Immunothrombosis and new-onset atrial fibrillation in the general population: the Rotterdam Study.
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ABSTRACT: Background
Atrial fibrillation (AF) is the most common age-related cardiac arrhythmia. The etiology underlying AF is still largely unknown. At the intersection of the innate immune system and hemostasis, immunothrombosis may be a possible cause of atrial remodeling, and therefore be an underlying cause of AF.Methods
From 1990 to 2014, we followed participants aged 55 and over, free from AF at inclusion. Immunothrombosis factors fibrinogen, von Willebrand factor, ADAMTS13, and neutrophil extracellular traps (NETs) levels were measured at baseline. Participants were followed until either onset of AF, loss-to-follow-up, or reaching the end-date of 01-01-2014. Cox proportional hazard modelling was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for cardiovascular risk factors.Results
We followed 6174 participants (mean age 69.1 years, 57% women) for a median follow-up time of 12.8 years. 364 men (13.7%, incidence rate 13.0/1000 person-years) and 365 women (10.4%, incidence rate 8.9/1000 person-years) developed AF. We found no significant association between markers of immunothrombosis and new-onset AF after adjusting for cardiovascular risk factors [HR 1.00 (95% CI 0.93-1.08) for fibrinogen, 1.04 (0.97-1.12) for von Willebrand factor, 1.00 (1.00-1.01) for ADAMTS13, and 1.01 (0.94-1.09) for NETs]. In addition, we found no differences in associations between men and women.Conclusion
We found no associations between markers of immunothrombosis and new-onset AF in the general population. Inflammation and immunothrombosis may be associated with AF through other cardiovascular risk factors or predisposing conditions of AF. Our findings challenge the added value of biomarkers in AF risk prediction.
SUBMITTER: Tilly MJ
PROVIDER: S-EPMC8766396 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background Limited population-based data on the (sex-specific) link between subclinical measures of peripheral atherosclerosis and new-onset atrial fibrillation (AF) exist. Methods and Results Subclinical measures of peripheral atherosclerosis including carotid intima-media thickness (cIMT), carotid plaque, and ankle-brachial index (ABI) were assessed at baseline and follow-up examinations. A total of 12 840 participants free of AF at baseline from the population-based Rotterdam Study were included. Cox proportional hazards models and joint models, adjusted for cardiovascular risk factors, were used to determine the associations between baseline and longitudinal measures of cIMT, carotid plaque, and ABI with new-onset AF. During a median follow-up of 9.2 years, 1360 incident AF cases occurred among 12 840 participants (mean age 65.2 years, 58.3% women). Higher baseline cIMT (fully-adjusted hazard ratio [HR], 95% CI, 1.81, 1.21-2.71; P=0.0042), presence of carotid plaque (fully-adjusted HR, 95% CI, 1.19, 1.04-1.35; P=0.0089), lower ABI (fully-adjusted HR, 95% CI, 1.57, 1.14-2.18; P=0.0061) and longitudinal measures of higher cIMT (fully-adjusted HR, 95% CI, 2.14, 1.38-3.29; P=0.0021), presence of carotid plaque (fully-adjusted HR, 95% CI, 1.61, 1.12-2.43; P=0.0112), and lower ABI (fully-adjusted HR, 95% CI, 4.43, 1.83-10.49; P=0.0007) showed significant associations with new-onset AF in the general population. Sex-stratified analyses showed that the associations for cIMT, carotid plaque, and ABI were mostly prominent among women. Conclusions Baseline and longitudinal subclinical measures of peripheral atherosclerosis (carotid atherosclerosis, and lower extremity peripheral atherosclerosis) were significantly associated with an increased risk of new-onset AF, especially among women. Registration URL: https://www.trialregister.nl, https://www.apps.who.int/trialsearch/; Unique identifier: NL6645/NTR6831.
| S-EPMC9075211 | biostudies-literature
Project description: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. 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. 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. 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.
