Circulatory MicroRNAs in Plasma and Atrial Fibrillation in the General Population: The Rotterdam Study

Background: MicroRNAs (miRNAs), small non-coding RNAs regulating gene expression, have been shown to play an important role in cardiovascular disease. However, limited population-based data regarding the relationship between circulatory miRNAs in plasma and atrial fibrillation (AF) exist. Moreover, it remains unclear if the relationship differs by sex. We therefore aimed to determine the (sex-specific) association between plasma circulatory miRNAs and AF at the population level. Methods: Plasma levels of miRNAs were measured using a targeted next-generation sequencing method in 1999 participants from the population-based Rotterdam Study. Logistic regression and Cox proportional hazards models were used to assess the associations of 591 well-expressed miRNAs with the prevalence and incidence of AF. Models were adjusted for cardiovascular risk factors. We further examined the link between predicted target genes of the identified miRNAs. Results: The mean age was 71.7 years (57.1% women), 98 participants (58 men and 40 women) had prevalent AF at baseline. Moreover, 196 participants (96 men and 100 women) developed AF during a median follow-up of 9.0 years. After adjusting for multiple testing, miR-4798-3p was significantly associated with the odds of prevalent AF among men (odds ratio, 95% confidence interval, 0.39, 0.24–0.66, p-value = 0.000248). No miRNAs were significantly associated with incident AF. MiR-4798-3p could potentially regulate the expression of a number of AF-related genes, including genes involved in calcium and potassium handling in myocytes, protection of cells against oxidative stress, and cardiac fibrosis. Conclusions: Plasma levels of miR-4798-3p were significantly associated with the odds of prevalent AF among men. Several target genes in relation to AF pathophysiology could potentially be regulated by miR-4798-3p that warrant further investigations in future experimental studies.

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Association between circulatory microRNAs in plasma and atrial fibrillation among men and women from the general population

European Journal of Preventive Cardiology ◽

10.1093/eurjpc/zwab061.170 ◽

2021 ◽

Vol 28 (Supplement_1) ◽

Author(s):

S Geurts ◽

MMJ Mens ◽

MM Bos ◽

MA Ikram ◽

M Ghanbari ◽

...

Keyword(s):

Atrial Fibrillation ◽

General Population ◽

Plasma Levels ◽

Target Genes ◽

Cardiac Fibrosis ◽

Medical Center ◽

Experimental Studies ◽

Population Based ◽

Public Institution ◽

Men And Women

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. This project is further supported by the Gender and Prevention grant (555003017) from ZonMw. Background MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression. They have shown to play an important role in cardiovascular disease, but there is limited population-based data regarding the relationship between circulatory miRNAs in plasma and atrial fibrillation (AF). Moreover, it remains unclear if the associations between miRNAs with AF differ by sex. Purpose To determine the association of miRNAs with the risk of prevalent and incident AF among men and women from the general population. Methods Plasma levels of circulatory miRNAs were measured in 858 men and 1141 women from a large prospective population-based cohort study. Logistic regression and Cox Proportional Hazards models were used to assess the associations of 591 well-expressed miRNAs with the prevalence and incidence of AF. Models were adjusted for age and cardiovascular risk factors. We further examined the link between predicted target genes of identified miRNAs and AF. Results The mean age was 71.7 years (57.1% women), 58 men and 40 women had prevalent AF at baseline. Moreover, 96 men and 100 women developed AF during a median follow-up of 9.0 years. After adjusting for multiple testing, miR-4798-3p was significantly associated with prevalent AF among men; odds ratio: 0.39 (95% CI 0.24-0.66). No miRNAs were significantly associated with incident AF. MiR-4798-3p could potentially regulate the expression of AF-related genes, including genes involved in calcium and potassium handling in myocytes, protection of cells against oxidative stress, and cardiac fibrosis. Conclusions Plasma levels of miR-4798-3p were significantly associated with prevalent AF among men. Various target genes in relation to AF pathophysiology could potentially be regulated by miR-4798-3p that warrant further investigations in future experimental studies.

