeat sleep assessment on average 8y after their first. Results In the baseline cohort, Cox proportional hazards models showed that moderate (aggregate scores=4-5) and severe (scores=6-9) poor sleep burden groups were 18% (hazard ratio 1.18 [95% confidence interval 1.08-1.28], p<0.001) and 57% (1.57 [1.38-1.80], p<0.001), more likely to develop delirium respectively. The latter risk magnitude is equivalent to two additional cardiovascular risks. These findings appeared robust when restricted to postoperative delirium and after exclusion of underlying dementia. Higher sleep burden was also associated with delirium in the follow-up cohort. Worsening sleep burden (score increase ≥2 vs. no change) further increased the risk for delirium (1.79 [1.23-2.62], p=0.002) independent of their baseline sleep score and time-lag. The risk was highest in those under 65y at baseline (p for interaction <0.001). Conclusion Poor sleep burden and worsening trajectory were associated with increased risk for delirium; promotion of sleep health may be important for those at higher risk.

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Supper Timing and Cardiovascular Mortality: The Japan Collaborative Cohort Study

Nutrients ◽

10.3390/nu13103389 ◽

2021 ◽

Vol 13 (10) ◽

pp. 3389

Author(s):

Jingyun Tang ◽

Jia-Yi Dong ◽

Ehab S. Eshak ◽

Renzhe Cui ◽

Kokoro Shirai ◽

...

Keyword(s):

Hemorrhagic Stroke ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Stroke Mortality ◽

Hazard Ratios ◽

Risk Of Mortality ◽

Increased Risk ◽

Study Participants

Evidence on the role of supper timing in the development of cardiovascular disease (CVD) is limited. In this study, we examined the associations between supper timing and risks of mortality from stroke, coronary heart disease (CHD), and total CVD. A total of 28,625 males and 43,213 females, aged 40 to 79 years, free from CVD and cancers at baseline were involved in this study. Participants were divided into three groups: the early supper group (before 8:00 p.m.), the irregular supper group (time irregular), and the late supper group (after 8:00 p.m.). Cox proportional hazards regression models were used to calculate hazard ratios (HRs) for stroke, CHD, and total CVD according to the supper time groups. During the 19-year follow-up, we identified 4706 deaths from total CVD. Compared with the early supper group, the multivariable HR of hemorrhagic stroke mortality for the irregular supper group was 1.44 (95% confidence interval [CI]: 1.05–1.97). There was no significant association between supper timing and the risk of mortality from other types of stroke, CHD, and CVD. We found that adopting an irregular supper timing compared with having dinner before 8:00 p.m. was associated with an increased risk of hemorrhagic stroke mortality.

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Abstract 2646: Aortic Arch Plaques and Risk of Vascular Events in Subjects Without Prior Stroke

Circulation ◽

10.1161/circ.118.suppl_18.s_760 ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Cesare Russo ◽

Zhezhen Jin ◽

Ralph L Sacco ◽

Shunichi Homma ◽

Tatjana Rundek ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Aortic Arch ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Study Cohort ◽

Vascular Events ◽

Increased Risk ◽

Prior Stroke

BACKGROUND: Aortic arch plaques (AAP) are a risk factor for cardiovascular embolic events. However, the risk of vascular events associated with AAP in the general population is unclear. AIM: To assess whether AAP detected by transesophageal echocardiography (TEE) are associated with an increased risk of vascular events in a stroke-free cohort. METHODS: The study cohort consisted of stroke-free subjects over age 50 from the Aortic Plaques and Risk of Ischemic Stroke (APRIS) study. AAP were assessed by multiplane TEE, and considered large if ≥ 4 mm in thickness. Vascular events including myocardial infarction, ischemic stroke and vascular death were recorded during the follow-up. The association between AAP and outcomes was assessed by univariate and multivariate Cox proportional hazards models. RESULTS: A group of 209 subjects was studied (mean age 67±9 years; 45% women; 14% whites, 30% blacks, 56% Hispanics). AAP of any size were present in 130 subjects (62%); large AAP in 50 (24%). Subjects with AAP were older (69±8 vs. 63±7 years), had higher systolic BP (146±21 vs.139±20 mmHg), were more often white (19% vs. 8%), smokers (20% vs. 9%) and more frequently had a history of coronary artery disease (26% vs. 14%) than those without AAP (all p<0.05). Lipid parameters, prevalence of atrial fibrillation and diabetes mellitus were not significantly different between the two groups. During the follow up (94±29 months) 30 events occurred (13 myocardial infarctions, 11 ischemic strokes, 6 vascular deaths). After adjustment for other risk factors, AAP of any size were not associated with an increased risk of combined vascular events (HR 1.07, 95% CI 0.44 to 2.56). The same result was observed for large AAP (HR 0.94, CI 0.34 to 2.64). Age (HR 1.05, CI 1.01 to 1.10), body mass index (HR 1.08, CI 1.01 to 1.15) and atrial fibrillation (HR 3.52, CI 1.07 to 11.61) showed independent association with vascular events. In a sub-analysis with ischemic stroke as outcome, neither AAP of any size nor large AAP were associated with an increased risk. CONCLUSIONS: In this cohort without prior stroke, the incidental detection of AAP was not associated with an increased risk of future vascular events. Associated co-factors may affect the AAP-related risk of vascular events reported in previous studies.

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