| S-EPMC8775308 | biostudies-literature
Project description:Higher height and weight are known to be associated with higher risk of atrial fibrillation (AF); however, whether the risk of AF is related to abdominal obesity is unclear. We studied 501 690 adults (mean age: 47.6±14.3 years; 250 664 women [50.0%]) without baseline AF in the National Sample Cohort released by the National Health Insurance Service in Korea. Body mass index (underweight defined as <18.5; normal, 18.5 to <25.0; overweight, 25.0 to <30.0; and obese, ≥30.0) and waist circumference (abdominal obesity defined as ≥90 cm for men and ≥80 cm for women) were evaluated. During a mean follow-up of 3.9±1.3 years, 3443 participants (1432 women [41.6%]) developed AF. In multivariable models adjusted for clinical variables, the AF risk of underweight, overweight, and obese individuals increased by 21% (95% confidence interval, 1.01-1.45, P=0.043), 14% (95% confidence interval, 1.06-1.23, P<0.001), and 52% (95% confidence interval, 1.30-1.78, P<0.001), respectively, compared with those with normal body mass index. AF risk with confounder-adjusted hazards for abdominal obesity was 18% (95% confidence interval, 1.10-1.27, P<0.001). The increased AF risk was present in abdominally obese individuals regardless of body mass index except for the obese group. In subgroup analysis, abdominal obesity by waist circumference conferred increased risk of new-onset AF, particularly in participants without comorbidities. Abdominal obesity is an important, potentially modifiable risk factor for AF in nonobese Asian persons. These data suggest that interventions to decrease abdominal obesity may reduce the population burden of AF.
| S-EPMC5669144 | biostudies-literature
Project description:Massachusetts General Hospital Atrial Fibrillation Study
| PRJNA297616 | ENA
Project description:BACKGROUND:Being obese or underweight, and having diabetes are important risk factors for new-onset atrial fibrillation (AF). However, it is unclear whether there is any interaction between body weight and diabetes in regard to development of new-onset AF. We aimed to evaluate the role of body weight status and various stage of diabetes on new-onset AF. METHODS:This was a nationwide population based study using National Health Insurance Service (NHIS) data. A total of 9,797,418 patients who underwent national health check-ups were analyzed. Patients were classified as underweight [body mass index (BMI) < 18.5], normal reference group (18.5 ≤ BMI < 23.0), upper normal (23.0 ≤ BMI < 25.0), overweight (25.0 ≤ BMI < 30.0), or obese (BMI ≥ 30.0) based on BMI. Diabetes were categorized as non-diabetic, impaired fasting glucose (IFG), new-onset diabetes, diabetes < 5 years, and diabetes ≥ 5 years. Primary outcome end point was new-onset AF. New-onset AF was defined as one inpatient or two outpatient records of International Classification of Disease, Tenth Revision (ICD-10) codes in patients without prior AF diagnosis. RESULTS:During 80,130,161 patient*years follow-up, a total of 196,136 new-onset AF occurred. Obese [hazard ration (HR) = 1.327], overweight (HR = 1.123), upper normal (HR = 1.040), and underweight (HR = 1.055) patients showed significantly increased risk of new-onset AF compared to the normal reference group. Gradual escalation in the risk of new-onset AF was observed along with advancing diabetic stage. Body weight status and diabetes were independently associated with new-onset AF and at the same time, had synergistic effects on the risk of new-onset AF with obese diabetic patients having the highest risk (HR = 1.823). CONCLUSIONS:Patients with obesity, overweight, underweight, and diabetes had significantly increased risk of new-onset AF. Body weight status and diabetes had synergistic effects on the risk of new-onset AF. The risk of new-onset AF increased gradually with advancing diabetic stage. This study suggests that maintaining optimal body weight and glucose homeostasis might prevent new-onset AF.
