Clinical trial NCT01882114: Atherosclerosis in Atrial Fibrillation
Official title: Study of Atherosclerotic Risk Factors and Oxidative Stress in Atrial Fibrillation. Relation to Cardiovascular Events
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Atrial Fibrillation
Metabolic Syndrome
Oxidative Stress
Atherosclerosis
Disorders, Blood Coagulation
Keywords: atherosclerosis
cardiovascular events
ankle-brachial index
carotid disease
echocardiography
mediterranean diet
platelet activation
Lead sponsor: University of Roma La Sapienza
Sponsor class: OTHER
First posted: 2013-06-20
Enrollment: 3000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Prospective single-center study including consecutive patients with NVAF referring to our center for monitoring and management of antithrombotic therapies of the Department of Internal Medicine and Medical Specialties of Sapienza-University of Rome from November 2007.

Brief summary: The prevalence of metabolic syndrome in patients suffering from non valvular atrial fibrillation is derived from studies regarding recurrences of atrial fibrillation after catheter ablation. Prospective studies in european countries are lacking. Furthermore, the impact of metabolic syndrome on cardiovascular events in patients with non valvular atrial fibrillation is still unknown.

Detailed description: Atrial fibrillation (AF) is the most common cardiac arrhythmia that is associated with a high risk of cardiovascular events and increased morbidity and mortality. Cardiovascular events are prevalently localized in the cerebral circulation in which AF is responsible for ischemic stroke. Clinical characteristics of ischemic stroke from AF are almost severe and thromboembolism is considered the most important cause. Thus, ischemic stroke is deemed to origin from thrombus formation generated in the left atrium with ensuing embolism in the cerebral circulation.

Patients with AF are typically associated with different risk factors of atherothrombosis including, overall, hypertension which may be detected in about 70-80% of the population; other risk factors are diabetes and dyslipidemia. This accounts for instrumental evidence of systemic atherosclerosis associated to AF. Thus, signs of atherosclerosis have been detected in the thoracic aorta, as represented by aortic plaque assessed by trans-esophageal echocardiography; patients with complex aortic plaque had fourfold increased rate of stroke compared to plaque-free patients.

Metabolic syndrome (MetS) is a constellation of atherosclerotic risk factors including, according to the modified National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII), hypertension, low HDL, impaired glycaemic control, hypertriglyceridemia and central obesity as assessed by waist circumference; the presence of MetS is associated with an increased risk of developing cardiac and cerebral ischemic events.

An higher risk to develop atrial fibrillation (AF) has been well recognized in patients with MetS. In a prospective, community-based, observational cohort study with annual health check-up 28449 subjects without AF the age-adjusted rates of AF were higher in subjects with compared to those without metabolic syndrome during a mean follow-up of 4.5 years.

Few studies reported on the prevalence of MetS in AF population are still lacking. Some data can be inferred from studies regarding recurrence of AF after catheter ablation reporting a prevalence ranging from 18.8% to 49.4% . The only population study so far published included 741 chinese patients and reported a prevalence of the MetS in AF of 46.3%. Taking into account the thresholds of waist circumference recommended by international societies for different ethnic groups, it is unclear if such prevalence can be extrapolated to population of western countries.

Furthermore the impact of MetS on the incidence of cardiovascular events in patients with non valvular AF (NVAF) taking oral anticoagulant therapy (OAT) has never been investigated.

Therefore, our aim was to investigate the prevalence of MetS in a population of NVAF patients under oral coagulation treatment and its impact on cardiovascular events during a prospective study.

The study has been modified and approved by local ethical board of Sapienza University of Rome to include patients treated with non-vitamin K oral anticoagulants (dabigatran, apixaban, edoxaban, rivaroxaban) on April 11, 2014 (Prot. 417/14).

Eligibility criteria: Inclusion Criteria:

* non valvular atrial fibrillation
* age \>18 years
* any antithrombotic treatment

Exclusion Criteria:

* prosthetic heart valves, or the presence of any severe valvulopathies, severe cognitive impairment, chronic infectious (HIV, hepatitis C, HBV) or autoimmune systemic disease. Furthermore, subjects were excluded from the study if they had active neoplastic diseases or liver insufficiency (eg, cirrhosis).

