Takayasu's arteritis (TA) is a granulomatous vasculitis of the aorta and its major branches. Although TA predominantly affects Asian and South American ethnic groups, rare cases of the disease are reported in other races, too [1]. TA incidence varies from 0.8 to 2.6 cases per 1, 000, 000 adult population depending on the geographical area of residence and ethnicity [2]. At present, no epidemiological data are available on the prevalence of this disease in the Russian Federation. Because of untimely diagnosis and delayed treatment, patients with TA can develop major adverse cardiovascular events (MACE) leading to premature yet preventable death.
At its onset, TA can mimic a wide range of conditions. Specific symptoms that may not be present in the early stages include asymmetric pulse or blood pressure in the upper extremities accompanied by pronounced hypertension, impaired vision, and abdominal pain.
The aim of this retrospective study was to describe the clinical manifestations, laboratory and radiographic findings, the course and outcome of TA in 183 patients residing in the Middle Ural.

METHODS

Our retrospective cohort study included 183 patients (139 females and 44 males) with verified TA who had received treatment at Sverdlovsk Clinical Hospital No. 1 between 1979 and 2018. The age at diagnosis was 9 to 62 years in females (mean: 33.5; median: 35; 25%–75% IQR: 24–43) and 12 to 59 years in male patients (mean: 35.18; median: 34; 25%–75% IQR: 26.5–42). The duration of the disease was 0.6 to 64 years in women (mean: 12.3 years; median: 10 years; 25%–75% IQR: 4–18) and 0.6 to 32 years in men (mean: 9 years; median: 7 years; 25%–75% IQR: 4–14.5). The time elapsed between the onset of the first clinical symptoms and the established diagnosis was 0.6–54 years in females (mean: 5.7 years; median: 3 years; 25%–75% IQR: 1–7) and 0.6–33 years in men (mean: 6 years; median: 4 years; 25%–75% IQR: 1.5–8) (tab. 1).
The primary diagnosis of TA specified in the patients’ medical records was verified according to the criteria proposed by the American College of Rheumatology in 1990 [3].
Following the unified protocol, we collected and analyzed demographic data, clinical, laboratory and angiography findings, and information about TA-related surgical interventions. Moriwaki’s classification criteria were applied to describe arterial damage [4]. Because our retrospective study covered a long time period that had seen an evolution in clinical practices and technologies, the imaging modalities used to identify arterial stenosis, occlusion, dilation, dissection, etc. were different and included conventional catheter angiography and/or CTA and/or MRA and/or ultrasonography. Importantly, for every patient, ultrasonography findings were confirmed by at least one contrast-enhanced imaging technique.

To obtain information about the clinical manifestations and angiographic demonstration of the disease in other ethnicities, we searched the PubMed database using Takayasu's arteritis as keywords. Similar to the present study, the inclusion criteria used in the PubMed articles were based on ACR 1990 [3]. Among them were: the presence of 3 or more TA symptoms (90% sensitivity, 97.8% specificity), including 40 years at onset, claudication (muscle weakness and pain in the extremities during movement), pulse deficit in one or both brachial arteries, blood pressure difference > 10 mmHg in the brachial arteries, bruits over the subclavian arteries or abdominal aorta, and a narrowed lumen or occlusion of the aorta or its major branches in the proximal upper and lower extremities not associated with atherosclerosis, fibromuscular dysplasia and spasm.
A reference dataset was compiled from Elibrary, a free Russian academic database of research works on biomedicine and natural sciences. We ran a search using Takayasu's arteritis and TA as keywords in order to obtain information about clinical and angiographic TA manifestations in Russian patients [1, 14, 19, 20].

Statistical analysis

The data were processed in Statistica 7.0 (Statsoft inc; USA). Categorial variables were analyzed using a chi-square test. All statistical tests applied were two-tailed; differences were considered significant at р < 0.05. The Kaplan–Meier method was used to analyze the factors affecting patients’ survival. Between the groups, survival distributions were compared using the log-rank test.

RESULTS

Demographic data and clinical manifestations of the disease

At the time of examination, the most common clinical symptoms were malaise (47.5%), elevated blood pressure (53%), pulse asymmetry in the upper extremities (49%), pain, weakness or numbness in the upper extremities (49%), and headache (47%) (tab. 2).
Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and high-sensitivity CRP were elevated (tab. 2). The most common pattern of arterial involvement was Moriwaki’s type V (the aortic arch, its major branches, the abdominal aorta and/or renal arteries).
Pathological lesions were typically found in the subclavian, carotid and renal arteries. Stenosis was the most common pathology (tab. 3).

Surgical interventions were performed on 66 (36%) patients (23 men and 43 women). Among the indications for surgery were: hemodynamically significant stenosis, occlusion or thrombosis of the involved vessels; hypertension caused by renal artery or subtotal aortic stenosis; symptoms of end-stage upper/lower limb ischemia. The surgical interventions performed can be broken down into two groups: endovascular procedures (stenting, bypass grafting, angioplasty) and open reconstructive surgeries. Besides, one patient with aneurysm and thrombosis of renal arteries had to undergo nephrectomy and kidney autotransplantation (tab. 4).
In the majority of cases, medication therapy included glucocorticoids (96 patients; 52%) and antiplatelet agents, such as aspirin and dipyridamole (116 patients; 63%) (tab. 5).