| S-EPMC6774211 | biostudies-other
Project description:Currently, the potential risk of atrial fibrillation associated with antihyperglycemic drug use has been a topic of considerable interest. However, it remains uncertain whether different classes of antihyperglycemic drug therapy are associated with the risk of atrial fibrillation risk. Here, we investigated the association between different classes of antihyperglycemic drugs and new-onset atrial fibrillation (NAF). A case-matched study was performed based on the National Health Insurance Program in Taiwan. Patients who had NAF were considered the NAF group and were matched in a 1:4 ratio with patients without NAF, who were assigned to the non-NAF group. Patients were matched according to sex, age, diabetes mellitus duration, index date, and Charlson Comorbidity Index score. We used multivariate logistic regression controlling for potential confounders to examine the association between different classes of antihyperglycemic drug use and the risk of NAF. Overall, we identified 2,882 cases and 11,528 matched controls for the study. After adjusting for sex, age, comorbidities, and concurrent medications, users of biguanides or thiazolidinediones were at a lower risk of developing NAF when compared with non-users (odds ratio [OR] 0.81, 95% confidence interval [CI] 0.71-0.95 and OR 0.72, 95% CI 0.63-0.83, respectively). In contrast, users of insulin were at a higher risk of developing NAF than were non-users (OR 1.19, 95% CI 1.06-1.35). Sulfonylureas, glinides, α-glucosidase inhibitors, and dipeptidyl peptidase-4 inhibitors were not associated with developing the risk of NAF. In conclusion, the use of biguanides or thiazolidinediones may be associated with a low risk of NAF, whereas insulin may be associated with a significant increase in the risk of NAF in patients with type 2 diabetes mellitus during long-term follow-up. Further prospective randomized studies should investigate which specific class of antihyperglycemic drug treatment for diabetes mellitus can prevent or postpone NAF.
| S-EPMC6116917 | biostudies-literature
Project description:CONTEXT:Although the heritability of atrial fibrillation (AF) is established, the contribution of familial AF to predicting new-onset AF remains unknown. OBJECTIVE:To determine whether familial occurrence of AF is associated with new-onset AF beyond established risk factors. DESIGN, SETTING, AND PARTICIPANTS:The Framingham Heart Study, a prospective community-based cohort study started in 1948. Original and Offspring Cohort participants were aged at least 30 years, were free of AF at the baseline examination, and had at least 1 parent or sibling enrolled in the study. The 4421 participants in this analysis (mean age, 54 [SD, 13] years; 54% women) were followed up through December 31, 2007. MAIN OUTCOME MEASURES:Incremental predictive value of incorporating different features of familial AF (any familial AF, premature familial AF [onset ?65 years old], number of affected relatives, and youngest age of onset in a relative) into a risk model for new-onset AF. RESULTS:Across 11,971 examinations during the period 1968-2007, 440 participants developed AF. Familial AF occurred among 1185 participants (26.8%) and premature familial AF occurred among 351 participants (7.9%). Atrial fibrillation occurred more frequently among participants with familial AF than without familial AF (unadjusted absolute event rates of 5.8% and 3.1%, respectively). The association was not attenuated by adjustment for AF risk factors (multivariable-adjusted hazard ratio, 1.40; 95% confidence interval [CI], 1.13-1.74) or reported AF-related genetic variants. Among the different features of familial AF examined, premature familial AF was associated with improved discrimination beyond traditional risk factors to the greatest extent (traditional risk factors, C statistic, 0.842 [95% CI, 0.826-0.858]; premature familial AF, C statistic, 0.846 [95% CI, 0.831-0.862]; P = .004). Modest changes in integrated discrimination improvement were observed with premature familial AF (2.1%). Net reclassification improvement (assessed using 8-year risk thresholds of <5%, 5%-10%, and >10%) did not change significantly with premature familial AF (index statistic, 0.011; 95% CI, -0.021 to 0.042; P = .51), although categoryless net reclassification was improved (index statistic, 0.127; 95% CI, 0.064-0.189; P = .009). CONCLUSIONS:In this cohort, familial AF was associated with an increased risk of AF that was not attenuated by adjustment for AF risk factors including genetic variants. Assessment of premature familial AF was associated with a very slight increase in predictive accuracy compared with traditional risk factors.
