scholarly journals Immunothrombosis and new-onset atrial fibrillation in the general population: the Rotterdam Study

Author(s):  
Martijn J. Tilly ◽  
Sven Geurts ◽  
Samantha J. Donkel ◽  
M. Arfan Ikram ◽  
Natasja M. S. de Groot ◽  
...  

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. Graphic abstract

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
M.J Tilly ◽  
S Geurts ◽  
S.J Donkel ◽  
M.A Ikram ◽  
N.M.S De Groot ◽  
...  

Abstract Background Atrial fibrillation (AF) is the most common, age-related cardiac arrhythmia. However, the etiology underlying atrial fibrillation 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. Purpose We aim to evaluate the association between markers of immunothrombosis and new-onset AF in the general population Methods From 1990 to 2014, we followed 6,174 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, death, loss-to-follow-up, or reaching the end-date of 01–01–2014. Cox proportional hazard modelling was used to calculated hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for cardiovascular risk factors. Results We followed 6,174 participants (mean age 69.1 years, 57% women) for a median follow-up time of 12.8 years. 364 men (13.7%, incidence rate 13.0/100 person-years) and 365 women (10.4%, incidence rate 8.9/1000 person-years) developed AF. We found no significant associations 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]. Additionally, we found no significant differences in associations between men and women. Conclusion We found no association between markers of immunothrombosis and new-onset AF in the general population. Our findings imply that inflammation and immunothrombosis may be associated with AF by other cardiovascular risk factors or predisposing conditions of AF. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Netherlands Organization for the Health Research and Development (ZonMw) Erasmus MC Mrace grant


2009 ◽  
Vol 29 (01) ◽  
pp. 32-38 ◽  
Author(s):  
P. Paulinska ◽  
A. Spiel ◽  
B. Jilma

SummaryPlasma levels of von Willebrand factor (VWF) are increased in patients with cardiovascular risk factors. Various studies aimed to elucidate the relation of VWF with thrombo - embolic cardiovascular events, ischaemic stroke as well as with peripheral arterial occlusive disease. In the general population, there is only a weak association between VWF levels and future cardiovascular events or stroke. In contrast, VWF levels are predictive in patients with documented vascular disease. Those patients with increased VWF suffer a higher incidence of major adverse cardiac events including death. The extent of the VWF release and its levels independently predict clinical outcome in patients with acute coronary syndromes. Elevated VWF levels have also been observed in patients with atrial fibrillation compared to controls and predict outcome. This may at least in part be attributable to the association of VWF with underlying cardiovascular risk factors. Hence, VWF correlates with Framingham and CHADS stroke risk stratification score and can be used as a marker in patients with AF. However, VWF is not only a predictor; it also plays a crucial role in thrombogenesis. This fact has made VWF a promising target for research into new antiplatelet therapies that specifically inhibit VWF.This review focuses on the role of VWF in ACS, ischaemic stroke and peripheral arterial disease and the relevance of therapeutic interventions targeting VWF for ACS patients.


2021 ◽  
Vol 10 (6) ◽  
pp. 1314
Author(s):  
Rebeca Lorca ◽  
Isaac Pascual ◽  
Andrea Aparicio ◽  
Alejandro Junco-Vicente ◽  
Rut Alvarez-Velasco ◽  
...  

Background: Coronary artery disease (CAD) is the most frequent cause of ST-segment elevation myocardial infarction (STEMI). Etiopathogenic and prognostic characteristics in young patients may differ from older patients and young women may present worse outcomes than men. We aimed to evaluate the clinical characteristics and prognosis of men and women with premature STEMI. Methods: A total 1404 consecutive patients were referred to our institution for emergency cardiac catheterization due to STEMI suspicion (1 January 2014–31 December 2018). Patients with confirmed premature (<55 years old in men and <60 in women) STEMI (366 patients, 83% men and 17% women) were included (359 atherothrombotic and 7 spontaneous coronary artery dissection (SCAD)). Results: Premature STEMI patients had a high prevalence of classical cardiovascular risk factors. Mean follow-up was 4.1 years (±1.75 SD). Mortality rates, re-hospitalization, and hospital stay showed no significant differences between sexes. More than 10% of women with premature STEMI suffered SCAD. There were no significant differences between sexes, neither among cholesterol levels nor in hypolipemiant therapy. The global survival rates were similar to that expected in the general population of the same sex and age in our region with a significantly higher excess of mortality at 6 years among men compared with the general population. Conclusion: Our results showed a high incidence of cardiovascular risk factors, a high prevalence of SCAD among young women, and a generally good prognosis after standardized treatment. During follow-up, 23% suffered a major cardiovascular event (MACE), without significant differences between sexes and observed survival at 1, 3, and 6 years of follow-up was 96.57% (95% CI 94.04–98.04), 95.64% (95% CI 92.87–97.35), and 94.5% (95% CI 91.12–97.66). An extra effort to prevent/delay STEMI should be invested focusing on smoking avoidance and optimal hypolipemiant treatment both in primary and secondary prevention.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Aro ◽  
A Holkeri ◽  
A Eranti ◽  
T Kerola ◽  
M J Junttila ◽  
...  