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Physical activity types and atrial fibrillation risk in the middle-aged and elderly: The Rotterdam Study

European Journal of Preventive Cardiology ◽

10.1177/2047487318780031 ◽

2018 ◽

Vol 25 (12) ◽

pp. 1316-1323 ◽

Cited By ~ 7

Author(s):

Marijn Albrecht ◽

Chantal M Koolhaas ◽

Josje D Schoufour ◽

Frank JA van Rooij ◽

M Kavousi ◽

...

Keyword(s):

Physical Activity ◽

Atrial Fibrillation ◽

Proportional Hazards ◽

Population Based ◽

Cox Proportional Hazards ◽

Total Physical Activity ◽

Rotterdam Study ◽

Cox Proportional Hazards Models ◽

Activity Types ◽

Study Population

Background The association between physical activity and atrial fibrillation remains controversial. Physical activity has been associated with a higher and lower atrial fibrillation risk. These inconsistent results might be related to the type of physical activity. We aimed to investigate the association of total and types of physical activity, including walking, cycling, domestic work, gardening and sports, with atrial fibrillation. Design Prospective cohort study. Methods Our study was performed in the Rotterdam Study, a prospective population-based cohort. We included 7018 participants aged 55 years and older with information on physical activity between 1997–2001. Cox proportional hazards models were used to examine the association of physical activity with atrial fibrillation risk. Models were adjusted for biological and behavioural risk factors and the remaining physical activity types. Physical activity was categorised in tertiles and the low group was used as reference. Results During 16.8 years of follow-up (median: 12.3 years, interquartile range: 8.7–15.9 years), 800 atrial fibrillation events occurred (11.4% of the study population). We observed no association between total physical activity and atrial fibrillation risk in any model. After adjustment for confounders, the hazard ratio and 95% confidence interval for the high physical activity category compared to the low physical activity category was: 0.71 (0.80–1.14) for total physical activity. We did not observe a significant association between any of the physical activity types with atrial fibrillation risk. Conclusion Our results suggest that physical activity is not associated with higher or lower risk of atrial fibrillation in older adults. Neither total physical activity nor any of the included physical activity types was associated with atrial fibrillation risk.

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Abstract P005: Comparative Effectiveness of Rivaroxaban versus Warfarin for the Treatment of Patients with Non-valvular Atrial Fibrillation

Circulation ◽

10.1161/circ.133.suppl_1.p005 ◽

2016 ◽

Vol 133 (suppl_1) ◽

Author(s):

Faye L Norby ◽

Lindsay G Bengtson ◽

Lin Y Chen ◽

Richard F MacLehose ◽

Pamela L Lutsey ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Real World ◽

Proportional Hazards ◽

Large Population ◽

Population Based ◽

Cox Proportional Hazards ◽

Gi Bleeding ◽

Cox Proportional Hazards Models ◽

The Us

Background: Rivaroxaban is a novel oral anticoagulant approved in the US in 2011 for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF). Information on risks and benefits among rivaroxaban users in real-world populations is limited. Methods: We used data from the US MarketScan Commercial and Medicare Supplemental databases between 2010 and 2013. We selected patients with a history of NVAF and initiating rivaroxaban or warfarin. Rivaroxaban users were matched with up to 5 warfarin users by age, sex, database enrollment date and drug initiation date. Ischemic stroke, intracranial bleeding (ICB), myocardial infarction (MI), and gastrointestinal (GI) bleeding outcomes were defined by ICD-9-CM codes in an inpatient claim after drug initiation date. Cox proportional hazards models were used to assess the association between rivaroxaban vs. warfarin use and outcomes adjusting for age, sex, and CHA2DS2-VASc score. Separate models were used to compare a) new rivaroxaban users with new warfarin users, and b) switchers from warfarin to rivaroxaban to continuous warfarin users. Results: Our analysis included 34,998 rivaroxaban users matched to 102,480 warfarin users with NVAF (39% female, mean age 71), in which 487 ischemic strokes, 179 ICB, 647 MI, and 1353 GI bleeds were identified during a mean follow-up of 9 months. Associations of rivaroxaban vs warfarin were similar in new users and switchers; therefore we pooled both analyses. Rivaroxaban users had lower rates of ICB (hazard ratio (HR) (95% confidence interval (CI)) = 0.72 (0.46, 1.12))) and ischemic stroke (HR (95% CI) = 0.88 (0.68, 1.13)), but higher rates of GI bleeding (HR (95% CI) = 1.15 (1.01, 1.33)) when compared to warfarin users (table). Conclusion: In this large population-based study of NVAF patients, rivaroxaban users had a non-significant lower risk of ICB and ischemic stroke than warfarin users, but a higher risk of GI bleeding. These real-world findings are comparable to results reported in published clinical trials.