Primary outcomes:
measure: Prevalence of metabolic syndrome in anticoagulated nonvalvular atrial fibrillation patients
timeFrame: At baseline
Secondary outcomes:
measure: Progression of atherosclerosis in non valvular atrial fibrillation patients receiving oral anticoagulant therapy.
timeFrame: One year
measure: Analysis of oxidative stress markers in atrial fibrillation
timeFrame: At baseline
measure: Changing in glomerular filtration rate of anticoagulated patients with non valvular atrial fibrillation
timeFrame: One year
measure: Determinants of Time in Therapeutic Range
timeFrame: Patients will be followed for an expected mean time of 25 months
measure: Use of digoxin in atrial fibrillation
timeFrame: At baseline
measure: Echocardiographic characteristics in patients with paroxysmal or persistent/permanent atrial fibrillation
timeFrame: At baseline
Other outcomes:
measure: Mediterranean diet adherence in non valvular atrial fibrillation
timeFrame: At baseline
Locations:
city: Rome
country: Italy
facility: Umberto I Policlinico di Roma, Sapienza Università di Roma
Study officials:
affiliation: Sapienza Università di Roma
name: Francesco Violi, Prof
role: STUDY_DIRECTOR
References:
citation: Pignatelli P, Pastori D, Farcomeni A, Nocella C, Bartimoccia S, Vicario T, Bucci T, Carnevale R, Violi F. Mediterranean diet reduces thromboxane A2 production in atrial fibrillation patients. Clin Nutr. 2015 Oct;34(5):899-903. doi: 10.1016/j.clnu.2014.09.011. Epub 2014 Sep 28.
citation: Pignatelli P, Pastori D, Carnevale R, Farcomeni A, Cangemi R, Nocella C, Bartimoccia S, Vicario T, Saliola M, Lip GY, Violi F. Serum NOX2 and urinary isoprostanes predict vascular events in patients with atrial fibrillation. Thromb Haemost. 2015 Mar;113(3):617-24. doi: 10.1160/TH14-07-0571. Epub 2014 Nov 13.
citation: Pastori D, Pignatelli P, Angelico F, Farcomeni A, Del Ben M, Vicario T, Bucci T, Raparelli V, Cangemi R, Tanzilli G, Lip GYH, Violi F. Incidence of myocardial infarction and vascular death in elderly patients with atrial fibrillation taking anticoagulants: relation to atherosclerotic risk factors. Chest. 2015 Jun;147(6):1644-1650. doi: 10.1378/chest.14-2414.
citation: Pastori D, Farcomeni A, Bucci T, Cangemi R, Ciacci P, Vicario T, Violi F, Pignatelli P. Digoxin treatment is associated with increased total and cardiovascular mortality in anticoagulated patients with atrial fibrillation. Int J Cardiol. 2015 Feb 1;180:1-5. doi: 10.1016/j.ijcard.2014.11.112. Epub 2014 Nov 18.
citation: Pastori D, Carnevale R, Bartimoccia S, Nocella C, Tanzilli G, Cangemi R, Vicario T, Catena M, Violi F, Pignatelli P. Does Mediterranean Diet Reduce Cardiovascular Events and Oxidative Stress in Atrial Fibrillation? Antioxid Redox Signal. 2015 Sep 10;23(8):682-7. doi: 10.1089/ars.2015.6326. Epub 2015 Apr 28.
citation: Pignatelli P, Pastori D, Vicario T, Bucci T, Del Ben M, Russo R, Tanzilli A, Nardoni ML, Bartimoccia S, Nocella C, Ferro D, Saliola M, Cangemi R, Lip GY, Violi F. Relationship between Mediterranean diet and time in therapeutic range in atrial fibrillation patients taking vitamin K antagonists. Europace. 2015 Aug;17(8):1223-8. doi: 10.1093/europace/euv127. Epub 2015 May 19.
citation: Pastori D, Pignatelli P, Saliola M, Carnevale R, Vicario T, Del Ben M, Cangemi R, Barilla F, Lip GY, Violi F. Inadequate anticoagulation by Vitamin K Antagonists is associated with Major Adverse Cardiovascular Events in patients with atrial fibrillation. Int J Cardiol. 2015 Dec 15;201:513-6. doi: 10.1016/j.ijcard.2015.08.054. Epub 2015 Aug 5.
citation: Pastori D, Pignatelli P, Farcomeni A, Cangemi R, Hiatt WR, Bartimoccia S, Nocella C, Vicario T, Bucci T, Carnevale R, Lip GY, Violi F. Urinary 11-dehydro-thromboxane B2 is associated with cardiovascular events and mortality in patients with atrial fibrillation. Am Heart J. 2015 Sep;170(3):490-7.e1. doi: 10.1016/j.ahj.2015.05.011. Epub 2015 May 22.
