As the main preventable risk factor for the development of chronic non-infectious diseases and death, obesity is a growing public health issue in the modern world. The prevalence of obesity has nearly doubled between 1975 and 2016. In Croatia, 57.4% persons older than 18 have a body-mass index (BMI) higher than 25 kg/m², of which 38.7% are overweight and 18.7% obese. When stratified according to sex, obesity is present in 20.8% men and 16.8% women. (1) Studies have shown that increase in mean BMI from 1.31 kg/m² in women and 1.41 kg/m² in men reduces the expected lifespan by one year. (2)

The association and influence between obesity and the development of atrial fibrillation (AF) has become clearer after the publication of a metanalysis according to which every round-number increase in BMI increased the risk of AF by 3.5-5.3%. (3) Obesity (defined as BMI >30 kg/m²) together with arterial hypertension (defined as increased arterial pressure values >139/89 mmHg), excessive consumption of alcohol, diabetes, smoking, and hyperlipidemia causes deterioration of the diastolic function of the heart and leads to inflammation and fatty tissue deposits in the pericardium. (4, 5)

The influence of obesity on AF can be evaluated through several other variables:

Development of AF has been observed in inflammatory states such as pericarditis and myocarditis as well as after these states as a consequence of various cardiosurgical procedures. (18) Obesity is, as an inflammatory state, also a possible trigger for AF development. Many studies have focused on establishing the association between adiponectin and leptin and development of AF, and animal models have shown that leptin has a role in the scarring of the atrium and consequent development of AF. (19) Adiponectin was considered a protective factor in inflammation caused by excess fatty tissue deposits. However, current studies show that increased levels of adiponectin sometimes have a protective role. (20)

Although many studies have examined the influence of body mass on AF prognosis, the results are still controversial, so every study is important in order to contribute to better understanding of this increasingly common issue in the modern lifestyle.

This study was conducted in the Day Hospital of the Endocrinology Department at the Zagreb University Hospital Centre (UHC) between 2013 and 2016 to examine the effect of weight loss on cardiovascular risk factors and structural and functional remodeling of the heart. We included 85 obese participants (56 women and 29 men) with an average age of 58 (range 36-71). The control group comprised 40 patients of similar age and sex who only received advice for losing weight but were not regularly monitored, while 45 patients underwent an intensive program for losing body weight known as the Clinical Five-day Weight Loss Program at the Zagreb UHC Day Hospital. Differences between sexes were not compared.

The Clinical Five-day Weight Loss Program comprised professionally structured and guided lifestyle changes, changes in diet, increase in physical activity, and regulation of sleep duration and quality. All patients were clinically monitored through the polyclinic over a period of 12 months in three-month intervals, and received recommendations to improve their lifestyle (e.g. reduction in meals, dietary reduction in kcal) and to increase awareness of dietary habits (food with a lower glycemic index, adequate hydration with 1600 mL of water, increased physical activity with individual advisement more frequent than every 3 months, and the option for early phone consultations). At the start and during the monitoring, as well as at the end of the 12-month period, we performed an analysis of cardiovascular risk factors, echocardiography, ergometry, 24-hour Holter monitoring, and 24-hour continuous arterial pressure monitoring (CAPM). CRP levels, insulin and glycemia levels, and the HOMA index (determining insulin resistance; fasting serum insulin (μU/mL) × fasting plasma glucose (mmol/L) / 22.5) were measured in all patients at the start of the study and after monitoring. (21)

We excluded patients with chronic kidney disease, diabetes type 2, diabetes type 1, infection, or any acute condition.

Patients signed a written informed consent form, and the study was conducted in adherence with ethical principles.

All results were analysed with the t-test for small binary samples who served as their own controls.

The results of the study showed a statistically significant improvement of left and right atrial volume, a reduction in ventricular mass, reduction in systolic pressure, and improved ergometry results. Insulin resistance measured with the HOMA index was also significantly reduced, with a significant drop in CRP.

Holter ECG showed a significant reduction in AF episodes and supraventricular extrasystoles (SVES). Ejection fraction changed somewhat less significantly after 12 months of weight loss. The number of SVES in the guided group was almost three times lower in comparison with the baseline values, whereas there were no significant changes in the control group. The average number of AF paroxysms (longer than 30 seconds) evidenced in Holter ECG was 3 times lower compared with baseline values, but there were also statistically significantly less paroxysms in the control group as well. All the above results are shown in Table 1.

