Combination of Atrial Fibrillation and Coronary Heart Disease in Patients in Clinical Practice: Comorbidities, Pharmacotherapy and Outcomes (Data from the REСVASA Registries)

Aim. Assess the structure of comorbid conditions, cardiovascular pharmacotherapy and outcomes in patients with atrial fibrillation (AF) and concomitant coronary artery disease (CAD) included in the outpatient and hospital RECVASA registries. Materials and methods. 3169 patients with AF were enrolled in outpatient RECVASA (Ryazan), RECVASA AF-Yaroslavl registries and hospital RECVASA AF (Moscow, Kursk, Tula). 2497 (78.8%) registries of patients with AF had CAD and 703 (28.2%) of CAD (67.8%) than in its absence (74.5%), especially the prescription of anticoagulants (39.1% and 66.2%; p <0.0001), as well as in the presence of the previous MI (63.3%) than in its absence (74.3%). The presence of CAD and, in particular, the previous MI, was significantly associated with a higher risk of death (risk ratio [RR]=1.58; 95% confidence interval [CI] was 1.33-1.88; p <0.001 and RR=1.59; 95% CI was 1.33-1.90; p <0.001), as well as with a higher risk of developing a combined cardiovascular endpoint (RR=1.88; 95% CI was 1.17-3 , 00; p <0.001 and RR=1.75; 95% CI was 1.44-2.12; p<0.001, respectively). Conclusion. 78.8% of patients from AF registries in 5 regions of Russia were diagnosed with CAD, of which 28.2% had previously suffered myocardial infarction. Patients with a combination of AF and CAD more often than in the absence of CAD had hypertension, chronic heart failure, diabetes, chronic kidney disease and anemia. Patients with the previous MI had higher incidence of diabetes than those without the previous MI. The frequency of proper cardiovascular pharmacotherapy was insufficient, and to a greater extent in the presence of CAD and the previous MI than in their absence. All-cause mortality was recorded in patients with a combination of AF and CAD more often than in the absence of CAD. All-cause mortality and the incidence of nonfatal myocardial infarction were higher in patients with AF and the previous MI than in those without the previous MI. The presence of CAD and, in particular, the previous MI, was significantly associated with a higher risk of death, as well as a higher risk of developing a combined cardiovascular endpoint.


Introduction
Atrial fibrillation (AF) is the most common heart rhythm disorder, increasing the risk of stroke fivefold and associated with higher mortality [1][2][3]. Analysis of statistical data shows that the AF incidence is approximately 3% in adults aged 20 and over and is more common in the elderly, as well as in the presence of associated cardiovascular (CVD) and non-cardiac diseases, including arterial hypertension (AH), chronic heart failure (CHF), coronary heart disease (CHD), structural heart abnormalities, obesity, diabetes mellitus (DM) or chronic kidney disease (CKD) [4,5].
Atrial fibrillation is closely associated with coronary heart disease, while the mechanism of pathogenetic influence on the development of AF is due, among other things, to ischemia of atrial cardiomyocytes [2]. The Framingham study found an increase in the prevalence of CHD in patients with newly diagnosed AF [4]. AF in patients with acute coronary syndrome may be associated with an increased risk of ST-segment elevation myocardial infarction [5]. In general, 10-15% of patients with AF undergo percutaneous coronary intervention for CHD [6]. The data of international and Russian studies, which analyzed multimorbidity, pharmacotherapy and outcomes in patients with a combination of atrial fibrillation and CHD, including those with previous myocardial infarction, are limited [7].
Prospective medical registries are the most effective way to study combined CVDs and the quality of drug treatment in real clinical practice [8,9]. Therefore, the actual aim of this study is to assess the structure of comorbid conditions, cardiovascular pharmacotherapy and outcomes in patients with atrial fibrillation and concomitant CHD included in the outpatient and hospital RECVASA registries.

Materials and methods
Patients with AF were included in 5 cities of the Russian of the registry study design was published by us earlier [10,11], and we also provided detailed information on the conduct of anticoagulant therapy and the frequency dynamics of its prescription during prospective observation [11].
Inclusion criteria in the study: 1) indication of the AF diagnosis in the outpatient card or in the clinical diagnosis of the disease hospital history; 2) Contacting a polyclinic or hospitalization in a hospital during the above periods of inclusion in the registers. The characteristics of combined CVD and concomitant chronic noncardiac diseases among patients with AF and the presence/absence of CHD are presented in Table 1.
Patients with a combination of AF and CHD significantly more often than in the absence of CHD were diagnosed with AH, CHF, diabetes mellitus, CKD and anemia. at the same time, only diseases of the digestive system were de- Patients with a combination of AF and CHD with a history of myocardial infarction were significantly more likely to be diagnosed with a paroxysmal form than in the absence of PICS (   AH -arterial hypertension, CHD -coronary heart disease, CHF -chronic heart failure, ACA -acute cerebrovascular accident, COPD -chronic obstructive pulmonary disease.

