Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting more than 33 million people worldwide. It is the leading cause of cardiovascular disease and death in the world. The most common complications are thromboembolic incidents and bleeding. Ischemic stroke as a complication of AF represents about 6-24% of all ischemic strokes. Previous studies have shown that the frequency of AF increases with age and that it occurs more often in men (1, 2). Through its association with heart failure (HF) and stroke, AF has a very large impact on the quality and duration of life for millions of people (3, 4).

Hypertension is one of the most important factors for the occurrence of AF. It increases the incidence of AF by 50% in men and 40% in women (5). In the Atherosclerosis Risk in Communities study, hypertension was the main factor contributing to the development of AF and was present in about 20% of new AF cases (6), whereas in patients who have previously had AF, hypertension was present in 60-80% of cases (7). Pathophysiological mechanisms due to hypertension result in reduced left ventricular contractility, diastolic dysfunction, and left ventricular hypertrophy, in addition to increased cardiac wall tension, increased left ventricular filling pressure, and activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) (8). Epidemiological studies have shown that hypertension is associated with a ×1.8 higher risk of developing new-onset AF and a ×1.5 increased risk of AF progression to a permanent form (5, 9). Additionally, studies have significantly improved our understanding of AF and its causes. Structural and electrical remodeling of the left atrium has therefore been increasingly recognized as a process that precedes and contributes to the development of AF. Since elevated systemic pressures affect the size and function of the left atrium, uncontrolled hypertension is a key factor contributing to the development of AF (10).

Numerous studies have shown that, in addition to hypertension, there are numerous cardiac and non-cardiac conditions that are associated with the risk of developing AF. Among structural heart diseases, valvular heart disease (especially mitral valve disease) and HF significantly increase the risk of AF. The main mechanism is atrial remodeling, although other factors play a role in patients with HF. AF is also more common in patients with coronary artery disease with preserved ejection fraction (11).

It is well-known that ischemic stroke is the most common complication in patients with AF. The hemodynamic mechanism responsible for increased thromboembolic risk is Virchow’s triad. Vascular thrombi are mainly composed of fibrin strands, red blood cells, and platelets (12). These concepts have evolved over the years and are relevant to the development of arterial thrombosis (13). An important part of the clinical treatment of AF includes making a decision on oral anticoagulant therapy, given that oral anticoagulant therapy significantly reduces the risk of stroke (by 64%) and mortality from all causes (by 26%) compared with placebo (14).

In this retrospective cohort study, we included 43 patients with AF who attended a regular check-up at the Family Medicine Service of the Lukavac Health Center in the period from January to March 2023. Information on their disease history was collected from the patients. Other data such as left ventricular ejection fraction (EF), comorbidities, anticoagulant therapy, and complications were extracted from their medical records.

Patients were divided into three categories according to age: young (0-14 years old), working age persons (15-64 years old), and the elderly (>65 years old). The following data were used to classify EF: HF with preserved ejection fraction – HFpEF (≥50%), HF with mid-range EF – HFmrEF (41-49%), and HF with reduced EF – HFrEF (≤40%).

Descriptive data were presented as percentages. Student t-test was used in data processing. The statistical significance of the difference was considered relevant if p<0.05.

All patients voluntarily agreed to be included in this study and signed an informed consent form. The study protocol was approved by the Ethics Committee of the Lukavac Health Centar.

The study group included 43 patients, 21 men (48.8%) and 22 women (51.2%). According to the age structure, the majority of respondents belonged to the group of people over 65 years of age (81.4%), while the rest were people of working age from 15 to 64 years old (18.6%).

Hypertension was present in 40 respondents (93.0%), while 18 respondents in the study (41.9%) were diagnosed with diabetes mellitus type 2 in addition to hypertension.

In this study, 35 patients had verified EF using transthoracic echocardiography (81.4%). The majority, 18 of them (51.4%), had HFpEF, while 8 patients (22.9%) had HFmrEF, and HFrEF was verified in 9 patients with AF (25.7%).

The most significant complications of AF were thromboembolic events. More than half of the patients (53.5%) had some thromboembolic event; 8 of them (18.6%) had a myocardial infarction noted in their medical records, while 13 subjects (30.2%) experienced a stroke as a complication of AF. 9 subjects who experienced a stroke (69.2%) were previously on anticoagulant therapy due to verified AF. There was no statistically significant difference in the age of subjects with a previous stroke compared with subjects who had a recorded myocardial infarction (66.85 years vs. 72.75 years, p=0.92). In addition to myocardial infarction and stroke, pulmonary embolism was recorded in 2 patients (4.6%).