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Empowering thyroid hormone research in human subjects using OMICs technologies

Journal of Endocrinology ◽

10.1530/joe-18-0117 ◽

2018 ◽

Vol 238 (1) ◽

pp. R13-R29 ◽

Cited By ~ 10

Author(s):

Maik Pietzner ◽

Tim Kacprowski ◽

Nele Friedrich

Keyword(s):

Thyroid Hormone ◽

Thyroid Hormones ◽

Target Genes ◽

Human Subjects ◽

Experimental Studies ◽

Analytical Techniques ◽

Population Based ◽

Whole Body ◽

Hormone Research ◽

Whole Body Metabolism

OMICs subsume different physiological layers including the genome, transcriptome, proteome and metabolome. Recent advances in analytical techniques allow for the exhaustive determination of biomolecules in all OMICs levels from less invasive human specimens such as blood and urine. Investigating OMICs in deeply characterized population-based or experimental studies has led to seminal improvement of our understanding of genetic determinants of thyroid function, identified putative thyroid hormone target genes and thyroid hormone-induced shifts in the plasma protein and metabolite content. Consequently, plasma biomolecules have been suggested as surrogates of tissue-specific action of thyroid hormones. This review provides a brief introduction to OMICs in thyroid research with a particular focus on metabolomics studies in humans elucidating the important role of thyroid hormones for whole body metabolism in adults.

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Disparities in receipt of radiotherapy and survival by age, sex, and race among patients with nonmetastatic squamous cell carcinoma of the anus.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.721 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 721-721

Author(s):

Doug Baughman ◽

Krishna Bilas Ghimire ◽

Binay Kumar Shah

Keyword(s):

Proportional Hazards ◽

Proportional Hazards Model ◽

Survival Rates ◽

Relative Survival ◽

Population Based ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

P Value ◽

Hazards Model ◽

To Receive

721 Background: Combination chemoradiotherapy is the standard of care for treatment of non-metastatic squamous cell carcinoma of the anus (SCCA). This population-based study evaluated disparities in receipt of radiotherapy (RT) and its effect on survival in patients with localized and regional SCCA in the United States. Methods: The Surveillance, Epidemiology, and End Results (SEER) 18 database was used to identify patients with localized and regional SCCA diagnosed between 1998 and 2008. We used univariate and multivariate logistic regression to model the relationships between receipt of RT and age, sex, marital status, stage, and race. Relative survival rates were calculated and compared using two sample z-tests. A Cox proportional hazards model was used to find adjusted hazard ratios (HR). Results: A total of 3,971 patients with localized or regional SCCA as the only primary malignancy were included in the study, of which 3,278 (82.6%) received RT. After adjusting for covariates, those 65 years and older (adjusted OR 0.82, p=0.029) were less likely to receive RT. Females were more likely to receive RT compared to males (adjusted OR 1.54, p<0.001). We found no difference in receipt of RT by race. Comparisons of 1- and 5-year relative survival rates showed lower survival for blacks (p-value <0.01 at 1-year and <0.0001 at 5-years), those 65 years and older, and males. A 1-year survival disparity was found for those not receiving RT (p-value <0.0001 at 1-year), but no difference was observed at 5-years. A Cox proportional hazards model adjusting for all covariates showed greater hazard for blacks (adjusted HR 1.36, p=0.001), those not receiving RT (adjusted HR 1.23, p=0.03), patients 65 years or older, and males. Conclusions: This population based study identified older patients as less likely to receive RT and females as more likely to receive RT. Survival analysis identified blacks, males, older patients, and those not receiving RT as having lower rates of survival.