Discussion
According to the results of the present study, CHD was diagnosed in 78.8% of patients from AF registers, and 28.2% of them had had myocardial infarction before.
According to the data of AF international registries, the incidence of CHD is 14-45%, [12][13][14], which is significantly less than our data. The AF incidence in acute coronary syndrome (ACS) ranges from 2 to 23% [15]. According to the data of the RECVASA outpatient register of cardiovascular diseases, a simultaneous combination of AF, AH, CHD and CHF was detected in 93.2% of patients with AF.
In this group of patients, the highest incidence of myocardial infarction and cerebral stroke in the anamnesis was revealed

Events Patients with AF in a Patients with AF without a combination with CHD combination of CHD (n=2497) (n=672) p
All-cause mortality, n (%) 580 ( Table 6. The frequency of fatal and non-fatal events according to the prospective observation data of patients with an AF and CHD combination in the presence/absence of previous myocardial infarction cording to the results of a prospective population study conducted in Rotterdam, the risk of newly registered AF in patients with myocardial infarction increases by 60-77% [19]. Several mechanisms may explain the association of previous myocardial infarction with AF development. Atrial dilation due to myocardial infarction can lead to an increase in atrial pressure, with catecholamines released in response to atrial dilatation, which increases the AF risk [20]. It was also suggested that AF may develop secondary due to left ventricular dysfunction and hemodynamic disturbances after myocardial infarction. Finally, atrial ischemia can create both triggers for the AF onset and a substrate for its subsequent maintenance [21].  CVD -cardiovascular diseases, RR -risk ratio, CI -confidence interval, CHD -coronary heart disease. CVD -cardiovascular diseases, RR -risk ratio, CI -confidence interval, CHD -coronary heart disease.  [11,26]. According to the data of the atrial fibrillation registers ORBIT-AF I, ORBIT-AF II and GARFIELD-AF, in Western Europe the frequency of prescribing anticoagulants to patients with AF is significantly higher and amounts to 60-80% [27]. At the same time, observational studies have shown that patients with AF and ACS are less likely to receive appropriate antithrombotic therapy [28] and are more likely to experience adverse outcomes [29] than patients with ACS without AF. In the BALKAN-AF registry, which included 2,712 AF patients, it was shown that antithrombotic therapy was suboptimal in multimorbid patients with AF, and 18% of multimorbid patients didn't receive anticoagulants, while the presence of CHD and myocardial infarction were independent predictors of the absence of oral anticoagulants prescription in multimorbid patients with newly diagnosed AF [30]. Our study revealed that all-cause death (by 2.9 times) and non-fatal myocardial infarction (by 3.1 times) were more often recorded in patients with a combination of AF and CHD than in the absence of CHD.  [32]. Several other studies have also shown an association of myocardial infarction with an increased risk of death in AF patients [33,34]. According to the registry, which included 6,000 patients with acute myocardial infarction, patients admitted with acute myocardial infarction and AF had a higher risk of acute stroke, nosocomial death, and readmission within 30 days [35]. Also, T. Pilgrim et al. showed that AF increases the risk of ischemic and hemorrhagic stroke among patients with stable CHD who underwent percutaneous coronary intervention [36].

Conclusion
CHD was diagnosed in 78.8% of patients from AF registers in 5 regions of Russia, and 28.2% of them had had myocardial infarction before. The presence of an AF and CHD combination in patients was associated with a higher frequency of diagnosing AH, CHF, diabetes mellitus, CKD, and anemia. Chronic renal failure, characterized by a decrease in GFR, was more often detected with an AF and CHD combination. The frequency of proper cardiovascular pharmacotherapy was insufficient, and to a greater extent in the presence of CHD than in its absence, as well as in the presence of PICS than in its absence. Allcause death and nonfatal cerebral stroke were more often recorded in patients with an AF and CHD combination than in the absence of CHD. All-cause mortality and the incidence of nonfatal myocardial infarction were higher in patients with AF and previous myocardial infarction during the follow-up period than in those without a myocardial infarction history. According to multivariate analysis, taking into account age and gender factors, the presence of CHD and, in particular, PICS, was significantly associated with a higher risk of death, as well as a higher risk of developing events corresponding to the combined cardiovascular endpoint.

Relationships and Activities:
The article was published with the financial support of the Pfizer company. Pfizer did not participate in the data acquisition and writing of the article. The opinion of the author may not coincide with the opinion of the company.

Funding:
The study was performed with the support of the National Medical Research Center for Therapy and Preventive Medicine.