In 2010, 12.6 million women and 20.9 million men were suffering from AF across the world. (22) It is estimated that by 2030 the EU will have 14 to 17 million patients with AF, i.e. that 120 000 to 250 000 new patients are diagnosed every year. As the population ages, prevalence and costs associated with AF are constantly increasing, and research that can contribute to insights into preventive measures for this issue is more than necessary.

Today, risk factors for AF are usually increased BMI, advanced age, and arterial hypertension. The underlying cause is a process of atherosclerosis progression that is exacerbated by elevated levels of adipocytes, leptin, interleukin (IL)-6, and MCP-1 that are secreted by adipocytes as well as tumor necrosis factor (TNFα) and MCP-1 secreted from inflammation-stimulated macrophages, with lipid deposition in fatty tissue, followed by muscles, liver, epicardium, and other organs. (23) Such accumulation exacerbates the inhibition of the insulin signal pathway by phosphorylation of the insulin receptor substrate in place of serine (due to elevated TNFα levels) instead of tyrosine. (23) Fatty tissue is an additional source of angiotensin, which is usually produced in the liver, and adipocytes also have an angiotensin receptor (AR-1) on their membrane which increases systemic arterial pressure. (24) Binding IL-6 to hepatocytes causes increased secretion of C-reactive protein (CRP), whose role in atherogenesis is considered in the light of possible causes of myocardial infarction, stroke, and peripheral artery disease. (25)

The lowered plasma CRP levels in participants together with the reduction in the number of AF paroxysms and LA volume support theories that point to the influence of CRP on the development and treatment of AF.

Girerd et al. demonstrated that elevated CRP along with increased waist circumference contribute to elevated risk for the development of postoperative AF after heart bypass surgery. (4) Research on animal models corroborates these facts. (26) In addition to total weight loss, a study by Pathak et al. also considered the fluctuations in body weight, i.e. the speed of weight loss between measurements. Participants who lost >10% of body weight had six times higher chances of not developing arrhythmias compared with those who lost <3% of body weight. On the other hand, participants with a >5% body mass fluctuation had a much higher risk for the development of recurrent AF than those with a <2% fluctuation. Therefore, AF development is facilitated by high body mass as well as large fluctuations in body mass loss. (27)

The present study showed a significant reduction in heart volume and arterial pressure as well as a reduction in arrhythmogenicity and supraventricular extrasystole episodes in the group with supervised guided weight loss, which can also be attributed to structural and electric remodeling of the heart caused by obesity. The group of patients left to pursue their own weight loss plans had poorer results than the professionally guided group. Left ventricular ejection fraction did not change significantly in either group, which could be explained by the short follow-up period.

The progression of paroxysmal to permanent AF is also associated with body mass. Tsang et al. examined 3248 participants with paroxysmal AF and found that 557 participants developed permanent AF over a period of 5 years. After excluding other risk factors such as age and sex, body weight was found to be an independent predictor in the development of permanent AF. (28)

The HOMA index is one of the markers for insulin resistance, which was very high in the present study compared with other studies, at 8.5-12.0. For example, in persons without diabetes the HOMA index is 1.85 in man and 2.07 in middle-aged women of 50 years of age. (29)

This study demonstrated that a structured approach to lifestyle changes to reduce obesity leads to significant recovery in the cardiometabolic profile. After one year of follow-up, all measured parameters were significantly reduced, except for the HOMA index.

Limitations of the study include the fact that patients were not separately analysed based on the presence or absence of sleep apnea as well as the short monitoring period for structural changes on echocardiographic examination. Additionally, no comparison was made between the male and female sexes. We plan to continue the study by following the patients over a longer period of time and to attempt to correct these limitations.

A structured and monitored weight loss plan reduces cardiometabolic risk within one year, and consequently also reduces insulin resistance and inflammatory processes in the body that contribute to the development of AF. We observed a significant reduction in heart volume and arterial pressure, as well as reduced frequency of AF and the number of supraventricular extrasystoles. In obese patients, we believe that gradual body mass reduction of at least 10% should be insisted upon, with the adoption of an individualized approach to every patient.