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Examining the Relationship between Heavy Alcohol Use and Assaults: With Adjustment for the Effects of Unmeasured Confounders

BioMed Research International ◽

10.1155/2015/596179 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

Wenbin Liang ◽

Tanya Chikritzhs

Keyword(s):

Alcohol Use ◽

Randomized Clinical Trials ◽

Experimental Studies ◽

Real Life ◽

Population Based ◽

Population Based Study ◽

Heavy Alcohol ◽

Heavy Alcohol Use ◽

The Relationship ◽

Unmeasured Confounders

Background. Experimental studies suggest that alcohol can lead to aggression in laboratory settings; however, it is impossible to test the causal relationship between alcohol use and real-life violence among humans in randomized clinical trials.Objectives. (i) To examine the relationship between heavy alcohol use and assaults in a population based study; (ii) to demonstrate the proxy outcome method, as a means of controlling the effects of unknown/unmeasured confounders in observational studies.Methods. This study used data collected from three waves of the National Survey on Drug Use and Health (NSDUH). The effects of heavy alcohol use on assault were measured using multivariable logistic regressions in conjunction with the proxy outcome method.Results. Application of the proxy outcome method indicated that effect sizes of heavy alcohol use on the risk of assault were overestimated in the standard models. After adjusting for the effects of unknown/unmeasured confounders, the risk of assault remained 43% and 63% higherP<0.05among participants who consumed 5+ drinks/day for 5–8 days/month and 9–30 days/month, respectively.Conclusions. Even after adjustment for unknown/unmeasured confounders the association between heavy alcohol use and risk of violence remained significant. These findings support the hypothesis that heavy alcohol use can cause violence.

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Evaluation of hyperalgesic effect of sitagliptin in albino mice

IP International Journal of Comprehensive and Advanced Pharmacology ◽

10.18231/j.ijcaap.2021.025 ◽

2021 ◽

Vol 6 (3) ◽

pp. 140-143

Author(s):

Lalit Mohan ◽

Manoj Kumar ◽

Manish Kumar ◽

Saajid Hameed ◽

Amritanshu Shekhar

Keyword(s):

Acetic Acid ◽

Experimental Studies ◽

P Value ◽

Distilled Water ◽

Hot Plate ◽

Plate Method ◽

Writhing Test ◽

Albino Mice ◽

The Relationship ◽

Rule Out

Various studies have showed the increased incidence of joint pain with the use of DPP-4 inhibitors. There is also some evidence of increase in inflammatory mediators like substance P, SDF-1 and other cytokines with the inhibition of DPP-4 from some experimental studies. But this association is still unclear and DPP-4 inhibitor continue to be prescribed in inflammatory disorders. So, this study was planned to assess the development of hyperalgesia in albino mice with the use of sitagliptin.Sitagliptin dissolved in saline was administered in the doses of 10, 20, 30 mg/kg to Albino mice of either sex weighing 25-30 gm. Hyperalgesia was assessed in the mice with hot plate method and acetic acid induced writhing test. We found that reaction time of the mice receiving higher dose of Sitagliptin in hot plate method was lower than that of mice receiving lower doses or distilled water (P-Value <0.05). We also found that after injection of acetic acid, the number of writhing observed in the mice receiving higher dose of Sitagliptin was greater than that of mice receiving lower doses or distilled water (P-Value <0.05). Our findings show that in a cohort of mice receiving Sitagliptin and distilled water at baseline, there was significant association between dose of Sitagliptin and hyperalgesia. However, P-Value was greater than 0.01, but with these finding we can’t rule out this association and need for further prospective studies to assess the relationship between DPP-4 inhibitors and hyperalgesia.

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Insomnia in the context of short sleep increases suicide risk

SLEEP ◽

10.1093/sleep/zsaa245 ◽

2020 ◽

Author(s):

Hedström Anna Karin ◽

Ola Hössjer ◽

Rino Bellocco ◽

Weimin Ye ◽

Lagerros Ylva Trolle ◽

...