Based on the inspection of the participants’ medical records, 38 of them (88.4%) were on anticoagulant therapy. The majority of patients received rivaroxaban as anticoagulant therapy, 26 of them (60.5%), while 6 patients were on warfarin (13.9%) and 6 on apixaban (13.9%). In 4 participants (10.5%), anticoagulant therapy was included after a stroke. In addition to anticoagulant therapy, 11 respondents (25.6%) also had antiplatelet drugs in their therapy, while aspirin was used in 8 patients (18.6%) and dual antiplatelet therapy (aspirin and clopidogrel) in 3 patients (7.0%). 8 patients included in this study (18.6%) were on both anticoagulant and antiplatelet therapy.

Atrial fibrillation is the most common arrhythmia in the general population, which increases with age. AF is associated with significant morbidity and mortality, and the increasing number of people with AF will have major implications for public health (15-17). There are numerous risk factors that play a role in the development of AF, such as age, hypertension, obesity, HF, and diabetes mellitus type 2.

Published studies state that the average age of patients in most reports is between 65 and 70 years (18, 19), similar to results in the present study, where the majority of respondents belonged to the group of elderly people over 65 years of age (81.4%). As the population ages, the number of patients with hypertension increases.

A Bosnian study group that recently reported on hypertension stated that the high prevalence of hypertension today is the result of unhealthy lifestyle habits, such as poor dietary choices, obesity, lack of physical activity, smoking, and high exposure to stress (20). Our results show that the majority of respondents (93.0%) had a diagnosis of hypertension in their medical records. Hypertension was identified as one of the most significant factors that increase the risk of developing AF (5, 21). Successfully controlling hypertension with antihypertensive drugs can reduce the risk of the onset and development of AF. It is believed that the above-mentioned risk factors lead to structural and electrical atrial remodeling, which is considered an important element in the development of AF. Although significant progress has been made, these phenomena remain incompletely or poorly understood, which likely contributes to the limited effectiveness of therapeutic approaches for AF (22). In addition to hypertension, AF occurs extremely often together with diabetes mellitus, for which large randomized studies are needed to determine the definitive role and link with the occurrence of AF.

As is already known, the most common thromboembolic incident related to AF is ischemic stroke. In a study that included 739 patients with stroke, AF was registered in 20.7% (23). Our results for stroke in patients with AF onset correspond to previous findings in Bosnia and Herzegovina (23). This is also consistent with several worldwide studies that have confirmed the relationship between stroke and AF and their impact on high mortality and disability (24-26).

Nabil et al. found that most patients with AF were on anticoagulant therapy (vitamin K antagonists and new oral anticoagulants), 44.2%, while a slightly smaller percentage were on antiplatelet therapy: about 22% of patients (27). In our study, we obtained similar results, which significantly more patients on oral anticoagulants then antiplatelet therapy, but regardless of that, the prescription of anticoagulant therapy without prior hospitalization is much less frequent. Costs and hospitalizations attributable to AF have increased markedly over recent decades and are expected to increase in the future due to ageing populations (28, 29).

Increasingly often, patients who use oral anticoagulant therapy still have a thromboembolic incident, which raises the question of probable negligence and irregular use of drugs, as well as lack of education about possible complications. A regional study reported that 73% of patients with previously diagnosed AF were not adequately treated to prevent thromboembolic events (30). Nevertheless, anticoagulant therapy provides the greatest extent of protection and is still the first line of prevention against the occurrence of thromboembolic incidents.

Atrial fibrillation is caused by HFrEF due to unfavorable structural and electrical atrial remodeling (31, 32). Moreover, AF worsens HF, causing worsening symptoms, hospitalizations, and mortality (33). Several studies have shown that HFpEF and HFmrEF have a higher prevalence of AF than HFrEF (34, 35). More than half of the patients in this study (74.3%) had HFpEF and HFmrEF, which corresponds to the results of the previously mentioned studies.

This study had several limitations: the study was conducted in only one health center on a relatively small number of subjects, and in a short period of time; therefore, further research is necessary that will include a larger number of respondents in two or more health centers in Bosnia and Herzegovina.

This study shows that hypertension is the most common and greatest risk factor for AF. This indicates the need to reduce risk factors and control hypertension. In addition to hypertension, the frequency and association with diabetes mellitus was high, which requires further research. The frequency was higher in patients with preserved EF, which paves the way for future studies, whether this is the result of well-controlled AF and other risk factors, or whether other mechanisms are involved. Ischemic stroke in a large percentage of patients is of cardioembolic origin, as our study showed, which increases the number of hospitalizations as well as disability and mortality in patients.

The overarching goal should be to develop a national registry of AF that would serve as a reference for all further activities in the management of AF, complications, and comorbidities.