Since 1979, 31 patients have died, including 18 men and 13 women. The mean age at death was 38 years in women (Мe [25%–75%] — 36 [32–44]) and 49 years in men (Мe [25%– 75%] — 50 [40–57]). On average, the time elapsed from the established diagnosis to the moment of death was 9.25 years (6.5 [3–16]) in men and 9 years (5 [3–10]) in women. Information about the causes of death was obtained from autopsy protocols (n = 22) and in conversations with the close relatives of the deceased (n = 9) (tab. 6).
Data on the patients’ survival is shown in figure. The 5-year survival rate was 92%; 10-year survival, 90%; and 15-year survival, 80%. (median: 34 [20–41]).
A total of 72 patients (27 men and 45 women) developed cardiovascular complications. On average, age at TA onset was Me [25%–75%] — 33 [26–43]. TA duration before the onset of a cardiovascular even was Me [25%–75%] — 10 [5–20]. Age at the onset of cardiovascular complications was 38 [30–49.5] (tab. 7).

DISCUSSION

In spite of being considered a rare disease, Takayasu's arteritis is studied all over the world because it poses a significant social and economic burden: patients with TA develop serious cardiovascular complications causing disabilities and premature death in young people.
Although the arsenal of available diagnostic techniques is vast, the diagnosis of TA still remains a challenge due to the variability of its symptoms and the lack of knowledge of the disease demonstrated by public health practitioners. This leads to misdiagnosis during the initial examination or delays the correct diagnosis.
Our sample of the Ural residents was dominated by women: 139 (76%) of 183 participants were female. In other countries, the male to female ratio varies between 1 : 2.4 and 1 : 8 in Israel, 6.9 : 1 in Mexico and 8 : 1 in Japan [5–8]. In our study, the demographic characteristics, early clinical symptoms and the course of the disease were consistent with the previously published data indicating that TA strikes at young age [6–12].
Headache, hypertension (systolic blood pressure of 140 mmHg and/or diastolic blood pressure of 90 mmHg and above) were similarly frequent in all studies including our cohort of patients [9–14] (tab. 8).

The most commonly involved vessels were the subclavian, carotid and renal arteries. Stenosis was the most common lesion type. The most prevalent (43%) TA type was type V (according to Moriwaki’s classification). The carotid and subclavian arteries suffered the same types of lesions in all analyzed studies, including ours. Similar to other cohorts, the Ural sample demonstrated rare involvement of the vertebral, pulmonary and iliac arteries. Interestingly, damage to the ascending aorta and coronary arteries was very frequent in the Korean population [9, 15–18] (tab. 9).
There are reports that the brachiocephalic artery is affected in 85% of Russian patients with TA, whereas damage to the renal artery is observed in 23% cases [19, 20] (tab. 10).

Except for the Serbian study, all other research works indicate that type V of arterial involvement is the most frequent, while type III is the most rare. The Serbian sample is characterized by a high frequency of types I and IIa damage. Type IIb prevails in the Korean population. Type IV is relatively widespread in India and Brazil. Both genetic and environmental factors can contribute to the clinical manifestations of TA (tab. 11) [15–17, 21–24].
In our cohort of patients, survival rates were similar to those reported in previous publications [17, 25–27]. However, there are reports of different 5- and 10-year survival rates (69 and 36%, respectively) [28]. In the Arab population, the 5-year survival rate is as low as 50% [29]. The record-breaking 100% survival rate is reported in Japan [30].

A national TA registry is needed to estimate the prevalence of the disease in different ethnic groups. It will provide valuable information about TA presentation and clinical course necessary to establish the timely diagnosis. The actual prevalence of TA can be higher than suggested in the literature. Timely diagnosis and treatment will help to improve patient outcomes.
The main limitation of the present study is its retrospective design. Besides, the study was conducted in inpatients only. In different time periods, the diagnostic procedures used in the patients were different, which also complicates data interpretation.

CONCLUSIONS

The clinical presentations of TA are diverse. Timely diagnosis can be a challenge when a patient presenting with general inflammation has a healthy pulse pattern, develops collateral circulation and demonstrates no specific symptoms of arterial damage. Patients with TA should be warned against a high risk of cardiovascular complications and advised to monitor and control their blood pressure, lipid counts and blood coagulability. Hemodynamically significant stenosis, occlusion or thrombosis of damaged arteries can be corrected surgically, contributing to antihypertensive therapy, helping to eliminate the symptoms of ischemia and prevent new vascular complications. The majority of patients in our cohort had Moriwaki’s type V of arterial damage. High survival rates can be explained by a young age and a capacity to develop collateral circulation.