Keyword(s):

Sleep Duration ◽

Suicide Risk ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Total Effect ◽

P Value ◽

Short Sleep ◽

Cox Proportional Hazards Models ◽

The Relationship ◽

Insomnia Symptoms

Abstract Study Objectives The relationship between insomnia and suicide risk is not completely understood. We aimed to investigate the influence of insomnia on suicide risk, taking both sleep duration and depression into consideration. Methods The present study is based on a Swedish prospective cohort study of 38,786 participants with a mean follow-up time of 19.2 years. Cox proportional hazards models with attained age as time-scale were used to estimate hazard ratios (HRs) of death by suicide with 95% confidence intervals (CI) for participants categorized by frequency of insomnia symptoms. Causal mediation analysis was performed to assess to what extent the relationship between insomnia and suicide risk is mediated by depression. Results Insomnia was only associated with suicide risk among short sleepers, whereas no significant association was observed among those who slept 7 h/night or more. The total effect of insomnia in the context of short sleep on suicide risk, expressed on the HR scale, was 2.85 (95% CI 1.42–5.74). The direct effect was 2.25 (95% CI 1.12–4.54) and the indirect effect, mediated by depression, was 1.27 (95% CI 1.05–1.53). Of the total effect, 32% was mediated by depression. The association between insomnia and suicide risk became more pronounced with decreasing depressive symptoms (p value for trend <0.05). Conclusions Insomnia in the context of short sleep increases suicide risk, both directly and indirectly by affecting the risk of depression. Abnormalities of sleep duration and insomnia symptoms should be evaluated when assessing suicide risk.

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Association of irritable bowel syndrome in patients with atrial fibrillation: a nationwide population-based investigation

Perfusion ◽

10.1177/0267659120912363 ◽

2020 ◽

Vol 35 (8) ◽

pp. 847-852

Author(s):

Wei-Syun Hu ◽

Cheng-Li Lin

Keyword(s):

Atrial Fibrillation ◽

Irritable Bowel Syndrome ◽

Proportional Hazards ◽

Female Gender ◽

Population Based ◽

Cox Proportional Hazards ◽

Regression Methods ◽

Proportional Hazards Regression ◽

Kaplan Meier ◽

Irritable Bowel

Objective: We seek to characterize the association between atrial fibrillation and irritable bowel syndrome. Methods: We identify 11,642 cases (atrial fibrillation) and 46,487 sex-, age-, and index year–matched controls (non-atrial fibrillation) from Longitudinal Health Insurance Database. Kaplan–Meier, Cox proportional hazards regression methods and competing risk analysis methods were used to assess the association of atrial fibrillation with outcome of irritable bowel syndrome. Results: After adjustment for gender, age, comorbidities and medications, patients with atrial fibrillation had a significant higher risk (adjusted hazard ratio = 1.12, p < 0.01) to develop irritable bowel syndrome than patients without atrial fibrillation. Compared to participants without atrial fibrillation, those with atrial fibrillation had 1.13-fold (p < 0.05) and 1.11-fold (p < 0.05) risk of irritable bowel syndrome in female and male subgroup, respectively. Among subjects aged ≥65 years, those with AF had 1.11-fold risk of irritable bowel syndrome than non-AF cohort (P < 0.01). Among participants with any one of the comorbidities, those with atrial fibrillation had 1.10-fold risk of irritable bowel syndrome than non-atrial fibrillation cohort (p < 0.05). Conclusion: We report that the presence of atrial fibrillation is associated with greater incidence of irritable bowel syndrome and the association is stronger among female gender, age 65 years or above, and with comorbidities.

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Atrial fibrillation and cardiac fibrosis

European Heart Journal ◽

10.1093/eurheartj/ehz786 ◽

2019 ◽

Vol 41 (10) ◽

pp. 1123-1131 ◽

Cited By ~ 15

Author(s):

Christian Sohns ◽

Nassir F Marrouche

Keyword(s):

Atrial Fibrillation ◽

Cardiac Fibrosis ◽

Resonance Imaging ◽

Powerful Predictor ◽

Gadolinium Enhancement ◽

Complex Concept ◽

Clinical Observations ◽

Multicentre Trials ◽

The Individual ◽

The Relationship

Abstract The understanding of atrial fibrillation (AF) evolved from a sole rhythm disturbance towards the complex concept of a cardiomyopathy based on arrhythmia substrates. There is evidence that atrial fibrosis can be visualized using late gadolinium enhancement cardiac magnetic resonance imaging and that it is a powerful predictor for the outcome of AF interventions. However, a strategy of an individual and fibrosis guided management of AF looks promising but results from prospective multicentre trials are pending. This review gives an overview about the relationship between cardiac fibrosis and AF focusing on translational aspects, clinical observations, and fibrosis imaging to emphasize the concept of personalized paths in AF management taking into account the individual amount and distribution of fibrosis.

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