| S-EPMC3073054 | biostudies-literature
Project description:Cardiovascular complications remain the major problems contributing to morbidity and mortality in patients with polycystic kidney disease (PKD). Therefore, the authors hypothesized that atrial fibrillation (AF) is closely associated with PKD. The authors conducted a nationwide population-based cohort study to investigate the risk of AF in patients with PKD. Using data from inpatient claims, the authors enrolled 7203 patients aged over 20 years who were diagnosed with PKD from 1998 to 2010 with no history of AF as the PKD cohort. They randomly selected 28,739 people without PKD as controls and frequency matched them with patients with PKD according to their age, sex, and baseline comorbidity. In total, 247 PKD patients were diagnosed with AF, representing an incidence of 7.08 per 1000 person-years, whereas 807 cases of AF occurred in the comparison cohort, yielding an incidence of 4.98 per 1000 person-y, with an adjusted HR (aHR) of 1.31 (95% CI = 1.14-1.51). The risk of AF increased from an aHR of 1.59 (95% CI = 1.15-2.21) to 3.64 (95% CI = 1.93-6.85) when the number of risk factors increased from 1 to more than 5 in comparison with patients without risk factors. A remarkably high incidence rate and risk was observed in patients with PKD when multiple risk factors were combined. A high index of suspicion should be maintained when examining PKD patients with irregular betas. Early prophylactic therapy is warranted in these patients.
| S-EPMC5291589 | biostudies-literature
Project description:Atrial fibrillation (AF) is the most common chronic arrhythmia and it increases the risk of cardiovascular morbidity and mortality. Still there is not a complete understanding of its etiology and underlying pathways. Vitamin D might regulate renin-angiotensin-aldosterone system and might be involved in inflammation, both implicated in the pathophysiology of AF. The objective of this work was to investigate the association between vitamin D status with the risk of AF in the elderly. This study was conducted within the Rotterdam Study, a community-based cohort of middle-aged and elderly participants in Rotterdam, The Netherlands. We had 3,395 participants who were free of AF diagnosis at the start of our study and who had vitamin D data available. We analyzed the association between serum 25-hydroxivitamin D (25(OH)D) and incidence of AF using Cox regression models. Vitamin D deficiency was defined as serum 25(OH)D concentrations <50 nmol/l, insufficiency between 50 nmol/l and 75 nmol/l, while serum 25(OH)D concentrations equal to and above 75 nmol/l were considered as adequate. After mean follow-up of 12.0 years 263 (7.7%) participants were diagnosed with incident AF. Vitamin D status was not associated with AF in any of the 3 multivariate models tested (model adjusted for socio-demographic factors and life-style factors: HR per 10 unit increment in serum 25(OH)D 0.96, 95% CI: 0.91-1.02; HR for insufficiency: 0.82, 95%CI: 0.60-1.11,and HR for adequate status: 0.76, 95%CI: 0.52-1.12 compared to deficiency). This prospective cohort study does not support the hypothesis that vitamin D status is associated with AF.
| S-EPMC4416919 | biostudies-literature
Project description:AimsThe underlying mechanisms of atrial fibrillation (AF) are largely unknown. Inflammation may underlie atrial remodelling. Autoimmune diseases, related to increased systemic inflammation, may therefore be associated with new-onset AF.Methods and resultsParticipants from the population-based UK Biobank were screened for rheumatic fever, gastrointestinal autoimmune diseases, autoimmune diseases targeting the musculoskeletal system and connective tissues, and neurological autoimmune diseases. Between 2006 and 2022, participants were followed for incident AF. Cox proportional hazards regression analyses were performed to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) to quantify associations. 494 072 participants free from AF were included (median age 58.0 years, 54.8% women). After a median of 12.8 years, 27 194 (5.5%) participants were diagnosed with new-onset AF. Rheumatic fever without heart involvement (HR, 95% CI: 1.47, 1.26-1.72), Crohn's disease (1.23, 1.05-1.45), ulcerative colitis (1.17, 1.06-1.31), rheumatoid arthritis (1.39, 1.28-1.51), polyarteritis nodosa (1.82, 1.04-3.09), systemic lupus erythematosus (1.82, 1.41-2.35), and systemic sclerosis (2.32, 1.57-3.44) were associated with a larger AF risk. In sex-stratified analyses, rheumatic fever without heart involvement, multiple sclerosis, Crohn's disease, seropositive rheumatoid arthritis, psoriatic and enteropathic arthropathies, systemic sclerosis and ankylosing spondylitis were associated with larger AF risk in women, whereas only men showed a larger AF risk associated with ulcerative colitis.ConclusionsVarious autoimmune diseases are associated with new-onset AF, more distinct in women. Our findings elaborate on the pathophysiological differences in autoimmunity and AF risk between men and women.
| S-EPMC10062304 | biostudies-literature