citation: Pastori D, Farcomeni A, Poli D, Antonucci E, Angelico F, Del Ben M, Cangemi R, Tanzilli G, Lip GY, Pignatelli P, Violi F. Cardiovascular risk stratification in patients with non-valvular atrial fibrillation: the 2MACE score. Intern Emerg Med. 2016 Mar;11(2):199-204. doi: 10.1007/s11739-015-1326-1. Epub 2015 Oct 15.
citation: Pastori D, Pignatelli P, Perticone F, Sciacqua A, Carnevale R, Farcomeni A, Basili S, Corazza GR, Davi G, Lip GYH, Violi F; ARAPACIS (Atrial Fibrillation Registry for Ankle-Brachial Index Prevalence Assessment-Collaborative Italian Study) study group. Aspirin and renal insufficiency progression in patients with atrial fibrillation and chronic kidney disease. Int J Cardiol. 2016 Nov 15;223:619-624. doi: 10.1016/j.ijcard.2016.08.224. Epub 2016 Aug 14.
citation: Pastori D, Pignatelli P, Farcomeni A, Menichelli D, Nocella C, Carnevale R, Violi F. Aging-Related Decline of Glutathione Peroxidase 3 and Risk of Cardiovascular Events in Patients With Atrial Fibrillation. J Am Heart Assoc. 2016 Sep 8;5(9):e003682. doi: 10.1161/JAHA.116.003682.
citation: Pastori D, Pignatelli P, Farcomeni A, Nocella C, Bartimoccia S, Carnevale R, Violi F. Age-related increase of thromboxane B2 and risk of cardiovascular disease in atrial fibrillation. Oncotarget. 2016 Jun 28;7(26):39143-39147. doi: 10.18632/oncotarget.9826.
citation: Pastori D, Carnevale R, Menichelli D, Nocella C, Bartimoccia S, Novo M, Leo I, Violi F, Pignatelli P. Is There an Interplay Between Adherence to Mediterranean Diet, Antioxidant Status, and Vascular Disease in Atrial Fibrillation Patients? Antioxid Redox Signal. 2016 Nov 10;25(14):751-755. doi: 10.1089/ars.2016.6839. Epub 2016 Sep 30.
citation: Pastori D, Carnevale R, Nocella C, Novo M, Santulli M, Cammisotto V, Menichelli D, Pignatelli P, Violi F. Gut-Derived Serum Lipopolysaccharide is Associated With Enhanced Risk of Major Adverse Cardiovascular Events in Atrial Fibrillation: Effect of Adherence to Mediterranean Diet. J Am Heart Assoc. 2017 Jun 5;6(6):e005784. doi: 10.1161/JAHA.117.005784.
citation: Carnevale R, Pignatelli P, Frati G, Nocella C, Stanzione R, Pastori D, Marchitti S, Valenti V, Santulli M, Barbato E, Strisciuglio T, Schirone L, Vecchione C, Violi F, Volpe M, Rubattu S, Sciarretta S. C2238 ANP gene variant promotes increased platelet aggregation through the activation of Nox2 and the reduction of cAMP. Sci Rep. 2017 Jun 19;7(1):3797. doi: 10.1038/s41598-017-03679-9.
citation: Pastori D, Nocella C, Farcomeni A, Bartimoccia S, Santulli M, Vasaturo F, Carnevale R, Menichelli D, Violi F, Pignatelli P; ATHERO-AF Study Group. Relationship of PCSK9 and Urinary Thromboxane Excretion to Cardiovascular Events in Patients With Atrial Fibrillation. J Am Coll Cardiol. 2017 Sep 19;70(12):1455-1462. doi: 10.1016/j.jacc.2017.07.743.
citation: Pastori D, Pignatelli P, Sciacqua A, Perticone M, Violi F, Lip GYH. Relationship of peripheral and coronary artery disease to cardiovascular events in patients with atrial fibrillation. Int J Cardiol. 2018 Mar 15;255:69-73. doi: 10.1016/j.ijcard.2017.12.076. Epub 2017 Dec 24.
citation: Pastori D, Menichelli D, Lip GYH, Sciacqua A, Violi F, Pignatelli P; ATHERO-AF study groupdagger. Family History of Atrial Fibrillation and Risk of Cardiovascular Events: A Multicenter Prospective Cohort Study. Circ Arrhythm Electrophysiol. 2020 Sep;13(9):e008477. doi: 10.1161/CIRCEP.120.008477. Epub 2020 Jul 27.
citation: Pastori D, Pignatelli P, Menichelli D, Violi F, Lip GYH. Integrated Care Management of Patients With Atrial Fibrillation and Risk of Cardiovascular Events: The ABC (Atrial fibrillation Better Care) Pathway in the ATHERO-AF Study Cohort. Mayo Clin Proc. 2019 Jul;94(7):1261-1267. doi: 10.1016/j.mayocp.2018.10.022. Epub 2018 Dec 11.
citation: Pastori D, Carnevale R, Cangemi R, Saliola M, Nocella C, Bartimoccia S, Vicario T, Farcomeni A, Violi F, Pignatelli P. Vitamin E serum levels and bleeding risk in patients receiving oral anticoagulant therapy: a retrospective cohort study. J Am Heart Assoc. 2013 Oct 28;2(6):e000364. doi: 10.1161/JAHA.113.000364.