Abstract Background Sudden cardiac death (SCD) remains a major cause of premature mortality worldwide, so there has been an ongoing pursuit for tools for SCD risk stratification. Coronary artery disease is the major cause for SCD in adults, but the level of risk associated with multiple cardiovascular risk factors is not well established. Purpose To create a clinical risk score for estimating SCD risk in the general population. Methods Using data from a Finnish general population cohort of 7200 adults (mean age 51y, 46% male) with a mean follow-up of 24±11 years, we assessed the incremental SCD risk associated with the presence of several cardiovascular risk factors. SCD events were adjudicated based on death certificates according to the established criteria (autopsy was performed on 48% of SCD cases). Hazard ratios (HR) for SCD and all-cause mortality were calculated using the Cox proportional hazards model. Of the multiple parameters analysed, male sex, increasing age, diabetes, hypertension, smoking and previously diagnosed cardiac disease were independently associated with SCD in a multivariable model. Based on the magnitude of risk, a SCD risk score was created (2 points: age >70y; 1 point: male sex, age 60–70y, diabetes, hypertension, smoking, cardiac disease). Results 75.2% of the study subjects had 0–2 risk points, 12.8% 3 risk points, and 12.0% >3 risk points. During the follow-up, 400 SCDs occurred. Increasing risk score was associated with a progressively greater risk for SCD (Figure). Compared with subjects without risk factors, those with a risk score of 3 had a HR of 21.2 (95% CI 12.7–35.4, p<0.001) and those with a risk score of >3 had a HR of 52.6 (95% CI 31.3–88.3, p<0.001) for SCD. Clinical risk score predicted significantly also all-cause mortality (HR 31.5 with risk score >3 [95% CI 27.6–35.9, p<0.001]). Risk of SCD according to the risk score Conclusions Accumulation of multiple cardiovascular risk factors is associated with a markedly elevated risk for SCD in the general population. This highlights the need for SCD prevention efforts with lifestyle interventions and medical therapy in the high-risk subjects. Studies on focused SCD risk stratification may be warranted in the subjects at highest risk.


BMJ Open ◽  
2018 ◽  
Vol 8 (7) ◽  
pp. e021704 ◽  
Author(s):  
Trygve Berge ◽  
Magnus Nakrem Lyngbakken ◽  
Håkon Ihle-Hansen ◽  
Jon Brynildsen ◽  
Mohammad Osman Pervez ◽  
...  

ObjectivesTo investigate the sex-specific prevalence of atrial fibrillation (AF), including subclinical AF found by screening in a general population aged 63–65 years. The prevalence of cardiovascular risk factors and their association with AF will also be investigated.DesignCross-sectional analysis of an observational, prospective, longitudinal, population-based cohort study.SettingGeneral population in Akershus county, Norway.ParticipantsWomen and men born in 1950. We included 3706 of 5827 eligible individuals (63.6%); 48.8% were women.MethodsAll participants underwent extensive cardiovascular examinations, including 12-lead ECG. History of AF and other cardiovascular diseases were self-reported. Subsequent validation of all reported or detected AF diagnoses was performed.ResultsMean age was 63.9±0.7 years. Prevalence of ECG-verified AF was 4.5% (women 2.4%, men 6.4%; p<0.001), including screen-detected AF in 0.3% (women 0.1%, men 0.6%; p<0.01). Hypertension was found in 62.0% (women 57.8%, men 66.0%; p<0.001). Overweight or obesity was found in 67.6% (women 59.8%, men 74.9%; p<0.001). By multivariate logistic regression, risk factors associated with AF were height (OR 1.67 per 10 cm; 95% CI 1.26 to 2.22; p<0.001), weight (OR 1.15 per 10 kg; 95% CI 1.01 to 1.30; p=0.03), hypertension (OR 2.49; 95% CI 1.61 to 3.86; p<0.001), heart failure (OR 3.51; 95% CI 1.71 to 7.24; p=0.001), reduced estimated glomerular filtration rate (OR 2.56; 95% CI 1.42 to 4.60; p<0.01) and at least one first-degree relative with AF (OR 2.32; 95% CI 1.63 to 3.31; p<0.001), whereas male sex was not significantly associated (OR 1.00; 95% CI 0.59 to 1.68; p=0.99).ConclusionIn this cohort from the general population aged 63–65 years, we found a higher prevalence of known AF than previously reported below the age of 65 years. The additional yield of single time point screening for AF was low. Body size and comorbidity may explain most of the sex difference in AF prevalence at this age.Trial registration numberNCT01555411; Results.


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